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pubmed_132_25234
AIMS Women with gestational diabetes (GDM) have a 20% risk of developing diabetes in the 10 years following pregnancy, but the risk may be as high as 70% in higher risk populations. Guidelines recommend screening for diabetes postpartum, but screening rates are low. We evaluated the effect of a physician reminder on postpartum screening and in women with GDM. METHODS We conducted a retrospective chart review among women with GDM seen at our urban, academic endocrine clinic in Toronto, Canada between 2006 and 2010. Our primary outcome was to evaluate the effect of a reminder checklist on postpartum diabetes screening rates. RESULTS We included 314 women in our study, 173 had a checklist on their chart. Women had a mean age of 34.9 years, 45% were Caucasian and 23% had a previous GDM. The checklist was associated with a 3 fold increase in odds of being screened postpartum, and nearly 4 fold increase in postpartum follow up visits (OR 2.99, 95% CI 1.84-4.85 and OR 3.71, 95% CI 2.26-6.11). CONCLUSION A physician based reminder system is an effective way to improve postpartum screening rates. To further increase screening rates, a multilevel approach targeting both patients and physicians is required.
10.1016/j.diabres.2011.10.023
pubmed_468_18392
International infectious disease surveillance has been conducted by the United States (U.S.) Department of Defense (DoD) for many years and has been consolidated within the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) since 1998. This includes activities that monitor the presence of antimicrobial resistance among pathogens. AFHSC-GEIS partners work within DoD military treatment facilities and collaborate with host-nation civilian and military clinics, hospitals and university systems. The goals of these activities are to foster military force health protection and medical diplomacy. Surveillance activities include both community-acquired and health care-associated infections and have promoted the development of surveillance networks, centers of excellence and referral laboratories. Information technology applications have been utilized increasingly to aid in DoD-wide global surveillance for diseases significant to force health protection and global public health. This section documents the accomplishments and activities of the network through AFHSC-GEIS partners in 2009.
10.1186/1471-2458-11-S2-S8
pubmed_352_15100
The endoscopic finding of a visible vessel in the base of a bleeding gastrointestinal lesion is a well-known indicator of the possibility of recurrent hemorrhage. We carried out a multivariate analysis of 277 patients with gastrointestinal hemorrhage, but no chronic liver disease, of the clinical history and parameters in relation to hemorrhage, in order to select patients at risk for this endoscopic picture. A clinical history of associated disease, the absence of ulcerogenic drug intake, presentation of bleeding in the form of hematemesis and active hemorrhage on admission had predictive value for visible vessel, The incidence of visible vessel was significantly greater in anastomotic stoma ulcers than in gastric and duodenal sulcers. On the basis of the clinical parameters mentioned, patients with a high probability of having a bleeding lesion with a visible vessel can be selected for priority endoscopy.
10.1055/s-2007-1018217
pubmed_864_14419
Breast cancer metastasis suppressor 1 (BRMS1) is able to suppress tumor metastasis without affecting primary tumor growth in various cancers. Here, we report a novel transcript variant of human BRMS1, termed BRMS1.vh. BRMS1.vh is identical to the major BRMS1 variant (BRMS1.v1) except for missing base pairs 683-775, encoding a 215-amino acid protein lacking a functional nuclear localization sequence. Expression of BRMS1.vh in hepatocellular carcinoma (HCC) cells suppressed NF-κB signaling pathway, sensitized cells to apoptotic stimuli, leading to suppressed tumor growth. Taken together, our results suggest a potential role for BRMS1.vh in regulating cell apoptosis and tumor growth in HCC.
pubmed_864_14419
others_14_4938
As part of the model building process, parameter estimation is of great importance in view of accurate prediction making. Confidence limits on the predicted model output are largely determined by the parameter estimation accuracy that is reflected by its parameter estimation covariance matrix. In view of the accurate estimation of the Square Root model parameters, Bernaerts et al. have successfully applied the techniques of optimal experiment design for parameter estimation [Int. J. Food Microbiol. 54 (1-2) (2000) 27]. Simulation-based results have proved that dynamic (i.e., time-varying) temperature conditions characterised by a large abrupt temperature increase yield highly informative cell density data enabling precise estimation of the Square Root model parameters. In this study, it is shown by bioreactor experiments with detailed and precise sampling that extreme temperature shifts disturb the exponential growth of Escherichia coli K12. A too large shift results in an intermediate lag phase. Because common growth models lack the ability to model this intermediate lag phase, temperature conditions should be designed such that exponential growth persist even though the temperature may be changing. The current publication presents (i) the design of an optimal temperature input guaranteeing model validity yet yielding accurate Square Root model parameters, and (ii) the experimental implementation of the optimal input in a computer-controlled bioreactor. Starting values for the experiment design are generated by a traditional two-step procedure based on static experiments. Opposed to the single step temperature profile, the novel temperature input comprises a sequence of smaller temperature increments. The structural development of the temperature input is extensively explained. High quality data of E. coli K12 under optimally varying temperature conditions realised in a computer-controlled bioreactor yield accurate estimates for the Square Root model parameters. The latter is illustrated by means of the individual confidence intervals and the joint confidence region. © 2002 Elsevier Science B.V. All rights reser
10.1016/S0168-1605(01)00645-6
pubmed_774_22343
PURPOSE There has yet to be a quantitative measurement of communicative resilience processes as outlined in the Communicative Theory of Resilience (CTR). This study aims to determine the structure, reliability, and validity of the Dyadic Communicative Resilience Scale (DCRS) in cancer patients and partners. METHOD The DCRS was administered to 584 participants, including 312 cancer patients and 272 partners of cancer patients along with the common coping subscale of the dyadic coping inventory, the cancer-related communication problems with couples scale, and the resilience promoting scale. RESULTS Exploratory and confirmatory factor analyses revealed nine dimensions of dyadic communicative resilience within the five resilience processes outlined in the CTR. Structure reliability was shown with Cronbach's alphas between .77 and .88 and good to excellent model fit for the nine factors. Convergent and discriminant validities were demonstrated by significant Pearson correlations with relevant, established coping/resilience measures. CONCLUSIONS The DCRS has a clear nine factor structure and demonstrates good reliability. The measure has good convergent and discriminate validity indicating its utility in future research examining resilience in cancer populations.
10.1007/s00520-019-04763-8
pubmed_103_5477
Alkyl Grignard reagents (Et, nBu, iPr, cyclohexyl), with the exception of tBuMgCl, undergo exclusive or exceptionally highly regioselective 1,4-addition reactions to α,β-γ,δ-unsaturated ketones, while aryl and heteroaryl Grignard reagents give mixed results ranging from exclusive 1,4-addition (1-naphthyl, 2-N-methylpyrrolyl) to regioselective 1,2-addition (2-furyl, 2:1). All alkyl, aryl, and heteroaryl Grignard reagents examined gave exclusive 1,4-addition reactions with α,β-γ,δ-unsaturated thiol esters, with the exception of tBuMgCl, which gave an 80:20 mixture of 1,4:1,6-addition products. The high chemo- and regioselectivity observed for these reactions is attributed to a radical or radical-like pathway for the alkyl Grignard reagents and possibly a carbanion pathway for aryl Grignard reagents. The α,γ-dienyl thiol esters provide for a one-pot tandem 1,4-addition-nucleophilic acyl substitution reaction sequence to afford 3-substituted 4-enone moieties.
10.1021/acs.joc.6b02769
pubmed_796_22380
We describe the development of resistance to trimetrexate and piritrexim (BW 301U) by a stepwise selection protocol in Chinese hamster ovary cells. Selection in trimetrexate resulted in initial resistance as a result of dihydrofolate reductase gene amplification. Several trimetrexate-resistant variants that display 250-340-fold and 25-50-fold resistance to lipophilic and hydrophilic antifolates, respectively, were established. Increased antifolate resistance was associated with a prominent overexpression of dihydrofolate reductase as determined from the elevated folate reductase activity, cellular labeling with fluorescein-methotrexate, and steady-state mRNA levels as a result of a consistent dihydrofolate reductase gene amplification. However, upon subsequent incremental increases in trimetrexate, further resistance was also associated with amplification of the multidrug resistance gene. This resulted in overexpression of P-glycoprotein and a subsequent 20-50-fold collateral resistance to pleiotropic drugs such as adriamycin, actinomycin D, vinca alkaloids, etoposide, and colchicine. In contrast, initial resistance following selection with low piritrexim concentrations resulted from an unknown mechanism(s) not involving overproduction of either dihydrofolate reductase or P-glycoprotein. This piritrexim resistance was shared with trimetrexate but not with methotrexate. Upon further selection with piritrexim, resistant variants emerge with amplified dihydrofolate reductase but not with multidrug resistance genes. These variants were subsequently resistant to both hydrophilic and lipophilic folate antagonists but retained sensitivity to pleiotropic drugs. The pattern of resistance with methotrexate, trimetrexate, and piritrexim shared a common mechanism, dihydrofolate reductase gene amplification, but differed regarding the additional amplification of the multidrug resistance gene in trimetrexate-resistant cells as well as the emergence of an additional unknown mechanism(s) of resistance to lipid-soluble antifolates upon initial selection in piritrexim.
pubmed_796_22380
pubmed_885_18550
The aim of the present volumetric study was to explore the neuro-anatomical correlates of autobiographical memory loss in Alzheimer's patients and healthy elderly, in terms of the delay of retention, with a particular interest in the medial temporal lobe structures. Fifteen patients in early stages of the disease and 11 matched control subjects were included in the study. To assess autobiographical memory and the effect of the retention delay, a modified version of the Crovitz test was used according to five periods of life. Autobiographical memory deficits were correlated to local atrophy via structural MRI using Voxel Based Morphometry. We used a 'lateralized index' to compare the relative contribution of hippocampal sub-regions (anterior vs posterior, left vs right) according to the different periods of life. Our results confirm the involvement of the hippocampus proper in autobiographical memory retrieval for both recent and very remote encoding periods, with larger aspect for the very remote period on the left side. Contrary to the prominent left-sided involvement for the young adulthood period, the implication of the right hippocampus prevails for the more recent periods and decreases with the remoteness of the memories, which might be associated with the visuo-spatial processing of the memories. Finally, we suggest the existence of a rostrocaudal gradient depending on the retention duration, with left anterior aspects specifically related to retrieval deficits of remote memories from the young adulthood period, whereas posterior aspects would result of simultaneous encoding and/or consolidation and retrieval deficit of more recent memories.
10.1371/journal.pone.0046200
pubmed_1125_14997
This study examines the feasibility of coupling a Catalytic Wet Air Oxidation (CWAO), with activated carbon (AC) as catalyst, and an aerobic biological treatment to treat a high-strength o-cresol wastewater. Two goals are pursued: (a) To determine the effect of the main AC/CWAO intermediates on the activated sludge of a municipal WasteWater Treatment Plant (WWTP) and (b) To demonstrate the feasibility of coupling the AC/CWAO effluent as a part of the influent of a municipal WWTP. In a previous study, a high-strength o-cresol wastewater was treated by AC/CWAO aiming to establish the distribution of intermediates and the biodegradability enhancement. In this work, the biodegradability, toxicity and inhibition of the most relevant intermediates detected in the AC/CWAO effluent were determined by respirometry. Also, the results of a pilot scale municipal WWTP study for an integrated AC/CWAO-aerobic biological treatment of this effluent are presented. The biodegradation parameters (i.e. maximum oxygen uptake rate and oxygen consumption) of main AC/CWAO intermediates allowed the classification of the intermediates into readily biodegradable, inert or toxic/inhibitory compounds. This detailed study, allowed to understand the biodegradability enhancement exhibited by an AC/CWAO effluent and to achieve a successful strategy for coupling the AC/CWAO step with an aerobic biological treatment for a high-strength o-cresol wastewater. Using 30%, as COD, of AC/CWAO effluent in the inlet to the pilot scale WWTP, the integrated AC/CWAO-biological treatment achieved a 98% of total COD removal and, particularly, a 91% of AC/CWAO effluent COD removal without any undesirable effect on the biomass.
10.1016/j.chemosphere.2006.09.035
pubmed_1121_6055
This study was conducted to assess the frequency of pre-operative malnourishment in patients being treated for oral cavity squamous cell carcinoma. A retrospective chart review was carried out at the Aga Khan University Hospital, Karachi, on 62 patients. Patients were screened pre-operatively through a standard nutritional assessment tool at the time of admission to assess for malnutrition. Mean age of presentation was 48.34±13.11 years, mean height was 165 ± 8.62cm, weight 66.09±14.98 kg and BMI of 24.09±4.84. Males were 82.3% and 17.7% were females. At the time of admission, a significant number or patients, 12 (19.4%) were prone to malnourishment, while 3 (4.8%) patients were malnourished: Assessment was done by using a standardised nutritional assessment tool.
10.47391/JPMA.243
pubmed_754_9728
The pathologist has critically important responsibilities as a consultant in the management of patients with breast cancer. The clinical evaluation of the anatomic extent of cancer before treatment, the clinical-diagnostic stage, crudely estimates whether the cancer is localized to the breast, or whether there are regional or distant metastases. The pathologist establishes the diagnosis of cancer microscopically in a biopsy and reports the significant characteristics which can be used in the selection of therapy. The pathologist's additional gross and microscopic examinations after mastectomy, which more precisely document the anatomic extent of the cancer, are the basis of the postsurgical treatment-pathologic stage and provide additional information used to estimate prognosis and determine whether adjunctive therapy is needed. The pathology information used in staging includes the tumor size, histologic type, histologic grade, and presence or absence of axillary of other metastases. These and other pathological factors of significance which are discussed include the gross contour of the tumor as well as the presence or absence of necrosis, and any of the spectrum of cancers that we categorize as "minimal breast cancer" (in situ lobular carcinoma, intraductal carcinoma, invasive carcinoma smaller than 0.5 cm). Furthermore, the prognostic implications of the various histologic types are considered, as well as histologic and cytologic differentiation (grade), multicentricity, vascular invasion, cellular infiltration, and various other factors such as mucin or lipid production, steroid hormone receptors, and the nature of the tumor bed. The presence or absence of axillary lymph node metastases remains the single most significant variable in estimating prognosis for most breast cancers. In addition, combinations of the parameters noted above may have greater prognostic significance than any considered individually. Therefore, the pathologist, through the routine examination and documentation of breast biopsies and mastectomies, can provide important information which can be used to aid in the selection of treatment and in the estimation of prognosis.
pubmed_754_9728
pubmed_973_5126
A modification to a Jarrell-Ash model 23-100 recording microphotometer used to read spectroscopic plates is described. The modification allows the motion of the plate to drive incrementally a stepper motor chart recorder. The modification uses inexpensive off-the-shelf components and was installed in the field. The plate reading accuracy of the instrument was improved by a factor of 2-5, and problems associated with occasional plate drive slippage were eliminated.
