Dietary quality indices modify the effects of apolipoprotein B polymorphisms on biochemical and anthropometric factors in type 2 diabetes mellitus.
We tried to identify the interaction between dietary quality indices and apolipoprotein B Ins/Del and EcoR1 polymorphisms on biochemical and anthropometric factors in patients with type 2 diabetes mellitus (T2DM). This cross-sectional study recruited 700 adults with T2DM in Tehran. The genotypes of Ins/Del and EcoR1 single nucleotide polymorphisms (SNP) were explored via polymerase chain reaction (PCR). Dietary quality index-international (DQI-I), healthy eating index-2015 (HEI-2015) and dietary phytochemical index (DPI) were calculated by semi-quantitative food frequency questionnaire (FFQ). In both crude and adjusted model for confounding factors, we observed significant interactions between DQI-I and Ins/Del SNP on leptin in and 8-iso-prostaglandin F2 α (8-iso-PGF2α), DPI and EcoR1 SNP on total cholesterol (TC) and between Ins/Del SNP and HEI-2015 on interleukin-18 (IL-18). Furthermore, in crude model there were close to meaningful interactions between EcoR1 SNP and DQI-I on total antioxidant capacity (TAC) and between EcoR1 SNP and HEI-2015 on serum leptin and superoxide dismutase (SOD) levels. Our finding indicated that the association between DQI-I, HEI-2015 and DPI with IL-18, TC, leptin and 8-iso-PGF2α in patients with T2DM might be dependent on Ins/Del and EcoR1 variants in ApoB gene.


Reactive transport modelling of groundwater chemistry in a chalk aquifer at the watershed scale.
This study investigates thermodynamics and kinetics of water-rock interactions in a carbonate aquifer at the watershed scale. A reactive transport model is applied to the unconfined chalk aquifer of the Champagne Mounts (France), by considering both the chalk matrix and the interconnected fracture network. Major element concentrations and main chemical parameters calculated in groundwater and their evolution along flow lines are in fair agreement with field data. A relative homogeneity of the aquifer baseline chemistry is rapidly reached in terms of pH, alkalinity and Ca concentration since calcite equilibrium is achieved over the first metres of the vadose zone. However, incongruent chalk dissolution slowly releases Ba, Mg and Sr in groundwater. Introducing dilution effect by rainwater infiltration and a local occurrence of dolomite improves the agreement between modelling and field data. The dissolution of illite and opal-CT, controlling K and SiO(2) concentrations in the model, can be approximately tackled by classical kinetic rate laws, but not the incongruent chalk dissolution. An apparent kinetic rate has therefore been fitted on field data by inverse modelling: 1.5×10(-5) mol(chalk)L (-1) water year (-1). Sensitivity analysis indicates that the CO(2) partial pressure of the unsaturated zone is a critical parameter for modelling the baseline chemistry over the whole chalk aquifer.


Acute myeloid leukemia cells require 6-phosphogluconate dehydrogenase for cell growth and NADPH-dependent metabolic reprogramming.
Acute myeloid leukemia (AML) cells are highly dependent on glycolytic pathways to generate metabolic energy and support cell growth, hinting at specific, targetable vulnerabilities as potential novel targets for drug development. Elevated levels of NADPH, a central metabolic factor involved in redox reactions, are common in myeloid leukemia cells, but the significance or biochemical basis underlying this increase is unknown. Using a small molecule analog that efficiently inhibits NADPH-producing enzymes, we found that AML cells require NADPH homeostasis for cell growth. We also found that inhibiting NADPH production through knockdown of 6-phosphogluconate dehydrogenase (6PGD) within the pentose phosphate pathway was sufficient to reduce cell growth and lactate production, a measure of metabolic reprogramming. Further, inhibition of 6PGD activity reduced NADH levels and enzymatic activity of the oxidized NADH-dependent sirtuin-1. Targeting 6PGD and NADPH production was sufficient to block growth of AML cell lines resistant to the chemotherapeutics daunorubicin and cytarabine. Importantly, stromal cell-mediated resistance to targeted inhibition of oncogenic FLT3 kinase activity by quizartinib was circumvented by 6PGD knockdown. Overall, these data suggest that the dependency of AML cells on NADPH to permit increased glycolytic flux creates a potential vulnerability of possible therapeutic benefit, since much of the enhanced production of NADPH is dependent on the activity of a single enzyme, 6PGD.


[Morphology of the endocrine portion of the teleost pancreas].
Endocrine component of the crucian (Carassius carassius), carp (Cyprinus carpio), tench (Tinca tinca) and silurus (Silurus glanis) pancreas is structurally organized in the form of pancreatic islets. Gorbusha (Oncorhynchus gorbuscha) has, besides the islets, some Brockman's bodies. Endocrine component of the pancreas of Teleostei possesses A-, B-, D and acinar-islet cells "B". All types of cells are shoot-shaped and all have contacts with the capillaries. Extrusion of the hormones from the endocrine cells is carried out via emiocytosis, and in gorbusha at the time of migration--by microapocrine means. Secretory granules were observed to get into the capillaries and make hormonal storage necessary for fish migration. It was demonstrated that endocrine component of the pancreas in Teleostei is highly rich in innervation, neuronal fibers containing small granular vesicles.


Unexpected structural and functional consequences of the R33Q homozygous mutation in cardiac calsequestrin: a complex arrhythmogenic cascade in a knock in mouse model.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by life threatening arrhythmias elicited by physical and emotional stress in young individuals. The recessive form of CPVT is associated with mutation in the cardiac calsequestrin gene (CASQ2). We engineered and characterized a homozygous CASQ2(R33Q/R33Q) mouse model that closely mimics the clinical phenotype of CPVT patients. CASQ2(R33Q/R33Q) mice develop bidirectional VT on exposure to environmental stress whereas CASQ2(R33Q/R33Q) myocytes show reduction of the sarcoplasmic reticulum (SR) calcium content, adrenergically mediated delayed (DADs) and early (EADs) afterdepolarizations leading to triggered activity. Furthermore triadin, junctin, and CASQ2-R33Q proteins are significantly decreased in knock-in mice despite normal levels of mRNA, whereas the ryanodine receptor (RyR2), calreticulin, phospholamban, and SERCA2a-ATPase are not changed. Trypsin digestion studies show increased susceptibility to proteolysis of mutant CASQ2. Despite normal histology, CASQ2(R33Q/R33Q) hearts display ultrastructural changes such as disarray of junctional electron-dense material, referable to CASQ2 polymers, dilatation of junctional SR, yet normal total SR volume. Based on the foregoings, we propose that the phenotype of the CASQ2(R33Q/R33Q) CPVT mouse model is portrayed by an unexpected set of abnormalities including (1) reduced CASQ2 content, possibly attributable to increased degradation of CASQ2-R33Q, (2) reduction of SR calcium content, (3) dilatation of junctional SR, and (4) impaired clustering of mutant CASQ2.


[Immunocytochemical detection of substances related to methionine enkephalin in the tentacles and food of the snail (Helix aspersa)].
Immunocytochemistry reveals the presence of methionine-enkephalin-like substance(s) in the collar cells of the two kinds of tentacles and in the foot of the snail Helix aspersa. The density of the immunoreactive material is higher in young animals than in adults. The greater part of the substance(s) is released at the surface of the epidermis and probably mixed with the mucus. A possible neuroendocrine and/or neuromodulatory function can be considered especially for the collar cells connected with the tentacular ganglia.


Screen Hours and Sleep Symptoms: The US National Health and Nutrition Examination Survey.
Few studies have examined the relationship between television viewing, computer use, and sleep symptoms. We hypothesized that television and computer time was associated with sleep symptoms. Screen hours were the sum of daily TV hours and computer hours. A total of 4342 participants 20 years and older had data on screen hours. After adjusting for confounders, 4 or more screen hours were significantly associated with increased odds of reporting long sleep latency, nighttime awakening, high sleep hours, and snoring (P < .05). These findings suggest that increased screen/TV time is an important risk factor for sleep symptoms.


Hematologic β-tubulin VI isoform exhibits genetic variability that influences paclitaxel toxicity.
Cellular microtubules composed of α-β-tubulin heterodimers that are essential for cell shape, division, and intracellular transport are valid targets for anticancer therapy. However, not all the conserved but differentially expressed members of the β-tubulin gene superfamily have been investigated for their role in these settings. In this study, we examined roles for the hematologic isoform β-tubulin VI and functional genetic variants in the gene. β-tubulin VI was highly expressed in blood cells with a substantial interindividual variability (seven-fold variation in mRNA). We characterized DNA missense variations leading to Q43P, T274M, and R307H, and a rare nonsense variant, Y55X. Because variations in the hematologic target of microtubule-binding drugs might alter their myelosuppressive action, we tested their effect in cell lines stably expressing the different β-tubulin VI full-length variants, finding that the T274M change significantly decreased sensitivity to paclitaxel-induced tubulin polymerization. Furthermore, patients treated with paclitaxel and carrying β-tubulin VI T274M exhibited a significantly lower thrombocytopenia than wild-type homozygous patients (P = 0.031). Together, our findings define β-tubulin VI as a hematologic isotype with significant genetic variation in humans that may affect the myelosuppresive action of microtubule-binding drugs. A polymorphism found in a tubulin isoform expressed only in hemapoietic cells may contribute to the patient variation in myelosuppression that occurs after treatment with microtubule-binding drugs.


[Spirometry quality in preschool children].
Carrying out quality spirometric maneuvers in preschool children in both the diagnosis and follow-up of respiratory diseases continues to be very scarce. This is due to several reasons, including a lack of consensus on quality criteria and the acceptability of the test. The purpose of this study is therefore to obtain reference norms from a population of healthy preschool children from the Autonomous Community of Navarre (Spain). A total of 114 healthy preschool children aged between 3 and 7 years of age, without prior experience in carrying out lung function tests, were included. A total of 76 were able to realize at least two acceptable spirometric maneuvers, and 60 of them maneuvers that were acceptable and reproducible, according to ATS/ERS criteria. This represents a global success percentage of 59%. The most common failing was premature and brusque termination of the spirometric maneuver, followed by an inadequate peak in breathing. Over half of the preschool children were able to realize quality spirometric maneuvers. Our data make it possible to recommend the proposed quality criteria as being suitable for routine use, and to encourage the use of spirometry in regular clinical practice within the setting of specialized care.


