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pubmed_339_23669 | Atypical handedness patterns, i.e., persons being less exclusively right-handed, have been found previously in large samples of male and female homosexuals and in small samples of male and female transsexuals compared to controls. The posited role of prenatal androgen influencing both cerebral hemispheric dominance and psychosexual development warrants further study with large samples of transsexuals. 443 male-to-female transsexuals and 93 female-to-male transsexuals were studied for their use of the right or left hand in six common one-handed tasks. Both male and female transsexuals were more often nonright-handed than male and female controls were. Results suggest an altered pattern of cerebral hemispheric organisation in male and female transsexuals. | 10.1023/a:1011908532367 |
pubmed_152_19656 | Possible circadian fluctuations and long-term changes in concentrations of reproductive hormones in peripubertal female birds is poorly documented in comparison with mammalian species. Our objective was to document changes in concentrations of several reproductive hormones the several days before and after initial pubertal preovulatory surges of LH in turkey hens photostimulated with either constant (24L:0D) or diurnal (14L:10D) lighting. The hens were cannulated for hourly blood sampling, starting 10 days after photostimulation and continuing until all hens had laid at least two eggs. First eggs were oviposited between 16 and 24 days after photostimulation, and egg production ranged from two to nine eggs/hen during the experimental period. With both lighting treatments, concentrations of LH declined slightly, concentrations of progesterone (P(4)) increased, and concentrations of estradiol-17beta (E(2)) were constant the 3-4 days prior to initial LH surges with no circadian fluctuations in hormone concentrations. Most (10 of 13) initial preovulatory surges of LH were coupled with ovulations, and all LH surges were coupled with P(4) surges. Those LH and P(4) surges not coupled with ovulations (blind surges) occurred with both lighting treatments, but the incidence of blind surges was higher with diurnal lighting. The interval between LH and P(4) surges was longer between the first and second surges than between subsequent surges, when the interval was approximately 26 h. The duration of LH surges (7.4 +/- 3.0 h) was shorter than that of P(4) surges (10.0 +/- 2.0 h). We conclude that, in the peripubertal female turkey, 1) prior to puberty (first LH-P(4) surges), there are no circadian fluctuations in concentrations of LH, P(4), and E(2), 2) 3 days prior to initial LH surges, E(2) concentrations are stable, LH concentrations decline slightly, and P(4) concentrations increase, and 3) surges of LH are coupled to surges of P(4) but LH-P(4) surges are not always coupled to ovipositions (blind surges), possibly because of internal ovulations. | 10.1095/biolreprod67.2.591 |
pubmed_1123_11487 | We develop a unique algorithm implemented in the program MOSAICS (Methodologies for Optimization and Sampling in Computational Studies) that is capable of nanoscale modeling without compromising the resolution of interest. This is achieved by modeling with customizable hierarchical degrees of freedom, thereby circumventing major limitations of conventional molecular modeling. With the emergence of RNA-based nanotechnology, large RNAs in all-atom representation are used here to benchmark our algorithm. Our method locates all favorable structural states of a model RNA of significant complexity while improving sampling accuracy and increasing speed many fold over existing all-atom RNA modeling methods. We also modeled the effects of sequence mutations on the structural building blocks of tRNA-based nanotechnology. With its flexibility in choosing arbitrary degrees of freedom as well as in allowing different all-atom energy functions, MOSAICS is an ideal tool to model and design biomolecules of the nanoscale. | 10.1073/pnas.1119918109 |
pubmed_232_21932 | AIM
To study the anatomical and visual performance following implantation of a model of artificial cornea and to evaluate the postoperative long term complications.
METHODS
11 eyes of 11 patients with bilateral corneal blindness considered as potentially having high risk of failure of penetrating corneal keratoplasty were implanted with biocolonisable Kpro keratoprosthesis (BIOKOP I, FCI, Rantigny, France) in the period between January 1996 and May 1998. Only one eye was implanted in all patients and followed up for a period of 60 months. The visual outcome, anatomical and functional stability, complications, and the general performance of the keratoprosthesis were evaluated.
RESULTS
The keratoprosthesis (BIOKOP I) only 36.3% remained in position to date. In the patients' last visit five eyes (45.4%) were blind and one (9.0%) showed a slight improvement in the best corrected visual acuity (BCVA) in comparison to preoperative tests. Six eyes (54.5%) showed improved BCVA before having postoperative complications. Four eyes underwent replacement of a BIOKOP I Kpro with a BIOKOP II as a result of extrusion. The keratoprostheses remained anatomically in situ for a mean of 25.5 months and their functional performance period was limited to a mean of 22 months.
CONCLUSION
Corneal keratoprosthesis (BIOKOP I, II) does not provide a stable anatomical relation with the surrounding ocular structures. Its ability to restore vision is limited to a short postoperative period in eyes implanted with severe ocular surface disease. | 10.1136/bjo.2004.046375 |
pubmed_5_13874 | We isolated pgi1-1, an Arabidopsis mutant with a decreased plastid phospho-glucose (Glc) isomerase activity. While pgi1-1 mutant has a deficiency in leaf starch synthesis, it accumulates starch in root cap cells. It has been shown that a plastid transporter for hexose phosphate transports cytosolic Glc-6-P into plastids and expresses restricted mainly to the heterotrophic tissues. The decreased starch content in leaves of the pgi1-1 mutant indicates that cytosolic Glc-6-P cannot be efficiently transported into chloroplasts to complement the mutant's deficiency in chloroplastic phospho-Glc isomerase activity for starch synthesis. We cloned the Arabidopsis PGI1 gene and showed that it encodes the plastid phospho-Glc isomerase. The pgi1-1 allele was found to have a single nucleotide substitution, causing a Ser to Phe transition. While the flowering times of the Arabidopsis starch-deficient mutants pgi1, pgm1, and adg1 were similar to that of the wild type under long-day conditions, it was significantly delayed under short-day conditions. The pleiotropic phenotype of late flowering conferred by these starch metabolic mutations suggests that carbohydrate metabolism plays an important role in floral initiation. | 10.1104/pp.123.1.319 |
pubmed_879_24468 | AIM
The aim of this study was to assess the influence of adrenomedullary secretion on the plasma glucose, lactate, and free fatty acids (FFAs) during running exercise in rats submitted to intracerebroventricular (i.c.v.) injection of physostigmine (PHY). PHY i.c.v. was used to activate the central cholinergic system.
METHODS
Wistar rats were divided into sham-saline (sham-SAL), sham-PHY, adrenal medullectomy-SAL, and ADM-PHY groups. The plasma concentrations of glucose, lactate, and FFAs were determined immediately before and after i.c.v. injection of 20 μL of SAL or PHY at rest and during running exercise on a treadmill.
RESULTS
The i.c.v. injection of PHY at rest increased plasma glucose in the sham group, but not in the ADM group. An increase in plasma glucose, lactate, and FFAs mobilization from adipose tissue was observed during physical exercise in the sham-SAL group; however, the increase in plasma glucose was greater with i.c.v. PHY. Moreover, the hyperglycemia induced by exercise and PHY in the ADM group were blunted by ADM, whereas FFA mobilization was unaffected.
CONCLUSION
These results indicate that there is a dual metabolic control by which activation of the central cholinergic pathway increases plasma glucose but not FFA during rest and exercise, and that this hyperglycemic response is dependent on adrenomedullary secretion. | 10.1159/000519807 |
pubmed_162_606 | Purpose The purpose of this study was to gain a deeper understanding about mothers' experiences of transitioning their emerging adult with type 1 diabetes mellitus to college. Methods A descriptive, qualitative study was conducted with 9 mothers of high school seniors with type 1 diabetes (T1DM) using semi-structured questions via recorded telephone interviews. Results Among the 9 participants, 8 had daughters, and 1 had a son. The thematic analysis resulted in 4 themes: (1) concern for health and safety at college, (2) evolving roles of the parent and emerging adult dyad, (3) communication dynamics, and (4) social support systems. Conclusions Results indicate that mothers of emerging adults with T1DM experience heightened levels of concern during the college transition. These concerns are above and beyond those that are experienced by mothers of emerging adults without T1DM. Findings indicated that increasing levels of support for both parents as well as emerging adults with T1DM during the college transition may serve to decrease maternal stress and enhance the development of preparedness for diabetes self-management. Recommendations for diabetes educators in clinical practice include a family-centered approach focusing on the transition before the late adolescent period, interventions from colleges to promote a smooth transition, and interventions that address concerns of both the emerging adult with T1DM and the parent. Further research is necessary to identify barriers and facilitators to support parent/emerging adult dyads during the college transition period. | 10.1177/0145721718759980 |
pubmed_103_15001 | We study possible smooth deformations of the generalized free conformal field theory in arbitrary dimensions by exploiting the singularity structure of the conformal blocks dictated by the null states. We derive in this way, at the first nontrivial order in the ε expansion, the anomalous dimensions of an infinite class of scalar local operators, without using the equations of motion. In the cases where other computational methods apply, the results agree. | 10.1103/PhysRevLett.118.061601 |
pubmed_585_12145 | Recent studies have suggested that 2 lesions of the fetal membranes, linear necrosis at the choriodecidual junction and chorionic membrane microcysts, are markers of uteroplacental ischemia. To evaluate this hypothesis, we examined 807 placentas from unselected, consecutive deliveries at a single hospital over approximately 6 months with specific recording of the presence of chorionic microcysts or linear membrane necrosis. Clinical factors that might indicate uteroplacental ischemia were abstracted from the pathology report, including small for gestational age, pregnancy-induced hypertension, meconium macrophages in the membranes, infarctions, and small placenta. We found that both chorionic microcysts and linear membrane necrosis are very common lesions in unselected placentas, involving 28% and 18% of all placentas, respectively. There was no correlation between the presence of chorionic membrane microcysts and any marker of uteroplacental ischemia. Linear necrosis correlated only with the presence of meconium macrophages. We conclude that these membrane changes are not a useful marker of ischemia in an unselected population of placentas. We suggest caution in the interpretation of these findings, to avoid overdiagnosing ischemia or other pathologic processes. | 10.2350/11-08-1072-OA.1 |
pubmed_163_20789 | PURPOSE
Schistosoma japonicum-infected IL-33 and ST2 gene deficiency (IL-33 -/- and ST2 , respectively) mice were used to explore the role of the IL-33/ST2 axis in liver pathology targeting regulatory T cells (Treg)/T helper 17 cells (Th17).
MATERIALS AND METHODS
Each mouse was infected percutaneously with 20 S. japonicum cercariae. Hepatic mass index (HMI), liver egg granulomas, hepatic fibrosis biomarkers and serum levels of alanine aminotransferase (ALT) were investigated. Treg and Th17 frequency was determined by flow cytometry. Expressions of Foxp3, ST2, TGF-β1, IL-10, RORγt, and IL-17A were measured via quantitative real-time polymerase chain reaction (qRT-PCR). Concentrations of TGF-β1, IL-10 and IL-17A were tested with ELISA. In vitro experiments, mRNA expressions of Foxp3, TGF-β1, IL-10, Atg5, Beclin-1 and p62 associated with polarization of Treg by recombinant mouse IL-33 (rmIL-33) were detected by qRT-PCR.
RESULTS
An increased expression of IL-33/ST2 was shown in S. japonicum-infected mice. Deficiency of IL-33 or ST2 gene led to an aggravated liver pathology, which was evidenced by elevated hepatic granuloma volume, HMI and ALT levels and fibrosis, which was demonstrated by increased hepatic collagen deposition in the infected mice. Injection of rmIL-33 into the infected IL-33 mice strongly abrogated the liver pathology and fibrosis, whereas no detectable effect with injecting rmIL-33 into the infected ST2 mice. Furthermore, depletion of the IL-33/ST2 axis inhibited Treg, accompanied by increased Th17. rmIL-33 treatment upregulated Treg and downregulated Th17 in the infected IL-33 mice, while no effect in the infected ST2 mice. rmIL-33 led to elevated expressions of Atg5, Beclin-1 and inhibited expression of p62 in expansion of Treg.