10.1364/AO.13.002236
pubmed_958_16273
Flies display a sophisticated suite of aerial behaviours that require rapid sensory-motor processing. Like all insects, flight control in flies is mediated in part by motion-sensitive visual interneurons that project to steering motor circuitry within the thorax. Flies, however, possess a unique flight control equilibrium sense that is encoded by mechanoreceptors at the base of the halteres, small dumb-bell-shaped organs derived through evolutionary transformation of the hind wings. To study the input of the haltere system onto the flight control system, I constructed a mechanically oscillating flight arena consisting of a cylindrical array of light-emitting diodes that generated the moving image of a 30 degrees vertical stripe. The arena provided closed-loop visual feedback to elicit fixation behaviour, an orientation response in which flies maintain the position of the stripe in the front portion of their visual field by actively adjusting their wing kinematics. While flies orientate towards the stripe, the entire arena was swung back and forth while an optoelectronic device recorded the compensatory changes in wing stroke amplitude and frequency. In order to reduce the background changes in stroke kinematics resulting from the animal's closed-loop visual fixation behaviour, the responses to eight identical mechanical rotations were averaged in each trial. The results indicate that flies possess a robust equilibrium reflex in which angular rotations of the body elicit compensatory changes in both the amplitude and stroke frequency of the wings. The results of uni- and bilateral ablation experiments demonstrate that the halteres are required for these stability reflexes. The results also confirm that halteres encode angular velocity of the body by detecting the Coriolis forces that result from the linear motion of the haltere within the rotating frame of reference of the fly's thorax. By rotating the flight arena at different orientations, it was possible to construct a complete directional tuning map of the haltere-mediated reflexes. The directional tuning of the reflex is quite linear such that the kinematic responses vary as simple trigonometric functions of stimulus orientation. The reflexes function primarily to stabilize pitch and yaw within the horizontal plane.
10.1098/rstb.1999.0442
others_402_16469
Eighteen indigenous plants are reported (with their Xhosa and English vernacular names) which are commonly used in the traditional medicine of the Transkei region of South Africa, for the treatment of digestive tract disorders. Most vegetative and reproductive parts of the plants are used for the preparations. In spite of western civilization the great majority of the people in Transkei still strongly believe in the efficacy of herbal medicin
others_402_16469
pubmed_556_11479
PURPOSE Analysis of elimination of four human radioresistant malignant cell lines to mono-energetic and non mono-energetic incoming carbon ion beams, characterized by different linear energy transfer (LET) qualities is performed. Comparisons with protons from the middle of the therapeutic spread out Bragg peak (SOBP) and reference γ-rays are also included. MATERIALS AND METHODS HTB140 cells were irradiated at five positions, with different LET, along the 62 MeV carbon pristine Bragg peak. To provide reliable reproducibility of irradiations at INFN-LNS, as the carbon Bragg peak is very narrow, precise positioning of samples for desired LET value is complicated. The peak was slightly widened using two ripple filters. After defining irradiation position and LET at the peak itself where cell killing is almost the highest, irradiation position with the same LET value was found within somewhat broadened peak. HTB140, MCF-7, HTB177 and CRL5876 cells were irradiated at the two described positions. Additionally, irradiations in the middle of 62 MeV proton SOBP and reference γ-rays were performed. Doses ranged from 0.5 to 16 Gy. Cell survival and corresponding radiobiological parameters were assessed seven days after irradiations. RESULTS When moving irradiation position along the carbon Bragg curve, LET rises from 85 to 747 keV/µm, while surviving fraction at 2 Gy (SF2) for HTB140 cells, falls from 0.72 to 0.57 further rising to 0.73 on the distal fall-off part of the curve. Improved cell radiosensitivity is seen for the doses below 4 Gy. Relative biological effectiveness (RBE) increases from 4.56 to 7.69 and drops to 4.23. Almost the highest cell killing LET, being ∼200 keV/µm, is used to irradiate HTB140, MCF-7, HTB177 and CRL5876 cells within the pristine and slightly broadened Bragg peak. After irradiations with protons of the mid SOBP, carbon ions of the pristine and slightly widened Bragg peak RBE ranges for HTB140 cells from 2.08, 4.81 to 7.06, for MCF-7 from 1.70, 3.28 to 4.17, for HTB177 from 1.98, 4.18 to 5.08 and for CRL5876 from 1.33, 2.57 to 3.51. CONCLUSIONS Significant elimination of HTB140 cells is observed along the carbon Bragg curve. The highest one is achieved by LET that is at the level of already reported. For the same LET, mono-energetic carbon ions provide higher cell elimination than the non mono-energetic. For all cell lines, both carbon ion beams, more the monoenergetic one, express stronger killing rate than protons and especially γ-rays.
10.1080/09553002.2020.1820609
pubmed_353_489
Intrathoracic schwannomas are solitary in general. We report a rare case of intrathoracic multiple schwannomas arising from a single intercostal nerve. A 27-year-old man was admitted with multiple tumors, along with the fourth intercostal nerve in the posterior chest wall. Thoracoscopic surgical exploration found a small tumor at 2 cm distal to the main tumors, which had not been detected preoperatively. All these tumors were completely resected en bloc and were diagnosed as schwannomas of the fourth intercostal nerve.
10.1016/j.athoracsur.2008.02.004
pubmed_862_1238
PURPOSE Ixabepilone, a semisynthetic analog of natural epothilone B, was developed for use in cancer treatment. This study extends previous findings regarding the efficacy of ixabepilone and its low susceptibility to tumor resistance mechanisms and describes the pharmacokinetics of this new antineoplastic agent. METHODS The cytotoxicity of ixabepilone was assessed in vitro in breast, lung, and colon tumor cell lines and in vivo in human xenografts in mice. Antitumor activities of ixabepilone and taxanes were compared in multidrug-resistant models in vivo. Differential drug uptake of ixabepilone and paclitaxel was assessed in a P-glycoprotein (P-gp)-resistant colon cancer model in vitro. The pharmacokinetic profile of ixabepilone was established in mice and humans. RESULTS Ixabepilone demonstrated potent cytotoxicity in a broad range of human cancer cell lines in vitro and in a wide range of xenografts in vivo. Ixabepilone was *3-fold more potent than docetaxel in the paclitaxel-resistant Pat-21 xenograft model (resistant due to overexpression of betaIII-tubulin and a lack of betaII-tubulin). Ixabepilone activity against P-gp-overexpressing breast and colon cancer was confirmed in in vivo models. Cellular uptake of ixabepilone, but not paclitaxel, was established in a P-gp-overexpressing model. The pharmacokinetics of ixabepilone was characterized by rapid tissue distribution and extensive tissue binding. CONCLUSIONS Cytotoxicity studies against a range of tumor types in vitro and in vivo demonstrate that ixabepilone has potent and broad-spectrum antineoplastic activity. This is accompanied by favorable pharmacokinetics. Ixabepilone has reduced susceptibility to resistance due to P-gp overexpression, tubulin mutations, and alterations in beta-tubulin isotype expression.
10.1007/s00280-008-0727-5
pubmed_922_23612
Objectives: To scrutinize the influence of HLA-B51 to each clinical manifestation of patients with Behçet's disease (BD) using a database of the Ministry of Health, Labour and Welfare of Japan.Methods: The database of newly registered patients with BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met International Criteria for Behçet's Disease (ICBD) and had data for HLA-B51 were selected and analyzed.Results: Among the 3044 analyzable cases, 1334 (43.8%) were men and 1710 (56.2%) were women; the median age was 38 years (IQR 29-48). HLA-B51 was positive for 1334 (44.5%). Prevalence of selected manifestations was 98.5% for oral ulceration, 85.5% for skin lesion, 42.1% for ocular lesion, 69.1% for genital ulceration, and 29.0% for gastrointestinal symptom. HLA-B51-positive patients had higher risk for ocular lesion (OR 1.59, 95%CI: 1.37-1.84; p < .001) and lower risk for genital ulceration (OR 0.72, 95%CI: 0.62-0.84; p < .001) and gastrointestinal symptom (OR 0.65, 95%CI: 0.55-0.77; p < .001). No significant difference was observed for other organ involvement; oral ulceration, skin lesion, positive pathergy test, arthritis, epididymitis, vascular lesion, or neurological manifestation. Subgroup analyses revealed that HLA-B51 was not related to genital ulceration in the cases with an ICBD score of 6 or higher and that HLA-B51 tended to more largely affect the risk of three manifestations for men compared to that for women.Conclusion: HLA-B51 positive is a risk factor for ocular lesion and vice versa for genital ulceration and gastrointestinal symptoms in patients with Japanese BD.
10.1080/14397595.2019.1649103
pubmed_516_24557
Efforts to understand and prevent intimate violence have often focused on the intergenerational transmission of intimate violence. Although witnessing and/or experiencing abuse in the family of origin is well supported in the literature as a key component of the intergenerational transmission of intimate violence, there has been less attention to other family-of-origin factors that contribute to or mediate and/or moderate future intimate violence. Particularly, a focus on the effect of parenting on future intimate violence is needed beyond the effect of modeling abusive behavior. In this article, corporal punishment and poor parenting are reviewed as family-of-origin factors related to future intimate violence. In addition, attachment theory, interpersonal skills, and emotional and behavioral regulation and/or conduct disorder are reviewed as variables that may result and mediate the relationship between family-of-origin factors and future intimate violence. Implications for preventing intimate violence by intervening in the family of origin are also identified.
10.1177/1524838006288932
pubmed_150_8010
This study reports on the 3-, 6-, 12-, and 18-month outcomes of 118 newly hired registered nurses (RNs) who completed a 12-month transition-to-practice program at a pediatric hospital. Experienced RNs (n = 42) and new graduate RNs (n = 76) showed improved organization, prioritization, communication, and leadership skills over time. The experienced RNs reported better communication and leadership skills than the new graduate nurses. Results inform transition program development for both new and experienced nurses.
10.1097/NND.0000000000000260
pubmed_159_13735
Hearing impairment is a major health and economic concern worldwide. Currently, the cochlear implant (CI) is the standard of care for remediation of severe to profound hearing loss, and in general, contemporary CIs are highly successful. But there is great variability in outcomes among individuals, especially in children, with many CI users deriving much less or even marginal benefit. Much of this variability is related to differences in auditory nerve survival, and there has been substantial interest in recent years in exploring potential therapies to improve survival of the cochlear spiral ganglion neurons (SGN) after deafness. Preclinical studies using osmotic pumps and other approaches in deafened animal models to deliver neurotrophic factors (NTs) directly to the cochlea have shown promising results, especially with Brain-Derived Neurotrophic Factor (BDNF). More recent studies have focused on the use of NT gene therapy to force expression of NTs by target cells within the cochlea. This could provide the means for a one-time treatment to promote long-term NT expression and improve neural survival after deafness. This review summarizes the evidence for the efficacy of exogenous NTs in preventing SGN degeneration after hearing loss and reviews the animal research to date suggesting that NT gene therapy can elicit long-term NT expression in the cochlea, resulting in significantly improved SGN and radial nerve fiber survival after deafness. In addition, we discuss NT gene therapy in other non-auditory applications and consider some of the remaining issues with regard to selecting optimal vectors, timing of treatment, and place/method of delivery, etc. that must be resolved prior to considering clinical application.
10.1016/j.heares.2020.107955
pubmed_257_13636
Cathepsin D activity was determined in alveolar macrophages (AM) and cell-free bronchoalveolar lavage fluid (BALF) from volunteers who were current cigarette smokers and compared with that found in lifetime nonsmokers. Enzyme activity was determined with a highly sensitive and specific substrate [D-Phe-Ser(0-CH2-C6H5)-Phe-Phe-Ala-Ala-pAB]. Specific activity was more than three times higher in AM from smokers than in cells from nonsmokers (37,880 +/- 2,090 versus 10,300 +/- 1,200; p less than 0.001) and approximately seven times higher in BALF from smokers than from nonsmokers (3,620 +/- 490 versus 515 +/- 165; p less than 0.001). This study demonstrated that cigarette smoke is a potent inducer of cathepsin D activity in AM in vivo. Because cathepsin D is capable of degrading a variety of proteins, the finding of high concentrations of the enzyme in AM and BALF from smokers, along with previous observations of elevated cathepsin B activity, suggests that lysosomal enzymes may cause or contribute to structural lung damage associated with cigarette smoking.
10.1164/ajrccm/140.4.958
pubmed_340_18521
beta-Mannosidosis is a lysosomal storage disorder caused by deficiency of beta-mannosidase. Thirteen families with cases of beta-mannosidosis have been described including one case previously reported by our group. We present clinical and biochemical data in a new adult case, and the molecular analyses in both this new case and the one previously reported. We detected four novel mutations: p.R182W, p.G392E, p.W466X and c.1848delA. Discrepancies between genomic DNA and cDNA results when detecting this last deletion suggested a nonsense-mediated decay cell process (NMD).
10.1016/j.ymgme.2006.07.001
pubmed_330_12312
By the method of co-culture and using cell density as the main indicator, this paper studied the allelopathic effect of Corallina pilulifera on Heterosigma akashiwo and its responses to UV-B irradiation. Under normal condition, the fresh tissue and aqueous extracts of C. pilulifera had significant inhibitory effects on the growth of H. akashiwo (P < 0.05), indicating their allopathic effect on H. akashiwo, while the dry power and culture media filtrate of C. pilulifera had less effect (P > 0.05). After pre-treated with different dose UV-B radiation and then co-cultured with H. akashiwo, C. pilulifera had some changes in the allelopathic activity of its fresh tissue, dry powder, and aqueous extracts. High-dose UV-B radiation (3.0 J x m(-2)) induced the decrease of the allelopathic effect, whereas low-dose UV-B radiation (0.9 J x m(-2)) was in adverse (P < 0.05).
pubmed_330_12312
pubmed_21_22675
BACKGROUND In Cameroonian traditional medicine various extracts of Gladiolus dalenii Van Geel (Iridaceae) have been used as a cure for various ailments that include headaches, digestive problems, muscle and joint aches, and some central nervous system disorders such as epilepsy, schizophrenia and mood disorders. Owning to this background, the aim of the study was to investigate whether an aqueous macerate of the bulb of Gladiolus dalenii has any antidepressant activity focusing specifically on depression-like behaviours associated with epilepsy. METHOD We used the combined administration of atropine and pilocarpine to rats as our animal model of epilepsy. The forced swim test and spontaneous locomotor activity in the open field test were the two tools used to assess the presence of depression-like behaviour in epileptic and control animals. The following depression-related parameters were determined: plasma ACTH, plasma corticosterone, adrenal gland weight and hippocampal levels of brain-derived neurotrophic factor (BDNF). The effects of Gladiolus dalenii were compared to that of fluoxetine. RESULTS Our results showed that we had a valid animal model of epilepsy-induced depression as all 3 measures of construct, predictive and face validity were satisfied. The data indicated that Gladiolus dalenii significantly reduced the immobility times in the forced swim test and the locomotor activity as assessed in the open field. A similar pattern was observed when the HPA axis parameters were analysed. Gladiolus dalenii significantly reduced the levels of ACTH, corticosterone, but not the adrenal gland weight. Gladiolus dalenii significantly increased the level of BDNF in the hippocampus. In all parameters measured the effects of Gladiolus dalenii were significantly greater than those of fluoxetine. CONCLUSION The results show that Gladiolus dalenii has antidepressant-like properties similar to those of fluoxetine in epilepsy-associated depressive states. The antidepressant activity of Gladiolus dalenii is likely to be mediated by restoring the activity of the HPA axis and increasing the levels of BDNF in the hippocampus.
10.1186/1472-6882-13-272
pubmed_182_12498
Type I interferon (IFN) production within the tumor microenvironment is important in shaping the immune response to the tumor. In this issue of Immunity, Marcus et al. (2018) reveal that tumor cells produce 2'3'-cGAMP, which activates the STING pathway in non-tumor cells and leads to type I IFN production and the priming of natural killer cells for tumor rejection.
