[Migration and rehabilitation of mental diseases -- perspectives and limitations in the reporting of official data of service providers].
Health and social monitoring are important foundations of political decision making. In order to make statements about populations and subgroups different sources of information are generally used. The potential contribution which aggregated official health data of service providers can make is discussed in the exemplary context of the utilisation of medical rehabilitation of mental diseases. Age specific rates and age standardised ratios show a significantly increased utilisation of services for depression and somatoform disorders amongst women in general and the migrant population in particular. It is demonstrated that the interpretation of such results raises new research questions rather than providing explanations that could prove to be conducive for practical measures. In a methodological discussion it is stated that the reason for this has to be seen in the fact that important structures of action within the care system are concealed by the specific method of collecting and processing official health data. Nevertheless, conceivable interpretations are given regarding the psycho-social living conditions of large parts of the migrant population as well as their difficulties in the interaction with the medical system. This enables the formulation of a hypothetical framework for further research which could help to clarify statistical phenomena found in the official data of service providers.


Agreement and Accuracy of Medication Persistence Identified by Patient Self-report vs Pharmacy Fill: A Secondary Analysis of the Cluster Randomized ARTEMIS Trial.
Pharmacy fill data are increasingly accessible to clinicians and researchers to evaluate longitudinal medication persistence beyond patient self-report. To assess the agreement and accuracy of patient-reported and pharmacy fill-based medication persistence. This post hoc analysis of the cluster randomized clinical trial ARTEMIS (Affordability and Real-world Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) enrolled patients at 287 US hospitals (131 randomized to intervention and 156 to usual care) from June 5, 2015, to September 30, 2016, with 1-year follow-up and blinded adjudication of major adverse cardiovascular events. In total, 8373 patients with myocardial infarction and measurement of P2Y12 inhibitor persistence by both patient self-report and pharmacy data were included. Serum P2Y12 inhibitor drug levels were measured for 944 randomly selected patients. Data were analyzed from May 2018 to November 2019. Patients treated at intervention-arm hospitals received study vouchers to offset copayments at each P2Y12 inhibitor fill for 1 year after myocardial infarction. Nonpersistence was defined as a gap of 30 days or more in P2Y12 inhibitor use (patient report) or supply (pharmacy fill) and as serum P2Y12 inhibitor levels below the lower limit of quantification (drug level). Among patients in the intervention arm, a "criterion standard" definition of nonpersistence was a gap of 30 days or more in P2Y12 inhibitor use by both voucher use and pharmacy fill. Major adverse cardiovascular events were defined as adjudicated death, recurrent myocardial infarction, or stroke. Of 8373 patients included in this analysis, the median age was 62 years (interquartile range, 54-70 years), 5664 were men (67.7%), and 990 (11.8%) self-reported as nonwhite race/ethnicity. One-year estimates of medication nonpersistence rates were higher using pharmacy fills (4042 patients [48.3%]) compared with patient self-report (1277 patients [15.3%]). Overall, 4185 patients (50.0%) were persistent by both pharmacy fill data and patient report, 1131 patients (13.5%) were nonpersistent by both, and 3057 patients (36.5%) were discordant. By application of the criterion standard definition, the 1-year nonpersistence rate was 1184 of 3703 patients (32.0%); 892 of 3318 patients (26.9%) in the intervention arm who self-reported persistence were found to be nonpersistent, and 303 of 1487 patients (20.4%) classified as nonpersistent by pharmacy fill data were actually persistent. Agreement between serum P2Y12 inhibitor drug levels and either patient-reported (κ = 0.11-0.23) or fill-based (κ = 0.00-0.19) persistence was poor. Patients who were nonpersistent by both pharmacy fill data and self-report had the highest 1-year major adverse cardiac event rate (18.3%; 95% CI, 16.0%-20.6%) compared with that for discordant patients (9.7%; 8.7%-10.8%) or concordantly persistent patients (8.2%; 95% CI, 7.4%-9.0%). Patient report overestimated medication persistence rates, and pharmacy fill data underestimated medication persistence rates. Patients who are nonpersistent by both methods have the worst clinical outcomes and should be prioritized for interventions that improve medication-taking behavior. ClinicalTrials.gov Identifier: NCT02406677.