CONCLUSION
The IL-33/ST2 axis plays a protective role in S. japonicum infected mice, which is closely related to increasing Treg responses as well as suppressing Th17 responses. Expansion of Treg by IL-33 may be associated with its regulation of autophagy. | 10.2147/JIR.S336404 |
pubmed_665_21739 | IFN-gamma is of central importance for the induction of robust cell-mediated immunity and for the activation of APC. Recent studies using experimental murine systems have now suggested a fundamental role for APC-derived IFN-gamma during infection with intracellular pathogens. It is currently unknown whether human dendritic cells (DC) can respond to bacterial stimulation with production of IFN-gamma. To test this question, we used human monocyte-derived DC stimulated by Mycobacterium bovis bacillus Calmette-Guérin as a model system. We demonstrate production of IFN-gamma mRNA and protein on the single cell level. IFN-gamma in DC cultures was not simply produced by contaminating lymphocytes because production of DC-IFN-gamma could also be demonstrated in highly purified DC cultures containing virtually no T, B, and NK cells. TLR2 was identified as a key receptor involved in triggering production of DC-IFN-gamma. Interestingly, DC-IFN-gamma seems to participate in an autocrine DC activation loop, and production of DC-IFN-gamma could be enhanced by costimulation of DC with IL-12/IL-15/IL-18. In conclusion, we have demonstrated production of IFN-gamma by human DC on the single cell level, identified TLR2 as a pattern recognition receptor involved in this process, and elucidated some of the functional consequences of autocrine IFN-gamma production by human DC. | 10.4049/jimmunol.176.9.5173 |
pubmed_878_18844 | Patterns in time-course gene expression data can represent the biological processes that are active over the measured time period. However, the orthogonality constraint in standard pattern-finding algorithms, including notably principal components analysis (PCA), confounds expression changes resulting from simultaneous, non-orthogonal biological processes. Previously, we have shown that Markov chain Monte Carlo nonnegative matrix factorization algorithms are particularly adept at distinguishing such concurrent patterns. One such matrix factorization is implemented in the software package CoGAPS. We describe the application of this software and several technical considerations for identification of age-related patterns in a public, prefrontal cortex gene expression dataset. | 10.1007/978-1-62703-721-1_6 |
pubmed_454_17155 | A method is proposed to estimate the optical parameters in a fluorescing turbid medium with strong absorption for which traditional Kubelka-Munk theory is not applicable, using a model for the radiative properties of optically thick fluorescent turbid media of finite thickness proposed in 2009 [J. Opt. Soc. Am. A26, 1896 (2009)]. The method is successfully applied to uncoated papers with different thicknesses. It is found that the quantum efficiency of fluorescent whitening agents (FWAs) is nearly independent of the fiber type, FWA type, FWA concentration, and filler additive concentration used in this study. The results enable an estimation of the model parameters as function of the FWA concentration and substrate composition. This is necessary in order to use the model for optimizing fluorescence in the paper and textile industries. | 10.1364/AO.50.002784 |
pubmed_26_13026 | Obesity is associated with increased susceptibility to dyslipidemia, insulin resistance, and hypertension, a combination of traits that comprise the traditional definition of the metabolic syndrome. Recent evidence suggests that obesity is also associated with the development of nonalcoholic fatty liver disease (NAFLD). Despite the high prevalence of obesity and its related conditions, their etiologies and pathophysiology remains unknown. Both genetic and environmental factors contribute to the development of obesity and NAFLD. Previous genetic analysis of high-fat, diet-induced obesity in C57BL/6J (B6) and A/J male mice using a panel of B6-Chr(A/J)/NaJ chromosome substitution strains (CSSs) demonstrated that 17 CSSs conferred resistance to high-fat, diet-induced obesity. One of these CSS strains, CSS-17, which is homosomic for A/J-derived chromosome 17, was analyzed further and found to be resistant to diet-induced steatosis. In the current study we generated seven congenic strains derived from CCS-17, fed them either a high-fat, simple-carbohydrate (HFSC) or low-fat, simple-carbohydrate (LFSC) diet for 16 weeks and then analyzed body weight and related traits. From this study we identified several quantitative trait loci (QTLs). On a HFSC diet, Obrq13 protects against diet-induced obesity, steatosis, and elevated fasting insulin and glucose levels. On the LFSC diet, Obrq13 confers lower hepatic triglycerides, suggesting that this QTL regulates liver triglycerides regardless of diet. Obrq15 protects against diet-induced obesity and steatosis on the HFSC diet, and Obrq14 confers increased final body weight and results in steatosis and insulin resistance on the HFSC diet. In addition, on the LFSC diet, Obrq 16 confers decreased hepatic triglycerides and Obrq17 confers lower plasma triglycerides on the LFSC diet. These congenic strains provide mouse models to identify genes and metabolic pathways that are involved in the development of NAFLD and aspects of diet-induced metabolic syndrome. | 10.1007/s00335-008-9165-2 |
pubmed_1095_21262 | Cystic tumours of the spleen are generally rare, and a parasitic origin is relatively unlikely. The present case report shows, however that when a splenic cyst is found, the differential diagnosis must always consider the possibility of echinococcosis. We report the case of a patient suffering from a cystic lesion of the spleen where surgery and histopathology yielded the diagnosis of splenic echinococcosis. Abdominal pain in the left upper quadrant and splenomegaly detected by simple abdominal radiology are the most commonly found indicators for this disease. The treatment should be surgical, attempting to preserve as much splenic tissue as possible, although conservative treatment is frequently unfeasable due to massive involvement of the spleen. Although rare, splenic hydatidosis should be included in the differential diagnosis when a cystic splenic lesion is identified with sonography or CT scan. | pubmed_1095_21262 |
pubmed_1055_19789 | The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is recognized as the master regulator of mitochondrial biogenesis. However, recently a novel isoform, PGC-1α4, that specifically regulates muscle hypertrophy was discovered. Because stimulation of mechanistic target of rapamycin complex 1 (mTORC1) activity is tightly coupled to hypertrophy, we hypothesized that activation of this pathway would upregulate PGC-1α4. Eight male subjects performed heavy resistance exercise (10 × 8-12 repetitions at ∼75% of 1 repetition maximum in leg press) on four different occasions, ingesting in random order a solution containing essential amino acids (EAA), branched-chain amino acids (BCAA), leucine, or flavored water (placebo) during and after the exercise. Biopsies were taken from the vastus lateralis muscle before and immediately after exercise, as well as following 90 and 180 min of recovery. Signaling through mTORC1, as reflected in p70S6 kinase phosphorylation, was stimulated to a greater extent by the EAA and BCAA than the leucine or placebo supplements. Unexpectedly, intake of EAA or BCAA attenuated the stimulatory effect of exercise on PGC-1α4 expression by ∼50% (from a 10- to 5-fold increase with BCAA and EAA, P < 0.05) 3 h after exercise, whereas intake of leucine alone did not reduce this response. The 60% increase (P < 0.05) in the level of PGC-1α1 mRNA 90 min after exercise was uninfluenced by amino acid intake. Muscle glycogen levels were reduced and AMP-activated protein kinase α2 activity and phosphorylation of p38 mitogen-activated protein kinase enhanced to the same extent with all four supplements. In conclusion, induction of PGC-1α4 does not appear to regulate the nutritional (BCAA or EAA)-mediated activation of mTORC1 in human muscle. | 10.1152/ajpendo.00154.2016 |
pubmed_11_5367 | OBJECTIVES
To evaluate the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) on retinal vascular leakage, and inflammatory markers in endotoxin-induced uveitis (EIU) in rats.
METHODS
EIU was induced in rats by lipopolysaccharide (LPS). Topical 0.5% indomethacin, 0.09% bromfenac and 0.1% nepafenac were given before and after LPS. Twenty-four hours after LPS, the animals were euthanized and plasma along with retina were collected to assess prostaglandin-E2 (PGE2 ) and C-reactive protein (CRP) levels using enzyme-linked immunosorbent assay. Retinal vascular leakage was assessed by Evans blue. Molecular modelling was used to evaluate interaction of compounds with cyclooxygenase-2 (COX-2).
KEY FINDINGS
All NSAIDs tested significantly prevented PGE2 production with higher effect of indomethacin and bromfenac in comparison with nepafenac. The three drugs did not affect plasma CRP levels. The analysis of retinal vascular leakage revealed a significant (P<0.01) decrease after treatment with indomethacin, but no significant changes were observed after treatment with bromfenac and nepafenac. Indomethacin had a different interaction with COX-2 in comparison with bromfenac and amfenac (active metabolite of nepafenac).
CONCLUSIONS
Topical treatment with indomethacin, bromfenac and nepafenac has significant anti-inflammatory effects. However, only indomethacin was able to prevent retinal vascular leakage in LPS-injected rats, likely due to the distinctive molecular mechanism. | 10.1111/jphp.12224 |
pubmed_101_18893 | Background:Mobility and independence of older adults are influenced by age-related capabilities and limitations, as well as environmental factors such as non-optimum design of public seating (e.g., inappropriate seat height, angle, and compressibility as well as armrests). This study was the first part of a multi-stage investigation of the impact of public seating on older adults. Method:One hundred and six older adults (aged 65 and over) completed an online survey regarding difficulties experienced with standing up from public seating (e.g. frequency; location; type of seating; effects). Results:A majority (59.4%) reported experiencing problems, with seat height the most common issue. Shopping malls, cafes and restaurants, doctor's offices, outdoor locations, and public toilets were the most common locations. Effects included inconvenience, embarrassment, discomfort, pain, and needing help from another person to stand. Discussion:Further research is needed to explore the locations and features of seating that can contribute to this problem. | 10.1080/0361073X.2021.1884445 |
others_304_2124 | Four kinds of plant pollen were tested as an alternative food source for rearing the predatory mite Euseius scutalis (Athias-Henriot) under laboratory conditions of 26°C and 70%RH. Pollen grains were extracted from date palm Pheonyx dactylefira L., sour orange Citrus aurantium L., castor bean Ricinus communis L. and alfalfa Medicago sativa L. Individuals of the predatory mite were collected from leaves of eggplant in Hail district during spring 2010. Mite individuals were provided and reared on the aforementioned pollens for their whole life span. Total developmental period significantly affected by kind of pollen. Date palm pollen highly shortened the development followed by alfalfa, citrus and castor bean. Feeding on date palm pollen caused the highest rate of survival (94%) and gradually declined to 92, 90 and 89% when mites were provided with citrus, alfalfa and castor bean pollen, respectively. During adulthood, female deposited 42.62, 30.22, 21.16 and 13.46 eggs in approximately 12.42, 10.82, 9.44 and 7.22 days when fed date palm, alfalfa, castor bean and citrus pollen, respectively. Mean generation time (T) averaged 17.19, 17.86, 19.08 and 20.47 days; net reproductive rate (R0) 34.93, 30.81, 15.59 and 18.51 fern ale/female/day; intrinsic rate of natural increase (rm) 0.20, 0.192, 0.134 and 0.153; finite rate of increase erm (λ) 1.22, 1.21, 1.14 and 1.15 when mites fed the same kinds of pollen, respectively. The tested plant pollen is considered a suitable alternative food source and meet the nutritional requirements of E. scutalis in Hail, Saudi Arabia. © 2011 Academic Journals I | 10.3923/je.2011.365.374 |
pubmed_597_23600 | RATIONALE
Physical activity, and specifically exercise, has shown promise as an intervention for drug addiction; however, the exercise conditions that produce the most efficacious response, as well as its underlying mechanism, are unknown.
OBJECTIVE
In this study, we examined the dose-dependent effects of wheel running, an animal model of exercise, during abstinence on subsequent cocaine-seeking and associated changes in prefrontal cortex (PFC) brain-derived neurotrophic factor (Bdnf) exon IV expression, a marker of epigenetic regulation implicated in cocaine relapse and known to be regulated by exercise.
METHODS
Cocaine-seeking was assessed under a within-session extinction/cue-induced reinstatement procedure following extended access cocaine or saline self-administration (24-h/day, 4 discrete trials/h, 10 days, 1.5 mg/kg/infusion) and a 14-day abstinence period. During abstinence, rats had either locked or unlocked running wheel access for 1, 2, or 6 h/day. Bdnf exon IV expression was assessed using quantitative real-time polymerase chain reaction.
RESULTS
Cocaine-seeking was highest under the locked wheel condition, and wheel running dose dependently attenuated this effect. Cocaine increased Bdnf exon IV expression, and wheel running dose dependently attenuated this increase, with complete blockade in rats given 6-h/day access. Notably, the efficacy of exercise was inversely associated with Bdnf exon IV expression, and both its efficacy and its effects on Bdnf exon IV expression were mimicked by treatment during abstinence with sodium butyrate, a histone deacetylase inhibitor that, like exercise, modulates gene transcription, including Bdnf exon IV expression.
CONCLUSION
Taken together, these results indicate that the efficacy of exercise is dose dependent and likely mediated through epigenetic regulation of PFC Bdnf. | 10.1007/s00213-013-3321-4 |
pubmed_358_20024 | This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%. Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with >50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria >1.0 g/d (P = 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at biopsy (P = 0. 008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD. | 10.1681/ASN.V1181439 |
pubmed_538_15602 | All4312, encoded by open reading frame all4312 in the genome of the heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120, exhibits a CheY-like receiver domain and an output domain similar to that of OmpR, characteristic of two-component response regulators. Expression of all4312 was directly regulated by NtcA, the global transcriptional regulator of nitrogen assimilation in cyanobacteria. Features characteristic of NtcA-activated promoters were also found upstream from genes encoding All4312 homologues in several other cyanobacterial genomes. Expression of all4312 was however unaffected in a mutant of hetR, which encodes a regulator triggering heterocyst development. The function of All4312 may be related to the cellular response to nitrogen deprivation. | 10.1111/j.1574-6968.2006.00136.x |
pubmed_531_20423 | There have been examined 93 patients with the tuberculosis of bones and joints, 28 patients with chronic hematogenic osteomyelitis. All patients have been typed in accordance with the antigens of loci HLA-A, B, C and DR by means of standard microlymphocytotoxic test. 135 healthy donors have been typed according to the same loci++ HLA as controls (105 persons have been typed according to antigens of locus HLA-DR). All examined persons have been Uzbeks. There have been stated that in the patients with the tuberculosis of bones and joints, as compared with osteomyelitis, is observed the increase of frequency of antigens HLA-B27 and HLA-DR2, while in case of bone osteomyelitis is noted association with antigens HLA-A9, B7 and B18. | pubmed_531_20423 |
pubmed_678_13901 | The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and demonstrate supersaturation and precipitation of dipyridamole and ketoconazole. We therefore conclude that the GIS has been shown to be a good biopredictive tool to predict in vivo bioperformance of BCS class IIb drugs that can be used to optimize oral formulations. | 10.1016/j.ejps.2017.02.042 |
pubmed_783_18814 | Phytotherapy has been described as an alternative method for the control of gastrointestinal nematodes in small ruminants. Goal of the encapsulation of essential oils in biopolymer matrices is to optimize the biological effects of these oils. The aim of the present study was to evaluate the in vitro and in vivo anthelmintic activity of encapsulated Eucalyptus staigeriana essential oil (EncEs) on the eggs and larvae of Haemonchus contortus. Therefore, the egg hatching test (EHT), larval development test (LDT) and worm load evaluation were performed to evaluate Meriones unguiculatus experimentally infected with H. contortus. The chemical constituents of E. staigeriana essential oil (EsEO) and the in vitro oil release profile from the chitosan matrix at a pH of 1.2 and 7.0 were also characterized. EncEs and EsEO inhibited larval hatching by 97.19% and 99.96% at doses of 1.5 and 1.0 mg ml(-1), respectively. In the LDT, EncEs and EsEO induced a larvicidal effect greater than 95% at concentrations of 5.8 and 8 mg ml(-1), respectively. EncEs and EsEO decreased H. contortus load in M. unguiculatus by 40.51% and 46.44%, respectively. The major chemical constituents of EsEO were (+)-Limonene (72.9%), 1,8-Cineole (9.5%) and o-Cimene (4.6%). The release profile of EsEO was 30% in acid and 25% at neutral pH. The similar efficacy of EncEs and EsEO demonstrates that there was no optimization of anthelmintic action following the encapsulation process. Therefore, the use of new encapsulation matrices with controlled release in the pH of the abomasum should be investigated. | pubmed_783_18814 |
pubmed_143_22310 | Transient receptor potential cation channels are emerging as important physiological and therapeutic targets. Within the vanilloid subfamily, transient receptor potential vanilloid 2 (TRPV2) and 4 (TRPV4) are osmo- and mechanosensors becoming critical determinants in cell structure and activity. However, knowledge is scarce regarding how TRPV2 and TRPV4 are trafficked to the plasma membrane or specific organelles to undergo quality controls through processes such as biosynthesis, anterograde/retrograde trafficking, and recycling. This review lists and reviews a subset of protein-protein interactions from the TRPV2 and TRPV4 interactomes, which is related to trafficking processes such as lipid metabolism, phosphoinositide signaling, vesicle-mediated transport, and synaptic-related exocytosis. Identifying the protein and lipid players involved in trafficking will improve the knowledge on how these stretch-related channels reach specific cellular compartments. | 10.3390/biom9120791 |
pubmed_558_21428 | OBJECTIVE
To identify determinants for the discontinuation of non-ergoline dopamine agonist (DA) treatment in patients with Parkinson’s disease (PD) and to identify genetic determinants in genes encoding dopamine receptor (DR)D2 and DRD3 in a exploratory analysis.
