index
stringlengths 10
17
| text
stringlengths 101
29.2k
| doi
stringlengths 2
94
|
|---|---|---|
pubmed_447_12984 | In order to elucidate the interaction between cyproheptadine (CPH) and tipepidine (TP), the disposition of CPH and its metabolites from plasma and the hepatic drug metabolizing enzyme activities in rats dosed singly or repeatedly were investigated. The elimination of CPH and its metabolites, desmethylCPH (DMCPH) and DMCPH-epoxide (DMCPHEPO), from plasma after a single intravenous (i.v.) administration of both CPH and TP was not significantly altered compared with that after CPH alone, although the i.v. administration of DMCPH and TP enhanced the plasma levels of DMCPHEPO. The elimination of TP from plasma was not affected by the coadministration with CPH. The single oral administration of both CPH and TP (50 mg/kg) significantly enhanced the plasma levels of CPH and DMCPH compared with those after CPH alone, consequently resulting in their delayed elimination. However, the coadministration with TP at a low dose (5 mg/kg) hardly affected the plasma decay of CPH and its metabolites. The repeated dosing of them for 7 d obscured the interactive effect. The hepatic drug-metabolizing enzyme activities, cytochrome P-450 and aminopyrine demethylase activity, were greatly increased after the repeated administration of CPH, especially showing much more increased activities after the coadministration with TP. These results suggest that the competition of hepatic oxidative metabolism between CPH or its metabolites and TP based on the depletion of the enzymes might largely be involved in the drug interaction on a single dosing of them and that the repeated dosing of them would dissolve the depletion due to their strongly inductive effect. | 10.1248/bpb1978.14.643 |
pubmed_1037_11707 | BACKGROUND
Most spinal meningiomas primarily grow in the intradural extramedullary location. Epidural meningiomas are uncommon; if detected, they usually coexist with intradural lesions. They inhere more aggressive and invasive characteristics compared with their counterparts inside the dura.
CASE DESCRIPTION
We report a 22-year-old female who was admitted to the hospital with weakness and numbness in both lower limbs. Her cervical magnetic resonance imaging revealed an en-plaque and dumbbell-shaped lesion located from C5 to C8. After gadolinium injection, the whole mass was enhanced and unveiled two portions: intradural and extradural. The bone window of the computed tomography scan revealed calcification inside the lesion. The patient underwent tumor removal surgery. The pathology findings showed a psammomatous meningioma. After 6 months of surgery, the patient has been able to walk with walkers.
CONCLUSION
We should consider spinal meningioma as a differential diagnosis when encountering an extradural lesion in the cervical region. The optimal surgical treatment for young patient with epidural meningiomas is radical surgery with dura attachment removal. | 10.25259/SNI_615_2021 |
pubmed_711_725 | A fluorescence high performance liquid chromatographic method using an immobilized 3 alpha-hydroxysteroid dehydrogenase column as a post-column enzymatic reactor was developed for the determination of corticosteroid metabolites in the urine of subjects with congenital adrenal hyperplasia. 3 alpha-Hydroxysteroids, such as pregnanetriol, pregnanediol and pregnanetriolone, in the eluate from mu-Bondapak phenyl column (300 x 3.9 mm I.D.) using 0.05% ammonium phosphate buffer (pH 7.1)-acetonitrile-methanol (100:55:15) as the mobile phase was mixed with NAD+ solution in the enzyme column at 30 degrees C to generate NADH, which was monitored by a fluorophotometric detector. Each steroid was measured at the 2.5 micrograms/dl at the highest sensitivity of the detector. The mean recoveries and reproducibilities were 91.5-108.2% with 0.9-6.5% (CV%). | 10.1002/bmc.1130010102 |
others_293_13239 | 1. 1. Carnivore red cells lose their Na/K pump capability as they develop from erythroblasts to reticulocytes to mature cells. They defend their fluid volume by utilizing the Ca/Na exchanger as a Na extrusion pump, the energy for which is ultimately derived from active Ca transport. 2. 2. Swelling-induced [K-Cl] cotransport and shrinkage-induced Na/H exchange are regulated in a coordinated fashion in dog red cells. Circumstantial evidence points to a regulatory protein kinase-phosphatase system. 3. 3. Dog red cells detect changes in their fluid volume, not by virtue of membrane distortion, but by alterations in the concentrations of cytoplasmic macromolecules induced by swelling or shrinkage. © 1992 | 10.1016/0300-9629(92)90713-Z |
pubmed_699_7603 | The astigmatic interferometric particle imaging (AIPI) model reveals that the fringe orientation shifts with droplet depth displacement, and their relationships are quantitatively formulated. The depth displacement is directly evaluated from the relative angular shift of the fringes with angular cross power spectral density, and this algorithm isolates the uncertainty of droplet depth position from depth displacement. Proof-of-concept experiments on micrometer-sized transparent droplets with a 5 kHz AIPI system demonstrates that droplet three-dimensional (3D) trajectories are accurately obtained with the accuracy of depth displacement up to tens of micrometers, improving an order of magnitude from hundreds of microns in a traditional Lagrangian framework by comparing droplet depth positions. | 10.1364/OL.461480 |
pubmed_505_1473 | This paper presents procedures for implementing the EM algorithm to compute REML estimates of variance covariance components in Gaussian mixed models for longitudinal data analysis. The class of models considered includes random coefficient factors, stationary time processes and measurement errors. The EM algorithm allows separation of the computations pertaining to parameters involved in the random coefficient factors from those pertaining to the time processes and errors. The procedures are illustrated with Pothoff and Roy's data example on growth measurements taken on 11 girls and 16 boys at four ages. Several variants and extensions are discussed. | 10.1186/1297-9686-32-2-129 |
pubmed_266_12062 | Unipolar atrial fibrillation (AF) electrograms (EGMs) require far-field ventricle cancellation to recover hidden atrial activations. Current methods cannot achieve real-time cancellation because of the temporal delay they introduce. We propose a new real-time ventricular cancellation (RVC) method based on causal implementation optimized for real-time functioning. The method is similar to the classical average beat subtraction (ABS) method but it computes the ventricular contribution before the ventricular activation finishes. We compare the proposed method to the ABS on synthetic and real EGM databases for the time and frequency domains. All parameters and their optimal values are analyzed and validated. The RVC method provides a good reconstruction of the unipolar EGMs and a better local activation time detection than the classical approach with average F1scores 0.7307 and 0.7125, respectively. The spectral analysis shows that the average power after ventricular cancellation is reduced for frequency bands between 3 and 5.5 Hz, demonstrating that the proposed method removes the ventricular component present in the unipolar EGM signals compared to the ABS method. The phase mapping analysis on the RVC method presented lower error when comparing the annotated EGM cycles with the phase inversion intervals. In terms of performance ABS and RVC behave similarly, but the real-time capability of the latter justifies its preference over the offline implementations. In the clinical environment other online investigations, e.g., rotational activity assessment, dominant frequency or local activation time mapping, might benefit from the real-time potential of the proposed cancellation method. | 10.3389/fbioe.2020.00789 |
pubmed_139_7341 | T-cell growth factor (TCGF) produced by the MLA 144 gibbon ape T-lymphosarcoma cell line was biosynthetically radiolabelled with [35S]methionine and isolated by reverse-phase h.p.l.c. [Milstone & Parker (1983) Biochem. Biophys. Res. Commun. 115, 762-768]. Two predominant species, of Mr 16300 and pI 6.8 and of Mr 14300 and pI 7.5, were resolved. Analysis of TCGF labelled with a mixture of [3H]glucosamine and [14C]methionine demonstrated that only the 16300-Mr protein contained detectable carbohydrate label, approx. 50% of which was present in sialic acid residues, which were largely responsible for the charge difference observed between the two forms of TCGF. The 14300-Mr protein was labelled within 5 min after addition of [35S]methionine and was the predominant intracellular form of TCGF, whereas the 16300-Mr protein was not detected until 25 min later and was the predominant extracellular form of TCGF. Pulse-chase experiments were consistent with the hypothesis that the 14300-Mr protein is an intracellular precursor that is glycosylated to form the 16300-Mr protein, which is then preferentially secreted from the cell. | 10.1042/bj2360371 |
pubmed_249_13775 | PURPOSE
To determine the profile and motivations of patients who are candidates for refractive surgery.
MATERIAL
and
METHODS
We studied 102 patients with low myopia (less than 6 diopters) in a single-center investigation.
RESULTS
Among the total population studied, the motivation for refractive surgery was essentially comfort and appearance. Fewer men wore contact lenses than women and had worn them for a shorter period of time. Those involved in sports were more often in individual sports. Contact-lens wearers were most often students or in the paramedical professions.
DISCUSSION
The population interested in refractive surgery was very young. The proportion of candidates who had never worn contact lenses was surprisingly high.
CONCLUSION
This analysis suggests that patients too often consider refractive surgery as an easy option. | pubmed_249_13775 |
pubmed_435_13660 | Research synthesis on simple yet general hypotheses and ideas is challenging in scientific disciplines studying highly context-dependent systems such as medical, social, and biological sciences. This study shows that machine learning, equation-free statistical modeling of artificial intelligence, is a promising synthesis tool for discovering novel patterns and the source of controversy in a general hypothesis. We apply a decision tree algorithm, assuming that evidence from various contexts can be adequately integrated in a hierarchically nested structure. As a case study, we analyzed 163 articles that studied a prominent hypothesis in invasion biology, the enemy release hypothesis. We explored if any of the nine attributes that classify each study can differentiate conclusions as classification problem. Results corroborated that machine learning can be useful for research synthesis, as the algorithm could detect patterns that had been already focused in previous narrative reviews. Compared with the previous synthesis study that assessed the same evidence collection based on experts' judgement, the algorithm has newly proposed that the studies focusing on Asian regions mostly supported the hypothesis, suggesting that more detailed investigations in these regions can enhance our understanding of the hypothesis. We suggest that machine learning algorithms can be a promising synthesis tool especially where studies (a) reformulate a general hypothesis from different perspectives, (b) use different methods or variables, or (c) report insufficient information for conducting meta-analyses. | 10.1002/jrsm.1363 |
pubmed_801_5131 | In several mammalian species females undergo postpartum estrus, a brief period of ovulation and sexual receptivity that in rats usually occurs during the first 24h following parturition. The maximal lordotic expression occurs at 12h after the initiation of parturition and depends on intracellular progesterone receptor (PR). We studied the regulation of PR expression by its antagonist, RU486 in the hypothalamus and the preoptic area of the rat during postpartum estrus by Western blot. Adult female rats were treated with RU486 (1.25 and 5mg) 3h after parturition, and Western blot was performed to assess the expression of PR-A and PR-B at 12h postpartum. RU486 (1.25 and 5mg) reduced the expression of PR-A (63% and 95%) and that of PR-B (75% and 99%), respectively in the preoptic area whereas it had no effects in the hypothalamus. These results suggest a differential regulation of PR expression in the rat brain during postpartum estrus. | 10.1016/j.neulet.2011.09.016 |
pubmed_261_10104 | Antibiotic resistance in Klebsiella pneumoniae strains is an increasing problem in a lot of hospitals. It is a public health emergency because it relates with high mortality rate among patients in Intensive Care Unit (ICU). From 1/1/2009 to 31/08/2010, in ICU of SS Annunziata Hospital of Taranto, 140 isolated Klebsiella pneumoniae strains were detected. The strain identification and antimicrobial susceptibility testing were performed using a Vitek2 automated system. These isolate showed a low level of susceptibility to levofloxacin (3.4%), ciprofloxacin (6.2%), ceftazidime (2.8%) and piperacillin/tazobactam (8%). We reported also that the 10% and 13.9% of them were susceptible to meropenem and imipenem. An anti-Klebsiella pneumoniae activity in vitro to tigecycline was present in 64.6% of isolates while almost all strains (56/58) tested to colistin were susceptible. In order to our data of worryng high multiclass drug resistance including tygecicline, it needs to apply appropriate measures of surveillance and antibiotic prescription to avoid rapid spread of these mutiresistant strains in other areas. | 10.1701/1127.12430 |
pubmed_1119_12155 | We analysed the effect of exposure to tobacco smoke during pregnancy on fetal growth parameters in 129 term newborns. Children were classified into four depending on exposure on the basis of a questionnaire completed by the mother. The results confirmed that tobacco smoking reduced weight, length, cranial and thoracic perimeters at birth when exposure was due to either active or passive smoking. Weight deficits of infants whose mothers smoked heavily (458 g) were higher than those whose mothers were exposed to passive smoking (192 g). We conclude that passive smoking is a very important variable and should be taken into account in any study of neonatal growth parameters. | 10.1111/j.1651-2227.1995.tb13592.x |
pubmed_726_16035 | INTRODUCTION
Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used for acute pain management. Lornoxicam is a nonselective NSAID for oral and intravenous administration. It has been available for human use since two decades and there is a growing body of evidence supporting its efficacy and tolerability for management of acute pain.
AREAS COVERED
Public domain literature around the clinical use of lornoxicam for acute pain management has been reviewed.