Methodologies for studying peripheral O₂ chemosensing: past, present, and future.
The reduction of molecular oxygen in individual cells during the process of oxidative phosphorylation is central to oxidative metabolism and bioenergetic homeostasis. As such, any insufficiency in molecular oxygen availability represents a severe threat to sustained life. Thus, as with other similar multicellular organisms, the human body has evolved various peripheral chemosensory pathways that play a key role in sampling arterial PO₂ values and initiating corrective reflex responses so as to maintain homeostasis. Research on these peripheral chemosensors can trace their origins to the cross circulation studies of Corneille Heymans in the early 20th century. Since then, it has become increasingly apparent that defects in these chemosensory pathways play a key role in various pathological conditions, e.g. Sudden Infant Death Syndrome (SIDS), and therefore an understanding of the underlying mechanisms is of critical importance. This review aims to discuss the advantages and disadvantages of the various experimental models employed in studying the mechanisms by which acute peripheral chemosensing occurs.


Pesticide mediated silent neurotoxicity and its unmasking: An update on recent progress.
Being human's one of the most protected organs, brain is yet most vulnerable to xenobiotics exposure. Though pesticide-mediated neurotoxicity is well-explored, the fraternity of neurotoxicologists is less focused on the phenomenon of "silent" or "clinically undetectable" neurotoxicity. Silent neurotoxicity defines continual trivial changes in the nervous system that do not manifest any overt signs of toxicity unless unmasked by any natural or experimental event. Although this perception is not novel, insufficient experimental and epidemiological evidence makes it an outlier among toxicological research. A report in 2016 highlighted the need to investigate silent neurotoxicity and its potential challenges. The limited existing experimental data unveiled the unique responsiveness of neurons following silent neurotoxicity unmasking. Concerned studies have shown that low-dose developmental exposure to pesticides sensitizes the nigrostriatal dopaminergic system towards silent neurotoxicity, making it vulnerable to advanced cumulative neurotoxicity following pesticide challenges later in life. Therefore, conducting such studies may explain the precise etiology of pesticide-induced neurological disorders in humans. With no updates on this topic since 2016, this review is an attempt to acquaint the neurotoxicologist with silent neurotoxicity as a serious threat to human health, and proof-of-concept through a narrative using relevant published data so far with future perspectives.


Biased VH gene usage in early lineage human B cells: evidence for preferential Ig gene rearrangement in the absence of selection.
Certain VH genes are predominantly expressed in mature B cells. We hypothesized that several, mutually nonexclusive VH-dependent mechanisms operating at distinct stages during B cell development may be responsible for overrepresentation of these VH genes. In the present study, we have assessed whether one of the mechanisms involves preferential rearrangement at the pro-B cell stage. The frequency of individual VH4 and VH3 genes in rearrangement libraries from FACS-purified human CD34+/CD19+ pro-B and CD34-/CD19+ pre-B cells was assessed. The in-frame and out-of-frame rearrangements from both cell populations were analyzed using a high resolution PAGE system. The frequencies of individual VH gene segments among out-of-frame rearrangements from pro-B cells were determined, because these frequencies should reflect only processes before the translation of the mu-heavy chain and should not be biased by selection mechanisms. Our results demonstrate that, at the pro-B cell stage, the V4-34, V4-39, and V4-59 gene segments are the most frequently rearranged VH4 family genes, and the V3-23 and V3-30 gene segments are the most frequently rearranged VH3 family genes. This finding suggests that the predominant expression of these VH genes in peripheral mature B cells is determined to a significant degree by their preferential rearrangement during V-DJ recombination.


