index
stringlengths
10
17
text
stringlengths
101
18k
doi
stringlengths
2
72
pubmed_147_16082
Using nanofluidic channels in PDMS of cross section 500 nm × 2 μm, we demonstrate the trapping and interrogation of individual, isolated mitochondria. Fluorescence labeling demonstrates the immobilization of mitochondria at discrete locations along the channel. Interrogation of mitochondrial membrane potential with different potential sensitive dyes (JC-1 and TMRM) indicates the trapped mitochondria are vital in the respiration buffer. Fluctuations of the membrane potential can be observed at the single mitochondrial level. A variety of chemical challenges can be delivered to each individual mitochondrion in the nanofluidic system. As sample demonstrations, increases in the membrane potential are seen upon introduction of OXPHOS substrates into the nanofluidic channel. Introduction of Ca(2+) into the nanochannels induces mitochondrial membrane permeabilization (MMP), leading to depolarization, observed at the single mitochondrial level. A variety of applications in cancer biology, stem cell biology, apoptosis studies, and high throughput functional metabolomics studies can be envisioned using this technology.
10.1021/ac4010088
pubmed_637_4558
OBJECTIVE This study was initiated to investigate the effects of Roux-en-Y gastric bypass (RYGB) surgery on hepatic glucose metabolism and hepatic expression of protein tyrosine phosphatase 1B (PTP1B) in obese rats. METHODS Body weight, glucose, intraperitoneal glucose, insulin, and pyruvate tolerance tests were performed pre- and postoperatively, and plasma lipid, insulin and glucagon-like peptide 1 (GLP-1) were measured. The mRNA levels of G6Pase, Pepck, Gsk-3β and Gys-2, and the expression levels of PTP1B mRNA, protein, and other components of the insulin signaling pathway were measured by using RT-PCR and western blotting. The intracellular localization of PTP1B and hepatic glycogen deposition was also observed. RESULTS RYGB surgery-treated rats showed persistent weight loss, significantly improved glucose tolerance, pyruvate tolerance, and dyslipidemia, as well as increased insulin sensitivity, hepatic glycogen deposition and increased plasma GLP-1 in obese rats. RT-PCR analyses showed Pepck, G6Pase, and Gsk-3β mRNA to be significantly decreased, and Gys-2 mRNA to be significantly increased in liver tissue in the RYGB group (p < 0.05 vs. high-fat diet (HFD) or HFD + sham group); in addition, the expression of PTP1B were significantly decreased and insulin signaling were improved in the RYGB group (p < 0.05 vs. HFD or HFD + sham group). CONCLUSION RYGB can improve hepatic glucose metabolism and down-regulate PTP1B in obese rats. An increased circulating GLP-1 concentration may be correlated with the effects following RYGB in obese rats.
10.1159/000470912
pubmed_801_21579
PURPOSE Loss of pin fixation in supracondylar fractures can occur with failure to achieve bicortical fixation. Bicortical fixation may be challenging for those pins that attempt to penetrate the diaphyseal cortex, where the bone is thick. Lateral-entry Steinmann pins may allow for better penetration through cortical bone because they are more rigid than typical Kirschner wires. METHODS A retrospective review of 16 children with type III supracondylar fractures treated by a single surgeon using Steinmann pins was undertaken. The average age at presentation was 6 years. Following closed reduction, all fractures were maintained with three lateral-entry pins. At least one Steinmann pin was placed in the lateral column of the distal humerus in each pin construct. RESULTS Follow-up radiographs indicated a mean Baumann's angle of 72.9° (range 64°-82°). There was no statistically significant change in the Baumann's angle or axial alignment at final follow-up. All but one fracture healed in an anatomic position on the lateral view. CONCLUSIONS Steinmann pins placed through a lateral-entry point are effective in controlling the reduction of high-grade supracondylar fractures. The fixation is excellent and avoids potential ulnar nerve complications of medial entry.
10.1007/s11832-010-0283-5
pubmed_932_1246
Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
10.1089/omi.2011.0118
pubmed_745_75
In this collaborative study involving 27 European medical centers, the plasma GH response to a single iv bolus dose of 2 micrograms/kg BW synthetic GHRH-(1-44)NH2 was determined in 574 children with growth failure of various etiologies. Analysis of the plasma GH response to GHRH was performed in 394 validated prepubertal children; these children were subdivided into 3 groups according to the degree of GH deficiency assessed within 6 months by conventional provocative tests (insulin, arginine, etc.): normal GH status (n = 210), partial GH deficiency (n = 73), or severe GH deficiency (n = 111). The mean peak GH values (+/- 2 SEM) after GHRH treatment in the three groups were 45.8 +/- 4.8, 29.2 +/- 6.3, and 16.8 +/- 3.1 microU/mL, respectively, and were greater than those after the conventional tests. The GH responses were consistent with the degree of GH deficiency based on the responses to the conventional tests. In addition, the areas under the GH response curves in the three groups were significantly different (P less than 0.0001). Among children with severe idiopathic GH deficiency 77% had a peak plasma GH level after GHRH above 10.0 microU/mL and 39% had a peak GH above 20.0 microU/mL. In these children, a single GHRH injection provides information on both their GH secretory capacity and the putative supresellar etiology of their GH deficiency, and may be of potential therapeutic value.
10.1210/jcem-65-3-387
pubmed_579_19869
CD8(+) T cells play a critical role in controlling hepatotropic viral infections, such as those caused by hepatitis B and hepatitis C viruses. The capacity of these cells to protect against such pathogens is mediated by antigen-experienced effector cells and relies on their ability to home to the liver, recognize pathogen-derived antigens, and deploy effector functions. Here, we review how dynamic imaging of hepatic effector CD8(+) T cell migration and function in mouse models of hepatitis B virus pathogenesis has recently revealed a unique and novel mode of adaptive immune surveillance. Circulating effector CD8(+) T cells initially arrest within liver sinusoids by docking onto adherent platelets and then actively crawl along the liver vasculature, probing hepatocytes for the presence of antigens by extending protrusions through the fenestrated sinusoidal endothelial cells. Hepatocellular antigen recognition and effector functions occur while CD8(+) T cells are still confined to the intravascular space and are inhibited by the pathologic processes that characterize liver fibrosis. A detailed understanding of the spatiotemporal dynamics of effector CD8(+) T cells within the liver is important for the rational design of targeted immunotherapeutic approaches for chronic liver infections.
10.1189/jlb.4MR0415-150R
pubmed_1018_11735
OBJECTIVE To describe a patient with multifocal cerebral ischemia whose only identified potential risk factors were use of postmenopausal hormone replacement and heterozygosity to factor V Leiden mutation. DESIGN A case report. SETTING A tertiary care center. PATIENT A 51-year-old woman taking hormone replacement (0.625 mg/d of estrogen alternating with 10 mg/d of medroxyprogesterone) presented with a generalized tonic-clonic seizure. She had persistent multifocal non-enhancing lesions on magnetic resonance imaging of the brain. A stereotactic biopsy of the brain performed to exclude gliomatosis cerebri was consistent with cerebral ischemia. An extensive evaluation to uncover the cause of stroke revealed only heterozygosity to factor V Leiden mutation. MAIN OUTCOME AND RESULTS Hormonal replacement was discontinued and the patient had no recurrent ischemic strokes. CONCLUSIONS Postmenopausal hormonal replacement may be a risk factor for ischemic stroke in women with the factor V Leiden mutation. Ongoing trials of hormonal replacement provide an opportunity to test this hypothesis.
10.1001/archneur.55.8.1137
pubmed_297_7060
Adoptive cell transfer therapy for cancer has existed for decades and is experiencing a resurgence in popularity that has been facilitated by improved methods of production, techniques for genetic modification, and host preconditioning. The trafficking of adoptively transferred lymphocytes and infiltration into the tumor microenvironment is sine qua non for successful tumor eradication; however, the paradox of extremely poor trafficking of lymphocytes into the tumor microenvironment raises the issue of how best to deliver these cells to optimize entry into tumor tissue. We examined the route of administration as a potential modifier of both trafficking and antitumor efficacy. Femoral artery cannulation and tail vein injection for the intra-arterial (IA) and IV delivery, respectively, were utilized in the B16-OVA/OT-I mouse model system. Both IV and IA infusions showed decreased tumor growth and prolonged survival. However, although significantly increased T-cell tumor infiltration was observed in IA mice, tumor growth and survival were not improved as compared with IV mice. These studies suggest that IA administration produces increased early lymphocyte trafficking, but a discernable survival benefit was not seen in the murine model examined.
10.1097/CJI.0000000000000235
pubmed_99_3655
Treatment with L-carnitine greatly enhanced the formation and excretion of short-chain acylcarnitines in three patients with propionic acidemia and in three normal controls. The use of fast atom bombardment mass spectrometry and linked scanning at constant magnetic (B) to electric (E) field ratio identified the acylcarnitine as propionylcarnitine in patients with propionic acidemia. The normal children excreted mostly acetylcarnitine. Propionic acidemia and other organic acidurias are characterized by the intramitochondrial accumulation of short-chain acyl-Coenzyme A (CoA) compounds. The substrate specificity of the carnitine acetyltransferase enzyme and its steady state nature appears to facilitate elimination of propionyl groups while restoring the acyl-CoA:free CoA ratio in the mitochondrion. We suggest that L-carnitine may be a useful therapeutic approach for elimination of toxic acyl CoA compounds in several of these disorders.
10.1172/JCI111387
pubmed_187_10222
Astrocytes are known to play multi-functional roles in support of many homeostatic mechanisms in the central nervous system including host defense mechanisms. Despite the ability of cytokines to alter gene expression and cellular activity, their effect on receptor-mediated poly-phosphoinositide (poly-PI) signaling pathway has not been examined in detail. In this study, an immortalized astrocyte cell line (DITNC) was used to test the effect of IL-1 beta exposure on the poly-PI signaling pathway. Similar to primary astrocytes, DITNC cells exhibit P2-purinergic receptor response to ATP and UTP leading to transient increases in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and intracellular calcium concentration, [Ca2+]i. Upon exposure of DITNC cells to IL-1 beta (100 U/ml) for 24 hrs, an increased response to the poly-PI agonists was observed. The increase in ATP-mediated Ins(1,4,5)P3 release could not be attributed to a shift in the ATP dose or an alteration of the time profile for the release of Ins(1,4,5)P3. Since the increase in response required a lag time of 4 hr after IL-1 beta exposure, it is unlikely that this effect was due to a direct interaction of IL-1 beta with the purinergic receptor. On the other hand, an increase in ATP response could be observed in DITNC cells exposed to conditioned medium obtained after IL-1 beta treatment. It can be concluded that exposure of astrocytes to cytokines may lead to an increase in receptor-mediated poly-PI signaling activity and this may involve compounds secreted into the culture medium, e.g., the secretory phospholipase A2.
10.1023/a:1021949417127
pubmed_647_8805
HIV infection is associated with subnormal GSH levels. An increase in glutathione levels has been observed in HIV-infected adults under oral whey protein supplementation. We studied the features associated with a whey protein concentrate supplementation in children with rapidly progressive AIDS. A prospective double-blind clinical trial was carried out for 4 months with 18 vertically HIV-infected children (1.98-6.37 years), under antiretroviral therapy, who had received whey protein, maltodextrin (placebo) or none. Erythrocyte glutathione concentration, T lymphocyte counts (CD4+ and CD8+) and occurrence of associated co-infections were evaluated. Wilcoxon's and Fischer's Exact tests were used to assess differences between whey protein-supplemented and control (placebo and non-supplemented) groups. A significant median increase of 16.14 mg/dl (p = 0.018) in erythrocyte glutathione levels was observed in the whey protein-supplemented group; the TCD4/CD8 lymphocyte ratio showed a non significant increase and lower occurrence of associated co-infections was also observed. In conclusion, whey protein concentrate supplementation can stimulate glutathione synthesis and, possibly, decrease the occurrence of associated co-infections.
10.1093/tropej/fmi074
pubmed_51_280
We show how a recent framework combining Markov chain Monte Carlo (MCMC) with particle filters (PFMCMC) may be used to estimate population state-space models. With the purpose of utilizing the strengths of each method, PFMCMC explores hidden states by particle filters, while process and observation parameters are estimated using an MCMC algorithm. PFMCMC is exemplified by analyzing time series data on a red kangaroo (Macropus rufus) population in New South Wales, Australia, using MCMC over model parameters based on an adaptive Metropolis-Hastings algorithm. We fit three population models to these data; a density-dependent logistic diffusion model with environmental variance, an unregulated stochastic exponential growth model, and a random-walk model. Bayes factors and posterior model probabilities show that there is little support for density dependence and that the random-walk model is the most parsimonious model. The particle filter Metropolis-Hastings algorithm is a brute-force method that may be used to fit a range of complex population models. Implementation is straightforward and less involved than standard MCMC for many models, and marginal densities for model selection can be obtained with little additional effort. The cost is mainly computational, resulting in long running times that may be improved by parallelizing the algorithm.
10.1890/11-0797.1
pubmed_592_5677
Evaluation of safety and efficacy of new drugs is based largely on data from clinical trials involving a limited number of patients. This approach does not necessarily detect the rare adverse events that may only be observed when very large numbers of patients are studied. Consequently, we designed a double-blind 12-week trial comparing the new angiotensin-converting enzyme (ACE) inhibitor, quinapril (n = 5,053), with a well-established beta-adrenergic receptor blocker, metoprolol (n = 506). Essentially hypertensive patients (diastolic blood pressure 95-114 mm Hg) received either 10 mg quinapril or 50 mg metoprolol once daily, and the doses were doubled at 4-week intervals to a maximum of 40 and 200 mg, respectively, in nonresponders. Responder rates were similar under both regimens. Adverse events were assessed by interview as well as by a standard questionnaire. The overall prevalence of adverse events reported by standard questionnaire was higher than that reported spontaneously during interviews. With respect to typical ACE inhibitor adverse reactions (e.g. cough and taste disturbances), there was no difference between quinapril and metoprolol independent of the mode of reporting. In summary, both drugs showed comparable overall tolerance and safety. The discrepancy between spontaneously reported and questionnaire-reported adverse events was noteworthy, and this finding prevailed in a volunteer group of 327 patients who were treated with quinapril for 52 weeks. Thus, a questionnaire is of great significance in addition to the patient history/interview in a large-scale, double-blind study designed to learn about details of drug safety.