Bayesian model of Snellen visual acuity.
A Bayesian model of Snellen visual acuity (VA) has been developed that, as far as we know, is the first one that includes the three main stages of VA: (1) optical degradations, (2) neural image representation and contrast thresholding, and (3) character recognition. The retinal image of a Snellen test chart is obtained from experimental wave-aberration data. Then a subband image decomposition with a set of visual channels tuned to different spatial frequencies and orientations is applied to the retinal image, as in standard computational models of early cortical image representation. A neural threshold is applied to the contrast responses to include the effect of the neural contrast sensitivity. The resulting image representation is the base of a Bayesian pattern-recognition method robust to the presence of optical aberrations. The model is applied to images containing sets of letter optotypes at different scales, and the number of correct answers is obtained at each scale; the final output is the decimal Snellen VA. The model has no free parameters to adjust. The main input data are the eye's optical aberrations, and standard values are used for all other parameters, including the Stiles-Crawford effect, visual channels, and neural contrast threshold, when no subject specific values are available. When aberrations are large, Snellen VA involving pattern recognition differs from grating acuity, which is based on a simpler detection (or orientation-discrimination) task and hence is basically unaffected by phase distortions introduced by the optical transfer function. A preliminary test of the model in one subject produced close agreement between actual measurements and predicted VA values. Two examples are also included: (1) application of the method to the prediction of the VAin refractive-surgery patients and (2) simulation of the VA attainable by correcting ocular aberrations.


Hereditary Thrombotic Thrombocytopenic Purpura in a 9-Month-old: Diagnosing and Managing an Ultra-rare Disorder.
Hereditary thrombotic thrombocytopenic purpura is an ultra-rare disorder caused by biallelic mutations in the ADAMTS13 gene. Because it can be difficult to diagnose, plasma ADAMTS13 activity assessment should be considered in patients with thrombocytopenia, anemia, and schistocytes on peripheral blood smear. We present the diagnostic evaluation of a patient with hereditary thrombotic thrombocytopenic purpura. Genetic testing revealed one known pathogenic mutation and one novel mutation of ADAMTS13 classified as likely pathogenic on the basis of parental genetic testing and in silico analyses. We further discuss off-label use of prophylactic plasma-derived Factor VIII (Koate-DVI) and the benefit of rare disease registries.


Amplitude modulating frequency overrides carrier frequency in tACS-induced phosphene percept.
The amplitude modulated (AM) neural oscillation is an essential feature of neural dynamics to coordinate distant brain areas. The AM transcranial alternating current stimulation (tACS) has recently been adopted to examine various cognitive functions, but its neural mechanism remains unclear. The current study utilized the phosphene phenomenon to investigate whether, in an AM-tACS, the AM frequency could modulate or even override the carrier frequency in phosphene percept. We measured the phosphene threshold and the perceived flash rate/pattern from 12 human subjects (four females, aged from 20-44 years old) under tACS that paired carrier waves (10, 14, 18, 22 Hz) with different envelope conditions (0, 2, 4 Hz) over the mid-occipital and left facial areas. We also examined the phosphene source by adopting a high-density stimulation montage. Our results revealed that (1) phosphene threshold was higher for AM-tACS than sinusoidal tACS and demonstrated different carrier frequency functions in two stimulation montages. (2) AM-tACS slowed down the phosphene flashing and abolished the relation between the carrier frequency and flash percept in sinusoidal tACS. This effect was independent of the intensity change of the stimulation. (3) Left facial stimulation elicited phosphene in the upper-left visual field, while occipital stimulation elicited equally distributed phosphene. (4) The near-eye electrodermal activity (EDA) measured under the threshold-level occipital tACS was greater than the lowest power sufficient to elicit retinal phosphene. Our results show that AM frequency may override the carrier frequency and determine the perceived flashing frequency of AM-tACS-induced phosphene.


Recovery of ventilatory response to carbon dioxide after thiopentone, morphine and fentanyl in man.
Ventilatory responses to CO2 (delta VI/delta PCO2) were measured half, one, two and four hours after infusions of thiopentone, morphine, fentanyl and saline in healthy men in order to test the idea that variation in clinical recovery and control of breathing after anaesthetic drugs are associated with interindividual differences in control measurements of delta VI/delta PCO2. Ventilatory response to CO2 was profoundly reduced one half hour after each drug, in contrast to the observation during air breathing that ventilation and end tidal PCO2 had returned to within 10 per cent of control. Mean delta VI/delta PCO2 increased progressively at one, two, and four hours, returning to near control after thiopentone, but remaining less than 80 per cent of control four hours after morphine and fentanyl. From the regression equations of each ventilatory response, ventilation at PCO2 of 58 and 70 mmHg (VI58 and VI70) were computed to estimate displacement of the response curves by the drugs. Following thiopentone there was no significant change of V158. In contrast ther was a highly siginificant fall of VI58 one half hour after fentanyl (p less than 0.01), with progressive return towards control at one, two, and four hours; similar changes were observed after morphine. For each drug, changes of VI70 were substantially greater than corresponding changes of V158. At all times during these recovery measurements, subjects were conscious and co-operative and, by traditional clinical criteria, were judged to have recovered from the effects of the drugs. Differences between high and low responding subjects were assessed by plotting control measurements against values obtained half and one hour after drugs. No systematic differences were found. These findings suggest that delta VI/delta PCO2 is a sensitive indicator of central nervous activity, but do not support the concepts that individuals with low delta VI/delta PCO2 might be more susceptible to the ventilatory depressant effects of anaesthetic drugs, or that low delta VI/delta PCO2 might be associated with delayed return of spontaneous breathing after general anaesthesia. Plasma thiopentone levels at half, one, and four hours were highly reproducible, in contrast to the wide variation of delta VI/delta PCO2 among subjects in this study. These findings together support the notion that wide variation in clinical recovery from anaesthesia may have a primary physiological basis in addition to variation caused by interindividual differences in drug dosage, biotransformation and excretion.


Bioinformatic identification and expression analysis of banana microRNAs and their targets.
MicroRNAs (miRNAs) represent a class of endogenous non-coding small RNAs that play important roles in multiple biological processes by degrading targeted mRNAs or repressing mRNA translation. Thousands of miRNAs have been identified in many plant species, whereas only a limited number of miRNAs have been predicted in M. acuminata (A genome) and M. balbisiana (B genome). Here, previously known plant miRNAs were BLASTed against the Expressed Sequence Tag (EST) and Genomic Survey Sequence (GSS), a database of banana genes. A total of 32 potential miRNAs belonging to 13 miRNAs families were detected using a range of filtering criteria. 244 miRNA:target pairs were subsequently predicted, most of which encode transcription factors or enzymes that participate in the regulation of development, growth, metabolism, and other physiological processes. In order to validate the predicted miRNAs and the mutual relationship between miRNAs and their target genes, qRT-PCR was applied to detect the tissue-specific expression levels of 12 putative miRNAs and 6 target genes in roots, leaves, flowers, and fruits. This study provides some important information about banana pre-miRNAs, mature miRNAs, and miRNA target genes and these findings can be applied to future research of miRNA functions.


Identification of alternative promoter usage for the matrix Gla protein gene. Evidence for differential expression during early development in Xenopus laevis.
Recent cloning of the Xenopus laevis (Xl) matrix Gla protein (MGP) gene indicated the presence of a conserved overall structure for this gene between mammals and amphibians but identified an additional 5'-exon, not detected in mammals, flanked by a functional, calcium-sensitive promoter, 3042 bp distant from the ATG initiation codon. DNA sequence analysis identified a second TATA-like DNA motif located at the 3' end of intron 1 and adjacent to the ATG-containing second exon. This putative proximal promoter was found to direct transcription of the luciferase reporter gene in the X. laevis A6 cell line, a result confirmed by subsequent deletion mutant analysis. RT-PCR analysis of XlMGP gene expression during early development identified a different temporal expression of the two transcripts, strongly suggesting differential promoter activation under the control of either maternally inherited or developmentally induced regulatory factors. Our results provide further evidence of the usefulness of nonmammalian model systems to elucidate the complex regulation of MGP gene transcription and raise the possibility that a similar mechanism of regulation may also exist in mammals.


In-situ electrical addressing of one-dimensional gold nanoparticle assemblies.
Substrates with 1-dimensional nanosize grooves were prepared using extreme-ultraviolet interference lithography (EUV-IL), wherein gold nanoparticles were self-assembled to form 1-dimensional structures. To measure the electrical properties of gold nanoparticle chains we introduce a novel in-situ measuring method based on nanomanipulator system in a scanning electron microscope. This method comprises enormous versatility for the precisely electrical addressing of low-dimensional nanoscale structures and may even be applied to routinely addressing of structures in the sub-10 nm range.


Comparison of the effectiveness of combination of fennel extract/vitamin E with ibuprofen on the pain intensity in students with primary dysmenorrhea.
Dysmenorrhea is a common gynecologic disorder affecting as many as 60% of menstruating women. In the United States, work absenteeism due to dysmenorrhea is estimated to be 600 million work hours per year, and the economic consequences are estimated at $2 billion per year; therefore, it is a public problem nowadays. The purpose of this study was to compare the effects of combination of fennel extract/vitamin E with ibuprofen on the intensity of pain in primary dysmenorrhea among the students of Tabriz city in 2007-2009. This study was done by using double-blinded quasi-experimental research method. After taking the required licenses from ethics committee, 68 students from Medical and Tabriz universities, who were living in the dormitory, suffering from primary dysmenorrhea, and were eligible for the study, were randomly divided into two groups of 34 students each (the two groups used combination of fennel extract/vitamin E and ibuprofen cross-over form in the 2 months). We used Visual Analogue Scale (VAS) tool for ranking the intensity of the pain. Data analysis was done by using SPSS Ver. 14. The mean of peak pain intensity in the first, second, third, sixth, and forty-eighth hours in the group that had used combination of fennel extract/vitamin E was lower than the group that had used ibuprofen, and statistical differences were observed between the two groups in the first and second hours; combination of fennel extract/vitamin E was more effective than ibuprofen in the first hour (P < 0.03) and second hour (P < 0.04). Combination of fennel extract/vitamin E is effective on decreasing the intensity of pain of primary dysmenorrhea, and it is advised to those who cannot use chemical drugs.