Intense Acute Swimming Induces Delayed-Onset Muscle Soreness Dependent on Spinal Cord Neuroinflammation.
Unaccustomed exercise involving eccentric contractions, high intensity, or long duration are recognized to induce delayed-onset muscle soreness (DOMS). Myocyte damage and inflammation in affected peripheral tissues contribute to sensitize muscle nociceptors leading to muscle pain. However, despite the essential role of the spinal cord in the regulation of pain, spinal cord neuroinflammatory mechanisms in intense swimming-induced DOMS remain to be investigated. We hypothesized that spinal cord neuroinflammation contributes to DOMS. C57BL/6 mice swam for 2 h to induce DOMS, and nociceptive spinal cord mechanisms were evaluated. DOMS triggered the activation of astrocytes and microglia in the spinal cord 24 h after exercise compared to the sham group. DOMS and DOMS-induced spinal cord nuclear factor κB (NFκB) activation were reduced by intrathecal treatments with glial inhibitors (fluorocitrate, α-aminoadipate, and minocycline) and NFκB inhibitor [pyrrolidine dithiocarbamate (PDTC)]. Moreover, DOMS was also reduced by intrathecal treatments targeting C-X3-C motif chemokine ligand 1 (CX3CL1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β or with recombinant IL-10. In agreement, DOMS induced the mRNA and protein expressions of CX3CR1, TNF-α, IL-1β, IL-10, c-Fos, and oxidative stress in the spinal cord. All these immune and cellular alterations triggered by DOMS were amenable by intrathecal treatments with glial and NFκB inhibitors. These results support a role for spinal cord glial cells, via NFκB, cytokines/chemokines, and oxidative stress, in DOMS. Thus, unveiling neuroinflammatory mechanisms by which unaccustomed exercise induces central sensitization and consequently DOMS.


The role of texture summary statistics in material recognition from drawings and photographs.
Material depictions in artwork are useful tools for revealing image features that support material categorization. For example, artistic recipes for drawing specific materials make explicit the critical information leading to recognizable material properties (Di Cicco, Wjintjes, & Pont, 2020) and investigating the recognizability of material renderings as a function of their visual features supports conclusions about the vocabulary of material perception. Here, we examined how the recognition of materials from photographs and drawings was affected by the application of the Portilla-Simoncelli texture synthesis model. This manipulation allowed us to examine how categorization may be affected differently across materials and image formats when only summary statistic information about appearance was retained. Further, we compared human performance to the categorization accuracy obtained from a pretrained deep convolutional neural network to determine if observers' performance was reflected in the network. Although we found some similarities between human and network performance for photographic images, the results obtained from drawings differed substantially. Our results demonstrate that texture statistics play a variable role in material categorization across rendering formats and material categories and that the human perception of material drawings is not effectively captured by deep convolutional neural networks trained for object recognition.


No association between ACTN3 R577X polymorphism and elite judo athletic status.
The authors compared ACTN3 R577X genotype and allele frequencies in the majority of all-time-best Spanish judo male athletes (n = 108) and 343 ethnically matched nonathletic men. No between-groups differences were found in allele (P = .077) or genotype distributions (P = .178). Thus, the R577X polymorphism was not significantly associated with the status of being an elite judo athlete, at least in the Spanish population. The contribution of genetics to sports-related phenotype traits is undeniable with some genotypes, of which ACTN3 R577X is currently the leading candidate, partly distinguishing individuals predisposed to either endurance or power sports. However, few athletic events can be categorized as purely power or endurance based. Although genetic testing (ie, for ACTN3 R577X) is already being marketed to predict sports talent and potential of young children, its usefulness is still questionable, at least in competitive judo.


Validating new toxicology tests for regulatory acceptance.
Before a new or revised toxicology test is considered acceptable for safety evaluation of new substances, the test users and the industrial and regulatory decision makers must feel comfortable with it, and the decisions it supports. Comfort with, and the acceptance of, a new test comes after knowing that it has been validated for its proposed use. The validation process is designed to determine the operational characteristics of a test, that is, its reliability and relevance, in addition to its strengths and limitations. The reliability of a test is measured by its reproducibility. Its relevance is judged by its mechanistic relationship to the health effects of concern, and its ability to predict or identify those effects. The U.S. government has recently formed the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to work with federal agencies and test developers to coordinate the evaluation and adoption of new test methods. The ICCVAM will provide guidance to agencies and other stakeholders on criteria and processes for development, validation, and acceptance of tests; coordinate technical reviews of proposed new tests of interagency interest; facilitate information sharing among agencies; and serve as an interagency resource and communications link with parties outside of the federal government on matters of test method validation.