EXPERT OPINION
There are a growing number of clinical studies documenting lornoxicam effects for short-term treatment of acute postoperative pain following various surgical procedures. It has in the majority of comparative studies been shown superior as compared to paracetamol, non-inferior compared to other NSAIDs, and commonly similarly effective as standard clinical doses of opioids, but associated with better tolerability. Its effect on other acute pain, for example, headache, back pain, or sports injury is not well studied. Lornoxicam 8 mg twice daily is a seemingly effective and tolerable alternative NSAID for use as sole agent or as part of multimodal analgesia in adults. Available data does however not show any outstanding benefits or special risk. The general precautions with regard to the use of NSAIDs, the potential risks, for example, gastrointestinal bleeding and or cardiovascular side effects must be acknowledged. | 10.1517/14656566.2013.805745 |
pubmed_460_21154 | Hyperbaric oxygen (HBO2) causes CO2 retention in the brain that leads to the increase in cerebral blood flow (CBF) by poorly understood mechanisms. We have tested the hypothesis that NO is implicated in CBF-responses to hypercapnia under hyperoxic conditions. Alert rats were exposed to HBO2 at 5 ata and blood flow in the striatum measured by H2 clearance every 10 min. Acetazolamide, the inhibitor of carbonic anhydrase, was used to increase brain PCO2. CBF responses to acetazolamide administration (30 mg/kg, i.p.) were assessed in rats breathing air at 1 ata or oxygen at 5 ata with and without NOS inhibition (L-NAME, 30 mg/kg, i.p.). In rats breathing air, acetazolamide increased CBF by 34 +/- 7.4% over 30 min and by 28 +/- 12% over 3 hours while NOS inhibition with L-NAME attenuated acetazolamide-induced cerebral vasodilatation. HBO2 at 5 ata reduced CBF during the first 30 min hyperoxia, after that CBF increased by 55 +/- 19% above pre-exposure levels. In acetazolamide-treated animals, no HBO, induced vasoconstricton was observed and striatal blood flow increased by 53 +/- 18% within 10 min of hyperbaric exposure. After NOS inhibition, cerebral vasodilatation in response to acetazolamide during HBO2 exposure was significantly attenuated. The study demonstrates that NO is implicated in acetazolamide (CO2)-induced cerebral hyperemia under hyperbaric oxygen exposure. | pubmed_460_21154 |
pubmed_920_20777 | Lab-on-a-chip (LOC) and organ-on-a-chip (OOC) devices are highly versatile platforms that enable miniaturization and advanced controlled laboratory functions (i.e., microfluidics, advanced optical or electrical recordings, high-throughput screening). The manufacturing advancements of LOCs/OOCs for biomedical applications and their current limitations are briefly discussed. Multiple studies have exploited the advantages of mimicking organs or tissues on a chip. Among these, we focused our attention on the brain-on-a-chip, blood-brain barrier (BBB)-on-a-chip, and neurovascular unit (NVU)-on-a-chip applications. Mainly, we review the latest developments of brain-on-a-chip, BBB-on-a-chip, and NVU-on-a-chip devices and their use as testing platforms for high-throughput pharmacological screening. In particular, we analyze the most important contributions of these studies in the field of neurodegenerative diseases and their relevance in translational personalized medicine. | 10.3390/biom11060916 |
pubmed_586_10183 | The pertinence of a rating scale capable of characterizing presenting psychopathology and measuring degrees of change for psychoneurotic patients treated in an outpatient setting is described. Data for 328 patients who represent 1191 rating profiles were used to develop the factor structure for the New Physician's Rating List, a rating scale completed by health professionals after Patient interviews. Findings were used to develop the new Brief Outpatient Psychopathology Scale. A proposed factor structure is discussed. The structures of both scales include an Anxiety Syndrome composed of Anxiety and Psychomotor Activation Factors. The scales also include Depression and Somatization factors. | 10.1002/1097-4679(197707)33:3<677::aid-jclp2270330315>3.0.co;2-m |
pubmed_368_8870 | Considering a fatal case of an aged individual, who died due to falling down stairs, the cause of the fatal fall was investigated through experiments. A witness, who was with the victim, when the fatal accident occurred, stated that the aged individual had miss-footed, lost balance at the top of the stairs, and fell accidently from an upper floor to a lower floor. It was very questionable whether or not this witness's statements were true. The true cause of the fatal fall was unclear, because of the witness's inconsistent statements, which showed discrepancies between the initial and later statements. The cause of a fatal fall can be presumed from external and internal damages to the body and other circumstantial evidences. But it was difficult to prove the true cause of a fatal fall only from the results of the autopsy and investigation of circumstantial evidences. The author was officially requested to conduct experiments to elucidate possible falling patterns. Judging from the experimental results, deep questions about the witness's statements arose. These experimental methods and analyses in this paper could be applied to elucidate possible falling patterns of fatal falls from stairs where the fatal causes are controversial. | 10.2486/indhealth.2014-0092 |
pubmed_222_12360 | Army families in the UK have been observed to have a higher infant mortality compared with the civilian population. Little is known about the reasons for the higher mortality. We report a comparative study of the health of army and civilian babies and their families in a UK garrison town, the aim being to investigate any differences in risk factors which may have explained the differences in mortality. A total of 250 first born army and civilian babies fulfilling the selection criteria were recruited to the study. Army babies had a lower birth weight distribution and both maternal and paternal smoking rates were higher in army families. In addition, social support and in particular, contact with close family members appeared to be available to fewer army mothers. The study highlighted the needs of this population and prompted a number of local health services to work together to address the issues it raised. | 10.1038/sj.ph.1900381 |
others_314_28652 | Homeostasis in high-turnover tissues depends on precise yet plastic regulation of stem cell daughter fates. In Drosophila, intestinal stem cells (ISCs) respond to unknown signals to switch from asymmetric to symmetric divisions during feeding-induced growth. Here, we show that this switch is controlled by dynamic reorientation of mitotic spindles by a Jun-N-terminal Kinase (JNK) / Wdr62 / Kif1a interaction. JNK promotes Wdr62 localization at the spindle and represses transcription of the kinesin Kif1a. This activity of JNK results in over-abundance of symmetric divisions in stress conditions, and contributes to the loss of tissue homeostasis in the aging animal. Restoring normal ISC spindle orientation by perturbing the JNK/Wdr62/Kif1a axis is sufficient to improve intestinal physiology and extend lifespan. Our findings reveal a critical role for the dynamic control of SC spindle orientation in epithelial maintenan | 10.1101/365981 |
pubmed_992_5613 | Macrophages perform critical functions in both innate immunity and cholesterol metabolism. Here, we report that activation of Toll-like receptor 4 (TLR4) in macrophages causes lanosterol, the first sterol intermediate in the cholesterol biosynthetic pathway, to accumulate. This effect is due to type I interferon (IFN)-dependent histone deacetylase 1 (HDAC1) transcriptional repression of lanosterol-14α-demethylase, the gene product of Cyp51A1. Lanosterol accumulation in macrophages, because of either treatment with ketoconazole or induced conditional disruption of Cyp51A1 in mouse macrophages in vitro, decreases IFNβ-mediated signal transducer and activator of transcription (STAT)1-STAT2 activation and IFNβ-stimulated gene expression. These effects translate into increased survival to endotoxemic shock by reducing cytokine secretion. In addition, lanosterol accumulation increases membrane fluidity and ROS production, thus potentiating phagocytosis and the ability to kill bacteria. This improves resistance of mice to Listeria monocytogenes infection by increasing bacterial clearance in the spleen and liver. Overall, our data indicate that lanosterol is an endogenous selective regulator of macrophage immunity. | 10.1016/j.celrep.2017.05.093 |
pubmed_308_8676 | CH3NH3PbI(3-x)Cl(x)(MAPbI(3-x)Cl(x)) mixed halide perovskite powder with uniform composition was synthesized via simple solution chemistry, which demonstrates highly reproducible, efficient planar type MAPbI(3-x)Cl(x) mixed halide perovskite solar cells. Pure MAPbI(3-x)Cl(x) mixed halide perovskite powder was synthesized by reacting a 3 : 1 molar ratio of MAI : PbCl2 powder mixture in isopropanol (IPA) solution for 30 min at 60 °C with subsequent repeated centrifugation and washing in IPA. IPA functions as both the reaction medium for the formation of MAPbI(3-x)Cl(x) mixed halide and a selective remover of unreacted MAI and MACl byproducts. Accordingly, we could deposit a pinhole-free dense MAPbI(3-x)Cl(x) mixed halide perovskite film on a TiO2/FTO substrate through a simple one step spin-coating of pure MAPbI(3-x)Cl(x) mixed halide perovskite powder in DMF solution with HI additive, without further long heat-treatment processes. The deposited MAPbI(3-x)Cl(x) mixed halide perovskite film revealed uniform composition throughout the entire area, and the ratio of Cl to I + Cl and I + Cl to Pb was constant at ∼0.03 and ∼1/3, respectively. On the other hand, the conventional MAPbI(3-x)Cl(x) mixed halide perovskite film prepared by the long heat-treatment process had non-uniform composition because the ratio of Cl to I + Cl fluctuated greatly from 0 to 7.2. The average efficiency of planar type MAPbI(3-x)Cl(x) mixed halide perovskite solar cells was 18.65% ± 0.30% and the champion cell had 1.11 V V(oc), 22.1 mA cm(-2) J(sc), 77% F.F., and 18.9% η for forward scan conditions and 1.11 V V(oc), 22.1 mA cm(-2) J(sc), 78% F.F., and 19.1% η for reverse scan conditions. Although the thickness of the MAPbI(3-x)Cl(x) mixed halide perovskite layer varied from ∼500 nm to ∼900 nm, the efficiency was within the range of 18.3%-19.0%. | 10.1039/c5nr08458j |
pubmed_191_13117 | The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG), in comparison with placebo and with a group of controls in 23 patients with superficial vein thrombophlebitis (SVTPH) of the arms. SVTPH was consequent to infusional treatment with an intravenous catheter. The 4-week study evaluated the average skin temperature and an analogue symptomatic score. In patients treated with active EG, the decrease in score and in composite skin temperature was significantly larger than in the placebo and control groups. No intolerance was observed. The decrease in score and temperature in the placebo group was mainly due to skin manipulation and massage and to spontaneous resolution. In conclusion treatment with EG in arm SVTPH improves signs /symptoms and decreases skin temperature faster. This study confirms earlier observations on the effective, local use of EG in SVTPH. | 10.1177/0003319701052003S12 |
pubmed_1136_20078 | BACKGROUND
The aim of this study was to examine how different environmental factors (temperature, solar radiation, and vapour-pressure deficit [VPD]) influenced nutritional quality and flavour of cherry tomato fruits (Solanum lycopersicum L. cv. Naomi) grown in two types of experimental Mediterranean greenhouses: parral (low technology) and multispan (high technology).
RESULTS
Fruits were sampled three times during 3 years (2004, 2005 and 2006): at the beginning, middle and end of the fruit production period. Values for temperature, solar radiation, and VPD peaked in the third sampling in both greenhouses; values were higher in the parral-type greenhouse, triggering abiotic stress. This stress reduced the accumulation of lycopene and essential elements, augmenting the phytonutrient content and the antioxidant capacity of tomatoes. During the third sampling, sugars were increased while organic acid content diminished, producing tomatoes with a sweeter-milder flavour. The parral greenhouse produced tomatoes with higher phenolic compounds and ascorbic acid contents, together with a greater antioxidant capacity, without showing differences in flavour parameters.