Degradation of functional triose phosphate isomerase protein underlies sugarkill pathology.
Triose phosphate isomerase (TPI) deficiency glycolytic enzymopathy is a progressive neurodegenerative condition that remains poorly understood. The disease is caused exclusively by specific missense mutations affecting the TPI protein and clinically features hemolytic anemia, adult-onset neurological impairment, degeneration, and reduced longevity. TPI has a well-characterized role in glycolysis, catalyzing the isomerization of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P); however, little is known mechanistically about the pathogenesis associated with specific recessive mutations that cause progressive neurodegeneration. Here, we describe key aspects of TPI pathogenesis identified using the TPI(sugarkill) mutation, a Drosophila model of human TPI deficiency. Specifically, we demonstrate that the mutant protein is expressed, capable of forming a homodimer, and is functional. However, the mutant protein is degraded by the 20S proteasome core leading to loss-of-function pathogenesis.


Glycopolymer-Based Antiswelling, Conductive, and Underwater Adhesive Hydrogels for Flexible Strain Sensor Application.
With the fast development of soft electronics, underwater adhesion has become a highly desired feature for various sensing uses. Currently, most adhesive hydrogels are based on catechol-based structures, such as polydopamine, pyrogallol, and tannic acid, with very limited structural variety. Herein, a new type of glycopolymer-based underwater adhesive hydrogel has been prepared straightforwardly by random copolymerization of acrylic acid, acetyl-protected/unprotected glucose, and methacrylic anhydride in dimethyl sulfoxide (DMSO). By employing a DMSO-water solvent exchange strategy, the underwater adhesion was skillfully induced by the synergetic effects of hydrophobic aggregation and hydrogen bonding, leading to excellent adhesion behaviors on various surfaces, including pig skins, glasses, plastics, and metals, even after 5 days of storage in water. In addition, the underwater adhesive hydrogels with simple and low-cost protected/unprotected carbohydrate compositions showed good mechanical and rheological properties, together with cytocompatibility and antiswelling behavior in water, all of which are beneficial for underwater adhesions. In application as a flexible strain sensor, the adhesive hydrogel exhibited stable and reliable sensing ability for monitoring human motion in real time, suggesting great potential for intelligent equipment design.


Endogenous intracellular calcium buffering and the activation/inactivation of HVA calcium currents in rat dentate gyrus granule cells.
Granule cells acutely dissociated from the dentate gyrus of adult rat brains displayed a single class of high-threshold, voltage-activated (HVA) Ca2+ channels. The kinetics of whole-cell Ca2+ currents recorded with pipette solutions containing an intracellular ATP regenerating system but devoid of exogenous Ca2+ buffers, were fit best by Hodgkin-Huxley kinetics (m2h), and were indistinguishable from those recorded with the nystatin perforated patch method. In the absence of exogenous Ca2+ buffers, inactivation of HVA Ca2+ channels was a predominantly Ca(2+)-dependent process. The contribution of endogenous Ca2+ buffers to the kinetics of inactivation was investigated by comparing currents recorded from control cells to currents recorded from neurons that have lost a specific Ca(2+)-binding protein, Calbindin-D28K (CaBP), after kindling-induced epilepsy. Kindled neurons devoid of CaBP showed faster rates of both activation and inactivation. Adding an exogenous Ca2+ chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), to the intracellular solution largely eliminated inactivation in both control and kindled neurons. The results are consistent with the hypothesis that endogenous intraneuronal CaBP contributes significantly to submembrane Ca2+ sequestration at a concentration range and time domain that regulate Ca2+ channel inactivation.


Conditions under which genome-wide association studies will be positively misleading.
Genome-wide association mapping is a popular method for using natural variation within a species to generate a genotype-phenotype map. Statistical association between an allele at a locus and the trait in question is used as evidence that variation at the locus is responsible for variation of the trait. Indirect association, however, can give rise to statistically significant results at loci unrelated to the trait. We use a haploid, three-locus, binary genetic model to describe the conditions under which these indirect associations become stronger than any of the causative associations in the organism--even to the point of representing the only associations present in the data. These indirect associations are the result of disequilibrium between multiple factors affecting a single trait. Epistasis and population structure can exacerbate the problem but are not required to create it. From a statistical point of view, indirect associations are true associations rather than the result of stochastic noise: they will not be ameliorated by increasing sampling size or marker density and can be reproduced in independent studies.


Erectile dysfunction management: a critical appraisal of clinical practice guidelines with the AGREE II instrument.
Our study aimed to assess the methodological strengths and weaknesses of erectile dysfunction clinical practice guidelines (CPGs) for individuals using the AGREE II tool. Erectile dysfunction related CPGs were identified from three databases: the National Guideline Clearinghouse, the Guidelines International Network, and PubMed between 2000 and 2020. We designed an independent assessment for each of the erectile dysfunction related CPGs using the AGREE II tool. Four appraisers performed these assessments. The literature search identified 8 CPGs that met our inclusion criteria. The evaluation of the AGREE II domains of each individual revealed that the median scores of domains related to applicability were quite low (39%). Also, the median scores of domains related to the rigour of development and the stakeholder involvement were relatively low (53% and 63%). We determined the highest median scores in three AGREE II domains: clarity of presentation (80.5%), editorial independence (77%), and scope and purpose (89.5%). We found that the European Association of Urology (EAU), the American Urological Association (AUA), and the British Society for Sexual Medicine (BSSM) guidelines had >60% in >4 domains and that their average AGREE II scores were over 70%. In the Canadian Diabetic Association (CDA) and the Japanese Society for Sexual Medicine (JSSM) guidelines, we found that >4 domains were >60%, but their average AGREE II scores were below 70%. The British Medical Journal (BMJ), the Canadian Urologic Association (CUA), and the Malaysian Urologic Association (MUA) guidelines had >60% in <3 domains. We highly recommended EAU, AUA and BSSM guidelines, while we moderately recommended CDA and JSSM guidelines. BMJ, CUA and MUA guidelines were weakly recommended. The quality of the guidelines for erectile dysfunction was variable according to AGREE II. We noted significant deficiencies in the methodological quality of the CPGs developed by different organisations in the areas of applicability and rigour of development.


The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: a randomized, double-blind placebo-controlled study.
Finding an effective treatment for acne that is well tolerated by the patients is a challenge. One study has suggested the efficacy of tea tree oil in treatment of the acne vulgaris. To determine the efficacy of tea tree oil in mild to moderate acne vulgaris. This was a randomized double-blind clinical trial performed in 60 patients with mild to moderate acne vulgaris. They were randomly divided into two groups and were treated with tea tree oil gel (n=30) or placebo (n=30). They were followed every 15 days for a period of 45 days. Response to treatment was evaluated by the total acne lesions counting (TLC) and acne severity index (ASI). The data was analyzed statistically using t-test and by SPSS program. There were no significant differences regarding demographic characteristics between the two groups. There was a significant difference between tea tree oil gel and placebo in the improvement of the TLC and also regarding improvement of the ASI. In terms of TLC and ASI, tea tree oil gel was 3.55 times and 5.75 times more effective than placebo respectively. Side-effects with both groups were relatively similar and tolerable. Topical 5% tea tree oil is an effective treatment for mild to moderate acne vulgaris.


Quality of Living and Dying: Pediatric Palliative Care and End-of-Life Decisions in the Netherlands.
In 2002, The Netherlands continued its leadership in developing rules and jurisdiction regarding euthanasia and end-of-life decisions by implementing the Euthanasia Act, which allows euthanasia for patients 12 years of age and older. Subsequently, in 2005, the regulation on active ending of life for newborns was issued. However, more and more physicians and parents have stated that the age gap between these two regulations-children between 1 and 12 years old-is undesirable. These children should have the same right to end their suffering as adults and newborn infants. An extended debate on pediatric euthanasia ensued, and currently the debate is ongoing as to whether legislation should be altered in order to allow pediatric euthanasia. An emerging major question regards the active ending of life in the context of palliative care: How does a request for active ending of life relate to the care that is given to children in the palliative phase? Until now, the distinction between palliative care and end-of-life decisions continues to remain unclear, making any discussion about their mutual in- and exclusiveness hazardous at best. In this report, therefore, we aim to provide insight into the relationship between pediatric palliative care and end-of-life decisions, as understood in the Netherlands. We do so by first providing an overview of the (legal) rules and regulations regarding euthanasia and active ending of life, followed by an analysis of the relationship between these two, using the Dutch National Guidelines for Palliative Care for Children. The results of this analysis revealed two major and related features of palliative care and end-of-life decisions for children: (1) palliative care and end-of-life decisions are part of the same process, one that focuses both on quality of living and quality of dying, and (2) although physicians are seen as ultimately responsible for making end-of-life decisions, the involvement of parents and children in this decision is of the utmost importance and should be regarded as such.