Characterization of a putative grapevine Zn transporter, VvZIP3, suggests its involvement in early reproductive development in Vitis vinifera L.
Zinc (Zn) deficiency is one of the most widespread mineral nutritional problems that affect normal development in plants. Because Zn cannot passively diffuse across cell membranes, it must be transported into intracellular compartments for all biological processes where Zn is required. Several members of the Zinc-regulated transporters, Iron-regulated transporter-like Protein (ZIP) gene family have been characterized in plants, and have shown to be involved in metal uptake and transport. This study describes the first putative Zn transporter in grapevine. Unravelling its function may explain an important symptom of Zn deficiency in grapevines, which is the production of clusters with fewer and usually smaller berries than normal. We identified and characterized a putative Zn transporter from berries of Vitis vinifera L., named VvZIP3. Compared to other members of the ZIP family identified in the Vitis vinifera L. genome, VvZIP3 is mainly expressed in reproductive tissue - specifically in developing flowers - which correlates with the high Zn accumulation in these organs. Contrary to this, the low expression of VvZIP3 in parthenocarpic berries shows a relationship with the lower Zn accumulation in this tissue than in normal seeded berries where its expression is induced by Zn. The predicted protein sequence indicates strong similarity with several members of the ZIP family from Arabidopsis thaliana and other species. Moreover, VvZIP3 complemented the growth defect of a yeast Zn-uptake mutant, ZHY3, and is localized in the plasma membrane of plant cells, suggesting that VvZIP3 has the function of a Zn uptake transporter. Our results suggest that VvZIP3 encodes a putative plasma membrane Zn transporter protein member of the ZIP gene family that might play a role in Zn uptake and distribution during the early reproductive development in Vitis vinifera L., indicating that the availability of this micronutrient may be relevant for reproductive development.


The introduction of cochlear implants (CI) for pediatric populations with deafness has changed life conditions for deaf children markedly. A new generation of children with CI has emerged, and this review investigates how it has been documented that early intervention with CI and enrolment in family-centered auditory-verbal intervention allow children to close the language gap and develop age-equivalent language before entering school. At the school level, children keep up the language level. Most importantly children assess themselves to have levels of social well-being comparable to their peers with normal hearing.


UNCERTAINTY ON RADIATION DOSES ESTIMATED BY BIOLOGICAL AND RETROSPECTIVE PHYSICAL METHODS.
Biological and physical retrospective dosimetry are recognised as key techniques to provide individual estimates of dose following unplanned exposures to ionising radiation. Whilst there has been a relatively large amount of recent development in the biological and physical procedures, development of statistical analysis techniques has failed to keep pace. The aim of this paper is to review the current state of the art in uncertainty analysis techniques across the 'EURADOS Working Group 10-Retrospective dosimetry' members, to give concrete examples of implementation of the techniques recommended in the international standards, and to further promote the use of Monte Carlo techniques to support characterisation of uncertainties. It is concluded that sufficient techniques are available and in use by most laboratories for acute, whole body exposures to highly penetrating radiation, but further work will be required to ensure that statistical analysis is always wholly sufficient for the more complex exposure scenarios.


Reactive Pulmonary Capillary Hemangiomatosis and Pulmonary Veno-Occlusive Disease in a Patient with Repaired Scimitar Syndrome.
Pulmonary capillary hemangiomatosis (PCH) is a rare histological substrate within the spectrum of pulmonary arterial hypertension that possibly represents an unusual manifestation of pulmonary veno-occlusive disease (PVOD). One of the histological hallmarks of PCH is the proliferation of pulmonary capillaries in the alveolar septa that infiltrate adjacent structures such as bronchioles, vessels, and visceral pleura. The hyperplastic process involving the smallest vessels of the pulmonary vascular bed might reflect uncontrolled angiogenesis, but whether this vascular proliferation is idiopathic or, conversely, a reactive process remains to be elucidated. Here we discuss the pathogenesis of PCH exemplified by the first reported case of a young patient with repaired scimitar syndrome that developed unilateral PCH.