10.1016/j.immuni.2018.10.001
pubmed_336_12690
BACKGROUND Mucoceles occur as a result of accumulation and retention of mucous secretions in a paranasal sinus and are uncommon in the pediatric age group. Persistent or intermittent closure of its ostium through a variety of causes, including previous surgery, is implicated in etiology. The authors report 2 cases of frontoethmoidal mucocele that followed box osteotomies for the treatment of orbital dystopia, with medical literature review and discussion of possible causal factors and events. METHODS Case histories and radiological imaging are presented on 2 patients presenting with frontoethmoidal mucoceles following craniofacial surgery. Both had transcranial craniofacial techniques where all orbital walls and globe are moved en bloc as a "box." RESULTS Patient 1, a 12-year-old male patient with Crouzon syndrome, developed mucoceles within 18 months of monobloc distraction surgery and box osteotomies. This was successfully marsupialized with a combined external and endoscopic surgical approach. The second patient, a 15-year-old boy with previously corrected right-sided facial cleft, developed mucocele 9 years following box osteotomies; this was successfully managed by endoscopic drainage. Of 3 other patients having similar box osteotomies in our unit, no other mucoceles were noted as complications. CONCLUSIONS Mucoceles are a rare complication of craniofacial surgery, and literature review confirms a paucity of reports. Only 1 case has previously been alluded to of mucocele complicating box osteotomy for orbital dystopia. Our 2 cases illustrate and highlight a successful management approach in a multidisciplinary craniofacial unit.
10.1097/SCS.0000000000000074
pubmed_680_4593
We aimed to evaluate the association between adipose tissue (AT) dysfunction, autoimmunity, and disease activity in rheumatoid arthritis (RA). A cross-sectional study including 150 RA patients and 50 healthy donors and longitudinal study with 122 RA patients treated with anti-tumor necrosis factor (TNF)-α, anti-interleukin 6 receptor (IL6R) or anti-CD20 therapies for 6 months were carried out. In vitro experiments with human AT and adipocyte and macrophage cell lines were performed. A collagen-induced arthritis mouse model was developed. The insulin resistance and the altered adipocytokine profile were associated with disease activity, the presence of anti-citrullinated proteins anti-bodies (ACPAs), and worse response to therapy in RA. AT in the context of arthritis is characterized by an inflammatory state alongside the infiltration of macrophages and B/plasmatic cells, where ACPAs can have a direct impact, inducing inflammation and insulin resistance in macrophages and promoting a defective adipocyte differentiation, partially restored by biologicals.
10.1016/j.isci.2022.104893
pubmed_847_12800
Covalent protein kinase inhibitors exploit currently noncatalytic cysteines in the adenosine 5'-triphosphate (ATP)-binding site via electrophiles directly appended to a reversible-inhibitor scaffold. Here, we delineate a path to target solvent-exposed cysteines at a distance >10 Å from an ATP-site-directed core module and produce potent covalent phosphoinositide 3-kinase α (PI3Kα) inhibitors. First, reactive warheads are used to reach out to Cys862 on PI3Kα, and second, enones are replaced with druglike warheads while linkers are optimized. The systematic investigation of intrinsic warhead reactivity (kchem), rate of covalent bond formation and proximity (kinact and reaction space volume Vr), and integration of structure data, kinetic and structural modeling, led to the guided identification of high-quality, covalent chemical probes. A novel stochastic approach provided direct access to the calculation of overall reaction rates as a function of kchem, kinact, Ki, and Vr, which was validated with compounds with varied linker lengths. X-ray crystallography, protein mass spectrometry (MS), and NanoBRET assays confirmed covalent bond formation of the acrylamide warhead and Cys862. In rat liver microsomes, compounds 19 and 22 outperformed the rapidly metabolized CNX-1351, the only known PI3Kα irreversible inhibitor. Washout experiments in cancer cell lines with mutated, constitutively activated PI3Kα showed a long-lasting inhibition of PI3Kα. In SKOV3 cells, compounds 19 and 22 revealed PI3Kβ-dependent signaling, which was sensitive to TGX221. Compounds 19 and 22 thus qualify as specific chemical probes to explore PI3Kα-selective signaling branches. The proposed approach is generally suited to develop covalent tools targeting distal, unexplored Cys residues in biologically active enzymes.
10.1021/jacs.1c13568
pubmed_877_10918
Label-free separation of viable cancer cells using vortical microfluidic flows has been introduced as a feasible cell collection method in oncological studies. Besides the clinical importance, the physics of particle interactions with the vortex that forms in a wall-confined geometry of a microchannel is a relatively new area of fluid dynamics. In our previous work [Haddadi and Di Carlo, J. Fluid. Mech. 811, 436-467 (2017)], we have introduced distinct aspects of inertial flow of dilute suspensions over cavities in a microchannel such as breakdown of the separatrix and formation of stable limit cycle orbits for finite size polystyrene particles. In this work, we extend our experiments to address the engineering-physics of cancer cell entrapment in microfluidic cavities. We begin by studying the effects of the channel width and device height on the morphology of the vortex, which has not been discussed in our previous work. The stable limit cycle orbits of finite size cancer cells are then presented. We demonstrate effects of the separatrix breakdown and the limit cycle formation on the operation of the cancer cell separation platform. By studying the flow of dilute cell suspensions over the cavities, we further develop the notion of the cavity capacity and the relative rate of cell accumulation as optimization criteria which connect the device geometry with the flow. Finally, we discuss the proper placement of multiple cavities inside a microchannel for improved cell entrapment.
10.1063/1.5009037
pubmed_660_8523
PURPOSE We evaluated the ability of diffusion-weighted imaging (DWI) at 3 tesla for diagnosing T stage and detecting stalks in bladder cancer. METHODS In total, 39 consecutive patients with bladder tumors underwent magnetic resonance (MR) imaging that included T2-weighted imaging (T2WI) and DWI using a 3T MR scanner. Two radiologists interpreted T2WI plus DWI and T2WI for diagnosis of T stage and for detection of stalks. We used McNemar's test to examine differences in diagnostic performance and Fisher's exact test to evaluate differences in stalk detection frequency. RESULTS Specificity and accuracy in differentiating T1 tumors from T2 to T4 tumors were significantly better with T2WI plus DWI (83% [20/24] and 85% [33/39]) than T2WI (50% [12/24] and 67% [26/39]; P = 0.02), and accuracy for diagnosing tumor stage was significantly better with T2WI plus DWI (82% [32/39]) than T2WI alone (59% [23/39]; P = 0.03). The observers identified stalks in 11 tumors by T2WI (48% [11/23]) and 17 by DWI (74% [17/23]) (P < 0.03). CONCLUSION DWI at 3T was superior to T2WI for evaluating the T stage of bladder cancer, particularly in differentiating T1 tumors from those T2 or higher, and in detecting stalks of papillary bladder tumors.
10.2463/mrms.2013-0104
pubmed_603_18344
AtNUDT7 was reported to be a negative regulator of EDS1-mediated immunity in Arabidopsis. However, the underlying molecular and genetic mechanism of the AtNUDT7-regulated defense pathway remains elusive. Here we report that AtNUDT7 and its closest paralog AtNUDT6 function as novel negative regulators of SNC1, a TIR-NB-LRR-type R gene. SNC1 is upregulated at transcriptional and possibly post-transcriptional levels in nudt6-2 nudt7. The nudt6-2 nudt7 double mutant exhibits autoimmune phenotypes that are modulated by temperature and fully dependent on EDS1. The nudt6-2 nudt7 mutation causes EDS1 nuclear accumulation shortly after the establishment of autoimmunity caused by the temperature shift. We found that a low ammonium/nitrate ratio in growth media leads to a higher level of nitrite-dependent nitric oxide (NO) production in nudt6-2 nudt7, and NO acts in a positive feedback loop with EDS1 to promote the autoimmunity. The low ammonium/nitrate ratio also enhances autoimmunity in snc1-1 and cpr1, two other autoimmune mutants in Arabidopsis. Our study indicates that Arabidopsis senses the ammonium/nitrate ratio as an input signal to determine the amplitude of the EDS1-mediated defense response, probably through the modulation of NO production.
10.1111/tpj.12032
pubmed_614_10374
Central mucoepidermoid carcinomas (MECs) are extremely rare tumors, comprising 2-3% of all MECs reported in the literature. We report a rare case of clear cell variant of central MEC with calcifications occurring in the left posterior mandible in a 37-year-old male patient.
10.4103/0973-1482.138038
pubmed_837_5962
Normal human neutrophils triggered by precipitating immune complexes (IC), soluble IC (sIC) or heat-aggregated IgG (HAIgG) displayed low levels of cytotoxicity towards nonsensitized target cells. Catalase, but not heated catalase, completely impaired this nonspecific cytotoxicity (NSC), suggesting a key role for hydrogen peroxide (H2O2) in the lysis of target cells. Superoxide dismutase (SOD) and certain HO. and 1O2 scavengers were unable to exert significant effects. Three haem-enzyme inhibitors, sodium azide, sodium cyanide and 3-amino-1,2,4-triazole did not decrease neutrophil NSC, but markedly enhanced it. This data suggest that the mechanism involved was not dependent upon myeloperoxidase (MPO). The analysis of neutrophil-mediated ADCC indicates that oxygen-dependent but MPO-independent mechanisms appeared to be operative in this system. It was also found that the microfilament disrupting agents, cytochalasin B (CB) and dihydrocytochalasin B (dhCB), as well as the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), significantly enhanced NSC. In contrast, these compounds partially inhibited ADCC. This cytotoxic system provides a suitable model to study events that may occur during the course of immune complex diseases and also permits the evaluation of alternative lytic mechanisms triggered through neutrophil Fc gamma receptors.
pubmed_837_5962
pubmed_616_3945
Genetic association studies of the human genome often omit the X chromosome because of the unique analytical challenges it presents. A concerted effort to undo this exclusion could offer medically relevant insights into basic biology that might otherwise be missed.
10.1038/nm.4445
others_218_8037
Herein, we report a male patient underwent a video-assisted thoracoscopic resection of left lower lobe intralobar bronchopulmonary sequestration that developed unilateral postobstructive pulmonary edema following double-lumen endobronchial tube intubation. Pulmonary edema subsided after receiving positive pressure ventilation at positive end-expiratory pressure of 5 cm H2O and the patient was extubated 24 h later. To prevent this complication, correct placement of the tube should be assessed by auscultation during intermittent ventilation of each lung and fiberoptic bronchoscope should always be performed through both tracheal and bronchial lumens after intubation. © 2008 Elsevier Ltd. All rights reser
10.1016/j.rmedc.2007.12.003
pubmed_166_23811
Neuroendocrine tumours (NET) are clinically challenging due to their unpredictable behaviour. Nomograms, grading and staging systems are predictive tools with multiple roles in clinical practice, including patient prognostication. The NET nomogram allocates scores for various clinicopathological parameters, calculating percentage estimates for 5- and 10-year disease-specific survival of patients with small bowel (SB) NET. We evaluated the clinical utility of three prognostic systems in 70 SB NET patients: the NET nomogram, the World Health Organisation (WHO)/European Neuroendocrine Tumour Society (ENETS) grading system and the American Joint Commission on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) TNM staging method. Using Kaplan-Meier methodology, neither the WHO/ENETS grade (P = 0.6) nor the AJCC/UICC stage (P = 0.276) systems demonstrated significant differences in patient survival in the cohort. The NET nomogram was well calibrated to our data set, displaying favourable prediction accuracy. Harrel's C-index for the nomogram (a measure of predictive power) was 0.65, suggesting good prediction ability. On Kaplan-Meier analyses, there were significant differences in patient survival when stratified into nomogram score-based risk groups: low-, medium- and high-risk tumours were associated with median estimated survivals of 156, 129 and 112 months, respectively (P = 0.031). Our data suggest that a multivariable analysis-based NET nomogram may be clinically useful for patient survival prediction. This study identifies the limitations of the NET nomogram and the imperfections of other currently used single or binary parameter methodologies for assessing neuroendocrine disease prognosis. The future addition of other variables to the NET nomogram will likely amplify the accuracy of this personalised tool.
10.1530/EC-16-0114
pubmed_398_20244
There are two kinds of the acoustic microscope, the one is the Scanning Laser Acoustic Microscope, SLAM and the other the Mechanical Scanned Acoustic Microscope, SAM. In the acoustic microscope, high frequency ultrasound of 100 MHZ to 500 MHZ was used and the resolving power was in the range of 5 to 10 microns. The propagating speed and attenuation of ultrasound from the C-mode image which was obtained by mechanically scan with laser or ultrasound. From the results of the experiments by using the SAM to analyze acoustic characteristics of the tissue specimens which were taken from the patients with cardiac sarcoidosis, HCM, DCM, gastric and kidney cancer, clinical significances and usefulness of the evaluation for physical characteristics of the tissue were discussed in this paper.
pubmed_398_20244
pubmed_747_11042
The StaT4 test is a technically simple test of thyroxine measurement, which apparently gives results in good agreement with those derived by radioimmunoassay in most patients. In pregnancy, however, falsely low serum thyroxine values were found with the StaT4 test when compared with either a radioimmunoassay or the Thyopac-4 test. Detailed studies showed that the discrepancy resulted from the extraction technique used in the StaT4 test, which appears to allow the patient's thyroxine binding proteins to remain in the assay system. Similar method discrepancies were observed in other clinical conditions associated with elevated thyroxine binding globulin concentration. This study, as well as being of practical clinical importance, has implications for the design of competitive protein binding tests of thyroid function.
10.1177/000456327801500145
pubmed_175_6403
The Al-Mg-MnO2 composite is a MnO2 particulate reinforced Al metal matrix composite. Its substantial ductility makes it promising composite for study. The Al-3Mg-MnO2 and Al-8Mg-MnO2 composites were synthesized by stirring 3, 5, and 8 wt% of MnO2 particulates in Al-3Mg melt and Al-8Mg melt to study their mechanical properties. Their microstructure shows intermetallic precipitates of Al, Mg, and Mn at dendrites, grain boundaries and within the grains. In both sets of composites, the hardness, and the yield strength increases with increasing MnO2 content in the cast and forged composites. Both the groups of composites show an increase in tensile strength with increasing particle content from 3 to 5 wt%, a further increase in particle content to 8 wt%, leads to an abrupt decrease in tensile strength in both the group of composites. The percentage elongations in forged composites are lower than those in cast composites, but this decrease is more prominent in Al-8Mg-MnO2 composites in comparison to Al-3Mg-MnO2 composites. The J value decreases as the percentage of MnO2 particles increases in Al-3Mg-MnO2 and Al-8Mg-MnO2 composites. Forging increases J values in both the class of composites in comparison to their cast counterparts due to work hardening and healing of pores. Crack growth toughness also decreases as the MnO2 particle content increases in Al-3Mg-MnO2 and Al-8Mg-MnO2 composites. Forged Al-3Mg-MnO2 shows decreased T/E ratio in comparison to their cast counterparts except at 8wt%. However, forged Al-8Mg-MnO2 shows improved T/E at 3wt% and a drop at 5wt% and 8wt% MnO2. Variation of crack growth toughness between cast and forged Al-8Mg-MnO2 is minimal in comparison to that between cast and forged Al-3Mg-MnO2 composites.
