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pubmed_959_21012
Recently the vaginal route consider as an ideal route for drug delivery systems (DDS) administration. This is because, it is suitable for lower drug dosage, higher drug concentration in the genital tract tissues and lower drug concentration in pregnant women blood circulation. However, the vaginal route administration faces many challenges due to the physiology as well as the complexity of vaginal tissue histology. Here in this study, during diestrus stage (optimal condition for foreign substance internalization), single or dual size of fluorescent thiol-organosilica nanoparticles (tOS-NPs) were administrated intravaginally. The biodistribution and reactivity of tOS-NPs in different tissues of the female genital tract were investigated under the fluorescence microscope. Furthermore, using immunohistochemical staining, the expression of F4/80 protein and the role of macrophages in transport and re-location of tOS-NPs from vaginal lumen into different genital tissues or other organs were investigated. This study showed that, tOS-NPs size and type of tissue are important in biodistribution and uptake of tOS-NPs in the genital tract. Small size (100 nm) of tOS-NPs was highly accumulated in the genital tract tissues especially endometrial epithelium compared with large tOS-NPs (1000 nm). Contradictory, the large size induced the expression of F4/80 protein and the number of vaginal macrophages compared with small size. However, both small and large sizes of tOS-NPs were found co-localized with F4/80+ macrophages, located in the vaginal, endometrial and ovarian tissues. The tOS-NPs intravaginally administrated were found in the splenic tissues, indicating its ability to enter the blood circulation from the vaginal lumen. Additionally, the high accumulation of tOS-NPs in the endometrial epithelium indicated the endometrial first pass effect of tOS-NPs. As a result, high concentration of tOS-NPs in the endometrial epithelium may reduce the concentration of tOS-NPs-based DDS in the blood circulation and their side effects. Furthermore, during vaginal tissue optimal condition (diestrus stage), understanding the fate and biodistribution of tOS-NPs will introduce important data about the development of save and effective DDS for the pregnant women.
10.1007/s00418-021-01974-1
pubmed_494_5618
PURPOSE To evaluate the correlation between surgical outcome after phototherapeutic keratectomy in patients with autosomal dominant transforming growth factor, beta-induced (TGFBI)-linked corneal dystrophies (CD) and molecular genetic findings regarding the TGFBI gene. METHODS Twelve patients were examined to investigate genotype by direct sequencing of the TGFBI gene. Twenty eyes of 12 patients were treated with phototherapeutic keratektomy (PTK) to remove superficial corneal opacifications and to decrease recurrent erosions. Surgical outcome, including visual improvement, recurrence of opacifications, postoperative complications, and additional therapeutic proceedings were reported and compared with the molecular genetic results. RESULTS Four different missense mutations were identified within the coding region of the TGFBI gene: Arg124Cys in one eye, Arg555Trp in nine eyes, Arg124His in four eyes and Gly623Arg in six eyes. In all eyes the PTK was successful without clinically significant recurrent opacifications after a mean follow-up time of 17.6 months (min 3 months, max 42 months). The best corrected visual acuity (BCVA) improved with an average increase of 3.1 lines (minimum 2 lines, maximum 5 lines). In one eye (Arg124Cys), we observed delayed wound healing and a delayed increase in BCVA, in two eyes we performed an Epilasik to correct remaining hyperopia, and in four eyes we fitted rigid gas-permeable tricurve contact lenses to correct the remaining irregular astigmatism. CONCLUSIONS The variable genotypes in patients with TGFBI-linked corneal dystrophies lead to significantly different results after surgical treatment. The Gly623Arg mutation seems to be an optimum genotype on which to perform PTK even in older patients. It is essential to determine the genotype in order to standardize the PTK treatment and to evaluate the success in TGFBI-linked corneal dystrophies.
10.1007/s00417-008-0931-3
pubmed_391_2465
The mechanism by which Ca2+ mediates gene induction in response to membrane depolarization was investigated. The adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) was shown to function as a Ca(2+)-regulated transcription factor and as a substrate for depolarization-activated Ca(2+)-calmodulin-dependent protein kinases (CaM kinases) I and II. CREB residue Ser133 was the major site of phosphorylation by the CaM kinases in vitro and of phosphorylation after membrane depolarization in vivo. Mutation of Ser133 impaired the ability of CREB to respond to Ca2+. These results suggest that CaM kinases may transduce electrical signals to the nucleus and that CREB functions to integrate Ca2+ and cAMP signals.
10.1126/science.1646483
pubmed_874_18889
CXCR4 and its ligand CXCL12 can promote the proliferation, survival, and invasion of cancer cells. They have been shown to play an important role in regulating metastasis of breast cancer to specific organs. High CXCR4 expression was also correlated to poor clinical outcome. Previous study also showed that tumor cells express a high level of CXCR4 and that tumor metastasis target tissues (lung, liver, and bone) express high levels of the ligand CXCL12, allowing tumor cells to directionally migrate to target organs via a CXCL12-CXCR4 chemotactic gradient. However, the exact mechanisms of how CXCR4 and CXCL12 enhance metastasis and/or tumor growth and their full implications on breast cancer progression are unknown. Yet it is likely that chemokine receptor signaling may provide more than just a migrational advantage by also helping the metastasized cells establish and survive in secondary environments. In this study, we investigated CXCR4 and CXCL12 expression in breast cancer and analyzed its association with clinicopathological factors by immunohistochemistry first. Then, we detected the mRNA and protein expression of CXCR4 and CXCL12 in breast cancer cell lines by Western blot and RT-PCR. The MDA-MB-231 has CXCR4 expression and very weak CXCL12 expression. So, we constructed the functional CXCL12 expression in MDA-MB-231 using a gene transfection technique. Further experiments were conducted to evaluate the effect of CXCL12 transfection on the biological behaviors of MDA-MB-231. The cell proliferation of MDA-MB-231-CXCL12 was accessed by MTT assay; the apoptosis was analyzed by an AnnexinV-FITC/propidium iodide double staining of flow cytometry method; and the cell invasive ability was examined by Matrigel invasion assay. Immunohistochemical analysis showed the co-expression of CXCR4 and CXCL12 correlated with lymph node metastasis and TNM stage (p < 0.01). It suggested that the chemokine CXCL12 and its sole ligand CXCR4 play important role in the malignance of breast cancer. To gain a deeper insight into it, we picked CXCR4-expressing cells MDA-MB-231 to be transfected with CXCL12 stably. The decreased cellular proliferation, increased apoptosis, and invasive ability were found in MDA-MB-231 with successful CXCL12 transfection (p < 0.05). Our findings underlined the CXCL12-CXCR4 axis correlated tightly with breast cancer metastasis. CXCL12-CXCR4 axis can increase the invasion and apoptosis of MDA-MB-231 simultaneously. These data strongly support the hypothesis that CXCL12-CXCR4 axis promotes the natural selection of breast cancer cell metastasis. Our findings could have significant implications in terms of breast cancer aggressiveness and the effectiveness of targeting the receptors and downstream signaling pathways for the treatment of breast cancer.
10.1007/s13277-014-1816-1
pubmed_918_14624
BACKGROUND The association between sarcopenia and postoperative outcomes in patients who undergo laparoscopic-assisted gastrectomy is unclear. We aimed to determine the predictive value of sarcopenia for adverse postoperative outcomes after laparoscopic-assisted gastrectomy for gastric cancer. MATERIALS AND METHODS We prospectively collected the clinical data of patients who underwent elective radical laparoscopic-assisted gastrectomy for gastric cancer in two large centers from August 2014 to October 2017. The third lumbar vertebra skeletal muscle index, handgrip strength, and 6-m usual gait speed were measured to diagnose sarcopenia. Subsequently, we aimed to identify the risk factors for postoperative complications. RESULTS The study included 313 patients and 37 (11.8%) patients were classified as sarcopenic. Compared with non-sarcopenic patients, sarcopenic patients were significantly older (P < 0.001), had higher nutritional risk screening 2002 scores (P = 0.013), Charlson comorbidity index (CCI) scores (P = 0.033), and neutrophil to lymphocyte ratio (P = 0.004), and lower body mass index (P < 0.001), preoperative serum albumin (P < 0.001), and hemoglobin (P < 0.001). Sarcopenic patients had higher postoperative complication rate (P = 0.002), longer postoperative hospital stays (P = 0.020) and higher total cost of hospitalization (P = 0.001). Multivariate analysis revealed that CCI score ≥1 (odds ratio [OR]: 2.424, 95% confidence interval [CI]: 1.309-4.487; P = 0.005) and sarcopenia (OR: 2.752, 95% CI: 1.274-5.944; P = 0.010) were independent risk factors for short-term postoperative complications. CONCLUSION Sarcopenia is an independent clinical predictor of short-term postoperative complications after laparoscopic-assisted gastrectomy.
10.1016/j.ejso.2018.09.030
others_192_12522
The goal of this study was to determine whether the susceptibility of the blood-brain barrier to disruption during acute hypertension is altered in aged rats. Intravital fluorescent microscopy and fluorescein-labeled albumin were used to evaluate disruption of the blood-brain barrier during acute hypertension in adult Wistar rats (6-8 mo) and aged Wistar rats (24-26 mo). Permeability of the blood-brain barrier was quantitated by calculating clearance of fluorescent-labeled albumin and by counting the number of microvascular leaky sites under control conditions and during acute arterial hypertension in adult and aged rats. Pressure in pial venules, which are the primary site of disruption of the blood-brain barrier during acute hypertension, and in pial arterioles was measured using a servo-null device. In adult rats, when systemic arterial pressure was increased from 124 ± 5 (means ± SE) to 190 ± 5 mmHg, clearance of albumin increased from 0.10 ± 0.05 to 1.64 ± 0.76 x 10-6 ml/s. In aged rats, when systemic arterial pressure was increased from 116 ± 4 to 185 ± 3 mmHg, clearance of albumin increased from 0.10 ± 0.03 to 1.56 ± 0.49 x 10-6 ml/s. Increases in pial venular pressure and pial arteriolar pressure also were similar in adult and aged rats. Thus the findings suggest that the susceptibility of the blood-brain barrier to disruption during acute hypertension is similar in adult and aged rats
10.1152/ajpheart.1990.258.6.h1735
pubmed_975_10276
The effect of Helicobacter mustelae infection on gastric epithelial proliferation was studied in ferrets colonized with H.mustelae and specific pathogen-free (SPF) ferrets not infected with H.mustelae. Thirteen H. mustelae-infected ferrets between the ages of 13 and 32 months and 16 SPF ferrets between 6 and 18 months were analyzed. Bacterial cultures, urease tests and Warthin-Starry stains were used to identify H.mustelae. Tissues obtained from the antrum and the body regions of the stomach were assayed by proliferating cell nuclear antigen (PCNA) immunohistochemistry and measured using a computerized color image analysis system. PCNA-expressing gastric epithelia in the antrum and the body regions were significantly increased in the H.mustelae-infected ferrets versus the SPF ferrets (P < 0.001). PCNA positivity in the antrum regions of both the H.mustelae-infected ferrets and SPF ferrets was significantly higher than that of the body regions (P < 0.001). Comparison of the histopathology of infected ferrets indicated that PCNA positivity correlated with the histological severity of gastritis. This study suggests that cell proliferation in ferret gastric mucosa increases with H.mustelae infection and provides evidence that PCNA is a useful biomarker for studying the changes in cell kinetics in the ferret stomach. The data also further support the use of the H.mustelae-infected ferret as an animal model for studying the pathogenesis of Helicobacter pylori-induced gastric diseases of humans.
10.1093/carcin/16.8.1927
pubmed_60_3443
BACKGROUND Here we provide the most comprehensive study to date on the cranial ossification sequence in Lipotyphla, the group which includes shrews, moles and hedgehogs. This unique group, which encapsulates diverse ecological modes, such as terrestrial, subterranean, and aquatic lifestyles, is used to examine the evolutionary lability of cranial osteogenesis and to investigate the modularity of development. RESULTS An acceleration of developmental timing of the vomeronasal complex has occurred in the common ancestor of moles. However, ossification of the nasal bone has shifted late in the more terrestrial shrew mole. Among the lipotyphlans, sequence heterochrony shows no significant association with modules derived from developmental origins (that is, neural crest cells vs. mesoderm derived parts) or with those derived from ossification modes (that is, dermal vs. endochondral ossification). CONCLUSIONS The drastic acceleration of vomeronasal development in moles is most likely coupled with the increased importance of the rostrum for digging and its use as a specialized tactile surface, both fossorial adaptations. The late development of the nasal in shrew moles, a condition also displayed by hedgehogs and shrews, is suggested to be the result of an ecological reversal to terrestrial lifestyle and reduced functional importance of the rostrum. As an overall pattern in lipotyphlans, our results reject the hypothesis that ossification sequence heterochrony occurs in modular fashion when considering the developmental patterns of the skull. We suggest that shifts in the cranial ossification sequence are not evolutionarily constrained by developmental origins or mode of ossification.
10.1186/2041-9139-2-21
pubmed_214_8634
Pluronics, due to its high water-soluble and thermoreversible ability, attracted much in biomedical applications. They are mainly utilized in drug delivery, gene therapy, and tissue remodeling. The study aims to explore the cytocompatibility of Pluronics F-127, which has gained much popularity due to its various properties. The cells were exposed to varying concentrations of Pluronics F-127 in A549 cells for 24 h. According to the MTT and neutral red assay, A549 cells displayed dose-dependent cell viability. The cell's morphology was preserved after treatment, as seen in phase-contrast and Giemsa staining. When exposed to PF-127, lysosomal, cytoskeletal, and nuclear integrity were maintained. The percentage of live cells in all the treated groups was more significant than 90%, according to the live/dead flow cytometric analyses. The study identified the cytocompatibility of Pluronics F-127 required for the breakthrough in biomedical applications.
10.1007/s11356-022-20925-4
pubmed_18_4308
Dopaminergic receptors are expressed on neural precursor cells (NPCs) in the subventricular zone (SVZ) and are known to regulate NPC proliferation and differentiation fate in this region. We now report that this optimally requires the simultaneous activation of both D1-like and D2-like dopaminergic receptors with the agonists Bromocriptine, SKF-38393 and 7-OH-pipat maleate (BSP) in vitro. This is consistent with our previous findings that dopamine stimulates NPC proliferation through an EGF paracrine mechanism within the SVZ. Furthermore this combined dopamine agonist therapy rescues NPC proliferation in the SVZ in the 6-OHDA animal model of PD and importantly significantly increases neuronal differentiation in the olfactory bulb to a greater extent than we showed previously with levodopa. This result has implications for the use of dopaminergic therapies in PD and in the development of such therapies focusing on upregulating SVZ neurogenesis.