Effect of Cucurbit Host, Production Region, and Season on the Population Structure of Pseudoperonospora cubensis in Florida.
Pseudoperonospora cubensis, the causal agent of Cucurbit downy mildew (CDM), is one of the most important diseases affecting cucurbit production in the United States. This disease is especially damaging to Florida production areas, as the state is a top producer of many cucurbit species. In addition, winter production in central and south Florida likely serves as a likely source of P. cubensis inoculum for spring and summer cucurbit production throughout the eastern U.S. where CDM is unable to overwinter in the absence of a living host. Over two years (2017 and 2018) and four seasons (spring 2017, spring 2018, fall 2017, and fall 2018) 274 P. cubensis isolates were collected from cucurbit hosts at production sites in south, central and north Florida. The isolates were analyzed with ten simple sequence repeat (SSR) markers to establish population structure and genetic diversity, and further assigned to a clade based on a qPCR assay. Results of population structure and genetic diversity analyses differentiated isolates based on cucurbit host and clade (1 or 2). Of the isolates assigned to clade by qPCR, butternut squash, watermelon, and zucchini were dominated by clade 1 isolates, whereas cucumber isolates were split 34% and 59% between clades 1 and 2, respectively. Clade assignments agreed with isolate clustering observed within discriminant analysis of principal components (DAPC) based on SSR markers, although watermelon isolates formed a group distinct from the other clade 1 isolates. For seasonal collections from cucumber at each location, isolates were typically skewed to one clade or the other and varied across locations and seasons within each year of the study. This variable population structure of cucumber isolates could have consequences for regional disease management. This is the first study to characterize P. cubensis populations in Florida, evaluating the effect of cucurbit host and clade-type on isolate diversity and population structure, with implications for CDM management in Florida and other U.S. cucurbit production areas.


Bile salts and glycine as cogerminants for Clostridium difficile spores.
Spore formation by Clostridium difficile is a significant obstacle to overcoming hospital-acquired C. difficile-associated disease. Spores are resistant to heat, radiation, chemicals, and antibiotics, making a contaminated environment difficult to clean. To cause disease, however, spores must germinate and grow out as vegetative cells. The germination of C. difficile spores has not been examined in detail. In an effort to understand the germination of C. difficile spores, we characterized the response of C. difficile spores to bile. We found that cholate derivatives and the amino acid glycine act as cogerminants. Deoxycholate, a metabolite of cholate produced by the normal intestinal flora, also induced germination of C. difficile spores but prevented the growth of vegetative C. difficile. A model of resistance to C. difficile colonization mediated by the normal bacterial flora is proposed.


Maternal stress and internalizing symptoms in preschoolers: the moderating role of narrative coherence.
In the present study, we examined whether maternal psychosocial stress and children's coherence in story-stem narratives are associated with preschool children's internalizing symptoms and disorders, and whether narrative coherence moderates the association between maternal stress and children's internalizing symptoms and disorders. The sample consists of 236 preschool children (129 girls, 107 boys; Mage = 5.15 years) and their mothers. Mothers completed questionnaires on their psychosocial stress burden and on child symptoms. A diagnostic interview (the Preschool Age Psychiatric Assessment; Egger & Angold, 2004) was conducted with one of the parents to assess children's psychiatric diagnoses. Children completed 8 story stems of the MacArthur Story Stem Battery (Bretherton & Oppenheim, 2003). Story-stem narratives were coded for narrative coherence. Multivariate analyses were controlled for children's age, gender, verbal performance, and externalizing symptoms. Results showed that maternal psychosocial stress was significantly associated with child internalizing symptoms and disorders. Neither maternal stress nor children's internalizing symptoms or disorders were associated with narrative coherence. However, narrative coherence moderated the association between maternal stress and child internalizing symptoms. For children with more incoherent narratives, the association between maternal psychosocial stress and children's internalizing symptoms was significantly stronger than for children with more coherent narratives. The moderation effect of narrative coherence concerning children's internalizing disorders was found not to be significant. Our findings indicate that preschool children's cognitive-emotional organization in dealing with relational conflict themes seems to buffer their mental health when exposed to adverse circumstances in their everyday family life.


Green extraction of hemp (Cannabis sativa L.) using microwave method for recovery of three valuable fractions (essential oil, phenolic compounds and cannabinoids): a central composite design optimization study.
Solvent-free microwave-assisted extraction (MAE) is a green extraction method capable of boosting the yield and quality profile of hemp essential oil when compared with other conventional extraction techniques. During this process, two by-products are produced, namely the aqueous residue containing bioactive phenolics and the residual deterpenated biomass, which can be used for further extraction and purification of phytocannabinoids. To date, the hemp industry has not utilized these products, although they can be valuable for the food, cosmetic, nutraceutical and pharmaceutical market. This study assessed and optimized the variables affecting MAE efficiency, namely microwave irradiation power, extraction time and added water, which were studied using a central composite design approach, and results were used to optimize the extraction process for recovering three valuable fractions: essential oil, polyphenols and phytocannabinoids. The products obtained using the optimized conditions were characterized in terms of yield, chemical profile and antioxidant potential. Moreover, the by-products obtained during the optimized run were further analyzed in terms of their biological activity using both enzymatic and non-enzymatic assays. The aqueous residue demonstrated a powerful α-glucosidase inhibition, a good activity in terms of superoxide radical scavenging activity, a modest efficacy in terms of inhibition of advanced glycation end products formation and no activity in terms of lipase inhibition. The residual deterpenated biomass did not possess significant biological activity. This work demonstrated valorization of industrial hemp essential oil and its by-products, obtained by a sustainable and eco-friendly extraction method, through an almost waste-free approach. Cannabinoids as well as other valuable bioactive compounds such as glycosidic flavones may be recovered from the residues of the essential oil extraction, representing interesting substances in the pharmaceutical, cosmetic and nutraceutical fields. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


In vitro and in vivo fitness costs associated with Mycobacterium tuberculosis RpoB mutation H526D.
There is controversy regarding the potential fitness costs of rifampicin (RIF) resistance-conferring mutations in the Mycobacterium tuberculosis (Mtb) rpoB gene. We characterized the pathogenicity of an Mtb RpoB H526D mutant. A mutant containing the RpoB H526D mutation was isolated from wild-type Mtb grown on RIF-containing plates and complemented for determination of in vitro and in vivo fitness costs. The RpoB H526D mutant showed reduced survival relative to control strains during progressive hypoxia and delayed growth following resuscitation from nutrient starvation (p < 0.05), which was associated with reduced expression of the resuscitation-promoting factor genes rpfB, rpfC and rpfE. Relative to the isogenic wild-type strain, the mutant showed significantly attenuated growth and long-term survival as well as reduced inflammation in mouse lungs. Conclusion & future perspective: Our data suggest that RpoB H526D mutation confers a fitness cost during growth-limiting conditions in vitro and in mouse lungs.


Simplified body-composition analysis using deuterium dilution and deuteron photodisintegration.
A number of approaches to estimating human body composition (water, lean mass, and fat) are available, and each approach has its own limitations. Deuterium dilution is a comparatively safe and valid procedure for assessing body composition; however, its use has been restricted by the relative complexity of measuring deuterium at low concentrations. A simplified scheme for quantifying low levels of deuterium in body fluid samples promises to expand the use of D2O in body composition studies. The deuterons are quantified by measuring the neutron emission induced by gamma-ray irradiation from 228Th(2.61 MeV). The in vitro aspects of the procedure exhibit coefficients of variation of under 1% throughout the range of assay and near 100% recovery of added D2O. In vivo comparison studies with a reference tritium dilution procedure indicate close agreement in a group of 38 subjects. The chief advantages of the procedure are a small oral dose of D2O and the use of either serum or urine samples. The physical condition of the sample does not affect the measurement so distillation is not required. Thus, small medical facilities can enjoy the advantages of low cost, minimum patient inconvenience, and technical simplicity by submitting subject samples to larger agencies for analysis.


Mental health service utilization among patients with severe mental disorders.
In light of healthcare reforms, the study aims to assess variables associated with mental healthcare service utilization in general and in both primary and specialized care by patients with severe mental disorders (SMD, mainly schizophrenia). The study is based on a sample of 140 patients with SMD from five regions in Quebec (Canada). Variables were organized in accordance with Andersen's conceptual model into four factors: predisposing, enabling, needs, and service utilization. Secondary analyses were also conducted comparing patients who were hospitalized or used emergency rooms (H.ER-Group) with patients who did not use such services (WH.ER-Group). Accessibility of services, continuity of care, and having a case manager appear to be core variables that enable service utilization. Compared with the WH.ER-Group, the H.ER-Group used twice as many services. The study highlights the importance of developing a gamut of coordinated services, easily accessible in local networks, including case managers, family physicians, and shared-care development.


Exploring biomarkers associated with severity of knee osteoarthritis in Southern China using widely targeted metabolomics.
Metabolomics is a tool to study the pathogenesis of diseases and their associated metabolites, but there are still insufficient metabolomic studies on severe knee osteoarthritis.To investigate the differences in serum metabolites between healthy populations and knee osteoarthritis (KOA) patients in Southern China using widely targeted metabolomics, and to explore biomarkers and their metabolic pathways that could be associated with the severity of KOA. There were 10 healthy individuals in the control group and 32 patients with KOA. According to the Kellgren-Lawrence (KL) grading system, KOA was further divided into mild (n = 13, KL grade 1 and 2) and severe (n = 19, KL grade 3 and 4). Serum samples from all participants were collected and analyzed metabolomics based on ultra-performance liquid chromatography/electrospray ionization/tandem mass spectrometry. We screened for differential metabolites between patients and controls, and between mild and severe KOA. We explored the metabolic pathways involved in differential metabolism using the Kyoto Encyclopedia of Genes and Genomes database. Sixty-one metabolites were differentially expressed in the sera of the patient group compared with the control group (45 upregulated and 16 downregulated). Analysis of the mild and severe KOA groups showed a total of 12 differential metabolites. Receiver operating characteristic curve analysis showed N-alpha-acetyl-L-asparagine was a good predictor of advanced osteoarthritis(OA).Differential metabolites are enriched in multiple pathways such as arachidonic acid metabolism. Widely targeted metabolomics found that upregulation of the amino acid metabolite N-α-acetyl-L-asparagine was significantly associated with severe KOA and could be a biomarker for predicting severity of KOA. Arachidonic acid metabolism may play an important role in patients with severe KOA.