10.1016/j.heliyon.2020.e03275
pubmed_565_7696
BACKGROUND In the general HIV-infected population, there are few data on the prevalence and risk factors for anal condyloma, precursor lesions for anal cancer. METHODS Screening for perianal and endoanal condyloma with an anoscopy was systematically proposed to 516 consecutive outpatients, followed in a university hospital in Paris. For each point, HIV characteristics and sexual behaviors assessed through semi-directive questionnaire were collected. FINDINGS The 473 (92%) examined patients, consisted of 200 homosexual men, 123 heterosexual men, 150 women; 76% were receiving HAART, HIV-RNA was<50 copies/ml in 60%, mean (+/-SD) CD4 cell count were 484 (+/-274)/mm(3). Overall, 108 (23%) pts had histologically-confirmed anal condyloma (36, 15 and 11% of the respective populations), including 51 (47%) pts with only endoanal localisation. Intraepithelial neoplasia of grade I was noted in 59 patients, of grade II in 10 and of grade III in 2 and an invasive endoanal cancer in 1. In multivariate regression analysis, condyloma independent risk factor were history of gonococcia or syphilis (OR=0.54 (0.29-0.99)), and history of previous anal condyloma (OR=2.05 (1.07-3.92) in homosexual men, history of previous penis condyloma (OR=26.8 (2.3-309.6), and unprotected sexual intercourse (OR=7.5 (2.1-26.3)) in heterosexual men and CD4 cell count below 200/mm(3), (OR=8.9 (1.5-51.6)), receptive anal intercourse (OR=6.7 (1.7-25.8)) and history of previous anal condyloma (OR=25.4 (3.4-188.2)) in women. INTERPRETATION In the HAART era, systematic screening revealed a high rate of anal condyloma in all HIV positive pts (not only in homosexual men). Anal examination should be proposed systematically to all HIV-infected patients.
10.1016/j.medmal.2005.02.013
pubmed_613_20965
BACKGROUND This study aims to establish a stable chronic rejection model for orthotopic liver transplantation in the rat and to describe the pathological features of this model. METHODS The livers from different strains of rats were transplanted in various allogeneic donor-recipient combinations with appropriate syngeneic grafts used as controls. The rats were untreated after surgery (acute rejection model) or treated with cyclosporin A (1 mg/kg) and hydrocortisone (0.75 mg/kg) to establish chronic rejection as determined by rejection activity index scores from pathological examination of liver specimens. RESULTS Acute rejection occurred in all of the untreated recipients of allogeneic orthotopic liver transplants, and all died within 30 days. Among the treated recipients, the combinations of Lewis with brown Norway and dark agouti with Lewis rats developed acute rejection, and no changes characteristic of chronic rejection were observed in the few rats that survived beyond 30 days. In contrast, the treated Lewis recipients of livers from Sprague-Dawley rats exhibited chronic rejection in the liver specimens. CONCLUSION We have established an animal model for chronic rejection after transplantation of livers from Sprague-Dawley to Lewis rats under short-term immunosuppression induced by small doses of cyclosporin A and hydrocortisone.
10.1159/000322856
pubmed_28_13707
Micro-organisms have long been implicated in the construction of stromatolites. Yet, establishing a microbial role in modern stromatolite growth via molecular analysis is not always straightforward because DNA in stromatolites can have multiple origins. For example, the genomic material could represent the microbes responsible for the construction of the stromatolite (i.e., "builders"), microbes that inhabited the structure after it was built (i.e., "tenants"), or microbes/organic matter that were passively incorporated after construction from the water column or later diagenetic fluids (i.e., "squatters"). Disentangling the role of micro-organisms in stromatolite construction, already difficult in modern systems, becomes more difficult as organic signatures degrade, and their context is obscured. To evaluate our ability to accurately decipher the role of micro-organisms in stromatolite formation in geologically recent settings, 16/18S SSU rRNA gene sequences were analyzed from three systems where the context of growth was well understood: (a) an actively growing stromatolite from a silicic hot spring in Yellowstone National Park, Wyoming, where the construction of the structure is controlled by cyanobacteria; (b) a mixed carbonate and silica precipitate from Little Hot Creek, a hot spring in the Long Valley Caldera of California that has both abiogenic and biogenic components to accretion; and (c) a near-modern lacustrine carbonate stromatolite from Walker Lake, Nevada that is likely abiogenic. In all cases, the largest percentage of recovered DNA sequences, especially when focused on the deeper portions of the structures, belonged to either the tenant or squatter communities, not the actual builders. Once removed from their environmental context, correct interpretation of biology's role in stromatolite morphogenesis was difficult. Because high-throughput genomic analysis may easily lead to incorrect assumptions even in these modern and near-modern structures, caution must be exercised when interpreting micro-organismal involvement in the construction of accretionary structures throughout the rock record.
10.1111/gbi.12429
pubmed_263_7928
Given the significant land holdings of the U.S. Department of Defense, and the importance of those lands to support a variety of inherently damaging activities, application of sound natural resource conservation principles and proactive monitoring practices are necessary to manage military training lands in a sustainable manner. This study explores a method for, and the utility of, analyzing vegetation condition and trends as sustainability indicators for use by military commanders and land managers, at both the national and local levels, in identifying when and where vegetation-related environmental impacts might exist. The BFAST time series decomposition method was applied to a ten-year MODIS NDVI time series dataset for the Fort Riley military installation and Konza Prairie Biological Station (KPBS) in northeastern Kansas. Imagery selected for time-series analysis were 16-day MODIS NDVI (MOD13Q1 Collection 5) composites capable of characterizing vegetation change induced by human activities and climate variability. Three indicators related to gradual interannual or abrupt intraannual vegetation change for each pixel were calculated from the trend component resulting from the BFAST decomposition. Assessment of gradual interannual NDVI trends showed the majority of Fort Riley experienced browning between 2001 and 2010. This result is supported by validation using high spatial resolution imagery. The observed versus expected frequency of linear trends detected at Fort Riley and KPBS were significantly different and suggest a causal link between military training activities and/or land management practices. While both sites were similar with regards to overall disturbance frequency and the relative spatial extents of monotonic or interrupted trends, vegetation trajectories after disturbance were significantly different. This suggests that the type and magnitude of disturbances characteristic of each location result in distinct post-disturbance vegetation responses. Using a remotely-sensed vegetation index time series with BFAST and the indicators outlined here provides a consistent and relatively rapid assessment of military training lands with applicability outside of grassland biomes. Characterizing overall trends and disturbance responses of vegetation can promote sustainable use of military lands and assist land managers in targeting specific areas for various rehabilitation activities.
10.1016/j.jenvman.2014.08.002
pubmed_580_2059
The quantity of circulating reticulocytes is an important indicator of erythropoietic activity in response to a wide range of haematological pathologies. While most modern laboratories use flow cytometry to quantify reticulocytes, most field laboratories still rely on 'subvital' staining. The specialist 'subvital' stains, New Methylene Blue (NMB) and Brilliant Crésyl Blue are often difficult to procure, toxic, and show inconsistencies between batches. Here we demonstrate the utility of Giemsa's stain (commonly used microbiology and parasitology) in a 'subvital' manner to provide an accurate method to visualize and count reticulocytes in blood samples from normal and malaria-infected individuals.
10.1371/journal.pone.0060303
pubmed_875_6007
For spintronic devices excited by a sudden magnetic or optical perturbation, the torque acting on the magnetization plays a key role in its precession and damping. However, the torque itself can be a dynamical quantity via the time-dependent anisotropies of the system. A challenging problem for applications is then to disentangle the relative importance of various sources of anisotropies in the dynamical torque, such as the dipolar field, the crystal structure or the shape of the particular interacting magnetic nanostructures. Here, we take advantage of a range of colloidal cobalt ferrite nanocubes assembled in 2D thin films under controlled magnetic fields to demonstrate that the phase, ϕPrec, of the precession carries a strong signature of the dynamical anisotropies. Performing femtosecond magneto-optics, we show that ϕPrec displays a π-shift for a particular angle θH of an external static magnetic field, H. θH is controlled with the cobalt concentration, the laser intensity, as well as the interparticle interactions. Importantly, it is shown that the shape anisotropy, which strongly departs from those of equivalent bulk thin films or individual noninteracting nanoparticles, reveals the essential role played by the interparticle collective effects. This work shows the reliability of a noninvasive optical approach to characterize the dynamical torque in high density magnetic recording media made of organized and interacting nanoparticles.
10.1021/acs.nanolett.6b02618
pubmed_84_404
Enzymatically genierated superoxide radical. by reactitng with hydrogen peroxide to prduce the hydroxyl radical, depolymerized puirified hyaluronic acid and bovine synovial flulid. Since phagocytizing polymorphonuclear leukocytes produce superoxide radicals, this reac-tion is sutggested and shown to be quantitatively feasible as the ini vivo mechanism of synovial fluid degradation in anl inflamed joint. Superoxide dismutase, and catalase protect synaovial fluid against such degradation in vitro.
10.1126/science.185.4150.529
pubmed_381_9276
The nontuberculous mycobacterial pulmonary disease (NTM-PD) caused by Mycobacterium species has increased in prevalence all over the world. The distributions of NTM-PD are possibly determined by the westerly wind traveling at high altitudes over East Asia. However, the long-range transport of Mycobacterium species has not been demonstrated by analyzing the bacterial communities in aerosols such as desert mineral particles and anthropogenic pollutants transported by the westerly wind. Here, airborne bacterial compositions were investigated including Mycobacterium species in high-elevation aerosols, which were captured in the snow cover at 2,450 m altitude on Mt. Tateyama. This was further compared to the ground-level or high-altitude aerosols collected at six sampling sites distributed from Asian-dust source region (Tsogt-Ovoo) to downwind areas in East Asia (Asian continental cities; Erenhot, Beijing, Yongin, Japanese cities; Yonago, Suzu, Noto Peninsula). The cell concentrations and taxonomic diversities of airborne bacteria decreased from the Asian continent to the Japan area. Terrestrial bacterial populations belonging to Firmicutes and Actinobacteria showed higher relative abundance at high-elevation and Japanese cities. Additionally, Mycobacterium species captured in the snow cover on Mt. Tateyama increased in relative abundance in correspondence to the increase of black carbon concentrations. The relative abundance of Mycobacterium sequences was higher in the aerosol samples of Asian continental cities and Japanese cities than in the desert area. Presumably, anthropogenic pollution over East Asia carries potential Mycobacterium species, which induce NTM-PD, thereby impacting upon the public health.
10.1016/j.envint.2022.107471
pubmed_281_9225
Ammonia-oxidising archaea (AOA) are a ubiquitous component of microbial communities and dominate the first stage of nitrification in some soils. While we are beginning to understand soil virus dynamics, we have no knowledge of the composition or activity of those infecting nitrifiers or their potential to influence processes. This study aimed to characterise viruses having infected autotrophic AOA in two nitrifying soils of contrasting pH by following transfer of assimilated CO2-derived 13C from host to virus via DNA stable-isotope probing and metagenomic analysis. Incorporation of 13C into low GC mol% AOA and virus genomes increased DNA buoyant density in CsCl gradients but resulted in co-migration with dominant non-enriched high GC mol% genomes, reducing sequencing depth and contig assembly. We therefore developed a hybrid approach where AOA and virus genomes were assembled from low buoyant density DNA with subsequent mapping of 13C isotopically enriched high buoyant density DNA reads to identify activity of AOA. Metagenome-assembled genomes were different between the two soils and represented a broad diversity of active populations. Sixty-four AOA-infecting viral operational taxonomic units (vOTUs) were identified with no clear relatedness to previously characterised prokaryote viruses. These vOTUs were also distinct between soils, with 42% enriched in 13C derived from hosts. The majority were predicted as capable of lysogeny and auxiliary metabolic genes included an AOA-specific multicopper oxidase suggesting infection may augment copper uptake essential for central metabolic functioning. These findings indicate virus infection of AOA may be a frequent process during nitrification with potential to influence host physiology and activity.
10.1038/s41396-022-01341-5
pubmed_946_10825
The coexistence of renal artery stenosis and pheochromocytoma has been recognized since 1958 and a total of 36 patients reported. This article provides an additional patient with an extra adrenal pheochromocytoma and fibrous bands constricting the left renal artery. Hypertension was confirmed to occur from both excess catecholamine production and hyperreninemia from the left kidney. Surgical removal of the functioning paraganglioma and correction of the renal artery stenosis restored the postoperative plasma catecholamine, renin, and blood pressure to normal. A literature review confirmed the coexistence of these two lesions but failed to provide a common etiology to explain the pathophysiology encountered. However, when the two diseases occur simultaneously, both must be diagnosed accurately and treated in a definitive manner.
10.1097/00000658-198304000-00019
pubmed_65_17321
Twenty-four male patients with myocardial infarction (MI) without clinical and electrocardiographic signs of right ventricular (RV) involvement were selected to enter the study. All the patients were divided into two groups: Group I consisted of 12 patients with anterior MI and infarct-related left anterior descending artery and Group II included 12 patients with inferior MI and infarct-related right coronary artery. Patients of Group II had higher right atrial pressure and right atrial pressure/pulmonary capillary wedge pressure ratio (p<0.01, p<0.01) and lower values of pulmonary flow velocity, mean acceleration, and pulmonary flow velocity2/acceleration time ratio than patients of Group I (p<0.01, p<0.01, p<0.01, respectively). Pulmonary flow indices correlated inversely and significantly with hemodynamic dysfunction in patients with inferior myocardial infarction and right coronary proximal lesions (p<0.01).
10.1177/000331979905001004
others_300_15285
Filtration of haemolymph in insects to remove waste products is performed by nephrocytes, which comprise accessory cells of the circulatory system that are not connected to Malpighian tubules. There are two types of nephrocytes in Drosophila: ventral cells, situated around the junction between the cardia and the oesophagus, and pericardial cells, situated around the heart. In the present study, the expression of dopamine D1 (DopR) and D2-like (DD2R) receptors in the ventral nephrocytes of Drosophila melanogaster Meigen (Diptera: Drosophilidae) is investigated. Immunohistochemical staining with polyclonal antibodies against DopR and DD2R demonstrates the presence of these receptors in adult nephrocytes. The functioning of D. melanogaster nephrocytes is investigated by evaluation of mortality rates in flies treated with silver nitrate (AgNO3) compared with untreated controls. To determine whether a change in the level of dopamine receptors has an effect on the functioning of nephrocytes, the antisense suppressor of DD2R gene together with a nephrocyte-specific driver is used in the UAS-GAL4 system. The suppression of DD2R in nephrocytes results in a significant decrease of mortality under toxic conditions. Taken together, the data obtained in the present study indicate that dopamine takes part in the control of ventral nephrocyte functioning in D. melanogaster. © 2013 The Royal Entomological Society
10.1111/phen.12044
pubmed_773_3238
Fifteen red cell enzyme activities of growth-retarded patients with and without growth hormone (GH) deficiency were investigated before and after GH administration. The 15 enzymes were Hexokinase, phosphoglucomutase, glucose phosphate, isomerase, phosphofructokinase, fructose diphosphate aldolase, glyceraldehyde-3-phosphae dehydrogenase, triosephosphate isomerase, 2,3-diphosphoglycerate mutase, 3-phosphoglycerate kinase, 3-phosphoglycerate mutase, enolase, pyruvate kinase, glycose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, glutathione reducase. Sixty-six subjects were studied: 30 normal control subjects (group N) and 36 patients (aged 5-23 years) with short stature. Complete endocrine evaluation showed 21 (group I) to have GH deficiency (10 patients with isolated GH deficiency) and 15 (group II) to have normal hypothalamic and pituitary function except for two patients with a moderate hypothyroidism. Both had been receiving thyroid hormone treatment for a long time before our studies. All 36 patients were treated with 2 mg human growth hormone intramuscularly for 7 days. Before GH treatment no significant difference was observed between hematologic data in group I (GH deficiency) and group II (no GH deficiency). After GH therapy there was a significant increase in reticulocyte count in both groups of patients with short stature. The mean pretreatment value in group I was 1.294% +/- 0.084 (SEM); the mean post-treatment value was 2.081% +/- 0.287 (SEM)< P less than 0.005. The mean pretreatment value in group II was 1.0% 0.184 (SEM); the mean post-treatment value was 1.407% +/- 0.193 (SEM), P less than 0.01. In group II (no GH deficiency) mean pretreatment erythrocyte enzyme activities were not significantly different from those activities observed in normal control subjects (group N). However, in patients who lacked GH, the pretreatment activities of five red cell enzymes (glucose phosphate isomerase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, 2,3-diphosphoglycerate mutase, 3-phosphoglycerate kinase) were significantly decreased before GH administration compared with the values in normal control subjects...