CONCLUSION
The higher phytonutrients content and antioxidant activity during the environmental stress, more pronounced in parral than multispan greenhouse, together with the sweeter-milder flavour, conferred a notable nutritional benefit, which considerably improved the nutritional and organoleptic quality of these tomatoes. | 10.1002/jsfa.4166 |
pubmed_920_20586 | The Tribbles family of proteins-comprising TRIB1, TRIB2, TRIB3 and more distantly related STK40-play important, but distinct, roles in differentiation, development and oncogenesis. Of the four Tribbles proteins, TRIB1 has been most well characterised structurally and plays roles in diverse cancer types. The most well-understood role of TRIB1 is in acute myeloid leukaemia, where it can regulate C/EBP transcription factors and kinase pathways. Structure-function studies have uncovered conformational switching of TRIB1 from an inactive to an active state when it binds to C/EBPα. This conformational switching is centred on the active site of TRIB1, which appears to be accessible to small-molecule inhibitors in spite of its inability to bind ATP. Beyond myeloid neoplasms, TRIB1 plays diverse roles in signalling pathways with well-established roles in tumour progression. Thus, TRIB1 can affect both development and chemoresistance in leukaemia; glioma; and breast, lung and prostate cancers. The pervasive roles of TRIB1 and other Tribbles proteins across breast, prostate, lung and other cancer types, combined with small-molecule susceptibility shown by mechanistic studies, suggests an exciting potential for Tribbles as direct targets of small molecules or biomarkers to predict treatment response. | 10.3390/cancers13123060 |
pubmed_120_17926 | Cases diagnosed with portosystemic shunting between the years 1993 and 2001 were reviewed. Sensitivities of screening tests and abdominal ultrasonographic evaluation for the detection of portosystemic shunting were evaluated. Prognosis for surgically treated shunts was also evaluated. Results indicated that both paired serum bile acids and blood ammonia levels were useful screening tests for portosystemic shunting. However, paired bile acid tests were significantly more sensitive than blood ammonia levels. Overall postoperative mortality rates for extrahepatic shunts and intrahepatic shunts were 8.7% and 20%, respectively. Postoperative mortality rates were slightly higher for animals treated with partial ligation when compared to those treated with ameroid ring placement, although this did not reach statistical significance. Long-term complication rates for animals with single extrahepatic portosystemic shunts treated with complete ligation, ameroid ring placement, and partial ligation alone were 9%, 15.4%, and 42%, respectively. Animals >2 years of age with extrahepatic shunts had almost identical postoperative mortality and long-term complication rates as animals < or = 2 years of age. No animal in this study had paired bile acid samples within the reference range postoperatively, indicating continued abnormal liver function after surgery. | 10.5326/0390169 |
pubmed_1045_4553 | Alzheimer's disease is a clinical syndrome reflecting the topography and rate of progression of amyloid-associated cell death and dysfunction. Abnormal processing of amyloid precursor protein or enhanced accumulation of brain amyloid incites multiple pathogenetic pathway including inflammation, oxidation, and tau protein hyperphosphorylation that lead to neuronal death. The molecular biology of Alzheimer's disease provides insight into the clinical phenotype. The steps of the amyloid cascade present multiple targets for drug development and identification of effective disease-modifying anti-Alzheimer's disease treatments. | 10.1053/scnp.2003.50005 |
pubmed_1067_4441 | The purpose of this study was to characterize the contributions of individual muscles to forward progression and vertical support during walking. We systematically perturbed the forces in 54 muscles during a three-dimensional simulation of walking, and computed the changes in fore-aft and vertical accelerations of the body mass center due to the altered muscle forces during the stance phase. Our results indicate that muscles that provided most of the vertical acceleration (i.e., support) also decreased the forward speed of the mass center during the first half of stance (vasti and gluteus maximus). Similarly, muscles that supported the body also propelled it forward during the second half of stance (soleus and gastrocnemius). The gluteus medius was important for generating both forward progression and support, especially during single-limb stance. These findings suggest that a relatively small group of muscles provides most of the forward progression and support needed for normal walking. The results also suggest that walking dynamics are influenced by non-sagittal muscles, such as the gluteus medius, even though walking is primarily a sagittal-plane task. | 10.1016/j.jbiomech.2005.08.017 |
others_314_203728 | The Nucleocapsid (N) protein of SARS-CoV-2 compacts the RNA genome into viral ribonucleoprotein (vRNP) complexes within virions. Assembly of vRNPs is inhibited by phosphorylation of the N protein SR region. Several SARS-CoV-2 variants of concern carry N protein mutations that reduce phosphorylation and enhance the efficiency of viral packaging. Variants of the dominant B.1.1 viral lineage also encode a truncated N protein, termed N* or {Delta}(1-209), that mediates genome packaging despite lacking the N-terminal RNA-binding domain and SR region. Here, we show that {Delta}(1-209) and viral RNA assemble into vRNPs that are remarkably similar in size and shape to those formed with full-length N protein. We show that assembly of {Delta}(1-209) vRNPs requires the leucine-rich helix (LH) of the central disordered region, and that the LH promotes N protein oligomerization. We also find that fusion of a phosphomimetic SR region to {Delta}(1-209) inhibits RNA binding and vRNP assembly. Our results provide new insights into the mechanisms by which RNA binding promotes N protein self-association and vRNP assembly, and how this process is modulated by SR phosphoryla | 10.1101/2023.08.16.553581 |
pubmed_909_23905 | The progressive increase of insulin resistance observed in pregnancy contributes to the pathophysiology of gestational diabetes mellitus (GDM). There is controversy whether vitamin D deficiency contributes to abnormal glycemic regulation in pregnancy. We tested the associations between first trimester 25-hydroxyvitamin D (25OHD) levels and: 1) the risk of developing GDM; 2) insulin resistance/sensitivity, beta cell function and compensation indices in a large population-based prospective cohort of pregnant women. Participants (n = 655) were seen at first (6-13 weeks) and second (24-28 weeks) trimesters for blood samples. At first trimester, 25OHD levels were measured. At second trimester, glucose and insulin were measured 3 times during the oral glucose tolerance test to estimate insulin resistance (HOMA-IR), beta cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUCins/gluc) and beta cell compensation (ISSI-2). Based on IADPSG criteria, 54 participants (8.2 %) developed GDM. Lower first trimester 25OHD levels were associated with higher risk of developing GDM even after adjustment for vitamin D confounding factors and GDM risk factors (OR = 1.48 per decrease of one SD in 25OHD levels; P = 0.04). Lower first trimester 25OHD levels were associated with higher HOMA-IR (r = - 0.08; P = 0.03), lower Matsuda index (r = 0.13; P = 0.001) and lower ISSI-2 (r = 0.08; P = 0.04). After adjustment for confounders, we found no significant association with HOMA-B and AUCins/gluc. Our results suggest that low levels of 25OHD at first trimester are (1) an independent risk factor for developing GDM and (2) associated with insulin resistance at second trimester. | 10.1007/s00592-014-0564-4 |
pubmed_337_31 | 1. The absorption, metabolism and excretion of cobimetinib, an allosteric inhibitor of MEK1/2, was characterized in mass balance studies following single oral administration of radiolabeled (14C) cobimetinib to Sprague-Dawley rats (30 mg/kg) and Beagle dogs (5 mg/kg). 2. The oral dose of cobimetinib was well absorbed (81% and 71% in rats and dogs, respectively). The maximal plasma concentrations for cobimetinib and total radioactivity were reached at 2-3 h post-dose. Drug-derived radioactivity was fully recovered (∼90% of the administered dose) with the majority eliminated in feces via biliary excretion (78% of the dose for rats and 65% for dogs). The recoveries were nearly complete after the first 48 h following dosing. 3. The metabolic profiles indicated extensive metabolism of cobimetinib prior to its elimination. For rats, the predominant metabolic pathway was hydroxylation at the aromatic core. Lower exposures for cobimetinib and total radioactivity were observed in male rats compared with female rats, which was consistent to in vitro higher clearance of cobimetinib for male rats. For dogs, sequential oxidative reactions occurred at the aliphatic portion of the molecule. Though rat metabolism was well-predicted in vitro with liver microsomes, dog metabolism was not. 4. Rats and dogs were exposed to the two major human circulating Phase II metabolites, which provided relevant metabolite safety assessment. In general, the extensive sequential oxidative metabolism in dogs, and not the aromatic hydroxylation in rats, was more indicative of the metabolism of cobimetinib in humans. | 10.3109/00498254.2016.1157645 |
pubmed_26_5179 | Although short-lived vertebrates can serve as model animals for understanding the mechanism of aging, whether the annual fish Nothobranchius rachovii is suitable for studying aging remains an open question. In this study, histochemical, biochemical, and genetic techniques were used to determine the age-related markers at three different developmental stages of the annual fish N. rachovii. Histochemical studies revealed that the expression of senescence-associated beta-galactosidase and accumulation of lipofuscin increased with age. In biochemical assays, lipid peroxidation and protein oxidation increased with age, whereas the activities of catalase, glutathione peroxidase, and superoxide dismutase decreased with age. Genetic analysis established that the activities of telomerase had no apparent relationship with age, but telomere lengths reduced with age from 11.5 +/- 1.98 to 3.58 +/- 0.74 kb. Taken together, these results indicate that the annual fish N. rachovii may be useful as an animal model for the study of aging. | 10.1093/gerona/63.12.1267 |
pubmed_693_1034 | Protein translocation systems which are inhibited by vinblastine, colchicine, and low calcium concentrations have been found in the cells of the brain slice. The early steps in the translocation pathways of newly synthesized protein have been studied by use of a double-label experiment in conjunction with subcellular fractionation. Certain subcellular particles have been positioned on the pathways with reference to vinblastine-sensitive translocation steps. There appears to be many subcellular organelles that are located downstream from a vinblastine-sensitive translocation step and which receive significant quantities of translocated protein within an hour of its synthesis. Some of these organelles co-enrich with the enzyme marker 5'-AMPase. Myelinated axons, Golgi derived vesicles, and smooth and rough endoplasmic reticulum all are enriched in fractions which contain a net vinblastine-sensitive importation of protein. The major particles, which lie upstream from a vinblastine-sensitive translocation step and are net exporters of protein on this system, are found in a brain capillary fraction. It is suggested that the most likely exporter present in these capillaries are the end feet of astrocyte glial cells. | 10.1002/neu.480100607 |
pubmed_511_16900 | OBJECTIVE
Patient perceived level of force is commonly used to regulate exercise load. This study determined the accuracy of perceived force as a method of regulating exercise load for the cervical flexors and extensors.
METHODS
Thirty healthy individuals performed submaximal isometric cervical flexion and extension exercise at perceived intensities (25%, 50%, and 75%) of their maximal voluntary contraction (MVC) with no feedback in a neck dynamometer. Measurements of "actual" versus "perceived" force levels were compared before and after the performance of an MVC. Data were analyzed descriptively and the relationship between performance error, test, and participant factors examined.
RESULTS
With the exception of the 25% MVC extension trials post-MVC, an underestimation of force was observed over all conditions that worsened as the target force increased (50% and 75%) with only some improvement following the experience of an MVC (p < 0.001). Linear mixed modeling indicated participants familiar with exercise may have better accuracy (p = 0.07).
CONCLUSION
Regulating isometric resistance exercise load of the neck based on a perceived proportion of MVC force may only be accurate at low intensities (25% MVC) but not for moderate to high (50-75%) intensities. | 10.1080/09593985.2018.1455250 |
pubmed_595_9646 | BACKGROUND
Anti-cardiolipin antibodies have been associated with both arterial and venous thrombosis, but their overall impact on all-cause or vascular mortality is unknown. In this study, we evaluated the influence of anti-cardiolipin antibodies on all-cause and vascular mortality.
METHODS
All individuals who fulfilled the inclusion criteria (completeness of data, no admission from an intensive care unit, unique identification with name and date of birth) and whose anti-cardiolipin antibodies were measured between October 2002 and February 2004 were included in this study (n = 4756; 64% female; median age, 46 years). Death/survival and cause of death were obtained from the Austrian Death Registry. The median observation period was 1.5 years, and the study comprised 7189 person-years.
RESULTS
During the study period, 184 patients (3.9%) died. There were no associations between either anti-cardiolipin IgM or IgG antibodies and both vascular death and noncancer mortality as outcome variables in a Cox regression analysis adjusted for age and sex. In contrast, the risk of cancer-related mortality was increased 2.6-fold.
CONCLUSIONS
Anti-cardiolipin antibodies are associated with cancer mortality, likely as an epiphenomenon of malignancy, but they are not predictive of vascular mortality or noncancer mortality. Hence, although a clear association between anti-cardiolipin antibodies and (mostly nonfatal) vascular events has been described in the literature, our data indicate that this finding is not necessarily associated with an increase in vascular mortality. | 10.1373/clinchem.2005.063925 |
others_314_91441 | The rhomboid protease PARL is a critical regulator of mitochondrial homeostasis through its cleavage of substrates such as PINK1, PGAM5, and Smac, which have crucial roles in mitochondrial quality control and apoptosis. To gain insight into the catalytic properties of the PARL protease, we expressed human PARL in yeast and used FRET-based kinetic assays to measure proteolytic activity in vitro. We show PARL activity in detergent is enhanced by cardiolipin. Significantly higher turnover rates are observed for PARL reconstituted in proteoliposomes, with Smac being cleaved most rapidly at a rate of 1 min-1. PGAM5 is cleaved with the highest efficiency compared to PINK1 and Smac. In proteoliposomes, a truncated {beta}-cleavage form of PARL is more active than the full-length enzyme for hydrolysis of PINK1, PGAM5 and Smac. Multiplex substrate profiling reveals a substrate preference for PARL with a bulky side chain Phe in P1, which is distinct from small side chain residues typically found with bacterial rhomboid proteases. This study using recombinant PARL provides fundamental insights into its catalytic activity and substrate preferences | 10.1101/2020.07.27.224220 |
others_304_9419 | The purpose of this research was to quantify the spatial pattern and develop a sampling program for larvae of Lobesia botrana Denis & Schiffermüller (Lepidoptera: Tortricidae), an important vineyard pest in northern Greece. Taylor's power law and Iwao's patchiness regression were used to model the relationship between the mean and the variance of larval counts. Analysis of covariance was carried out, separately for infestation and injury, with combined second and third generation data, for vine and half-vine sample units. Common regression coefficients were estimated to permit use of the sampling plan over a wide range of conditions. Optimum sample sizes for infestation and injury, at three levels of precision, were developed. An investigation of a multistage sampling plan with a nested analysis of variance showed that if the goal of sampling is focusing on larval infestation, three grape clusters should be sampled in a half-vine: if the goal of sampling is focusing on injury, then two grape clusters per half-vine are recommended. © 2006 Entomological Society of Amer | 10.1093/jee/99.5.1890 |
pubmed_722_8429 | Of 362 fecal specimens collected from infants and children hospitalized with acute gastroenteritis in Sri Lanka from September 2005 to August 2006, 30 (8.3%) were positive for human parechovirus (HPeV). Six different HPeV genotypes, including HPeV1, -3, -4, -5, -10, and -11, were identified, of these, HPeV11 was reported for the first time. | 10.1128/JCM.02151-10 |
pubmed_238_16522 | Amyloid-β (Aβ) dimers are the smallest toxic species along the amyloid-aggregation pathway and among the most populated oligomeric accumulations present in the brain affected by Alzheimer's disease (AD). A proposed therapeutic strategy to avoid the aggregation of Aβ into higher-order structures is to develop molecules that inhibit the early stages of aggregation, i.e., dimerization. Under physiological conditions, the Aβ dimer is highly dynamic and does not attain a single well-defined structure but is rather characterized by an ensemble of conformations. In a recent study, a highly heterogeneous library of conformers of the Aβ dimer was generated by an efficient sampling method with constraints based on ion mobility mass spectrometry data. Here, we make use of the Aβ dimer library to study the interaction with two curcumin degradation products, ferulic aldehyde and vanillin, by molecular dynamics (MD) simulations. Ensemble docking and MD simulations are used to provide atomistic detail of the interactions between the curcumin degradation products and the Aβ dimer. The simulations show that the aromatic residues of Aβ, and in particular 19FF20, interact with ferulic aldehyde and vanillin through π-π stacking. The binding of these small molecules induces significant changes on the 16KLVFF20 region. | 10.1021/acs.jpcb.2c05846 |