Validation of Arabic versions of three sleep surveys.
Research on sleep health is lacking in developing countries, particularly among the Sudanese population. This contributes to a number of social and safety risks such as workplace injury, daytime sleepiness, automobile accidents, and more. The current study aims to validate three Arabic questionnaires related to sleep health, namely the Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Restless Legs Syndrome (RLS). A random sample of 83 Sudanese participants was surveyed for the purpose of testing the reliability and validity of the Arabic version of the ESS, ISI, and RLS. The present study used exploratory factor analysis (EFA) of item scores to examine a potential single-factor structure of the ESS, ISI, and RLS. Reliability and validity of the instruments were assessed by internal consistency and construct validity, respectively. The internal consistency within the ESS, ISI, and RLS subscales was high, with Cronbach's alpha of 0.84, 0.87, and 0.94, respectively. EFA results showed the RLS and ISI scales were dominated by a single-factor structure that explained at least 84.2% and 65.70% respectively of the total variance. The ESS required a two-factor solution that explained 64.5% of the total variance, so the single-factor structure does not appear to be a good measure of the Arabic version of the ESS. The Arabic versions of the ESS, ISI, and RLS are valid and reliable tools. The RLS and ISI seem to have better psychometric properties than the ESS.


[Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction].
Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.


Electrochemical sensors in the development of selective methods for antiepileptic drugs determination.
The measurement of antiepileptic drugs (AEDs) in different samples has received considerable attention due to the directly correlation between clinical effects and plasma concentration. Numerous methods have been extensively applied to the analysis of AEDs since many years ago providing reliable and accurate results. This paper provides an overview of electrochemical techniques used for the analysis of different AEDs. More than sixty papers from refereed analytical chemistry journals on the analysis of AEDs in pharmaceutical formulations and biological samples are included. The present review shows the development of novel measurement electrochemical based on the use of different types of electrodes including mercury electrodes, screen-printed electrodes (SPEs) and electrodes modified with metal films and nanoparticles. Electrochemical biosensors and immunosensors developed for the analysis of AEDs have been also reviewed.


Psychometric Properties of the Strengths and Difficulties Questionnaire and Mental Health Problems Among Children With Hearing Loss.
More knowledge is needed about the characteristics of mental health problems among deaf or hard of hearing (D/HH) children. This study investigates the factor structure of one of the most widely used screening tools, the Strengths and Difficulties Questionnaire (SDQ), and the prevalence of mental health problems among D/HH children. Our data were derived from two independent samples of D/HH children, one from 2007 of children (N = 334) in bilingual/bicultural educational programs and another from 2014 of children (N = 233) in mostly mainstream oral educational programs with cochlear implants. Teacher-SDQs were collected for the 2007 sample and parent-SDQs for the 2014 sample. The factor structure of the SDQ was examined from both Exploratory Factor Analytic (EFA) and Confirmatory Factor Analytic (CFA) perspectives and internal consistency was examined. Mean problem scores were presented. The five-factor structure of the SDQ was overall found for both the 2007 and the 2014 samples using EFA. However, problems with the Conduct scale and the reversed items loading onto the Prosocial scale were observed. The five-factor model was superior to a one- and a two-factor model from a CFA perspective in both samples. Better internal consistency was observed for the 2007 sample rated by teachers. Both samples showed higher mean scores on all SDQ problem subscales compared to a cohort of Danish children without hearing loss. The five-factor structure of the SDQ is recommended to be used among D/HH children.


Concomitant thyroid cancer in patients with primary hyperparathyroidism in an endemic goitre region.
Primary hyperparathyroidism (pHPT) is often accompanied by underlying thyroid pathology and 1 to 36% of these thyroid pathologies are malignant. How the identification of these lesions affects patient management is unclear. We present a single-center experience with the prevalence of concomitant thyroid cancer in patients who underwent parathyroidectomy for pHPT. This was a retrospective cohort study. Two hundred-two patients with primary hyperparathyroidism included study. Demographic data, clinical findings, and final histopathological diagnosis were recorded retrospectively. Preoperative cervical ultrasound examination revealed co-existent thyroid abnormalities in 117 (57.9%) patients. Mean age of these patients was 57.8 ± 12.2 years and 88% were female. Sixty-three (53.9%) of the patients with thyroid abnormalities, underwent preoperative fine needle aspiration biopsy (FNAB). Cytology result was malignant in one (1.6%) patient, benign in 47(85.7%) patients, indeterminate in six (9.5%) patients and Hurthle cell neoplasm in two (3.2%) patients. Ninety-four (80.3%) of the patients underwent simultaneous thyroid surgery. Final pathology of the thyroid specimen was malignant in 26 (12.9%) patients. Sixteen of the malignant patients had preoperative FNAB. Preoperative FNAB result of these patients was malignant in one patient, indeterminate in two patients and benign in 13 patients. By implementing a comprehensive approach to patients with pHPT who present with thyroid disease, concomitant pathology may be elucidated preoperatively. But, this approach will not facilitate the detection of otherwise unsuspected thyroid cancer in an endemic goitre region. Cancer, Parathyroid adenoma, Parathyroidectomy, Thyroid, Thyroidectomy.


Obesity and its related diseases in Taiwan.
Obesity is related to increased morbidity and mortality, and prevails worldwide. It has become an important health issue and requires urgent attention. In Taiwan, overweight and obesity are defined as body mass index > or = 24 and 27 kg m(-2), respectively. These cut-offs differ from Caucasian standards, as Asians have higher comorbidities and fat mass at lower BMI levels than Caucasians. The prevalence of obesity and overweight in Taiwan are 19.2% and 30.5% in men, 13.4% and 21.3% in women. This implies that a more profound increase in obesity prevalence is found in men than in women. A high-fat diet, sedentary lifestyle and betel nut chewing may increase substantially this obesity epidemic. Recently, type 2 diabetes mellitus has been found to be the most common type of diabetes, and obesity is significantly related to type 2 diabetes in children. In addition, obesity is associated with cardiovascular diseases risk factors and cannot be neglected in elderly. Therefore, a comprehensive prevention and management programme of obesity is urgently warranted for controlling the growing obesity trend and its related diseases in Taiwan.


Viral Metagenomic Profiling of Croatian Bat Population Reveals Sample and Habitat Dependent Diversity.
To date, the microbiome, as well as the virome of the Croatian populations of bats, was unknown. Here, we present the results of the first viral metagenomic analysis of guano, feces and saliva (oral swabs) of seven bat species (Myotis myotis, Miniopterus schreibersii, Rhinolophus ferrumequinum, Eptesicus serotinus, Myotis blythii, Myotis nattereri and Myotis emarginatus) conducted in Mediterranean and continental Croatia. Viral nucleic acids were extracted from sample pools, and analyzed using Illumina sequencing. The presence of 63 different viral families representing all seven Baltimore groups were confirmed, most commonly insect viruses likely reflecting the diet of insectivorous bats. Virome compositions of our samples were largely impacted by the sample type: invertebrate-infecting viruses were most frequently found in feces, bacterial viruses in guano, whereas vertebrate-infecting viruses were most common in swabs. Most vertebrate-infecting virus sequences were assigned to retroviruses, parvoviruses, iridoviruses, and poxviruses. We further report the complete genome sequence of a novel adeno-associated virus, densovirus and a near complete length genome sequence of a novel iflavirus. Additionally, one of the most interesting findings in this study was the difference in viromes between two contrasting habitats, the continental and Mediterranean Croatia.


Bacterial RTX toxins allow acute ATP release from human erythrocytes directly through the toxin pore.
ATP is as an extracellular signaling molecule able to amplify the cell lysis inflicted by certain bacterial toxins including the two RTX toxins α-hemolysin (HlyA) from Escherichia coli and leukotoxin A (LtxA) from Aggregatibacter actinomycetemcomitans. Inhibition of P2X receptors completely blocks the RTX toxin-induced hemolysis over a larger concentration range. It is, however, at present not known how the ATP that provides the amplification is released from the attacked cells. Here we show that both HlyA and LtxA trigger acute release of ATP from human erythrocytes that preceded and were not caused by cell lysis. This early ATP release did not occur via previously described ATP-release pathways in the erythrocyte. Both HlyA and LtxA were capable of triggering ATP release in the presence of the pannexin 1 blockers carbenoxolone and probenecid, and the HlyA-induced ATP release was found to be similar in erythrocytes from pannexin 1 wild type and knock-out mice. Moreover, the voltage-dependent anion channel antagonist TRO19622 had no effect on ATP release by either of the toxins. Finally, we showed that both HlyA and LtxA were able to release ATP from ATP-loaded lipid (1-palmitoyl-2-oleoyl-phosphatidylcholine) vesicles devoid of any erythrocyte channels or transporters. Again we were able to show that this happened in a non-lytic fashion, using calcein-containing vesicles as controls. These data show that both toxins incorporate into lipid vesicles and allow ATP to be released. We suggest that both toxins cause acute ATP release by letting ATP pass the toxin pores in both human erythrocytes and artificial membranes.


The most common method of suicide in Tehran 2000-2004: implications for prevention.
The likelihood of completing suicide depends to some extent on knowledge of effective means and also on the availability and/or acceptability of such methods. Since studying suicide methods may have an implication for prevention, the focus of this study was on the most favored method of suicide in Tehran, Iran. The study uses confirmed suicide data provided by the Beheshet Zahra Organization (BZO), which gathers all mortality data within Tehran and enters them into a computerized database, from which the relevant information for all the recorded suicide cases during the year 2000 to 2004 were obtained and analyzed. There were 703 cases of suicide (632 males and 71 females) in the BZO database, with a sex ratio of 8.9. The mean (standard deviation) of age at suicide for those who chose hanging and for those who have chosen other methods of suicide were 33.93 (14.2) and 34.60 (13.4) years, respectively. Hanging was the method favored by 572 (85.9%) of cases. Use of hanging was higher in females (61, 85.9%) than in males (511, 80.9%), and higher among the married (304, 53.6%) than among singles (268, 46.4%). The high proportion of persons using hanging as a method of suicide in Tehran may reflect the fact that this method is more acceptable and/or easily available and/or less likely to be misclassified as accidental or undetermined death. The prevention of such suicides is extremely difficult in the general population. Therefore, it is suggested that, to prevent suicide by hangings, the authorities should focus on the causal factors of suicide rather than on the acceptability and/or the availability of this method.