10.1203/00006450-197609000-00008
pubmed_1090_17720
Findings of this paper indicate that leucocyte copper has a significant link with the level of atherosclerosis found within the groups studied. Therefore copper may be involved in the mechanisms associated with ischaemic heart disease (IHD).
10.1042/bst0181186
pubmed_1095_25
BACKGROUND The effects of long-term environmental management on airway obstruction and inflammation in horses with recurrent airway obstruction (RAO) are unknown. HYPOTHESIS Horses with RAO maintained in low-dust environments have persistent airway obstruction and neutrophilic inflammation. ANIMALS Study horses were treated for RAO and then maintained in low-dust environments with no medical management. Horses were classified into 3 groups by years after diagnosis: 1 year (time 1, n = 9), 2-3 years (time 2, n = 7), and 5-6 years (time 3, n = 8). The comparison groups were age-matched healthy horses. METHODS In this cross-sectional study, a clinical examination was performed, and the clinical score was calculated. Standard lung function, forced expiratory maneuvers, and the cytology of bronchoalveolar lavage fluid (BALF) were evaluated. RESULTS The clinical scores of the RAO horses were higher than those of the non-RAO horses at time 2 (P = .018). Standard lung function data were not different between the groups at any time point. The forced expiratory flow between 75-95% of exhaled vital capacity was lower in RAO horses than in non-RAO horses at all time points (P < .02), indicating persistent peripheral airway obstruction. Cytologic evaluation of BALF revealed no difference in total nucleated cell numbers or differential cell counts between RAO and non-RAO horses at any time point. CONCLUSIONS AND CLINICAL IMPORTANCE The peripheral airway obstruction detected in horses with RAO maintained in low-dust environments likely is due to irreversible airway remodeling but is not associated with cytologic evidence of airway inflammation.
10.1892/0891-6640(2007)21[1060:lfaacp]2.0.co;2
pubmed_781_1267
BACKGROUND CONTEXT Various modifications to standard "rigid" anterior cervical plate designs (constrained plate) have been developed that allow for some degree of axial translation and/or rotation of the plate (semi-constrained plate)-theoretically promoting proper load sharing with the graft and improved fusion rates. However, previous studies about rigid and dynamic plates have not examined the influence of simulated muscle loading. PURPOSE The objective of this study was to compare rigid, translating, and rotating plates for single-level corpectomy procedures using a robot testing system with follower load. STUDY DESIGN In-vitro biomechanical test. METHODS N = 15 fresh-frozen human (C3-7) cervical specimens were biomechanically tested. The follower load was applied to the specimens at the neutral position from 0 to 100 N. Specimens were randomized into a rigid plate group, a translating plate group and a rotating plate group and then tested in flexion, extension, lateral bending and axial rotation to a pure moment target of 2.0 Nm under 100N of follower load. Range of motion, load sharing, and adjacent level effects were analyzed using a repeated measures analysis of variance (ANOVA). RESULTS No significant differences were observed between the translating plate and the rigid plate on load sharing at neutral position and C4-6 ROM, but the translating plate was able to maintain load through the graft at a desired level during flexion. The rotating plate shared less load than rigid and translating plates in the neutral position, but cannot maintain the graft load during flexion. CONCLUSIONS This study demonstrated that, in the presence of simulated muscle loading (follower load), the translating plate demonstrated superior performance for load sharing compared to the rigid and rotating plates.
10.1007/s00586-015-4203-8
pubmed_58_1800
Plant cellulose fibers of width and length ∼0.03 mm and ∼3 mm, respectively, can be completely converted to individual cellulose nanofibers of width and length ∼3 nm and ∼1 µm, respectively, by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation under aqueous conditions and subsequent gentle mechanical disintegration of the oxidized cellulose in water. The obtained TEMPO-oxidized cellulose nanofibers (TOCNs) are new bio-based, crystalline nanomaterials with applications in the high-tech and commodity product industries. Sodium carboxylate groups, which are densely, regularly, and position-selectively present on the crystalline TOCN surfaces, can be efficiently ion-exchanged with other metal and alkylammonium carboxylate groups in water to control the biodegradable/stable and hydrophilic/hydrophobic properties of the TOCNs. TOCNs are therefore promising nanomaterials that can be prepared from the abundant wood biomass resources present in Japan. Increased production and use of TOCNs would stimulate a new material stream from forestry to industries, helping to establish a sustainable society based on wood biomass resources.
10.2183/pjab.94.012
pubmed_53_1
Routine immunization against virus influenza is not recommended at this time because of the appearance of new strains not included in present-day vaccines. As more strains of the virus are included in this vaccine, its efficiency is being improved. Vaccination of adults and children is discussed. Final judgment must await further laboratory and clinical investigation.
pubmed_53_1
pubmed_179_7139
BACKGROUND Research productivity forms a vital part of the resident selection process and can markedly affect the chance of a successful match. Current reports regarding the publication record among prospective orthopaedic surgery residents are likely inaccurate. Potential applicants have a poor understanding of the strength of their research credentials in comparison to other candidates. METHODS We identified matched applicants from the 2013 to 2017 orthopaedic surgery residency application cycles. We performed a bibliometric analysis of these residents using Scopus, PubMed, and Google Scholar to identify published articles and calculate the h-index of each applicant at the time of application. Details were collected on medical school, advanced degrees, publication type, first authorship, and article relatedness to orthopaedic surgery. RESULTS We included 3,199 matched orthopaedic surgery applicants. At the time of application, the median h-index was 0, the median number of publications was 1, and 40% of successful candidates did not hold any publications. The h-index (R 0.08, P < 0.0001) and median number of publications of matched orthopaedic surgery residency candidates significantly increased (R 0.09, P < 0.0001) across application cycles. Furthermore, the proportion of matched applicants without publications at the time of application significantly decreased (R -0.90, P = 0.0350). Conversely, the percentage of articles first-authored by applicants decreased (R -0.96, P = 0.0093), but article relatedness to orthopaedic surgery remained constant (R 0.82, P = 0.0905). Strikingly, notable changes were observed in the type of articles published by successful applicants: the proportion of preclinical studies decreased (R -0.07, P = 0.0041), whereas clinical research articles increased (R 0.07, P = 0.0024). CONCLUSION The publication count held by successful orthopaedic surgery applicants is substantially lower than the nationally reported average. Matched orthopaedic surgery candidates demonstrate increasingly impressive research achievements each application cycle. However, increased academic productivity comes at the cost of reduced project responsibility and a shift toward faster-to-publish articles.
10.5435/JAAOS-D-20-00727
pubmed_68_527
In utero exposure to cocaine results in neurobehavioral abnormalities in both clinical and laboratory studies. Cocaine administration from embryonic day 13 to parturition disrupts the distribution of S-100-positive astrocytes in the hippocampus and subplate region of the cortex in cocaine-exposed animals. Postnatal treatment with ipsapirone, a 5-HT1A agonist, shown to stimulate glial release of S-100, alleviated the cellular disruptions and growth retardation caused by prenatal cocaine exposure.
10.1016/0304-3940(94)90259-3
pubmed_670_3785
The New Approaches to Coronary Intervention (NACI) Registry was developed to collect in-depth data about patients whose coronary artery lesions are being treated with new interventional techniques such as atherectomy, stents, and laser devices. The NACI Registry database distinguishes among several possible "modes" for device use, such as preparatory, planned definitive, and bailout use. Common definitions are used for data collection across all devices, and device-specific forms are used to record procedural details. NACI's unique modular form design facilitates thorough data collection, even for the most complex treatment scenarios. The database structure allows for data analysis at the patient, procedure, lesion, and device levels, as required to perform in-depth analyses of the immediate and long-term success of new devices. Once adequate knowledge of basic device performance has been collected, the Registry structure can also allow expeditious planning and performance of randomized trials comparing a new device to conventional PTCA.
10.1002/ccd.1810230409
pubmed_917_4039
Class I histocompatibility antigens (HLA) are expressed on the surface of almost all nucleated mammalian cells; the expression of this surface antigenic molecule may be changed or abrogated by several factors. In this paper, a modification in HLA expression in a human carcinoma cell line following exposure to the neurotoxicant 2,5 hexanedione is reported. This compound is known to produce a wide spectrum of subcellular pathological events; in this study, we describe an effect on the surface and cytoplasmic distribution of both light and heavy subunits of HLA antigens, demonstrated by immunocytochemical and immunoelectron microscopy techniques. Human carcinoma cells, which under normal growing conditions express the HLA, abrogate the surface expression of this glycoprotein after exposure to 2,5 hexanedione and an intracytoplasmic accumulation seems to occur. Several possibilities are discussed, such as an effect of the toxicant on the transport of the nascent glycoprotein.
10.1007/BF00119914
pubmed_450_20799
STUDY OBJECTIVE To evaluate the impact of pill burden on outcomes in patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) receiving antiretroviral therapy (ART) as a single-tablet regimen (STR) or multiple-tablet regimen (MTR). DESIGN Retrospective cohort study. DATA SOURCES South Carolina Medicaid medical and pharmacy paid claims data were obtained from the South Carolina Revenue and Fiscal Affairs Office; laboratory data were obtained from the South Carolina Department of Health and Environmental Control. PATIENTS A total of 2174 patients covered by South Carolina Medicaid who were dispensed a complete ART STR (580 patients) or MTR (1594 patients) lasting at least 60 days between January 1, 2006, and December 31, 2013. MEASUREMENTS AND MAIN RESULTS Outcomes were ART adherence; risk of, time to, and total number of hospitalizations; and viral load suppression. Patients were followed from the index date (start date of their complete ART regimen) until the earliest date of one of the following: treatment discontinuation; treatment switch from MTR to STR, or vice versa; end of study period; last date of Medicaid eligibility; or death. Differences in outcomes were evaluated by using bivariate χ(2) and Wilcoxon rank sum tests, as well as multivariate regression models controlling for covariates measured during a 6-month baseline period. The STR and MTR cohorts were, on average, similar in terms of age at index date, Charlson Comorbidity Index score, sex, drug abuse, and mental health diagnoses, but they differed significantly in racial composition, index year of regimen, previous treatment, baseline viral load, and CD4 measures. The bivariate analysis revealed that the STR cohort was more adherent (p<0.0001), had a lower risk of hospitalization (p=0.0076), and had a higher proportion of patients with viral suppression (64.5% vs 49.5%, p<0.0001). In addition, multivariate regression models revealed that the STR cohort was more adherent and was associated with a lower risk of hospitalization (hazard ratio 0.71, 95% confidence interval 0.59-0.86), but no significant difference in viral load suppression was noted between the STR and MTR cohorts. CONCLUSION The STR was associated with higher adherence rates and a lower risk of hospitalization (both in the adjusted and unadjusted analyses) in South Carolina Medicaid patients with HIV infection and AIDS. A higher proportion of patients in the STR cohort had viral suppression during the follow-up period in the unadjusted analysis compared with the MTR cohort; however, no significant difference in viral suppression was observed when controlling for adherence.
10.1002/phar.1728
pubmed_1022_24162
Calcific aortic valve disease (CAVD) is a chronic disorder characterized by an abnormal mineralization of the leaflets, which is accelerated in bicuspid aortic valve (BAV). It is suspected that mechanical strain may promote/enhance mineralization of the aortic valve. However, the effect of mechanical strain and the involved pathways during mineralization of the aortic valve remains largely unknown. Valve interstitial cells (VICs) were isolated and studied under strain conditions. Human bicuspid aortic valves were examined as a model relevant to increase mechanical strain. Cyclic strain increased mineralization of VICs by several-fold. Scanning electron microscope (SEM) and energy dispersive X-ray (EDX) analyses revealed that mechanical strain promoted the formation of mineralized spheroid microparticles, which coalesced into larger structure at the surface of apoptotic VICs. Apoptosis and mineralization were closely associated with expression of ENPP1. Inhibition of ENPP1 greatly reduced mineralization of VIC cultures. Through several lines of evidence we showed that mechanical strain promoted the export of ENPP1-containing vesicles to the plasma membrane through a RhoA/ROCK pathway. Studies conducted in human BAV revealed the presence of spheroid mineralized structures along with the expression of ENPP1 in areas of high mechanical strain. Mechanical strain promotes the production and accumulation of spheroid mineralized microparticles by VICs, which may represent one important underlying mechanism involved in aortic valve mineralization. RhoA/ROCK-mediated export of ENPP1 to the plasma membrane promotes strain-induced mineralization of VICs.
pubmed_1022_24162
pubmed_175_9516
Biomaterials with tunable biophysical properties hold great potential for tissue engineering. The adaptive immune system plays an important role in bone regeneration. Our goal is to investigate the regeneration potential of cell-laden alginate hydrogels depending on the immune status of the animal model. Specifically, the regeneration potential of rat mesenchymal stromal cell (MSC)-laden, void-forming alginate hydrogels, with a stiffness optimized for osteogenic differentiation, is studied in 5-mm critical-sized femoral defects, in both T cell-deficient athymic Rowett Nude (RNU) rats and immunocompetent Sprague Dawley rats. Bone volume fraction, bone mineral density, and tissue mineral density are higher for athymic RNU nude rats 6 weeks postsurgery. In addition, these animals show a significantly higher number of total cells and cells with non-lymphocyte morphology at the defect site, while the number of cells with lymphocyte-like morphology is lower. Hydrogel degradation is slower and the remaining alginate fragments are surrounded by a thicker fibrous capsule. Ossification islands originating from alginate residues suggest that encapsulated MSCs differentiate into the osteogenic lineage and initiate the mineralization process. However, this effect is insufficient to fully bridge the bone defect in both animal models. Alginate hydrogels can be used to deliver MSCs and thereby recruit endogenous cells through paracrine signaling, but additional osteogenic stimuli are needed to regenerate critical-sized segmental femoral defects.