10.4161/cc.8.18.9512
pubmed_919_20892
Rapid tissue destruction in group A streptococcal (GAS) necrotizing fasciitis/myonecrosis often necessitates extensive debridement to ensure survival. The mechanisms responsible for this fulminant process remain unknown; we hypothesized that toxin-induced ischemia contributes to necrosis. In a rat model, Doppler flowmetry was used to measure local blood flow at the site of the intramuscular injection of exotoxins from an invasive M-type 1 GAS, which caused a rapid, dose-dependent decrease in perfusion that was irreversible at the highest toxin concentration tested. Videomicroscopic results revealed that blood flow was impeded by occlusive intravascular cellular aggregates. Flow-cytometric results confirmed that GAS toxins induced the coaggregation of platelets and neutrophils, that this activity was attributable to streptolysin O, and that platelet/neutrophil complex formation was largely mediated by platelet P-selectin (CD62P). Strategies that target platelet adherence molecules may prevent vascular occlusion, maintain tissue viability, and reduce the need for amputation in necrotizing GAS infections.
10.1086/432729
pubmed_56_311
The penultimate enzyme in the histidine biosynthetic pathway catalyzes dephosphorylation of l-histidinol 1-phosphate (HOLP) into l-histidinol. The recently discovered in Arabidopsis thaliana plant-type histidinol phosphate phosphatase (HPP) shares no homology with the two other HPP superfamilies known previously in prokaryotes and resembles myo-inositol monophosphatases (IMPases). In this work, identification of an HPP enzyme from a model legume, Medicago truncatula (MtHPP) was based on the highest sequence identity to A. thaliana enzyme. Biochemical assays confirmed that MtHPP was able to cleave inorganic phosphate from HOLP but not from d-myo-inositol-1-phosphate, the main substrate of IMPases. Dimers of MtHPP, determined by size exclusion chromatography, in the presence of CO2 or formaldehyde form mutual, methylene-bridged cross-links between Lys(158) and Cys(245) residues. Four high resolution crystal structures, namely complexes with HOLP (substrate), l-histidinol (product), and PO4 (3-) (by-product) as well as the structure showing the cross-linking between two MtHPP molecules, provide detailed structural information on the enzyme. Based on the crystal structures, the enzymatic reaction mechanism of IMPases is accustomed to fit the data for MtHPP. The enzymatic reaction, which requires Mg(2+) cations, is catalyzed mainly by amino acid residues from the N-terminal domain. The C-terminal domain, sharing little identity with IMPases, is responsible for the substrate specificity (i.e. allows the enzyme to distinguish between HOLP and d-myo-inositol-1-phosphate). Structural features, mainly the presence of a conserved Asp(246), allow MtHPP to bind HOLP specifically.
10.1074/jbc.M115.708727
pubmed_602_13072
Human cytochrome P450 (CYP) 1B1 is a key enzyme in the metabolism of 17beta-estradiol (E2). CYP1B1 is mainly expressed in endocrine-regulated tissues, such as mammary, uterus, and ovary. Because many CYP enzymes are likely to be induced by the substrates themselves, we examined whether the human CYP1B1 expression is regulated by E2 in the present study. Real-time reverse transcription-PCR analysis revealed that treatment with 10 nM E2 for 12 h induced CYP1B1 mRNA expression in estrogen receptor (ER)-positive MCF-7 cells. Luciferase reporter assays using MCF-7 cells showed a significant transactivation up to 7-fold by E2 with a reporter plasmid containing a region from -152 to +25 of the human CYP1B1 gene. A computer-assisted homology search indicated a putative estrogen response element (ERE) between -63 and -49 in the CYP1B1 promoter region. Specific binding of ERalpha to the putative ERE was demonstrated by chromatin immunoprecipitation assays and gel shift analyses. With reporter plasmids containing the wild or mutated putative ERE on the CYP1B1 gene and the wild or mutated ERalpha expression vectors, luciferase assays using Ishikawa cells demonstrated that the putative ERE and ERalpha are essential for the transactivation by E2. Because endometrial tissue is highly regulated by estrogens, the expression pattern of CYP1B1 protein in human endometrial specimens was examined by immunohistochemistry. The staining of CYP1B1 was stronger in glandular epithelial cells during a proliferative phase than those during a secretory phase, consistent with the pattern of estrogen secretion. These findings clearly indicated that the human CYP1B1 is regulated by estrogen via ERalpha. Because 4-hydroxylation of estrogen by CYP1B1 leads to decrease of the estrogenic activity but the produced metabolite is toxicologically active, our findings suggest a clinical significance in the estrogen-regulated CYP1B1 expression for the homeostasis of estrogens as well as estrogen-dependent carcinogenesis.
10.1158/0008-5472.can-04-0166
pubmed_344_22002
The Association of American Medical Colleges has released a report on clinical-care conflicts of interest and what physicians should disclose to patients. While some doctors are concerned that such reporting would be perceived as negative, others think it's a good idea. "If you ask them (patients) what they wanted to know about their doctors' conflicts, the majority want to know a lot," says Guy Chisolm of the Cleveland Clinic, left.
pubmed_344_22002
pubmed_791_22932
OBJECTIVE To evaluate reports from the published literature of all randomized clinical trials (RCT) comparing postoperative sedation with dexmedetomidine versus propofol in adult patients, after open cardiac surgery. DESIGN A computerized search on Medline, EMBASE, Web of Science, and Agency for Healthcare Research and Quality databases was completed through June 2020. Meta-analysis of all published RCT comparing dexmedetomidine versus propofol utilization in the postoperative phase, using the standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. SETTING Assemblage and critical discussion of 11 RCTs comparing postoperative sedation from standard published reports from 2003 to 2019. PARTICIPANTS The study comprised 1,184 patients and analyzed critical discussion of time-based parameters (time to extubation, intensive care unit length of stay, and hospital length of stay) and nontime-dependent factors (delirium, bradycardia, and hypotension). MEASUREMENTS AND MAIN RESULTS Time to extubation was significantly reduced in the dexmedetomidine group (standardized mean difference [SMD] = -0.70, 95% confidence interval [CI] -0.98 to -0.42, p < 0.001); however, no difference in mechanical ventilation time was observed (SMD = -0.72, 95% CI -1.60 to 0.15, N.S.). Dexmedetomidine significantly reduced the intensive care unit length of stay (SMD = 0.23, 95% CI -1.06 to -0.16, p = 0.008), but this did not translate into a reduced hospital length of stay (SMD = -1.13, 95% CI -2.43 to 0.16, N.S). For nontime-dependent factors, incidence of delirium was unaffected between groups (odds ratio [OR]: 0.68, 95% CI 0.43-1.06, N.S), and higher rates of bradycardia (OR: 3.39, 95% CI: 1.20-9.55, p = 0.020) and hypotension (OR: 1.68, 95% CI 1.09-2.58, p = 0.017) were reported with propofol. CONCLUSIONS Despite the ICU time advantages afforded by dexmedetomidine over propofol, the former did not seem to contribute to an overall reduction in hospital length of stay or improvement in postoperative outcomes of heart valve surgery and CABG patients.
10.1053/j.jvca.2020.10.022
pubmed_659_17445
Introduction Clinical leadership is an essential skill for physicians, empowering them to lead and coordinate teams, communicate clearly under various conditions, model positive behaviors, display emotional intelligence, and ultimately improve patient care outcomes. However, there are currently no standardized residency curricula or competency-based assessments for clinical leadership, as residents often assimilate leadership skills through trial-and-error or observation of their clinical faculty. By utilizing a comprehensive needs assessment and synthesizing evidence-based practices, we developed and implemented a longitudinal and skills-based clinical leadership curriculum for pediatric residents. Methods We modeled our clinical leadership curriculum after Kern's 6-step approach to curricular development and the Accreditation Council for Graduate Medical Education competency requirements for professionalism. We identified topics based on a resident needs assessment and synthesized evidence from published practices. The curriculum was implemented through both monthly facilitated group sessions and independent learning modules. Results 44 postgraduate year-2 (PGY-2) and PGY-3 pediatric residents participated in at least one monthly session of the clinical leadership curriculum. 27 (61%) completed the survey to evaluate the efficacy of the curriculum. Of the respondents, 23 (85%) residents found the leadership sessions useful, 4 (15%) were neutral, and none (0%) rated the sessions as not useful. 26 (96%) residents reported that the sessions should be continued. Conclusion The clinical leadership curriculum has been received favorably by senior pediatric residents at our institution. Our next steps are to pilot the curriculum within residency programs of different specialties at our own institution as well as with pediatric residencies at other institutions.
10.1177/23821205221096354
pubmed_617_9431
BACKGROUND Signaling through MEK-->ERK1/2 and PI3 kinases is implicated in many aspects of cell physiology, including the survival of oxidant exposure. Oxidants play a role in numerous physiological and pathophysiological processes, many of which rely on transport in and out of the nucleus. However, how oxidative stress impacts nuclear trafficking is not well defined. METHODOLOGY/PRINCIPAL FINDINGS To better understand the effect of stress on nucleocytoplasmic trafficking, we exposed cells to the oxidant diethyl maleate. This treatment activated MEK-->ERK1/2 as well as PI3 kinase-->Akt cascades and triggered the inhibition of classical nuclear import. To define the molecular mechanisms that regulate nuclear transport, we examined whether MEK and PI3 kinase signaling affected the localization of key transport factors. Using recently developed tools for image acquisition and analysis, the subcellular distributions of importin-alpha, CAS, and nucleoporins Nup153 and Nup88 were quantified in different cellular compartments. These studies identified specific profiles for the localization of transport factors in the nucleus and cytoplasm, and at the nuclear envelope. Our results demonstrate that MEK and PI3 kinase signaling as well as oxidative stress control nuclear trafficking and the localization of transport components. Furthermore, stress not only induced changes in transport factor distribution, but also upregulated post-translational modification of transport factors. Our results are consistent with the idea that the phosphorylation of importin-alpha, CAS, Nup153, and Nup88, and the O-GlcNAc modification of Nup153 increase when cells are exposed to oxidant. CONCLUSIONS/SIGNIFICANCE Our studies defined the complex regulation of classical nuclear import and identified key transport factors that are targeted by stress, MEK, and PI3 kinase signaling.
10.1371/journal.pone.0008420
pubmed_1127_17445
Plants are generally considered to represent a promising heterologous expression system for the production of valuable recombinant proteins. Minimal upstream plant production cost is a salient feature driving the development of plant expression systems used for the synthesis of recombinant proteins. For such a plant expression system to be fully effective, it is first essential to improve plant productivity by plant biomass after inserting genes of interest into a suitable plant. Plant productivity is related closely to its growth and development, both of which are affected directly by environmental factors. These environmental factors that affect the cultivation conditions mainly include temperature, light, salinity, drought, nutrition, insects and pests. In addition, genetic factors that affect gene expression at the transcriptional, translational, and post-translational levels are considered to be important factors related to gene expression in plants. Thus, these factors influence both the quality and quantity of recombinant protein produced in transgenic plants. Among the genetic factors, the post-translational process is of particular interest as it influences subcellular localization, protein glycosylation, assembly and folding of therapeutic proteins, consequently affecting both protein quantity and biological quality. In this review, we discuss the effects of cultivation condition and genetic factors on recombinant protein production in transgenic plants.
10.1016/j.biotechadv.2009.07.004
pubmed_825_16255
Increasingly, images are being acquired of the same patient using two or more diagnostic imaging modalities. If one such modality is MRI then a data set showing essentially anatomical information is produced. If the second is SPECT using HMPAO then a data set showing cerebral perfusion is also produced. The ability to conjoin such anatomical and functional data is an important goal in radiology. In this technical report five display strategies are investigated as a means of conveying simultaneously to the radiologist all the information from two such data sets. Illustrative examples are given for each display technique. Preliminary observations are made regarding comprehensibility, information loss and efficiency in conveying all the information simultaneously, for all five techniques.
10.1016/0895-6111(91)90138-l
pubmed_682_31
OBJECTIVE The methane mitigating potential of various plant-based polyphenol sources is known, but effects of combinations have rarely been tested. The aim of the present study was to determine whether binary and 3-way combinations of such phenol sources affect ruminal fermentation less, similar or more intensively than separate applications. METHODS The extracts used were from Acacia mearnsii bark (acacia), Vitis vinifera (grape) seed, Camellia sinensis leaves (green tea), Uncaria gambir leaves (gambier), Vaccinium macrocarpon berries (cranberry), Fagopyrum esculentum seed (buckwheat), and Ginkgo biloba leaves (ginkgo). All extracts were tested using the Hohenheim gas test. This was done alone at 5% of dry matter (DM). Acacia was also combined with all other single extracts at 5% of DM each, and with two other phenol sources (all possible combinations) at 2.5%+2.5% of DM. RESULTS Methane formation was reduced by 7% to 9% by acacia, grape seed and green tea and, in addition, by most extract combinations with acacia. Grape seed and green tea alone and in combination with acacia also reduced methane proportion of total gas to the same degree. The extracts of buckwheat and gingko were poor in phenols and promoted ruminal fermentation. All treatments except green tea alone lowered ammonia concentration by up to 23%, and the binary combinations were more effective as acacia alone. With three extracts, linear effects were found with total gas and methane formation, while with ammonia and other traits linear effects were rare. CONCLUSION The study identified methane and ammonia mitigating potential of various phenolic plant extracts and showed a number of additive and some non-linear effects of combinations of extracts. Further studies, especially in live animals, should concentrate on combinations of extracts from grape seed, green tea leaves Land acacia bark and determine the ideal dosages of such combinations for the purpose of methane mitigation.
10.5713/ajas.18.0665
pubmed_326_12196
We describe a 54-year-old man with heterotopic heart transplantation, who had severe exertional angina and dyspnea related to native heart ischemic disease. Because of drug resistant atrial fibrillation and atrial flutter of the native heart with fast ventricular response (130 beats/min), right-sided radiofrequency ablation of the His bundle was undertaken, followed by permanent pacemaker linkage of donor and native hearts. The procedure was successful and uneventful. Remarkable relief of symptoms was achieved.
10.1111/j.1540-8159.1996.tb03343.x
pubmed_70_25008
A computer tool, based on an acoustic transmission line model, was developed for modeling and predicting sound propagation and reflections in cascaded tube segments. This subroutine considered the number of interconnected tubes, their dimensions and wall properties, as well as medium properties to create a network of cascaded transmission line model segments, from which the impulse response of the network was estimated. Acoustic propagation was examined in air-filled cascaded tube networks and model predictions were compared to measured acoustic pulse responses. The model was able to accurately predict the location and morphology of reflections. The developed code proved to be a useful design tool for applications such as the guidance of catheters through compliant air-filled biological conduits.