Variation and the response to variation as a basis for successful cooperation.
In applying game theory to problems in biology, differences between individuals are often ignored. In particular, when analysing the evolution of cooperation it is often implicitly assumed that ignoring variation will produce predictions that approximate the solution when differences are included. This need not be true. As we demonstrate, differences are not innocuous noise, but can fundamentally change the nature of a game. Even small amounts of variability can stabilize cooperation by, for example, maintaining the need to deal with cheaters. Differences promote the need to learn about others in an interaction, leading to contingent behaviour that can reduce conflict, and to negotiated outcomes that may or may not be more cooperative than unconditional actions. Once there are mechanisms such as mutation and environmental influences that maintain variation within populations, whether cooperation evolves may depend on the variation in the cooperativeness trait. Variation means that it may be worth taking a chance that a partner is cooperative by being cooperative. When there are markets, so that individuals can break off interactions to seek a better partner, variation promotes choosiness and hence penalizes those uncooperative individuals, who are rejected. Variation promotes the need to monitor the previous behaviour of others, and once this social sensitivity exists, the need to maintain a good reputation can promote cooperation.


The Effectiveness of Cervical Strengthening in Decreasing Neck-Injury Risk in Wrestling.
Clinical Scenario: In wrestling, athletes often support a large amount of weight on their heads or are forced into extreme ranges of motion. These suboptimal movement conditions lead to a high prevalence of neck injuries in wrestlers. A large portion of the work done by the cervical musculature in wrestling is theorized to be eccentric or isometric types of contractions. Strengthening of these cervical muscles is clinically considered to play a vital role in being competitive on the wrestling mat. The cervical stability provided by strengthening these muscles may also play a part in injury prevention among wrestlers. Focused Clinical Question: Does increased cervical strength lead to a decreased risk of injury in wrestling? Summary of Search, "Best Evidence" Appraised, and Key Findings: The literature was searched for studies of level 4 evidence or higher using the Oxford Centre for Evidence-Based Medicine level of evidence system that investigated the relationship between cervical strength and injury risk in wrestling. No studies were found comparing cervical strength to injury risk in wrestling, but 2 related studies were found and have been included in this critically appraised topic. Clinical Bottom Line: There is poor evidence to support a relationship between cervical strength and injury risk in wrestling. Strength of Recommendation: There is grade C evidence to indicate that increased cervical strength decreases the risk of injury in wrestling.


Biomarker detection for disease diagnosis using cost-effective microfluidic platforms.
Early and timely detection of disease biomarkers can prevent the spread of infectious diseases, and drastically decrease the death rate of people suffering from different diseases such as cancer and infectious diseases. Because conventional diagnostic methods have limited application in low-resource settings due to the use of bulky and expensive instrumentation, simple and low-cost point-of-care diagnostic devices for timely and early biomarker diagnosis is the need of the hour, especially in rural areas and developing nations. The microfluidics technology possesses remarkable features for simple, low-cost, and rapid disease diagnosis. There have been significant advances in the development of microfluidic platforms for biomarker detection of diseases. This article reviews recent advances in biomarker detection using cost-effective microfluidic devices for disease diagnosis, with the emphasis on infectious disease and cancer diagnosis in low-resource settings. This review first introduces different microfluidic platforms (e.g. polymer and paper-based microfluidics) used for disease diagnosis, with a brief description of their common fabrication techniques. Then, it highlights various detection strategies for disease biomarker detection using microfluidic platforms, including colorimetric, fluorescence, chemiluminescence, electrochemiluminescence (ECL), and electrochemical detection. Finally, it discusses the current limitations of microfluidic devices for disease biomarker detection and future prospects.


Detection of apoptosis and necrosis in normal human lung cells using 1H NMR spectroscopy.
This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P < 0.01). In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.


Isolated tuberosity fractures of the proximal humeral: current concepts.
Despite the relatively common occurrence of fractures of the proximal humeral amongst the elderly, the subgroup of isolated greater and lesser tuberosity fractures have remained less well understood. While the majority of two-part fractures result from a standing-height fall onto an outstretched hand, isolated tuberosity fractures are also commonly associated with glenohumeral dislocations or direct impact to the shoulder region. Inasmuch as isolated greater tuberosity fractures are considered uncommon, isolated lesser tuberosity fractures are generally considered exceedingly rare. Non-operative treatment including a specific rehabilitation protocol has been advocated for the majority of non-displaced and minimally displaced fractures, with generally good outcomes expected. The treatment for displaced fractures, however, has included both arthroscopically assisted fixation and open or percutaneous reduction and internal fixation (ORIF). The choice of fixation and approach depends not only on fracture type and characteristics, but also on a multitude of patient-related factors. With an expected increase in the level of physical activity across all age groups and overall longer lifespans, the incidence of isolated tuberosity fractures of the proximal humeral is expected to rise. Orthopaedic surgeons treating shoulder trauma should be aware of treatment options, as well as expected outcomes.


Individuals with psychosis present a reduced lung diffusion capacity and early spirometry alterations: Results from a cross-sectional study.
Individuals with psychosis present a greater prevalence of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). These chronic respiratory diseases are preceded by early lung function alterations; such as preserved ratio impaired spirometry (PRISm) or normal spirometry but low diffusion capacity of the lung for carbon monoxide (DLCO). However, there is no previous evidence on these lung function alterations in psychosis. The aim of this study is to evaluate the risk of having spirometry and DLCO alterations in subjects with psychosis compared with a control group. Cross-sectional study on a cohort of 170 individuals including 96 subjects with psychosis and 74 sex-age-and smoking habit matched healthy controls. All subjects were under 60 years-old, and without COPD or asthma. Respiratory function was evaluated through spirometry. Clinical characteristics and DLCO values were recorded. Patients with psychosis showed lower spirometry results, both in terms of absolute and percentage of Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1). Absolute and percentage levels of diffusion were also lower in patients with psychosis. The percentage of individuals with DLCO<80% was higher among patients with psychosis (75% vs. 40%, p < 0.001). And the prevalence of PRISm was higher among patients with psychosis (10.4% vs. 1.4%, p < 0.001). Multivariate logistic regression analysis indicated that psychosis was an independent predictor of DLCO<80% (OR 5.67, CI95% 1.86-17.27). Patients with psychosis and females had early alterations in lung function. These results suggest that early screening for lung disease should be encouraged in psychosis.


[Liver transplant and hepatocellular carcinoma in Peru: outcome after 15 years in the transplant department of the Guillermo Almenara Hospital - EsSalud].
Hepatocellular carcinoma (HCC) is a neoplasm with significant incidence and prevalence in the world. In large percentage it originates from a cirrhotic liver. Liver transplantation under special conditions is effective in the simultaneous treatment of both conditions. Information is scarce in Latin America. This is a cross-sectional study of the first 200 liver transplants of our series (Years 2000-2015). During this period, 26 (13%) patients had a diagnosis of HCC. Of the 26 transplanted with HCC, 21 (81%) patients were male. The average age was 59.7 years. The most frequent cirrhotic etiology was NASH with nine (35%) cases, followed by HCV and OH with six (23%). The average of AFP pre-transplant was 113.3. Downstaging was performed in four patients. The overall survival obtained is 90.9% over 5 years. The recurrence-free survival in our series is 95.5% at 5 years.


Zinc deposition in Acid lakes: the role of diffusion.
Steep negative concentration gradients of dissolved zinc are present between the overlying waters and the anoxic pore waters of two acid lakes. In the anoxic pore waters, the low zinc concentrations can be explained as due to the formation of relatively insoluble zinc sulfide minerals. Downward diffusive fluxes of dissolved zinc account for at least 50 to 75 percent of the recent zinc deposition to the sediments of these lakes. This downward diffusion occurs to a depth of 2 to 3 centimeters below the sediment water interface, where pronounced maxima in total zinc are observed. These subsurface peaks in total zinc have been interpreted as an indication of recent lake acidification. The present observations indicate that such subsurface peaks may also result from a diagenetic activity unrelated to recent changes in lake acidity.


A Contemporary Clinicopathologic Analysis of Patients With Renal Cell Carcinoma and Vena Cava Involvement.
Renal cell carcinoma (RCC) is occasionally associated with vena cava involvement. Despite recent advances in therapeutic modalities, the 5-year survival in this population continues to be poor. Therefore, further studies are required to better characterize this patient population, especially from the clinicopathologic standpoint. A comprehensive review of patients with RCC and vena cava involvement managed at our institution from 2014 to 2022 was performed. Multiple clinicopathologic parameters including follow-up were obtained. A total of 114 patients were identified. The mean patient age was 63 years (range: 30-84 years). The cohort consisted of 78/114 (68%) males and 36/114 (32%) females. The mean primary tumor size (excluding tumor thrombus) was 11 cm. The majority of tumors (104/114, 91%) were unifocal. Tumor stages were categorized as follows: pT3b (51/114, 44%), pT3c (52/114, 46%), and pT4 (11/114, 10%). Most of the tumors were clear cell RCC 89/114 (78%), although other more aggressive RCC subtypes were also present. Most tumors were WHO/ISUP grade 3 (44/114, 39%) or 4 (67/114, 59%) with sarcomatoid differentiation present in 39/67 (58%). Necrosis was present in 94/114 (82%) tumors. Twenty-three of 114 (20%) tumors were categorized as pM1 and the ipsilateral adrenal gland was the most common site of metastasis. Of the 91 patients categorized as pM, not applicable at nephrectomy, 42/91 (46%) subsequently developed metastasis, most frequently to the lung. Of all patients, only 16/114 (14%) had positive vascular margins and 7/114 (6%) had positive soft tissue margins despite having very advanced disease and a subset considered inoperable at other centers.