10.1089/ten.TEA.2019.0310
pubmed_46_5077
Ito cells play a key role in the development of liver fibrosis associated with chronic liver diseases. Both ETA (20%) and ETB (80%) receptors were identified in human Ito cells. ET-1 did not stimulate proliferation of Ito cells. In contrast, ET-1 inhibited DNA synthesis stimulated by serum or PDGF-BB, through an ETB-mediated pathway. The mechanism leading to growth inhibition involved elevation of cAMP leading to inhibition of serum-stimulated MAP kinase and selective reduction of c-jun expression. Finally, ET receptors were upregulated by cAMP, providing a positive feedback loop that would amplify ET-1-induced growth inhibition. We conclude that ET-1 is a potent growth inhibitory peptide and may exert positive or negative control of cell growth, depending on cell type. Moreover, this peptide may play a key role in the negative control of liver fibrogenesis.
pubmed_46_5077
pubmed_830_15601
Chronic lung disease is a major worldwide health concern but better tools are required to understand the underlying pathologies. Ventilation/perfusion (V/Q) single photon emission computed tomography (SPECT) with per-voxel analysis allows for non-invasive measurement of regional lung function. A clinically adapted V/Q methodology was used in healthy mice to investigate V/Q relationships. Twelve week-old mice were imaged to describe normal lung function while 36 week-old mice were imaged to determine how age affects V/Q. Mice were ventilated with Technegas™ and injected with (99m)Tc-macroaggregated albumin to trace ventilation and perfusion, respectively. For both processes, SPECT and CT images were acquired, co-registered, and quantitatively analyzed. On a per-voxel basis, ventilation and perfusion were moderately correlated (R = 0.58±0.03) in 12 week old animals and a mean log(V/Q) ratio of -0.07±0.01 and standard deviation of 0.36±0.02 were found, defining the extent of V/Q matching. In contrast, 36 week old animals had significantly increased levels of V/Q mismatching throughout the periphery of the lung. Measures of V/Q were consistent across healthy animals and differences were observed with age demonstrating the capability of this technique in quantifying lung function. Per-voxel analysis and the ability to non-invasively assess lung function will aid in the investigation of chronic lung disease models and drug efficacy studies.
10.1371/journal.pone.0042187
pubmed_394_18526
This study compares Latino host, Latino immigrant, Asian-American host, Asian-American immigrant and European-American host groups of adolescents with respect to four acculturation-related variables: ethnic identity exploration, ethnic identity affirmation/belonging, outgroup orientation, and American identity. Using the five ethno-generational categories as a grouping variable, we conducted analyses of 313 survey responses to the acculturation items at two time periods, 9 weeks apart. Results showed that differences among the three host racial/ethnic groups can best be explained by a group dominance perspective, whereby the two racial/ethnic minority groups are more similar to each other than they are to the European-American group. Furthermore, the relationship between American identity and ethnic identity components is stronger among the three host groups, as compared to the immigrant groups. Implications for future research with adolescent members of the host group whose heritage culture is non-European are drawn.
10.1007/s10464-008-9205-9
pubmed_225_13999
Previous work in our laboratory has shown that microvascular pericytes sort muscle and nonmuscle actin isoforms into discrete cytoplasmic domains (Herman, I. M., and P. A. D'Amore. 1985. J. Cell Biol. 101:43-52; DeNofrio, D.T.C. Hoock, and I. M. Herman. J. Cell. Biol. 109:191-202). Specifically, muscle (alpha-smooth) actin is present on the stress fibers while nonmuscle actins (beta and gamma) are located on stress fibers and in regions of moving cytoplasm (e.g., ruffles, lamellae). To determine the form and function of beta actin in microvascular pericytes and endothelial cells recovering from injury, we prepared isoform-specific antibodies and cDNA probes for immunolocalization, Western and Northern blotting, as well as in situ hybridization. Anti-beta actin IgG was prepared by adsorption and release of beta actin-specific IgG from electrophoretically purified pericyte beta actin bound to nitrocellulose paper. Anti-beta actin IgGs prepared by this affinity selection procedure showed exclusive binding to beta actin present in crude cell lysates containing all three actin isoforms. For controls, we localized beta actin as a bright rim of staining beneath the erythrocyte plasma membrane. Anti-beta actin IgG, absorbed with beta actin bound to nitrocellulose, failed to stain erythrocytes. Simultaneous localization of beta actin with the entire F-actin pool was performed on microvascular pericytes or endothelial cells and 3T3 fibroblasts recovering from injury using anti-beta actin IgG in combination with fluorescent phalloidin. Results of these experiments revealed that pericyte beta actin is localized beneath the plasma membrane in association with filopods, pseudopods, and fan lamellae. Additionally, we observed bright focal fluorescence within fan lamellae and in association with the ends of stress fibers that are preferentially associated with the ventral plasmalemma. Whereas fluorescent phalloidin staining along the stress fibers is continuous, anti-beta actin IgG localization is discontinuous. When injured endothelial and 3T3 cells were stained through wound closure, we localized beta actin only in motile cytoplasm at the wound edge. Staining disappeared as cells became quiescent upon monolayer restoration. Appearance of beta actin at the wound edge correlated with a two- to threefold increase in steady-state levels of beta actin mRNA, which rose within 15-60 min after injury and returned to noninjury levels during monolayer restoration. In situ hybridization revealed that transcripts encoding beta actin were localized at the wound edge in association with the repositioned protein. Results of these experiments indicate that beta actin and its encoded mRNA are polarized at the membrane-cytoskeletal interface within regions of moving cytoplasm.
10.1083/jcb.112.4.653
pubmed_537_9931
This articicle is a part of a research focusing on the relationship among child-prostitution, health-sickness-process linked to sexuality and violence; the three categories found in the environment of street girls. This paper, however, only deals with health-sickness-process linked to sexuality revealed by the girls themselves. After the considerations about the research as a whole and about sexuality in general, the street girls are characterized in their social scenery. Within that scenery, data about sexuality are analysed. Based on this analysis, the author concluded, among other aspects, that the education is necessary to enable Public Health to focus on this matter.
10.1590/s0104-11691996000100014
pubmed_349_20692
OBJECTIVE To estimate the prevalence of alcohol consumption during pregnancy among the general population of Latin America and the Caribbean, by country, in 2012. METHODS Three steps were taken: a comprehensive, systematic literature search; meta-analyses, assuming a random-effects model for countries with published studies; and regression modelling (data prediction) for countries with either no published studies or too few to obtain an estimate. RESULTS Based on 24 existing studies, the pooled prevalence of alcohol consumption during pregnancy among the general population was estimated for Brazil (15.2%; 95% confidence interval [95%CI]: 10.4%-20.8%) and Mexico (1.2%; 95%CI: 0.0%-2.7%). The prevalence of alcohol consumption during pregnancy among the general population was predicted for 31 countries and ranged from 4.8% (95%CI: 4.2%-5.4%) in Cuba to 23.3% (95%CI: 20.1%-26.5%) in Grenada. CONCLUSIONS Greater prevention efforts and measures are needed in the countries of Latin America and the Caribbean to prevent pregnant women from consuming alcohol during pregnancy and decrease the rates of Fetal Alcohol Spectrum Disorder. Additional high quality studies on the prevalence of alcohol consumption during pregnancy in Latin America and the Caribbean are also needed.
pubmed_349_20692
pubmed_1020_24485
The Tcra repertoire is generated by multiple rounds of Vα-Jα rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens primary Vα use to diversify the Tcra repertoire in mice. We reveal that use of Trav15-dv6 family V gene segments in Tcrd recombination imparts diversity in the Tcra repertoire by instigating use of central and distal Vα segments. Moreover, disruption of the regions containing these genes and their cis-regulatory elements identifies the Trav15-dv6 family as being responsible for driving central and distal Vα recombinations beyond their roles as substrates for Tcrd recombination. Our study demonstrates an indispensable role for Tcrd recombination in general, and the Trav15-dv6 family in particular, in the generation of a combinatorially diverse Tcra repertoire.
10.1084/jem.20211581
pubmed_218_19384
CONCLUSION A developmental histologic study of the otic capsule indicates that it grows a system of lamellar bone with abundant interconnecting intraosseous channels. These include the 'cartilage canals' in the cartilage model, the chondro-osseous and Haversian-like (Volkmann's) canals in the ossified otic capsule, the fissula ante fenestram, which seems to function as a lifelong manufacturer of the latter two channels, and the inner layer (vestibular arch) of the vestibular aqueduct, which is a complex series of Volkmann's canals and microcanals. Chemical changes, possibly produced by breakdown of cells within the channels, may provide a homeostatic environment for the functions of hearing and balance that take place in the endolymphatic fluid. OBJECTIVES We studied the development of the otic capsule to clarify the cellular appearances that we had previously described in the normal vestibular arch and the changes in that structure in Ménière's disease. METHODS Step sections from 84 temporal bones, including those from fetuses, children and adults from a variety of ages were examined histologically. RESULTS Cartilage canals, bringing blood vessels and mesenchymal cells from perichondrium to the depths of the cartilage model to mediate ossification, are found early in fetal life and disappear when ossification is complete at about 24 weeks. The otic capsule is formed of chondro-osseous canals, which are composed of trabeculae of mineralized cartilage lacunae containing mesenchymal cells that undergo ossification (globuli ossei); also Volkmann's canals (like Haversian canals in long bones but multidirectional), which are produced from osteoblasts. The lumina of the latter frequently link up with chondro-osseous canals. Lamellar bone forms the background of the otic capsule. The fissula ante fenestram is present from early in the cartilage model and then throughout life. It appears to mediate bone production and the new formation of chondro-osseous channels and Volkmann's canals. The internal layer of the vestibular aqueduct (vestibular arch) is seen in the cartilage model of the otic capsule (present in early fetal life) as a vascular layer of perichondrally derived connective tissue (not cartilage) surrounding the endolymphatic duct. When endochondral ossification starts, the bone from the adjoining cochlear and vestibular sides embrace this connective tissue layer to form the outer bony layer of the vestibular aqueduct. Osteoblasts then fill the inner layer with lamellar bone and macro- and mini-Volkmann's canals. At 1 year osteoblasts in the walls of macro-Volkmann's canals, proliferating thereafter throughout life, produce large numbers of microcanals. It is possible that slow breakdown of these osteoblasts and of similar cells in the canals of the otic capsule proper may contribute to the homeostasis of the endolymphatic duct and that of the rest of the membranous labyrinth, respectively.
10.3109/00016480903253561
pubmed_113_23415
INTRODUCTION Crotalidae immune F(ab')2 (Fab2AV) became available in the USA in 2019 for treatment of rattlesnake envenomation. In the clinical trial comparing Fab2AV to crotalidae immune polyvalent fab (FabAV), Fab2AV was associated with less late hemotoxicity. The purpose of this study was to describe outcomes following use of Fab2AV in patients with rattlesnake envenomation in Arizona. METHODS This is an observational study of patients admitted to a medical toxicology service at two hospitals in Arizona between January 1, 2019 and December 31, 2020. Patients with rattlesnake envenomation who received Fab2AV were included. Patients who received FabAV, alone or in combination with Fab2AV, were excluded. The main outcomes of interest were antivenom dose, adverse reactions, late hemotoxicity, and hospital readmission or retreatment. RESULTS Forty-six patients were included. The mean age was 40 years, with 15% under 12 years of age. All exhibited swelling, 20% thrombocytopenia, and 35% coagulopathy. Median time to treatment was 3 h and median total Fab2AV dose was 20 vials. Three patients had an acute reaction to Fab2AV which was non-life-threatening and resolved with antihistamines and/or steroids. In the follow-up period, one case of delayed thrombocytopenia (platelets = 108 K/mm3) and one case of recurrent thrombocytopenia (platelets = 111 K/mm3) were identified. There was no late coagulopathy. Five patients reported symptoms consistent with mild serum sickness. CONCLUSIONS In this series of patients with rattlesnake envenomation in Arizona who were treated with Fab2AV, there were no cases of clinically significant late hemotoxicity, and no patients required late retreatment with antivenom. Acute and delayed reactions did occur in some patients but were mild and easily treated.
10.1007/s13181-021-00859-y
others_359_3071
In November and December 1992, an outbreak of parvovirus B19 infection occurred among patients and staff on an adult mixed surgical ward at a large hospital in London. Three patients and 15 staff members were serologically confirmed as acute cases. The attack rate among susceptible members of staff was 47%. In those infected, arthralgia (80%) and rash (67%) were the most common symptoms. Of six susceptible in-patients on the ward, three became infected. One of the in-patients who had carcinoma of the mouth was viraemic for more than 10 days with marrow suppression resulting in the postponement of chemotherapy until intravenous immunoglobulin was given and he was no longer viraemic. Control measures taken included closure of the ward to new admissions, transfer of only immune staff to the ward, and restriction of the ward nursing staff to working only on that ward. Although no specific exposure was conclusively identified as a risk factor, there was a suggestion of an increased risk of acquiring parvovirus B19 infection among those staff who did not adopt strict hand washing procedures after each physical contact with a patient (RR = 2·33; P = 0·07). Knowledge of parvovirus B19 among interviewed health care workers was poor: only 42% reported knowing about parvovirus B19 and only 38% could name a patient category at risk of a severe outcome following infection. This is the first report of a nosocomial outbreak affecting an adult ward and of possible transmission of parvovirus B19 infection from staff to in-patients. Hospital control of infection teams should include parvovirus B19 in their outbreak containment plans. © 1994, Cambridge University Press. All rights reser
10.1017/S0950268800051773
pubmed_418_18921
Glucocorticoid drugs are widely used to treat immune-related diseases, but their use is limited by side effects and by resistance, which especially occurs in macrophage-dominated diseases. In order to improve glucocorticoid therapies, more research is required into the mechanisms of glucocorticoid action. In the present study, we have used a zebrafish model for inflammation to study glucocorticoid effects on the innate immune response. In zebrafish larvae, the migration of neutrophils towards a site of injury is inhibited upon glucocorticoid treatment, whereas migration of macrophages is glucocorticoid resistant. We show that wounding-induced increases in the expression of genes that encode neutrophil-specific chemoattractants (Il8 and Cxcl18b) are attenuated by the synthetic glucocorticoid beclomethasone, but that beclomethasone does not attenuate the induction of the genes encoding Ccl2 and Cxcl11aa, which are required for macrophage recruitment. RNA sequencing on FACS-sorted macrophages shows that the vast majority of the wounding-induced transcriptional changes in these cells are inhibited by beclomethasone, whereas only a small subset is glucocorticoid-insensitive. As a result, beclomethasone decreases the number of macrophages that differentiate towards a pro-inflammatory (M1) phenotype, which we demonstrated using a tnfa:eGFP-F reporter line and analysis of macrophage morphology. We conclude that differentiation and migration of macrophages are regulated independently, and that glucocorticoids leave the chemotactic migration of macrophages unaffected, but exert their anti-inflammatory effect on these cells by inhibiting their differentiation to an M1 phenotype. The resistance of macrophage-dominated diseases to glucocorticoid therapy can therefore not be attributed to an intrinsic insensitivity of macrophages to glucocorticoids.