pubmed_106_3561 | Spindle cell lipoma (SCL) is a relatively uncommon benign lipomatous tumor characterized by a mixture of mature adipocytes and bland spindle cells on a fibromyxoid background. These lipomas usually arise as solitary nodules in the subcutaneous tissue of the posterior neck, shoulder and back in adult men. Multiple SCLs account for 0.5% to 3% of all SCLs. In the literature, there have been 15 cases of intraoral SCL, including 6 cases of SCL in the tongue. We report a case of multiple SCLs on the bilateral margins of the tongue of a 75-year-old Japanese man. The tumors were removed surgically, and they exhibited the classic histopathological features of SCL, being well-circumscribed masses composed of a mixture of adipocytes and fibroblast-like spindle cells within a fibromyxoid stroma. Immunohistochemical analysis revealed that the spindle cells were strongly positive for CD 34 and bcl-2. To our knowledge, this is the first report of a case of multiple SCLs of the tongue. | 10.1034/j.1600-0463.2003.1110507.x |
pubmed_318_712 | Lipids from the sputum of patients with asthma and with cystic fibrosis were isolated and characterized. In both cases, lipids constituted approximately 30% of the dry material. Phosphatidlycholine was the most abundant lipid, Significant amounts of phosphatidylethanolamine and phosphatidylglycerol were present. Hexosyl ceramides, sphingomyelin, phosphatidylinositol, lysophosphatidylcholine, and lysophosphatidylethanolamine were present as minor lipid components. Apperciable quantities of neutral lipids were present, of which triglycerides and cholesterol were the main constituents. Phosphatidylcholine, sphingomyelin, and phosphatidylgycerol were highly saturated. Large amounts of phosphatidylcholine containing mostly palmitic acid, particularly in the asthmatic sputum, suggest htat this highly saturated. Large amounts of phosphatidylcholine containing mostly palmitic acid, particularly in the asthmatic sputum, suggests that this highly saturated phospholipid is synthesized in the upper airways for reasons other than its beneficial surface-active properties in the alveoli. | 10.1007/BF00917319 |
pubmed_332_22631 | Recently, we reported that an initial decrease followed by recovery of food intake was observed during four days of amphetamine (AMPH) treatment and suggested that these changes in response were mediated by changes in neuropeptide Y (NPY) and proopiomelanocortin (POMC). Here we investigated if Y1 receptor (Y1R) and/or Y5 receptor (Y5R) might be involved in this regulation. Rats were treated daily with AMPH for four days. Changes in the expression levels of Y1R, Y5R, melanocortin receptor 3 (MC3R), and NPY were assessed and compared. Results showed that Y1R and MC3R increased, with a maximal increase of about 210% on Day 2 but with a restoration to the normal level on Day 4. In contrast, NPY decreased with a biggest reduction of about 45% on Day 2 and the pattern of expression during AMPH treatment was opposite to those of Y1R and MC3R, while the expression of Y5R was not changed. Central inhibitions of NPY formation or Y1R activity modulated the anorectic response of AMPH and the reciprocal regulation of NPY and MC3R, revealing a crucial role of Y1R in this action. It is suggested that Y1R participates in the reciprocal regulation of NPY- and MC3R-containing neurons in the hypothalamus during the anorectic effect of AMPH. These results may further the understanding of Y1R in the control of eating. | 10.1016/j.neuropharm.2012.06.018 |
pubmed_129_557 | This study evaluated the antigenicity of LH-ovalbumin complexes produced using different conjugation techniques. Two homobifunctional cross-linkers, glutaraldehyde (Glut) and carbodiimide (ECDI), were evaluated together with one heterobifunctional reagent, m-maleimido-benzoyl N-hydroxysuccinimide ester (MBS). Polyacrylamide gel electrophoresis and Western transfer techniques were used to confirm conjugation of LH. Forty-four beef heifers were assigned randomly to seven treatment groups. Two groups of heifers were immunized against glutaraldehyde conjugates (Glut-I and Glut-II), two against MBS conjugates (MBS-I and MBS-II) and one against a carbodiimide conjugate (ECDI). Control animals were immunized against nonconjugated LH (LH-only) or ovalbumin alone (Oval). Heifers received one primary injection of antigen followed by two boosters at a 3-wk interval. The Glut conjugates induced the highest (P less than .05) LH antibody activity (Glut-II, 18 +/- 4%; Glut-I, 14 +/- 4%). The ECDI (11 +/- 4%), and MBS-I (11 +/- 2%) conjugates induced greater LH binding than MBS-II (4 +/- 1%), LH-only (4 +/- 1%) or Oval (2 +/- 1%). Glutaraldehyde produced an LH-ovalbumin conjugate of greater LH immunogenicity than either ECDI or the heterobifunctional reagent, MBS. | 10.2527/1990.68113747x |
pubmed_1021_14117 | Authors have performed 29 septic operations by a TLS61 60 W CO2 laser apparatus. In accordance with international experience, favorable results have been obtained in laser surgery of vascularized, hemophilic and bacterium penetrated alterations and infected wounds. | pubmed_1021_14117 |
pubmed_410_8147 | OBJECTIVE
This study investigated the subgingival microbial profile of rheumatoid arthritis (RA) patients and its associations with disease parameters and the inflammation-related antimicrobial peptide, LL-37.
METHODS
RA and non-RA (NRA) patients were assessed for periodontal status and divided into periodontitis (CP), gingivitis (G), and healthy (H) groups. Subgingival plaque 16s rRNA gene sequencing data was processed and analyzed using the CLC Genomic Workbench (Qiagen). Bacterial diversity and co-occurrence patterns were examined. Differential abundance between groups was also investigated. Associations between bacterial genera with disease parameters and LL-37 levels were explored qualitatively using canonical correlation analysis.
RESULTS
Subgingival microbial community clustered in CP status. Co-occurrence network in NRA-H was dominated by health-associated genera, while the rest of the networks' key genera were both health- and disease-associated. RA-CP displayed highly inter-generic networks with a statistically significant increase in periodontal disease-associated genera (p<0.05). In NRA-H, disease parameters and LL-37 were correlated positively with disease-associated genera while negatively with health-associated genera. However, in the remaining groups, mixed positive and negative correlations were noted with genera.
CONCLUSION
RA patients demonstrated subgingival microbial dysbiosis where the bacteria networks were dominated by health- and disease-associated genera. Mixed correlations with disease parameters and LL-37 levels were noted.
CLINICAL RELEVANCE
The subgingival microbial dysbiosis in RA may predispose these patients to developing periodontal inflammation with an associated detrimental effect on host immune responses. Routine periodontal assessment may allow initiation of treatment strategies to minimize the effects of gingival inflammation on the existing heightened immune response present in RA patients. | 10.1007/s00784-022-04388-y |
pubmed_1127_5627 | Thermal imaging measurements using ultrasound phase contrast have been performed in tissue phantoms heated with a focused ultrasound source. Back projection and reflex transmission imaging principles were used to detect sound speed-induced changes in the phase caused by an increase in the temperature. The temperature was determined from an empirical relationship for the temperature dependence on sound speed. The phase contrast was determined from changes in the sound field measured with a hydrophone scan conducted before and during applied heating. The lengthy scanning routine used to mimic a large two-dimensional array required a steady-state temperature distribution within the phantom. The temperature distribution in the phantom was validated with magnetic resonance (MR) thermal imaging measurements. The peak temperature was found to agree within 1 degrees C with MR, and good agreement was found between the temperature profiles. The spatial resolution was 0.3x0.3x0.3mm, comparing favorably with the 0.625x0.625x1.5-mm MR spatial resolution. | 10.1016/j.ultrasmedbio.2009.05.019 |
pubmed_808_23157 | The polarized IR spectra of isotopically neat and isotopically substituted monocrystalline samples of 2-phenyl-1H-imidazole (2PI) and 4-phenyl-1H-imidazole (4PI) were recorded at two temperatures of 293 K and 77 K. The room-temperature ATR-FTIR and Raman spectra of 2PI and two polymorphic forms of 4PI were also recorded. Theoretical analysis of the vibrational spectra of selected imidazole derivatives reflected similar characteristics of their hydrogen-bond networks and allowed us to obtain the information about the mechanism of the H/D isotopic "self-organization" phenomenon. The distribution of protons and deuterons in the lattices of the isotopically diluted crystalline samples of 2PI and 4PI was found to be non-random. In the crystals of the hydrogen- and deuterium-bonded imidazole derivatives the strongest vibrational exciton interactions favored the intrachain ("tail-to-head")-type exciton coupling widespread at 77 K via the π-electrons. At room temperature a weak interchain ("through-space")-type exciton coupling was also partially responsible for the IR spectra generation. Differential scanning calorimetry (DSC) measurements showed that the two polymorphic forms of 4PI exhibit an extensive supercooling of crystallization process and cold crystallization on reheating. Additionally, both polymorphic modifications of 4PI are monotropically related. 2PI exhibits only the crystallization and melting processes. | 10.1016/j.saa.2017.04.062 |
pubmed_433_19696 | Inwardly rectifying K+ (Kir) channels are expressed in multiple organs and cell types and play critical roles in cellular function. Most notably, Kir channels are major determinants of the resting membrane potential and K+ homeostasis. The renal outer medullary K+ channel (Kir1.1) was the first renal Kir channel identified and cloned in the kidney over two decades ago. Since then, several additional members, including classical and ATP-regulated Kir family classes, have been identified to be expressed in the kidney and to contribute to renal ion transport. Although the ATP-regulated Kir channel class remains the most well known due to severe pathological phenotypes associated with their mutations, progress is being made in defining the properties, localization, and physiological functions of other renal Kir channels, including those localized to the basolateral epithelium. This review is primarily focused on the current knowledge of the expression and localization of renal Kir channels but will also briefly describe their proposed functions in the kidney. | 10.1152/ajprenal.00523.2019 |
pubmed_1091_4582 | Background
The vascular endothelial growth factor antibody bevacizumab (Avastin®), received approval for the treatment of recurrent glioblastoma in many countries including the USA and Switzerland, but not the European Union, in 2009. Here, we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level.
Patients and methods
The prognostic significance of epidemiological, molecular genetic, and clinical data including treatment for glioblastoma patients diagnosed from 2010 to 2014 in the Canton of Zurich, Switzerland, was retrospectively analyzed using log-rank test and Cox proportional hazards models. Data were compared with data for the years 2005-2009.
Results
In total, 310 glioblastoma patients were identified in the years 2010-2014. Median overall survival was 13.5 months for patients with known isocitrate dehydrogenase (IDH) wild-type (wt) (IDH1R132H-non-mutant) tumors (N = 248), compared with 11.3 months for IDH wt patients (P = 0.761) before (2005-2009). In the IDH wt cohort, bevacizumab use at any time increased from 19% in 2005-2009 to 49% in 2010-2014. Multivariate analysis did not identify bevacizumab exposure at any time to be associated with survival. Yet, upon the second-line treatment, baseline doses of corticosteroids were reduced by more than half in 83% of patients on bevacizumab compared with 48% of the patients treated with bevacizumab-free regimens (P = 0.007).
Conclusion
This epidemiological study of a small, but clinically well-annotated patient cohort fails to support the assumption that the strong increase of bevacizumab use since 2010 improved survival in glioblastoma although clinical benefit associated with decreased steroid use may have been achieved. | 10.1093/annonc/mdy106 |
pubmed_80_6515 | A novel high-quality custom-made macroscope optics, dedicated to high-resolution time-resolved X-ray tomographic microscopy at the TOMCAT beamline at the Swiss Light Source (Paul Scherrer Institut, Switzerland), is introduced. The macroscope offers 4× magnification, has a very high numerical aperture of 0.35 and it is modular and highly flexible. It can be mounted both in a horizontal and vertical configuration, enabling imaging of tall samples close to the scintillator, to avoid edge-enhancement artefacts. The macroscope performance was characterized and compared with two existing in-house imaging setups, one dedicated to high spatial and one to high temporal resolution. The novel macroscope shows superior performance for both imaging settings compared with the previous systems. For the time-resolved setup, the macroscope is 4 times more efficient than the previous system and, at the same time, the spatial resolution is also increased by a factor of 6. For the high-spatial-resolution setup, the macroscope is up to 8.5 times more efficient with a moderate spatial resolution improvement (factor of 1.5). This high efficiency, increased spatial resolution and very high image quality offered by the novel macroscope optics will make 10-20 Hz high-resolution tomographic studies routinely possible, unlocking unprecedented possibilities for the tomographic investigations of dynamic processes and radiation-sensitive samples. | 10.1107/S1600577519004119 |
pubmed_402_14765 | Hematopoietic cells require cytokine-initiated signals for survival as well as proliferation. The pathways that transduce these signals, ensuring timely regulation of cell fate genes, remain largely undefined. The NFIL3 (E4BP4) transcription factor, Bcl-xL, and constitutively active mutants of components in Ras signal transduction pathways have been identified as key regulation proteins affecting murine interleukin-3 (IL-3)-dependent cell survival. Here we show that expression of NFIL3 is regulated by oncogenic Ras mutants through both the Raf-mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. NFIL3 inhibits apoptosis without affecting Bcl-xL expression. By contrast, Bcl-xL levels are regulated through the membrane proximal portion in the cytoplasmic domain of the receptor (betac chain), which is shared by IL-3 and granulocyte-macrophage colony-stimulating factor. Activation of either pathway alone is insufficient to ensure cell survival, indicating that multiple independent signal transduction pathways mediate the survival of developing B-lymphoid cells. | 10.1128/MCB.19.4.2754 |
pubmed_195_12375 | Adolescents at-risk for problem behaviors can have more difficulties in developing a firm sense of personal identity. Hence the purpose of this prospective longitudinal study was to scrutinize how externalizing problems in early adolescence impact identity development in middle to late adolescence. Participants were 443 (43.12% female) Dutch adolescents. Teachers rated their externalizing problem behaviors when participants were 11 or 12 years old and their identity formation was studied during five consecutive years (from 14 to 18 years of age). The sample was divided into four groups: boys and girls with a high versus a low-risk for externalizing problem behaviors. Participants completed a self-report measure of identity commitment, in-depth exploration, and reconsideration of commitment. Multi-group Latent Growth Curve and profile stability analyses were used to evaluate identity development across adolescence. Findings indicated that high-risk boys and girls reported a less structured identity, with lower levels of commitment and higher levels of reconsideration of commitment. Since externalizing problems behaviors and lack of a coherent sense of identity might reinforce each other, early intervention for high-risk adolescents might foster positive youth development. | 10.1007/s10964-013-9924-6 |
pubmed_649_5295 | The pressure of pericardial constraint was measured in 20 patients undergoing elective cardiac surgery (10 in Group I with normal cardiac size; 10 in Group II with cardiomegaly) using a catheter with a collapsible latex end balloon. Right atrial pressure and other hemodynamic variables including right ventricular stroke work index were also measured before and after the pericardium was widely opened. The pericardium was grossly normal in all patients and only small physiologic effusions were present. In Group I mean pericardial pressure was 8 +/- 2 mm Hg as was mean right atrial pressure. In Group II mean pericardial pressure was 6 +/- 2 mm Hg versus mean right atrial pressure of 10 +/- 5 mm Hg (p less than 0.05). Excluding 2 of the 20 patients with outlying data, pericardial pressure showed linear correlation with right atrial pressure (r = 0.689). In Group I right ventricular stroke work index rose from 5.0 +/- 2.0 to 6.4 +/- 2.1 g-m/m2 (p less than 0.01) after pericardiotomy with no significant increase in mean right atrial pressure; similar findings in Group II were consistent with removal of external constraint. Thus, even in the absence of an abnormal effusion the normal pericardium exerts a significant pressure on the heart, which is often similar in magnitude to right atrial pressure. In certain notable exceptions, however, right atrial pressure far exceeds pericardial pressure. Such pericardial constraint has important implications for ventricular diastolic mechanics. | 10.1016/s0735-1097(86)80299-6 |
pubmed_742_21229 | BACKGROUND
Gemcitabine is used for the treatment of several solid tumours and exhibits high inter-individual pharmacokinetic variability. In this study, we explore possible predictive covariates on drug and metabolite disposition.