Identification of a novel member of the snail/Gfi-1 repressor family, mlt 1, which is methylated and silenced in liver tumors of SV40 T antigen transgenic mice.
DNA methylation is the only known mechanism for an epigenetic genomic DNA modification that is capable of altering gene expression. A recent study reveals that the pattern of CpG island methylation is largely characteristic of tumor type, suggesting that distinct sets of genes are inactivated by methylation during development of each tumor type. We compared previously the methylation status between normal liver and liver tumors in SV40 T/t antigen transgenic mice (MT-D2 mice) using Restriction Landmark Genomic Scanning for Methylation (RLGS-M) and identified several loci/spots that appeared to be methylated frequently in liver tumors. One of these spots, B236, identified a locus on chromosome 12 (D12Ncvs7) syntenic with human 14q12-q21 that is frequently lost in certain human cancers. Shotgun sequencing of a bacterial artificial chro mosome clone containing this spot/locus was performed to identify genes within this region. The Genescan program predicted an open reading frame of a novel, intron-less gene adjacent to the B236 spot that encodes a putative 493-amino acid protein containing the SNAG repressor motif in the NH2-terminal region and five C2H2-type zinc finger motifs in the COOH-terminal half. This putative gene, methylated in liver tumor (mlt 1), is a novel member of the SNAG transcriptional repressor family with 43% amino acid identity to insulinoma-associated protein 1. An open reading frame encoding a protein quite similar to mouse mlt 1 (56% amino acid identity) was located in the syntenic region of the human genome, indi cating that mlt 1 is evolutionarily conserved in human. Northern blot analysis revealed that mlt 1 is normally expressed in brain, spleen, stom ach, and liver. However, mlt 1 expression was silenced in the liver tumors of MT-D2 mice. The putative promoter region of mlt 1 is unmethylated in normal tissues but methylated in all liver tumors from 11 MT-D2 mice We also found that mlt 1 was methylated and not expressed in N18TG-22 cells, a mouse neuroblastoma cell line. Treatment of N18TG-2 cells with a demethylating agent, 5-aza-deoxycytidine, resulted in an expression of mlt 1, indicating that the repression of mlt 1 is attributable to methylation Thus, mlt 1 is a novel target gene that is silenced by methylation during liver tumorigenesis initiated by SV40 T antigen.


Element-arrangement textures in multiple objective tasks.
In his long years of studying visual perception, Jacob Beck made many contributions. This article is a short review of one line of his research--that we shared in--and then a presentation of some results from on-going research down the same line. In the 1980s Beck and his colleagues introduced a new kind of visual stimulus: element-arrangement texture patterns. A series of studies with these patterns has shown that a model containing spatial-frequency and orientation-selective channels can explain many aspects of texture perception as long as two kinds of nonlinear processes are also included; the published studies are briefly summarized. The new results come from multiple objective tasks requiring the observer to make simple discriminations between second-order element-arrangement textures. Results with the objective tasks replicate previously published results using subjective ratings, and the use of the objective tasks allows us to explore several more fine-grained questions about complex (second-order) channels and normalization.


High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance.
Although HLA class I alleles can bind epitopes up to 14 amino acids in length, little is known about the immunogenicity or the responding T-cell repertoire against such determinants. Here, we describe an HLA-B*3508-restricted cytotoxic T lymphocyte response to a 13-mer viral epitope (LPEPLPQGQLTAY). The rigid, centrally bulged epitope generated a biased T-cell response. Only the N-terminal face of the peptide bulge was critical for recognition by the dominant clonotype SB27. The SB27 public T-cell receptor (TcR) associated slowly onto the complex between the bulged peptide and the major histocompatibility complex, suggesting significant remodeling upon engagement. The broad antigen-binding cleft of HLA-B*3508 represents a critical feature for engagement of the public TcR, as the narrower binding cleft of HLA-B*3501(LPEPLPQGQLTAY), which differs from HLA-B*3508 by a single amino acid polymorphism (Arg156 --> Leu), interacted poorly with the dominant TcR. Biased TcR usage in this cytotoxic T lymphocyte response appears to reflect a dominant role of the prominent peptide x major histocompatibility complex class I surface.