Rare neonatal interstitial lung disease masquerading as pulmonary hemosiderosis.
A preterm 32-week neonate presented on the 14th day of life with respiratory distress and cyanosis. The respiratory distress worsened progressively, which was managed with continuous positive airway pressure support. The neonate had blood-tinged oral secretions on the 39th day of life, for which bronchoscopy was performed, whose findings were suggestive of pulmonary hemosiderosis. Lung biopsy confirmed the diagnosis of pulmonary interstitial glycogenosis with pulmonary arterial hypertension. The neonate was treated successfully with systemic corticosteroids and discharged home at 3 months of age.


In situ diets of the bloom-forming dinoflagellate Noctiluca scintillans in Daya Bay.
Red Noctiluca scintillans is a common heterotrophic dinoflagellate that forms blooms in temperate, subtropical, and tropical coastal ecosystems. The diet of this species plays an important role in its cell growth, development, and reproduction. Because limited gene diversity data are available regarding prey of this species, its diet in Daya Bay during a boreal winter bloom is reported using an integrated approach involving light microscopy, single cell isolation and plastid 16S rDNA cloning, and 18S rDNA V4 and V9 region amplification using isolated cells and environmental DNA as templates with high-throughput sequencing. While conventional light microscopy reveals the diet of this species to comprise Coscinodiscus sp. and Stephanopyxis turris (diatoms), copepod eggs, and detritus, plastid gene diversity identifies a diet comprising diatoms, cyanobacteria, and bacteria, and 18S rDNA high-throughput sequencing reveals a diet comprising 36 eukaryote families (primarily copepods, as well as diatoms, dinoflagellates, Ochrophyta, Haptophytes, Chordata, Cercozoans, Chlorophyta, Polychaeta, and ciliates). Dietary staples include copepods, diatoms, dinoflagellates, Ochrophyta, and Synechococcus. High copepod abundance in prey may reflect their relatively high abundance in environmental seawater. Thus, N. scintillans is generally omnivorous but prefers dominant phytoplankton taxa, including Rhizosoleniaceae, Leptocylindraceae, and Cymatosiraceae (diatoms), as well as Gonyaulacaceae (dinoflagellates). An integrated multi-disciplinary approach provides a more comprehensive picture of N. scintillans diet in Daya Bay, and an improved understanding of this species' ecological niche and trophic role in marine ecosystems.


Germline Genetic Risk Variants for Progressive Multifocal Leukoencephalopathy.
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the brain caused by reactivation of the JC virus (JCV), a polyomavirus that infects at least 60% of the population but is asymptomatic or results in benign symptoms in most people. PML occurs as a secondary disease in a variety of disorders or as a serious adverse event from immunosuppressant agents, but is mainly found in three groups: HIV-infected patients, patients with hematological malignancies, or multiple sclerosis (MS) patients on the immunosuppressant therapy natalizumab. It is severely debilitating and is deadly in ~50% HIV cases, ~90% of hematological malignancy cases, and ~24% of MS-natalizumab cases. A PML risk prediction test would have clinical utility in all at risk patient groups but would be particularly beneficial in patients considering therapy with immunosuppressant agents known to cause PML, such as natalizumab, rituximab, and others. While a JC antibody test is currently used in the clinical decision process for natalizumab, it is suboptimal because of its low specificity and requirement to periodically retest patients for seroconversion or to assess if a patient's JCV index has increased. Whereas a high specificity genetic risk prediction test comprising host genetic risk variants (i.e., germline variants occurring at higher frequency in PML patients compared to the general population) could be administered one time to provide clinicians with additional risk prediction information that is independent of JCV serostatus. Prior PML case reports support the hypothesis that PML risk is greater in patients with a genetically caused immunodeficiency disorder. To identify germline PML risk variants, we performed exome sequencing on 185 PML cases (70 in a discovery cohort and 115 in a replication cohort) and used the gnomAD variant database for interpretation. Our study yielded 19 rare variants (maximum allele frequency of 0.02 in gnomAD ethnically matched populations) that impact 17 immune function genes (10 are known to cause inborn errors of immunity). Modeling of these variants in a PML genetic risk test for MS patients considering natalizumab treatment indicates that at least a quarter of PML cases may be preventable.


Improved total parenteral nutrition therapy management by a nutritional support team.
This study was performed to identify and document the benefits associated with a multidisciplinary consult-based nutritional support team. The adequacy of nutritional support and incidence of metabolic complications were prospectively studied in 28 adult patients receiving total parenteral nutrition in a large private tertiary care institution during a 2-week period. Estimated daily caloric and protein requirements were met significantly more often in patients followed by our NST than in control group patients. Chloride and bilirubin abnormalities occurred significantly less often in the NST group than in the control group. The incidence of blood urea nitrogen, creatinine, and glucose abnormalities were also decreased in the NST patients, but these differences were not statistically significant. Patients followed by the NST were more likely to receive adequate nutrition and experience fewer metabolic abnormalities than when TPN therapy was guided solely by a physician.


[Sudden hearing loss and HIV infection].
A case is reported of left sudden hearing loss in a 29-year-old male with HIV infection and a history right sudden hearing loss 2 years earlier. The low frequency of sudden hearing loss in HIV+ patients is discussed. Neurosyphilis and cryptococcus infection were ruled out. The patient recovered his hearing in the left ear after three days of treatment with intravenous piracetam, 10 g/day.


Do speakers avoid ambiguities during dialogue?
What affects speakers' production of ambiguous utterances in dialogue? They might consider ease of production for themselves, or ease of comprehension for their addressees. Previous research has demonstrated that ease of production plays a role in speakers' syntactic choices, but that ease of comprehension does not. However, such studies have not employed dialogues that involve role swapping on a turn-by-turn basis. In our experiment, participants alternated in giving and following instructions to move objects around on a grid. They tended to repeat the syntactic form just used by their interlocutor, reflecting sensitivity to ease of production. More interestingly, they were more likely to disambiguate their utterances when the visual context was potentially ambiguous than when it was not, reflecting sensitivity to ease of comprehension. We conclude that speakers pay attention to their beliefs about their addressees' ease of comprehension, in addition to considering ease of production for themselves.


Dual Ratio and Ultraprecision Quantification of Mitochondrial Viscosity in Ferroptosis Enabled by a Vibration-Based Triple-Emission Fluorescent Probe.
Ferroptosis is a new mode of cell death with major morphological changes in mitochondria, including structural shrinkage and increased membrane density, indicating the mitochondrial abnormality during this process. Viscosity, as one of the crucial microenvironmental parameters for characterizing the mitochondrial state, is thought to be highly involved in the ferroptosis. Herein, we present a single fluorescent probe (PPAC-C4) for the dual ratio and ultrahigh-accuracy quantification of mitochondrial viscosity. This probe is constructed by linking a mitochondria-targeting cation fragment on a vibration-based fluorescent scaffold whose fluorescence exhibits the rare triple emission (480, 533, and 628 nm) depending on the viscosity. The intensity ratios of 480 nm/628 nm and 533 nm/628 nm can be used to monitor the viscosity changes in a double self-calibration manner and finally afford an average viscosity value with improved precision. By virtue of this pattern, we reveal that the mitochondrial viscosity will increase from 43.58 to 152.05 cP in A549 cells during the ferroptosis. This dual-ratio probe with triemission not only shows great potential in the study of ferroptosis and ferroptosis-related diseases but also proposes a new concept for ultraprecision quantitative analysis.


Ultra-fast synthesis of water soluble MoO3-x quantum dots with controlled oxygen vacancies and their near infrared fluorescence sensing to detect H2O2.
We report a facile method for the synthesis of water soluble MoO3-x quantum dots (QDs) at room temperature by injecting hydrochloric acid and mercaptosuccinic acid into ammonium molybdate solution within 5 seconds. The optical properties and oxygen vacancy concentration of the QDs could be well controlled by the competitive absorption of a carboxyl group and sulfhydryl group of the ligand with QDs by coordination interaction. The obtained QDs could be used as near infrared region (NIR) fluorescence probes to detect hydrogen peroxide with a low detection limit (3 nM).


Inhibition of furin-like enzymes blocks interleukin-1alpha/oncostatin M-stimulated cartilage degradation.
To investigate the role of furin-like enzymes in the proteolytic cascades leading to cartilage breakdown and to examine which collagenase(s) contribute to collagen degradation. Bovine nasal cartilage was stimulated to resorb with the addition of interleukin-1alpha (IL-1alpha)/oncostatin M (OSM) in the presence or absence of a furin inhibitor, Dec-RVKR-CH(2)Cl, or selective matrix metalloproteinase 1 (MMP-1) inhibitors. Collagen and proteoglycan levels were determined by assay of hydroxyproline and sulfated glycosaminoglycan, respectively. Collagenase and gelatinase activity were measured using (3)H-acetylated collagen and gelatin zymography, respectively. The addition of Dec-RVKR-CH(2)Cl to stimulated cartilage reduced the release of collagen fragments and the levels of active collagenase and MMP-2, suggesting that furin-like enzymes are involved in the cascades leading to activation of procollagenases. At MMP inhibitor concentrations that selectively inhibit MMP-1, no inhibition of collagen release was observed, but increasing the concentration to the 50% inhibition concentration for MMP-13 resulted in a 50% blockage of collagen release. The addition of Dec-RVKR-CH(2)Cl to resorbing cartilage also partially blocked proteoglycan release, thus demonstrating a role for furin-activated enzymes in the pathways leading to proteoglycan degradation. Furin-like enzymes are involved in cascades leading to activation of procollagenases and degradation of collagen. MMP-13, which can be activated by furin-processed membrane-type 1 MMP-1, appears to be a major collagenase involved in collagen degradation induced by IL-1alpha/OSM. Furin-like enzymes also appear to play a role in the pathways leading to proteoglycan degradation. These findings are of importance when considering proteinase inhibition as a target for therapeutic intervention in arthritic diseases.