METHODS
Forty patients were enrolled. Gemcitabine and dFdU concentrations in the plasma and dFdCTP concentrations in peripheral blood mononuclear cell were measured to 72 h post infusion, and pharmacokinetic parameters were estimated by nonlinear mixed-effects modelling. Patient-specific covariates were tested in model development.
RESULTS
The pharmacokinetics of gemcitabine was best described by a two-compartment model with body surface area, age and NT5C2 genotype as significant covariates. The pharmacokinetics of dFdU and dFdCTP were adequately described by three-compartment models. Creatinine clearance and cytidine deaminase genotype were significant covariates for dFdU pharmacokinetics. Rate of infusion of <25 mg m(-2) min(-1) and the presence of homozygous major allele for SLC28A3 (CC genotype) were each associated with an almost two-fold increase in the formation clearance of dFdCTP.
CONCLUSION
Prolonged dFdCTP systemic exposures (≥72 h) were commonly observed. Infusion rate <25 mg m(-2) min(-1) and carriers for SLC28A3 variant were each associated with about two-fold higher dFdCTP formation clearance. The impacts of these covariates on treatment-related toxicity in more selected patient populations (that is, first-line treatment, single disease state and so on) are not yet clear. | 10.1038/bjc.2013.738 |
pubmed_13_21898 | BACKGROUND Synovitis is an important disease that cause intractable pain in temporomandibular joint (TMJ), and the inflammation process played a crucial role in the initiation and development of temporomandibular joint disorder. A series of investigations suggested that the increasing expression of interleukin-(IL) 1β secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In this present study, we investigated the signaling pathways which regulate the expression of IL-1β. MATERIAL AND METHODS The occlusal interference animal model was created to induce synovial injury. Forty-eight rats were divided into 4 groups: 1) control group, 2) occlusal interference group, 3) TAK-242 (a specific inhibitor targeting the Toll-like receptor (TLR)-4) group, and 4) SB203580 (a specific inhibitor targeting the p38) group. The inflammation changes were observed, and the expression of p38 and IL-1β in the synovial membranes were assayed. RESULTS The results showed that downstream p38 MAPK (mitogen-activated protein kinase) signaling was triggered following the activation of TLR4. Moreover, the injection of SB203580 could inhibit the inflammatory reactions and the increased expression of IL-1β at both mRNA and protein levels. CONCLUSIONS The results prompted us that TLR4 may stimulates synovial inflammatory reactions and increased expression of IL-1β in rats through the activation of p38 MAPK signaling pathway, p38 was an important mediator in the mechanisms of the initiation and development of synovial injury by regulating the expression of IL-1β in synovial membranes. | 10.12659/MSM.908526 |
pubmed_72_12616 | BACKGROUND
The Platelia Aspergillus Ag assay (Bio-Rad) is designed for detecting Aspergillus galactomannan (GM) and is widely used for diagnosing invasive aspergillosis but is hampered by variable occurrences of unreproducible positive results. Frequency and origin of these unreproducible results have not been formally studied.
METHODS
Different technicians simultaneously performed four tests on 550 consecutive sera from adult patients (Test#1-Test#2 for extraction#1 and Test#3-Test#4 for extraction#2). The samples were classified as confirmed negative [all tests with GM optical density index (GM-ODI) <0.5], confirmed positive (all tests with GM-ODI ≥0.5), extraction unreproducible positive (Test#1 and Test#2 ODIs ≥0.5, and Test#3 and Test#4 GM-ODIs <0.5, or conversely), and ELISA unreproducible positive (only one test with GM-ODI ≥0.5). The samples with positive and negative GM-ODIs within the assay coefficient of variation values were classified as non-conclusive. Four similar additional tests were performed after ≤72h storage at 4 °C and a new GM test after 8 months at -20 °C.
RESULTS
Five-hundred-twenty sera (94.5%) were confirmed negative, 15 (2.7%) confirmed positive, 4 (0.7%) extraction unreproducible positive, 6 (1.1%) ELISA unreproducible positive, and 5 (0.9%) non-conclusive. Upon retesting, the unreproducible positive results turned negative except for one which turned non-conclusive. The confirmed positive and non-conclusive had similar GM-ODIs (p>0.4) upon retesting after storage ≤72h at 4 °C (n = 20) or eight months at -20 °C (n = 17).
CONCLUSIONS
Operational unreproducible positives represent 33% of the GM-positive results and a second sample evaluation appears mandatory to avoid useless investigations or treatments. When operational artifacts are excluded, GM remains stable at standard storage conditions. | 10.1371/journal.pone.0124044 |
pubmed_483_8745 | Wax, a hydrophobic structure that provides an effective waterproof barrier to the leaves, is an important drought adaptation trait for preventing water loss. However, limited knowledge exists regarding the molecular mechanisms underlying wax biosynthesis in trees. Here, PeSHN1, an AP2/ethylene response factor transcription factor, was isolated from a fast-growing poplar Populus × euramericana cv. 'Neva' clone. To study the potential biological functions of PeSHN1, transgenic 84K poplar (Populus alba × Populus glandulosa) plants overexpressing PeSHN1 were generated. PeSHN1 overexpression resulted in decreased transpiration, increased water-use efficiency (WUE) and increased drought tolerance. The transgenic poplar plants exhibited increased wax accumulation and altered wax composition, mainly because of a substantial increase in long-chain (>C30) fatty acids, aldehydes and alkanes. Gene expression analyses revealed that many genes involved in wax biosynthesis were induced in the PeSHN1 overexpression plants. In addition, chromatin immunoprecipitation-PCR assays and dual luciferase assays revealed that at least one of those genes, LACS2, is likely targeted by PeSHN1. Moreover, the PeSHN1 overexpression plants maintained higher photosynthetic activity and accumulated more biomass under drought stress conditions. Taken together, these results suggest that PeSHN1 regulates both WUE and drought tolerance in poplar by modulating wax biosynthesis and that altered PeSHN1 expression could represent a novel approach (altering the wax trait on leaf surfaces to increase WUE) for breeding drought-tolerant plants. | 10.1093/treephys/tpz033 |
pubmed_902_383 | BACKGROUND
Idiopathic infantile arterial calcification is a rare disorder that often results in fetal or neonatal demise. Few reports have detailed an early diagnosis, complete antenatal and postnatal imaging, and postmortem findings.
CASE
A patient presented at 33 weeks of gestation with hydrops fetalis. Idiopathic infantile arterial calcification was diagnosed using a fetal echocardiogram, and fetal demise occurred shortly thereafter. A complete postmortem evaluation included radiography and pathology. The patient's postpartum course was complicated by maternal respiratory distress and pulmonary edema.
CONCLUSION
Finding calcified vessels in the context of fetal hydrops should lead one to consider idiopathic infantile arterial calcification. This diagnosis has important maternal and fetal implications. The detailed evaluation in this case is useful to clinicians in making a definitive diagnosis of idiopathic infantile arterial calcification. Clinicians should be aware that serious maternal complications can occur in these types of cases. | 10.1097/AOG.0b013e3181cb8809 |
pubmed_405_24788 | AIM
Stafne's bone cavity (SBC) is a very rare defect, affecting only selected parts of the mandibular bone. Its etiology is unknown. On two-dimensional images, it appears as a narrowed cavity and might be interpreted as a space-occupying process inside the bone. The aim of the present study was to investigate the prevalence of SBC on panoramic views, and compare these results to published reports.
MATERIALS AND METHODS
A total of 14,005 panoramic views were examined retrospectively with regard to the presence of SBC. All images were analyzed regarding typical characteristics as originally described by Stafne.
RESULTS
A total of 11 cases fulfilled diagnostic criteria of SBC (0.08%). All patients were men (100%), at a mean age of 58.1 years (range=38-75 years). Eight patients (72.7%) had SBC on the left side, three patients on the right side (27.3%). In eight cases, SBC was found in the mandibular corpus (72.7%), and in three cases in the mandibular angle (27.3%). Correlating with published results, SBC was found at a relative frequency of 0.13%.
CONCLUSION
SBC on panoramic views or other imaging modalities should alert the clinician to exclude other potential pathologies. In doubtful cases, surgical procedures might be necessary to verify the diagnosis. | pubmed_405_24788 |
others_314_147223 | Mitochondria are subcellular organelles present in almost all eukaryotic cells, which play a central role in cellular metabolism. Different tissues, health and age conditions are characterised by a difference in mitochondrial structure and composition. The visual data mining platform mitoXplorer 1.0 was developed to explore the expression dynamics of genes associated with mitochondrial functions that could help explain these differences. It however lacked functions aimed at integrating mitochondria in the cellular context and thus, identifying regulators that help mitochondria adapt to cellular needs. To fill this gap, we upgraded the mitoXplorer platform to version 2.0 (mitoXplorer 2.0). In this upgrade we implemented two novel integrative functions, Network Analysis and the transcription factor- (TF-) Enrichment, to specifically help identify signalling or transcriptional regulators of mitochondrial processes. In addition, we implemented several other novel functions to allow the platform to go beyond simple data visualisation, such as an enrichment function for mitochondrial processes, a function to explore time-series data, the possibility to compare datasets across species as well as an IDconverter to help facilitate data upload. We demonstrate the usefulness of these functions in 3 specific use cases. mitoXplorer 2.0 is freely available without login at http://mitoxplorer2.ibdm.univ-mrs.f | 10.1101/2022.01.31.478461 |
pubmed_604_3158 | The spiro form fluorescein hydrazide (1) bearing a cleavable active bond is characterized as a highly selective and sensitive fluorescence probe for Cu2+. In 0.01 M Tris-HCl buffer (pH 7.2), the probe displays a highly selective fluorescence-on response to Cu2+ only, instead of other common metal ions. The reaction mechanism has been explored and proposed as that the hydrazide group of 1 recognizes and binds Cu2+, and the subsequent complexation of Cu2+ promotes hydrolytic cleavage of the amide bond, causing the release of fluorophore (fluorescein) and thereby the retrievement of fluorescence. Conditions for fluorescence measurement were optimized, generating a calibration curve that is linear over the concentration range of 0.1-10 microM Cu2+. The detection limit for Cu2+ is 64 nM based on 11 blank determinations (k=3), also showing a highly sensitive feature. The fluorescence-on reaction described here has been used for the determination of trace Cu2+ in real biological fluids with satisfactory results. | 10.1016/j.aca.2006.05.097 |
pubmed_283_12258 | The potential of Staphylococcus aureus cheese isolates to grow and produce staphylococcal enterotoxin A under conditions typical for cheese making was investigated in three broth experiments. The effect of the concentration of undissociated lactic acid (HLac) in conjunction with specific pH values was studied by adjusting pH at a single concentration of lactic acid. First, the time-to-growth of S. aureus was modelled by using survival analysis and absorbance data obtained from an automated turbidity reader. The fitted model describes the time to growth and indicates the growth ⁄ no growth boundary of S. aureus as a function of HLac concentration, temperature and water activity. Second, growth rates and lag times of S. aureus were estimated after two different pre-treatments in skim milk at three HLac concentrations and two temperatures based on optical detection times of serial dilutions of bacterial solutions. Growth rates differed between strains, and increased with increasing temperature and decreasing HLac concentration. Preliminary results indicate that lag times were dependent on pre-treatment suggesting that the growth potential of S. aureus in cheese curd may be greater if milk is used immediately after milking compared to holding at 4°C after milking. Third, growth, inactivation, and enterotoxin A production of S. aureus strains were investigated at twelve combinations of HLac concentration and temperature. Concentrations of enterotoxin A increased linearly during the first four days, with a production rate increasing with increasing temperature and decreasing HLac concentration. Significant amounts of enterotoxin A were produced during extended incubation, up to 14days, but then initial pH had changed. This highlights a potential limitation of modelling based on the initial environmental conditions in batch experiments. In summary, ranges of time-to-growth, growth rates, lag times and enterotoxin A production rates of S. aureus in the presence of HLac were estimated. The results can be used together with process data to indicate the range and magnitude of growth and enterotoxin A production during initial stages of cheese production. | pubmed_283_12258 |
pubmed_371_3936 | OBJECTIVES
To investigate the relationship between antithyroid antibody elevation and thyrotropin (TSH) elevation.