Protection against oxidative DNA damage and stress in human prostate by glutathione S-transferase P1.
The pi-class glutathione S-transferase (GSTP1) actively protect cells from carcinogens and electrophilic compounds. Loss of GSTP1 expression via promoter hypermethylation is the most common epigenetic alteration observed in human prostate cancer. Silencing of GSTP1 can increase generation of reactive oxygen species (ROS) and DNA damage in cells. In this study we investigated whether loss of GSTP1 contributes to increased DNA damage that may predispose men to a higher risk of prostate cancer. We found significantly elevated (103%; P < 0.0001) levels of 8-oxo-2'-deoxogunosine (8-OHdG), an oxidative DNA damage marker, in adenocarcinomas, compared to benign counterparts, which positively correlated (r = 0.2) with loss of GSTP1 activity (34%; P < 0.0001). Silencing of GSTP1 using siRNA approach in normal human prostate epithelial RWPE1 cells caused increased intracellular production of ROS and higher susceptibility of cells to H2 O2 -mediated oxidative stress. Additionally, human prostate carcinoma LNCaP cells, which contain a silenced GSTP1 gene, were genetically modified to constitutively express high levels of GSTP1. Induction of GSTP1 activity lowered endogenous ROS levels in LNCaP-pLPCX-GSTP1 cells, and when exposed to H2 O2 , these cells exhibited significantly reduced production of ROS and 8-OHdG levels, compared to vector control LNCaP-pLPCX cells. Furthermore, exposure of LNCaP cells to green tea polyphenols caused reexpression of GSTP1, which protected the cells from H2 O2 -mediated DNA damage through decreased ROS production compared to nonexposed cells. These results suggest that loss of GSTP1 expression in human prostate cells, a process that increases their susceptibility to oxidative stress-induced DNA damage, may be an important target for primary prevention of prostate cancer.


Development and assessment of a verbal response scale for the Patient-Specific Functional Scale (PSFS) in a low-literacy, non-western population.
The Patient-Specific Functional Scale (PSFS) is a routinely used measure of physical function with a 0-10 response scale. We aimed to develop verbal response options for the PSFS, pre-test it for use in a multilingual, low-literacy country- Nepal, and compare preference and error rates between numeric and verbal scale. We hypothesized that a verbal scale would be preferred by respondents and yield fewer errors. We interviewed 42 individuals with musculoskeletal, neurological, and cardiopulmonary conditions to understand how people describe varying levels of physical ability. Transcripts were thematically analyzed, and through consensus, we developed two sets of verbal responses for the PSFS. Next, we pre-tested the scales on an additional 119 respondents following which participants were asked to specify their preferred scale. Error rates were analyzed retrospectively using pre-specified criteria. Participants described their ability in terms of the quality (95%) and the quantity of task performance (88%). Although the verbal scales were preferred over the numeric scale (50% versus 12%), there was no significant difference in error rates between numeric (34%) and verbal scales (32% and 36%). Higher error rates were associated with greater age, fewer years of education, and inexperience with numeric scales. Despite a higher preference for verbal scale, 1 out of 3 patients made errors in using the PSFS, even with an interview format. The error rates were higher among participants with low literacy. The findings raise questions about the utility of PROMs in countries with low literacy rates.


Biopsychosocial predictors of depressive symptoms in the perimenopause-findings from the Swiss Perimenopause Study.
The perimenopause is associated with increased hormone fluctuations and an elevated risk of depression. A number of predictors of depressive symptoms in the menopausal transition have previously been suggested. The purpose of this study was to investigate a set of biopsychosocial predictors of depressive symptoms in perimenopausal women. This cross-sectional study, investigating 114 perimenopausal women (according to the STRAW criteria) aged 40-56 years, was conducted within the scope of the Swiss Perimenopause Study. Multiple regression analyses were performed to identify the most accurate model predicting perimenopausal depressive symptoms. Depressive symptoms were assessed with the German version of the Center of Epidemiologic Studies Depression Scale (CES-D). Validated questionnaires were used to examine psychophysiological complaints, stress, self-esteem, self-compassion, body image, and social support. Estradiol (E2) and progesterone (P4) were assessed through saliva samples, and follicle-stimulating hormone and luteinizing hormone were determined through dried blood spot samples. Seven saliva samples per participant were used to investigate absolute levels and fluctuations of sex steroids. All other variables were measured once. Multiple regression analyses revealed that E2 fluctuations (β=0.15, P = 0.015), history of depression (β=0.14, P = 0.033), menopausal symptoms (β=0.47, P < 0.0001), perceived stress (β=0.17, P = 0.014), body image (β= -0.25, P = 0.014) and self-esteem (β=-0.35, P < 0.0001) were predictive of perimenopausal depressive symptoms (R2 = 0.60). P4 fluctuations and absolute levels of hypothalamic-pituitary-gonadal hormone were not statistically significant. E2 fluctuations were shown to be predictive of depressive symptoms in the perimenopause. Moreover, the presence of burdensome complaints and chronic stress as well as a poor self-evaluation seem to promote depressive symptoms in perimenopausal women.