METHODS
Patients included were first-time users of the non-ergoline DA ropinirole or pramipexole who had been diagnosed with PD before 2005. Treatment discontinuation was defined as a gap of 180 days or more between two refills of the DA. Non-genetic determinants for discontinuation were studied in the overall population, and genetic determinants [DRD2 141C Ins/Del, DRD2 (CA)n STR, DRD2 TaqIA, DRD3 MscI single nucleotide polymorphism (SNP) and DRD3 MspI SNP] were studied in a subgroup. Cox proportional hazard analysis was used to estimate the hazard ratios (HR) for the discontinuation of non-ergoline DA treatment.
RESULTS
The study population comprised 90 patients. Apomorphine use was associated with non-ergoline DA discontinuation, although the apomorphine group consisted only of three patients [HR 6.26; 95% confidence interval (CI) 1.85–21.2]. Daily levodopa dosages between 500 and 1000 mg were positively associated with discontinuation (HR 2.31; 95% CI 1.08–4.93). Included in the exploratory pharmacogenetic analysis were 38 patients. The absence of a 15× DRD2 CA repeat allele was significantly related with a decreased discontinuation of non-ergoline treatment (HR 0.23; 95% CI 0.07–0.81). The DRD3 MspI polymorphism showed a non-significant allele dose effect, suggestive of a causal relationship.
CONCLUSION
This study identified apomorphine use and levodopa dosages between 500 and 1000 mg as non-genetic and the 15× DRD2 CA repeat allele as genetic determinants for the discontinuation of non-ergoline DA treatment in patients with PD. More research is needed to replicate these findings. | 10.1007/s00228-009-0708-6 |
pubmed_386_10381 | OBJECTIVES
The aims of the present systematic literature analysis were to evaluate, over a 10-year period, the trend of the proportion of RCT, SR, MA published on endodontic surgery, and to investigate if the impact factor (IF) of the main endodontic Journals correlates with the proportion of RCT, SR, MA they publish.
METHODS
An electronic search of the RCT, SR and MA published on the topic "endodontic surgery" from 2001 to 2010 was performed on Medline and Cochrane CENTRAL database using specific search terms combined with Boolean operators. Endodontic Journals impact factor was retrieved by the Thomson Scientific database. The proportion of each study type over the total number of articles on endodontic surgery published per year was estimated. The correlation between the number of high-evidence level studies published on the main endodontic Journals and the IF of such Journals per year was estimated.
RESULTS
From a total of 900 articles published in 2001-2010 on endodontic surgery, there were 114 studies of high evidence level. A significant increase of the proportion of either RCT, SR and MA over the years was found. A modest to unclear correlation was found between the Journal IF and the number of high-evidence articles published.
CONCLUSIONS
There is a positive trend over the years among researchers in performing studies of good quality in endodontic surgery. The impact factor of endodontic Journals is not consistently influenced by publication of high-evidence level articles. | pubmed_386_10381 |
pubmed_40_24379 | Flavobacterium columnare is a bacterial fish pathogen that affects many freshwater species worldwide. The natural reservoir of this pathogen is unknown, but its resilience in closed aquaculture systems posits biofilm as the source of contagion for farmed fish. The objectives of this study were (i) to characterize the dynamics of biofilm formation and morphology under static and flow conditions and (ii) to evaluate the effects of temperature, pH, salinity, hardness, and carbohydrates on biofilm formation. Nineteen F. columnare strains, including representatives of all of the defined genetic groups (genomovars), were compared in this study. The structure of biofilm was characterized by light microscopy, confocal laser scanning microscopy, and scanning electron microscopy. F. columnare was able to attach to and colonize inert surfaces by producing biofilm. Surface colonization started within 6 h postinoculation, and microcolonies were observed within 24 h. Extracellular polysaccharide substances and water channels were observed in mature biofilms (24 to 48 h). A similar time course was observed when F. columnare formed biofilm in microfluidic chambers under flow conditions. The virulence potential of biofilm was confirmed by cutaneous inoculation of channel catfish fingerlings with mature biofilm. Several physicochemical parameters modulate attachment to surfaces, with the largest influence being exerted by hardness, salinity, and the presence of mannose. Maintenance of hardness and salinity values within certain ranges could prevent biofilm formation by F. columnare in aquaculture systems. | 10.1128/AEM.01192-13 |
pubmed_210_19064 | Alzheimer's disease (AD) is commonly an age-associated dementia with neurodegeneration. The pathogenesis of AD is complex and still remains unclear. The inflammation, amyloid β (Aβ), and neurofibrillary tangles as well misfolded tau protein in the brain may contribute to the occurrence and development of AD. Compared with tau protein, Aβ is less toxic. So far, all efforts made in the treatments of AD with targeting these pathogenic factors were unsuccessful over the past decades. Recently, many studies demonstrated that changes of the intestinal environment and gut microbiota via gut-brain axis pathway can cause neurological disorders, such as AD, which may be involved in the pathogenesis of AD. Thus, remodeling the gut microbiota by various ways to maintain their balance might be a novel therapeutic strategy for AD. In the review article, we analyzed the characteristics of gut microbiota and its dysbiosis in AD and its animal models and investigated the possibility of targeting the gut microbiota in the treatment of the patients with AD in the future. | 10.3389/fnagi.2020.544235 |
pubmed_926_7486 | BACKGROUND
Variations in femoral and acetabular version are becoming increasingly recognized as contributing factors to the development of hip pain in patients with femoroacetabular impingement (FAI) and hip dysplasia. It is still unknown what the true prevalence of these rotational abnormalities is in this patient population.
PURPOSE
To determine (1) the prevalence of femoral version abnormalities in symptomatic hips with FAI and hip dysplasia, (2) the prevalence of combined abnormalities of femoral and acetabular version in these patients, and (3) which specific hip morphologies are associated with abnormalities of femoral version.
STUDY DESIGN
Cross-sectional study; Level of evidence, 3.
METHODS
A total of 462 symptomatic patients (538 hips) were included who had hip pain attributed to FAI or hip dysplasia and who presented to our tertiary referral center for hip preservation surgery between 2011 and 2015. We retrospectively examined femoral and acetabular version among 11 subgroups with predefined hip morphologies and compared findings with a control group. The allocation to each subgroup was based on morphologic reference values for femoral head coverage, lateral center edge angle, alpha angle, and neck-shaft angle calculated on plain radiographs.
RESULTS
Of the 538 hips included, 52% were found to have abnormal femoral version; severe abnormalities were found in 17%. Severely decreased femoral version (<0°) was found in 5%; moderately decreased femoral version (0°-10°), in 17%; moderately increased femoral version (26°-35°), in 18%; and severely increased femoral version (>35°), in 12%. The most frequent abnormal combination was increased femoral version combined with normal acetabular version (22%). We found significantly lower mean femoral version for the cam-type FAI group (15°) and significantly higher mean femoral version for the Perthes hips (32°; ie, Legg-Calvé-Perthes disease) as compared with the control group (22°). The mean femoral version of the study group was 19°; for male patients, 15°; and for female patients, 22°.
CONCLUSION
Abnormalities in femoral version are highly prevalent in patients with hip pain who are eligible for hip preservation surgery, and severe abnormalities are prevalent in 1 of 6 patients (17%). Based on these results, the evaluation of young patients with hip pain should always include an assessment of femoral version and acetabular version to best decide what treatment approach should be undertaken to optimize outcomes. | 10.1177/0363546517726983 |
pubmed_267_10601 | We are interested in membrane phospholipid and triglyceride synthesis and turnover in aging cells. As a preliminary, short-term feasibility study we have used an established in vivo-in vitro technique to estimate the initial rates of [1-14C] palmitate (complexed to albumin) esterification to triglycerides and phospholipids in adipocytes and non-adipocytes in the epididymal fat pads of aging mice (8-92 weeks). We have expressed our data in terms of unit cell, unit triglyceride mass and unit (membrane) phospholipid mass. Fat pad and adipocyte size, cell surface area, and adipocyte volume changes were measured and found to follow the same relations as reported in the literature, with some exceptions in very old mice (retired breeders). Rates of fatty acid esterification to triglycerides were about 100 times faster than those to phospholipids in adipocytes. Aging caused a marked fall in the rates of triglyceride fatty acid formation from added palmitate; thus, the rate of fatty acid esterification to triglycerides fell from 0.75 to 0.13 nequiv. fatty acid per min per fat pad (youngest most active group, cf. oldest group). Esterification of fatty acids into phospholipids in adipocytes of the oldest mice was significantly lower than in those of the young and middle-aged groups. Contamination of adipocytes by non-adipocytes was observed in fat pads from old, but not from young, mice. The non-adipocytes accounted for about half of the phospholipid fatty acid esterification. The rate of phospholipid esterification was so slow in adipocytes (all ages) and so relatively fast in non-adipocytes that further studies of phospholipid fatty acid turnover in adipocytes using this system are not considered feasible, especially as a means for studying removal rates of autoxidized fatty acids from membrane phospholipids in vivo during aging. | 10.1016/0047-6374(82)90018-5 |
pubmed_449_12036 | Leopard Syndrome is a rare autosomal dominant condition affecting multiple systems. We report a 35-year-old woman with hypertrophic obstructive cardiomyopathy, pigmented naevi and growth retardation. We are unaware of previous cases reported in Scotland. | 10.1177/003693308302800318 |
pubmed_704_16958 | Loadings in temporomandibular joints (TMJs) are essential factors in dysfunction of TMJs, and are barely noticed in treatment of maxillofacial deformity. The only approach, which can access stresses in TMJs, could expend day's even weeks to complete. The objective of the study was to compare the differences of the morphological and biomechanical characteristics of TMJs between asymptomatic subjects and patients with mandibular prognathism, and to preliminarily analyze the connection between the two kinds of characteristics. Morphological measurements and finite element analysis (FEA) corresponding to the central occlusion were carried out on the models of 13 mandibular prognathism patients and 10 asymptomatic subjects. The results indicated that the joint spaces of the patients were significantly lower than those of the asymptomatic subjects, while the stresses of patients were significantly greater than those of asymptomatic subjects, especially the stresses on discs. The results of Pearson correlation analysis showed that weak or no correlations were found between the von Mises stresses and the joint spaces of asymptomatic subjects, while moderate, even high correlations were found in the patients. Thus, it was shown to be a feasible way to use morphological parameters to predict the internal loads of TMJs. | pubmed_704_16958 |
pubmed_1049_4281 | Paraneoplastic encephalomyelitis or subacute sensory neuronopathy associated with small-cell lung cancer (SCLC) and high titers of anti-HuD antibodies, also called the "anti-Hu syndrome," is believed to result from an immune response triggered by tumor antigens and misdirected to the neurons. To further assess the issue of cell-mediated immunity in this disease, the peripheral blood lymphocyte surface phenotype was studied in 15 patients suffering from the anti-Hu syndrome (seropositive group) and in two control groups consisting of 12 seronegative SCLC patients without neurological syndrome and 15 healthy volunteers. In addition, the recombinant human HuD protein was used to stimulate in vitro peripheral blood mononuclear cells of 10 seropositive patients and of 10 patients from each control group. Phenotypic analysis of the peripheral blood lymphocytes revealed a significant increase of the memory helper (CD45RO+CD4+) T cells in the seropositive group in comparison with the two control groups. Antigen-specific proliferation of peripheral blood mononuclear cells, measured by [3H]thymidine uptake after HuD antigen stimulation, was much higher in the seropositive group than in the two control groups, and phenotypic analysis of proliferating cells revealed a significant expansion of the CD45RO subpopulation of T cells in the seropositive group. Furthermore, after HuD stimulation, a significant increase of the interferon-gamma/interleukin-4 ratio was found in culture supernatants of the seropositive group compared with seronegative SCLC patients and normal controls. Taken together, these results indicate that HuD protein is an antigenic target for autoreactive CD4+ T cells, presumably of the Th1 subtype, which could therefore be directly involved in cell-mediated injury of the nervous system as well as in antitumoral immunity. | 10.1002/1531-8249(199902)45:2<162::aid-ana5>3.0.co;2-r |
pubmed_937_1557 | In metropolitan France, newborn screening for sickle cell disease has been performed at the Hĵpital Henri Mondor, Créteil, since 1985. After confirmation of the diagnosis, children are enrolled in a comprehensive medical-care program. Our aim was to evaluate the effectiveness of this program in France where most families are first generation immigrants with cultural and social differences that can interfere with medical follow-up. We compared the complications of sickle cell disease in two populations of homozygous SS children aged more than two years at their last medical visit, and recruited from an initial register of 134 SS children: (1) 38 diagnosed by neonatal screening; (2) 69 controls, diagnosed at a mean age of 24 months. Mean age at the last medical visit is 58 months in both groups. Splenic sequestrations and painful crises were significantly reduced in the screened group. Two screened children, belonging to the initial register from which the 38 other screened children were collected, died from overwhelming infection at 15 and 23 months, respectively. Neonatal diagnosis of sickle cell disease, coupled with specific preventive measures may lead, in the initial six years of life, to reduced painful events and splenic sequestration episodes. Education of parents is one of the hallmarks of preventive measures and may be difficult in first generation immigrants. Because of the bias of this type of study, a large prospective follow-up since birth is necessary to have a better understanding of the clinical course. | 10.1081/hem-120015024 |
pubmed_1112_118 | BACKGROUND
Covalent linkage of the ubiquitin-like protein ISG15 interferes with viral infection and USP18 is the major protease which specifically removes ISG15 from target proteins. Thus, boosting ISG15 modification by protease inhibition of USP18 might represent a new strategy to interfere with viral replication. However, so far no heterologous expression system was available to yield sufficient amounts of catalytically active protein for high-throughput based inhibitor screens.
RESULTS
High-level heterologous expression of USP18 was achieved by applying a chaperone-based fusion system in E. coli. Pure protein was obtained in a single-step on IMAC via a His6-tag. The USP18 fusion protein exhibited enzymatic activity towards cell derived ISG15 conjugated substrates and efficiently hydrolyzed ISG15-AMC. Specificity towards ISG15 was shown by covalent adduct formation with ISG15 vinyl sulfone but not with ubiquitin vinyl sulfone.