10.1159/000177129
pubmed_465_8634
Initial studies from our institution demonstrated beneficial anti-ischemic effects of short-term infusion of intravenous nitroglycerin in patients with acute myocardial infarction. At lower doses, nitroglycerin was shown to be principally a venodilator; at higher doses, a mixed venous and arterial dilating effect was demonstrated. The acute hemodynamic effects of nitroglycerin varied in the presence or absence of left ventricular failure; patients with the most severe degree of left ventricular dysfunction had the most beneficial hemodynamic effect. Similar differential effects have been demonstrated for nitroprusside in other studies. A comparison of the arterial vasodilating potency of nitroglycerin and nitroprusside in patients in whom acute hypertension develops following coronary artery bypass surgery revealed that equal lowering of arterial pressure and systemic vascular resistance could be demonstrated in 85 percent of the patients with comparable infusion rates. Review of previous clinical and laboratory studies in animals, in which the effects of nitroglycerin and nitroprusside were compared, in most cases revealed opposite effects on intercoronary collateral flow and, thereby, opposite effects on the severity of regional ischemia. Our recently completed randomized placebo-controlled clinical trial employing a 48-hour infusion of nitroglycerin demonstrated a higher incidence of significant improvement in abnormalities noted on scintigraphy when nitroglycerin treatment was initiated within 10 hours of the onset of symptoms. Beneficial effects of early nitroglycerin treatment have also been demonstrated in previous clinical trials. In similar studies, which utilized nitroprusside infusions in patients with acute myocardial infarction, some investigators found an increase in short-term mortality with early nitroprusside treatment whereas others found benefit. The uniformly favorable results of the clinical trials that utilized intravenous nitroglycerin, although not necessarily supporting its routine use in all patients, would support a preference for nitroglycerin over nitroprusside for the treatment of congestive heart failure and/or acute hypertension complicating acute myocardial infarction.
10.1016/0002-9343(83)90855-0
pubmed_183_7742
The compounds 2,4-dichlorophenol (2,4-DCP) and 2,4-dichloro-6-nitrophenol (6-nitro-2,4-DCP) have been detected at microg L(-1) levels (10(-9)-10(-8) M) during the summer season 2005 in the water of the Rhône river delta. Compound 2,4-DCP would mainly derive from the transformation of the herbicide dichlorprop, heavily used in flooded rice farming (1400 kg in the delta region in 2005), in addition to being an impurity of the commercial herbicide. Field data show a fast concentration decrease of 2,4-DCP in the period June 21st to July 5th, accompanied by a corresponding increase of 6-nitro-2,4-DCP. This could imply a possible nitration process of 2,4-DCP into 6-nitro-2,4-DCP, with quite elevated yield (33%). Nitration of 2,4-DCP can be induced by photoproduced *NO2, the reaction kinetics (calculated in the presence of Fe(III) + nitrite under irradiation as model system) being d[6-nitro-2,4-DCP]/dt = 650 [2,4-DCP] [*NO2]. Interestingly, the yield of the process (38%) is similar to that suggested by field data. An indirect assessment of [*NO2] in surface water in different sites of the Rhône delta indicated that 2,4-DCP could be transformed into 6-nitro-2,4-DCP in a couple of weeks or less in the shallow water (10 cm depth) of the rice fields, a time scale that is compatible with field data. Photonitration of 2,4-DCP is thus a possible process to account for the occurrence of 6-nitro-2,4-DCP in the Rhône delta.
10.1021/es0626638
pubmed_697_19736
BACKGROUND Observational associations between cannabis and schizophrenia are well documented, but ascertaining causation is more challenging. We used Mendelian randomization (MR), utilizing publicly available data as a method for ascertaining causation from observational data. METHOD We performed bi-directional two-sample MR using summary-level genome-wide data from the International Cannabis Consortium (ICC) and the Psychiatric Genomics Consortium (PGC2). Single nucleotide polymorphisms (SNPs) associated with cannabis initiation (p < 10-5) and schizophrenia (p < 5 × 10-8) were combined using an inverse-variance-weighted fixed-effects approach. We also used height and education genome-wide association study data, representing negative and positive control analyses. RESULTS There was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [odds ratio (OR) 1.04 per doubling odds of cannabis initiation, 95% confidence interval (CI) 1.01-1.07, p = 0.019]. There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation (OR 1.10 per doubling of the odds of schizophrenia, 95% CI 1.05-1.14, p = 2.64 × 10-5). Findings were as predicted for the negative control (height: OR 1.00, 95% CI 0.99-1.01, p = 0.90) but weaker than predicted for the positive control (years in education: OR 0.99, 95% CI 0.97-1.00, p = 0.066) analyses. CONCLUSIONS Our results provide some that cannabis initiation increases the risk of schizophrenia, although the size of the causal estimate is small. We find stronger evidence that schizophrenia risk predicts cannabis initiation, possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation.
10.1017/S0033291716003172
pubmed_520_864
Prostate cancer gene expression marker 1 (PCGEM1) has abnormal expression level in a variety of malignant tumor. However, the relationship between PCGEM1 and colorectal cancer is still unclear yet. This study is aimed at identifying the role of PCGEM1 in colorectal cancer. qRT-PCR was used to examine the expressions of the expression of lncRNA PCGEM1 and SOX4 in CRC tissues and cell lines. The biological functions of lncRNA PCGEM1 and SOX4 were examined by CCK-8 assay, Transwell assay, immunohistochemistry, western blotting, RNA interference, and gene overexpression techniques. Bioinformatics analysis was used to find the potential downstream molecule of PCGEM1 and miR-129-5p. The relationship between PCGEM1, miR-129-5p, and SOX4 was assessed by dual luciferase activity assay. We found that PCGEM1 is overexpressed in colorectal cancer cells and tissues, while miR-129-5p is underexpressed. SOX4 is overexpressed in colorectal cancer cells and tissues. Functionally, PCGEM1 silencing can significantly inhibit the proliferation, invasion, and migration of colorectal cancer cells. Mechanically, PCGEM1 acted as a sponge for miR-129-5p and absorbed its expression, and miR-129-5p was found to target SOX4, constructing the axis of PCGEM1/miR-129-5p/SOX4 in colorectal cancer. In conclusion, PCGEM1 mediates the proliferation, invasion, and migration of colorectal cancer cells by targeting miR-129-5p/SOX4 axis.
10.1155/2022/2876170
pubmed_313_22454
A comparison of P4 activations mediated by low-valent β-diketiminato (L) cobalt complexes is presented. The formal Co0 source [K2 (L3 Co)2 (μ2 :η1 ,η1 -N2 )] (1) reacts with P4 to form a mixture of the monoanionic complexes [K(thf)6 ][(L3 Co)2 (μ2 :η4 ,η4 -P4 )] (2) and [K(thf)6 ][(L3 Co)2 (μ2 :η3 ,η3 -P3 )] (3). The analogue CoI precursor [L3 Co(tol)] (4 a), however, selectively yields the corresponding neutral derivative [(L3 Co)2 (μ2 :η4 ,η4 -P4 )] (5 a). Compound 5 a undergoes thermal P atom loss to form the unprecedented complex [(L3 Co)2 (μ2 :η3 ,η3 -P3 )] (6). The products 2 and 3 can be obtained selectively by an one-electron reduction of their neutral precursors 5 a and 6, respectively. The electrochemical behaviour of 2, 3, 5 a, and 6 is monitored by cyclic voltammetry and their magnetism is examined by SQUID measurements and the Evans method. The initial CoI -mediated P4 activation is not influenced by applying the structurally different ligands L1 and L2 , which is proven by the formation of the isostructural products [(LCo)2 (μ2 :η4 ,η4 -P4 )] [L=L3 (5 a), L1 (5 b), L2 (5 c)].
10.1002/chem.201605451
pubmed_851_23422
Six laboratories associated with the Vitamin D Standardization Program (VDSP) participated in an interlaboratory comparison of LC with tandem MS (MS/MS) methods for the determination of 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in human serum. The laboratories analyzed two different serum-based Standard Reference Materials (SRMs) intended for use in the determination of 25-hydroxyvitamin D and 30 samples from the Vitamin D External Quality Assessment Scheme (DEQAS). All laboratory methods for 24,25(OH)2D3 were based on isotope dilution LC-MS/MS; three of the methods used derivatization of the vitamin D metabolites before LC-MS/MS. Laboratory results were compared to the National Institute of Standards and Technology (NIST) results, which were obtained using their newly developed candidate reference measurement procedure for 24,25(OH)2D3. Laboratory results for the SRM samples varied in comparability to the NIST results, with one laboratory in excellent agreement (-1.6% mean bias), three laboratories at 10-15% mean bias, and the remaining laboratory at 36% mean bias. For the 30 DEQAS samples, the mean bias for the five laboratories ranged from 6 to 15%; however, the SD of the bias ranged from 8 to 29%. As a result of this intercomparison study, one laboratory discovered and corrected a method calculation error and another laboratory modified and improved their LC-MS/MS method.
10.5740/jaoacint.17-0183
pubmed_108_18321
The aim of the study was to study the parameters of the lipid peroxidation system and antioxidant protection in saliva in lung cancer of various histological types. In the case-control study, 740 volunteers participated in the study, which were divided into 3 groups: primary (lung cancer, n = 347), comparison group (non-malignant pulmonary pathologies, n = 178) and control (conditionally healthy, n = 215). Questioning, biochemical examination of saliva, histological verification of the diagnosis were conducted to all participants. The parameters of lipoperoxidation and antioxidant protection are determined spectrophotometrically. Intergroup differences are estimated by a nonparametric criterion. Against the background of lung cancer, the development of oxidative stress is observed, which is manifested in the increase in the level of lipid peroxidation products, as well as in the reduction of antioxidant protection in saliva. It is shown that the activity of the enzymes of the first link of antioxidant protection is significantly reduced (p<0.0001), whereas the activity of salivary peroxidases increases (p = 0.0037). The parameters of non-enzymatic protection vary in different directions: the level of uric acid in lung pathologies decreases (p = 0.0399), whereas albumin concentration increases, under these conditions, it begins to exhibit pro-oxidant properties. Differences between non-small cell and neuroendocrine lung cancer have been revealed by the nature of the dynamics of antioxidant protection indices. In general, the disturbance of the balance of the lipid peroxidation system and antioxidant protection is the result of a disruption in the coordination of immunometabolic processes and indicates a decrease in adaptive reactions of the organism.
10.18821/0869-2084-2018-63-9-530-537
pubmed_918_24741
The starvation-predation hypothesis predicts that, during resource shortages, prey forego antipredator behavior and forage as much as possible to avoid starvation, even when risk of predation is high. We tested this hypothesis using GPS locations collected simultaneously from moose (Alces alces) and wolves (Canis lupus) in the Greater Yellowstone Ecosystem of North America. We assessed shifts in the speed, displacement, and habitat selection of moose 24 h following encounter with wolves (0-1,500 m distance). We examined whether the strength of antipredator behaviors would weaken as winter progressed and the nutritional condition of moose declined. Moose responded to wolf encounters by increasing their rate of movement in early winter, but only within 500 m distance. Importantly, these responses attenuated as winter progressed. Moose did not avoid their preferred foraging habitat (riparian areas) following encounters with wolves at any distance, and instead they more strongly selected riparian areas, especially in early winter. Our findings support theoretical predictions that resource deficits should dampen prey antipredator behavior, and suggest that nutritional condition of prey may buffer against run-away risk effects in food webs involving large mammalian predators and prey.
10.1002/ecy.2618
pubmed_984_22683
This study sought to determine whether adolescents' strategic management of information about their misbehavior was associated with behavior problems and whether the associations were moderated by parental trust or adolescent authority beliefs. Data were provided by 218 mother-adolescent dyads. Adolescents (49% female; M age=12 years) reported their use of two disclosing (i.e., telling all, telling if asked) and three concealing (i.e., omitting details, secret keeping, lying) strategies following misbehavior. More disclosing and less concealing were associated with less depressed mood and with less antisocial and rule-breaking behavior. Associations between strategy use and antisocial and rule-breaking behavior were attenuated when parents reported high trust or adolescents reported strong authority beliefs. Greater use of concealing strategies following misbehavior is more likely to be a sign of trouble than a sign of emerging autonomy, but the negative effects of concealment are attenuated in some relational contexts.
10.1016/j.adolescence.2009.05.018
pubmed_448_24060
INTRODUCTION Although systematic reviews have shown how decision aids about cancer-related clinical decisions improve selection of key options and shared decision-making, whether or not particular decision aids, defined by their specific presentation formats, delivery methods and other attributes, can perform better than others in the context of cancer-screening decisions is uncertain. Therefore, we planned an overview to address this issue by using standard umbrella review methods to repurpose existing systematic reviews and their component comparative studies. METHODS AND ANALYSIS We will search PubMed, Embase, the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects from inception through 31 December 2021 with no language restriction and perform full-text evaluation of potentially relevant articles. We will include systematic reviews of randomised controlled trials or non-randomised studies of interventions that assessed a decision aid about cancer-screening decisions and compared it with an alternative tool or conventional management in healthy average-risk adults. Two reviewers will extract data and rate the study validity according to standard quality assessment measures. Our primary outcome will be intended and actual choice and adherence to selected options. The secondary outcomes will include attributes of the option-selection process, achieving shared decision-making and preference-linked psychosocial outcomes. We will qualitatively assess study, patient and intervention characteristics and outcomes. We will also take special care to investigate the presentation format, delivery methods and quality of the included decision aids and assess the degree to which the decision aid was delivered and used as intended. If appropriate, we will perform random-effects model meta-analyses to quantitatively synthesise the results. ETHICS AND DISSEMINATION Ethics approval is not applicable as this is a secondary analysis of publicly available data. The review results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42021235957.
10.1136/bmjopen-2021-051156
pubmed_475_6521
INTRODUCTION The orthographic depth hypothesis (Katz and Feldman, 1983) posits that different reading routes are engaged depending on the type of grapheme/phoneme correspondence of the language being read. Shallow orthographies with consistent grapheme/phoneme correspondences favor encoding via non-lexical pathways, where each grapheme is sequentially mapped to its corresponding phoneme. In contrast, deep orthographies with inconsistent grapheme/phoneme correspondences favor lexical pathways, where phonemes are retrieved from specialized memory structures. This hypothesis, however, lacks compelling empirical support. The aim of the present study was to investigate the impact of orthographic depth on reading route selection using a within-subject design. METHOD We presented the same pseudowords (PWs) to highly proficient bilinguals and manipulated the orthographic depth of PW reading by embedding them among two separated German or French language contexts, implicating respectively, shallow or deep orthography. High density electroencephalography was recorded during the task. RESULTS The topography of the ERPs to identical PWs differed 300-360 ms post-stimulus onset when the PWs were read in different orthographic depth context, indicating distinct brain networks engaged in reading during this time window. The brain sources underlying these topographic effects were located within left inferior frontal (German > French), parietal (French > German) and cingular areas (German > French). CONCLUSION Reading in a shallow context favors non-lexical pathways, reflected in a stronger engagement of frontal phonological areas in the shallow versus the deep orthographic context. In contrast, reading PW in a deep orthographic context recruits less routine non-lexical pathways, reflected in a stronger engagement of visuo-attentional parietal areas in the deep versus shallow orthographic context. These collective results support a modulation of reading route by orthographic depth.