10.1109/IEMBS.2007.4352761
others_87_10014
Ground observations illustrate the speed of and efficiency with which wolves Canis lupus can kill caribou Rangifer tarandus groenlandicus calves: a single wolf killed 3 calves on one occasion and 3, possibly 4 calves on a 2nd occasion at average kill rates of 1 calf/min, and 1 calf/8min or a calf/6min between the 1st and last deaths. The surplus killing of newborn caribou calves is attributed to their high densities and their vulnerability on the calving grounds. Distinction should be made between 'surplus killing' and 'excessive killing' by predators.-from Authors
10.1139/z85-045
pubmed_1033_13013
PURPOSE This study sought to aggregate literature data on in vitro failure loads and failure modes of prefabricated fiber-reinforced composite (FRC) post systems and to compare them to those of prefabricated metal, custom-cast, and ceramic post systems. MATERIALS AND METHODS The literature was searched using MEDLINE from 1984 to 2003 for dental articles in English. Keywords used were (post or core or buildup or dowel) and (teeth or tooth). Additional inclusion/exclusion steps were conducted, each step by two independent readers: (1) Abstracts describing post-and-core techniques to reconstruct endodontically treated teeth and their mechanical and physical characteristics were included (descriptive studies or reviews were excluded); (2) articles that included FRC post systems were selected; (3) in vitro studies, single-rooted human teeth, prefabricated FRC posts, and composite as the core material were the selection criteria; and (4) failure loads and modes were extracted from the selected papers, and failure modes were dichotomized (distinction was made between "favorable failures," defined as reparable failures, and "unfavorable failures,"defined as irreparable [root] fractures). RESULTS The literature search revealed 1,984 abstracts. Included were 244, 42, and 12 articles in the first, second, and third selection steps, respectively. Custom-cast post systems showed higher failure loads than prefabricated FRC post systems, whereas ceramic showed lower failure loads. Significantly more favorable failures occurred with prefabricated FRC post systems than with prefabricated and custom-cast metal post systems. CONCLUSION The variable "post system" had a significant effect on mean failure loads. FRC post systems more frequently showed favorable failure modes than did metal post systems.
pubmed_1033_13013
pubmed_796_17176
We have evaluated the possible effect of RU 41.740 (Biostim), a mixture of two glycoproteins extracted from K. pneumoniae, on the in vitro interleukin-2 (IL-2)-induced generation of NK cells from bone marrow (BM) precursors and on the in vivo reconstitution of splenic NK activity in lethally irradiated (9 Gy) and BM reconstituted mice. Our results show that RU 41.740 is able to augment the generation of NK cells when added (1-0.01 micrograms/ml) to normal or 5-fluorouracil-resistant BM, cultured in the presence of recombinant IL-2. Also, in vivo treatment of lethally irradiated mice, transplanted with syngeneic BM cells, with RU 41.740 (1-0.1 mg/kg i.v.) from day 0 through day 4 after BM graft, resulted in a significant augmentation of NK activity reconstitution.
10.1016/0192-0561(89)90102-1
pubmed_38_13347
BACKGROUND Acute upper gastrointestinal hemorrhage (UGIH) is a common reason for hospitalization with substantial associated morbidity, mortality, and cost. Differentiation of high- and low-risk patients using established risk scoring systems has been advocated. The aim of this study was to determine whether these scoring systems are more accurate than an emergency physician's clinical decision making in predicting the need for endoscopic intervention in acute UGIH. METHODS Patients presenting to a tertiary care medical center with acute UGIH from 2003 to 2006 were identified from the hospital database, and their clinical data were abstracted. One hundred ninety-five patients met the inclusion criteria and were included in the analysis. The clinical Rockall score and Blatchford score (BS) were calculated and compared with the clinical triage decision (intensive care unit vs non-intensive care unit admission) in predicting the need for endoscopic therapy. RESULTS Clinical Rockall score greater than 0 and BS greater than 0 were sensitive predictors of the need for endoscopic therapy (95% and 100%) but were poorly specific (9% and 4%), with overall accuracies of 41% and 39%. At higher score cutoffs, clinical Rockall score greater than 2 and BS greater than 5 remained sensitive (84% and 87%) and were more specific (29% and 33%), with overall accuracies of 48% and 52%. Clinical triage decision, as a surrogate for predicting the need for endoscopic therapy, was moderately sensitive (67%) and specific (75%), with an overall accuracy (73%) that exceeded both risk scores. CONCLUSIONS The clinical use of risk scoring systems in acute UGIH may not be as good as clinical decision making by emergency physicians.
10.1016/j.ajem.2010.11.007
pubmed_875_3527
Perineuriomas are rare peripheral nerve sheath tumors arising from or differentiating along the lines of normal perineurial cells. They can be divided into intraneural and soft tissue types, with the latter category including a significant number of morphological variants. Herein, we further expand their morphological spectrum to include "pseudolipoblastic" perineuriomas. These lesions occurred in the tongue of a 30-year-old man and in the triceps of a 67-year-old woman and were characterized by bland, epithelioid cells with striking intracytoplasmic vacuolization. The architecture varied, with some areas showing a striking "net-like" or "microreticular" pattern and smaller areas having a more typical spindled and whorled appearance. Clinical follow-up (5months and 52months, respectively) showed no evidence of local recurrence or metastasis. Multiple perineurial markers, including epithelial membrane antigen, claudin-1, GLUT-1, and collagen IV, were diffusely positive. Both cases were submitted in consultation out of concern that they represented high-grade liposarcomas. To the best of our knowledge, this unusual morphological variant of perineurioma has not been reported. These tumors appear to be entirely benign and should be cured with simple excision. Pseudolipoblastic perineuriomas should be distinguished from round cell and epithelioid pleomorphic liposarcomas, as well as from other tumors that may show prominent intracytoplasmic vacuolization.
10.1016/j.humpath.2016.06.017
pubmed_443_21406
To determine the relation between endocarditis/septicemia and systemic inflammatory response syndrome (SIRS), septic shock, MODS, we performed a retrospective analysis in 196 HIV-negative patients, with endocarditis/septicemia. No deaths were observed between 20 patients with endocarditis without severe infective SIRS/septic shock. On the other hand among 10 patients with endocarditis with severe infective SIRS/septic shock we registered 3 deaths (P = 0.052). No deaths were registered among 93 patients with septicemia without severe infective SIRS/septic shock. Between 73 patients with septicemia and severe infective SIRS/septic shock 9 (12.3%) patients died and, precisely, 7/61 in severe infective SIRS (11.4%) and 2/.12 (16.6%) in septic shock (P = 0.003). The definition of septicemia according to Schottmüller (1914), as a generalized bacterial infection with a persistent bacteremia is still justified. The term "sepsis" has become ambiguous because it has been used as synonym of "acute response to infection", while in the past and presently, at least in Europe, it is synonym of septicemia, persistent bacteremia. The term of SIRS could avoid the misunderstanding. The words: "infective SIRS", "severe infective SIRS", may label properly the reactive events mounted by the host as a useful defence against infections but they become dangerous and bring about septic shock, organ failure and mortality when excessive.
pubmed_443_21406
others_314_66565
The impact of type 1 diabetes (T1D) on muscle endurance and oxidative capacity is currently unknown. PurposeMeasure muscle endurance and oxidative capacity of adults with T1D compared to controls. MethodsA cross-sectional study design with a control group was used. Subjects (19-37 years old) with T1D (n=17) and controls (n=17) were assessed with hemoglobin A1c (HbA1c) and casual glucose. Muscle endurance was measured with an accelerometer at stimulation frequencies of 2, 4, and 6 Hz for a total of nine minutes. Mitochondrial capacity was measured using near-infrared spectroscopy after exercise as the rate constant of the rate of recovery of oxygen consumption. ResultsT1D and control groups were similar in age, sex, height, and race. The T1D group had slightly higher BMI values and adipose tissue thickness over the forearm muscles. Casual glucose was 150{+/-}70 mg/dL for T1D and 98{+/-}16 mg/dL for controls (P=0.006). HbA1c of T1D subjects was 7.1{+/-}0.9% and 5.0{+/-}0.4% for controls (P<0.01). Endurance indexes at 2, 4, and 6 Hz were 94.5{+/-}5.2%, 81.8{+/-}8.4%, and 68.6{+/-}13.5% for T1D and 94.6{+/-}4.1%, 85.9{+/-}6.3%, and 68.7{+/-}15.4% for controls (p = 0.97, 0.12, 0.99, respectively). There were no differences between groups in mitochondrial capacity (T1D= 1.9{+/-}0.5 min-1 and control=1.8{+/-}0.4 min-1, P=0.29) or reperfusion rate (T1D= 8.8{+/-}2.8s and control=10.3{+/-}3.0s, P=0.88). There were no significant correlations between HbA1c and either muscle endurance, mitochondrial capacity or reperfusion rate. ConclusionsAdults with T1D did not have reduced oxidative capacity, muscle endurance or muscle reperfusion rates compared to controls. HbA1c also did not correlate with muscle endurance, mitochondrial capacity or reperfusion rates. Future studies should extend these measurements to older people or people with poorly-controlled T1D
10.1101/862086
pubmed_576_3159
The use of hybrid methods, involving both quantum mechanics and molecular mechanics, to model the mechanism of enzyme-catalysed reactions, is discussed. Two alternative approaches to treating the electrostatic interactions between the quantum mechanical and molecular mechanical regions are studied, involving either the inclusion of this term in the electronic Hamiltonian (QM/MM), or evaluating it purely classically (MO + MM). In the latter scheme, possible problems of using force fields that are standard for macromolecular modelling are identified. The use of QM/MM schemes to investigate the mechanism of the enzymes thymidine phosphorylase (ThdPase) and protein tyrosine phosphatase (PTP) is described. For both systems, transition states have been identified using a PM3 Hamiltonian. For ThdPase, concerted motion of the enzyme during the course of the reaction is suggested and, for PTP, a two-step dephosphorylation reaction is indicated, both with quite low barriers.
10.1039/a801719k
pubmed_674_11227
We have functionally characterized the role of two putative mitochondrial enzymes in valine degradation using insertional mutants. Prior to this study, the relationship between branched-chain amino acid degradation (named for leucine, valine and isoleucine) and seed development was limited to leucine catabolism. Using a reverse genetics approach, we show that disruptions in the mitochondrial valine degradation pathway affect seed development and germination in Arabidopsis thaliana. A null mutant of 3-hydroxyisobutyryl-CoA hydrolase (CHY4, At4g31810) resulted in an embryo lethal phenotype, while a null mutant of methylmalonate semialdehyde dehydrogenase (MMSD, At2g14170) resulted in seeds with wrinkled coats, decreased storage reserves, elevated valine and leucine, and reduced germination rates. These data highlight the unique contributions CHY4 and MMSD make to the overall growth and viability of plants. It also increases our knowledge of the role branched-chain amino acid catabolism plays in seed development and amino acid homeostasis.
10.1111/tpj.13538
pubmed_830_25093
PURPOSE Although the efficacy of selective neck dissection (SND) in the management of a node-negative neck is established, its utility in the management of node-positive disease remains controversial. The objective of this study was to evaluate the oncologic safety of SND in the management of N1/N2 oral cavity squamous cell carcinoma. MATERIALS AND METHODS From a prospectively collected electronic database of patients with oral cavity cancer, a retrospective analysis was conducted of patients with nonrecurrent, clinical, and/or pathologic N1/N2 oral cavity squamous cell carcinoma who underwent SND of levels I to III/IV. The patients were stratified into 2 groups: clinical N0 but pathologic N1/N2 (cN0-pN1/N2) and clinical N1/N2 (cN1/N2). The primary outcome variable of the study was the ipsilateral regional recurrence rate. Categorical data were analyzed by the 2-sided Fisher exact test, and 3-year Kaplan-Meier ipsilateral regional control rate, regional recurrence-free survival, disease-free survival, and overall survival were estimated. RESULTS Forty-nine patients constituted the study sample, with 37 patients in the cN1/N2 group and 12 patients in the cN0-pN1/N2 group. During the follow-up period of 3 years, 2 patients (∼4%) developed ipsilateral neck recurrence, and these patients were in the cN1/N2 group. The 3-year Kaplan-Meier ipsilateral regional control rate was 95%. CONCLUSIONS SND may produce a satisfactory ipsilateral regional control rate in patients with early-stage node-positive oral squamous cell carcinoma. A prospective, randomized clinical trial comparing SND with modified radical neck dissection may be required for a categorical conclusion of these findings.
pubmed_830_25093
pubmed_1005_19310
Purpose: Extremity soft tissue leiomyosarcoma (LMS) with metastasis is a rare disease with a poor prognosis. The purpose of our study was to define clinical features of extremity soft tissue LMS with metastasis as well as to identify multivariable predictors of survival. Methods: During 1973-2015, 239 patients with metastatic extremity soft tissue LMS were identified from the Surveillance, Epidemiology, and End Results (SEER) program database. The prognostic analysis was performed using the Kaplan-Meier method and a Cox proportional hazards regression model. Results: This group comprised 126 females (52.7%) and 113 males (47.3%), whose ages ranged from 8 to 95 years (median 67 years). The overall survival (OS) and cancer-specific survival (CSS) rates of the entire group at 3 years were 22.6% and 23.4%, respectively. The median OS and CSS were 14.0±1.5 and 15.0±2.3 months, respectively. Multivariate analysis revealed that tumor size >10 cm, no surgery and no chemotherapy were independent risk factors of decreased OS and CSS. Radiotherapy was not significantly associated with OS or CSS. Conclusion: Extremity soft tissue LMS patients who present with metastasis at diagnosis had a poor prognosis. Patients who performed surgery for primary tumors and chemotherapy had a better chance for prolonged survival.
10.7150/jca.29874
pubmed_813_20440
Homocysteine is a sulfhydryl amino acid formed during metabolism of methionine. Increasing evidence suggests that homocyst(e)ine may act as an independent risk factor for ischemic heart disease, cerebrovascular disease, and peripheral arterial disease. Recent prospective data have shown that homocyst(e)ine levels in the top 20% of the population increase the risk for ischemic heart disease by approximately twofold. Homocyst(e)ine seems to promote the progression of atherosclerosis by causing endothelial dysfunction, increasing oxidant stress, and promoting vascular smooth muscle growth. Recent human studies using methionine loading to experimentally induce moderate hyperhomocyst(e)inemia have demonstrated rapid and profound impairment of resistance and conduit artery endothelial function. No data are available from randomized, controlled trials of the effects of lowering plasma homocyst(e)ine on atherosclerotic vascular events; however, screening for hyperhomocyst(e)inemia should be actively considered in individuals with progressive and unexplained atherosclerosis. Both fasting and postmethionine load homocyst(e)ine levels should be measured. B vitamins, including folic acid and vitamins B6 and B12 are the mainstay of treatment of patients with hyperhomocyst(e)inemia. Primary prevention strategies await the completion of long-term, randomized, prospective studies.
10.1097/00001573-199907000-00002
pubmed_482_22443
Biochar can be used as a soil amendment. However, it generally possesses unique physicochemical properties and complex organics, which could affect soil methanogenesis. In this study,straw-based biochars obtained at 300 °C (BC300), 500 °C (BC500) and 700 °C (BC700) were added to the paddy soil. Compared with the blank group, BC300 significantly increased paddy soil methane emissions by about 38%. However, this promoting effect gradually disappeared with the increase of pyrolysis temperature, and the inhibition even appeared in the BC700 group with the methane reduction by 18.2%. This might be related to the organics released from biochar. Van Krevelen (VK) diagram showed that the aromaticity of BC700 and BC500 were significantly higher than BC300. Fluorescent analysis further revealed that BC300 increased the amount of degradable fluorescent organics in the soil, which could provide more substrate for methane production. Moreover, as pyrolysis temperature increased, the fluorescent organics released were more likely to be non-biodegradable humus. In addition, it was shown that BC700 could adsorb some inherent organics in the soil, and thus reduced the total organic content and inhibited soil methane emissions. Microbial analysis showed that methanogenesis had a positive correlation with the abundance of syntrophic bacteria (e.g. Desulfobacca and Clostridium) which had ability to further degrade various types of organics and provided substrates to the methanogens. This article provides a deeper understanding regarding for the effects of biochar on methane emission from paddy soil in terms of organics and microbial perspectives.