CONCLUSION
The results presented here show that a chaperone fusion system can provide high yields of proteins that are difficult to express. The USP18 protein obtained here is suited to setup high-throughput small molecule inhibitor screens and forms the basis for detailed biochemical and structural characterization. | 10.1186/1472-6750-12-56 |
pubmed_64_3055 | INTRODUCTION
The DAWN trial demonstrated the effectiveness of late endovascular treatment in acute ischemic stroke patients selected on the basis of a clinical-core mismatch. We explored in a real-world sample of endovascular treatment patients if a clinical-ASPECTS (Alberta Stroke Program Early CT Score) mismatch was associated with an outcome benefit after late endovascular treatment.
METHODS
We retrospectively analyzed all consecutive acute ischemic stroke patients admitted 6-24 h after last proof of good health in two stroke centers, with initial National Institutes of Health Stroke Scale (NIHSS) ≥10 and an internal carotid artery or M1 occlusion. We defined clinical-ASPECTS mismatch as NIHSS ≥ 10 and ASPECTS ≥ 7, or NIHSS ≥ 20 and ASPECTS ≥ 5. We assessed the interaction between the presence of the clinical-ASPECTS mismatch and late endovascular treatment using ordinal shift analysis of the three-month modified Rankin Scale and adjusting for multiple confounders.
RESULTS
The included 337 patients had a median age of 73 years (IQR = 61-82), admission NIHSS of 18 (15-22), and baseline ASPECTS of 7 (5-9). Out of 196 (58.2%) patients showing clinical-ASPECTS mismatch, 146 (74.5%) underwent late endovascular treatment. Among 141 (41.8%) mismatch negative patients, late endovascular treatment was performed in 72 (51.1%) patients. In the adjusted analysis, late endovascular treatment was significantly associated with a better outcome in the presence of clinical-ASPECTS mismatch (adjusted odd ratio, aOR = 2.83; 95% confidence interval, CI: 1.48-5.58) but not in its absence (aOR = 1.32; 95%CI: 0.61-2.84). The p-value for the interaction term between clinical-ASPECTS mismatch and late endovascular treatment was 0.073.
CONCLUSIONS
In our retrospective two-site analysis, late endovascular treatment seemed effective in the presence of a clinical-ASPECTS mismatch, but not in its absence. If confirmed in randomized trials, this finding could support the use of an ASPECTS-based selection for late endovascular treatment decisions, obviating the need for advanced imaging. | 10.1177/17474930211009806 |
others_40_13404 | The native pasture legume, Glycine latifolia, growing in experimental plots in south-east Queensland sometimes showed a yellow mosaic symptom, which was associated with a sap-transmissible virus identified as alfalfa mosaic virus. Inoculation with the virus reproduced the yellow mosaic disease in three lines of G. latifolia, but two other lines showed resistance in both inoculation tests and the fiel | 10.1071/AP97017 |
pubmed_854_13156 | We report here development of a rapid, homogeneous, aptamer-based fluorescence assay ("molecular beacons") for detecting proteins. The assay involves protein-induced coassociation of two aptamers recognizing two distinct epitopes of the protein. The aptamers contain short fluorophore-labeled complementary "signaling" oligonucleotides attached to the aptamer by non-DNA linker. Coassociation of the two aptamers with the protein results in bringing the two "signaling" oligonucleotides into proximity, producing a large change of fluorescence resonance energy transfer between the fluorophores. We used thrombin as a model system to provide proof-of-principle evidence validating this molecular beacon design. Thrombin beacon was capable of detecting the protein with high selectivity (also in complex biological mixtures), picomolar sensitivity, and high signal-to-background ratio. This is a homogeneous assay requiring no sample manipulation. Since the design of molecular beacons described here is not limited to any specific protein, it will be possible to develop these beacons to detect a variety of target proteins of biomedical importance. | 10.1021/ac0487449 |
pubmed_450_1945 | HIV-1 exhibits a characteristically high genetic diversity, with the M group, responsible for the pandemic, being classified into nine subtypes, 72 circulating recombinant forms (CRFs) and numerous unique recombinant forms (URFs). Here we characterize the near full-length genome sequence of an HIV-1 BG intersubtype recombinant virus (X3208) collected in Galicia (Northwest Spain) which exhibits a mosaic structure coincident with that of a previously characterized BG recombinant virus (9601_01), collected in Germany and epidemiologically linked to Portugal, and different from currently defined CRFs. Similar recombination patterns were found in partial genome sequences from three other BG recombinant viruses, one newly derived, from a virus collected in Spain, and two retrieved from databases, collected in France and Portugal, respectively. Breakpoint coincidence and clustering in phylogenetic trees of these epidemiologically-unlinked viruses allow to define a new HIV-1 CRF (CRF73_BG). CRF73_BG shares one breakpoint in the envelope with CRF14_BG, which circulates in Portugal and Spain, and groups with it in a subtype B envelope fragment, but the greatest part of its genome does not appear to derive from CRF14_BG, although both CRFs share as parental strain the subtype G variant circulating in the Iberian Peninsula. Phylogenetic clustering of partial pol and env segments from viruses collected in Portugal and Spain with X3208 and 9691_01 indicates that CRF73_BG is circulating in both countries, with proportions of around 2-3% Portuguese database HIV-1 isolates clustering with CRF73_BG. The fact that an HIV-1 recombinant virus characterized ten years ago as a URF has been shown to represent a CRF suggests that the number of HIV-1 CRFs may be much greater than currently known. | 10.1371/journal.pone.0148549 |
pubmed_315_16811 | In this paper we describe the feeding habits of the Red snapper (Lutjanus peru) in the southern coast of Guerrero state, Mexico. This data could be relevant to local fisheries management. In total 385 full stomachs (206 from females and 179 from males) were collected monthly in 1993 and 1994, from commercial catches. Stomach contents were identified to species level when possible. Food items were grouped into taxonomically coherent groups, and their numbers, weight and frequency of occurrence obtained. The index of relative importance (IRI) was calculated for the total sample, by month, sex and size class. In 1993, a total of 42 different food items were obtained, and 43 in 1994. Food items consisted of fishes, crustaceans, and mollusks. The grouping of prey species, genera, or families rendered 14 food groups, as follows: Mollusks, Amphipods, Copepods, Stomatopods, Penaeus vannamei, Brachiuran Larvae, Stomatopods Larvae, Family Albuneidae Larvae, Other crustaceans, Anchoa ischana, Anchoa lucida, Other fishes, Salps and Unidentified organic matter. Anchoa ischana dominated the trophic spectrum in both years. Although, Amphipods, Anchoa lucida and Other fishes had important indexes in 1994. There was high variability in the diet composition by month. Nevertheless, in 1993, from February to August, crustaceans as a whole dominated the diet. In 1994, crustaceans only dominated in March and August. No differences in food habits were found between immature fish, males and females. The diet of the Red snapper varies as they grow, although the same food groups are found always. At the adult phase, in length classes over 261 mm FL, there is some degree of specialization, as they consume more fish, particularly engraulids. | pubmed_315_16811 |
pubmed_32_8481 | The use of various pulsed-field electrophoresis methodologies under different conditions allowed us to determine the Leishmania infantum karyotype. A total of 25 chromosomal bands ranging in size from 375 to 3300 kb were resolved amounting to a minimum genomic DNA mass of about 2.6 x 10(7) pb. By molecular hybridization and on the basis of the karyotype, specific gene sequences could be assigned to particular chromosomes. A bias in the chromosomal distribution of different markers was found since 9 out of the 12 analysed gene markers hybridize with chromosomal bands XIXa and XIXb. We infer that chromosomal bands XIXa and XIXb, differing in about 30 kb, could be representing a pair of homologous chromosomes and that another pair of homologs may be also defined by chromosomal bands XVII and XVIII. | 10.1016/0378-1097(95)00129-S |
pubmed_881_17799 | The requirements for inducing downregulation of alpha/beta T cell receptor (TCR) molecules on naive major histocompatibility complex class I-restricted T cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression on the responder cells and was heavily dependent upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). These stringent requirements did not apply to TCR downregulation. Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides. TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation. In marked contrast to T cell activation, TCR downregulation was resistant to various metabolic inhibitors. The biological significance of TCR downregulation is unclear, but could be a device for protecting T cells against excessive signaling. | 10.1084/jem.185.4.641 |
pubmed_161_14222 | The MEMOLOG 500 system is a very simple instrument for the data-recording of various physiological or physical parameters. It is a very light (370 g), two-channel instrument which allows the storing in its memory of 512 values for each of two parameters. The data are then extracted and processed by a preprogrammed microcomputer, the MEMOSCAN 510 system. An example of application is illustrated. | pubmed_161_14222 |
pubmed_713_1817 | Deafness is one of the most common sensory disorders found in humans; notably, >60% of all cases of deafness have been attributed to genetic factors. Variants in potassium voltage‑gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to a type of progressive hearing loss, deafness non‑syndromic autosomal dominant 2A (DFNA2A). In the present study, whole‑exome sequencing (WES) was performed on three members of a five‑generation Chinese family with 46 members with hearing loss. Pure tone audiometry and Sanger sequencing were performed for 11 family members to determine whether the novel variant in the KCNQ4 gene was segregated with the affected family members. In addition, evolutionary conservation analysis and computational tertiary structure protein prediction of the wild‑type KCNQ4 protein and its variant were performed. The family exhibited autosomal dominant, progressive, post‑lingual, non‑syndromic sensorineural hearing loss. A novel co‑segregating heterozygous missense variant (c.857A>G; p.Tyr286Cys) in the glycine‑tyrosine‑glycine signature sequence in the pore region of the KCNQ4 channel was identified. This variant was predicted to result in a tyrosine‑to‑cysteine substitution at position 286 in the KCNQ4 protein. The tyrosine at position 286 is well conserved across different species. The substitution of tyrosine with cysteine would affect the structure of the pore region, resulting in the loss of channel function. The KCNQ4 gene is one of the most common mutated genes observed in patients with autosomal dominant, non‑syndromic hearing loss. Taken together, for the family analyzed in the present study, performing WES in conjunction with Sanger sequencing has led to the detection of a novel, potentially causative variant (c.857 A>G; p.Tyr286Cys) in exon 6 of the KCNQ4 gene. The present study has added to the number of pathogenic variants observed in the KCNQ4 gene, and the findings may prove to be useful for both the diagnosis of DFNA2A and in the design of early interventional therapies. | pubmed_713_1817 |
pubmed_602_743 | Invertebrate pathologists have multiple definitions for the terms pathogenicity and virulence, and these definitions vary across disciplines that focus on host-pathogen interactions. We surveyed various literatures, including plant pathology, invertebrate pathology, evolutionary biology, and medicine, and found most define pathogenicity as the broader term, which incorporates virulence. Virulence is seen as the severity of disease manifestation that can only be measured in infected individuals. These definitions readily apply to both lethal and non-lethal diseases. Invertebrate pathologists commonly use dose-response bioassays to estimate LD(50) or LC(50) (dose or concentration needed to kill 50% of hosts exposed). These bioassays measure pathogenicity if the bioassay includes a transmission component, and measure virulence if the bioassay is measured in infected individuals only. Another common bioassay estimate is LT(50) (median time to death of infected hosts), which is a measure of virulence as long as survivors are not included in its calculation. | 10.1016/j.jip.2004.01.006 |
pubmed_293_23253 | Earthquakes are one of the most devastating natural disasters that plague society. Skilled, reliable earthquake forecasting remains the ultimate goal for seismologists. Using the detrended fluctuation analysis (DFA) and conditional probability (CP) methods, we find that memory exists not only in interoccurrence seismic records but also in released energy as well as in the series of the number of events per unit time. Analysis of a standard epidemic-type aftershock sequences (ETAS) earthquake model indicates that the empirically observed earthquake memory can be reproduced only for a narrow range of the model's parameters. This finding therefore provides tight constraints on the model's parameters and can serve as a testbed for existing earthquake forecasting models. Furthermore, we show that by implementing DFA and CP results, the ETAS model can significantly improve the short-term forecasting rate for the real (Italian) earthquake catalog. | 10.1103/PhysRevE.99.042210 |
pubmed_442_22867 | A simple and feasible electrochemical sensing protocol was developed for the detection of bisphenol A (BPA) by employing the gold nanoparticles (AuNPs), prussian blue (PB) and functionalized carbon nanotubes (AuNPs/PB/CNTs-COOH). An aminated complementary DNA as a capture probe and specific aptamer against BPA as a detection probe was immobilized on the surface of a modified glassy carbon (GC) electrode via the formation of covalent amide bond and hybridization, respectively. The proposed nanoaptasensor combined the advantages of the in situ formation of PB as a label, the deposition of neatly arranged AuNPs, and the covalent attachment of the capture probe to the surface of the modified electrode. Upon addition of target BPA, the analyte reacted with the aptamer and caused the steric/conformational restrictions on the sensing interface. The formation of BPA-aptamer complex at the electrode surface retarded the interfacial electron transfer reaction of the PB as a probe. Sensitive quantitative detection of BPA was carried out based on the variation of electron transfer resistance which relevant to the formation of BPA- aptamer complex at the modified electrode surface. Under the optimized conditions, the proposed aptasensor exhibited a high sensitivity, wide linearity to BPA and low detection limit. This aptasensor also displayed a satisfying electrochemical performance with good stability, selectivity and reproducibility. | 10.1016/j.ab.2016.08.006 |
pubmed_730_21146 | To investigate the role of the central cholinergic system in the regulation of metabolism during exercise, we injected atropine (5 x 10(-7) mol) into the lateral cerebral ventricle of normal and adrenodemedullated (ADM) untrained rats submitted to exercise on a treadmill (15 m min(-1), 5% grade) until exhaustion. Concentrations of blood glucose, plasma free fatty acids (FFA), and lactate were measured before and every 10 min after the start of exercise for a period of 60 min. Adrenomedullectomy had no effect on the maximal capacity of exercise (MCE), but atropine administered intracerebroventricularly (i.c.v.) reduced the maximal capacity of exercise of both normal and ADM rats. In normal rats, blood concentrations of glucose and plasma free fatty acids remained essentially unchanged compared to the levels at rest, whereas in ADM rats a rapid increase in plasma glucose and plasma free fatty acids levels occurred during exercise. These data indicate that adrenomedullectomy disrupted the accuracy of the feedback mechanism that regulates the mobilization of extramuscular fuels during exercise in normal rats. In addition, ADM rats showed an increased lipid mobilization as a source of energy during exercise, which might explain the increased plasma glucose by an inhibition of muscle glucose uptake. These results suggest that central cholinergic neurons might be involved in the control of energy substrate adjustment during exercise, thereby reducing the maximal capacity of exercise. In addition, the results of this study suggest that the adrenal glands are important for an accurate feedback mechanism during exercise. | 10.1016/s0031-9384(98)00024-9 |