Phenotypic changes in the flavivirus Kunjin after a single cycle of growth in an Aedes albopictus cell line.
The properties of Kunjin virus produced during acute infections of Aedes albopictus (Aal) mosquito cells were compared with those of the virus progeny from the C6/36 clone of mosquito cells and from Vero cells. Titres of 10(8) p.f.u./ml or greater were obtained from all cells, but significant haemagglutinin activity was associated only with progeny from Vero and C6/36 cells. Kunjin virus from Aal cells adsorbed to goose erythrocytes and blocked haemagglutination by virus from Vero or C6/36 cells. High titres of virus from Aal cells were obtained only when the cells were grown in the presence of 10% or higher concentrations of foetal calf serum, and large losses were encountered when this virus was concentrated by pelleting or by precipitation with polyethylene glycol, and during rate-zonal sedimentation through sucrose gradients. Because of these losses, and because of poor incorporation of [35S]methionine in Aal cells, only analytical amounts of labelled structural proteins were recovered. Electropherograms showed that the presumptive envelope protein E of Kunjin virus from Aal cells migrated more rapidly than E of virions grown in C6/36 and Vero cells, and that the core (C) and membrane-like (M) proteins were not detectably labelled. All the observed changes in phenotype were reversed during one cycle of growth in Vero cells.


Construct validity and reliability of the Brazilian version of Hypertension Knowledge-Level Scale.
To validate the construct and test the reliability of the Brazilian version of Hypertension Knowledge-Level Scale. Methodological research with 220 participants in a primary health care unit from Curitiba, Paraná. The data were collected with a social demographic questionnaire and the Brazilian version of the scale. The construct validity and reliability were assessed using Cronbach's Alpha, Pearson's Correlation and Analysis of Variance. The discriminant validity was verified comparing groups of people with hypertension and without, using T test. Cronbach's Alpha was 0.74. The groups comparison showed that people with hypertension had better results (p<0,001). Pearson's Correlation showed that the questions measure different aspects of the same construct, justifying its organization in subdimensions. The Brazilian version of Hypertension Knowledge-Level Scale is a reliable instrument, which had its construct and criterion validated to measure knowledge about hypertension among Brazilian people. It can help health professionals with planning educative actions.


Motor Deficits in Youth with Concussion History: Issues with Task Novelty or Task Demand?
The present study expands previous work on eye-hand decoupling deficits in youth with concussion history. It examines whether deficits can be linked to difficulties adapting to new task constraints or meeting ongoing task demands. Data from 59 youth with concussion history (M=11 months post-concussion) and 55 no history controls were analyzed. All 114 participants (M=12.5 yrs.) performed two touchscreen-based eye-hand coordination tasks: A standard task with vision and motor action in alignment, and an eye-hand decoupling task with both spatially decoupled, with twenty trials per task condition. First (trial 1-4), middle (trial 9-12), and last (trial 17-20) trial blocks were analyzed in each condition across groups, as well as first and last blocks only. The latter analysis showed in the first block longer response times in the concussion history group in the eye-hand decoupling condition due to a general slowdown of the reaction times across blocks and a trend for higher movement times. Our findings suggest that youth with concussion history have difficulty to adapt to new task constraints associated with complex skill performance during a short series of trials. These results are relevant for athletic trainers, therapists and coaches who work with youth with concussion history.


Polarization-insensitive and widely tunable wavelength conversion for polarization shift keying signal based on four wave mixing in highly non-linear fiber.
A fiber-based polarization-insensitive and widely tunable all-optical wavelength conversion for polarization shift keying (PolSK) signal is experimentally demonstrated by means of four-wave-mixing (FWM) in highly non-linear fiber. Polarization sensitivity of our scheme is compared with the conventional one and the conversion performance of the PolSK signal is investigated. In our scheme, preservation of state of polarization (SOP) of input PolSK signal is possible on both of the converted spectral components in FWM spectrum. In addition, over 23 nm of wavelength tunable operation with high conversion performance is achieved and detailed bit-error-rate (BER) characteristics are measured for both the up- and down-converted signal.