10.3389/fnhum.2014.00083
pubmed_452_17678
BACKGROUND Compared with traditional open surgery for thymectomy, video-assisted thoracoscopic surgery (VATS) reduces hospital stay, decreases postoperative pain, and recovers faster. VATS has become increasingly popular in the past decade. VATS techniques to perform a thymectomy include subxiphoid video-assisted thoracoscopic surgery (SVATS) or lateral video-assisted thoracoscopic surgery (LVATS). In this study, our objective was to systematically review on VATS thymectomy and draw a meta-analysis on the outcomes between the two approaches. METHODS We searched online databases and identified studies from database inception to 2019 that compared SVATS to LVATS thymectomy. Study endpoints included operative time, operative blood loss, length of hospital stay, postoperative pleural drainage, postoperative complications, conversion to open, oncologic outcomes. RESULTS Four hundred seventy-one patients were included in this study, for which 200 and 271 patients underwent SVATS and LVATS thymectomy, respectively. Patients in the SVATS group had significantly less operative time, operative blood loss, length of hospital stay, and postoperative complications were identified. There was no statistical difference in postoperative pleural drainage, conversion to open and oncologic outcomes. No hospital deaths were recorded for either procedure. CONCLUSIONS While randomized controlled studies are required to make definitive conclusions, this meta-analysis suggests that SVATS thymectomy is safe and can achieve good and safe operative and perioperative outcomes similar or better to LVATS thymectomy.
10.1186/s13019-020-01135-w
pubmed_900_24556
The live and pretreated mycelial pellets/biomass of Trametes versicolor was used for the biosorption of a textile dye, reactive blue MR (RBMR) from aqueous solution. The parameters that affect the biosorption of RBMR, such as contact time, concentration of dye and pH, on the extent of RBMR adsorption were investigated. To develop an effective and accurate design model for removal of dye, adsorption kinetics and equilibrium data are essential basic requirements. Lagergren first-order, second-order and Bangham's model were used to fit the experimental data. Results of the kinetic studies showed that the second order kinetic model fitted well for the present experimental data. The Langmuir, Freundlich and Temkin adsorption models were used for the mathematical description of the biosorption equilibrium. The biosorption equilibrium data obeyed well for Langmuir isotherm and the maximum adsorption capacities were found to be 49.8, 51.6, 47.4 and 46.7 mg/g for live, autoclaved, acid- and alkali-pretreated biomass. The dye uptake capacity order of the fungal biomass was found as autoclaved > live > acid-treated > alkali-pretreated. The Freundlich and Temkin models were also able to describe the biosorption equilibrium on RBMR on live and pretreated fungal biomass. Acidic pH was favorable for the adsorption of dye. Studies on pH effect and desorption show that chemisorption seems to play a major role in the adsorption process. On comparison with fixed bed adsorption, batch mode adsorption was more efficient in adsorption of RBMR.
10.1002/biot.200600238
pubmed_703_11023
PURPOSE To investigate the prevalence and clinical features of ocular abnormalities in patients with cerebral palsy (CP) and the association with gross motor function. METHODS A complete ophthalmologic examination was performed in 88 consecutive patients with CP before and during orthopedic surgery in a tertiary hospital from July 2008 to March 2010. The prevalence and clinical features of ocular abnormalities and the association with gross motor function state were investigated. RESULTS Seventy-eight patients (89%) had ocular abnormalities. Refractive errors were found in 53 patients (60%). Strabismus including exotropia (50%), esotropia (9%), and hypertropia (9.1%) was found in 52 patients (59%). Posterior segment abnormalities were found in 19 patients (22%), cornea and lens abnormalities in 8 patients (9%), and epiblepharon in 5 patients (6%). Among 57 patients whose visual acuity could be measured, best-corrected visual acuity of the better eye was ≤ 20/40 in 18 patients (32%) and ≤ 20/200 in 3 patients (5%). Objective vision-impairing ocular abnormalities and vertical strabismus were significantly associated with poor gross motor function before orthopedic surgery. CONCLUSIONS Ocular abnormalities were present in the majority of CP patients and patients with poor gross motor function were more likely to be afflicted with vision-impairing ocular abnormalities. Ophthalmologic evaluation is deemed necessary in CP patients, especially in those with poor motor function.
10.1097/OPX.0b013e3182346711
pubmed_836_21507
OBJECTIVE To investigate the function of microtubules in volume overload cardiac hypertrophy of rat. METHODS The structure of microtubules was observed using an immunofluorescent microscope, while the pixel intensity and distribution of microtubule imaging was estimated from laser scanning confocal images of left ventricular cardiocytes immuno-labeled with an antibody to beta-tubulin. RESULTS The pixels of the microtubule image taken just after volume overload were not evenly distributed. At 6 hours after overload, the pixel intensity of the microtubule image was decreased to less than 150 (arbitrary units), which was the same as the pixel intensity and distribution of the colchicine depolymerized microtubule image. The changes were partially recovered to 200 (arbitrary units) after 4 more days. The pixel intensity of the control microtubule image was 250 (arbitrary units) and had an even distribution. The structuring of the microtubules was more disordered as volume overload hypertrophy developed. CONCLUSIONS There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in the hypertrophic myocardium and microtubule is one of the members of the signal transduction pathways governing the hypertrophic response of cardiomyocytes in the hypertrophic myocardium. The disordered microtubule array may be targeted during heart failure treatment.
pubmed_836_21507
pubmed_526_11477
Starting with a clinical case study, we present the potential risks of Hymenoptera envenomation and discuss the treatment of victims of multiple stings.
pubmed_526_11477
pubmed_314_793
Polycationic materials commonly used to delivery DNA to cells are known to induce cell membrane porosity in a charge-density dependent manner. It has been suggested that these pores may provide a mode of entry of the polymer-DNA complexes (polyplexes) into cells. To examine the correlation between membrane permeability and biological activity, we used two-color flow cytometry on two mammalian cell lines to simultaneously measure gene expression of a plasmid DNA delivered with four common nonviral vectors and cellular uptake of normally excluded fluorescent dye molecules of two different sizes, 668 Da and 2 MDa. We also followed gene expression in cells sorted based on the retention of endogenous fluorescein. We have found that cell membrane porosity caused by polycationic vectors does not enhance internalization or gene expression. Based on this single-cell study, membrane permeability is found to be an unwanted side effect that limits transfection efficiency, possibly through leakage of the delivered nucleic acid through the pores prior to transcription and translation and/or activation of cell defense mechanisms that restrict transgene expression.
10.1021/mp100027g
pubmed_428_6844
Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease.
10.1016/j.ajpath.2017.04.016
pubmed_465_5520
Human milk beta-N-acetylglucosaminide beta 1 leads to 4-galactosyltransferase (EC 2.4.1.38) was used to galactosylate ovine submaxillary asialomucin to saturation. The major [14C]galactosylated product chain was obtained as a reduced oligosaccharide by beta-elimination under reducing conditions. Analysis by Bio-Gel filtration and gas-liquid chromatography indicated that this compound was a tetrasaccharide composed of galactose, N-acetylglucosamine and reduced N-acetylgalactosamine in a molar ratio of 2:0.9:0.8. Periodate oxidation studies before and after mild acid hydrolysis in addition to thin-layer chromatography revealed that the most probable structure of the tetrasaccharide is Gal beta 1 leads to 3([14C]Gal beta 1 leads to 4GlcNAc beta 1 leads to 6)GalNAcol. Thus it appears that Gal beta 1 leads to 3(GlcNAc beta 1 leads to 6)GalNAc units occur as minor chains on the asialomucin. The potential interference of these chains in the assay of alpha-N-acetylgalactosaminylprotein beta 1 leads to 3-galactosyltransferase activity using ovine submaxillary asialomucin as an acceptor can be counteracted by the addition of N-acetylglucosamine.
10.1016/0304-4165(83)90269-6
pubmed_250_16753
Melatonin reduces proliferation in many different cancer cell lines. However, studies on the oncostatic effects of melatonin in the treatment of hepatocarcinoma are limited. In this study, we examined the effect of melatonin administration on HepG2 human hepatocarcinoma cells, analyzing cell cycle arrest, apoptosis and mitogen-activated protein kinase (MAPK) signalling pathways. Melatonin was dissolved in the cell culture media in 0.2% dimethyl sulfoxide and administered at different concentrations for 2, 4, 6, 8 and 10 days. Melatonin at concentrations 1000-10,000 microM caused a dose- and time-dependent reduction in cell number. Furthermore, melatonin treatment induced apoptosis with increased caspase-3 activity and poly(ADP-ribose) polymerase proteolysis. Proapoptotic effects of melatonin were related to cytosolic cytochrome c release, upregulation of Bax and induction of caspase-9 activity. Melatonin treatment also resulted in increased caspase-8 activity, although no significant change was observed in Fas-L expression. In addition, JNK 1,-2 and -3 and p38, members of the MAPK family, were upregulated by melatonin treatment. Growth inhibition by melatonin altered the percentage or cells in G0-G1 and G2/M phases indicating cell cycle arrest in the G2/M phase. The reduced cell proliferation and alterations of cell cycle were coincident with a significant increase in the expression of p53 and p21 proteins. These novel findings show that melatonin, by inducing cell death and cell cycle arrest, might be useful as adjuvant in hepatocarcinoma therapy.
10.1111/j.1600-079X.2008.00641.x
pubmed_367_14180
Although patients with obstructive jaundice are susceptible to bacterial infections and cancers, the mechanisms remain to be elucidated. In the present study, liver mononuclear cells (MNCs) of bile duct-ligated (BDL) mice were immunologically assessed. Liver natural killer T cells were greatly decreased within 24 h after BDL. Upon injection of Escherichia coli (E. coli; 10 colony-forming units) at 7 days after the procedure, all BDL mice had died, but no sham mice died. Consistently, an overgrowth of E. coli was seen in the livers of BDL mice. Although the serum IL-12 and IL-18 levels after E. coli challenge in BDL mice were higher than those in sham mice, the IFN-gamma level was greatly suppressed. However, exogenous IFN-gamma injection significantly increased BDL mouse survival after E. coli challenge. Furthermore, liver MNC of BDL mice exhibited a lower cytotoxic activity against tumors, and BDL mice intravenously injected with liver metastatic EL-4 cells showed markedly increased EL-4 metastases. The total bile acids, as well as the bile acid fractions, increased in the sera and liver. IFN-gamma production by liver MNC from normal mice stimulated with LPS in vitro was inhibited by the addition of bile acids, whereas, conversely, the production of IL-12 and IL-18 increased. In conclusion, liver natural killer T cells were diminished in BDL mice, and the function of liver MNC (IFN-gamma production) was also impaired presumably due to increased bile acids. This may partly explain the increased susceptibility of BDL mice to bacterial infections and tumor metastasis.
10.1097/SHK.0b013e3181c4e44a
pubmed_740_10236
BACKGROUND It is well accepted that both rosuvastatin and resveratrol exert neuroprotective effects on cerebral ischemia/reperfusion injury through some common pathways. Resveratrol has also been demonstrated to protect against cerebral ischemia/reperfusion injury through enhancing autophagy. Thus, we hypothesized that combined rosuvastatin and resveratrol pretreatment had synergistic effects on cerebral ischemia/reperfusion injury. MATERIALS AND METHODS Adult male Sprague Dawley rats receiving middle cerebral artery occlusion surgery as animal model of cerebral ischemia/reperfusion injury were randomly assigned to 4 groups: control, resveratrol alone pretreatment, rosuvastatin alone pretreatment, and combined rosuvastatin and resveratrol pretreatment. Rosuvastatin (10 mg/kg) or resveratrol (50 mg/kg) was administrated once a day for 7 days before cerebral ischemia onset. RESULTS We found that combined rosuvastatin and resveratrol pretreatment not only significantly decreased the neurologic defective score, cerebral infarct volume, the levels of caspase-3, and Interleukin-1β (IL-1β) but also significantly increased the ratios of Bcl-2/Bax and LC3II/LC3I, as well as the level of Becline-1, compared with resveratrol alone or rosuvastatin alone pretreatment group. Rosuvastatin alone pretreatment significantly increased the ratio of LC3II/LC3I and the level of Beclin-1. However, there were no significant differences in the neurologic defective score, cerebral infarct volume, the levels of caspase-3, IL-1β, and Beclin-1, and the ratios of Bcl-2/Bax and LC3II/LC3I between resveratrol pretreatment group and rosuvastatin pretreatment group. CONCLUSIONS Synergistically enhanced antiapoptosis, anti-inflammation, and autophagy activation might be responsible for the synergistic neuroprotective effects of combining rosuvastatin with resveratrol on cerebral ischemia/reperfusion injury.
10.1016/j.jstrokecerebrovasdis.2018.01.033
pubmed_111_15758
Clinical experience in the selection of patients for implantation of the artificial urinary sphincter and the surgical techniques for sphincter implantation indicate a need to provide suitable guidelines for patient followup and the management of post-implantation urinary incontinence. Two types of post-implantation incontinence are recognized: 1) immediate post-activation incontinence and 2) delayed or recurrent incontinence. The potential causes, and the diagnostic and management techniques are dependent on not only an understanding of device function but also on the use of already available clinical tools. Physical examination, inflate-deflate roentgenograms of the device, cystoscopy and retrograde urethrography each has an important role in determining the cause and, therefore, the appropriate remedy for the restoration of urinary control. Causes that result in loss of urinary control after implantation include improper operation of the device by the patient, detrusor hyperreflexia, occlusive cuff erosion, improper cuff sizing and device malfunction. Proper recognition of the precise cause of post-implantation incontinence and workable guidelines for management will provide for effective assurance that urinary control can be restored successfully.
10.1016/s0022-5347(17)49230-5
pubmed_36_1081
RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III-related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development.