SETTING
Large state veterans home.
METHODS
Seven hundred seventy-six residents were screened for TSH elevation. Seventy-two residents with TSH elevation and no history of thyroid disease or recent iodine exposure later had determinations of antithyroglobulin and antimicrosomal antibodies. The relationship between TSH levels and antibody titers was explored.
RESULTS
Eleven percent of the residents had TSH elevation. Thirty-two percent of men and 64% of women with TSH elevation had elevation of antithyroid antibodies. Those residents with the highest antithyroid antibody titers had significantly greater TSH elevation.
CONCLUSION
Previous investigators have found similar percentages of individuals with TSH elevation who lack antithyroid antibody elevation. We hypothesize that TSH elevation without elevated antibody titers may be the result of a previously described involutional histologic lesion of the thyroid. | 10.1111/j.1532-5415.1991.tb04047.x |
pubmed_177_17361 | Dairy cows display a partial preference for being outside, but little is known about what aspects of the outdoor environment are important to cows. The primary aim of this study was to test the preference of lactating dairy cattle for pasture versus an outdoor sand pack during the night. A secondary aim was to determine whether feeding and perching behavior changed when cows were provided outdoor access. A third objective was to investigate how the lying behavior of cows changed when given access to different outdoor areas. Ninety-six lactating pregnant cows were assigned to 8 groups of 12 animals each. After a baseline phase of 2 d in which cows were kept inside the freestall barn, cows were habituated to the outdoor areas by providing them access to each of the 2 options for 24 h. Cows were then given access, in random order by group, to either the pasture (pasture phase) or the sand pack (sand phase). As we tested the 2 outdoor options using space allowances consistent with what would be practical on commercial dairy farms, the space provided on pasture was larger (21,000 m2) than that provided on the sand pack (144 m2). Cows were tested at night (for 2 nights in each condition), from 2000 h until morning milking at approximately 0800 h, as preference to be outdoors is strongest at this time. During the next 3 nights cows were given access to both outside options simultaneously (choice phase). Feeding and perching behaviors were recorded when cows were indoors during the day and night periods. Lying behavior was automatically recorded by HOBO data loggers (Onset, Bourne, MA). Cows spent more time outside in the pasture phase (90.0 ± 5.9%) compared with the sand phase (44.4 ± 6.3%). When provided simultaneous access to both options, cows spent more time on pasture than on the sand pack (90.5 ± 2.6% vs. 0.8 ± 0.5%, respectively). Time spent feeding indoors during the day did not change regardless of what type of outdoor access was provided, but there was a decline in perching during the day when cows were provided access to either outdoor option at night. Lying time in the pasture phase was lower than in the baseline or sand phase. During the nighttime, lying time outside was not different between the sand (55.4 ± 7.9%) and pasture (52.0 ± 7.4%) phases. In summary, cows spent a considerable amount of time outside during the night when given the opportunity and showed a preference for a large pasture versus a small sand pack as an outdoor area. | 10.3168/jds.2017-13294 |
pubmed_370_14286 | The effects of ethanol on blood pH, PCO2, and PO2 were measured in LS and SS mice in an attempt to ascertain whether these lines of mice, which differ in CNS sensitivity to the behavioral effects of ethanol, also differ in sensitivity to physiological effects of this drug. Long-sleep (LS) female mice were injected intraperitoneally with 1.8, 2.5, 3.3, or 3.8 g/kg ethanol; short-sleep (SS) female mice were administered 2.5, 3.3, 4.1, or 4.7 g/kg. Blood pH, PCO2, and PO2 were assessed at 15, 30, 60, 120, or 180 min after injection of the 2.5 and 4.1 g/kg doses or at 60 min after injection of the 1.8, 2.5, 3.3, 3.8, 4.1, and 4.7 g/kg doses. Opposite effects on blood pH and PCO2 over time were obtained in LS and SS mice at the 2.5 g/kg dose. Acidosis characterized the LS line, whereas alkalosis characterized the SS. The results obtained with SS mice at 4.1 g/kg dose were similar to those obtained with LS mice at the 2.5 g/kg dose. The dose-response curve for the SS mice generated at 60 min post-injection lies to the right of that for the LS mice. The effects of high ethanol doses on SS mice resemble the effects of low doses on LS animals. Thus, the two lines of mice differ in response to the effects of ethanol on these parameters related to respiration. The difference in sensitivity to the respiratory depressant effects of ethanol may contribute to the differences in behavioral sensitivity between the two lines. | 10.1016/0031-9384(82)90208-6 |
pubmed_996_21688 | Despite equivalent p24 antigen production, HSB-2 T cells expressing glycosylphosphatidylinositol (GPi)-linked CD4 were productively infected without cell death or syncytium formation, unlike HSB-2 transfectants expressing wild-type CD4 (wtCD4). HSB-2 transfectants dually expressing wtCD4 and GPi-linked CD4 formed syncytia and died. Thus, wtCD4 expression is critical for human immunodeficiency virus cytopathic effect in HSB-2 transfectants. | 10.1128/JVI.68.6.4039-4042.1994 |
pubmed_708_12426 | Low temperature photolysis of nitric oxide from the nitrosyl complexes of ferric myoglobin (NO-Fe(III)Mb) and manganese(II)-porphyrin-substituted myoglobin (NO-Mn(II)Mb) was examined by electron paramagnetic resonance (EPR) spectroscopy in order to elucidate the electronic and structural natures of the photoinduced intermediates of these hemoprotein-ligand complexes trapped at low temperature. The photoproduct of NO-Fe(III)Mb at 5 K exhibited entirely new X-band EPR absorptions in the magnetic field strength from 0 to 0.4 tesla. The widespread absorption together with distinct, sharp zero-field absorption was consistently observed in the photoproduct of the isoelectronic NO-Mn(II)Mb. These novel ERP signals indicate a spin-coupled pair with an effective spin of S = 2 between the high spin metal center (S = 5/2) and the photodissociated NO (S = 1/2) trapped adjacent to the metal center. On the other hand, the photolyzed form of nitrosyl complexes of Fe(III)- and Mn(II)-Glycera hemoglobins, in which the distal histidine of Mb is replaced by a leucyl residue, exhibited somewhat broader EPR absorptions similar to those of the corresponding native Fe(III)- or unliganded Mn(II)-Glycera hemoglobins, respectively, indicating that the photodissociated NO molecule moved farther away from the metal center in the heme pocket. These observations show the importance of the interaction of the distal residue with the ligand in determining the nature of the photolyzed states. | pubmed_708_12426 |
pubmed_540_16561 | Lung cancer is one of the leading causes of cancer-related deaths. Thus, it is important to find its biomarkers. Furthermore, there is an increasing number of studies reporting that long noncoding RNAs (lncRNAs) demonstrate dense linkages with multiple human complex diseases. Inferring new lncRNA-disease associations help to identify potential biomarkers for lung cancer and further understand its pathogenesis, design new drugs, and formulate individualized therapeutic options for lung cancer patients. This study developed a computational method (LDA-RLSURW) by integrating Laplacian regularized least squares and unbalanced bi-random walk to discover possible lncRNA biomarkers for lung cancer. First, the lncRNA and disease similarities were computed. Second, unbalanced bi-random walk was, respectively, applied to the lncRNA and disease networks to score associations between diseases and lncRNAs. Third, Laplacian regularized least squares were further used to compute the association probability between each lncRNA-disease pair based on the computed random walk scores. LDA-RLSURW was compared using 10 classical LDA prediction methods, and the best AUC value of 0.9027 on the lncRNADisease database was obtained. We found the top 30 lncRNAs associated with lung cancers and inferred that lncRNAs TUG1, PTENP1, and UCA1 may be biomarkers of lung neoplasms, non-small-cell lung cancer, and LUAD, respectively. | 10.3389/fgene.2022.933009 |
pubmed_806_12890 | Many metals are toxic in human organism, as is the case of cadmium and lead. Therefore, the metal levels in food need to be controlled. In coffee, metals may present risks when they are extracted from the powder to be consumed as beverage. A flow injection analysis (FIA) system is proposed, with atomic absorption detection, to metal adsorption studies in coffee powder. Kinetic study, best isotherms and time, and mass influences were determined. They allowed analyzing the high lead and cadmium adsorption percentage in organic and conventional ground coffee. Metal adsorption occurs in multilayers, following Freundlich's model, and the kinetic model obeyed is the pseudo-second order. The cadmium adsorption suffered higher temperature influence, while the lead retention suffered higher mass influence. This study indicates that the majority of these toxic agents will be retained in the powder and will not be consumed by man, avoiding possible deleterious effects. | 10.2116/analsci.31.165 |
others_342_12910 | We describe a female infant with incontinentia pigmenti complicated by severe pulmonary arterial hypertension that was markedly improved by tadalafil administration. The infant was referred to our institution because of neonatal seizures and generalized skin rash at the age of 1 day. She was diagnosed with incontinentia pigmenti on skin biopsy findings. In addition to incontinentia pigmenti, she had pulmonary arterial hypertension without structural heart disease. The pulmonary hypertension rapidly worsened at the age of 2 months and was confirmed by cardiac catheterization. The pulmonary artery pressure was equal to systemic pressure but it decreased in response to nitric oxide inhalation. We, therefore, initiated treatment with tadalafil of 1 mg/kg/day. The follow-up cardiac catheterization performed at 9 months revealed dramatic improvement in the pulmonary artery pressure. An IKBKG mutation with deletion of exons 4–10 was detected in the blood of both the patient and her mother. Our experience indicates that tadalafil may be beneficial in treating pulmonary arterial hypertension associated with incontinentia pigmenti. © 2019 | 10.1016/j.ejmg.2019.103764 |
pubmed_203_14782 | The clover root weevil, Sitona lepidus, frequently feeds on N2 fixing rhizobial root nodules of white clover (Trifolium repens), which may contain isoflavonoids with defensive and plant regulatory properties. This study investigated the isoflavonoids present in N2 fixing (active) root nodules, root nodules that were not fixing N2 (inactive), and roots without nodules, and tested the behavioral responses of neonatal S. lepidus larvae to aglycones of the identified compounds. Formononetin concentrations were higher in the active nodules compared with inactive nodules and roots alone. Moreover, there was a statistically significant attraction to formononetin by S. lepidus in arena experiments, whereas the other isoflavonoids were unattractive. It is suggested that S. lepidus may have become tolerant to the toxic effects of formononetin with repeated exposure, and that it may play a role in root nodule location. Such coevolutionary relationships are widely reported for aboveground insects and plants, but the present study suggests they may also occur belowground. | 10.1007/s10886-005-6355-1 |
pubmed_1090_13261 | Interaction of myxovirus neuraminidases, in particular, that of influenza virus, with interferon (IFn) was established. When IFn is treated with viral neuraminidases, its antiviral activity tested in tissue culture does not change but it is eliminated from the body by the kidneys much more intensively and is more absorbed by the liver than native IFn. The degree of IFn elimination from the body is directly related to the level of enzymatic activity of viral neuraminidases affecting interferon. The homologous IFn treated with viruses, when inoculated into animals, is less capable than native IFn to protect mice from experimental influenza infection because of its more rapid elimination from the body. The presence of antineuraminidase antibodies in the blood of children slowed down endogenous IFn elimination which alleviates the course of influenza infection. | pubmed_1090_13261 |
pubmed_534_7658 | Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder. | 10.1007/s11126-015-9405-z |
pubmed_414_19423 | Reconstruction after excision of bone tumor of the proximal tibia is a challenging issue for the reconstructive surgeon. The combined use of a free fibular flap and allograft can provide a reliable reconstructive option in this location. This article describes the authors' long-term follow-up using this technique. Twenty-seven patients that had resection of proximal tibia bone tumors underwent reconstruction using this technique. Only 21 patients that had primary reconstruction were included in this study. All patients had their surgeries performed at least 24 months before the end of the study. The average age at time of operation was 18.1 years. The average follow-up time was 139.3 months. Limb salvage was 82.7%. The average length of the resected tibial segment was 15.3 cm and that of the residual proximal tibia remaining after resection was 2.7 cm. The average time of union of fibula was 5.4 months and for union of allograft was 19.1 months. Primary union of the allograft was achieved in 90.5% of cases. Full weight-bearing was achieved at an average of 21.6 months. Ten patients (47.6%) had 14 local complications. The (MTSRS) average score at final follow-up was 27.3. Local recurrences occurred in two patients (9.5%). Distant metastasis to the lung occurred in three patients (14.3%). One patient died of disease. This technique provides good long-term results in reconstruction of proximal tibia. The viability of the fibula is a cornerstone in both success of reconstruction as well as successful management of complications. | 10.1002/micr.20668 |
pubmed_512_4763 | Adequate management of hyperleukocytosis in patients with acute myeloid leukemia (AML) is essential for the prevention of life-threatening complications related to leukostasis and tumor lysis syndrome, but the optimal therapeutic strategy remains unclear. We report a 15-year-old girl with newly diagnosed AML who had extreme hyperleukocytosis (leukocyte count at diagnosis, 733,000/μl) leading to a brain hemorrhage. She was initially treated with hydroxyurea, but presented with brain hemorrhage due to leukostasis and underwent leukapheresis emergently with intensive care and mechanical ventilation. Full-dose standard induction chemotherapy was initiated after achieving gradual cytoreduction (leukocyte count, 465,000/μl) within five days after the initiation of therapy with hydroxyurea and leukapheresis. These treatments were successful and she experienced no complications. The patient ultimately recovered fully and was discharged with complete remission of AML. Although the effects of hydroxyurea and leukapheresis in the setting of hyperleukocytosis are still controversial, these initial treatments may contribute to successful bridging therapy followed by subsequent induction chemotherapy, especially in AML cases with extreme hyperleukocytosis or life-threatening leukostasis. | 10.11406/rinketsu.57.180 |
pubmed_561_1134 | Dietary inositol is incorporated into neuronal cell membranes as inositol phospholipids where it serves as a key metabolic precursor in G protein-coupled receptors. In the brain, several subtypes of adrenergic, cholinergic, serotonergic and metabotropic glutamatergic receptors are coupled to the hydrolysis of phosphoinositides (PI) with myo-inositol (MI) crucial to the resynthesis of PI and the maintenance and effectiveness of signalling. Despite a mode of action that remains illusive, MI has demonstrated therapeutic efficacy in obsessive-compulsive disorder (OCD), putative OCD-spectrum disorders, as well as panic and depression. Behavioural and biochemical studies indicate that this efficacy does not involve simply the replenishing of the membrane PI pool. In addition to its precursory role in cell signalling, inositol lipids alter receptor sensitivity, can direct membrane trafficking events, and have been found to modulate an increasing array of signalling proteins. These effects may afford MI an ability to modulate the interaction between neurotransmitters, drugs, receptors and signalling proteins. This paper reviews the neuromolecular and genetic aspects of OCD in terms of the PI-linked 5HT receptor subtypes and relates these to the behavioural and therapeutic effects of MI. Since OCD often is poorly responsive to current drug treatment, understanding the neuropharmacology of MI holds great promise for understanding the neuropathology of this and other MI-responsive disorders. | 10.1016/s0278-5846(01)00244-5 |
pubmed_1070_5350 | BACKGROUND
The workplace is an ideal setting for health promotion. Helping employees to be more physically active can not only improve their physical and mental health, but can also have economic benefits such as reduced sickness absence. The current paper describes the development of a three month theory-based intervention that aims to increase levels of moderate intensity physical activity amongst employees in sedentary occupations.