10.1242/dmm.037887
pubmed_60_3591
BACKGROUND Chromosome 13q14 deletion (del13q14), chromosome 1q21 gain (amp1q21) and chromosome 17p13 deletion (del17p13) are the most frequent chromosomal aberrations in multiple myeloma (MM). They play an important role in prognosis. The aim of this study was to investigate the clinical significance of the chromosomal changes in Chinese MM patients. METHODS Interphase fluorescence in situ hybridization (FISH) on bone marrow (BM) cells was performed in 72 enrolled MM patients. Relationships between chromosomal abnormalities and clinical features, response to therapies and prognosis were analyzed. RESULTS As a result of interphase FISH, 77.8% (56/72) patients had chromosome changes. The incidences of each probe were RB1 51.4% (37/72), D13S319 47.2% (34/72), 1q21 45.8% (33/72) and p53 22.2% (12/72). Osteolytic lesion, BM plasma cells index, serum calcium and serum M component were significantly correlated to del13q14. BM plasma cells and hemoglobin were correlated to amp1q21. Serum lactate dehydrogenase (LDH) was correlated with del17p13. Patients with del13q14 treated with bortezomib had a notably higher overall response rate than the patients treated with traditional chemotherapies (93% vs. 65%, P = 0.048). Patients carrying amp1q21 or/and del17p13 did not achieve satisfactory response to bortezomib. The median progression-free survival (PFS) for patients with amp1q21 was 5 months and patients without amp1q21 got 9-month PFS (P = 0.001). The median PFS for patients with del13q14 was 5 months (vs. 8 months, P = 0.026). The median PFS for patients with del17p13 was 3 months (vs. 8 months, P = 0.002). Patients with β(2)-microglobulin > 5.5 mg/L also had a worse outcome, whose median PFS was 5 months (vs. 8 months, P = 0.016). CONCLUSIONS The prevalence of chromosomal abnormalities of MM patients was similar in Chinese and Caucasian people. Genetic changes were associated with patients' responses to therapies and prognosis.
pubmed_60_3591
pubmed_931_799
Helicobacter pylori induces an acute inflammatory response followed by a chronic infection of the human gastric mucosa characterized by infiltration of neutrophils/polymorphonuclear cells (PMNs) and mononuclear cells. The H. pylori neutrophil-activating protein (HP-NAP) activates PMNs, monocytes, and mast cells, and promotes PMN adherence to the endothelium in vitro. By using intravital microscopy analysis of rat mesenteric venules exposed to HP-NAP, we demonstrated, for the first time in vivo, that HP-NAP efficiently crosses the endothelium and promotes a rapid PMN adhesion. This HP-NAP-induced adhesion depends on the acquisition of a high affinity state of beta(2) integrin on the plasma membrane of PMNs, and this conformational change requires a functional p38 MAPK. We also show that HP-NAP stimulates human PMNs to synthesize and release a number of chemokines, including CXCL8, CCL3, and CCL4. Collectively, these data strongly support a central role for HP-NAP in the inflammation process in vivo: indeed, HP-NAP not only recruits leukocytes from the vascular lumen, but also stimulates them to produce messengers that may contribute to the maintenance of the flogosis associated with the H. pylori infection.
10.4049/jimmunol.178.3.1312
pubmed_285_20888
BACKGROUND Gastric adenocarcinoma (GAC) is one of the most commonly diagnosed cancers worldwide. Two standard approaches for treatment of resectable GAC include adjuvant 5-fluorouracil-based chemoradiotherapy [per Intergroup 0116 (INT-0116) trial and perioperative epirubicin, cisplatin, fluorouracil (ECF) chemotherapy per Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial]. Controversy remains regarding the most appropriate treatment strategy to decrease recurrence rates and improve survival following surgery. The purpose of this study was to analyze how patterns of care for patients with GAC treated at Emory University Hospital changed following publication of the MAGIC trial in 2006. METHODS We analyzed a prospectively maintained database of 150 patients who underwent resection for GAC between December 2000 and June 2013. Patients were divided into two cohorts, Early [2000-2006] and late [2007-2013]. The primary objective was to compare the number of patients assigned to adjuvant chemoradiotherapy (aCRT) vs. perioperative chemotherapy (PC) throughout the study period and secondarily assess for recurrence patterns and survival outcomes for patients assigned to those two strategies. RESULTS Between 2000 and 2013, 124 patients received adjuvant therapy for GAC. Fifty-four patients were treated with PC and 70 patients with aCRT. The early cohort included 56 patients, and the late cohort included 94 patients. There was no statistical difference in the number of patients receiving aCRT between the Early and Late cohorts [n=23 (50%) vs. 35 (38%) respectively, P=0.21]. PC increased from 2 patients (3.6%) in the Early cohort to 32 patients (34%) in the Late cohort (P<0.001). Four-year overall survival (OS) was 32.6% for the Early cohort and 68.8% for the Late cohort (P=0.010). Overall recurrence rate was 25.3% with no significant difference in rates of recurrence seen between the Early and Late cohorts. CONCLUSIONS PC has become more prevalent in patients treated at Emory following publication of the MAGIC trial in 2006. OS, but not recurrence rates, has also improved since publication. Although improved survival is suggestive of improved care, the question of optimal treatment regimen remains open. Further prospective comparisons of PC and aCRT are needed to identify patient and disease parameters that may guide therapy selection.
10.3978/j.issn.2078-6891.2015.026
pubmed_80_9450
BACKGROUND Baltic amber teething necklaces have been popularized as a safe and natural alternative to conventional or pharmacological medicines for the management of teething pain. However, claims made by retailers regarding the efficacy and mechanism of action of these necklaces lack scientific or clinical basis. The claim most closely resembling science is the assertion that succinic acid will leach out of the beads and through the skin of the wearer and carry out anti-inflammatory and analgesic effects. The objective of the current research is to scientifically assess this claim. METHODS Beads from necklaces were powdered for identification by infrared spectroscopy, and dissolved in sulfuric acid for quantification of succinic acid using HPLC. Succinic acid release from beads was assessed by long-term submersion of amber beads (separated according to light, medium and dark brown colour) in solvents relevant to human skin conditions. The potential for succinic acid to have anti-inflammatory effects was assessed by measuring the release of inflammatory cytokines IL-1α, IL-1β, IL-8 and TNFα, and the inflammatory messenger PGE2, from THP-1 human macrophages after treatment with succinic acid and LPS. RESULTS Amber teething necklaces were positively identified as Baltic amber, by comparison of the beads' infrared spectrum to the literature, and by their succinic acid content (1.5 mg per bead; 1.44% w/w). However, whole amber beads submerged in octanol or pH 5.5 phosphate buffered saline did not release any measurable succinic acid, except for the light-coloured beads in octanol which broke into tiny fragments. Additionally, treatment of macrophages with succinic acid did not reduce the release of any inflammatory cytokines measured, and displayed toxicity to the cells at high concentrations. CONCLUSIONS While amber teething necklaces are genuine Baltic amber, we have found no evidence to suggest that the purported active ingredient succinic acid could be released from the beads into human skin. Additionally, we found no evidence to suggest that succinic acid has anti-inflammatory properties.
10.1186/s12906-019-2574-9
pubmed_38_24966
The title compound, C(12)H(12)N(12)O(3), was obtained by the hydro-thermal reaction of 1,3,5-tricyano-methoxy-benzene and (CH(3))(3)SiN(3). The mol-ecule is almost planar, with an r.m.s. deviation of 0.0976 Å from the plane through all atoms in the mol-ecule. The three tetra-zole rings make dihedral angles of 13.09 (19), 2.01 (19) and 11.56 (18)° with one another and corresponding angles of 8.66 (17), 5.44 (16) and 3.51 (17)° with the central benzene ring. In the crystal structure, inter-molecular N-H⋯N hydrogen bonds form well separated one-dimensional planar sheets.
10.1107/S1600536807062733
pubmed_199_914
In mammals, a number of liver-derived plasma proteins, termed acute phase reactants, are induced during an inflammation response. We have studied genetic variation in the structure and expression of several of these proteins in a variety of inbred and wild-derived mice. In a genetic cross, electrophoretic polymorphisms for the two alpha 1-acid glycoproteins, AGP-1 and AGP-2, co-segregated in 58 backcross progeny, indicating that either a single gene or two tightly-linked genes on chromosome 4 encode the AGPs. In the same backcross, segregation of variation in haptoglobin structure showed that the gene encoding this acute phase reactant is on chromosome 8. Structural variation in serum amyloid A correlated with restriction fragment length polymorphisms in the Saa gene determined by Taylor and Rowe (1984). Analysis of a number of highly diverged species of mice indicated that AGP expression has undergone considerable modification during evolution of the Mus genus; this is associated with alterations in Agp gene organization, which may include species-specific amplification and/or deletion events.
10.1007/BF00331347
pubmed_972_24280
OBJECTIVES This drug utilization study aims to evaluate the incidence and prevalence of prescribed antidepressants (SSRIs or SNRIs) and to describe treatment modalities in Italy during the period 2003-2009. METHODS This retrospective analysis on the prescription and treatment modalities of SSRIs or SNRIs is based on an Italian general practice database, which includes data on about 1,000,000 patients. Eligible patients should have age≥18 years, and ≥1 year of clinical history. Prevalence, incidence of use and adherence were calculated for SSRIs and SNRIs and for the individual agents. RESULTS The prevalence of SSRI use increased from 7.5% (2003) to 13.1% (2009) while the prevalence of SNRI use increased from 0.8% to 2.5%. The most evident increase was reported for escitalopram (+2.78%). The number of new antidepressant users (incidence rate) showed a modest decrease for SSRIs (-0.3%) and a slight increase for SNRIs (+0.9%). A higher percentage of continuers was reported for SSRIs versus SNRIs (15.1% vs 13.0%). Escitalopram was associated with the highest percentage of continuers and with the highest number of days of uninterrupted treatment. Overall, over 10% of antidepressant users switched their first choice during one year of follow-up. Escitalopram was associated with the highest frequency of 'high' adherers (28.5%). CONCLUSIONS SSRIs may be regarded as the elective treatment for depression. Of the SSRIs, escitalopram seems to be associated with the highest number of days of uninterrupted treatment, the lowest proportion of switchers and the highest adherence. This consideration might have practical relevance when comparing escitalopram to other SSRIs and to venlafaxine and duloxetine.
10.1185/03007995.2012.713341
pubmed_1133_17414
Loneliness is associated with life transitions such as new motherhood, yet there are few studies investigating the issue in this population. Using data from semi-structured interviews and an interpretative phenomenological analysis, this exploratory study sought to understand seven new mothers' experiences of loneliness. Experiences were organised around three themes, reflecting loneliness arising from making unfavourable self-comparisons with perceived mothering 'norms', from reduced social contact and relationships lacking in empathy. Accounts were homogeneous and point to potential solutions to ameliorate loneliness in new mothers; encouraging empathy in new mothers' partners and countering prevalent unrealistic representations of motherhood with more pragmatic accounts.
10.1177/1359105317723451
pubmed_699_19226
With the improvement of medical and health care level in our society, the demand for antibacterial materials is increasing. In this work, we prepared the antibacterial materials by loading silver nanoparticles (AgNPs) on the dialdehyde cellulose (DAC) with in-situ synthesis method. DAC was prepared by pretreating cellulose fiber with sodium metaperiodate (NaIO4) to convert the hydroxyl group into aldehyde group, and then reacted with silver nitrate (AgNO3) to obtain AgNPs loaded on DAC. UV-Vis results show that the characteristic absorption peak of AgNPs at 428 nm appeared in the AgNPs-loaded-DAC. It was observed by SEM that the spherical AgNPs were distributed uniformly on the DAC surface without obvious flocculation. The color of DAC was not changed significantly, indicating that a small amount of AgNPs was loaded. In addition, sodium citrate (Na3C6H5O7) was added in the reaction of DAC and AgNO3 and its effect on the formation of AgNPs was studied. The results demonstrated that the color of DAC turned deeper and finally dark yellow with reaction time extended. When the reaction time was 60 h, the spherical AgNPs were gradually grown and transformed into triangular prism on the DAC surface. The antibacterial properties of AgNPs showed inhibition zones of 4.90 mm and 7.35 mm (60 h) against Gram-negative (E. coli) and Gram-positive (S. aureus), respectively, which increased by 40.00% and 14.85% compared with spherical AgNPs (2.5 h) obtained without Na3C6H5O7. The research of AgNPs-loaded cellulose-based materials promotes the development prospect of new nano-antibacterial materials. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s10570-022-04692-6.
10.1007/s10570-022-04692-6
pubmed_537_2747
We assessed the therapeutic efficacy and outcome of mechanical ventilation (MV) in patients with acute respiratory failure (ARF) following ischemic stroke (IS) or intracerebral hemorrhage (ICH), retrospectively graded by patients with IS (n = 881) and ICH (n = 108) admitted to our service during 11 years, according to the severity of their clinical state and to whether we employed MV. Outcome was recorded in terms of survival and duration of MV and compared with patients with neuromuscular (NM) diseases. We found a very high in-hospital mortality in stroke patients who were treated with ventilation (90.5% for IS and 87.5% for ICH) compared with NM patients (29%). We conclude that MV in stroke patients with ARF is not life-saving, and its use should be considered only after considering other potentially important factors.
10.1212/wnl.47.3.657
pubmed_200_3153
Even though GPCR signaling in human platelets is directly involved in hemostasis and thrombus formation, the sequence of events by which G protein activation leads to αIIbβ3 integrin activation (inside-out signaling) is not clearly defined. We previously demonstrated that a conformationally sensitive domain of one G protein, i.e. Gα13 switch region 1 (Gα13SR1), can directly participate in the platelet inside-out signaling process. Interestingly however, the dependence on Gα13SR1 signaling was limited to PAR1 receptors, and did not involve signaling through other important platelet GPCRs. Based on the limited scope of this involvement, and the known importance of G13 in hemostasis and thrombosis, the present study examined whether signaling through another switch region of G13, i.e. Gα13 switch region 2 (Gα13SR2) may represent a more global mechanism of platelet activation. Using multiple experimental approaches, our results demonstrate that Gα13SR2 forms a bi-molecular complex with the head domain of talin and thereby promotes β3 integrin activation. Moreover, additional studies provided evidence that Gα13SR2 is not constitutively associated with talin in unactivated platelets, but becomes bound to talin in response to elevated intraplatelet calcium levels. Collectively, these findings provide evidence for a novel paradigm of inside-out signaling in platelets, whereby β3 integrin activation involves the direct binding of the talin head domain to the switch region 2 sequence of the Gα13 subunit.
10.1074/jbc.M115.650978
pubmed_912_9142
Nanotechnology produces basic structures that show a significant variability in their individual physical properties. This experimental fact may constitute a serious limitation for most applications requiring nominally identical building blocks. On the other hand, biological diversity is found in most natural systems. We show that reliable information processing can be achieved with heterogeneous groups of non-identical nanostructures by using some conceptual schemes characteristic of biological networks (diversity, frequency-based signal processing, rate and rank order coding, and synchronization). To this end, we simulate the integrated response of an ensemble of single-electron transistors (SET) whose individual threshold potentials show a high variability. A particular experimental realization of a SET is a metal nanoparticle-based transistor that mimics biological spiking synapses and can be modeled as an integrate-and-fire oscillator. The different shape and size distributions of nanoparticles inherent to the nanoscale fabrication procedures result in a significant variability in the threshold potentials of the SET. The statistical distributions of the nanoparticle physical parameters are characterized by experimental average and distribution width values. We consider simple but general information processing schemes to draw conclusions that should be of relevance for other threshold-based nanostructures. Monte Carlo simulations show that ensembles of non-identical SET may show some advantages over ensembles of identical nanostructures concerning the processing of weak signals. The results obtained are also relevant for understanding the role of diversity in biophysical networks.