pubmed_203_3309 | Bacterial contaminants of Vhuswa--a traditional maize-based weaning food, and domestic drinking-water stored in impoverished rural households in Venda of Limpopo province, South Africa, were determined. One hundred and twenty-five samples of Vhuswa fed to children aged less than five years were assessed for Escherichia coli, Campylobacter jejuni, Salmonella, and Shigella. The microbiological quality of 125 drinking-water samples was also evaluated using total coliforms, faecal coliforms, and faecal streptococci as indicators. The frequency of isolation of E. coli, Salmonella, Shigella, and C. jejuni from the Vhuswa samples was 70%, 5%, 5%, and 2% respectively. The geometric mean counts of total coliforms, faecal coliforms, and faecal streptococci in tap-water stored in household containers ranged from 4.9x10(2) to 5.8x10(3) cfu 100 mL(-1), 2.6x10(2) to 3.7x10(3) cfu 100 mL(-1), and 3.1x10(3) to 5.8x10(3) cfu 100 mL(-1) respectively, and for stored spring water it was 5.1x10(3) cfu 100 mL(-1), 3.2x10(3) cfu 100 mL(-1), and 5.1x10(3) cfu 100 mL(-1) respectively. The frequent contamination of water and food samples in this study has important implications for the health of children from impoverished communities. | pubmed_203_3309 |
pubmed_16_10928 | Revised criteria for the antiphospholipid syndrome were published in 2006. Major changes from the 1999 criteria are an increase in the time between two laboratory studies required for diagnosis from 6 to 12 weeks, the acceptance of antibody to beta2 glycoprotein I as a criterion, the exclusion of older age persons, and the acknowledgment of several associated findings such as livedo, heart valve disease, and antibody to prothrombin. New concepts of pathogenesis now invoke complement activation and participation of the innate immune system upstream to thrombosis. Warfarin remains the treatment of choice for patients who have suffered thrombosis, but antiplatelet agents and heparin are options. Target INR is 2.0-3.0. Treatment is potentially life-long, though options for withdrawal of treatment are under investigation. | pubmed_16_10928 |
pubmed_298_10246 | Sleep and health are closely interrelated and sleep quality is a well-known contributor to perceived health. However, effects of sleep-timing preference i.e. morningness-eveningness on health has yet to be revealed. In this study, we explored the relationship between morningness-eveningness and perceived health in a sample of female working professionals (N = 202). Sleep-timing preference was measured using the Composite Scale of Morningness. Perceived health was characterized by Center for Epidemiologic Studies Depression Scale, WHO Well-Being Scale-5 and Patient Health Questionnaire-15 scores. We also investigated possible mechanisms, including stress and health-impairing behaviours. In accordance with previous data, we found more depressive mood, lower well-being and poorer perceived health among evening types. To assess health-impairing behaviours we collected data on smoking habits, alcohol consumption, physical activity and diet. Among the possible mechanism variables, greater stress, less frequent physical activity and less healthy diet were associated with eveningness. Furthermore, stress diminished the strength of the association between morningness-eveningness and depressed mood. Physical activity attenuated the strength of the association between morningness-eveningness and well-being. No effects of alcohol consumption could be identified. Our data show that evening preference behaves as a health risk in terms of associating with poor perceived health. Our findings also suggest that this effect might be mediated by health behaviours and stress. | 10.3109/07420528.2014.911188 |
pubmed_547_22523 | Alpha-picolinic acid (PA), a metabolite of tryptophan and an inducer of apoptosis in the animal cell, has been reported to be a toxin produced by some of plant fungal pathogens and used in screening for disease resistant mutants. Here, we report that PA is an efficient apoptosis agent triggering cell death of hypersensitive-like response in planta. Confirmed by Fluorescence Activated Cell Sorter (FACS), rice suspension cells and leaves exhibited programmed cell death induced by PA. The PA-induced cell death was associated with the accumulation of reactive oxygen species that could be blocked by diphenylene iodonium chloride, indicating that the generation of reactive oxygen species was NADPH-oxidase dependent. We also demonstrated the induction of rice defense-related genes and subsequent resistant enhancement by PA against the rice blast fungus Magnaporthe grisea. Hence, it was concluded that the PA-stimulated defense response likely involves the onset of the hypersensitive response in rice, which also provides a simple eliciting tool for studying apoptosis in the plant cell. | 10.1038/sj.cr.7290199 |
pubmed_437_521 | BACKGROUND
Fixed-dose combinations of artemisinin combination therapy are strongly recommended to facilitate drug administration and compliance. New fixed-dose combinations must nevertheless be evaluated in relevant populations in terms of efficacy and pharmacokinetics.
METHODS
A single-arm, open-label, clinical trial was performed in Indian patients with acute uncomplicated Plasmodium falciparum malaria to investigate the efficacy and the pharmacokinetics of mefloquine when combined with artesunate in a fixed-dose combination (400/200 mg of mefloquine base/artesunate). The pharmacokinetic analysis was performed using a population approach.
RESULTS
Seventy-seven patients were included in the study. Mefloquine pharmacokinetics obeys a two-compartment model with first-order absorption and elimination. Mean parameter estimates (% inter-individual variability) were as follows: 0.16 h(-1) (75%) for the absorption rate constant, 1.13 L/h (30%) for the apparent plasma clearance, 271 L (21%) for the apparent central distribution volume, 344 L (54%) for the apparent peripheral distribution volume, and 1.43 L/h for the apparent distribution clearance. These values were consistent with the pharmacokinetic results described in Thai patients. No significant covariate was found for clearance. Body weight explained the inter-individual variability of the apparent central and peripheral distribution volumes. The PCR-adjusted efficacy of the treatment was 100%.
CONCLUSIONS
The lack of significant covariate explaining the inter-individual variability of mefloquine clearance, combined with the excellent efficacy, supports the use of the standard 200/400 mg of artesunate-mefloquine fixed-dose combination in Indian patients with uncomplicated P. falciparum malaria.
TRIAL REGISTRATION
CLINICAL TRIAL REGISTRATION
ISRCTN70618692. | 10.1186/1475-2875-13-187 |
pubmed_13_7179 | A benchmark study by Boileau et al tested 6 commonly used numerical schemes for 1D wave propagation, for their ability to capture the main features of pressure, flow, and area waveforms in large arteries. While all numerical schemes showed good agreement in pressure and flow waveforms for smaller arterial networks, the simplified trapezium rule method proposed by Kroon et al showed an overestimation for the systolic pressure of 1% in proximal regions and an underestimation of 3% in distal regions in comparison with the 5 other schemes when using a larger arterial network, published as the ADAN56 model. The authors attributed this difference to the neglection of the dynamic part of the pressure at vessel junctions. Carson et al resolved these differences by proposing 2 methods to implement the dynamic part of the pressure in the simplified trapezium rule method scheme. In the present study, an alternative method is introduced extending the work by Kroon et al. This alternative method consists of a new 0D element, which is placed at vessel junctions. The strength of this new element is the ease of implementation and its flexible coupling with other elements, without introducing additional degrees of freedom or the need of a penalty function. This new approach is compared with 5 other numerical schemes, which already have the dynamic part of the pressure incorporated. The new method shows excellent agreement with these schemes for the ADAN56 model. | 10.1002/cnm.3116 |
pubmed_1117_2446 | The growth and differentiation of B cells to immunoglobulin (Ig)-secreting cells is regulated by a variety of soluble factors. This study presents data that support a role for transforming growth factor (TGF)-beta in this regulatory process. B lymphocytes were shown to have high-affinity receptors for TGF-beta that were increased fivefold to sixfold after in vitro activation. The addition of picogram quantities of TGF-beta to B cell cultures suppressed factor-dependent, interleukin 2 (IL 2) B cell proliferation and markedly suppressed factor-dependent (IL 2 or B cell differentiation factor) B cell Ig secretion. In contrast, the constitutive IgG production by an Epstein Barr virus-transformed B cell line was not modified by the presence of TGF-beta in culture. This cell line was found to lack high-affinity TGF-beta receptors. The degree of inhibition of B cell proliferation observed in in vitro cultures was found to be dependent not only on the concentration of TGF-beta added but also on the concentration of the growth stimulatory substance (IL 2) present. By increasing the IL 2 concentrations in culture, the inhibition of proliferation induced by TGF-beta could be partially overcome. In contrast, the inhibition of Ig secretion induced by TGF-beta could not be overcome by a higher concentration of stimulatory factor, demonstrating that the suppression of B cell differentiation by TGF-beta is not due solely to its effects on proliferation. Furthermore, it was demonstrated that B lymphocytes secrete TGF-beta. Unactivated tonsillar B cells had detectable amounts of TGF-beta mRNA on Northern blot analysis, and B cell activation with Staphylococcus aureus Cowan (SAC) resulted in a twofold to threefold increase in TGF-beta mRNA. Supernatants conditioned by unactivated B cells had small amounts of TGF-beta, SAC activation of the B cells resulted in a sixfold to sevenfold increase in the amount of TGF-beta present in the supernatants. Thus, B lymphocytes synthesize and secrete TGF-beta and express receptors for TGF-beta. The addition of exogenous TGF-beta to cultures of stimulated B cells inhibits subsequent proliferation and Ig secretion. TGF-beta may function as an autocrine growth inhibitor that limits B lymphocyte proliferation and ultimate differentiation. | pubmed_1117_2446 |
pubmed_839_16404 | Reproductive toxicity testing of drugs is performed as a 2- or 3-segment package. The choice of species for routine studies with small molecule drugs is essentially limited to the rat, rabbit, mouse and minipig. The lack of alternative species is a threat to the successful screening of drugs for teratogenicity. A proposed revision of the ICH M3 guideline addresses contradictions concerning the timing of the various reproductive and juvenile studies. This M3 draft, however, raises questions concerning the confidence that can be attributed to preliminary embryotoxicity studies with as few as six females per group. The detection of reproductive hazards could be improved by implementing methods in routine use for the testing of chemicals, such as double staining of fetuses and primordial follicle counts. Modern imaging techniques hold promise for application in the morphological examination of fetuses. An assessment of developmental immunotoxicity should be included in any future revision of the reproductive toxicity guidelines. | 10.1016/j.reprotox.2009.03.013 |
pubmed_411_13962 | BACKGROUND
The COVID-19 pandemic response is affecting maternal and neonatal health services all over the world. We aimed to assess the number of institutional births, their outcomes (institutional stillbirth and neonatal mortality rate), and quality of intrapartum care before and during the national COVID-19 lockdown in Nepal.
METHODS
In this prospective observational study, we collected participant-level data for pregnant women enrolled in the SUSTAIN and REFINE studies between Jan 1 and May 30, 2020, from nine hospitals in Nepal. This period included 12·5 weeks before the national lockdown and 9·5 weeks during the lockdown. Women were eligible for inclusion if they had a gestational age of 22 weeks or more, a fetal heart sound at time of admission, and consented to inclusion. Women who had multiple births and their babies were excluded. We collected information on demographic and obstetric characteristics via extraction from case notes and health worker performance via direct observation by independent clinical researchers. We used regression analyses to assess changes in the number of institutional births, quality of care, and mortality before lockdown versus during lockdown.
FINDINGS
Of 22 907 eligible women, 21 763 women were enrolled and 20 354 gave birth, and health worker performance was recorded for 10 543 births. From the beginning to the end of the study period, the mean weekly number of births decreased from 1261·1 births (SE 66·1) before lockdown to 651·4 births (49·9) during lockdown-a reduction of 52·4%. The institutional stillbirth rate increased from 14 per 1000 total births before lockdown to 21 per 1000 total births during lockdown (p=0·0002), and institutional neonatal mortality increased from 13 per 1000 livebirths to 40 per 1000 livebirths (p=0·0022). In terms of quality of care, intrapartum fetal heart rate monitoring decreased by 13·4% (-15·4 to -11·3; p<0·0001), and breastfeeding within 1 h of birth decreased by 3·5% (-4·6 to -2·6; p=0·0032). The immediate newborn care practice of placing the baby skin-to-skin with their mother increased by 13·2% (12·1 to 14·5; p<0·0001), and health workers' hand hygiene practices during childbirth increased by 12·9% (11·8 to 13·9) during lockdown (p<0·0001).
INTERPRETATION
Institutional childbirth reduced by more than half during lockdown, with increases in institutional stillbirth rate and neonatal mortality, and decreases in quality of care. Some behaviours improved, notably hand hygiene and keeping the baby skin-to-skin with their mother. An urgent need exists to protect access to high quality intrapartum care and prevent excess deaths for the most vulnerable health system users during this pandemic period.
FUNDING
Grand Challenges Canada. | 10.1016/S2214-109X(20)30345-4 |
pubmed_809_10289 | PURPOSE
Dislocation of pectus bars after minimal invasive repair of pectus excavatum has been reduced by use of bar stabilizers. However, during bar removal, intense bone formation around the pectus bar and bar stabilizer makes it difficult to detach them from one another. A tool was designed to facilitate the detachment of the bar stabilizer from the pectus bar.
DESCRIPTION
The Bar Stabilizer Anvil (Walter Lorenz Surgical Inc, Jacksonville, FL) is a stainless steel tool placed directly on the bar stabilizer during surgery. Using a simple tapping action with a hammer on the tool, the bar stabilizer slides and detaches from the pectus bar.
EVALUATION
The first developed prototype was used in 5 patients during bar removal, but had to be redesigned with slight modifications. The second redesigned prototype of the bar stabilizer tool could be optimally inserted at the surgical site and enabled the detachments of the bar stabilizer with ease when employed in the second series of 5 patients.