10.1101/gr.176925.114
pubmed_714_12425
UNLABELLED The high prevalence of atrial fibrillation (AF) and its clinical complications, the poor efficacy of medical therapy for preventing recurrences, and dissatisfaction with alternative modes of therapy stimulated interest in implantable atrial and combined atrioventricular defibrillators. In a multicenter study, the safety and efficacy of a stand alone implantable atrial defibrillator, the Metrix system, were evaluated. The device was implanted in 51 patients with highly symptomatic episodes of AF refractory to pharmacological treatment. During a follow-up of 9 months, 96% of 227 spontaneous AF episodes were successfully converted to sinus rhythm in 41 patients. In 62 episodes (27%), several shocks and/or additional drug treatment were required to maintain stable sinus rhythm because of early recurrences of AF. A total of 3719 shocks were delivered and no induction of ventricular proarrhythmia or inaccurately synchronized shocks occurred. The AF detection algorithm exhibited a 100% specificity for the recognition of sinus rhythm and a 92.3% sensitivity for the detection of AF. The combined atrioventricular defibrillator, Jewel AF 7250, was evaluated in a multicenter, randomized, cross-over trial. The primary study objectives included: overall safety as determined by complications-free survival at 6 months, efficacy of tiered atrial pacing and defibrillation therapies for termination of spontaneous atrial tachycardias (AT) and AF, and relative sensitivity of a new dual-chamber detection algorithm. The device was implanted in 211 patients with either a history of ventricular tachyarrhythmias (VT/VF) alone or with a history of both AT/AF and VT/VF. During a mean follow-up of 4.5 months, it has been shown that the Jewel AF is safe and effective in treating atrial and ventricular tachyarrhythmias. Pace termination of 85% of AT episodes were achieved with painless delivery of antitachycardia pacing; additional 35% of AT episodes were terminated by high frequency burst pacing. CONCLUSIONS The stand alone implantable atrial defibrillator may be safe and clinically useful in selected patients for the treatment of highly symptomatic, drug resistant recurrences of AF. The combined atrioventricular defibrillator may be particularly indicated in patients presenting with both a history of atrial and ventricular tachyarrhythmias.
10.1023/a:1009819707643
pubmed_692_17685
The use of formamidine sulfinic acid in the textile industry goes back many years, particularly as an agent for the reduction or "vatting" of vat dyes, to form the water-soluble leuco species, when dyeing or printing cellulosic fibers. Many workers have labeled this agent as thiourea dioxide and theorized that its reducing power developed through the existence of two isomeric forms: thiourea dioxide (the sulfone), and formamidine sulfinate. This article has used solid and solution Fourier transform infrared (FT-IR) spectroscopy to show that the name thiourea dioxide is a misnomer since the compound does not exist in the six-valent state, but is stabilized in the four-valent state by formation of a strong internal zwitterion as shown in the article.
10.1366/13-07306
pubmed_1051_23456
Blue mold caused by Penicillium italicum is a severe postharvest disease in citrus fruits. In this study, the fermentation product (FP-E) of Aspergillus aculeatus GC-09, an endophytic fungus isolated from a citrus plant, was found to exhibit antifungal activity against P. italicum with a MIC of 0.3125 mg/mL. The fungus A. aculeatus GC-09 was identified based on the studies of morphology and ITS nucleotide sequence. FP-E significantly inhibited the spore germination and mycelial growth of P. italicum. Scanning electron microscopy (SEM) results of P. italicum treated with FP-E showed shrunken, distorted and collapsed hyphae and conidiospores, indicative of the cell membrane damage, which was further confirmed by the propidium iodide (PI) fluorescent staining analysis. Consistent with the microscopy observation, FP-E led to the leakage of cellular constituents from P. italicum, which is evident from the increase in electrical conductivity and nucleic acid contents in the mycelial solution incubated with FP-E. In addition, FP-E treatment considerably increased the intracellular reactive oxygen species (ROS) content, and reduced the enzyme activities of both catalase (CAT) and peroxidase (POD) in P. italicum cells. Furthermore, orange fruits treated with FP-E showed fewer disease symptoms compared to the untreated fruits. These results suggested that the antifungal activity of FP-E might be associated with the disruption of cell membrane integrity, the accumulation of ROS level, and the reduction of the antioxidant enzymes activity of P. italicum. Therefore, A. aculeatus GC-09 might be a potential microbial resource for the biocontrol of citrus postharvest blue mold.
10.1016/j.funbio.2021.12.006
pubmed_524_16666
Birds are strongly motivated to recognize various predators to secure survival and reproductive success. Thus, predator recognition provides a useful tool for the investigation of the process of discrimination and categorization in non-trained animals. The most important role in this process is usually attributed to the prominent unique features shared by all members within the wider category of predators (sharp teeth or beaks, claws, talons and conspicuous eyes). However, birds are also able to discriminate between particular predator species according to their species-specific features (based mainly on colouration). We manipulated general raptor salient features (hooked beak, talons with claws and eyes with supraorbital ridges) and/or species-specific plumage colouration on the dummy of a Eurasian kestrel (Falco tinnunculus) to investigate their importance in the recognition process of the red-backed shrikes (Lanius collurio) during nest defence. We showed that the presence of general raptor salient features is necessary for the recognition of a predator. The kestrel dummy with natural species-specific colouration with altered raptor salient features was treated by shrikes as a harmless bird. Nevertheless, pronounced changes in colouration also prevented successful recognition of the dummy as a kestrel, even when raptor salient features of a raptor were present.
10.1007/s10071-020-01450-8
pubmed_906_24043
Joint Implementation under the Climate Change Convention and Clean Development Mechanism of the Kyoto Protocol require a scientific understanding of current carbon stocks, fluxes, and sequestration potential, especially in tropical ecosystems where there are large carbon reservoirs, significant carbon emissions, and large land areas available for reforestation. Central Africa contains 10% of the world's remaining tropical moist forests and has received little attention in carbon studies. In 1980, above-ground carbon stocks in the central African ecosystem were 28.92 Pg and were reduced to 24.79 Pg by 1990. Improved forest management aimed at increasing biomass density could sequester 18.32 Pg of carbon, and over 500,000 km2 formerly forested land will be available by 2050 for reforestation with a capacity to offset 10 Pg carbon. Understanding the spatial distribution of biomass carbon and sequestration potential will be essential for carbon trading initiatives through Joint Implementation and Clean Development Mechanism.
10.1579/0044-7447-30.6.351
pubmed_76_7395
An ectoenzyme hydrolyzing diadenosine polyphosphates (ApnA) to AMP and Ap(n-1) has been studied in cultured chromaffin cells from bovine adrenal medulla. The KM value for extracellular Ap4A hydrolysis was 2.90 +/- 0.72 microM, the V(max) value obtained was 11.59 +/- 0.92 pmol/min x 10(6) cells (116 pmol/min.mg total protein). Ap3A, Ap5A, Ap6A, and Gp4G were competitive inhibitors of Ap4A hydrolysis with K(i) values of 3.65, 1.10, 1.20, and 2.65 microM, respectively. Phosphatidylinositol-specific phospholipase C removes the ApnA hydrolase activity from cultured chromaffin cells, suggesting an anchorage of this protein to the plasma membrane through the phosphatidylinositol. The turnover time for this enzyme calculated in the presence of cycloheximide was 38.94 +/- 1.53 hr for cultured chromaffin cells.
10.1016/0003-9861(92)90657-i
pubmed_1133_16042
BACKGROUND Returning to employment is a major modifiable factor affecting long-term health in brain injury which neurological and vocational rehabilitation attempts to address. In military patients, little is known about long-term employability, whether employment is sustained and how they fare in civilian roles. METHODS A telephone review was undertaken of every military patient having undergone inpatient neurorehabilitation between 2012 and 2014. This was compared to their employment outcomes one to three years post discharge. We further evaluated whether this employment was sustained over successive years in the same patients. Finally, we identify those rehabilitation interventions deemed most influential in improving employment outcomes in brain injury. RESULTS During this period, an average of 57 (51-61) such patients were discharged each year. A review conducted by telephone successfully contacted 46% (43%-49% across cohorts) of all possible patients; 71.4% (64-81) returned to work increasing to 80.7% (76-85) including those training/actively seeking-work. Overall, 31.7% (24-40) returned to full-time military-in those leaving, 89.6% (85.4-90.9) were discharged for medical reasons. Severity of brain injury was unrelated to successful employment; 63.6%/78.6% had the same vocational outcome over two consecutive years while 36.3%/21.4% showed improved outcomes. DISCUSSION Despite significant brain/neurological injury (graded by severity/Mayo Portland Adaptability Inventory 4), 80.7% (76-85) were working/training 2/3 years postdischarge from neurorehabilitation with 31.7% returning to full-time military role. Inability to continue within the military was not synonymous with inability to work. Return to work was independent of severity of brain/neurological injury and follow-up over consecutive years demonstrated sustained employment. The argument against inpatient neurorehabilitation has always been cost> This 3-year analysis reinforces that patients can and most likely will return to employment with all the benefits this brings to person/family/society. Vocational rehabilitation is therefore recommended for all brain/neurological injury.
10.1136/jramc-2016-000703
pubmed_359_21873
The pharynx and larynx represent very sophisticated regions and may be involved in a diverse range of pathologic conditions. Evaluation of the head and neck has developed significantly with the establishment of CT and MRI as they provide true insights into the endoscopically blind areas as well as depth of tumor infiltration, its submucosal growth and contralateral involvement, cartilage invasion, bone marrow invasion, and nonpalpable adenopathy. Inflammations in the head and neck region are only exceptionally imaged with CT or MRI; indications are the diagnosis of retrotonsillar and parapharyngeal abscesses and ensuing complications. The different imaging modalities of malignant pharyngeal and laryngeal tumors and their differential diagnosis are presented in this paper.
10.1007/s00117-005-1257-3
pubmed_351_2252
The present investigation was carried out to identify salivary components of mucosal pellicles in vivo and explore further the mechanism of interaction between salivary molecules and buccal epithelial cells. By using specific antisera and immunoprotein blotting, high-(MG1) and low-(MG2) molecular-mass salivary mucins, amylase, salivary cystatins and proline-rich proteins were detected within mucosal pellicle in vivo. In addition, the data indicated that the mucins and proline-rich proteins could be cleaved into lower-molecular-mass products, whereas the proline-rich proteins could also be cross-linked into higher-molecular-mass complexes. The role of buccal epithelial cell transglutaminase in these interactions was further studied by utilizing purified iodinated amylase, neutral cystatin SN and acidic proline-rich proteins 1 and 3 (APRP1 and 3). After incubation with buccal epithelial cells in vitro 125I-labelled APRPs appeared to undergo a greater degree of cross-linking than 125I-labelled cystatin SN, as determined by SDS/PAGE/autoradiography. Amylase did not appear to be cross-linked at all. Recovery of 125I-labelled APRPs and 125I-labelled cystatin SN with epithelial cell envelopes after repeated extraction suggested that both molecules were cross-linked to envelope proteins, but that 125I-labelled APRPs were cross-linked to a greater degree than 125I-labelled cystatin SN. Cross-linking in buccal epithelial cell preparations was inhibited by an excess of methylamine hydrochloride, a transglutaminase substrate. In a further assessment of amylase, cystatin and APRPs as transglutaminase substrates, only APRP3 and a partially purified preparation of APRPs acted as an amine acceptor for the cross-linking of [14C]methylamine by purified transglutaminase, as determined by SDS/PAGE/fluorography. This reaction was completely inhibited by excess EDTA. The combined data from this study suggest that during mucosal pellicle formation multiple components of saliva adsorb to buccal epithelial cell surfaces, and that, within this group, selected components are enzymically cross-linked by an epithelial transglutaminase and/or proteolytically cleaved into smaller fragments.
10.1042/bj2840557
pubmed_407_6957
Since its introduction in 1983, transanal endoscopic microsurgery (TEM) has emerged as a safe and effective method to treat rectal lesions including benign tumors, early rectal cancer, and rectal fistulas and strictures. This minimally invasive technique offers the advantages of superior visualization of the lesion and greater access to proximal lesions with lower margin positivity and specimen fragmentation and lower long-term recurrence rates over traditional transanal excision. In addition, over two decades of scientific data support the use of TEM as a viable alternative to radical excision of the rectum with less morbidity, faster recovery, and greater potential cost savings when performed at specialized centers.
10.7812/tpp/11-120
pubmed_421_708
BACKGROUND Many studies have been carried out in modelling COVID-19 pandemic. However, region-wise average duration of recovery from COVID-19 has not been attempted; hence, an effort has been made to estimate state-wise recovery duration of India's COVID-19 patients. Determining the recovery time in each region is intended to assist healthcare professionals in providing better care and planning of logistics. METHODS This study used database provided by Kaggle, which takes data from the Ministry of Health & Family Welfare. The simple Linear Regression model between incidence, prevalence, and duration was used to assess the duration of COVID-19 disease in various Indian states. RESULTS The fitted model suits ideal for most of the states, except for some union territories and northeastern states. The average time to recover from disease was ranging from 5 to 36 days in Indian states/union territories except for Madhya Pradesh. Tamil Nadu has an average recovery time of 7 days with an value of 0.96, followed by Odisha, Karnataka, West Bengal, Kerala and Chhattisgarh and the average recovery duration was estimated as 7, 13, 17, 11, 14 and 12 days respectively. CONCLUSION The average recovery from COVID-19 was ten or less days in twenty percentage of states, whereas in forty-four percentage of states/union territories had an average recovery duration between ten to twenty days. However, around twentyfour percentage of states/union territory recovered between twenty to thirty days. In the rest of Indian states/union territories, the average duration of recovery was more than thirty days.
10.1016/j.cegh.2021.100740
pubmed_729_2164
Special features of the use of homo- and heteronuclear correlation methods of NMR in one and two dimensions for studying the spatial structure and intramolecular dynamics of modified analogues of steroid hormones (MASH) are considered. The application of these methods to the assignment of resonances in the high-field 1H NMR region and to the determination of the most stereospecifically important parameters, such as the vicinal constants of spin-spin coupling (3JH-H) and nuclear Overhauser effects (NOE), are discussed using the example of NMR studies of some estrogens and androgens at 300 MHz and on the basis of literature data. The most efficient combination of the methods and the necessary modification of each of them may be chosen considering the spectral and relaxation parameters of MASH in liquid medium, including the anisotropy of the overall diffusive motion. The characteristics of MASH are the wide use of correlations through long-range couplings (COSY-45 and DQF-COSY), the application of the 4,5JH-H constants for the determination of spatial structure, and the advantage of heteronuclear HSQC methods with and without 13C decoupling over the corresponding HMQC methods in both resolution and sensitivity. In the conformationally rigid MASH molecules, the anisotropy of the MASH diffusive motion in liquid adversely affects the determination of interproton distances by the calibrating processing method for the NOE difference and NOESY spectra: it results in both overestimated and underestimated distance values depending on the polar angle ratios of the reference and the determined distances. Under certain conditions, conformationally mobile MASH demonstrate the additional contribution of the scalar relaxation mechanism between the indirectly (scalarly) bound protons. This mechanism is responsible for the underestimated values of NOE and the corresponding errors in the distance determination.