10.1016/j.scitotenv.2020.140725
pubmed_12_9717
The study discusses the results of treatment of 597 cases of stage I-IIa breast cancer who underwent either mastectomy after Halsted, Patey or Pirogov (434 patients), or organ-saving radical resection of the breast (163). The analysis of the data identified biologic, morphologic, psychologic and anthropometric criteria as well as laboratory tests which may serve as criteria for selecting candidates for organ-saving surgery and adjuvant radiotherapy. In a group of patients who met the criteria, sparing surgery yielded good results in terms of five-year survival rate (88.9%) and degree of socio-occupational rehabilitation.
pubmed_12_9717
pubmed_2_8181
Plant parasitic nematodes cause approximately 157 billion US dollars in losses worldwide annually. The soybean cyst nematode (SCN), Heterodera glycines, is responsible for an estimated one billion dollars in losses to the US farmer each year. A promising new approach for control of plant parasitic nematode control is gene silencing. We tested this approach by silencing the SCN gene HgALD, encoding fructose-1,6-diphosphate aldolase. This enzyme is important in the conversion of glucose into energy and may be especially important in actin-based motility during parasite invasion of its host. An RNAi construct targeted to silence HgALD was transformed into soybean roots of composite plants to examine its efficacy to reduce the development of females formed by SCN. The number of mature females on roots transformed with the RNAi construct designed to silence the HgALD gene was reduced by 58%. These results indicate that silencing the aldolase gene of SCN +can greatly decrease the number of female SCN reaching maturity, and it is a promising step towards broadening resistance of plants against plant-parasitic nematodes.
pubmed_2_8181
pubmed_1074_4965
Acute kidney injury (AKI) is one of the most prominent characteristics of hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus. The present study evaluated the incidence and severity of AKI classified by both the RIFLE and AKIN criteria in 120 HFRS patients at 48  h and 1 week of the patient admission. The agreements between RIFLE and AKIN and RIFLE and AKIN defined by serum creatinine (AKINc and RIFLEc) were examined by Kappa statistics. AKI occurred in 79.2% and 82.5% at 48  h and in 84.2% and 89.2% at 1 week of admission by RIFLE and AKIN criteria, respectively. RIFLE and AKIN showed very good agreement in classifying AKI at 48  h and 1 week of admission (κ > 0.900). RIFLE and RIFLEc and AKIN and AKINc at 48  h and 1 week of admission had almost perfect agreement (κ > 0.900). The classifications of RIFLE and RIFLEc and AKIN and AKINc at 48  h and 1 week were in good agreement (κ > 0.650). AKI classifications by RIFLE and AKIN were associated with mortality, occurrence of complications, and length of hospital stay. We conclude that AKI occurs in nearly 90% of HFRS patients during the disease course. RIFLE and AKIN classify AKI in HFRS with similar sensitivity. RIFLEc and AKINc may be used as alternatives of standard RIFLE and AKIN in the settings of general wards. The AKI classifications defined at 48  h of admission have predictive value for HFRS disease progression and severity.
10.1089/vbz.2010.0132
pubmed_204_17842
BACKGROUND Endometriosis is an oestrogen-dependent disease with an unclear aetiology and pathogenesis affecting 6-10% of the global female population, predominantly those of reproductive age. Herein, we profile the transcriptomes of approximately 55,000 single cells from three groups including ectopic endometrium, eutopic endometrium from women with endometriosis, and eutopic endometrium from healthy women to create a single-cell transcriptome atlas of endometriosis. RESULTS We have identified 9 cell types and performed single-cell analysis of fibroblasts, and determined a potential developmental trajectory associated with endometriosis. We also identified fibroblast subpopulations related to endometriosis development and found that StAR played an important role in this process. Moreover, T cells in endometriosis were less activated or inflammatory with decreased effector CD8 + T cells, while the composition ratio of natural killer cells decreased and the percentage of monocytes/macrophages increased in endometriosis cysts. In addition, the effectiveness of immune cells in endometriosis lesions, eutopic endometrium from women with endometriosis, and eutopic endometrium from healthy women was distinct. Cell-cell interaction analyses highlighted the imbalanced immune environment in endometriosis lesions and immune cells in endometriosis could promote the development of the disease. CONCLUSION Our study provided a systematic characterisation of endometriosis and insights into the aetiology and pathology of endometriosis.
10.1186/s13578-021-00637-x
pubmed_196_12556
Multiple sclerosis (MS) can create different kinds of symptoms by involving different fields of the central nervous system. Cognitive impairment (CI) is one of the symptoms that can be caused by the onset of the disease and provide a change in the patient's quality of life. Considering the course of the disease, CI usually worsens increasingly, and there is usually a severe CI in patients with end stage of MS. However, progressing CI can be so fast and severe in a few patients that it can disrupt the daily affairs of the individual. This paper plans to define the aggressive course of CIs in MS patients according to the reported cases. This definition explains that, the aggressive course of CI in MS patients happens in less than 5 years from the onset of the disease, and during this time, it causes dementia in the patient.
10.1016/j.jocn.2019.08.104
others_398_12162
Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable, neuropsychiatric disorder among children. Linkage studies in isolated populations have proved powerful to detect variants for complex diseases, such as ADHD. We performed a genome-wide linkage scan for ADHD in nine patients from a genetically isolated population in the Netherlands, who were linked to each other within 10 generations through multiple lines of descent. The genome-wide scan was performed with a set of 400 microsatellite markers with an average spacing of ± 10-12cM. We performed multipoint parametric linkage analyses using both recessive and dominant models. Our genome scan pointed to several chromosomal regions that may harbour ADHD susceptibility genes. None exceeded the empirical genome-wide significance threshold, but the Log of odds (LOD) scores were > 1.5 for regions 6p22 (Heterogenetic log of odds (HLOD) = 1.67) and 18q21 - 22 (HLOD = 2.13) under a recessive model. We followed up these two regions in a larger sample of ADHD patients (n = 21, 9 initial and 12 extra patients). The LOD scores did not increase after increasing the sample size (6p22 (HLOD = 1.51), 18q21 - 22 (HLOD = 1.83)). However, the LOD score on 6p22 increased to 2 when a separate analysis was performed for the inattentive type ADHD children. The linkage region on chromosome 18q overlaps with the findings of association of rs2311120 (P = 10-5) and rs4149601 (P = 10-4) in the genome-wide association analysis for ADHD performed by the Genetic Association Information Network consortium. Furthermore, there was an excess of regions harbouring serotonin receptors (HTR1B, HTR1E, HTR4, HTR1D, and HTR6) that showed a LOD score > 1 in our genome-wide s
10.1038/ejhg.2008.260
pubmed_98_23860
C1q domain-containing (C1qDC) proteins are a group of biopolymers involved in immune response as pattern recognition receptors (PRRs) in a lectin-like manner. A new protein MkC1qDC from the hemolymph plasma of Modiolus kurilensis bivalve mollusk widespread in the Northwest Pacific was purified. The isolation procedure included ammonium sulfate precipitation followed by affinity chromatography on pectin-Sepharose. The full-length MkC1qDC sequence was assembled using de novo mass-spectrometry peptide sequencing complemented with N-terminal Edman's degradation, and included 176 amino acid residues with molecular mass of 19 kDa displaying high homology to bivalve C1qDC proteins. MkC1qDC demonstrated antibacterial properties against Gram-negative and Gram-positive strains. MkC1qDC binds to a number of saccharides in Ca2+-dependent manner which characterized by structural meta-similarity in acidic group enrichment of galactose and mannose derivatives incorporated in diversified molecular species of glycans. Alginate, κ-carrageenan, fucoidan, and pectin were found to be highly effective inhibitors of MkC1qDC activity. Yeast mannan, lipopolysaccharide (LPS), peptidoglycan (PGN) and mucin showed an inhibitory effect at concentrations three orders of magnitude greater than for the most effective saccharides. MkC1qDC localized to the mussel hemal system and interstitial compartment. Intriguingly, MkC1qDC was found to suppress proliferation of human adenocarcinoma HeLa cells in a dose-dependent manner, indicating to the biomedical potential of MkC1qDC protein.
10.3390/md19120668
pubmed_30_5323
Invasive hemodynamic monitoring is frequently required in the management of patients in intensive care units. A fiberoptic flow-directed thermal dilution pulmonary artery catheter capable of continuously monitoring the mixed venous saturation, while more expensive than a conventional pulmonary artery catheter, theoretically could result in better patient care, and might be cost-effective if it resulted either in fewer blood tests being ordered or in less time in the intensive care unit. To test this hypothesis, we designed a randomized trial in our Medical Intensive Care Unit to compare a standard pulmonary artery catheter with a fiberoptic catheter. Twenty-six patients received a standard catheter and 25 patients received the fiberoptic catheter. There were no statistical differences between the groups in age, time in the intensive care unit, number of tests ordered, hours of mechanical ventilator therapy, hours of vasoactive drug therapy, or mortality rate. The only statistically significant differences between the groups were that (1) the fiberoptic catheter required a longer insertion time and (2) there were more technical problems in consistently obtaining the wedge pressure in the patients with the fiberoptic catheters. We conclude that routine substitution of a fiberoptic catheter for the standard pulmonary artery catheter is not indicated.
pubmed_30_5323
pubmed_922_20198
Cannabidiol (CBD), a natural phytocannabinoid without psychoactive effect, is a well-known anti-inflammatory and antioxidant compound. The possibility of its use in cytoprotection of cells from harmful factors, including ultraviolet (UV) radiation, is an area of ongoing investigation. Therefore, the aim of this study was to evaluate the effect of CBD on the regulatory mechanisms associated with the redox balance and inflammation in keratinocytes irradiated with UVA [30 J/cm2] and UVB [60 mJ/cm2]. Spectrophotometric results show that CBD significantly enhances the activity of antioxidant enzymes such as superoxide dismutase and thioredoxin reductase in UV irradiated keratinocytes. Furthermore, despite decreased glutathione peroxidase and reductase activities, CBD prevents lipid peroxidation, which was observed as a decreased level of 4-HNE and 15d-PGJ2 (measured using GC/MS and LC/MS). Moreover, Western blot analysis of protein levels shows that, under stress conditions, CBD influences interactions of transcription factors Nrf2- NFκB by inhibiting the NFκB pathway, increasing the expression of Nrf2 activators and stimulating the transcription activity of Nrf2. In conclusion, the antioxidant activity of CBD through Nrf2 activation as well as its anti-inflammatory properties as an inhibitor of NFκB should be considered during design of new protective treatments for the skin.
10.3390/cells8080827
pubmed_43_8283
BACKGROUND Serious adverse effects of fluoroquinolone antibiotics have been described for more than decade. Recently, several drug regulatory agencies have advised restricting their use in milder infections for which other treatments are available, given the potential for disabling and possibly persistent side effects. We aimed to describe variations in fluoroquinolone use for initial treatment of urinary tract infection (UTI), acute bacterial sinusitis (ABS), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the outpatient setting across Canada. METHODS Using administrative health data from six provinces, we identified ambulatory visits with a diagnosis of uncomplicated UTI, uncomplicated AECOPD or ABS. Antibiotic exposure was determined by the first antibiotic dispensed within 5 days of the visit. RESULTS We identified 4,303,144 uncomplicated UTI events among 2,170,027 women; the proportion of events treated with fluoroquinolones, mostly ciprofloxacin, varied across provinces, ranging from 18.6% (Saskatchewan) to 51.6% (Alberta). Among 3,467,678 ABS events (2,087,934 patients), between 2.2% (Nova Scotia) and 11.2% (Ontario) were dispensed a fluoroquinolone. For 1,319,128 AECOPD events among 598,347 patients, fluoroquinolones, mostly levofloxacin and moxifloxacin, ranged from 5.8% (Nova Scotia) to 35.6% (Ontario). The proportion of uncomplicated UTI and ABS events treated with fluoroquinolones declined over time, whereas it remained relatively stable for AECOPD. CONCLUSIONS Fluoroquinolones were commonly used as first-line therapies for uncomplicated UTI and AECOPD. However, their use varied widely across provinces. Drug insurance formulary criteria and enforcement may be a key to facilitating better antibiotic stewardship and limiting potentially inappropriate first-line use of fluoroquinolones.
10.1186/s12879-021-06467-z
pubmed_235_9917
The identification of the Mas-related G-protein-coupled receptors (Mrgpr) as targets of diverse stimuli of mast cells (MCs), including neuropeptides and pseudo-allergy causing drugs, has placed these receptors at a prime position in MC research. However, the species-dependent diversity of these receptors raises the need for an adequate model for investigating the human MRGPRX2 receptor. RBL-2H3 cells, stably transfected with MRGPRX2 (RBL-MRGPRX2), are increasingly used for this purpose. Therefore, we investigated whether ectopically expressed MRGPRX2, in rat MCs, recapitulates its authentic signaling. To this purpose, we performed a broad comparative study of the responses of human LAD-2 MCs that express MRGPRX2 endogenously, and RBL-MRGPRX2 cells to compound 48/80, substance P and vancomycin, three proto-type ligands of MRGPRX2. We demonstrate that both models share similar dose-response relationships, kinetics and sensitivities to a wide range of signaling targeting drugs. Therefore, our results indicate that ectopically expressed MRGPRX2 preserves the signaling pathways employed to evoke human MC degranulation, which we show to rely on ERK1/2 MAP kinases, phospholipase C (PLC) and autophagy-related signaling. Importantly, we also show that the underlying mechanisms of MRGPRX2-triggered MC degranulation in either LAD-2 or RBL-MRGPRX2 cells are different from those elicited by its rodent orthologs.
10.3390/cells10020376
pubmed_1084_4642
Carboxyhemoglobin is a specific biomarker of carbon monoxide (CO) exposition. The source of CO indoors are most often gas, oil or carbon furnaces and stoves or bathroom gas heaters. CO intoxication during fire or exposition to car fumes are sporadic. The aim of the study was: to present the frequency of CO intoxications diagnosed in Laboratory of Analytical Toxicology UJ Collegium Medicum in years 2002 - 2010, to present the season trends of CO intoxications, show sex and age structure of CO intoxicated patients. Material were Laboratory of Analytical Toxicology and Drug Monitoring data records from years 2002 - 2010. CO intoxication was confirmed and recognized when COHb blood concentration was higher than 10%. Annual number of CO poisonings was stable in the period of time, varied from 209 to 296 (mean 256,2 CO poisonings per year). Sex structure of CO poisoned patients showed little female dominance (54.6%). Carbon monoxide poisonings distribution was seasonal. The season of intensified CO intoxications lasted from October to March, the highest intensity was in December and January. The CO poisoning problem is still actual. Society education about security, recognition, diagnosis and practice in carbon monoxide exposition is still needful.
pubmed_1084_4642
pubmed_604_8156
The Voyager 2 encounter has enhanced our understanding of earlier results and provided measurements beyond 160 Jupiter radii (R(J)) in the magnetotail. Significant fluxes of energetic sulfur and oxygen nuclei (4 to 15 million electron volts per nucleon) of Jovian origin were observed inside 25 R(J), and the gradient in phase space density at 12 R(J) indicates that the ions are diffusing inward. A substantially longer time delay versus distance was found for proton flux maxima in the active hemisphere in the magnetotail at Jovicentric longitudes lambda(III), = 260 degrees to 320 degrees than in the inactive hemisphere at lambda(III), = 85 degrees to l10 degrees . These delays can be related to the radial motion of plasma expanding into the magnetotail, and differences in the expansion speeds between the active and inactive hemispheres can produce rarefaction regions in trapped particles. It is suggested that the 10-hour modulation of interplanetary Jovian electrons may be associated with the arrival at the dawn magnetopause of a rarefaction region each planetary rotation.