CONCLUSIONS
The Bar Stabilizer Anvil is a useful tool for the detachment of the stabilizer plate from the pectus bar after minimal invasive repair of pectus excavatum. | 10.1016/j.athoracsur.2007.04.014 |
pubmed_46_19806 | To investigate possible cell kinetic relations between benign prostatic hyperplasia (BPH), atypical adenomatous hyperplasia (AAH), prostatic intraepithelial neoplasia (PIN) and carcinoma, cell kinetic analyses were performed using radiolabelled DNA-precursors (3H-thymidine autoradiography), immunohistochemistry (proliferation marker Ki67/MIB1 and/or PCNA) and silver staining of nucleolar organizer regions (AgNOR). All methods yielded the lowest values for BPH and AAH, while maximal values were found in carcinoma of high malignancy. PIN was equal to GII-carcinomas, while AAH was between BPH and carcinoma of low malignancy. This investigation ranks BPH, AAH, low grade carcinoma, PIN and high grade carcinoma in order using different methods of cell kinetic analysis. The preneoplastic character of PIN is apparent whereas the character of AAH remains uncertain. | 10.1016/S0344-0338(11)80975-1 |
pubmed_339_10336 | Gerontology research is now of high concern, particularly to the media, and a risk could exist that gerontologists may give people false hopes or premature conclusions. This article describes two examples: the hypothesis that median longevity will be 150 years in 2100, and the recent results on telomerase. It is concluded that it is prudent for gerontologists to maintain a cautious attitude with the media. | 10.1023/a:1010021302608 |
pubmed_516_21996 | In the course of the synthesis of gamma-pyrones, well-known inhibitors of photosystem II electron transport, it turned out that the starting material, acyl derivatives of 2,2-dimethyl-1,3-dioxane-5,6-dione (Meldrum's acid) are potent inhibitors of photosystem II electron transport. Thus, in a simple one-step synthesis from commercial available substances, highly potent photosystem II inhibitors are generated. The biological activity of the acyl derivatives is in a parabolic fashion dependent from the length of the alkyl side chain. | 10.1016/j.bbabio.2006.05.009 |
pubmed_191_22119 | The application of zona pellucida proteins for contraception of wildlife and feral animals, including stray cats, has been promoted since it was demonstrated to be effective for free-roaming feral mares. Active immunization with zona pellucida proteins leads to either reversible or irreversible infertility. Therefore, knowledge of the timing and location of zona pellucida synthesis during oogenesis in cats is a key aspect of designing an immunocontraceptive for felids. Domestic cat ovaries obtained after ovariohysterectomy were used to produce a specific rabbit antibody against feline zonae pellucidae. Ultrathin sections (70 nm) of cat ovaries were treated with the anti-zona antibody followed by incubation with gold-labelled anti-rabbit IgG for ultrastructural investigation. The gold label was related to the ultrastructure of oocytes and granulosa cells. Cat follicles at different stages of development were examined. The antibody reacted very specifically with zona pellucida proteins in fully grown oocytes with a compact zona pellucida. In secondary follicles, gold labels were found on the zona pellucida and inside granulosa cells in the vicinity of oocytes. Primary follicles were labelled inside their cubic granulosa cells and on fragments of zona pellucida in the cleft between granulosa cells and the oocyte. Some primordial follicles were characterized by labelling of the granulosa cells. In conclusion, these results indicate that cat zona pellucida is produced exclusively by granulosa cells and not by oocytes. Synthesis of zona pellucida takes place at every stage of follicular development. | pubmed_191_22119 |
pubmed_18_12354 | As the key neuron-to-neuron interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. However, the signal transduction mechanisms by which stress mediates its lasting effects on synapse transmission and on memory are not fully understood. A key component of the stress response is the increased secretion of adrenal steroids. Adrenal steroids (e.g., cortisol) bind to genomic mineralocorticoid and glucocorticoid receptors (gMRs and gGRs) in the cytosol. In addition, they may act through membrane receptors (mMRs and mGRs), and signal transduction through these receptors may allow for rapid modulation of synaptic transmission as well as modulation of membrane ion currents. mMRs increase synaptic and neuronal excitability; mechanisms include the facilitation of glutamate release through extracellular signal-regulated kinase signal transduction. In contrast, mGRs decrease synaptic and neuronal excitability by reducing calcium currents through N-methyl-D-aspartate receptors and voltage-gated calcium channels by way of protein kinase A- and G protein-dependent mechanisms. This body of functional data complements anatomical evidence localizing GRs to the postsynaptic membrane. Finally, accumulating data also suggest the possibility that mMRs and mGRs may show an inverted U-shaped dose response, whereby glutamatergic synaptic transmission is increased by low doses of corticosterone acting at mMRs and decreased by higher doses acting at mGRs. Thus, synaptic transmission is regulated by mMRs and mGRs, and part of the stress signaling response is a direct and bidirectional modulation of the synapse itself by adrenal steroids. | 10.1126/scisignal.286re5 |
pubmed_968_24839 | Human motion intention detection is an essential part of the control of upper-body exoskeletons. While surface electromyography (sEMG)-based systems may be able to provide anticipatory control, they typically require exact placement of the electrodes on the muscle bodies which limits the practical use and donning of the technology. In this study, we propose a novel physical interface for exoskeletons with integrated sEMG- and pressure sensors. The sensors are 3D-printed with flexible, conductive materials and allow multi-modal information to be obtained during operation. A K-Nearest Neighbours classifier is implemented in an off-line manner to detect reaching movements and lifting tasks that represent daily activities of industrial workers. The performance of the classifier is validated through repeated experiments and compared to a unimodal EMG-based classifier. The results indicate that excellent prediction performance can be obtained, even with a minimal amount of sEMG electrodes and without specific placement of the electrode. | 10.3389/fnbot.2021.693110 |
pubmed_1042_17764 | Regulation of mitosis secures cellular integrity and its failure critically contributes to the development, maintenance, and treatment resistance of cancer. In yeast, the dual phosphatase Cdc14 controls mitotic progression by antagonizing Cdk1-mediated protein phosphorylation. By contrast, specific mitotic functions of the mammalian Cdc14 orthologue CDC14B have remained largely elusive. Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. We further demonstrate that WT1 functions as a mitotic transcription factor and specify CXCL8/IL-8 as a target gene of WT1 that conveys mitotic survival. Together, we describe a ubiquitin-dependent signaling pathway that directs a mitosis-specific transcription program to regulate mitotic survival. | 10.1038/s41467-020-15059-5 |
pubmed_250_7946 | Evolution is an essential concept for anyone who considers science to be the best way to understand the natural world. It is as fully established as any scientific principle can be and is the great unifying theme in all of biology, as integral to understanding life-forms as gravity is to understanding the cosmos. On the bicentennial of the birth of Charles Darwin in 1809, and 150 years after the publication of On the Origin of Species by Means of Natural Selection in 1859, we should remember the main features of eye evolution and the prominent place the eye holds in the development and refinement of evolutionary theory. A few highlights include the antiquity of rhodopsin, the ready capacity of an eye to evolve, the effect of eyes on the diversification of life-forms, and the promising influence of genetics on developmental and evolutionary biology. | 10.1001/archopht.126.11.1586 |
pubmed_673_9852 | How great the risk is that important and long-lasting psychic disturbances persist after sterilization cannot be forecast with certainty, even today. Increased susceptibility to abnormal psychic reactions and developments after sterilization is to be contemplated with certain personalities with overconscientious, asthenic or depressive traits. It is usually a matter of internal conflict situations at the level of self-esteem which, however, depend not only on the initial personality, but to a large extent are repeatedly reactualized through the behavior and reaction of the persons in the environment, so that finally mental developments arise which reach into the abnormal. This risk must be included in the calculation when making the indication and requires particular attention, because the legal effectiveness of the consent to sterilization is also dependent on the completeness of the advice on the consequences of this surgical operation. | pubmed_673_9852 |
others_201_2457 | Despite higher rates of SARS-CoV-2 infections and mortality, vaccine uptake in Black and Latinx populations remained disproportionately low, including in the Bronx, New York. In response, we used the Bridging Research, Accurate Information, and Dialogue (BRAID) model to elicit community members’ COViD-19 vaccine-related perspectives and informational needs and inform strategies to improve vaccine acceptance. We conducted a longitudinal qualitative study over 13 months (May 2021-June 2022), with 25 community experts from the Bronx including community health workers, and representatives from community-based organizations. Each expert participated in 1–5 of the 12 conversation circles conducted via Zoom. Clinicians and scientists, attended circles to provide additional information in content areas identified by the experts. Inductive thematic analysis was used to analyze the conversations. Five overarching themes, related to trust, emerged: (1) disparate and unjust treatment from institutions; (2) the impact of rapidly changing COVID messages in the lay press (a different story every day); (3) influencers of vaccine intention; (4) strategies to build community trust; and (5) what matters to community experts [us]. Our findings highlighted the influence of factors, such as health communication, on trust (or lack thereof) and vaccine intention. They also reinforce that creating safe spaces for dialogue and listening and responding to community concerns in real time are effective trust-building strategies. The BRAID model fostered open discussion about the factors that influence vaccine uptake and empowered participants to share accurate information with their community. Our experience suggests that the model can be adapted to address many public health issues. © 2023 The Authors | 10.1016/j.pmedr.2023.102253 |
pubmed_459_6402 | The aim of the study was to determine the fibre size distribution within the human m tibialis anterior. Ten-micron thick cross-sections of the whole muscle were enzyme histochemically stained for myofibrillar ATPase at pH 9.4. The cross-sectional area of 100 fibres with low (type 1) ATPase and high (type 2) ATPase activity was measured in three different regions (superficial, central and deep). Both the type 1 and type 2 fibres were found to be larger in the deep region than in the central or superficial regions. The variation in fibre size could not be explained by the cryofixation or cryo-embedding techniques used. The data suggest that muscle adaptation to physical demands may not only occur by means of variation in types and number of muscle fibres, but also by variation in fibre size over the muscle cross-section. | 10.1111/j.1748-1716.1985.tb07583.x |
pubmed_898_11981 | Epilepsy, characterized by recurrent seizures, affects 1% of the general population. Interestingly, 25% of diabetics develop seizures with a yet unknown mechanism. Hyperglycemia downregulates inwardly rectifying potassium channel 4.1 (Kir4.1) in cultured astrocytes. Therefore, the present study aims to determine if downregulation of functional astrocytic Kir4.1 channels occurs in brains of type 2 diabetic mice and could influence hippocampal neuronal hyperexcitability. Using whole-cell patch clamp recording in hippocampal brain slices from male mice, we determined the electrophysiological properties of stratum radiatum astrocytes and CA1 pyramidal neurons. In diabetic mice, astrocytic Kir4.1 channels were functionally downregulated as evidenced by multiple characteristics including depolarized membrane potential, reduced barium-sensitive Kir currents and impaired potassium uptake capabilities of hippocampal astrocytes. Furthermore, CA1 pyramidal neurons from diabetic mice displayed increased spontaneous activity: action potential frequency was ≈9 times higher in diabetic compared with non-diabetic mice and small EPSC event frequency was significantly higher in CA1 pyramidal cells of diabetics compared to non-diabetics. These differences were apparent in control conditions and largely pronounced in response to the pro-convulsant 4-aminopyridine. Our data suggest that astrocytic dysfunction due to downregulation of Kir4.1 channels may increase seizure susceptibility by impairing astrocytic ability to maintain proper extracellular homeostasis. | 10.3390/brainsci10020072 |
pubmed_362_23373 | BACKGROUND
Cervical artificial insemination (AI) with frozen-thawed semen results in unacceptably low pregnancy rates internationally. The exception is in Norway, where vaginal deposition of frozen-thawed semen to a natural oestrous routinely yields pregnancy rates in excess of 70%. Previous studies by our group has demonstrated that this is due to differences in cervical sperm transport. However, a potentially important contributory factor is that ewes are inseminated to a natural oestrous in Norway but to a synchronised oestrous across most of the rest of the world. In this study, we interrogated the gene expression of the sheep cervix of four ewe breeds with known differences in pregnancy rates following cervical AI using frozen-thawed semen under the effect of exogenous hormones to synchronise the oestrous cycle. These four ewe breeds (n = 8 to 11 ewes per breed) are from two countries: Ireland (Belclare and Suffolk; medium and low fertility, respectively) and Norway (Norwegian White Sheep (NWS) and Fur; both with high fertility compared to the Irish ewe breeds).
RESULTS
RNA extracted from cervical biopsies collected from these breeds was analysed by RNA-sequencing and differential gene expression analysis. Using the low-fertility Suffolk breed as a reference level; 27, 1827 and 2641 genes were differentially expressed in Belclare, Fur and NWS ewes, respectively (P < 0.05 and FC > 1.5). Gene ontology (GO) analysis revealed that Fur and NWS had an up-regulation of enriched pathways involved in muscle contraction and development compared to Suffolk. However, there was a down-regulation of the immune response pathway in NWS compared to Suffolk. In addition, GO analysis showed similar expression patterns involved in muscle contraction, extracellular matrix (ECM) development and cell-cell junction in both Norwegian ewe breeds, which differed to the Irish ewe breeds.