10.1023/a:1015704203799
pubmed_609_14450
Activation of the emergency medical services (EMS) system does not always result in transport of a patient to the hospital. This study assessed the outcomes of patients who refused medical assistance in the field, to determine if refusal of medical assistance (RMA) is associated with poor outcomes. Four high-volume suburban volunteer ambulance corps participated in the study. Consecutive patients who refused medical assistance were prospectively enrolled. Medical and identifying data were collected for each patient. Telephone follow-up was conducted to determine the patient's condition and if the patient sought further care after RMA. Primary endpoints were whether the patient sought further care, was admitted to a hospital, or died subsequent to RMA. Follow-up was successfully obtained for 199 of 321 patients enrolled (62%). Of these 199 patients, 95 (48%) sought further medical care within 1 week for the same complaint, with 13 being admitted to the hospital. Six of the 13 admitted patients had chief complaints of a cardiac or respiratory nature. One patient died during hospital admission. Even if none of the patients lost to follow-up had sought further care, a substantial number of patients who refuse out-of-hospital medical assistance seek further care. Some of these patients require hospital admission, especially those with cardiac or respiratory complaints. Efforts to minimize RMA should be especially focused on patients with such complaints.
10.1016/s0735-6757(96)90007-8
pubmed_624_11886
This article presents evidence that in 1983 excess demand was a prevailing characteristic of nursing home care markets in Wisconsin, a state with one of the highest bed to elderly population ratios. It further shows that excess demand is the source of at least three types of error in use-based estimates of the determinants of the need for nursing home care. First, if excess demand is present, estimates of the determinants of Medicaid use may simply represent a crowding out of Medicaid patients, driven by the determinants of private use. As a result, factors associated with greater overall need in an area will be correlated with fewer Medicaid patients in nursing homes, ceteris paribus. Second, estimates of the substitutability of home health care for nursing home care may be misleadingly insignificant if they are based on the bed supply-constrained behavior of Medicaid-eligible subjects. Third, because the determinants of bed supply become the determinants of overall use under excess-demand conditions, the determinants of use will reflect, to some extent, the nursing home's desire for profits. Because profitability considerations are reflected in use based estimates of need, these estimates are likely to be misleading.
pubmed_624_11886
pubmed_412_14755
The incidence of Clostridium difficile-associated diarrhoea has increased during the last few years. Treatment with vankomycin or metronidazol is usually effective, but relapses are not uncommon. Some good results have been reported with faecal enemas, but it is a controversal form of treatment. 18 patients with C. difficile-associated diarrhoea were given homologous faeces from one healthy donor. In 17 patients faeces was instillated via a coloscope and in one patient via a gastrostoma. C. difficile toxin was detected in all patients. Three patients with severe colitis did not respond to the treatment. The remaining patients were clinically cured, and no relapses were observed. Treatment of C. difficile-associated diarrhoea with faeces appears to be an alternative in moderate cases. In our limited number of patients we observed a poor correlation between the clinical picture, the endoscopic findings and the histological findings in colon biopsies. The ethical aspects of treatment with faeces will continue to be subject to discussion.
pubmed_412_14755
pubmed_786_7155
It is impossible for ICU clinicians to avoid caring for dying patients and their families. For many, this is an extremely rewarding aspect of their clinical practice. There is ample evidence that there is room to improve the care of patients who are near death in the ICU. Despite the considerable holes in our knowledge about optimal care of dying critically ill patients, there is considerable agreement on the general principles of caring for these patients and about how to measure the outcomes of palliative care in the ICU. Practical approaches to improving the quality of end-of-life care exist and should be implemented.
10.1016/s0272-5231(03)00093-5
pubmed_1110_10524
The aim of the European Reference Network for Rare Endocrine Disorders (Endo-ERN) is to ensure equal access to high-quality care for all those affected by a rare endocrine condition across Europe, such as a disorder/difference of sex development (DSD), both for children and adults. Although differences in resources, health care systems, and health insurances between the European countries are challenging and require political action, a European laboratory network within Endo-ERN could improve the diagnostic process in individuals with DSD, building on the work done by previous European collaborations such as the COST action DSDnet. In close collaboration, clinicians and laboratory specialists must make every effort to standardize diagnostic protocols, achieve necessary harmonization of various laboratory tests, e.g., the hCG stimulation test, and implement an external quality control system. This should ideally result in comparable quality across the network centers allowing the sharing of reference values. This would not only improve patient care but also greatly facilitate research.
10.1159/000486329
pubmed_732_20796
Alport syndrome is a progressive hereditary disease caused by mutations in the genes encoding type IV collagen. Persistent microscopic hematuria is the hallmark of Alport syndrome, occurring in almost all boys according to previous reports. We report the case of a 20-year-old man presented with proteinuria but no hematuria that was initially misdiagnosed with refractory nephrotic syndrome and was eventually diagnosed with Alport syndrome following kidney and skin biopsy. During the follow-up period, he experienced a rapid progression to end-stage renal disease. Timely diagnosis of Alport syndrome is important, because patients may benefit from early intervention and avoid suffering from unnecessary nephrotoxic drug use.
pubmed_732_20796
pubmed_78_7802
The surface dilational elasticity module E of a soluble cationic surfactant at the air-water interface is measured in a frequency range of 1-500 Hz. The data are then correlated with the lifetime of a foam lamella formed with the same surfactant solution. The surface rheological measurement have been performed with an improved design of the oscillating bubble technique that measures precisely the real and imaginary part of the complex dilational module E. The imaginary part captures a dissipative process which is interpreted as an intrinsic surface dilational viscosity kappa. The cationic surfactant 1-dodecyl-4-dimethylaminopyridinium bromide shows a transition between a surface elastic to a viscoelastic behavior with an increase of the bulk concentration. The transition corresponds to a striking increase in the lifetime of the foam lamella. The lamella lifetime of the viscoelastic system exceeds the one of an elastic system by 2 orders of magnitude while the absolute value of the E module remains comparable. The results suggest that surface dilational viscosity kappa is crucial for the ability of a surfactant system to form a stable foam. A simple picture that explains this observation is discussed.
10.1021/la050459c
pubmed_779_4331
Contact seeking with humans is documented in some domestic animals, mainly dogs, which have advanced communication skills. Domestication as a companion animal is thought to underlie this ability. However, also domesticated horses and goats display similar human-directed behaviors. This suggests either a broader effect of domestication on contact-seeking behavior, or alternatively, that social interactions with humans can result in the development of human contact seeking. As part of another study, we observed contact-seeking behavior in juvenile red junglefowl (Gallus gallus) chicks exposed to behavioral training since hatching, during a foraging task, where chicks were singly required to collect food rewards in a familiar arena using odor cues. If chicks left the arena, we recorded if they approached and looked up at the experimenter, or if they approached other objects (including another human). Chicks approached the experimenter significantly more often than they approached other objects. This behavior was not linked to a fast performance in the test arena, which gave some birds more time to explore the surroundings, or to learning ability measured in a cognitive task. Yet, the preference for the experimenter was lower for chicks that were handled more prior to the experiment. Also, approach probability was positively correlated with escape attempts in a novel arena test. The observed variation in approach behavior suggests a link to aspects of personality, and exposure to human interactions and experimental procedures. Our observations suggest that, although neither domesticated nor selectively bred, red junglefowl that are socialized with humans can potentially develop behavior used to describe contact seeking. Together with evidence from cognitive and behavioral studies, our results suggest that social experiences, not only domestication, can affect human-animal interactions. We propose how interactions between behavior, cognition and handling could be studied further in controlled settings to validate the preliminary findings of our study and uncover the underlying mechanisms.
10.3389/fpsyg.2021.675526
pubmed_91_13771
Ten women with specific chronic animal phobias were treated by graded exposure in vivo in two to four two-hour treatment sessions. Sessions were divided into four balanced half-hour epochs, half with visual feedback of true heart rate plus instructions to lower heart rate during approach to phobic stimulus. All patients improved significantly from the start to end of sessions on heart rate and on subjective anxiety. Feedback of heart rate plus instructions to lower it substantially reduced heart rate during epochs of feedback, compared to non-feedback epochs without instructions, but this effect did not generalize to skin conductance or to subjective anxiety in our short-term experiment.
10.1001/archpsyc.1975.01760250125014
pubmed_608_18212
BACKGROUND Medication adherence is a complex area of behaviour. Little is known about what influences chronic patients to take their medicines. This study has aimed to compare and contrast the health-related beliefs, experiences and types of behaviour typical among patients who have at least one chronic condition and are following a pharmacological treatment in accordance with their level of medication adherence. METHODS A questionnaire-based cross-sectional study, consisting of socio-demographic data, the 4-item Morisky-Green scale and 37 statements about health beliefs, perceptions and experiences, was conducted at different levels of healthcare (primary and tertiary settings). RESULTS A total of 577 questionnaires were analyzed. Respondents had a mean age of 64 and took an average of 4.6 drugs. Optimal adherence was reported by 58.6% of respondents. Bivariate analysis showed adherent subjects were older, took more medications, were in better spirits and had greater confidence and information regarding their treatment. Multivariate analysis found older age and the statements 'My doctor periodically reviews my treatment' and 'I am motivated to continue with the treatment' to be significantly related to medication adherence, while 'I make variations when taking medication depending on how I feel' was significant for medication non-adherence. CONCLUSION Medication non-adherence is common among chronic patients. Patient-centred approaches should be implemented in daily clinical practice as patient health beliefs, experiences and conduct influence medication-taking. Motivational interviewing might improve medication adherence in permitting emotional state managing and increasing educational skills, patient motivation and confidence between patients and healthcare providers.
10.1093/eurpub/cky259
pubmed_554_11661
Sex-specific responses to mycorrhiza have been reported in dioecious plant species, but little attention has been paid to the influence of arbuscular mycorrhizal (AM) fungi on competitive ability under intersexual competition. To further address whether this competition is affected by an additional AM fungi supply, Populus cathayana saplings were chosen and subjected to two mycorrhizal treatments [inoculated and non-inoculated (control) with an additional AM fungi Funneliformis mosseae] while growing with the opposite sex for 3 months. Compared with the control, the additional AM fungi inoculation induced P. cathayana saplings to exhibit significant sexual differences in root structure and nutrient uptake (e.g., cortical layer, cross-section area, radius of root tips, and N, K, and Mg content), and enlarged sexual differences in morphology and biomass accumulation (e.g., leaf number increment, shoot height increment, total leaf area, total specific root length, stem dry mass, leaf dry mass, and total dry mass). Meanwhile, inoculated females presented higher values in most of these traits mentioned above than males under intersexual competition. Therefore, we conclude that the intersexual competition can be increased by an additional AM fungi supply, with females gaining more symbiosis-mediated benefits than males.
10.3389/fpls.2018.00607
pubmed_51_13677
Laboratory studies show that altitude ascent impairs endurance performance. Limited data exist on football, and information from official matches is very scarce even for other team sports. The aim of this study was to examine the effect of altitude on football performance during the 2010 World Cup in South Africa. It was hypothesized that (a) total distance covered, an index of endurance, would be reduced above the altitude of 580 m, and (b) technical skills would be affected because altitude alters ball flight characteristics. Physical performance, goals scored, and goalkeepers' errors that resulted in goals conceded were recorded from the official game statistics of Fédération Internationale de Football Association during the South Africa 2010 World Cup. Matches were played at sea level (altitude: 0 m), 660, 1200-1400, and 1401-1753 m. After testing for data normality, mean differences were checked with a one-way analysis of variance. Results show a 3.1% lower total distance that was covered by the teams during the matches played at 1200-1400 and 1401-1753 m (p < 0.05) compared with sea level. Indices of technical skills, including number of goals scored per game and errors made by the goalkeepers that resulted in goals conceded, did not differ with altitude. It is concluded that playing football above 1200 m had negative effects on endurance but not on technical skills during World Cup 2010 matches. It seems that teams should follow several days of acclimatization before playing at altitude as low as 1200 m, to ameliorate the negative effects of altitude on physical performance.
10.1519/JSC.0b013e31825d999d
pubmed_469_7714
BACKGROUND Evaluation of socioeconomic status (SES) is an important aspect in community-based health studies and it is a major predictor of health and nutritional status as well as mortality and morbidity from many diseases. This study aimed to construct and validate socioeconomic status short-from questionnaire (SES-SQ) in Iranian population. METHODS This cross-sectional methodological study was conducted among 1437 Iranian general population. Face and content validity of the developed questionnaire was evaluated qualitatively. Internal consistency, construct validity using exploratory factor analysis (EFA) and latent class analysis (LCA), and convergent and known-group validity were also evaluated. RESULTS The SES-SQ consisted of 6 items. The overall Cronbach's alpha was 0.64, showing acceptable internal consistency. EFA resulted in two factors explaining 47.78% of total variance. Three SES classes (low/middle/high) were extracted by LCA. The score of SES-SQ ranged from 0 to 17; two cutoff scores of 4.5 and 8.5 were determined by receiver operating characteristic (ROC) analysis for differentiating low from middle and middle from high SES classes, respectively. CONCLUSION An efficient, reliable, and valid short-form questionnaire was developed for evaluating SES in Iranian general population. The relevancy of questionnaire items is not lost over time.
10.22122/arya.v17i0.2355
pubmed_464_25143
Phi 6 (Φ6) bacteriophage is a proposed surrogate to study pathogenic enveloped viruses including SARS-CoV-2-the causative agent of COVID-19-based on structural similarities, BSL-1 status, and ease of use. To determine the role of virus-contaminated hands in disease transmission, an enhanced understanding of buffer and method performance for Φ6 recovery needs to be determined. Four buffer types and three methodologies were investigated for the recovery of Φ6 from human fingerpads over a 30 min duration. Phosphate buffered saline (PBS), PBS + 0.1 % Tween, 0.1 M glycine + 3% beef extract, and viral transport medium were evaluated as buffers for recovery of Φ6 via a dish, modified glove juice, and vigorous swabbing method. Φ6 concentrations on fingerpads were determined at 0-, 5-, 10-, and 30-min post-inoculation. While there were observed differences in virus recovery across buffer and method types depending on the time point, log PFU recovery based on buffer type or methodology was not significantly different at any time point (P > 0.05). The results presented in this study will allow for future work on Φ6 persistence, transfer between hands and surfaces, and efficacy of hand hygiene methods to be performed using a well-characterized and validated recovery method.