METHODS
The intervention was developed using an intervention mapping protocol. The intervention was also informed by previous literature, qualitative focus groups, an expert steering group, and feedback from key contacts within a range of organisations.
RESULTS
The intervention was designed to target awareness (e.g. provision of information), motivation (e.g. goal setting, social support) and environment (e.g. management support) and to address behavioural (e.g. increasing moderate physical activity in work) and interpersonal outcomes (e.g. encourage colleagues to be more physically active). The intervention can be implemented by local facilitators without the requirement for a large investment of resources. A facilitator manual was developed which listed step by step instructions on how to implement each component along with a suggested timetable.
CONCLUSION
Although time consuming, intervention mapping was found to be a useful tool for developing a theory based intervention. The length of this process has implications for the way in which funding bodies allow for the development of interventions as part of their funding policy. The intervention will be evaluated in a cluster randomised trial involving 1350 employees from 5 different organisations, results available September 2009. | 10.1186/1471-2458-8-326 |
others_314_45131 | Intercellular bridges, also called ring canals (RCs), connect germline cells during gametogenesis in males and females. They form as a consequence of incomplete cytokinesis during cell division leaving groups of daughter cells connected in syncytia. In Drosophila females, RCs are required for oocyte growth but little is known about the role of RCs during spermatogenesis. Using live imaging, we document extensive intercellular movement of GFP and a subset of endogenous proteins through RCs during spermatogenesis from two-cell diploid spermatogonia to clusters of 64 post-meiotic haploid spermatids. Loss of the fusome, a large cytoplasmic structure extending through RCs that is known to be important during oogenesis, has minimal impact on RC development or intercellular protein movement during spermatogenesis. Our results reveal that male germline RCs remain persistently open and mediate extensive sharing of cytoplasmic information, supporting multiple roles for RCs throughout sperm developmen | 10.1101/581702 |
pubmed_1008_810 | In the light of recent findings concerning the presence of S-100 antigen in folliculo-stellate cells of the rat adenohypophysis, we investigated the possible presence of S-100-labelled cells in both the normal human adenohypophysis and in pituitary adenomas. Immunostaining enabled us to detect, with both light and electron microscopy, the presence of S-100-labelled folliculo-stellate cells in a significant number of pituitary adenomas, mostly growth-hormone secreting, and, as expected, in the normal human adenohypophysis. | 10.1007/BF02890202 |
pubmed_933_3178 | OBJECTIVE
To describe the long-term course of depressive symptoms up to 3 years post-stroke and to develop a prediction model for depressive symptoms 1 and 3 years post-stroke.
DESIGN
Longitudinal follow-up study.
PATIENTS
Data were analysed for 131 patients with a first-ever supratentorial stroke admitted for inpatient rehabilitation in the Netherlands
METHODS
The Center for Epidemiologic Studies-Depression scale was used to assess post-stroke depressive symptoms at 6 months, 1 and 3 years post-stroke.
RESULTS
Post-stroke depressive symptoms were present 6 months, 1 year and 3 years post-stroke in 23.7%, 25.2% and 16.0% of the patients, respectively. At all 3 assessments post-stroke depressive symptoms were absent in 65.6% of the patients and present in 12.2% of the patients. Of the patients with post-stroke depressive symptoms 6 months post-stroke, 41.9% had recovered from post-stroke depressive symptoms 3 years post-stroke. The most important predictor of post-stroke depressive symptoms 1 and 3 years post-stroke was post-stroke depressive symptoms 6 months post-stroke (area under the curve 0.75 and 0.85). Male gender was an additional predictor for post-stroke depressive symptoms 3 years post-stroke.
CONCLUSION
Long-term post-stroke depressive symptoms are highly predictable at 6 months post-stroke. If a patient has not recovered from post-stroke depressive symptoms within the first 6 months post-stroke there is a high risk of chronic post-stroke depressive symptoms. | 10.2340/16501977-0446 |
pubmed_391_17788 | A procedure based on polymerase chain reaction was developed for the study of rotaviruses. A full-length cDNA copy of the gene coding for major neutralizing glycoprotein VP7 of a human rotavirus isolate 1407 with the "long" electrophoretype (classified as the first electrophoretype) was cloned and sequenced. The primary structure of glycoprotein VP7 of isolate 1407 in A and C antigenic regions was found to be similar to that of serotype 1 virus. | pubmed_391_17788 |
pubmed_73_16207 | Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals. | 10.1093/rheumatology/keq183 |
pubmed_909_21349 | It is highly desirable and challenging when the chemzyme can be not only simply duplicating and imitating the properties of natural enzymes, but also introducing additional new features for practical applications. Herein, we report a zinc-finger-protein like α-helical chiral metallo-supramolecular complex ([Fe2L3](4+)) functionalized graphene oxide (GO-COOH) as a peroxidase mimic. This artificial enzyme integrates the characteristics of both chiral metallo-supramolecular complex and GO-COOH, and shows excellent catalytic activity. More intriguingly, the novel chemzyme turn out to have enantioselectivity and near-infrared photothermal effect. To the best of our knowledge, this is the first example that the chemzyme has such new features. Based on these properties, we have demonstrated three examples for the applications of our designed enzyme: 1) Intracellular H2O2 detection in PC12 cells against Alzheimer's disease; 2) Discrimination between the chiral drug, Levodopa (L-dopa), the gold standard for treating Parkinson's disease and its enantiomer, D-dopa. This is important because L-dopa is the most effective drug at present used to combat Parkinson's disease while D-dopa is inactive and can even cause side effects, thus for drug efficacy it must be free of D-dopa in the formulation; 3) Remote control of enzyme cascade biocatalysis reactions using high transparent, bio-friendly near-infrared (NIR) light. NIR allows remote activation with relatively high spatial and temporal precision. Our work will provide new insights into design and construction of novel chemzyme with more advanced features beyond intrinsic enzyme property. | 10.1002/smll.201302750 |
pubmed_229_22683 | Dissociated cultured rat hippocampal pyramidal neurons respond to estradiol with a time-dependent, twofold increase in density of their dendritic spines. This effect is mediated by an estrogen receptor, probably of the alpha nuclear receptor type. In searching for the molecular mechanisms leading from the initial activation of the estrogen receptor to the final formation of new dendritic spines, we found that estradiol acts on GABAergic interneurons expressing the estrogen receptor by decreasing their inhibitory tone. In culture, this is assumed to cause a shift in the balance between excitation and inhibition toward enhanced excitation, overactivation of the pyramidal neurons, and subsequent formation of novel dendritic spines. The action of estradiol on spine formation is mediated by phosphorylation of cyclic AMP response element binding protein in the pyramidal neurons and is blocked when inhibition is enhanced by diazepam and when excitation is blocked by tetrodotoxin. Progesterone blocks the effect of estradiol on dendritic spines through its conversion to tetrahydroprogesterone, which enhances GABAergic inhibition. Subsequent to formation of novel dendritic spines, there is an increase in the density of glutamatergic receptors in the affected cells, an increase in the cellular calcium response to glutamate, and an increase in network synaptic activity among the cultured neurons. | 10.1006/hbeh.2001.1688 |
pubmed_788_20104 | Protein effects in the activation of dioxygen by methane monooxygenase (MMO) were investigated by using combined QM/MM and broken-symmetry Density Functional Theory (DFT) methods. The effects of a novel empirical scheme recently developed by our group on the relative DFT energies of the various intermediates in the catalytic cycle are investigated. Inclusion of the protein leads to much better agreement between the experimental and computed geometric structures for the reduced form (MMOH(red)). Analysis of the electronic structure of MMOH(red) reveals that the two iron atoms have distinct environments. Different coordination geometries tested for the MMOH(peroxo) intermediate reveal that, in the protein environment, the mu-eta2,eta2 structure is more stable than the others. Our analysis also shows that the protein helps to drive reactants toward products along the reaction path. Furthermore, these results demonstrate the importance of including the protein environment in our models and the usefulness of the QM/MM approach for accurate modeling of enzymatic reactions. A discrepancy remains in our calculation of the Fe-Fe distance in our model of HQ as compared to EXAFS data obtained several years ago, for which we currently do not have an explanation. | 10.1021/ja0654074 |
pubmed_798_12061 | The activating natural killer (NK) cell receptor Ly49H recognizes the mouse cytomegalovirus (MCMV) m157 glycoprotein expressed on the surface of infected cells and is required for protection against MCMV. Although Ly49H has previously been shown to signal via DAP12, we now show that Ly49H must also associate with and signal via DAP10 for optimal function. In the absence of DAP12, DAP10 enables Ly49H-mediated killing of m157-bearing target cells, proliferation in response to MCMV infection, and partial protection against MCMV. DAP10-deficient Ly49H(+) NK cells, expressing only Ly49H-DAP12 receptor complexes, are partially impaired in their ability to proliferate during MCMV infection, display diminished ERK1/2 activation, produce less IFN-gamma upon Ly49H engagement, and demonstrate reduced control of MCMV infection. Deletion of both DAP10 and DAP12 completely abrogates Ly49H surface expression and control of MCMV infection. Thus, optimal NK cell-mediated immunity to MCMV depends on Ly49H signaling through both DAP10 and DAP12. | 10.1084/jem.20090168 |
pubmed_371_15057 | Despite there being a wide range of different epistaxis balloons their mode of action is unknown. Manufacturers' drawings depict balloons neatly filling the nasal cavity or precisely occluding the anterior and posterior nasal apertures. In view of the complexity of nasal internal anatomy these explanations seem unlikely. A better understanding of the configuration of these devices within the human nasal cavity may explain their mode of action and complications. This study aimed to delineate radiographically the configuration of 3 commonly used balloons within the noses of 4 human cadavers and to observe the effects of alterations in inflation volumes. The results showed that devices designed to fill the nasal cavity do not achieve this aim. Balloons do not conform to the contours of the nasal cavity but expand along pathways of least resistance and prolapse into the nasopharynx. The findings may explain the occurrence of complications such as headache and Eustachian tube obstruction. Accurate nasal tamponade is unlikely to be their true mode of action. These devices probably work by a combination of factors rather than as a result of specific design features. The possibility of rational design modifications is discussed. | 10.1111/j.1365-2273.1991.tb00955.x |
pubmed_484_22179 | The effect of daily oral administration of aqueous extract (600 mg/kg b.wt.) and methanol extract (200 mg/kg b.wt.) of Murraya koenigii Spreng leaves for a period of eight weeks was studied on blood glucose and plasma insulin level in alloxan-induced diabetic rats. Blood glucose levels of diabetic rats treated with aqueous and methanol extracts of Murraya koenigii Spreng showed significant reduction (P<0.05) as compared to diabetic control groups. Plasma insulin showed significantly high on 43rd and 58th days of treatment in aqueous and methanol extracts of Murraya koenigii treated groups. This suggests that the hypoglycemic effect may be mediated through stimulating insulin synthesis and/or secretion from the beta cells of pancreatic islets of Langerhans. | pubmed_484_22179 |
pubmed_628_5718 | Erectile dysfunction in the aging male is caused, in part, by inadequate relaxation of the corpora cavernosal smooth musculature. Calcitonin gene-related peptide (CGRP), a peptide neurotrasmitter localized in the corpora cavernosa, is down-regulated in the aging rat penis. We examined the hypothesis that this reduction in CGRP may contribute to decreased cavernosal smooth muscle relaxation. Therefore, we sought to determine whether adenoviral-mediated gene transfer of prepro-CGRP (AdRSVCGRP) could enhance erectile responses in aged rats. We found a significant decrease in CGRP concentrations and in cAMP and cGMP levels in aged rat cavernosal tissue compared to younger rats. Aged rats also had significantly lower erectile function as determined by cavernosal nerve stimulation compared to younger rats. Five days after transfection with AdRSVCGRP, these aged rats had an approximately threefold increase in cavernosal CGRP levels compared to animals transfected with adenoviruses encoding nuclear-targeted beta-galactosidase (AdRSV beta gal). The AdRSVCGRP-transfected animals also demonstrated an increase in CGRP mRNA and immunohistochemical localization of CGRP in the smooth muscle of the corpora cavernosa. In addition, cAMP levels in the corpora cavernosa were significantly increased, whereas cGMP levels remained unchanged. Adenoviral transduction efficiency of beta-galactosidase reporter gene was measured by chemiluminescence and was observed in cavernosal tissue 5 days after transfection with AdRSV beta gal. More importantly, 5 days after administration of AdRSVCGRP, a significant increase was observed in the erectile response to cavernosal nerve stimulation in the aged rat, similar to the response observed in younger rats. These data suggest that in vivo adenoviral gene transfer of CGRP can physiologically improve erectile function in the aged rat. | 10.1095/biolreprod65.5.1371 |
pubmed_1066_3153 | An improved CO coverage-dependent electrochemical interface model with an explicit solvent effect on Cu(100) is presented in this paper, by which theoretical insights into the potential-dependent C-C bond formation pathways occurring in CO2 electrochemical reduction to C2 products can be obtained. Our present studies indicate that CHO is a crucial intermediate toward C1 products on Cu(111), and dimer OCCO is found to not be a viable species for the production of C2 products on Cu(100). The reaction pathway of CHO with CO and CHO dimerization into dimers COCHO and CHOCHO may be C-C bond formation mechanisms at low overpotential. However, at medium overpotential, C-C bond coupling takes place preferentially through the reaction of COH with CO species and COH dimerization into dimers COCOH and COHCOH. The formed dimers COCHO, CHOCOH, and CHOCHO via reactions of CHO with CO, COH, and CHO species may lead to C2 products, which are regarded as C-C bond formation mechanisms at high overpotential. The difference of obtained adsorption isotherms of CO on Cu(100) with that of Cu(111) may be able to explain the effect of the crystal face of Cu on product selectivity. The excellent consistencies between our present obtained conclusions and the available experimental reports and partial theoretical studies validate the reasonability of the present employed methodology, which can be also used to systematically study potential-dependent CO2 electroreduction pathways toward C2 products on Cu(100) or other metal catalysts. | 10.1021/acsomega.1c01062 |
pubmed_836_11371 | During the past century explosive developments have taken place in the field of molecular medicine and genetics, vastly expanding our understanding of the normal physiological response to injury. We have been able to characterise specific molecular and cell biological processes and apply some of this knowledge to the treatment of multiply injured patients. Despite the significant steps we have made, there still remains much work to be done in this area. This review article highlights the current concepts of post-traumatic immunological changes and their impact in the management of trauma patients. | 10.1016/s0020-1383(02)00416-3 |
pubmed_367_5537 | OBJECTIVE
In the last decade several studies have been published using proteomics to unravel molecular pathways and to find biomarkers which can be used for diagnosis and/or prognostication in ovarian cancer. This review gives an overview of proteomic studies performed in ovarian cancer focusing on the nature of samples that have been used.