10.1126/science.206.4421.984
pubmed_724_19028
Although often listed together in review articles and case series, tracheobronchial and esophageal foreign bodies can be dissimilar. Airway foreign bodies can range widely in the severity of presentation. When to proceed with a diagnostic bronchoscopy is not always obvious and is based on three diagnostic tools: clinical history, physical examination, and radiography. Radiography plays a more central role in the diagnosis of an esophageal foreign body. In either condition, a delay in diagnosis leads to a greater complication rate. This article provides diagnostic and treatment guidelines in the management of aerodigestive foreign bodies.
10.1016/j.otc.2008.01.013
pubmed_935_1506
Several possible mechanisms to account for hormone-induced enlargement of receptive field areas of individual mechanoreceptive trigeminal neurons of the rat were investigated. Mechanoreceptor sensitivity was estimated by receptive field thresholds and showed no consistent change following systemic estrogen treatment. Alteration of the viscoelastic properties of skin was suggested as 10 days of estrogen treatment caused an acute epidermal hyperplasia (38.7%), but force-displacement measurements revealed no significant change in skin distensibility. Interestingly, both chemical (6-hydroxydopamine) and surgical sympathectomy mimicked the effect of estrogen on receptive field areas by promoting dramatic enlargement of individual neuronal fields without decreasing receptive field force thresholds. Among skin samples from estrogen, 6-hydroxydopamine and surgical sympathectomized animals, only 6-hydroxydopamine treatment caused any significant alteration in skin norepinephrine content. These results strongly suggest an indirect catecholamine involvement in estrogen-induced enlargement of receptive field areas.
10.1016/0006-8993(80)90809-4
pubmed_1105_21464
Multiple sclerosis (MS) is a chronic neurological disease that commonly affects lower urinary tract function. In fact, change in bladder function may be the presenting complaint in as many as 10% of patients suffering from this condition and eventually up to 80% of patients with MS will suffer bladder symptoms.
pubmed_1105_21464
pubmed_11_14595
Research has indicated that individuals of Asian descent, relative to other racial groups, demonstrate reduced emotional responding and lower prevalence rates of several anxiety disorders. It is unclear though whether these group differences extend to biomarkers of anxiety disorders and whether genetic differences play a role. This study compared self-identified Caucasian, Latino, and Asian persons (total N = 174) on startle response during a baseline period and while anticipating unpredictable threat-a putative biomarker for certain anxiety disorders--as well as predictable threat. In addition, the association between genetic ancestry and startle response was examined within each racial group to determine potential genetic influences on responding. For the baseline period, Asian participants exhibited a smaller startle response relative to Caucasian and Latino participants, who did not differ. Within each racial group, genetic ancestry was associated with baseline startle. Furthermore, genetic ancestry mediated racial group differences in baseline startle. For the threat conditions, a Race × Condition interaction indicated that Asian participants exhibited reduced startle potentiation to unpredictable, but not predicable, threat relative to Caucasian and Latino participants, who did not differ. However, genetic ancestry was not associated with threat-potentiated startle in any racial group. This study adds to the growing literature on racial differences in emotional responding and provides preliminary evidence suggesting that genetic ancestry may play an important role. Moreover, reduced sensitivity to unpredictable threat may reflect a mechanism for why individuals of Asian descent are at less risk for particular anxiety disorders relative to other racial groups.
10.1037/a0035776
pubmed_1060_6398
Although there has been considerable interest in the effects of nasal airway impairment on facial growth, the relationship is still unclear. This study examined the effect of nasal airway size on upper airway pressures during breathing. Three phases of data collection were involved. The first phase used a model to describe pressures during simulated normal and impaired respirations. The second phase involved subjects with normal airways, and the third used persons who were judged by an otolaryngologist to be nasally impaired. Aerodynamic assessment techniques were used to measure airway pressures during breathing and to assess nasal airway size. Results of the modeling study suggest that when nasal cross-sectional area is greater than 0.1 cm2, pressures associated with breathing are not excessive. These findings also suggest that slight lip opening (2 to 3 mm) would significantly reduce airway pressures. In addition, pressure magnitudes of the normal and nasally impaired groups were similar to the modeling data, and no significant difference in pressures was observed between the two groups. Accordingly, the assumptions that nasally impaired persons generate abnormal breathing pressures and that these pressures directly influence facial growth are questionable.
10.1016/0002-9416(86)90007-2
pubmed_929_10924
The elaboration, characterisation and efficiency of potential two-photon-excited photodynamic therapy (PDT) treatment of new poly(d,l-lactide-co-glycolide) nanoparticles loaded with ruthenium(II) complexs are presented. The materials are based on the encapsulation of RuII complexes through an all-biocompatible process. The size of the nanoparticles is around 100 nm. The internal concentration is several orders of magnitude higher than the overall concentration, which leads to a more efficient and targeted effect. The therapeutic potential for PDT of these nanoparticles has been studied in vitro on C6 glioma cells.
10.1002/cplu.201300242
pubmed_368_14061
Oxidative stress plays an important role in wound healing but data relating oxidative stress to fracture healing are scarce. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the major transcription factor that controls the cellular defence essential to combat oxidative stress by regulating the expression of antioxidative enzymes. This study examined the impact of Nrf2 on fracture healing using a standard closed femoral shaft fracture model in wild-type (WT) and Nrf2-knockout (Nrf2-KO)-mice. Healing was evaluated by histology, real-time RT-PCR, µCT and biomechanical measurements. We showed that Nrf2 expression is activated during fracture healing. Bone healing and remodelling were retarded in the Nrf2-KO compared to the WT-mice. Nrf2-KO-mice developed significantly less callus tissue compared to WT-mice. In addition, biomechanical testing demonstrated lower strength against shear stress in the Nrf2-KO-group compared to WT. The expression of vascular endothelial growth factor (VEGF) and osteocalcin is reduced during fracture healing in Nrf2-KO-mice. Taken together, our results demonstrate that Nrf2 deficiency in mice results in impaired fracture healing suggesting that Nrf2 plays an essential role in bone regeneration. Pharmacological activation of Nrf2 may have therapeutic potential for the enhancement of fracture healing.
10.1007/s00223-014-9900-5
pubmed_498_25625
Agomelatine is a novel melatonergic antidepressant, with a non-monoaminergic mechanism of action. The aim of this study was to evaluate its plasma concentrations after a single oral dose of 300 mg/dog in fasted and fed status. The research was carried out in 6 adult healthy Labrador dogs according to a randomized open, single-dose, two-treatment, two-phase, paired 2 × 2 cross-over study. At the end of the study all the animals had received the drug in fasted and fed conditions. The drug concentrations were detected in plasma by a validated LC-MS/MS analytical method. The plasma concentrations of agomelatine were found to be extremely variable in both groups as well as the pharmacokinetic profiles. Due to these variable findings the only reliable pharmacokinetic parameters were assessed as Cmax (31.8 vs 15.7 ng/mL), Tmax (0.75 vs 4 h) and AUC (155 vs 52 ng h/mL) in fasted and fed status, respectively. Unfortunately, as a pioneer study, the small animal sample size used along with the unanticipated variability did not allow to neither statistically estimate if food can affect the pharmacokinetics of agomelatine nor recommend agomelatine for off-label therapies in canine species. Further studies are warranted to clarify this issue.
10.1016/j.rvsc.2021.07.019
pubmed_245_10648
Circulating tumor cells (CTCs) have received a great deal of scientific and clinical attention as a biomarker for diagnosis and prognosis of many types of cancer. Given their potential significance in clinics, a variety of detection methods, utilizing the recent advances in nanotechnology and microfluidics, have been introduced in an effort of achieving clinically significant detection of CTCs. However, effective detection and isolation of CTCs still remain a tremendous challenge due to their extreme rarity and phenotypic heterogeneity. Among many approaches that are currently under development, this review paper focuses on a unique, promising approach that takes advantages of naturally occurring processes achievable through application of nanotechnology to realize significant improvement in sensitivity and specificity of CTC capture. We provide an overview of successful outcome of this biomimetic CTC capture system in detection of tumor cells from in vitro, in vivo, and clinical pilot studies. We also emphasize the clinical impact of CTCs as biomarkers in cancer diagnosis and predictive prognosis, which provides a cost-effective, minimally invasive method that potentially replaces or supplements existing methods such as imaging technologies and solid tissue biopsy. In addition, their potential prognostic values as treatment guidelines and that ultimately help to realize personalized therapy are discussed.
10.1016/j.addr.2017.12.005
pubmed_1074_15182
The pathogenesis of Acanthamoeba keratitis (AK) is complicated. In our previous studies, TLR4 was found involved in the process of infection by Acanthamoeba in human corneal cells. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signalling pathway in Wistar rats challenged with Acanthamoeba. The rat model of AK was established. Corneas were collected and analysed by real-time PCR to assess the mRNA levels of TLR 2, 4, myeloid differentiation protein (MyD)88, nuclear factor (NF)-κB, extracellular signal-regulated kinase (ERK), interleukin (IL)-8, tumour necrosis factor (TNF)-α and interferon (IFN) -β. Immunocytochemistry and Western blot were conducted to examine the proteins of TLR2, TLR4, p-Erk1/2 and p-IκB. Specific inhibitors PDTC and U0126 were used to pretreat the animals to determine the exact receptor and signalling pathway involved in pathogenesis. Expressions of TLR4, MyD88, all three cytokines, NF-κB, p-IκB and p-Erk1/2 were increased in Acanthamoeba-treated rat corneas. PDTC inhibited the production of IL-8 and TNF-α, while U0126 inhibited the synthesis of IFN-β. TLR4 was involved in sensing the challenge of Acanthamoeba and inducing production of cytokines through TLR4-NF-κB and TLR4-Erk1/2 pathways in corneas of Wistar rats.
10.1111/j.1365-3024.2010.01247.x
pubmed_960_20478
BACKGROUND Imatinib mesylate (ST1571) is the first-line drugfor chronic myeloid leukemia (CML), but development of resistance to this drug is a clinical problem. To explore the effective use of ST1571, we studied the combination treatment with histone deacetylase inhibitor (depsipeptide, FK228). MATERIALS AND METHODS FK228 and trichostatin A (TSA) were studied with respect to apoptosis of two Bcr-Abl-positive cell lines, K562 and TCC-S. Genetically-modified K562 cells by any of cyclin D1, c-Myc and active MEK genes were also studied. Apoptosis was examined by nuclear-morphology under a fluorescent microscope and by the expression of annexin V Changes of apoptosis-regulating genes and acetylated histone H4 were studied by immunoblot. RESULTS FK228 showed cytotoxicity at the nano-molar level. Combination treatment with STI571 and FK228 enhanced the induction of apoptosis significantly compared with each single treatment, although the histone acetylation level was not changed by the co-treatment. The combination treatment activated caspase-3 and cleaved PARP, but it did not induce any notable change in the expression of Bcl-XL, Bcl-2 and Bax compared with each single treatment. Enhanced apoptosis by the co-treatment was abrogated by ectopic expression of cyclin D1, c-Myc or active MEK CONCLUSION: The combination of FK228 with STI571 is a promising treatment for Bcr-Abl-positive CML, but the activation of the MEK/ERK pathway and its downstream target genes may bring resistance to the co-treatment in leukemic cells.
pubmed_960_20478
pubmed_305_2723
A variety of studies tried to examine the fundamental question of whether specific processing is "automatic," that is, occurs without attention, by manipulating attention toward stimuli via the set-size manipulation of perceptual load. The present paper invites re-extermination of this common methodology of altering the perceptual load of a relevant task to manipulate attention toward peripheral stimuli. Four main arguments that propose alternative interpretations to the notion of automaticity in this line of studies are discussed, suggesting that automaticity cannot be verified utilizing manipulation of load, and outlining a plan for moving forward.
10.3758/s13423-018-1444-7
pubmed_1057_11427
This study aimed to clarify the motivations and timing of the decision to become radiation oncologists. MATERIALS AND METHODS We conducted an online survey for new members of the Japanese Society for Radiation Oncology (JASTRO). RESULTS The response rate was 43.3%. Data of the 79 respondents who wanted to obtain a board-certification of JASTRO were analysed. We divided the respondents into two groups: Group A, those who entered a single radiation oncology department, and Group B, those who joined a radiology department in which the radiation oncology department and diagnostic radiology department were integrated. The most common period when respondents were most attracted to radiation oncology was "5th year of university" in Group A and "2nd year of junior residency" and "senior residency" in Group B. Furthermore, 79.5% of Group A and 40% of Group B chose periods before graduation from a university with a significant difference. The most common period when respondents made up their minds to become radiation oncologists was "2nd year of junior residency" in both groups. Internal medicine was the most common department to consider if they did not join the radiation oncology or radiology department. CONCLUSION To increase the radiation oncologists, it is crucial to enhance clinical training in the fifth year of university for Group A and to continue an active approach to maintain interest in radiation oncology until the end of junior residency. In Group B facilities, it is desirable to provide undergraduates more opportunities to come in contact with radiation oncology.
10.1093/jrr/rraa051
pubmed_898_10522
The authors are deeply sorry that, due to an unintentional mistake, the proof-editing procedure was skipped. A major mistake must be corrected: Fig. 2C contains pictures from a mislabeled folder and should be replaced as shown in the updated Fig. 2 below.
10.1007/s43032-020-00151-4
pubmed_190_10719
RATIONALE Individual differences in brain structure and function are suggested to exist prior to the onset of alcohol abuse. Cross-sectional studies have demonstrated abnormalities in brain regions underlying affective processes that may form a pathway to the emergence of later alcohol abuse and dependence in vulnerable individuals. However, no prospective studies have examined whether these abnormalities predict later problems with alcohol. OBJECTIVE This study aims to examine whether individual differences in affect and brain volume prospectively predict alcohol-related problems in adolescence. METHOD Adolescent drinkers (n = 98) were recruited from an ongoing prospective, longitudinal study examining adolescent emotional development. At age 12, participants underwent structural magnetic resonance imaging to obtain volumetric data on the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex (ACC), and completed a self-report measure of affective temperament. At age 16, participants completed a questionnaire measuring alcohol use, with 39 % reporting alcohol-related problems in the past year. RESULTS Pre-existing differences in the left ACC predicted problem drinking. Alcohol-related problems were associated with higher levels of temperamental negative affectivity; however, these were not correlated with anterior cingulate volumes. CONCLUSIONS These findings indicate that individual differences in the structural morphology of the anterior cingulate, a region implicated in affective processes, self-control, and drug addiction, predict later alcohol-related problems. Although this finding remained significant after controlling for other substance use and psychopathology, future research is required to test its specificity for alcohol use disorders.