10.1016/j.jviromet.2021.114307
pubmed_865_2633
OBJECTIVE To investigate the expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA in peripheral blood from the patients with non-small cell lung cancer and analyze their correlations with non-small cell lung cancer. METHODS The expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA were detected by nested reverse transcription-PCR assay in peripheral blood from the patients with non-small cell lung cancer (n = 120), benign pulmonary disease (n = 106) and from healthy subjects (n = 80) so as to further investigate their relationship with clinicopathological features and prognosis. Meantime we also examined the sensitivity, specificity and accuracy of combination detection. RESULTS The expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA in non-small cell lung cancer patients were 56.7%, 57.5%, 35.0%, higher than that of benign pulmonary disease (0.9%, 6.6%, 5.7%) and healthy groups (0, 3.8%, 0, all P < 0.05). The ROC curves indicated the sensitivity of combined detection was 84.3% and the specificity of combined detection was 94.6%. Univariate analysis revealed that the clinical stage, the ECOG score and the number of positive marker had significant association with overall survival (OS) (χ(2) = 67.928, 95.981, 60.285, all P = 0.000). Multivariate analysis indicated that the clinical stage, ECOG score and the number of positive marker was an independent prognostic factor each (HR = 2.866, 4.251, 1.845, all P = 0.000). CONCLUSION BJ-TSA-9, CK19 and Pre-proGRP mRNA may be the specific and sensitive markers to detect circulating tumor cells in the peripheral blood of non-small cell lung cancer patients.
pubmed_865_2633
pubmed_940_3968
This report presents preliminary results of studies on the growth stimulating properties of mineral dusts. The studies were carried out with Syrian hamster diploid embryonic fibroblasts and Chinese hamster fibroblasts, line B14F28. Toxicity testing was done by the determination of the plating efficiency as a measure of growth and viability. The following dusts were used: the modified UICC asbestos fibres amosite, (AFF) crocidolite (KFF), chrysotile (KFF): in addition glass fibre (GFF), corundum and quartz DQ12. Concentrations > 2 microg/cm2 of AFF, CFF, KFF and GFF depressed the plating efficiency of B14F28 cells in a dose-dependent manner, but all of the fibres and corundum increased colony sizes at concentrations of 0.16-0.33 microg/cm2, in the case of corundum, AFF, KFF, and CFF also at up to 0.66 or 1.32 microg/cm2. DQ12 did not enhance colony growth. The stimulation of proliferation could be demonstrated both in terms of colony size (diameter) and cell numbers. The factor(s) responsible for proliferation stimulation reside in the supernatant, since the medium of dust-treated cell cultures was able to stimulate colony growth after removal of the dusts by filtration. The results indicate the induction of growth factors (cytokines) by low concentrations of the mineral dusts. Experiments concerning the effect of dusts on embryonic golden hamster fibroblasts yielded similar results. The plating efficiency was inhibited by concentrations of GFF and CFF > 0.25 microg cm2 and by AFF, KFF, GFF and corundum at concentrations > 5 microg/cm2, but colony counts were significantly increased by AFF, KFF and corundum at concentrations of 0.25-3 microg/cm2. This biological reaction which was observed in different cell types appears to be especially relevant in the context of environmental exposure where low dust concentrations prevail.
10.1016/s0378-4274(98)00055-1
pubmed_909_7304
This study was aimed at generating baseline information for sustainable genetic improvement of Cirana forda larvae for entomophagy, through the use of gamma irradiation. Eggs of C. forda were irradiated with increasing doses of gamma rays from 0 to 200 Gy and raised through larval instal stages under laboratory conditions. The Body Weight (BW) and Head Capsule Width (HCW) of the larval instar stages were monitored as indices of productivity. Successful larval emergence was recorded for all irradiation doses tested and BW of the 1st and 2nd instar larvae were not significantly (p > 0.05) different between the control and treated groups (range = 0.021 +/- 0.003 g/larva in the 200 Gy treatment to 0.028 +/- 0.003 g/larva in the control group and 0.105 +/- 0.003 g/larva in 20 Gy treatment to 0.172 +/- 0.009 g/larva in the control group, respectively). On the other hand, BW during the 3rd and 4th larval instars were significantly (p < 0.05) lower among the irradiated treatments than control. Pattern of distribution of HCW was different from that of BW; as HCW increased with irradiation dose from 10-50 Gy during the 3rd and 4th larval instars. Also, HCW during the 5th instar larvae among the irradiated treatments (range = 5.256 +/- 0.012 to 5.662 +/- 0.026 mm) were not higher than that of the 6th instar in the control group (6.065 +/- 0.010 mm). These results suggest promising potentials of the use of gamma irradiation in sustainably improving the productivity of C. forda larvae for entomophagy.
10.3923/pjbs.2013.735.738
pubmed_494_13437
Reactive oxygen species (ROS) play a crucial role in ischemia-reperfusion (IR) injury after lung transplantation. We hypothesized that NADPH oxidase derived from bone marrow (BM) cells contributes importantly to lung IR injury. An in vivo mouse model of lung IR injury was employed. Wild-type C57BL/6 (WT) mice, p47(phox) knockout (p47(phox)-/-) mice, or chimeras created by BM transplantation between WT and p47(phox)-/- mice were assigned to either Sham (left thoracotomy) or six study groups that underwent IR (1 h left hilar occlusion and 2 h reperfusion). After reperfusion, pulmonary function was assessed using an isolated, buffer-perfused lung system. Lung injury was assessed by measuring vascular permeability (via Evans blue dye), edema, neutrophil infiltration (via myeloperoxidase [MPO]), lipid peroxidation (via malondialdyhyde [MDA]), and expression of proinflammatory cytokines. Lung IR resulted in significantly increased MDA in WT mice, indicative of oxidative stress. WT mice treated with apocynin (an NADPH oxidase inhibitor) and p47(phox)-/- mice displayed significantly reduced pulmonary dysfunction and injury (vascular permeability, edema, MPO, and MDA). In BM chimeras, significantly reduced pulmonary dysfunction and injury occurred after IR in p47(phox)-/--->WT chimeras (donor-->recipient) but not WT-->p47(phox)-/- chimeras. Induction of TNF-alpha, IL-17, IL-6, RANTES (CCL5), KC (CXCL1), MIP-2 (CXCL2), and MCP-1 (CCL2) was significantly reduced after IR in NADPH oxidase-deficient mice and p47(phox)-/--->WT chimeras but not WT-->p47(phox)-/- chimeras. These results indicate that NADPH oxidase-generated ROS specifically from BM-derived cells contributes importantly to lung IR injury. NADPH oxidase may represent a novel therapeutic target for the treatment of IR injury after lung transplantation.
10.1165/rcmb.2008-0300OC
pubmed_1131_20352
This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre-diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course.
10.1016/j.jpsychires.2016.05.014
pubmed_661_9549
A potassium channel in membranes of the insulin-secreting B-cell line, RIN m5F, was studied using the patch-clamp technique. In cell-attached patches, and for pipette solutions containing 140 mM KCl, the I-V curves exhibited a pronounced rectification, with the conductance being higher when the current flowed from the electrode into the cell (50 pS). Addition of glucose (5-7 mM) to the bath was sufficient to abolish the channel activity, while low doses of the metabolic inhibitor 2,4-dinitrophenyl enhanced it, indicating a link between channel activity and cell metabolism. In excised inside-out patches, the activity of a channel with similar conductive properties was inhibited by ATP in a dose-dependent fashion, the half-maximal concentration being approximately 70 microM. ADP also acted as an inhibitor, but with much lower potency. However, when ADP was present, the blocking effectiveness of ATP was reduced, suggesting a nonadditive interaction of the two nucleotides with the channel. In conclusion, complete closure of the K channel by glucose (5-7 mM) suggests that this channel may be responsible for the early phase of the B-cell depolarization, which is seen in normal cells for glucose increments up to similar values. In addition, since ATP and ADP are both present in the cells, the reduction by ADP of the blocking efficacy of ATP in excised patches may help one to understand why, in intact cells, the channel is still functional for intracellular ATP concentrations that in excised patches would completely suppress its activity.
10.1073/pnas.84.6.1721
pubmed_581_7576
A new and straightforward method for the synthesis of 5-bromotetracenes through PBr3-mediated cyclization of 1,7-diyn-3,6-bis(propargyl carbonate)s has been developed. This method offers several advantages such as easily accessible starting materials, high efficiency, and wide functional group compatibility. In addition, chloro- and iodo-substituted tetracenes were also synthesized using appropriate halogenating reagents. The utility of the 5-bromotetracene products has been illustrated by their efficient transformations through various palladium-catalyzed cross-coupling reactions.
10.1021/acs.joc.7b01519
pubmed_725_1255
Two groups (n = 20 each for pill and no pill groups) of young female social drinkers were tested with an acute ethanol dose (0.52 g/kg) as a 20% solution in water. Ethanol pharmacokinetics and acetaldehyde were repeatedly assayed from breath by a gas chromatograph. Cardiovascular indices were concurrently recorded. Groups did not differ on ethanol pharmacokinetics. However, the group on birth control pills reached a significantly higher acetaldehyde concentration than did the group of normally cycling females not on birth control pills (3.26 ng/ml vs. 1.45 ng/ml). Further, the pill (P) group showed significantly greater vasodilation 20 min postdrink as indexed by ear lobe plethysmography than did the no pill (NP) group (P = 160.3% vs. NP = 113.9%). Results are consistent with the interpretation that female sex steroids modulate aldehyde dehydrogenase function. Practical implications are that females with elevated steroids (either pregnant or on birth control pills) may be at greater risk for toxic effects of ethanol consumption.
10.1111/j.1530-0277.1984.tb05679.x
pubmed_176_19936
Previously, a modified HIV Env protein with a heterologous membrane anchor was found to be incorporated into HIV virus-like particles (VLPs) at 10-fold-higher levels than those of unmodified Env. To further improve the immunogenicity of such VLPs, membrane-anchored forms of bacterial flagellin (FliC) or a flagellin with a truncated variable region (tFliC) were constructed to be incorporated into the VLPs as adjuvants. HIV-specific immune responses induced by the resulting VLPs were determined in a guinea pig model. The VLPs induce enhanced systemic antibody responses by either systemic or mucosal vaccination and enhanced mucosal immunity by a mucosal immunization route, as demonstrated by high levels of HIV-specific serum IgG and mucosal IgG and IgA. The quality of the antibody responses was also improved, as shown by enhanced neutralization capacity. VLPs incorporating FliC were more effective in inducing systemic responses, while VLPs containing tFliC were more effective in inducing mucosal IgA responses. The IgG titers in sera were found to last for at least 5 months without a significant drop. These results indicate that HIV VLPs incorporating high levels of Env and a molecular adjuvant have excellent potential for further development as a prophylactic HIV vaccine.
pubmed_176_19936
pubmed_1128_16868
The inequitable distribution of medical services in Australia means that many rural dwellers do not have easy access to ophthalmic care. In regions with no medical personnel, appropriately trained rural health workers may provide ophthalmic assessment, primary treatment, and, in some circumstances, definitive care. In areas with overburdened services, these rural health workers may augment facilities already established. In an attempt to improve the accessibility and quality of ophthalmic services available to presently disadvantaged rural inhabitants, the aims, curriculum, and structure of a 'Basic Ophthalmic Assessment and Care Workshop', for the transfer of knowledge and skills to such rural health workers, is presented.
10.1111/j.1442-9071.1990.tb00591.x
pubmed_518_11662
Complex hygienic approach using psychophysiologic and clinical methods revealed features of occupational stress for various work intensity.
pubmed_518_11662
pubmed_547_18565
Carnivorous plants are known to secrete acid proteinases to digest prey, mainly insects, for nitrogen uptake. In the present study, we have purified, for the first time, to homogeneity two acid proteinases (nepenthesins I and II) from the pitcher fluid of Nepenthes distillatoria (a pitcher-plant known locally as badura) and investigated their enzymic and structural characteristics. Both enzymes were optimally active at pH approx. 2.6 towards acid-denatured haemoglobin; the specificity of nepenthesin I towards oxidized insulin B chain appears to be similar, but slightly wider than those of other APs (aspartic proteinases). Among the enzymic properties, however, the most notable is their unusual stability: both enzymes were remarkably stable at or below 50 degrees C, especially nepenthesin I was extremely stable over a wide range of pH from 3 to 10 for over 30 days. This suggests an evolutionary adaptation of the enzymes to their specific habitat. We have also cloned the cDNAs and deduced the complete amino acid sequences of the precursors of nepenthesins I and II (437 and 438 residues respectively) from the pitcher tissue of N. gracilis. Although the corresponding mature enzymes (each 359 residues) are homologous with ordinary pepsin-type APs, both enzymes had a high content of cysteine residues (12 residues/molecule), which are assumed to form six unique disulphide bonds as suggested by computer modelling and are supposed to contribute towards the remarkable stability of nepenthesins. Moreover, the amino acid sequence identity of nepenthesins with ordinary APs, including plant vacuolar APs, is remarkably low (approx. 20%), and phylogenetic comparison shows that nepenthesins are distantly related to them to form a novel subfamily of APs with a high content of cysteine residues and a characteristic insertion, named 'the nepenthesin-type AP-specific insertion', that includes a large number of novel, orthologous plant APs emerging in the gene/protein databases.
10.1042/BJ20031575
pubmed_630_25184
Factors that might exacerbate or mitigate the transmission of depressive symptoms from parents to adolescents and the continuity of depressive symptoms into early adulthood are poorly understood. This study tested the hypothesis that the intergenerational transmission and stability of depressive symptoms would be stronger for girls than boys over adolescence and into early adulthood, while considering the possibility that the pattern of gender moderation might vary depending on parent gender and developmental timing. The participants were 667 rural Midwestern adolescents (52 % female) and their parents. Survey data on maternal and paternal depressive symptoms (at youth age 11) and on adolescent and young adult depressive symptoms (at youth ages 11, 18, and 21) were analyzed via multiple group structural equation modeling. Maternal depressive symptoms predicted increased late adolescent depressive symptoms for girls but not boys, and adolescent depressive symptoms were more stable in girls. Paternal depressive symptoms predicted increased late adolescent depressive symptoms for all youth. The findings suggest the need for early, tailored interventions.