10.1371/journal.pone.0053821
others_317_16008
We present a case of fatal, progressive hepatotoxicity in a patient treated with lamotrigine. After presenting with a rash and fever, she developed elevated liver function tests and clinical sequelae of hepatic failure. The subacute course of her progressive liver damage is documented in serial liver biopsies. While her initial biopsy showed approximately 50% hepatocyte necrosis, her post mortem examination performed three weeks later displayed massive hepatic necrosis with extensive bile duct proliferation. Although she was taking other antipsychotics at the time, her clinical course best parallels other reports of lamotrigine-associated hepatotoxicity. Here we discuss not only the clinicopathologic findings of this case but also review the pertinent literatur
10.1023/A:1019627618972
pubmed_861_2928
Providing forage to feed-restricted pregnant sows may improve their welfare by reducing their high feeding motivation. The aim of this study was to determine sows' preferences for four forage mixtures cultivated in Canada. Forage mixtures were compared when offered either fresh or dry. The four forage mixtures were composed of different proportions and species of legumes (alfalfa (Alf) or red clover (Clo)) and grasses (tall fescue (F) and/or timothy (T)): (1) Alf-F, (2) Alf-F-T, (3) Clo-T and (4) Clo-F-T. Voluntary intake was measured, and preference tests were carried out for two experiments: one in spring for fresh forages ( n = 8) and the other in autumn for hays ( n = 8) with different sows housed in individual pens and fed a concentrated diet meeting their nutritional requirements for maintenance and foetal growth. Voluntary intake was measured by offering each forage mixture separately (one forage mixture/day) during 90 min according to a 4 × 4 Latin square design replicated four times. During preference tests, all six combinations of two forage mixtures were offered once (one combination/day) for 45 min to each sow. Individual forage intake was measured, and feeding behaviour was observed. Forages were analysed for botanical and chemical composition. Difference in voluntary intake among the four forage mixtures was determined using a variance analysis followed by Tukey tests for post hoc comparisons. In preference tests, differences between the two forage mixtures offered were determined using a paired Student's t test, and the most ingested forage mixture was considered the preferred one. Results from both experiments revealed clear preferences for some forage mixtures when offered either fresh or dry. Forage mixtures with a greater proportion of legumes (AlfT and CloT) were preferred over forage mixtures with a higher proportion of grasses (AlfFT and CloFT). The AlfFT and CloFT forage mixtures contained at least 30% of fescue; therefore, the greater preference for the AlfT and CloT forage mixtures could also be due to the absence of fescue. Sows preferred forages with low DM and NDF concentrations and high CP and non-structural carbohydrates concentrations. Based on results from previous studies, the preferences seen in the present study are most likely due to the greater proportion of legumes, although an effect of tall fescue in preference cannot be excluded. Therefore, offering forages with a high proportion of legumes would be a good strategy to maximise both fresh and dry forage intake in pregnant sows.
10.1017/S1751731119000958
pubmed_473_1099
Disopyramide (DP) is known to induce QT prolongation and Torsades de Pointes (TdP) when administered concomitantly with erythromycin (EM). To define and evaluate quantitatively the arrhythmogenic risk of the concomitant administration of DP and EM, we investigated the influence of EM on the pharmacokinetics and pharmacodynamics of DP in rats. The time profiles of change in QT interval and plasma concentration of each drug were evaluated during and after constant intravenous infusion of DP (6.0 or 15.0 mg/kg/h), EM (4.0 or 8.0 mg/kg/h), and coadministration of DP and EM (DP 6.0 mg/kg/h plus EM 4.0 mg/kg/h). Each agent induced QT prolongation at plasma concentrations within the therapeutic range in humans. DP-induced QT prolongation was proportional to its plasma concentration. In the case of EM, the Emax model with an "effect compartment" could explain the relationship between plasma EM concentrations and changes in QT interval. Although coadministration of EM with DP gave enhanced QT prolongation compared to dosing with DP alone, EM did not affect the pharmacokinetics of DP. In conclusion, it was shown that a pharmacodynamic interaction contributes to the electrocardiographic adverse reaction (i.e., QT prolongation) induced by coadministration of DP and EM in rats.
10.1021/js980256r
pubmed_758_7901
RNA folding into stable tertiary structures is remarkably sensitive to the concentrations and types of cations present; an understanding of the physical basis of ion-RNA interactions is therefore a prerequisite for a quantitative accounting of RNA stability. This article summarizes the energetic factors that must be considered when ions interact with two different RNA environments. "Diffuse ions" accumulate near the RNA because of the RNA electrostatic field and remain largely hydrated. A "chelated" ion directly contacts a specific location on the RNA surface and is held in place by electrostatic forces. Energetic costs of ion chelation include displacement of some of the waters of hydration by the RNA surface and repulsion of diffuse ions. Methods are discussed for computing both the free energy of the set of diffuse ions associated with an RNA and the binding free energies of individual chelated ions. Such calculations quantitatively account for the effects of Mg(2+) on RNA stability where experimental data are available. An important conclusion is that diffuse ions are a major factor in the stabilization of RNA tertiary structures.
10.1261/rna.5205404
pubmed_550_20729
A novel bipartite vector system consisting of the herpes simplex virus (HSV) amplicon and the Sleeping Beauty(SB) transposon was previously shown to efficiently deliver a "transgenon" (integrating transgene) in utero. This vector platform facilitated long-term transgenon expression specifically within neurons and neuronal precursor cells of the rodent brain. However, the mechanism underlying the neurospecificity of the HSV/SB amplicon in the setting of mouse embryogenesis is unknown. We find that embryonic cells expressing the Sox1 "neurocompetence" transcription factor represent the primary targets for HSV amplicon transduction in utero. These cells, which comprise the ependymal and subventricular zones (SVZs), express significant levels of high-mobility-group protein B1 (HMGB1), a co-factor shown to facilitate SB-mediated transposition. Using a conventional, non-integrating amplicon expressing Cre recombinase to "tag" transduced cells embryonically in ROSA26 Cre indicator mice in utero, we found transduced cells were exclusively of the neuronal lineage but that in comparison to HSV/SB-mediated in utero delivery, staining patterns were less widespread and "tagged" neuroprogenitor cells were absent. Our findings demonstrate that in utero HSV/SB amplicon gene transfer is primarily neurospecific owing to viral tropism and target cell populations present embryonically, where multi-potent cells of the developing embryo are supportive of SB-driven transposition.
10.1038/sj.mt.6300267
pubmed_19_3282
Supported lipid bilayers containing phosphatidylcholine headgroups are observed to undergo reorganization from a 2D fluid, lipid bilayer assembly into an array of complex 3D structures upon exposure to extreme pH environments. These conditions induce a combination of molecular packing and electrostatic interactions that can create dynamic morphologies of highly curved lipid membrane structures. This work demonstrates that fluid, single-component lipid bilayer assemblies can create complex morphologies, a phenomenon typically only associated with lipid bilayers of mixed composition.
10.1021/la2001305
pubmed_258_7036
BACKGROUND Accurate rapid diagnostic tests for SARS-CoV-2 infection would be a useful tool to help manage the COVID-19 pandemic. Testing strategies that use rapid antigen tests to detect current infection have the potential to increase access to testing, speed detection of infection, and inform clinical and public health management decisions to reduce transmission. This is the second update of this review, which was first published in 2020. OBJECTIVES To assess the diagnostic accuracy of rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Sources of heterogeneity investigated included setting and indication for testing, assay format, sample site, viral load, age, timing of test, and study design. SEARCH METHODS We searched the COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) on 08 March 2021. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions. SELECTION CRITERIA We included studies of people with either suspected SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen tests. We included evaluations of single applications of a test (one test result reported per person) and evaluations of serial testing (repeated antigen testing over time). Reference standards for presence or absence of infection were any laboratory-based molecular test (primarily reverse transcription polymerase chain reaction (RT-PCR)) or pre-pandemic respiratory sample. DATA COLLECTION AND ANALYSIS We used standard screening procedures with three people. Two people independently carried out quality assessment (using the QUADAS-2 tool) and extracted study results. Other study characteristics were extracted by one review author and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test, and pooled data using the bivariate model. We investigated heterogeneity by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status. MAIN RESULTS We included 155 study cohorts (described in 166 study reports, with 24 as preprints). The main results relate to 152 evaluations of single test applications including 100,462 unique samples (16,822 with confirmed SARS-CoV-2). Studies were mainly conducted in Europe (101/152, 66%), and evaluated 49 different commercial antigen assays. Only 23 studies compared two or more brands of test. Risk of bias was high because of participant selection (40, 26%); interpretation of the index test (6, 4%); weaknesses in the reference standard for absence of infection (119, 78%); and participant flow and timing 41 (27%). Characteristics of participants (45, 30%) and index test delivery (47, 31%) differed from the way in which and in whom the test was intended to be used. Nearly all studies (91%) used a single RT-PCR result to define presence or absence of infection. The 152 studies of single test applications reported 228 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies, with consistently high specificities. Average sensitivity was higher in symptomatic (73.0%, 95% CI 69.3% to 76.4%; 109 evaluations; 50,574 samples, 11,662 cases) compared to asymptomatic participants (54.7%, 95% CI 47.7% to 61.6%; 50 evaluations; 40,956 samples, 2641 cases). Average sensitivity was higher in the first week after symptom onset (80.9%, 95% CI 76.9% to 84.4%; 30 evaluations, 2408 cases) than in the second week of symptoms (53.8%, 95% CI 48.0% to 59.6%; 40 evaluations, 1119 cases). For those who were asymptomatic at the time of testing, sensitivity was higher when an epidemiological exposure to SARS-CoV-2 was suspected (64.3%, 95% CI 54.6% to 73.0%; 16 evaluations; 7677 samples, 703 cases) compared to where COVID-19 testing was reported to be widely available to anyone on presentation for testing (49.6%, 95% CI 42.1% to 57.1%; 26 evaluations; 31,904 samples, 1758 cases). Average specificity was similarly high for symptomatic (99.1%) or asymptomatic (99.7%) participants. We observed a steady decline in summary sensitivities as measures of sample viral load decreased. Sensitivity varied between brands. When tests were used according to manufacturer instructions, average sensitivities by brand ranged from 34.3% to 91.3% in symptomatic participants (20 assays with eligible data) and from 28.6% to 77.8% for asymptomatic participants (12 assays). For symptomatic participants, summary sensitivities for seven assays were 80% or more (meeting acceptable criteria set by the World Health Organization (WHO)). The WHO acceptable performance criterion of 97% specificity was met by 17 of 20 assays when tests were used according to manufacturer instructions, 12 of which demonstrated specificities above 99%. For asymptomatic participants the sensitivities of only two assays approached but did not meet WHO acceptable performance standards in one study each; specificities for asymptomatic participants were in a similar range to those observed for symptomatic people. At 5% prevalence using summary data in symptomatic people during the first week after symptom onset, the positive predictive value (PPV) of 89% means that 1 in 10 positive results will be a false positive, and around 1 in 5 cases will be missed. At 0.5% prevalence using summary data for asymptomatic people, where testing was widely available and where epidemiological exposure to COVID-19 was suspected, resulting PPVs would be 38% to 52%, meaning that between 2 in 5 and 1 in 2 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed. AUTHORS' CONCLUSIONS Antigen tests vary in sensitivity. In people with signs and symptoms of COVID-19, sensitivities are highest in the first week of illness when viral loads are higher. Assays that meet appropriate performance standards, such as those set by WHO, could replace laboratory-based RT-PCR when immediate decisions about patient care must be made, or where RT-PCR cannot be delivered in a timely manner. However, they are more suitable for use as triage to RT-PCR testing. The variable sensitivity of antigen tests means that people who test negative may still be infected. Many commercially available rapid antigen tests have not been evaluated in independent validation studies. Evidence for testing in asymptomatic cohorts has increased, however sensitivity is lower and there is a paucity of evidence for testing in different settings. Questions remain about the use of antigen test-based repeat testing strategies. Further research is needed to evaluate the effectiveness of screening programmes at reducing transmission of infection, whether mass screening or targeted approaches including schools, healthcare setting and traveller screening.
10.1002/14651858.CD013705.pub3
pubmed_399_7500
One of the risks of laryngeal laser surgery is the ignition of the disposable plastic endotracheal tubes used for ventilation. In 1985, Hunton and Oswal (Anaesthesia, 40: 1210, 1985) developed a metallic tube which is now available in France. In this study, the tube has been tested on 30 patients undergoing this type of surgery. The tube was sterilized in glutaraldehyde before re-using it. There never was any problem with placing the tube and surgical conditions were satisfactory. There was neither incident due to the laser, nor any difficulties with the use of high-frequency jet-ventilation. The blood gas values were satisfactory (mean PaO2: 19.4 +/- 4.2 kPa; mean PaCO2 5.0 +/- 0.46 kPa). After a use in 30 consecutive patients, the tube was not damaged. The advantages and disadvantages of this tube are discussed, considering the other types of special laser surgery endotracheal tubes. This metallic tube is not flammable, can be used several times, occupies only a small space and does not hurt tissues. Moreover, it is cheaper than disposable tubes when the price is calculated per patient. It would therefore seem that Hunton and Oswal's metallic tube, used with high-frequency jet-ventilation is a good alternative for tubes used today.
10.1016/s0750-7658(89)80172-8
pubmed_470_5183
Serotonin has long been implicated as a key neurotransmitter in migraine. There is a dearth of research specifically examining 5-HT1A receptor sensitivity in migraine despite the importance of this receptor in regulating central serotonergic tone. In this study we examined the hypothesis that migraine without aura is associated with hypersensitivity of central 5-HT1A receptors, using a 5-HT1A neuroendocrine challenge drug and comparing serum prolactin responses between a test group with migraine and a matched group of healthy controls. Twelve female subjects fulfilling International Headache Society (IHS) criteria for migraine without aura were evaluated. Following an overnight fast, subjects presented for testing at 9am. An intravenous canula was inserted and serum prolactin was assessed at baseline and every 30 min for 3 h following a single dose of 30 mg oral buspirone, a 5-HT1A-receptor agonist. Subjects were assessed during the first 5 days of the menstrual cycle. No subjects were taking psychotropic medication or migraine prophylactic treatment. Patients with current or previous psychiatric disorder, daily headache or analgesic overuse were excluded. 16 healthy female volunteers matched for age and menstrual status were also evaluated and served as controls. There was no difference in baseline prolactin between groups. There was a significant rise in prolactin following buspirone in both groups. Subjects with migraine had a significantly increased prolactin response to buspirone (delta max) compared to controls (P < 0.001). This study supports the hypothesis that migraine without aura is associated with a relative hypersensitivity of central 5-HT1A receptors. This is of relevance given the role of the 5-HT1A receptor in controlling raphe 5-HT tone and in the possible association between migraine and anxiety and depression.
10.1046/j.1468-2982.2003.00441.x
pubmed_503_1239
Evidence of the continuity of early problem behaviors in young girls and boys was examined developmentally. Data were gathered on 104 mother-child dyads from low-income families when children were between 1 and 5 years of age. Difficult temperament, aggression, and noncompliance from 12 to 24 months, and externalizing and internalizing problems at 36 and 60 months, were assessed. The results provide evidence for the continuity of early behavioral and emotional problems and support for the early differentiation between internalizing and externalizing problems. Implications of the current findings for prevention efforts are presented.
10.1023/a:1022647717926
pubmed_613_15757
Pressure sores are common in the debilitated elderly. Causal factors are unrelieved pressure, shearing forces, friction, and moisture. Preventive measures should be used for all high-risk patients, defined by general condition, mental status, degree of incontinence, amount of activity, and mobility. Principles of treating ulcers include pressure relief, reducing bacterial counts, debriding necrotic tissue, and providing a moist, clean environment.
pubmed_613_15757