CONCLUSIONS
This novel study has identified a number of conserved and breed-specific biological processes under the effect of oestrous synchronisation that may impact cervical sperm transport during the follicular phase of the reproductive cycle. | 10.1186/s12864-022-08603-8 |
pubmed_399_414 | Using the cannula inserting method, effects of cooling (from 37 degrees C to 27 degrees C) on norepinephrine (NE)- and KCI-induced vasoconstrictions were investigated in isolated, perfused simian and canine femoral arteries and veins. KCI-induced constrictions were much greater in simian vessels than in canine vessels. NE-induced constrictions were similar in both arteries, but were greater in simian veins than in canine veins. In both arteries, NE- and KCI-induced vasoconstrictions were markedly depressed to almost the same degree by cooling. In both veins, the vasoconstrictions were not significantly affected by cooling. | 10.1254/jjp.49.544 |
pubmed_918_10120 | This study examined the conceptualisation of Singaporean and Chinese parents' emotion socialisation in childhood and the relation to adolescents' emotion regulation with 601 adolescents aged 12-15. For both Singaporean and Chinese parents, we examined the factorial structure underlying six parental reactions to children's negative emotions, and the relations between the established factors with adolescents' cognitive reappraisal and response suppression. The findings revealed differences in the conceptualisation of parental reactions for Singaporean and Chinese parents, with the three- and four-factor models indicating good fit, respectively. For Singaporean parents, the factor comprising Expressive Encouragement, Emotion-Focused and Problem-Focused reactions was positively correlated with male adolescents' cognitive reappraisal, and the factor comprising Punitive and Distress Reactions was positively related to female adolescents' response suppression. For Chinese parents, the Expressive Encouragement factor was positively correlated with male adolescents' cognitive reappraisal. These findings on cultural differences in the factors underlying parental reactions and their relations with adolescents' emotion regulation support the emotion competency framework for understanding parents' emotion socialisation across cultures. | 10.1002/ijop.12576 |
pubmed_1096_16509 | Electrospinning has recently received considerable attention, showing notable potential as a novel method of scaffold fabrication for cartilage engineering. The aim of this study was to use a coculture strategy of chondrocytes combined with electrospun gelatin/polycaprolactone (GT/PCL) membranes, instead of pure chondrocytes, to evaluate the formation of cartilaginous tissue. We prepared the GT/PCL membranes, seeded bone marrow stromal cell (BMSC)/chondrocyte cocultures (75% BMSCs and 25% chondrocytes) in a sandwich model in vitro, and then implanted the constructs subcutaneously into nude mice for 12 weeks. Gross observation, histological and immunohistological evaluation, glycosaminoglycan analyses, Young's modulus measurement, and immunofluorescence staining were performed postimplantation. We found that the coculture group formed mature cartilage-like tissue, with no statistically significant difference from the chondrocyte group, and labeled BMSCs could differentiate into chondrocyte-like cells under the chondrogenic niche of chondrocytes. This entire strategy indicates that GT/PCL membranes are also a suitable scaffold for stem cell-based cartilage engineering and may provide a potentially clinically feasible approach for cartilage repairs. | 10.2147/IJN.S79461 |
pubmed_1121_7552 | Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used to treat hematological malignancies and genetic diseases. Graft-versus-host disease (GVHD) induced by donor immune system is the most common complication, contributing to severe morbidity and mortality after allo-HSCT. Currently, in terms of the prevention and treatment of GVHD, the major first-line therapeutic drugs are corticosteroids. However, most patients with systemic corticosteroid treatment are prone to steroid-refractory and poor prognosis. The use of several immune cells including Tregs, Bregs and mesenchymal stromal cells (MSCs) as an alternative on prevention or therapy of GVHD has been demonstrated to be beneficial. However, there are still many defects to a certain degree. Based on immune cells, it is promising to develop new and better approaches to improve GVHD. In this article, we will review the current advance of immune cells (Tregs, Bregs, MSCs) with negative regulation in the treatment of GVHD and present emerging strategies for the prevention and treatment of GVHD by other immune regulatory cells and chimeric antigen receptor (CAR) Tregs. In addition, these new therapeutic options need to be further evaluated in well-designed prospective multicenter trials to determine the optimal treatment for GVHD patients and improve their prognosis. | 10.1016/j.intimp.2020.107349 |
pubmed_948_6347 | Bile composition and the presence of cholesterol crystals in bile were studied in bile samples obtained at the time of surgery in patients with ulcerative colitis. Some patients were sampled before colectomy and others at a second operation months to years after a colectomy. Patients in the precolectomy group were found to have bile composition similar to control patients without gallstones, and few had crystals in their bile. In the postcolectomy group, cholesterol concentrations were very high, all biles were supersaturated, and almost all patients had cholesterol crystals in their bile. These findings are similar to those found in persons with cholesterol gallstones. Twenty patients have been followed for at least 3 years after colectomy and to date three have formed cholesterol gallstones. | 10.1097/00000658-199110000-00004 |
pubmed_279_3611 | Interleukin-6 (IL-6) is known to be an important modulator of acute phase (AP) protein expression in hepatocytes both in vivo and in vitro. In the present study the inducing activity of IL-6 on the expression of the AP protein haptoglobin (HP) by the human hepatoma cell line HepG2, has been evaluated. HP mRNA inducibility was analysed by Northern and slot-blot hybridization, while HP protein was detected by means of an ELISA procedure. A dose-response relationship from 0.3 to 4.8 ng/ml of a human recombinant IL-6 preparation derived from a Chinese hamster ovary (CHO) cell line was observed after 48 h of treatment. Comparable results were obtained by analysing both HP mRNA expression and HP protein secretion. Detectable induction of HP protein secretion was observed with as little as 25 pg/ml of IL-6. The effect of IL-6 was potentiated by dexamethasone, while an inhibition on HP mRNA inducibility could be prevented by lowering the foetal calf serum (FCS) concentration to 1%. Preliminary data indicate that neither IL-1 beta nor TNF-alpha were able to induce significantly HP mRNA expression and protein secretion. The activity ratio between two IL-6 preparations (from CHO and E. coli cells) obtained with a conventional IL-6 bioassay (i.e., T1165 cell growth assay) was comparable to that obtained in the induction of HP expression. The nominal specific activity of the CHO-derived IL-6 was two to three times higher with both responses. | 10.1016/0022-1759(94)90036-1 |
pubmed_306_15369 | OBJECTIVE
To introduce algorithms for effective segmentation of teeth MRI-UTE image.
METHODS
To construct second-segmentation algorithm process based on layer-dependent multi-constrained method. Firstly, a level set method was used to segment the initial boundary from the region determined by user in the reference slice. Secondly, both crown and root of the tooth were segmented by the improved level set method which took the information of the former layer's result as constraint conditions. Finally, the improved level set based on the information of the former and later layer's results was executed for the second time to improve the accuracy of segmentation, in which, the parameter of the overlapping ratio was considered.
RESULTS
The accuracy was 86.98% for the first-segmentation and was increased to 88.35% for the second-segmentation. Compared to the two other methods, the accuracy of the algorithms provided was improved significantly (P < 0.05).
CONCLUSIONS
The proposed algorithms can effectively achieve the segmentation of teeth MRI-UTE image and has a great improvement on accuracy. | pubmed_306_15369 |
pubmed_501_9394 | At studying various groups of the human lymph vessels (inguinal, axillary, peristernal, deep cervical, superior tracheobroncheal, etc.) a certain asymmetry in their structure has been noted. The number of similar lymph nodes at either side is not equal: their number is greater at the right side than at the left. As a rule, the range between maximum and minimum is greater in men than in women. Asymmetry of the male lymph nodes is more pronounced than that in the female. There are certain differences in size and position of the lymph nodes regarding large blood vessels. In most cases, the indices on number and size of the lymph vessels are inversely proportional. As to the microscopical structure of the lymph nodes, the asymmetry is revealed in different structure of only some structural components and separate cellular elements, which are assumed to be more labile at asymmetry of the human body functions. The data obtained on different structure of the left- and right-sided lymph nodes of the same name contribute to our knowledge on anatomy of these organs and can be used in practical medicine. | pubmed_501_9394 |
pubmed_157_913 | Schizophrenia (SZ) and Bipolar Disorder (BD) are highly inheritable chronic mental disorders with a worldwide prevalence of around 1%. Despite that many efforts had been made to characterize biomarkers in order to allow for biological testing for their diagnoses, these disorders are currently detected and classified only by clinical appraisal based on the Diagnostic and Statistical Manual of Mental Disorders. Olfactory neuroepithelium-derived neuronal precursors have been recently proposed as a model for biomarker characterization. Because of their peripheral localization, they are amenable to collection and suitable for being cultured and propagated in vitro. Olfactory neuroepithelial cells can be obtained by a non-invasive brush-exfoliation technique from neuropsychiatric patients and healthy subjects. Neuronal precursors isolated from these samples undergo in vitro the cytoskeletal reorganization inherent to the neurodevelopment process which has been described as one important feature in the etiology of both diseases. In this paper, we will review the current knowledge on microtubular organization in olfactory neurons of patients with SZ and with BD that may constitute specific cytoskeletal endophenotypes and their relation with alterations in L-type voltage-activated Ca(2+) currents. Finally, the potential usefulness of neuronal precursors for pharmacological screening will be discussed. | pubmed_157_913 |
pubmed_812_23360 | A liquid chromatographic/tandem mass spectrometric method is described for the determination of phencyclidine (PCP) in small volumes of rat serum (e.g. 50 microl). Samples were extracted using a mixed-mode strong cation-exchange column and then separated isocratically using a narrow-bore (2.1 mm i.d.) 3 microm Hypersil phenyl column and a mobile phase consisting of an ammonium formate buffer (pH 2.7) with 60% (v/v) methanol. Detection was accomplished using positive ion electrospray ionization in the multiple reaction monitoring mode. Mass spectra were obtained and peaks were observed at an m/z (% abundance) of 244 (100), 159 (25), and 86 (89). Tandem mass spectra were also obtained from the m/z 244 precursor ion with peaks observed at m/z 159 (100), 86 (96), and 91 (11). Optimum serum PCP sensitivity and precision were obtained at a transition of m/z 244 --> 159. Matrix-associated ion suppression did not significantly affect the accuracy (100-112%) or precision (CV < or =8%) of the assay. The lower limit of quantitation was 1 ng ml(-1) in 50 microl of serum. The method was used to study the serum pharmacokinetics of PCP in rats after an intravenous bolus dose of PCP. | 10.1002/jms.766 |
pubmed_401_22165 | Faced with the emergence of new pathologies and the prevalence of non-communicable diseases, public policies are using new tools, borrowed from social marketing, to increase the efficiency of their reach: Healthy Nudges. Within the architecture of choice, these nudges invite action to achieve the targeted public health objectives, without constraint. The flexibility of these instruments opens up new fields of intervention at all structural and institutional levels, adapting perfectly to Swiss federalism and supporting existing health policies. Opening the way to precision public health, these instruments of soft state intervention raise legal challenges such as the stigmatization of certain parts of the population and the transparency of state activity. | 10.53738/REVMED.2022.18.790.1398 |
pubmed_814_17350 | An interprofessional training session for health professionals was designed to optimize practice regarding goals of care at the end-of-life with patients and their families. The training session supported implementation of a new unified format, used in all healthcare establishments in Quebec since 2018, to document treatment preferences of persons with serious illness or advanced frailty. Three months after the training, participants revealed three main changes in their professional practices: (1) better use of the unified form as a communication tool to discuss end-of-life care with patients; (2) improved interprofessional practices in complex goals of care conversations situations through better affirmation of their role along with recognition of other professionals' roles in this decision-making process; and (3) assumption improved recognition of advocacy, support and enabler roles with patients and families during goals of care conversations. Change facilitators are related to the participants' personal characteristics, whereas the change constraints identified by participants mainly concern organizational factors. This implies potential recommendations to optimize patients' ability to mobilize in order to make informed decisions about their end-of-life care. | 10.1080/15524256.2021.1897922 |
pubmed_262_12689 | Human serum paraoxonase-1 (HuPON1) is difficult to either purify from plasma or functionally express in high yield from recombinant sources. Here, we describe the characterization of functional HuPON1 expressed and purified from Trichoplusia ni (T. ni) larvae infected with an orally active form of baculovirus. SDS-PAGE and anti-HuPON1 Western blot analyses yielded only three bands of approximately 41, 42, and 44 kDa. MALDI-TOF confirmed the identity of each of these bands as HuPON1 with greater than 95% confidence. These isoforms result from differential glycosylation of the enzyme as indicated by peptide mapping, mass analysis, and PNGase F deglycosylation experiments. Recombinant insect-produced HuPON1 hydrolyzed phenyl acetate, paraoxon, and the nerve agents GF, VX, and VR. The enzyme had dramatic stereoselectivity for the P+ isomers of VX and VR. T. ni larvae expressing HuPON1 were remarkably resistant to the pesticide chlorpyrifos. Together, these results demonstrate that the caterpillar of the T. ni moth can be used as an expression system to produce large quantities of functional recombinant HuPON1. Insect production of HuPON1 may provide a source for both in vitro enzymatic and crystallographic studies and in vivo stability and anti-nerve agent efficacy testing. | 10.1016/j.cbi.2010.02.022 |
pubmed_13_19639 | Animal studies have demonstrated anti-diabetic properties of several food-derived polyphenols, but data in humans remains unclear. This study aimed to review and meta-analyse evidence concerning the effect of the intake of several polyphenol-rich foods on gestational diabetes (GDM) risk. A systematic literature search was conducted in PubMed, Web of Science and Embase databases for observational studies on the association between dietary intake of foods/diets rich in polyphenols and GDM risk. Inclusion criteria were original research articles with full texts published in peer-reviewed English language journals, which investigated foods within the top 100 richest dietary sources of polyphenols and reported odds ratio/relative risk with their corresponding 95% confidence intervals. The quality of included studies was assessed using the Newcastle-Ottawa Scale. The intake of polyphenol-rich foods and dietary patterns in relation to GDM were pooled with fixed- and random-effects models. In total, 12 (10 cohort, 1 cross-sectional and 1 case-control) studies were included for the final systematic review, comprising 124,959 participants and including 5,786 women with GDM. Five studies found a significant, inverse association between the intake of polyphenol-rich foods or Mediterranean diet and GDM, whereas five studies reported no association and two exhibited a positive association. Meta-analyses further showed that the risk of GDM was about halved amongst women with the highest score of Mediterranean diet compared to those with the lowest score. The results suggest that dietary patterns rich in polyphenols may reduce the risk of GDM despite inconclusive evidence for polyphenol-rich food groups. | 10.1038/s41430-018-0218-7 |
pubmed_1109_2145 | OBJECTIVE
A preictal state exists minutes or hours prior to the clinical seizure. We investigated whether hemodynamic changes preceding temporal lobe seizures were detectable in frontal scalp recordings using near-infrared spectroscopy (NIRS). Patients undergoing video-EEG telemetry (VET) were studied.
METHODS
A NIRS sensor was placed over the frontal scalp ipsilateral to the patient's first recorded seizure. Regional cerebral oxygenation (rSO2) was recorded synchronously with VET data and peripheral oxygen saturation (SaO2). Periictal changes in rSO2 were compared with baseline interictal rSO2.
RESULTS
Eleven seizures were recorded in six patients. A mean peak preictal increase in rSO2 of 7.1% from the interictal baseline (p<0.001) occurred at a mean peak latency of 298.9s before seizure onset. rSO2 then decreased around seizure onset. SaO2 nadir occurred at a mean latency of 62s following rSO2 nadir. A postictal increase in rSO2 occurred with a mean duration of about 35 min. Periictal rSO2 changes occurred with both ipsi and contralateral temporal lobe seizures.
CONCLUSION
We have shown that preictal changes in cerebral oxygenation occur with a mean peak latency of about 4.98 min before seizure onset.