10.1007/s00213-014-3483-8
pubmed_434_13301
OBJECTIVE We investigated the effects of six months vitamin E administration on cognition evaluated by event-related potentials in exercising older subjects. DESIGN Randomised controlled trial. SETTING Retirement home in Antalya, Turkey. PARTICIPANTS Fifty-seven adults aged 60-85 years were randomly assigned to one of four groups: sedentary control (C), vitamin E (V), exercise training (E) and vitamin E under training (EV). INTERVENTION V and EV groups were received vitamin E at a dose of 900 IU/day P.O. for 6 months. Trained groups were subjected to walking exercise involved 3 sessions per week for 6 months. Walking duration was gradually increased during 8 weeks, and stayed constant until the end of training period. Participants were begun walking at % 70 heart rate reserve for 20 min/day at the first two weeks, and walking duration was increased by 5 minutes/day of each week until subjects were reached a level of 50 min/day by week 8. MEASUREMENTS Plasma vitamin E concentration, total antioxidant capacity and two parameters of event-related potentials namely P3 latency and amplitude were performed on all study groups both before and after training. RESULTS Significant improvement in P3 latency was found in exercising groups. However, no significant differences were found between vitamin and other groups for P3 latency. Amplitude measurements were found unaltered among all groups. CONCLUSION We concluded that although six months training results improvement in P3 latency, vitamin E supplementation does not affect cognitive function evaluated by event-related potentials in older subjects.
10.1007/s12603-010-0256-x
others_85_13758
Background: Morbidity and mortality related to cardiac injuries are serious health concerns worldwide. The cardiac injuries could be due to traumatic blunt-force injuries or due to natural events such as injuries secondary to ischemia and infarction. The most prevalent type of lethal injuries is due to physical trauma. Cardiovascular injuries due to natural events constitute 31% of total cardiac injuries. Aim: The aim of this retrospective study was to give an overview of the trends in cardiac injury epidemiology in Manipal during 2011 to 2015. Materials and Methodology: The research was conducted in the Department of Forensic Medicine, Kasturba Medical College, Manipal. All cases due to cardiac injuries between 2011 and 2015 were included in this study. The data collected included age, sex, and type of cardiac injury, which was tabulated and analyzed for descriptive statistics using Statistical Package for Social Sciences (SPSS) version 20. Results: Cardiac injuries constituted 35.8% of the total number of autopsies that were conducted during the study period. 80.5% of the victims were male. Maximum number of victims were from the 3 rd decade of life. Most of the cardiac injuries (38.4%) were caused by road traffic accidents. The most frequent cardiac abnormality seen in our study was subendocardial hemorrhage, 38.6 % of the total cardiac injuries. Due to traumatic events, the most frequent cardiac injury seen was contusion, 5.4% and lacerations, 4.1% of injuries. Hyperemic area was seen in 13% and white patch in 12.4% of cases. The most commonly occluded artery was the left anterior descending artery, 53.4%. The time interval between the occurrence of the incident and death of the victim ranged from few minutes to 2 months. Discussion: The findings of this study give us an insight to the pattern and magnitude of deaths due to cardiac injuries in a South Indian region, given that only a very low percentage of the patients who sustain cardiac injury reach hospital alive. The injury pattern helps the clinician and other researchers to concentrate on these injured parts while treating and conducting research, respectively. Conclusion: More autopsy studies should be conducted to define the characteristics of population based cardiac injuries. © 2018 Department of Forensic Medicine and Toxicology
10.5958/0974-0848.2018.00082.9
pubmed_1003_18796
INTRODUCTION In kidney transplant recipients leptin levels are often elevated and bone mineral density (BMD) decreased. However, to date there are no about correlations between leptin and BMD in this population. It has been suggested that leptin is a predictor of BMD in postmenopausal women. Moreover, leptin acts as a marker of fat stores. We examined the relationships between leptinemia, some markers of nutritional status, BMD, and bone metabolism in kidney transplant recipients. We also assessed whether leptin was a significant and independent predictor of BMD in this population. METHODS BMD and fat content (global, percentage, trunk) were measured using dual-energy X-ray absorptiometry in 27 kidney allograft recipients. Markers of bone turnover and leptin were studied using commercially available kits. RESULTS Leptin correlated with the percentage of body fat, trunk fat, lean body mass, serum creatinine, and urea. Insulin growth factor binding protein 1 was negatively related to waist-hip ratio and global and trunk fat, whereas BMD of the lumbar spine was correlated with the daily dose of prednisone, azathioprine, cyclosporine trough levels, serum calcium, as well as osteoprotegerin level. CONCLUSIONS Leptin levels are associated with graft function and body fat in kidney allograft recipients. Leptin is not related to nutritional status, BMD, or bone metabolism in kidney allograft recipients, but is associated with the current dosage of immunosuppressants and the serum calcium.
10.1016/j.transproceed.2005.03.001
pubmed_217_8655
Chronic obstructive pulmonary disease (COPD) is associated with cerebrovascular abnormalities and an overproduction of reactive oxygen species. We hypothesised that COPD patients have oxidant-related cerebrovascular dysfunction. Our main objective was to evaluate cerebrovascular reactivity and its relationship with oxidative stress in females with COPD. We studied eight females with moderate COPD and 10 healthy female control subjects of similar age. Transcranial Doppler ultrasound assessed cerebral blood flow (CBF) velocity during hypercapnia. Plasma was assessed at rest for DNA oxidation, advanced oxidation protein products, lipid peroxidation, nitrotyrosine, antioxidant enzyme activity (glutathione peroxidase and catalase) and end-products of nitric oxide metabolism. Moderate COPD patients showed decreased cerebrovascular sensitivity to carbon dioxide (CO(2)) (COPD 1.17 ± 0.54 versus control 2.15 ± 0.73 cm · s(-1) · mmHg(-1); p<0.01). COPD patients had higher levels of DNA and lipid oxidation, advanced oxidation protein products and higher glutathione peroxidase activity (p<0.05). Controlling for measures of oxidative stress (DNA and lipid oxidation, and advanced oxidation protein product) eliminates statistically significant differences between the COPD and control groups in the CBF sensitivity to CO(2). Females with moderate COPD were found to have cerebrovascular dysfunction. Our results suggest that increased levels of systemic oxidative stress may have implications in the cerebrovascular dysfunction observed during hypercapnia in COPD.
10.1183/09031936.00197211
pubmed_911_9282
Skin colonization with Staphylococcus aureus is often associated with atopic dermatitis, and staphylococcal enterotoxins have been implicated in the etiology of atopic disease. In this study, the colonization of patients with atopic dermatitis and their parents was investigated in order to evaluate the possibility of intrafamiliar transmission. S. aureus strains were isolated from 30 of 45 patients (66%). In 19 of 29 families (65%), at least one parent carried S. aureus, and the overall colonization rate of the parents was 48%. All strains were typed by pulsed-field gel electrophoresis (PFGE), and the presence of enterotoxin genes in the strains was assayed by multiplex PCR. A high percentage (84%) of the isolates present on the children and on at least one of their parents displayed identical PFGE and enterotoxin patterns as well as identical antibiotic resistance profiles, indicating intrafamiliar transmission. Forty-five percent of the strains did not carry any enterotoxin gene. The most frequently found enterotoxin genes were seg and sei, which were present in 36% of the strains, and seb, which was found in 24% of the strains. The other toxin genes occurred only in low frequencies. Most strains were resistant to penicillin (82%), and 15% showed resistance to more than one antibiotic. Intermediately-vancomycin-resistant S. aureus or methicillin-resistant S. aureus strains were not detected. In conclusion, this study indicates that the colonization rate of parents of atopic children is rather high and may increase the risk of recolonization of the child.
10.1128/JCM.01734-07
pubmed_997_18787
Light-induced rotation of microscopic objects is of general interest as the objects may serve as micromotors. Such rotation can be driven by the angular momentum of light or recoil forces arising from special light-matter interactions. However, in the absence of intensity gradient, simultaneously controlling the position and switching the rotation direction is challenging. Here, we report stable optical trapping and switchable optical rotation of nanoparticle (NP)-assembled micromotors with programmed phase of light. We imprint customized phase gradients into a circularly polarized flat-top (i.e., no intensity gradient) laser beam to trap and assemble metal NPs into reconfigurable clusters. Modulating the phase gradients allows direction-switchable and magnitude-tunable optical torque in the same cluster under fixed laser wavelength and handedness. This work provides a valuable method to achieve reversible optical torque in micro/nanomotors, and new insights for optical trapping and manipulation using the phase gradient of a spatially extended light field.
10.1126/sciadv.add6664
others_257_3309
Three levels (0, 400 or 800 mg S kg-1) of elemental sulfur (S°) or gypsum (CaSO4.2H2O) were applied to soil samples. The soil samples were incubated and analyzed weekly during an 8-week period to determine changes in soil pH, EC value, SO4-S and available Mn contents. Regardless of sources, sulfur application continuously decreased the soil pH and increased the electrical conductivity of soil during the eight week experimental period. The lowest pH value (pH 7.04) was observed with 800 mg S kg-1 elemental sulfur application, and the highest EC value (1330.33 μS cm-1) was obtained with 800 mg S kg-1 gypsum application. The tested soil SO4-S content variations depended on the incubation time, sulfur sources and application levels. SO4-S content of soil showed a linear increase throughout the 8 week incubation as S° was applied. The highest SO4-S value of 53.34 mg kg-1 about 20 folds higher than that of control was observed with 800 mg S kg-1 elemental sulfur application. Incubation time, sulfur sources and the application levels had significant effect on the available Mn contents
others_257_3309
pubmed_323_5458
STUDY QUESTION Does maternal socioeconomic status (SES) confound or modify the association between IVF and perinatal outcome among singleton births? SUMMARY ANSWER There were substantial socioeconomic differences in the frequency of IVF pregnancies, but maternal SES was not associated with the outcome of IVF pregnancies. WHAT IS KNOWN ALREADY The use of IVF is associated with SES. Additionally, women with lower SES tend to have an increased risk of adverse perinatal outcomes such as preterm birth and small for gestational age birth. STUDY DESIGN, SIZE, DURATION We conducted a population-based cohort study using the Finnish Medical Birth Register (2006-2010). PARTICIPANTS/MATERIALS, SETTING, METHODS We analyzed the total population of singleton births in Finland (n = 291 004) and then compared the unadjusted and adjusted incidences of adverse perinatal outcomes for singleton births after IVF (n = 5647) and non-IVF pregnancies (n = 285 357) in relation to SES. MAIN RESULTS AND THE ROLE OF CHANCE SES did not confound or modify the association between IVF and perinatal outcomes after adjustments for age, parity, smoking, gestational diabetes, maternal diabetes and pre-eclampsia. However, the prevalence of IVF pregnancies increased with SES; on average 1.9% of singleton infants were born after IVF pregnancies, while the corresponding percentages were 3.2 and 1.2% for the highest and lowest SES strata, respectively. IVF was statistically significantly associated with 1.27-, 1.49-, 1.63-, 1.47-, 1.35-, 1.40-, 4.97- and 1.14-fold higher incidences of admission to a neonatal unit, stillbirth, preterm birth, low birthweight, low Apgar scores (<7 at 5 min), Cesarean section, placenta previa and major congenital anomaly, respectively. Irrespective of the SES group, women who became pregnant through IVF were older and more often nulliparous and non-smokers compared with women with non-IVF pregnancies. LIMITATIONS, REASONS FOR CAUTION The occupation of 22% of the women was unknown and that of a further 25% did not match any of the criteria for our SES strata. Additionally, infertility is a problem for couples but the definition of SES in this study was based only on the mother's occupation at the time of birth. WIDER IMPLICATIONS OF THE FINDINGS The prevalence of IVF-conceived pregnancies was highest among the highest SES group, but SES did not confound the perinatal outcomes of IVF pregnancies after adjusting for background factors. However, the magnitude of risks associated with the IVF technique itself may be more significant than previously thought. STUDY FUNDING/COMPETING INTEREST(S) None of the authors received any funding specifically for this study, and we have no competing interests.
10.1093/humrep/det307
pubmed_586_10906
In this study, using radioimmunoassay techniques, we found that ions at concentrations in the order of 0.1 molar influence the antigen-antibody complex formation. The angiotensin I/anti-angiotensin I reaction was studied in detail. Particularly bivalent cations and anions with a strong chaotropic effect (SCN-, I- and ClO4-) were found to influence strongly the specific immunological reaction. However, NO3- had also a remarkably strong influence. We found that the equilibrium constant, rather than the number of binding sites of the antibody, is influenced by the ions. It should be borne in mind that relatively high concentrations of electrolyte (as compared with the concentrations of antigen and antibody) show this effect. Consequently, this effect is of less practical importance for routine radioimmunoassay than is, for example, the effect of pH. However, this phenomenon shows that the radioimmunoassay technique might be valuable not only for quantization of very low hormone concentrations in biological fluids, but has also important potential applications in physical and protein chemistry. Particularly, the high sensitivity of this technique and the possibility of studying a homogeneous reaction system might give it advantages over other techniques.
10.1016/0009-8981(77)90045-6
pubmed_301_23652
The clinical presentation of mitochondrial disorders in childhood is highly variable causing difficulties in diagnosis and management. We assessed records of 75 children (48 male, 27 female) with a biochemically and/or molecularly established mitochondrial disorder in a retrospective, multicentric study. The predominant biochemical defect was an isolated respiratory chain complex IV, followed by respiratory chain complex I, combined respiratory chain, and isolated pyruvate dehydrogenase complex (PDHC) deficiencies. For the 75 patients, the predominant clinical presentations were a nonspecific encephalomyopathy (n = 34) and Leigh syndrome (n = 17). Classical mitochondrial syndromes with associated mutations of the mitochondrial DNA were rare (n = 12). Eleven children had a lethal infantile mitochondrial disease (LIMD). This group comprised a considerable variety of clinical pictures, and the cohort was big enough to show the high frequency and wide spectrum of nonneuromuscular symptoms in mitochondrial disorders in childhood.