Creating consistency in the diagnosis of convergence insufficiency: screening methods.
To determine the sensitivity of various clinical tests in the diagnosis of convergence insufficiency. A total of 254 patients were recruited with complaints consistent with convergence problems but no prior history of strabismus surgery, eye exercises, prism use, recent concussion, or other ocular or neurological diseases. Each patient completed the convergence insufficiency symptom survey (CISS), and the following data were collected: ocular alignment at distance and near, convergence and divergence fusional amplitudes at distance and near, near-point of convergence (NPC) using an accommodative target and red lens, and assessment of quality of convergence movement (QoCM) and quality of fusional movements (QoFM). The sensitivity of each clinical test was calculated. Measurement of NPC using red lens and subjective assessment of the QoCM and QoFM were the most sensitive diagnostic tools for near symptoms consistent with convergence insufficiency: 93.3%, 98.4%, and 94.5% respectively. CISS score, convergence fusional amplitude at near, and exophoria at near had lower sensitivities: 62.9%, 46.0%, and 72.0%, respectively. Although the majority of our patients had a heterophoria or heterotropia at distance (96.8%) and/or near (98.8%), most presented with only small phorias. Furthermore, of those who had a deviation at near, only 22% had the near exophoria exceeding the distance exophoria by 10Δ. In our study cohort, NPC with red lens and subjective assessment of QoCM and QoFM proved to be the most sensitive screening tools for near symptoms consistent with convergence insufficiency.


Potential analytical interferences and seasonal variability in diethyltoluamide environmental monitoring programs.
N,N-diethyl-m-toluamide (DEET), the active component of many insect repellents, is among the most frequently detected compounds in aqueous environments with concentrations reported in the ng L(-1) to μg L(-1) range. However, DEET is often detected in blanks and reported concentrations differ significantly depending on the analytical technique employed. In addition, relatively sparse data are available regarding the seasonal variability of DEET concentrations in water and there are apparent inconsistencies with expected use patterns. Therefore, the present study investigates potential interferences affecting the detection and quantification of DEET then the geographical and seasonal variations of DEET concentrations. To examine potential analytical interferences, DEET was analyzed in five geographically-diverse wastewater effluents using both gas chromatography and liquid chromatography coupled to mass spectrometric detectors. At times, the concentrations quantified by the employed analytical methods varied significantly. Five compounds with similar molecular weights and structures as DEET were investigated as potential mimics and some were shown to induce an overestimation of DEET. Further experimentation suggested that the solvents used in sample preparation and HPLC analysis are another possible source of interference. Besides potential interferences, the seven-month weekly monitoring of DEET in the primary effluent of a wastewater treatment plant demonstrated a clear seasonal trend with decreasing concentration from summer to winter. These data collectively demonstrate that there are many challenges in the quantification of DEET in complex environmental samples and that co-occurrence of similarly structured substances present in the water sample and/or the solvents used for the analysis could induce analytical bias.


Under what circumstances does the capture and tagging of wild Atlantic salmon Salmo salar smolts affect probability of return as adults?
Adult return rates for wild Atlantic salmon Salmo salar smolts captured in a rotary screw trap and tagged with coded wire (CW) tags were compared with a control group, using detections from passive integrated transponder (PIT) antennae systems over 7 years in a small chalk stream in southern England, U.K. Compared with control smolts, capture and CW-tagging of experimental smolts affected detected return rates only under certain conditions, with a decreased return probability for smolts caught and tagged following mild winter river temperature anomalies and during the night. Similarly, analysis of the experimental smolts revealed that capture and CW-tagging following mild winters decreased their probability of return as adults. There were also marginal positive effects of length at PIT-tagging as parr and length at CW-tagging as smolts, on individual probability of return as adult. The results support the hypothesis that the effect of procedures involving the capture and tagging of migrating wild S. salar smolts will vary with the circumstances under which they are performed. The implications of the findings are considered in the context of ongoing investigations to derive and report marine return rates for S. salar in support of national and international stock assessments and in developing best practice.


Satiating effect of bombesin is mediated by receptors perfused by celiac artery.
The abdominal site or sites for the satiety action of exogenous, peripherally administered bombesin (BN) were investigated. By use of a chronic arterial catheterization technique, the effects of 1, 2, and 4 micrograms/kg BN on liquid food intake of nondeprived male rats were assessed. Comparisons were made between the effects of these doses infused into the celiac or superior mesenteric arteries or injected intraperitoneally. The satiating potency of exogenous BN was significantly enhanced by direct administration into the celiac artery, which directly perfuses the stomach, pancreas, liver, spleen, and proximal duodenum. By this route, 4 micrograms/kg BN produced greater than 60% suppression of 15-min food intake. By contrast, BN infused into the superior mesenteric artery was no more effective than intraperitoneal injection. Celiac infusion of 1 micrograms/kg BN produced a suppression (30%) of intake that was equivalent to, or exceeded, that obtained after intraperitoneal injection or superior mesenteric infusion of 4 micrograms/kg. These results strongly support an upper abdominal, and possibly gastric, site for the satiety action of peripherally administered BN.


Current status of and perspectives regarding neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.
The significance of neoadjuvant chemoradiotherapy (NACRT) for esophageal squamous cell carcinoma (ESCC) remains controversial with regard to the pathological response and long-term survival. We herein review the current status of and future perspectives regarding NACRT followed by esophagectomy for locally advanced ESCC. Some studies have suggested that a pathological complete response with NACRT is more common in patients with ESCC than in those with adenocarcinoma and that NACRT provided a survival benefit limited to patients with ESCC. However, NACRT may increase the risk of postoperative complications after esophagectomy. It is obvious that a favorable pathological response is the most important factor for obtaining a survival benefit, although no established parameters have been implemented clinically to predict the response to NACRT. Prospective clinical studies and basic research studies to identify predictive biomarkers for the response to NACRT are needed to aid in the development of NACRT treatment strategies for patients with ESCC.


A review of postpartum depression, preterm birth, and culture.
Postpartum depression (PPD) varies worldwide and is considered a serious issue because of its devastating effects on mothers, families, and infants or children. Preterm birth may be a risk factor for PPD. In 2005, the global incidence of preterm birth was estimated to be 9.6%, and of these births, 85% occurred in Africa and Asia. Among Asian countries, Pakistan has a preterm birth rate of 15.7% and the highest prevalence rate of PPD (63.3%). A literature review was therefore undertaken to better understand the potential contribution of preterm birth to PPD and to identify gaps in the scientific literature. Limited studies compare prevalence rates of PPD in mothers of full-term infants and mothers of preterm infants. Furthermore, meta-analyses examining predictors of PPD have not included preterm birth as a variable. The interrelationship between preterm birth and PPD may be explained by early parental stress and mother-infant interaction among mothers of preterm infants. Culture plays an important role in shaping communication between mothers and their infants and defines social support rituals that may or may not mediate PPD. More research is needed to provide evidence for practice.


Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. II. Directional selectivity and force-response relations.
1. The directional selectivity of peripheral otolith neurons was studied in the barbiturate-anesthetized squirrel monkey (Saimiri sciureus). Each unit's most sensitive axis was characterized by a functional polarization vector. The direction of a centrifugal force was varied with respect to the vector and to the macular plane. The neurons respond in an excitatory manner to shearing forces orthogonally disposed to the vector. The sensitivity to orthogonal shears was usually 10-15% of the sensitivity to parallel shearing forces. There was no significant response to orthogonal compressions, nor did compressions modify the response to shearing forces. 2. Force-response functions were obtained in the stimulus range of +/- 4.92 g. Forces were directed parallel to each unit's polarization vector. The functions are sigmoid shaped and possess both inhibitory and excitatory plateaus. The presumed physiological range of +/-1 g is represented in the lower (concave upward) portion of the function and has a dynamic range, expressed in terms of response magnitude, amounting to 20-40% of the potential dynamic range of the neuron. 3. There was considerable variation among units in their +/- 4.92 g force-response curves. The salient features of the functions are described by three factors, tentatively identified as a transduction gain, a receptor bias, and a mechanical gain. Both the resting discharge (do) and the +/-1 g sensitivity (so) vary in the same direction with changes in the factors related to transduction gain and receptor bias. It is shown that this covariation provides a quantitatively precise explanation for the positive relation between do and so.


The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity.
miR-124, a brain-specific microRNA, was originally considered as a key regulator in neuronal differentiation and the development of the nervous system. Here we showed that miR-124 expression was suppressed in patients with epilepsy and rats after drug induced-seizures. Intrahippocampal administration of a miR-124 duplex led to alleviated seizure severity and prolonged onset latency in two rat models (pentylenetetrazole- and pilocarpine-induced seizures), while miR-124 inhibitor led to shortened onset latency in pilocarpine-induced seizure rat models. Moreover, the result of local field potentials (LFPs) records further demonstrated miR-124 may have anti-epilepsy function. Inhibition of neuronal firing by miR-124 was associated with the suppression of mEPSC, AMPAR- and NMDAR-mediated currents, which were accompanied by decreased surface expression of NMDAR. In addition, miR-124 injection resulted in decreased activity and expression of cAMP-response element-binding protein1 (CREB1). a key regulator in epileptogenesis. A dual-luciferase reporter assay was used to confirm that miR-124 targeted directly the 3'UTR of CREB1 gene and repressed the CREB1 expression in HEK293T cells. Immunoprecipitation studies confirmed that the CREB1 antibody effectively precipitated CREB1 and NMDAR1 but not GLUR1 from rat brain hippocampus. These results revealed a previously unknown function of miR-124 in neuronal excitability and provided a new insight into molecular mechanisms underlying epilepsy.


[Complex treatment of patients with complicated forms of erysipelas].
The authors made an analysis of variants of treatment strategy and its results in patients with different forms of erysipelas. The use of complex conservative and operative treatment allowed lethality to be reduced from 4 to 1.9%, in patients with severe course of the disease the frequency of complications being reduced to 10%.