10.1007/s10964-016-0480-8
pubmed_974_17526
BACKGROUND The National Organization for Healthcare Provision (EOPYY) originates from the recent reform in Greek healthcare, aiming amidst economic predicament, at the rationalization of health expenditure and reactivation of the pivotal role of Primary Health Care (PHC). Health funding (public/private) mix is examined, alongside the role of pre-existing health insurance funds. The main pursuit of this paper is to evaluate whether EOPYY has met its goals. METHODS The article surveys for best practices in advanced health systems and similar sickness funds. The main benchmarks focus on PHC provision and providers' reimbursement. It then turns to an analysis of EOPYY, focusing on specific questions and searching the relevant databases. It compares the best practice examples to the EOPYY (alongside further developments set by new legislation in L 4238/14), revealing weaknesses relevant to non-integrated PHC network, unbalanced manpower, non-gatekeeping, under-financing and other funding problems caused by the current crisis. Finally, a new model of medical procedures cost accounting was tested in health centers. RESULTS An alternative operation of EOPYY functioning primarily as an insurer whereas its proprietary units are integrated with these of the NHS is proposed. The paper claims it is critical to revise the current induced demand favorable reimbursement system, via per capita payments for physicians combined with extra pay-for-performance payments, while cost accounting corroborates a prospective system for NHS's and EOPYY's units, under a combination of global budgets and Ambulatory Patient Groups (APGs) CONCLUSIONS Self-critical points on the limitations of results due to lack of adequate data (not) given by EOPYY are initially raised. Then the issue concerning the debate between 'copying' benchmarks and 'a la cart' selectively adopting and adapting best practices from wider experience is discussed, with preference to the latter. The idea of an 'a la cart' choice of international examples is proposed. The 'results' discussing EOPYY's dual function and induced-demand favorable reimbursement system are further critically examined. International experience shows evidence of effective alternatives, such as per capita and pay-for-performance payments for practicing doctors as well as per case reimbursement for health centers under global budget principles.
10.1186/s12913-014-0583-4
pubmed_201_14266
OBJECTIVES Obsessive-compulsive disorder (OCD) is notably a comorbid disorder in patients with schizophrenia. This study aimed to evaluate clinical features and correlates of early onset patients with schizophrenia with OCD. METHODS In the present study, we included 10 patients with both schizophrenia and OCD and 19 patients with schizophrenia without OCD. The mean antipsychotic doses the patients needed for treatment are standardized as chlorpromazine equivalent dose. RESULTS The mean antipsychotic doses at first episode were 491 ± 376 mg/d in schizophrenia comorbid OCD group and 290 ± 209 mg/d in the schizophrenia without OCD group (P = 0.018). This significant difference was also found for the mean doses at the assessment for the study (512.40 ± 336.22 mg/d in schizophrenia comorbid OCD and 296.05 ± 147.25 mg/d in patients with schizophrenia without OCD, P = 0.012). There was no statistical difference in the mean scores of Clinical Global Impression and Positive and Negative Syndrome Scale between schizophrenia with and without OCD group, respectively. (Clinical Global Impression: 5 ± 0.66 vs 4.36 ± 0.83, P = 0.094; Positive and Negative Syndrome Scale: 67.60 ± 11.84 vs 69.84 ± 14.62, P = 0.573). CONCLUSIONS Adolescents with schizophrenia and OCD needed more antipsychotic doses for acute exacerbation and the maintenance of reduction of psychosis severity than adolescents with only schizophrenia. We could suggest that OCD comorbidity in schizophrenia is more treatment resistant, although the severity of the schizophrenia was similar between study groups. There was no correlation between OCD and schizophrenia symptoms either.
10.1097/WNF.0000000000000248
pubmed_307_24617
We present a probabilistic model of how viewers may use defocus blur in conjunction with other pictorial cues to estimate the absolute distances to objects in a scene. Our model explains how the pattern of blur in an image together with relative depth cues indicates the apparent scale of the image's contents. From the model, we develop a semiautomated algorithm that applies blur to a sharply rendered image and thereby changes the apparent distance and scale of the scene's contents. To examine the correspondence between the model/algorithm and actual viewer experience, we conducted an experiment with human viewers and compared their estimates of absolute distance to the model's predictions. We did this for images with geometrically correct blur due to defocus and for images with commonly used approximations to the correct blur. The agreement between the experimental data and model predictions was excellent. The model predicts that some approximations should work well and that others should not. Human viewers responded to the various types of blur in much the way the model predicts. The model and algorithm allow one to manipulate blur precisely and to achieve the desired perceived scale efficiently.
pubmed_307_24617
pubmed_460_23581
Rising atmospheric carbon dioxide concentration ([CO(2)]) is widely recognized, but less appreciated is a concomitant rise in tropospheric ozone concentration ([O(3)]). In industrialized countries, [O(3)] has risen by 0.5% to 2.5% per year. Tropospheric [O(3)] is predicted to reach a global mean of >60 nL L(-1) by 2050 with greater averages locally. Previous studies in enclosures suggest that this level of [O(3)] will decrease leaf photosynthesis, thereby limiting growth and yield of Glycine max L. Merr. SoyFACE (Soybean Free Air gas Concentration Enrichment) is the first facility to elevate atmospheric [O(3)] (approximately 1.2x current) in replicated plots under completely open-air conditions within an agricultural field. Measurements of gas exchange (assimilation versus light and assimilation versus intercellular [CO(2)]) were made on excised leaves from control and treatment plots (n = 4). In contrast to expectations from previous chamber studies, elevated [O(3)] did not alter light-saturated photosynthesis (A(sat), P = 0.09), carboxylation capacity (V(c,max), P = 0.82), or maximum electron transport (J(max), P = 0.66) for the topmost most recently fully expanded leaf at any stage of crop development. Leaves formed during the vegetative growth stage did not show a significant ozone-induced loss of photosynthetic capacity as they aged. Leaves formed during flowering did show a more rapid loss of photosynthetic capacity as they aged in elevated [O(3)]. A(sat), V(c,max), and J(max) (P = 0.04, 0.004, and 0.002, respectively) were decreased 20% to 30% by treatment with ozone. This is noteworthy since these leaves provide photosynthate to the developing grain. In conclusion, a small (approximately 20%) increase in tropospheric [O(3)] did not significantly alter photosynthetic capacity of newly expanded leaves, but as these leaves aged, losses in photosynthetic carbon assimilation occurred.
10.1104/pp.104.043968
pubmed_57_920
5-aminolevulinic acid (5-ALA) introduction in the surgical management of Glioblastoma (GBM) enables the intra-operatively identification of cancer cells in the mass by means of fluorescence. Here, we analyzed the phenotype of GBM cells isolated from distinct tumour areas determined by 5-ALA (tumour core, 5-ALA intense and vague layers) and the potency of 5-ALA labelling in identifying GBM cells and cancer stem cells (CSCs) in the mass. 5-ALA identified distinct layers in the mass, with less differentiated cells residing in the core of the tumour. 5-ALA was able to stain up to 68.5% of CD133(+) cells in the 5-ALA intense layer and, although 5-ALA(+) cells retrieved from different tumour areas contained a similar proportion of CD133(+) cells (range 27.5-35.6%), those from the vague layer displayed the lowest ability to self-renew. In conclusion, our data demonstrate that a substantial amount of GBM cells and CSCs in the mass are able to avoid 5-ALA labelling and support the presence of heterogenic CSC populations in the GBM mass.
10.1007/s11060-013-1348-3
pubmed_315_19074
Increasing evidence suggests that cholesterol plays a central role in the pathophysiology of Alzheimer's disease (AD). Caveolin is a cholesterol-binding membrane protein involved in cellular cholesterol transport. We investigated the changes in the protein amount of hippocampal caveolin of autopsy-confirmed AD and aged-matched control subjects. Our results demonstrate that caveolin protein levels in the hippocampus and caveolin mRNA in the frontal cortex are up-regulated in AD by approximately two-fold, compared to control brains. These results suggest a relationship between caveolin-1 expression levels and a dysregulation of cholesterol homeostasis at the plasma membrane of brain cells. In support of this hypothesis, a significant increase in caveolin protein levels has also been observed in hippocampal tissue from ApoE-deficient (knockout) and aged wild-type mice; two situations associated with modifications of transbilayer distribution of cholesterol in brain synaptic plasma membranes. These results indicate that caveolin over-expression is linked to alterations of cholesterol distribution in the plasma membrane of brain cells and are consistent with the notion of a deterioration of cholesterol homeostasis in AD.
10.1016/j.neurobiolaging.2003.07.004
pubmed_67_23601
BACKGROUND The contemporaneous presence of immune defects and heart diseases in patients with 22q11.2 deletion syndrome (22q11.3DS) might represent risk factors for severe coronavirus 2019 disease (COVID-19). OBJECTIVE To analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcome in 22q11.2DS patients and immunogenicity of different doses of mRNA SARS-CoV-2 vaccine. METHODS Longitudinal observational study on SARS-CoV-2 outcome in 60 adults with 22q11.2DS (March 2020-June 2022). Anti-Spike, and anti-receptor binding domain (RBD) antibody responses, generation of Spike-specific memory B cells (MBCs) and Spike-specific T cells at different time points before and after the mRNA BNT162b2 vaccination were evaluated in 16 22q11.2DS patients. RESULTS We recorded a 95% rate of vaccination, with almost all patients being immunized with the booster dose. Twenty-one patients had SARS-CoV-2 infection. Three patients were infected before vaccine availability, 6 after receiving 2 doses of vaccine, and 12 after one booster dose. The SARS-CoV-2- infection had a mild course, except in one unvaccinated patient with several comorbidities who died from acute respiratory distress syndrome (fatality rate 5%). Infected patients had more frequently moderate/severe intellectual disability, lymphopenia, and lower CD4+ count. Despite major congenital heart diseases, COVID-19 did not impact cardiological conditions. The BNT162b2 vaccine induced S1-immunoglobulin G (IgG) responses, low serum S1-IgA, and slightly impaired specific MBCs response. Specific T-cell responses observed were related to lymphocytes and CD4+ T cell counts. CONCLUSIONS The SARS-CoV-2 infection had a mild course in most patients with 22q11.2DS, even in patients with major cardiovascular diseases. Immunization induced Spike-specific IgG responses and generated specific MBCs and memory T cells. The weaker memory responses in patients with lymphopenia suggested the need for additional doses.
10.1016/j.jaip.2022.10.010
pubmed_449_15497
The circadian change of gastric acidity was studied in 9 patients and 2 controls. Five patients were treated with gastrozepin, two with vicalin and buscolysin, two with biomet according to a schedule. Gastric content was aspirated at fixed intervals and pH determined separately of each portion. The data were juxtaposed to those of the gastric probe prior to the beginning of the treatment. They revealed that with the treatment with gastrozepin and biomet, the lowest pH values during the day were higher, with a statisticall significance, than those obtained at basal conditions prior to the treatment. During the night, pH over 3 was observed only in the treatment with biomet. The methodical conditions used ate suitable both for clinical-pharmacological investigations and for individualization of the treatment of some patients that failed to respond to the ordinary therapeutic combinations.
pubmed_449_15497
pubmed_128_9874
OBJECTIVE This review explores the series of published analyses from Massachusetts General Hospital to better understand how changes in medical specialization of burn medicine likely enabled the most important increase in survival from burns in the past 70 years. BACKGROUND Seventy years ago, survival from the most serious burn injuries was not possible even in the most advanced countries until critical advances were introduced. Insights into those few medical advances that actually impacted survival might be better understood from the consideration of a continuous series of survival analyses over 7 decades at Massachusetts General Hospital. METHODS Mortality data from previously reported probit and logit analyses from thousands of patients treated at Massachusetts General Hospital were reviewed. A comparison of mortality from these prior mortality analyses from a more recent multicenter study and a national data set was performed. RESULTS The only giant leap forward in survival occurred during the 1970s, with no improvement during either the preceding or subsequent 30-year intervals. Despite the many modern advances that have been added to the care of these patients since 1984, although these may have represented medical progress, these advances did not impact survival. CONCLUSIONS Survival rates from burn injury may have been maximized by current treatment approaches within medical centers of excellence in burn medicine. Further efforts to improve the quality of life of survivors of burn injury should ultimately have very favorable impact upon the long-term outcomes in these patients who now survive such devastating injuries.
10.1097/SLA.0000000000000623
pubmed_329_14692
BACKGROUND AND PURPOSE Kv 7 (Kv 7.1-7.5) channels play an important role in the regulation of neuronal excitability and the cardiac action potential. Growing evidence suggests Kv 7.4/Kv 7.5 channels play a crucial role in regulating vascular smooth muscle contractility. Most of the reported Kv 7 openers have shown poor selectivity across these five subtypes. In this study, fasudil - a drug used for cerebral vasospasm - has been found to be a selective opener of Kv 7.4/Kv 7.5 channels. EXPERIMENTAL APPROACH A perforated whole-cell patch technique was used to record the currents and membrane potential. Homology modelling and a docking technique were used to investigate the interaction between fasudil and the Kv 7.4 channel. An isometric tension recording technique was used to assess the vascular tension. KEY RESULTS Fasudil selectively and potently enhanced Kv 7.4 and Kv 7.4/Kv 7.5 currents expressed in HEK293 cells, and shifted the voltage-dependent activation curve in a more negative direction. Fasudil did not affect either Kv 7.2 and Kv 7.2/Kv 7.3 currents expressed in HEK293 cells, the native neuronal M-type K+ currents, or the resting membrane potential in small rat dorsal root ganglia neurons. The Val248 in S5 and Ile308 in S6 segment of Kv 7.4 were critical for this activating effect of fasudil. Fasudil relaxed precontracted rat small arteries in a concentration-dependent fashion; this effect was antagonized by the Kv 7 channel blocker XE991. CONCLUSIONS AND IMPLICATIONS These results suggest that fasudil is a selective Kv 7.4/Kv 7.5 channel opener and provide a new dimension for developing selective Kv 7 modulators and a new prospective for the use, action and mechanism of fasudil.
10.1111/bph.13639
pubmed_293_4306
The zebrafish embryo is a popular model for drug screening, disease modelling and molecular genetics. In this study, samples were obtained from zebrafish at different developmental stages. The stages that were chosen were 3/4, 4/5, 24, 48, 72 and 96 hours post fertilization (hpf). Each sample included fifty embryos. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Principle component analysis (PCA) was applied to get an overview of the data and orthogonal projection to latent structure discriminant analysis (OPLS-DA) was utilised to discriminate between the developmental stages. In this way, changes in metabolite profiles during vertebrate development could be identified. Using a GC-TOF-MS metabolomics approach it was found that nucleotides and metabolic fuel (glucose) were elevated at early stages of embryogenesis, whereas at later stages amino acids and intermediates in the Krebs cycle were abundant. This agrees with zebrafish developmental biology, as organs such as the liver and pancreas develop at later stages. Thus, metabolomics of zebrafish embryos offers a unique opportunity to investigate large scale changes in metabolic processes during important developmental stages in vertebrate development. In terms of stability of the metabolic profile and viability of the embryos, it was concluded at 72 hpf was a suitable time point for the use of zebrafish as a model system in numerous scientific applications.