10.1177/000992280304200806
pubmed_1058_1688
PURPOSE We believe that a three-dimensional (3D) registration of nonplanning (diagnostic) imaging data with the planning computed tomography (CT) offers a substantial improvement in tumor target identification for many radiation therapy patients. The purpose of this article is to review and discuss our experience to date. METHODS AND MATERIALS We reviewed the charts and treatment planning records of all patients that underwent 3D radiation treatment planning in our department from June 1994 to December 1995, to learn which patients had image registration performed and why it was thought they would benefit from this approach. We also measured how much error would have been introduced into the target definition if the nonplanning imaging data had not been available and only the planning CT had been used. RESULTS Between June 1994 and December 1995, 106 of 246 (43%) of patients undergoing 3D treatment planning had image registration. Four reasons for performing registration were identified. First, some tumor volumes have better definition on magnetic resonance imaging (MRI) than on CT. Second, a properly contrasted diagnostic CT sometimes can show the tumor target better than can the planning CT. Third, the diagnostic CT or MR may have been preoperative, with the postoperative planning CT no longer showing the tumor. Fourth, the patient may have undergone cytoreductive chemotherapy so that the postchemotherapy planning CT no longer showed the original tumor volume. In patients in whom the planning CT did not show the tumor volume well an analysis was done to determine how the treatment plan was changed with the addition of a better tumor-defining nonplanning CT or MR. We have found that the use of this additional imaging modality changed the tumor location in the treatment plan at least 1.5 cm for half of the patients, and up to 3.0 cm for 1/4 of the patients. CONCLUSIONS Multimodality and/or sequential imaging can substantially aid in better tumor definition in many patients undergoing 3D treatment planning. In some patients the appropriate nonplanning imaging source can change the perceived tumor location by several centimeters and is thus essential for proper treatment planning.
10.1016/s0360-3016(97)00546-4
pubmed_872_23101
AIMS To evaluate the efficacy of amplified fragment length polymorphism (AFLP)-based genetic profiling for taxonomic and epidemiological analyses of diverse Arcobacter species. METHODS AND RESULTS Seventy-two isolates of A. butzleri, A. cryaerophilus, A. skirrowii and A. nitrofigilis, and a previously unclassified porcine abortion strain were studied. AFLP profiling was performed using a BglII-Csp6I-based protocol previously used to characterize Campylobacter species. Duplicate profiles of 20 isolates were 93.25% similar, indicating high reproducibility. Numerical analysis of all 72 strains revealed five phenons at the 29% similarity level, four of which represented each of the known species studied. The remaining phenon was further characterized by phenotypic and 16S rDNA sequence analyses, the results of which indicated it to be a novel Arcobacter species. The genetically distinct subgroups of A. cryaerophilus were differentiated at the 39.5% similarity level. For strain typing, 62 distinct types were defined, with evidence of clonal lineages within A. butzleri, A. cryaerophilus and A. skirrowii. CONCLUSIONS AFLP profiling is an effective means of determining taxonomic and strain relationships for arcobacters. SIGNIFICANCE AND IMPACT OF THE STUDY First use of AFLP profiling for diverse Arcobacter species; indication of clonality in A. butzleri, A. cryaerophilus and A. skirrowii; potentially novel Arcobacter taxon identified.
10.1046/j.1365-2672.2003.02100.x
pubmed_203_12657
Adsorption and desorption characteristics for mercury ions using aminated chitosan bead which showed very high affinity to mercury ions were studied. The adsorption of mercury ions using aminated chitosan bead was an exothermic process since binding strength each other increased as the temperature decreased. And the adsorption of mercury ions was almost completed in 100 min at 150 rpm. In case that adsorbent dose increased, mercury uptake capacity decreased, while, removal efficiency increased. The beads were not greatly affected by the ionic strength, organic material and alkaline-earth metal ions. Mercury ions adsorbed on aminated chitosan bead were desorbed effectively about 95% by EDTA and the adsorption capacity of the recycled beads can still be maintained at 90% level at the 5th cycle.
10.1016/j.watres.2005.07.020
pubmed_852_1471
Adenoid squamous cell carcinoma (ASCC) is an uncommon but well recognized variant of squamous cell carcinoma. It has been reported to originate in the sun exposed skin of the head and neck region. Although rare, there are cases in records which have reported within the oral cavity and nasopharynx. Histologically the lesion shows areas of conventional squamous cell carcinoma along with atypical epithelial cells forming an adenoid pattern. There are insufficient reported cases to establish likely behaviour. Here we report two additional cases of adenoid squamous cell carcinoma, one developing in the floor of mouth and another in the maxillary sinus both were reported in March 2010 in Mangalore, India.
10.3126/kumj.v10i3.8028
pubmed_348_22547
OBJECTIVE To confirm the diagnosis of Asherman's syndrome in patients with scanty menses/amenorrhoea or infertility and to assess the effectiveness of hysteroscopy in the treatment of Asherman's syndrome. METHODS A hospital based descriptive study conducted on 20 patients presenting with amenorrhoea, oligomenorrhoea, or infertility from Jan 2004 to June 2005. They were selected after excluding hormonal imbalances, premature ovarian failure and congenital uterine abnormalities. All patients underwent diagnostic hysteroscopy and resection of adhesions. Specimens were sent for Histopathology and bacterial culture. RESULT A total of 20 patients were included in this study, the median age was 26 years, 65% had presented with scanty menses with secondary infertility, 20% with secondary ammenorrhoea, and 15% with primary infertility alone. Hysteroscopic findings showed thick fibrous adhesions in 45% patients, 40% had flimsy adhesions and 15% had muscular adhesions. It was seen that 65% had adhesions in the body of uterus, 25% at the site of internal os and 1% had adhesions in the cervical canal as well as the body of the uterus. Normal menstrual cycle was resumed in 95% patients, whereas two patients conceived and were followed to term. Dense fibrous tissue with few patches of calcification and no signs of secretory or proliferative cells was found in 35% patients. In 45% endometrium showed proliferative changes and collagen fibers. Only 1 patient had a positive AFB culture and the histopathology showed few graulomas with epitheloid cells most of the tissue replaced by necrotic tissue with patchy areas of caseation. CONCLUSION Hysteroscopy is an effective procedure for not only diagnosing Ashermans Syndrome, but is equally effective for treating it..
pubmed_348_22547
pubmed_613_23361
A counterpart of the Mollow triplet (luminescence line shape of a two-level system under coherent excitation) is obtained for the case of incoherent excitation in a cavity. The system acquires coherence through the strong-coupling between the cavity and the emitter. Analytical expressions, in excellent agreement with numerical results, pinpoint analogies and differences between the conventional resonance fluorescence spectrum and its cavity QED analogue under incoherent excitation. Most notably, the satellites broaden and split sublinearly with increasing incoherent pumping.
10.1103/PhysRevLett.105.233601
pubmed_219_1484
An abnormal increase in the incidence of dengue was reported at Vellore Corporation since September 2012. Intensive control operations supported with health education campaigns were carried out from September to November 2012 till the outbreak situation subsided. During December 2012, a cross sectional survey was conducted at Vellore Corporation to assess the impact of the health education campaigns on the knowledge, attitude and practice in the community and also to assess future needs. A total of 101 families from four different locations at Vellore corporation were interviewed on pre-structured formats. Though 80% of the respondents felt that dengue could be effectively prevented and controlled only with community participation, majority of them lacked awareness on the day time biting behaviour of Aedes mosquitos, their indoor resting and breeding habits and relevance of specific control measures focused on the bionomics of dengue vectors.
pubmed_219_1484
pubmed_131_310
We studied the role of ABH antigens in determining graft outcome in 104 patients who received HLA-identical bone marrow transplants for aplastic anaemia and acute leukaemia. ABH compatibility had no significant effect on incidence of graft rejection or graft-versus-host disease. Fifteen recipients ahd pre-transplant antibodies against donor ABH antigens. In 14, large volume plasma exchange and transfusion of donor-type erythrocytes was successful in reducing the antibody titre to low or undetectable levels. In one patient, plasma exchange was unsuccessful and red cells were removed from the marrow inoculum by unit gravity sedimentation. This approach prevented transfusion reaction, and permitted engraftment of all haematopoietic cell lines despite persistently elevated antibody titres. Parallel in vitro studies revealed that antibodies to ABH antigens failed to inhibit the growth of progenitor cells committed to both granulocyte-macrophage (CFU-C) and erythroid (BFU-E) development. These findings indicate that ABH-antigens are not clinically important transplantation antigens and suggest that ABH antigens are not operationally present on hematopoietic stem cells.
10.1111/j.1365-2141.1980.tb01184.x
pubmed_80_18472
There have been a number of angiogenic gene therapy trials, yielding mixed results as to efficacy, but demonstrating uniform short-term treatment safety. Data regarding long-term safety of angiogenic gene therapy are limited. Double-blind VIF-CAD trial (NCT00620217) assessed myocardial perfusion and clinical data in 52 refractory coronary artery disease (CAD) patients randomized into treatment (VIF; n = 33) and Placebo (n = 19) arms. VIF group received electromechanical system NOGA-guided intramyocardial injections of VEGF-A165/bFGF plasmid (VIF) into ischemic regions, while the Placebo group-placebo plasmid injections. Full 1-year follow-up data have been published. This study presents the results of over 10-year (median 133 months, range 95-149) safety follow-up of VIF-CAD patients. Overall, 12 (36.4%) patients died in VIF and 8 (42.1%) in Placebo group (P = .68). Cardiovascular mortality was 12/33 (36.4%) in the VIF group and 6/19 (31.6%) in Placebo group (P = .73). Two Placebo patients died due to malignancies, but no VIF patients (P = .17). The Kaplan-Meier curves of combined endpoint: cardiovascular mortality, myocardial infarction and stroke were similar for both patient groups (P = .71). Odds ratio of Placebo group increasing (reaching a worse) their CCS class versus VIF was non-significant (OR 1.28, 95% CI = 0.66-2.45; P = .47). However, CCS class improved in time irrespectively of treatment-OR of reaching a less favorable CCS class per each year of follow-up was 0.74 (95% CI 0.685-0.792; P < .0001, pooled data). There were no differences in readmission rates. Intramyocardial VEGF-A165/bFGF plasmid administration appears safe, with no evidence of an increase in the incidence of death, malignancy, myocardial infarction or stroke during 10-year follow-up in this limited patient population.
10.1016/j.ahj.2019.06.009
others_422_6183
Pectin methylesterase (PME) is a ubiquitous cell-wallassociated enzyme that catalyzes the demethylesterification of homogalacturonan in the cell wall. The activity is regulated in part by pectin methylesterase inhibitor (PMEI), which can bind to the active site of PME. This mechanism may result in either rigidification or softening of the cell wall depending on the mechanism of demethylesterification. This research aims to characterize the structure and function of the PME and PMEI gene family in A (Musa acuminata) and B (Musa balbisiana) banana genomes. We annotated based on domain PME (PF019095) and PMEI (PF04043) using the PFAM database. We analyzed the size, weight, isoelectric point of the protein, signal peptide, transmembrane domain, subcellular localization of proteins, prediction cleavage motif and position, phylogenetic analysis and conserved residues. As a result, we found great diversity of PME in the A genome (70 PME: 41 PME type 1 and 29 PME type 2; 23 PMEI) and B-genome (60 PME: 38 PME type 1,22 PME type 2; 23 PMEI) within the parameters. Phylogenetic analysis classified the PME into six monophyletic groups. The gene family of PME and PMEI in banana genomes had a wide variety of patterns of structural, biochemical and functional characteristics. © 2021 World Research Association. All rights reser
others_422_6183
pubmed_194_2187
The authors have reported the case of a 65 year old woman followed for almost 4 years with an akineticrigid Parkinsonian syndrome which responded well to levodopa. Waning of response finally occurred and despite the addition of a peripheral dopa decarboxylase inhibitor the patient died suddenly. Autopsy examination revealed pure nigro-striatal degeneration without any additional pathology. The report deals primarily with purity of the Parkinsonian picture and especially with the conspicuous and prolonged effect of levodopa.
pubmed_194_2187
pubmed_148_9299
In experiments on 16-19 day rats, studies have been made of the effect of 2-hour heat exposure (40-41 degrees ) and hydrocortizone injection (4 mg per 100 g of body weight) on gamma-amylolytic and invertase activities of homogenized ad inside-turned pieces of proximal, middle and distal parts of the small intestine. It was shown that thermal stress results in a sharp increase of the enzymic activities of homogenates and total pieces of proximal and middle parts of the intestine. In distal parts, the enzymic induction is less significant or even completely absent. Hydrocortizone injections evoke similar changes, although the latter are more evident. On the basis of the data obtained, it is suggested that the effect of thermal factor on the synthesis of intestinal enzymes is realized via the hormones of suprarenal cortex.
pubmed_148_9299
pubmed_664_8497
The histologic lesion underlying overuse rotator cuff tendinopathy is a failed healing response, with haphazard proliferation of tenocytes, disruption of tendon cells and collagen fibers, and increased noncollagenous extracellular matrix. Recent attention has focused on the biological pathways by which tendons heal, leading to the identification of several growth factors (GFs) involved in this process. No studies have been published on the time course of the various GFs during rotator cuff healing process in vivo, in humans. We review what is known about these GFs and their role in rotator cuff healing.
10.1097/JSA.0b013e3182250c78
pubmed_19_21926
Notwithstanding many years of progress, pedestrian recognition is still a difficult but important problem. We present a novel multilevel Mixture-of-Experts approach to combine information from multiple features and cues with the objective of improved pedestrian classification. On pose-level, shape cues based on Chamfer shape matching provide sample-dependent priors for a certain pedestrian view. On modality-level, we represent each data sample in terms of image intensity, (dense) depth, and (dense) flow. On feature-level, we consider histograms of oriented gradients (HOG) and local binary patterns (LBP). Multilayer perceptrons (MLP) and linear support vector machines (linSVM) are used as expert classifiers.
10.1109/TIP.2011.2142006
pubmed_262_6426
OBJECTIVE To investigate the molecular mechanisms leading to edema-induced decreases in intestinal smooth muscle myosin light-chain phosphorylation. Intestinal interstitial edema often develops during abdominal surgery and after fluid resuscitation in trauma patients. Intestinal edema causes decreased intestinal contractile activity via decreased intestinal smooth muscle myosin light-chain phosphorylation, leading to slower intestinal transit. Interstitial edema development is a complex phenomenon, resulting in many changes to the interstitial environment surrounding intestinal smooth muscle cells. Thus, the mechanism(s) by which intestinal edema development causes intestinal dysfunction are likely to be multifactorial. DESIGN Randomized animal study. SETTING University laboratory. SUBJECTS Male Sprague-Dawley rats, weighing 250-350 g. INTERVENTION Studies were performed in a rat model in which a combination of mesenteric venous hypertension and administration of resuscitative fluids induces intestinal edema, mimicking the clinical setting of damage control resuscitation. MEASUREMENTS AND MAIN RESULTS Microarray analysis of edematous intestinal smooth muscle combined with an in silico search for overrepresented transcription factor binding sites revealed the involvement of nuclear factor-kappaB in edema-induced intestinal dysfunction. Nuclear factor-kappaB deoxyribonucleic acid binding activity was significantly increased in edematous intestinal smooth muscle compared with controls. Inhibition of nuclear factor-kappaB activation blocked edema-induced decreases in basal intestinal contractile activity. Inhibition of nuclear factor-kappaB activation also attenuated edema-induced decreases in myosin light-chain phosphorylation. CONCLUSIONS We conclude that intestinal edema activates nuclear factor-kappaB, which, in turn, triggers a gene regulation program that eventually leads to decreased myosin light-chain phosphorylation and, thus, decreased intestinal contractile activity.