SIGNIFICANCE
NIRS has the potential for providing a noninvasively detected signal of an imminent seizure. | pubmed_1109_2145 |
pubmed_1107_11084 | Gastrointestinal tonometry is supposed to diagnose gut mucosal hypoxia using gastric luminal PCO2 and arterial bicarbonatemia, which are substituted in a modified Henderson-Hasselbach equation. This article reviews some of the problems inherent to the multiple assumptions underlying this technique. Tonometry is influenced by several local factors and by systemic acid-base imbalances that are unrelated to oxygenation. Tonometry is a rather crude and cumbersome method of gut capnometry, a technology that may provide valuable information regarding visceral perfusion, but not necessarily oxygenation. | 10.1016/s0749-0704(05)70264-5 |
pubmed_993_11360 | The effects of repeated freezing and thawing. on certain properties of early gestation amniotic fluid were studied. Six anmiotic fluids from 15- to 17-week gestations were investigated. Total protein determinations revealed that there was no significant loss of total protein with rapid freezing and thawing up to 10 times in the space of a few days. Immunoelectrophoresis revealed that the antigenic properties of the amniotic fluid, as ascertained by counting the number of precipitin bands, were unaltered by the repeated freezing and thawing | pubmed_993_11360 |
others_157_2819 | Purpose: Medulloblastomas (MBs) constitute the most common malignant brain tumor in children and adolescents. MYC-amplified Group 3 MBs are characterized by disease recurrence, specifically in the leptomeninges, whereby patients with these metastatic tumors have a mortality rate nearing 100%. Despite limited research on such tumors, studies on MB metastases at diagnosis suggest targeting kinases to be beneficial. Methods: To identify kinase inhibitors that eradicate cells driving therapy evasion and tumor dissemination, we utilized our established patient-derived xenograft (PDX) mouse-adapted therapy platform that models human MB metastatic recurrences following standard chemoradiotherapy. High-throughput screens of 640 kinase inhibitors were conducted against cells isolated from mouse spines in the PDX model and human fetal neural stem cells to reveal compounds that targeted these treatment-refractory, metastatic cells, whilst sparing healthy cells. Blood–brain barrier permeability assays and additional in vitro experimentation helped select top candidates for in vivo studies. Results: Recurrent Group 3 MB PDX spine cells were therapeutically vulnerable to a selective checkpoint kinase 1 (CHK1) inhibitor and small molecular inhibitor of platelet-derived growth factor receptor beta (PDGFRβ). Inhibitor-treated cells showed a significant reduction in MB stem cell properties associated with treatment failure. Mice also demonstrated survival advantage when treated with a CHK1 inhibitor ex vivo. Conclusion: We identified CHK1 and PDGFRβ inhibitors that effectively target MB cells fueling treatment-refractory metastases. With limited research on effective therapies for Group 3 MB metastatic recurrences, this work highlights promising therapeutic options to treat these aggressive tumors. Additional studies are warranted to investigate these inhibitors’ mechanisms and recommended in vivo administration. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Natur | 10.1007/s11060-023-04372-w |
pubmed_310_16682 | General principles of managing chronic, age-associated diseases apply as much to Alzheimer's disease (AD) and other late-life dementing disorders as they do to congestive heart failure or osteoarthritis. Beyond efforts to maintain residual tissue or organ function, important physician roles include promoting general well-being and helping patients and their caregivers adjust to disease-related limitations. Physicians provide essential information to patients and their families about the disease, its social and legal ramifications, and community resources to facilitate care. Therefore, physicians must be knowledgeable about broadly intersecting medical, legal, financial, and ethical issues surrounding the long-term management of AD and other dementias. The many challenges faced by patients with dementia and their caregivers over time underscore the need for an ongoing diagnostic and therapeutic alliance with primary care physicians. This article reviews salient aspects of long-term care for patients with AD and other dementias, highlighting the vital and varied roles of physicians in managing these chronic brain disorders. | 10.1016/s1098-3597(01)90048-1 |
pubmed_584_4287 | We have measured temperature dependences of sound velocity for both longitudinal and transverse sound in nuclear-ordered U2D2 solid 3He with several crystal orientations along the melting curve. The sound velocity change was proportional to T4 for all sound modes and crystal orientations and was attributed to the nuclear-spin part of the internal energy. We extracted six-independent elastic stiffness of the nuclear-spin part and obtained Grüneisen constants of the spin wave velocity for four-independent strains. Grüneisen constants for compressional strain were larger than those for shear strain. Using the multiple-spin-exchange model, we explain the anisotropy of Grüneisen constants in tetragonal symmetry. | 10.1103/PhysRevLett.91.115301 |
pubmed_1129_17229 | Background
Exposure to whole body vibration (WBV) is common in construction, agriculture, mining, and transportation. There is strong epidemiological evidence linking WBV with adverse health outcomes in the long-term, including low back pain. Fortunately, WBV exposure guidelines to prevent long-term musculoskeletal disorders and discomfort exist. In the shorter-term, it has been speculated that occupational levels of WBV may lead to increased risk of vehicle accidents and falls during egress; however, the acute effects of different vibration intensities remain poorly understood and it is uncertain whether established standards protect the worker from injurious short-term effects.
Objective
The aim of this study was to investigate the acute sensorimotor, physical, and cognitive effects of occupationally-relevant, simulated whole body vibration (WBV) at levels equivalent to international standard guideline thresholds for long-term discomfort and musculoskeletal disorder risk.
Method
Eighteen participants were recruited to perform four, 60-min conditions: (i) Control-no vibration, (ii) Low vibration-equivalent to the exposure action value, (iii) Shock-transient impacts at 1-min intervals superimposed on the Low condition, and (iv) High vibration-equivalent to the exposure limit value. Whole body vibration was simulated using data based on field-collected accelerations experienced by rural workers while operating an all-terrain vehicle. This vibration signal was manipulated to achieve required intensities for each condition and simulated with a 6 degree-of-freedom hexapod platform. Before and after each condition, we collected: rating of perceived body discomfort, rating of perceived headache, postural sway, blink frequency, King-Devick test, and psychomotor vigilance task. Pre- and post-condition data in each condition were submitted to either a paired t-test (parametric) or Wilcoxon signed-rank test (non-parametric). To determine differences between conditions, each condition's post-condition data was normalized to its pre-condition value and entered as the dependent variable in a repeated measures analysis of variance.
Results
All conditions, including Control, led to increased upper body discomfort when compared to pre-exposure baseline. The Low condition led to increased discomfort in seven body locations, headache (91% increase from baseline; t = -2.44, P = 0.03), and postural imbalance (53% increase from baseline; t = -2.88, P = 0.01), but the effect on cognitive functioning was less clear. Shock condition led to whole body discomfort, specifically at nine upper body and lower body locations. The High condition led to increased whole body discomfort at all 10 body locations, headache (154% increase from baseline; t = -2.91, P = 0.01), postural imbalance (61% increase from baseline; t = -2.57, P = 0.02), and decrements in vigilance (mean reaction time: 6% increase from baseline, t = -3.27, P = 0.005; Number of lapses: 100% increase from baseline, S = -42.5, P = 0.002).
Conclusion
Although the number of pre-post condition effects increased with higher vibration intensity, these effects were not significantly different from sitting without vibration. Therefore, current guideline thresholds might not protect the worker from acute WBV effects. However, further research is needed to discern these effects from other sources of WBV. Based on this study, future WBV interventions and action controls should not only address vibration reduction, but also consider potential effects from prolonged sitting. | 10.1093/annweh/wxy043 |
pubmed_443_10648 | OBJECTIVE
To evaluate cerebrospinal fluid (CSF) levels of amyloid beta protein ending at amino acid 42 (Abeta42) and tau as markers for Alzheimer disease (AD) and to determine whether clinical variables influence these levels.
DESIGN
Cohort study.
SETTING
Six academic research centers with expertise in dementia.
SUBJECTS
Eighty-two patients with probable AD, including 24 with very mild dementia (Mini-Mental State Examination score >23/30) (AD group); 60 cognitively normal elderly control subjects (NC group); and 74 subjects with neurological disorders, including dementia (ND group).
MAIN OUTCOME MEASURES
Levels of Abeta42 and tau were compared among AD, NC, and ND groups. Relationships of age, sex, Mini-Mental State Examination score, and apolipoprotein E (Apo E) genotype with these levels were examined using multiple linear regression. Classification tree models were developed to optimize distinguishing AD from NC groups.
RESULTS
Levels of Abeta42 were significantly lower, and levels of tau were significantly higher, in the AD group than in the NC or ND group. In the AD group, Abeta42 level was inversely associated with Apo E epsilon4 allele dose and weakly related to Mini-Mental State Examination score; tau level was associated with male sex and 1 Apo E epsilon4 allele. Classification tree analysis, comparing the AD and NC subjects, was 90% sensitive and 80% specific. With specificity set at greater than 90%, the tree was 77% sensitive for AD. This tree classified 26 of 74 members of the ND group as having AD. They had diagnoses difficult to distinguish from AD clinically and a high Apo E epsilon4 allele frequency. Markers in CSF were used to correctly classify 12 of 13 patients who later underwent autopsy, including 1 with AD not diagnosed clinically.
CONCLUSIONS
Levels of CSF Abeta42 decrease and levels of CSF tau increase in AD. Apolipoprotein E epsilon4 had a dose-dependent relationship with CSF levels of Abeta42, but not tau. Other covariates influenced CSF markers minimally. Combined analysis of CSF Abeta42 and tau levels discriminated patients with AD, including patients with mild dementia, from the NC group, supporting use of these proteins to identify AD and to distinguish early AD from aging. In subjects in the ND group with an AD CSF profile, autopsy follow-up will be required to decide whether CSF results are false positive, or whether AD is a primary or concomitant cause of dementia. | 10.1001/archneur.55.7.937 |
pubmed_65_2963 | A case of a patient who developed symptomatic phenytoin-induced folic acid deficiency is reported. Folate supplementation of 5 mg/d was followed by a decrease of serum phenytoin concentration to a subtherapeutic level with a breakthrough seizure. Estimation of phenytoin's Km-Vmax Michaelis-Menten pharmacokinetic parameters in this patient demonstrated that folate supplements indeed caused a significant decrease in the Km value. This decrease correlates with a greater affinity of the metabolizing hepatic enzymes for the drug, and hence, with the resultant increase in phenytoin's metabolism and decrease of its serum concentration and anticonvulsive effect. In an era of increasing knowledge of folate's pivotal role in various diseases, we call attention to this drug-vitamin interaction, and to the previously suggested recommendation that folate supplementation should be initiated whenever phenytoin therapy commences. Because folic acid dosages as low as 1 mg/d may perturbate phenytoin's metabolism, smaller deficiency preventive doses may be the advisable allowance for phenytointreated patients with normal pretreatment folate levels. This suggestion must be confirmed by a prospective study in a large cohort of patients. | pubmed_65_2963 |
pubmed_984_15438 | The copper(II) complex A0 induces a type of non-apoptotic cell death also known as paraptosis. Paraptosis involves extensive endoplasmic reticulum vacuolization in the absence of caspase activation. A wide panel of human cancer cell lines was used to demonstrate differences in cytotoxicity by the paraptosis-inducing drug A0 and the metal-based pro-apoptotic drug cisplatin. Gene expression profiling of the human fibrosarcoma HT1080 cells showed that, while cisplatin induced p53 targets, A0 up-regulated genes involved in the unfolded protein response (UPR) and response to heavy metals. The cytotoxic effects of A0 were associated with inhibition of the ubiquitin-proteasome system and accumulation of ubiquitinylated proteins, in a manner dependent on protein synthesis. Cycloheximide inhibited the accumulation of ubiquitinylated proteins and hampered A0-induced cell death process. The occurrence of the UPR during A0-induced death process was shown by the increased abundance of spliced XBP1 mRNA, transient eIF2alpha phosphorylation, and a series of downstream events, including attenuation of global protein synthesis and increased expression of ATF4, CHOP, BIP, and GADD34. Mouse embryonic fibroblasts expressing a mutant eIF2alpha, which could not be phosphorylated, were more resistant to A0 than wild type cells, pointing to a pro-death role of eIF2alpha phosphorylation. A0 may thus represent the prototypical member of a new class of compounds that cause paraptotic cell death via mechanisms involving eIF2alpha phosphorylation and the UPR. | 10.1074/jbc.M109.026583 |
pubmed_632_18314 | The occurrence and the subsequent development of pulmonary arterial hypertension (PAH) involve complicated mechanisms. Of these, the proliferation of pulmonary artery smooth muscle cells (PASMCs) has been indicated to be closely associated with its progression. Therefore, therapeutic methods targeting PASMCs to inhibit proliferation is an effective method for alleviating PAH. The present study was designed to determine the role of the adenosine A(2A) receptor (A2A receptor) in hypoxia‑induced rat PASMC (RPASMC) proliferation. Primary RPASMCs were isolated from the pulmonary artery of adult male SD rats, cultured and used for the following experiments. The mRNA level and protein expression of CXCR4 were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The cell proliferation of RPASMCs was measured using a cell proliferation assay kit. In the present study, it was demonstrated that the proliferation of RPASMCs was partially mediated by activation of the stromal cell‑derived factor 1 (SDF1)‑CXC chemokine receptor 4 (CXCR4) axis under hypoxic conditions. In addition, SDF1‑α alone upregulated the mRNA and protein expression levels of CXCR4, and stimulated the proliferation of RPASMCs. The protein expression of CXCR4 and the cell proliferation were markedly inhibited by application of A2A receptor agonist CGS21680 or cyclic adenosine monophosphate (cAMP) under hypoxic conditions or treatment with SDF1‑α and was reversed by the A2A receptor antagonist SCH58261 or 8‑bromoadenosine‑3',5'‑cyclic monophosphorothioate. These results demonstrated that the inhibition of SDF1‑CXC4 signaling by the activation of A2A receptor and subsequent increase in the level of cAMP may be a potential method to ameliorate PAH. | 10.3892/ijmm.2018.3626 |
pubmed_895_11151 | Osteogenesis Imperfecta (OI) results from gene mutation that causes defective or insufficient collagen formation. It may cause various anesthetic complications due to the difficulty in airway management, existence of spinal deformity, respiratory disorders, cardiac anomalies, thrombocyte function disorder, risk of hyperthermia, bacillary invagination, bone deformities and metabolic disorders. The anesthesia management of OI patients should be exercised with caution given certain risks of respiratory disorders. These risks are due to thorax deformity, bone fractures during moving or changing position, mandibular and cervical fractures related with intubation, difficult intubation and malignant hyperthermia. The anesthetic technique using Total Intravenous Anesthesia (TIVA) and laryngeal mask airway is suitable for pediatric patient care with OI. However, these techniques have not yet been reported as useful in neurosurgery case reports. In this study, we present the use of TIVA and ProSeal Laringeal Mask in a child with OI and epidural hemorrhage. We came to the conclusion that LMA and TIVA can safely be used in the anesthetic management of OI patients with severe anesthetic problems. | pubmed_895_11151 |
pubmed_291_5249 | Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) deposition in the brain, neuronal cell loss and cognitive decline. We show here that retinoic acid receptor (RAR)α signalling in vitro can prevent both intracellular and extracellular Aβ accumulation. RARα signalling increases the expression of a disintegrin and metalloprotease 10, an α-secretase that processes the amyloid precursor protein into the non-amyloidic pathway, thus reducing Aβ production. We also show that RARα agonists are neuroprotective, as they prevent Aβ-induced neuronal cell death in cortical cultures. If RARα agonists are given to the Tg2576 mouse, the normal Aβ production in their brains is suppressed. In contrast, neither RARβ nor γ-agonists affect Aβ production or Aβ-mediated neuronal cell death. Therefore, RARα agonists have therapeutic potential for the treatment of AD. | 10.1111/j.1460-9568.2010.07426.x |
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