METHODS
Recent literature regarding the role of proteomic studies in ovarian cancer has been reviewed.
RESULTS
Most studies have focused on finding biomarkers for early diagnosis of ovarian cancer using blood samples though proteins identified until now are mainly acute phase reactants. Studies regarding platinum sensitivity have only been performed on cell culture models and need confirmation in tissue samples. Proteomic studies using ovarian cancer tissue are sparse and mostly contain a low number of samples.
CONCLUSION
To date no biomarkers for early diagnosis or prognostication in ovarian cancer have been found using proteomics. We speculate that it would be interesting to investigate the tissue proteome in an attempt to overcome acute phase reactants and to facilitate the discovery of real tumor-specific biomarkers instead of the identification of secondary protein changes. | 10.1016/j.ygyno.2009.09.005 |
pubmed_832_24575 | Gene expression profiling was made more cost-effective by the NIH LINCS program that profiles only ∼1, 000 selected landmark genes and uses them to reconstruct the whole profile. The D-GEX method employs neural networks to infer the entire profile. However, the original D-GEX can be significantly improved. We propose a novel transformative adaptive activation function that improves the gene expression inference even further and which generalizes several existing adaptive activation functions. Our improved neural network achieves an average mean absolute error of 0.1340, which is a significant improvement over our reimplementation of the original D-GEX, which achieves an average mean absolute error of 0.1637. The proposed transformative adaptive function enables a significantly more accurate reconstruction of the full gene expression profiles with only a small increase in the complexity of the model and its training procedure compared to other methods. | 10.1371/journal.pone.0243915 |
pubmed_827_1814 | There is growing evidence that exposure to stress alters the acute effects of abused drugs on the CNS. However, it is not known whether stress augments the longer-term neurotoxic effects of psychostimulant drugs, such as methamphetamine. Methamphetamine at high doses decreases forebrain dopamine concentrations. The current study tested the hypothesis that 10 days of unpredictable stress augmented striatal dopamine depletions 7 days following four injections of either 7.5 or 10 mg/kg methamphetamine (1 injection every 2 h). Furthermore, to assess the effects of chronic stress on immediate responses to methamphetamine, extracellular striatal dopamine and methamphetamine concentrations, and rectal temperature were monitored during the methamphetamine injection regimen. Seven days following either a 7.5 mg/kg or 10 mg/kg methamphetamine injection regimen, male rats exposed to unpredictable stress showed greater depletions in striatal dopamine tissue content compared with non-stressed controls injected with methamphetamine. Stressed rats had increased hyperthermic responses and dopamine efflux in the striatum during the methamphetamine injections when compared with non-stressed control rats. Moreover, stressed rats had an increased mortality rate (33%) compared with non-stressed controls (16.7%) following four injections of 10 mg/kg methamphetamine. The enhanced acute and longer-term effects of methamphetamine in stressed rats was not due to a greater concentrations of methamphetamine in the striatum, as extracellular levels of methamphetamine during the injection regimen did not differ between the two groups. In summary, exposure to 10 days of chronic unpredictable stress augments longer-term depletions of dopamine in the striatum, as well as acute methamphetamine-induced hyperthermia and extracellular dopamine levels. These findings suggest that chronic stress increases the responsiveness of the brain to the acute pharmacological effects of methamphetamine and enhances the vulnerability of the brain to the neurotoxic effects of psychostimulants. | 10.1016/j.neuroscience.2003.12.007 |
pubmed_1042_11406 | BACKGROUND
Medicines are an integral part of the health system and the accessibility hugely depends on affordability and availability of medicines. Oral health is an integral component of overall well-being but is ironically often one of the most neglected areas of healthcare. There is paucity of data on the pharmaceutical cost components of dental disease, so this study aims to address this lacuna on the pricing of medicines.
OBJECTIVE
This research study can be considered a partial economic evaluation that focuses on an estimation of costs associated with medicines used in the treatment of selected oral diseases to suggest policy measures to reduce out-of-pocket expenditure on medicines.
METHODS
Using cost analysis research design on the PharmaTrac dataset and cross-comparing it with public procurement rates of the Rajasthan Medical Services Corporation (RMSC) indicates that the pharmaceutical cost of treating caries and periodontitis is approximately three times higher if median retail prices are considered instead of RMSC public procurement costs.
RESULTS
Medicine cost of treating a single episode of caries or periodontitis using RMSC medicine rates at all levels of care is approximately 1.9-2.5 times lower than retail prices of the same formulations.
CONCLUSION
Our results strongly suggest that centralized public procurement of dental medicines with an efficient monitoring and control can reduce the out-of-pocket expenditure. | 10.3233/JRS-191033 |
pubmed_1107_12338 | Certain types of neuronal ions channels have been demonstrated to be the major target sites of insecticides. The insecticide-channel interactions that have been studied most extensively are pyrethroid actions on the voltage-gated sodium channel and cyclodiene/lindane actions on the GABAA receptor chloride channel complex. With the exception of organophosphate and carbamate insecticides which inhibit acetylcholinesterases, most insecticide commercially developed act on the sodium channel and the GABA system. Pyrethroids show the kinetics of both activation and inactivation gates of sodium channels resulting in prolonged openings of individual channels. This causes membrane depolarization, repetitive discharges and synaptic disturbances leading to hyperexcitatory symptoms of poisoning in animals. Only a very small fraction (approximately 1%) of sodium channel population is required to be modified by pyrethroids to produce severe hyperexcitatory symptoms. This toxicity amplification theory applies to pharmacological and toxicological action of other drugs that go through a threshold phenomenon. Selective toxicity of pyrethroids between invertebrates and mammals can be explained based largely on the responses of sodium channels and partly on metabolic degradation. The pyrethroid-sodium channel interaction is also supported by Na+ uptake and batrachotoxin binding experiments. Cyclodienes and lindane exert a dual action on the GABAA system, the initial transient stimulation being followed by a suppression. The stimulation requires the presence of the gamma 2 subunit. The suppression of the GABA system is also documented by Cl- flux and ligand binding experiments. It appears that the sodium channel and the GABA system merit continuing efforts for development of newer and better insecticides. Nitromethylene heterocycles including imidacloprid act on nicotinic acetylcholine receptors. Insect receptors are more sensitive to these compounds than mammalian receptors. Single-channel analyses of the nicotinic acetylcholine receptor of PC12 cells have shown that imidacloprid increases the activity of subconductance state currents and decreases that of main conductance state currents. This may explain the imidacloprid suppression of acetylcholine responses. | 10.1111/j.1600-0773.1996.tb00234.x |
pubmed_980_17559 | The aim of this paper is to study the profile of persons with low vision in Jordan based on the clinical records of service users who attended the Vision Rehabilitation Center (VRC) at the German Jordanian University (GJU). A retrospective study was conducted by reviewing the archived data for persons with low vision attending the VRC over the period September 2012 to December 2017. The information collected included age, gender, referral, geographical distribution, chief functional visual problems, and ocular pathology. The records of 725 (28.9 ± 20.3 years old) persons out of 858 persons were analyzed. Almost half (50.6%) of the sample was less than 18 years old. The main cause of the low vision was retinal diseases (53.4%), followed by albinism. Gender and age showed no significant influence on ocular pathology distribution. For the referrals, ophthalmologists (37.8%) were the largest source of referral, followed by institutions for people with disabilities (14.9%). Near tasks were reported as the main functional problems for patients with low vision (74.9%), followed by distance tasks (8.3%). This study sets a precedent for determining the characteristics of persons with low vision in Jordan. Developing an efficient referral system between eye health care professionals and other health caregivers is important to ensure the best multidisciplinary services for low vision. | 10.3390/healthcare9010020 |
pubmed_901_10142 | One hundred fifty-seven fractured anterior teeth were restored with one of three acid-etch composite resin systems and were clinically and radiographically evaluated for 24 months. Of the three systems evaluated, the material activated by ultraviolet light provided the highest retention rate and clinical acceptance. | 10.14219/jada.archive.1978.0485 |
pubmed_72_8344 | OBJECTIVES
to identify the biomarkers to use in order to evaluate the level and trend of exposure to environmental pollutants from a plant which retrieves and refines precious metals and burns toxic waste.
DESIGN
human biomonitoring cross sectional study on a small sample of population resident in the study area.
SETTING AND PARTICIPANTS
blood and urinary samples, and questionnaires from volunteers resident at least for 10 years in Civitella in Val di Chiana area (Arezzo Province, Tuscany Region, Central Italy), where the plant is located, and in a control area; they had to be 5-year non-smokers or ex-smokers, in good health status and non occupationally exposed to heavy metals and/or combustion products.
MAIN OUTCOME MEASURES
geometric mean and 95th percentile (P95) of mercury (Hg) and cadmium (Cd) blood concentrations, and of the urinary concentrations of antimony (Sb), silver (Ag), arsenic (As), Cd, cobalt (Co), chromium (Cr), Hg, nickel (Ni), platinum (Pt), 1-hydroxypyrene, and trans, trans-muconic acid in the two populations; quantity and pattern of porphyrins in the 24-hour urines of Civitella volunteers. Student's "t" test calculated on the means of data with logarithmic transformation was used to compare the two groups. In case of significant differences linear regression analyses have been performed using questionnaire information. The distribution of observed data was compared with specific reference values.
RESULTS
Sb, Cd, and Ni concentrations were significantly higher in Civitella population (39 subjects), while Cr concentration was higher in the control group (18 subjects). No correlations with the individual characteristics have been observed. The 30.3%of subjects who gave their 24- hour urine had a distorted pattern of porphyrins.
CONCLUSION
the results confirmed the need to perform human biomonitoring in the Civitella area, increasing the number of samples, using urine as biological matrix, and monitoring at least Sb, Cd, Ni, Pt, Ag, and porphyrins. | pubmed_72_8344 |
pubmed_970_13276 | Although sleep is ubiquitous, its evolutionary purpose remains elusive. Though every species of animal, as well as many plants sleep, theories of its origin are purely physiological, e.g. to conserve energy, make repairs or to consolidate learning. An evolutionary reason for sleep would answer one of biology's fundamental unanswered questions. When environmental conditions change on a periodic basis (winter/summer, day/night) organisms must somehow confront the change or else be less able to compete in either niche. Seasonal adaptation includes the migration of birds, changes in honeybee physiology and winter abscission in plants. Diurnal adaptation must be more rapid, forcing changes in behavior in addition to physiology. Since organisms must exist in both environments, evolution has created a way to force a change in behavior, in effect creating "different" organisms (one awake, one asleep) adapted separately to two distinct niches. We sleep to allow evolving into two competing niches. The physiology of sleep forces a change to a different state for the second niche. The physiological needs for sleep are mechanisms that have evolved to achieve this goal. | 10.5334/jcr.189 |
Subsets and Splits