10.1371/journal.pone.0213661
pubmed_900_21897
Chronic myeloid leukaemia (CML) can be considered as a paradigm for neoplasias that evolve through a multi-step process. CML is also one of the best examples of a disease that can be targeted by molecular therapy; however, the success of new 'designer drugs' is largely restricted to the chronic phase of the disease. If not cured at this stage, CML invariably progresses and transforms into an acute-type leukaemia undergoing a 'blast crisis'. The causes of this transformation are still poorly understood. What mechanisms underlie this progression, and are they shared by other common cancers?
10.1038/nrc2147
pubmed_455_18843
BACKGROUND When evaluating cancer screening it is important to estimate the cumulative risk of false positives from periodic screening. Because the data typically come from studies in which the number of screenings varies by subject, estimation must take into account dropouts. A previous approach to estimate the probability of at least one false positive in n screenings unrealistically assumed that the probability of dropout does not depend on prior false positives. METHOD By redefining the random variables, we obviate the unrealistic dropout assumption. We also propose a relatively simple logistic regression and extend estimation to the expected number of false positives in n screenings. RESULTS We illustrate our methodology using data from women ages 40 to 64 who received up to four annual breast cancer screenings in the Health Insurance Program of Greater New York study, which began in 1963. Covariates were age, time since previous screening, screening number, and whether or not a previous false positive occurred. Defining a false positive as an unnecessary biopsy, the only statistically significant covariate was whether or not a previous false positive occurred. Because the effect of screening number was not statistically significant, extrapolation beyond 4 screenings was reasonable. The estimated mean number of unnecessary biopsies in 10 years per woman screened is.11 with 95% confidence interval of (.10,.12). Defining a false positive as an unnecessary work-up, all the covariates were statistically significant and the estimated mean number of unnecessary work-ups in 4 years per woman screened is.34 with 95% confidence interval (.32,.36). CONCLUSION Using data from multiple cancer screenings with dropouts, and allowing dropout to depend on previous history of false positives, we propose a logistic regression model to estimate both the probability of at least one false positive and the expected number of false positives associated with n cancer screenings. The methodology can be used for both informed decision making at the individual level, as well as planning of health services.
10.1186/1471-2288-3-11
pubmed_467_13431
Previous studies evaluated cues for masked tone detection using reproducible noise waveforms. Human results founded on this approach suggest that tone detection is based on combined energy and envelope (ENV) cues, but detection cues in nonhuman species are less clear. Decision variable correlation (DVC) was used to evaluate tone-in-noise detection cues in the budgerigar, an avian species with human-like behavioral sensitivity to many complex sounds. DVC quantifies a model's ability to predict trial-by-trial variance in behavioral responses. Budgerigars were behaviorally conditioned to detect 500-Hz tones in wideband (WB; 100-3000 Hz) and narrowband (NB; 452-552 Hz) noise. Behavioral responses were obtained using a single-interval, two-alternative discrimination task and two-down, one-up adaptive tracking procedures. Tone-detection thresholds in WB noise were higher than human thresholds, putatively due to broader peripheral frequency tuning, whereas NB thresholds were within ∼1 dB of human results. Budgerigar average hit and false-alarm rates across noise waveforms were consistent, highly correlated across subjects, and correlated to human results. Trial-by-trial behavioral results in NB noise were best explained by a model combining energy and ENV cues. In contrast, WB results were better predicted by ENV-based or multiple-channel energy detector models. These results suggest that budgerigars and humans use similar cues for tone-in-noise detection.
10.1121/10.0000621
pubmed_334_5591
PURPOSE OF REVIEW The current resuscitation guidelines consider ventilation and chest compression essential components of resuscitation and therefore only one methodology, standard cardiopulmonary resuscitation, is explicitly recommended for the treatment of both respiratory and cardiac arrests. Pathophysiological and experimental observations argue that this generalization results in suboptimal treatment for victims of cardiac arrest. RECENT FINDINGS For more than a decade animal studies have demonstrated that assisted ventilation is not essential during the initial treatment of a fibrillatory arrest; but only in the last year have these results been confirmed in humans. These new observations come from a handful of systems utilizing cardiocerebral resuscitation in their prehospital resuscitation of adult victims of presumed cardiac arrest. They have all demonstrated a dramatic increase in survival. Recent data also indicate that survival is significantly increased when laypersons perform chest-compression-only cardiopulmonary resuscitation. SUMMARY The current resuscitation guidelines regarding the prehospital treatment of victims of adult cardiac arrest should be modified to explicitly permit the use of continuous-chest-compression cardiopulmonary resuscitation.
10.1097/MCC.0b013e32814b0524
pubmed_340_1959
The study with satellite remote sensing technique and Costanza method showed that from 1984 to 2003, the total area of various ecosystems in the coastal tidal zone of Dongtai City, Jiangsu Province increased from 108.54 to 171.31 km2 or by 57.83% due to natural siltation, of which,the area of natural ecosystem decreased from 60. 82 to 21.64 km2 or by 64.42%, while that of artificial ecosystem increased from 47.72 to 195.23 km2 or by 309.12%. During the same period, the total value of ecosystem services in this zone increased by 76.96%, with natural ecosystem services value dropped from 56.26 x 10(4) to 17.19 x 10(4) US dollar or by 69.45%, while artificial ecosystem services value raised from 40.55 x 10(4) to 154.13 x 10(4) US dollar or by 280.10%. The decrease of natural ecosystem area and the increase of artificial ecosystem area illustrated clearly that the costal tidal ecosystem of this city was being degenerated seriously, and the decline of natural ecosystem services value was resulted from this degradation and the decrease of natural ecosystem area.
pubmed_340_1959
pubmed_511_19362
KEY POINTS The medial entorhinal cortex (mEC) has an important role in initiation and propagation of seizure activity. Several anatomical relationships exist in neurophysiological properties of mEC neurons; however, in the context of hyperexcitability, previous studies often considered it as a homogeneous structure. Using multi-site extracellular recording techniques, ictal-like activity was observed along the dorso-ventral axis of the mEC in vitro in response to various ictogenic stimuli. This originated predominantly from ventral areas, spreading to dorsal mEC with a surprisingly slow velocity. Modulation of inhibitory tone was capable of changing the slope of ictal initiation, suggesting seizure propagation behaviours are highly dependent on levels of GABAergic function in this region. A distinct disinhibition model also showed, in the absence of inhibition, a prevalence for interictal-like initiation in ventral mEC, reflecting the intrinsic differences in mEC neurons. These findings suggest the ventral mEC is more prone to hyperexcitable discharge than the dorsal mEC, which may be relevant under pathological conditions. ABSTRACT The medial entorhinal cortex (mEC) has an important role in the generation and propagation of seizure activity. The organization of the mEC is such that a number of dorso-ventral relationships exist in neurophysiological properties of neurons. These range from intrinsic and synaptic properties to density of inhibitory connectivity. We examined the influence of these gradients on generation and propagation of epileptiform activity in the mEC. Using a 16-shank silicon probe array to record along the dorso-ventral axis of the mEC in vitro, we found 4-aminopyridine application produces ictal-like activity originating predominantly in ventral areas. This activity spreads to dorsal mEC at a surprisingly slow velocity (138 μm s-1 ), while cross-site interictal-like activity appeared relatively synchronous. We propose that ictal propagation is constrained by differential levels of GABAergic control since increasing (diazepam) or decreasing (Ro19-4603) GABAA receptor activation, respectively, reduced or increased the slope of ictal initiation. The observation that ictal activity is predominately generated in ventral mEC was replicated using a separate 0-Mg2+ model of epileptiform activity in vitro. By using a distinct disinhibition model (co-application of kainate and picrotoxin) we show that additional physiological features (for example intrinsic properties of mEC neurons) still produce a prevalence for interictal-like initiation in ventral mEC. These findings suggest that the ventral mEC is more likely to initiate hyperexcitable discharges than the dorsal mEC, and that seizure propagation is highly dependent on levels of GABAergic expression across the mEC.
10.1113/JP275871
pubmed_486_11905
Hyaluronic acid (HA) is widely used in the biomedicine due to its biocompatibility, biodegradability, and nontoxic properties. It is crucial for cell signaling role during morphogenesis, inflammation, and wound repair. After hydrogel formation, HA easily is converted to elastic sheets in order to use in preclinical and clinical applications. In addition, HA-derived hydrogels are easily used as vectors for cell and medication in tissue repairing and regenerative medicine. Moreover, in comparison with other polymers, HA -based hydrogels play a key role in in cellular behavior, including stem cell differentiation. The current paper reviews both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications.
10.1055/a-0991-7585
pubmed_965_8014
Two trends of sample dispersion variation with carrier flow rate in a single flow-injection manifold are completely revealed for the first time and an inflection point in the dispersion coefficient (D) vs. flow rate (q) curve is discovered. With the increase of the flow rate, the value of D increases before the inflection point but decreases after the inflection point. The value of the carrier flow rate at the inflection point (q(m)) is independent of the sample injection volume, the tube length, the tube coil radius and the tube inner diameter. It is only affected by the substance diffusion coefficient (D(m)) of the analysis. The value of q(m) decreases as D(m) increases. Therefore, the value of D(m) for a sample can be estimated according to the D(m) vs. q(m) curve.
10.1016/0039-9140(95)01693-7
pubmed_367_2095
Adequate risk-adjustment is critical to the success of market-oriented healthcare reforms in many countries. Regulated competition among insurers and providers is often a crucial element in these reforms. Consumers may then choose among competing health insurance plans, which are largely financed through premium-replacing risk-adjusted capitation payments. Too crude risk-adjustment, which is common in 2003, provides health insurance plans with incentives for risk selection, which may threaten access to (good quality) healthcare, efficiency and consumer satisfaction. In this review the background and rationale for the implementation of risk-adjusted capitation payments is described. The authors are optimistic about the possibilities for improving the present, crude risk-adjusted capitation payment systems in order to reduce risk selection.
10.1586/14737167.3.5.541
pubmed_1140_22680
The Pseudomonas syringae type III secretion system (TTSS) translocates effector proteins into plant cells. Several P. syringae effectors require accessory proteins called type III chaperones (TTCs) to be secreted via the TTSS. We characterized the hopO1-1, hopS1, and hopS2 operons in P. syringae pv. tomato DC3000; these operons encode three homologous TTCs, ShcO1, ShcS1, and ShcS2. ShcO1, ShcS1, and ShcS2 facilitated the type III secretion and/or translocation of their cognate effectors HopO1-1, HopS1, and HopS2, respectively. ShcO1 and HopO1-1 interacted with each other in yeast two-hybrid and coimmunoprecipitation assays. Interestingly, ShcS1 and ShcS2 were capable of substituting for ShcO1 in facilitating HopO1-1 secretion and translocation and each TTC was able to bind the other's cognate effectors in yeast two-hybrid assays. Moreover, ShcO1, ShcS1, and ShcS2 all bound to the middle-third region of HopO1-1. The HopS2 effector possessed atypical P. syringae TTSS N-terminal characteristics and was translocated in low amounts. A site-directed HopS2 mutation that introduced a common N-terminal characteristic from other P. syringae type III secreted substrates increased HopS2 translocation, supporting the idea that this characteristic functions as a secretion signal. Additionally, hopO1-2 and hopT1-2 were shown to encode effectors secreted via the DC3000 TTSS. Finally, a DC3000 hopO1-1 operon deletion mutant produced disease symptoms similar to those seen with wild-type DC3000 but was reduced in its ability to multiply in Arabidopsis thaliana. The existence of TTCs that can bind to dissimilar effectors and that can substitute for each other in effector secretion provides insights into the nature of how TTCs function.
10.1128/JB.187.12.4257-4269.2005
pubmed_1098_4652
Part 1 of this essay argued that the root causes of primary care's problems lie in (1) the low percent of national health expenditures dedicated to primary care and (2) overly large patient panels that clinicians without a team are unable to manage, leading to widespread burnout and poor patient access. Part 2 explores policies and practice changes that could solve or mitigate these primary care problems.Initiatives attempting to improve primary care are discussed. Diffuse multi-component initiatives-patient-centered medical homes (PCMHs), accountable care organizations (ACOs), and Comprehensive Primary Care Plus (CPC+)-have had limited success in addressing primary care's core problems. More focused initiatives-care management, open access, and telehealth-offer more promise.To truly revitalize primary care, 2 fundamental changes are needed: (1) a substantially greater percent of health expenditures dedicated to primary care, and (2) the building of powerful teams that add capacity to care for large panels while reducing burnout.Part 2 of the essay reviews 3 approaches to increasing primary care spending: state-level legislation, eliminating Medicare's disparity between primary care and procedural specialty reimbursement, and efforts by health systems. The final section of Part 2 addresses the building of powerful core and interprofessional teams.
10.1370/afm.2859
pubmed_644_8912
OBJECTIVE Most clinical research evaluates diagnostic tests by accuracy measures such as sensitivity and specificity. This is stimulated by the Standards for Reporting of Diagnostic Accuracy initiative, which focuses on accuracy in the widely accepted guidelines. Referring to the clinical consequences of diagnostic tests, many epidemiologists recognize the importance of patient outcome studies in addition to accuracy studies. However, there is a theoretical argument that stipulates the need for patient outcome studies, which has thus far been overlooked. RESULTS Using a philosophical argument, we show that the definition of disease necessarily involves the concept of function, which in turn is inextricably related to outcome. Consequently, diagnostic tests that establish the presence or absence of disease cannot be evaluated without measuring patient outcome. Patient outcome studies are therefore the definitive means to assess the merits of a diagnostic test. CONCLUSION The need for patient outcome studies is not due to pragmatic reasons, as previous authors argued, but is based on a philosophical argument relating the definition of disease to the concept of function. We propose that authors justify the use of accuracy studies in papers reporting diagnostic test evaluation by describing the association between gold standard test and patient outcome.
10.1016/j.jclinepi.2008.02.005
pubmed_822_1070
Firefly luciferase is the most studied bioluminescence system, and its catalyzed reactions have been relatively well characterized. However, the color tuning mechanism that leads to firefly multicolor bioluminescence is still unknown, nor is consensual which is the yellow-green and red emitters. Computational studies have been essential in the study of oxyluciferin (OxyLH2) chemi- and bioluminescence and are responsible for most of our knowledge of this natural phenomenon. The objective of this manuscript is the analysis of the benefits and the conclusions derived from the theoretical studies of the light emitter, OxyLH2, and its applications on bioluminescence research.
10.1021/ct200003u