10.1097/CCM.0b013e3181ce4aaa
pubmed_622_9278
A cationic water-soluble conjugated polyelectrolyte, poly[9,9-bis(6''-(N,N,N-trimethylammonium)hexyl)fluorene-co-alt-2,5-bis(6'-(N,N,N-trimethylammonium)hexyloxyphenylene) tetrabromide], was synthesized. Fluorescence resonant energy transfer (FRET) experiments between the polymer and fluorescein-labeled single-stranded DNA (ssDNA-Fl) were conducted in aqueous buffer and THF/buffer mixtures. Weak fluorescence emission in aqueous buffer was observed upon excitation of the polymer, whereas addition of THF turned on the fluorescence. Fluorescence self-quenching of ssDNA-Fl in the ssDNA-Fl/polymer complexes as well as electron transfer from the polymer to fluorescein may account for the low fluorescence emission in buffer. The improved sensitization of fluorescence by the polymer observed in THF/buffer could be attributed to the weaker binding between the polymer and ssDNA-Fl and a decrease in dielectric constant of the solvent mixture, which disfavors electron transfer. THF-assisted signal sensitization was also observed for the polymer and fluorescein-labeled double-stranded DNA (dsDNA-Fl). These results indicate that the use of cosolvent provides a strategy to improve the detection sensitivity for biosensors based on the optical amplification provided by conjugated polymers.
10.1002/asia.200600257
pubmed_909_13857
BACKGROUND AND OBJECTIVES Neuropathic pain is related to the sustained activation of neuroglial cells and the production of proinflammatory cytokines in the spinal dorsal horn. Ghrelin, the endogenous ligand for growth hormone secretagogue receptor 1a (GHSR-1a), has been shown to inhibit the activation of microglia and the release of proinflammatory cytokines. The purpose of this study was to investigate the role of ghrelin/GHSR-1a signaling in neuropathic pain and to understand the associated mechanisms. METHODS A rat model of neuropathic pain was established by chronic constriction injury (CCI) of the sciatic nerve. Hyperalgesia and allodynia were evaluated by observing the mechanical withdrawal threshold and the thermal withdrawal latency. The expression levels of ghrelin and GHSR-1a were detected by semiquantitative reverse transcriptase-polymerase chain reaction and Western blot analysis. The levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α were detected using an enzyme-linked immunosorbent assay. The expression levels of p-p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-κB (NF-κB) p65 were determined by Western blot and immunohistochemistry analysis. RESULTS Both ghrelin and GHSR-1a were expressed in the spinal dorsal horns of normal rats and were not significantly different from that of sham rats. However, rats in the CCI model group developed severe hyperalgesia and allodynia, as well as significantly downregulated expression of ghrelin and GHSR-1a. Compared with CCI model rats, intrathecal injection of ghrelin clearly delayed thermal hyperalgesia and mechanical allodynia at 3, 5, and 7 days after CCI; reduced the levels of IL-1β, IL-6, and tumor necrosis factor-α; and inhibited the phosphorylation of p38 MAPK and the activation of NF-κBp65 in the spinal dorsal horn. In addition, the effect of ghrelin could be blocked by [D-Lys]-GHRP-6, a GHSR-1a antagonist. CONCLUSIONS Our present study demonstrated that ghrelin alleviated neuropathic pain through a GHSR-1a-mediated suppression of the p38 MAPK/NF-κB pathway.
10.1097/AAP.0000000000000050
pubmed_1021_17435
Simian virus 40 large T antigen is a helicase separating the complementary strands of double-stranded DNA in the presence of hydrolyzable ATP and of double-stranded RNA in the presence of non-ATP nucleotides (GTP, CTP or UTP). We have constructed partially single-stranded nucleic acid substrates consisting of RNA or DNA strands hydrogen bonded to either RNA or DNA complements. We found that ATP is utilized as a cofactor for the T-antigen-catalyzed unwinding reaction when the substrates contain overhanging single-stranded DNA, regardless of whether the double-stranded region is DNA or hybrid DNA.RNA. Conversely, non-ATP nucleotides are used when the overhanging single strand is RNA. Based on these and additional findings, we propose that the bound nucleic acid induces a conformational change in T antigen resulting in a proper orientation of both nucleic acid and nucleotide relative to the active center of the ATPase/helicase domain of the enzyme. The implications of our conclusion for the roles which T antigen may play in vivo are discussed.
10.1111/j.1432-1033.1991.tb15674.x
pubmed_487_14161
Vitamin E is the major lipid-soluble chain-breaking antioxidant in mammals and plays an important role in normal development and physiology. Deficiency (whether dietary or genetic) results in primarily nervous system pathology, including cerebellar neurodegeneration and progressive ataxia (abnormal gait). However, despite the widely acknowledged antioxidant properties of vitamin E, only a few studies have directly correlated levels of reactive oxygen species with vitamin E availability in animal models. We explored the relationship between vitamin E and reactive oxygen species in two mouse models of vitamin E deficiency: dietary deficiency and a genetic model (tocopherol transfer protein, Ttp-/- mice). Both groups of mice developed nearly complete depletion of alpha-tocopherol (the major tocopherol in vitamin E) in most organs, but not in the brain, which was relatively resistant to loss of alpha-tocopherol. F4-neuroprostanes, an index of lipid peroxidation, were unexpectedly lower in brains of deficient mice compared with controls. In vivo oxidation of dihydroethidium by superoxide radical was also significantly lower in brains of deficient animals. Superoxide production by brain mitochondria isolated from vitamin E-deficient and Ttp-/- mice, measured by electron paramagnetic resonance spectroscopy, demonstrated a biphasic dependence on exogenously added alpha-tocopherol. At low concentrations, alpha-tocopherol enhanced superoxide flux from mitochondria, a response that was reversed at higher concentrations. Here we propose a mechanism, supported by molecular modeling, to explain decreased superoxide production during alpha-tocopherol deficiency and speculate that this could be a beneficial response under conditions of alpha-tocopherol deficiency.
10.1074/jbc.M702572200
pubmed_345_17783
Even zeolite is promising in ammonia pollution disposing, its removal efficiency is frequently interfered by organics. As activated carbon has good removal efficiency on organic contaminants, combination of two adsorbents may allow their respective adsorption characteristics into full play. This paper provides a performance assessment of the combination for enhancing ammonium removal in micro-polluted raw water. Gel-filtration chromatography (GFC) was carried out to quantify the molecular weight (MW) range of organic contaminants that powdered activated carbon (PAC) and powdered zeolite (PZ) can remove. The polydispersity difference which also calculated from GFC may indicate the wider organic contaminants removal range of PAC and the relatively centralized removal range of PZ. The jar tests of combination dosing confirm a synergistic effect which promotes ammonium removing. Nevertheless, it also shows an antagonism hindering the due removal performance of the two adsorbents on CODMn, while it is not much evident on UV254. Furthermore, a comparison study with simulated coagulation-sedimentation process was conducted to evaluate the optimum dosing points (spatial and temporal) of PAC and PZ among follows: suction well, pipeline mixer, early and middle phase of flocculation. We suggest to dose both two adsorbents into the early phase of flocculation to maximize the versatile removal efficiency on turbidity, ammonium and organic contaminants.
pubmed_345_17783
pubmed_259_6685
Calbindin D(28K) is a six-EF-hand calcium-binding protein found in the brain, peripheral nervous system, kidney, and intestine. There is a paucity of information on the effects of calcium binding on calbindin D(28K) structure. To further examine the mechanism and structural consequences of calcium binding to calbindin D(28K) we performed detailed complementary heteronuclear NMR and microelectrospray mass spectrometry investigations of the calcium-induced conformational changes of calbindin D(28K). The combined use of these two powerful analytical techniques clearly and very rapidly demonstrates the following: (i). apo-calbindin D(28K) has an ordered structure which changes to a notably different ordered conformation upon Ca(2+) loading, (ii). calcium binding is a sequential process and not a simultaneous event, and (iii). EF-hands 1, 3, 4, and 5 take up Ca(2+), whereas EF-hands 2 and 6 do not. Our results support the opinion that calbindin D(28K) has characteristics of both a calcium sensor and a buffer.
10.1016/s0003-2697(03)00084-8
pubmed_653_22402
We demonstrate highly efficient Raman distributed feedback (DFB) fibre lasers for the first time with up to 1.6 W of continuous wave (CW) output power. The DFB Bragg gratings are written directly into two types of commercially available passive germano-silica fibres. Two lasers of 30 cm length are pumped with up to 15 W of CW power at 1068 nm. The threshold power is ~2 W for a Raman-DFB (R-DFB) laser written in standard low-NA fibre, and only ~1 W for a laser written in a high-NA fibre, both of which oscillate in a narrow linewidth of <0.01 nm at ~1117 nm and ~1109 nm, respectively. The slope efficiencies are ~74% and ~93% with respect to absorbed pump power in the low-NA fibre and high-NA fibre respectively. Such high conversion efficiency suggests that very little energy is lost in the form of heat through inefficient energy transfer. Our results are supported by numerical simulations, and furthermore open up for the possibility of having narrow linewidth all-fibre laser sources in wavelength bands not traditionally covered by rare-earth doped silica fibres. Simulations also imply that this technology has the potential to produce even shorter R-DFB laser devices at the centimetre-level and with mW-level thresholds, if Bragg gratings formed in fibre materials with higher intrinsic Raman gain coefficient than silica are used. These materials include for example tellurite or chalcogenide glasses. Using glasses like these would also open up the possibility of having narrow linewidth fibre sources with DFB laser oscillating much further into the IR than what currently is possible with rare-earth doped silica glasses.
10.1364/OE.20.005082
pubmed_1021_5157
Cocaine inhibits tritium-labeled dopamine ([3H]DA) uptake in rat (IC50 approximately 400 nM) and sheep (IC50 approximately 1 microM) striatum. GBR 12909, a selective DA uptake inhibitor, potently inhibits [3H]DA uptake in rat (IC50 less than 10 nM), but is less effective (only 60% of the uptake is inhibited at a concentration of 10 microM) and less potent (IC50 approximately 300 nM) in sheep. [3H]DA release from slices of rat or sheep striatum is stimulated by potassium (15-50 mM). In the presence of nomifensine (10 microM), cocaine (10 microM) had no effect on potassium-stimulated [3H]DA release in either species. [3H]DA release is increased by N-methyl-D-aspartate (NMDA) (10-1000 microM) in rat striatum but NMDA did not stimulate [3H]DA release in sheep striatum. These findings suggest that NMDA receptors either are absent from or do not regulate release of preloaded [3H]DA in sheep striatum.
10.1016/0024-3205(91)90064-i
pubmed_1114_22047
Numerous factors can be considered for the etiology of temporomandibular disorders (TMD). The aim of the present study was to investigate whether the presence of both nasal septal deviation (NSD) and habitual prone sleeping posture (HPSP) predisposes TMD. We evaluated 200 subjects in 4 groups. Group I (NSD-, HPSP-/control group), Group II (NSD+, HPSP-), Group III (NSD-, HPSP+), Group IV (NSD+, HPSP+). All patients were examined according to the research diagnostic criteria to determine the presence of TMD. Group IV had the highest value for TMD incidence (44 %). Thus, we found that the presence of both NSD and HPSP parameters increased TMD incidence in Group IV compared to the control group (p = 0.000). Additionally, Group IV showed significantly higher values than Group II (p = 0.012) and Group III (p = 0.039). For Group III (NSD-, HPSP+), TMD was determined higher compared to the control group (p = 0.009). A statistically higher value of presence of TMD was determined in Group II (NSD+, HPSP-) than control group (p = 0.029). The incidence of TMD was significantly higher in women than men (p = 0.020). We concluded that one having an unilateral obstructive nasal septal deviation in addition to a habit of sleeping in prone position must be alert for potential TMD.
10.1007/s00405-014-3476-6
pubmed_713_9675
BACKGROUND AND AIM OF THE WORK Many authors tried to clarify the palliative care nurses' role, overall in the home care setting, but little is known in different settings of care. We aim to present a Specialist profile of palliative care (PC) nurses in an Italian hospital-based Palliative Care Unit. METHODS With an organizational case study approach, we conducted a literature review on PC nurse's role, and we presented the Specialist PC nurses' profile, describing competences and key related activities. RESULTS Our specialist profile highlights that clinical activities are similar to the experiences described in the literature (symptom assessment and management, communication, interprofessional work), while training and research activities are new fields of interest that it's important to explore and promote, most of all in our country. CONCLUSIONS Sustaining the flexibility of the role, being recognized by colleagues and keeping the three dimensions connected are the major challenges: drawing up a specialist palliative care nurses' profile can help the team to better define the role framework in an interdisciplinary context.
10.23750/abm.v92iS2.11360
pubmed_866_11889
OBJECTIVE The impact, positive or negative, of youth sport specialisation (YSS) on short-term and long-term performance is not fully understood; however, the desire to maximise performance goals is generally considered the primary reason children and adolescents specialise at a young age. We performed a systematic review of original research to establish the association of YSS and task-focused or career-focused performance outcomes. DESIGN Systematic review. DATA SOURCES Databases searched include PubMed, EMBASE, Cochrane, CINAHL and SPORTDiscus. ELIGIBILITY CRITERIA We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify peer-reviewed research articles published in English between 1 January 1990 and 31 December 2018 that reported original findings on the association of YSS and performance outcomes. Studies without an explicit measure of sport specialisation, for example, volume measures without measuring sport specialisation, were excluded. RESULTS Twenty-two articles were included in the final review; 15 addressed career performance outcomes and 7 considered task performance outcomes. All identified studies were cross-sectional or retrospective in design. The proportion of elite athletes who specialised early ranged between 7% and 85%, depending on sport and definition of specialisation. Elite athletes often specialised between the ages of 14 and 15 compared with their non-elite or semi-elite peers who typically specialised prior to 13 years. In addition, neuromuscular control, anterior reach asymmetry and physical task outcomes did not differ by specialisation status. CONCLUSION The volume and methodological rigour of published research in this field are limited. Our review suggests that YSS is not required to achieve success at elite levels. YSS also does not appear to improve task-related performance (eg, anterior reach, neuromuscular control) outcomes for specialised athletes when compared with non-specialised athletes during childhood and adolescence.
10.1136/bjsports-2019-101365
pubmed_824_2085
OBJECTIVES The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum carcinoembryonic antigen (CEA) levels change after nCRT and after surgery as compared with before nCRT. METHODS The subjects were 149 patients with locally advanced rectal cancer who received nCRT between 2005 and 2013. The patients were divided into 4 groups according to the serum CEA levels: group 1, 55 patients with negative serum CEA levels before nCRT; group 2, 41 patients with positive serum CEA levels before nCRT that became negative after nCRT; group 3, 37 patients with positive serum CEA levels after nCRT that became negative after surgery; and group 4, 16 patients with positive serum CEA levels after nCRT as well as after surgery. RESULTS Pathological complete response, T downstaging, and tumor shrinkage were significantly higher in group 1 than in other groups. Disease-free survival was significantly poorer in group 4. The lack of a decrease in the serum CEA level in group 4 was most likely attributed to the persistence of micrometastases outside the resection field. CONCLUSIONS Changes in serum CEA levels measured before nCRT, after nCRT, and after surgery can be used to reliably predict the histologic response to nCRT and outcomes.
10.1159/000485511