Identification of a Pax6-dependent epidermal growth factor family signaling source at the lateral edge of the embryonic cerebral cortex.
In an emerging model, area patterning of the mammalian cerebral cortex is regulated in part by embryonic signaling centers. Two have been identified: an anterior telencephalic source of fibroblast growth factors and the cortical hem, a medial structure expressing winglessint (WNT) and bone morphogenetic proteins. We describe a third signaling source, positioned as a mirror image of the cortical hem, along the lateral margin of the cortical primordium. The cortical antihem is identified by gene expression for three epidermal growth factor (EGF) family members, Tgf(alpha), Neuregulin 1, and Neuregulin 3, as well as two other signaling molecules, Fgf7 and the secreted WNT antagonist Sfrp2. We find that the antihem is lost in mice homozygous for the Small eye (Pax6) mutation and suggest the loss of EGF signaling at least partially explains defects in cortical patterning and cell migration in Small eye mice.


Relation of physical activity time to incident disability in community dwelling adults with or at risk of knee arthritis: prospective cohort study.
To investigate whether objectively measured time spent in light intensity physical activity is related to incident disability and to disability progression. Prospective multisite cohort study from September 2008 to December 2012. Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island, USA. Disability onset cohort of 1680 community dwelling adults aged 49 years or older with knee osteoarthritis or risk factors for knee osteoarthritis; the disability progression cohort included 1814 adults. Physical activity was measured by accelerometer monitoring. Disability was ascertained from limitations in instrumental and basic activities of daily living at baseline and two years. The primary outcome was incident disability. The secondary outcome was progression of disability defined by a more severe level (no limitations, limitations to instrumental activities only, 1-2 basic activities, or ≥3 basic activities) at two years compared with baseline. Greater time spent in light intensity activities had a significant inverse association with incident disability. Less incident disability and less disability progression were each significantly related to increasing quartile categories of daily time spent in light intensity physical activities (hazard ratios for disability onset 1.00, 0.62, 0.47, and 0.58, P for trend=0.007; hazard ratios for progression 1.00, 0.59, 0.50, and 0.53, P for trend=0.003) with control for socioeconomic factors (age, sex, race/ethnicity, education, income) and health factors (comorbidities, depressive symptoms, obesity, smoking, lower extremity pain and function, and knee assessments: osteoarthritis severity, pain, symptoms, prior injury). This finding was independent of time spent in moderate-vigorous activities. These prospective data showed an association between greater daily time spent in light intensity physical activities and reduced risk of onset and progression of disability in adults with osteoarthritis of the knee or risk factors for knee osteoarthritis. An increase in daily physical activity time may reduce the risk of disability, even if the intensity of that additional activity is not increased.


Molecular and physiological manifestations and measurement of aging in humans.
Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging.


Agromyces iriomotensis sp. nov. and Agromyces subtropicus sp. nov., isolated from soil.
Three novel Gram-stain-positive bacteria, designated IY07-20(T), IY07-56(T) and IY07-113, were isolated from soil samples from Iriomote Island, Okinawa, Japan, and their taxonomic positions were investigated by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the three isolates were closely related to the members of the genus Agromyces, with similarity range of 95.6-98.7%. The isolates contained l-2,4-diaminobutylic acid, d-alanine, d-glutamic acid and glycine in their peptidoglycans. The predominant menaquinone was MK-12 and the major fatty acids were anteiso-C15:0 and anteiso-C17:0. The DNA G+C contents were 70.9-72.9 mol%. The chemotaxonomic characteristics of the isolates matched those described for members of the genus Agromyces. The results of phylogenetic analysis and DNA-DNA hybridization, along with differences in phenotypic characteristics between strains IY07-20(T), IY07-56(T) and IY07-113 and the species of the genus Agromyces with validly published names, indicate that the three isolates merit classification as representatives of two novel species of the genus Agromyces, for which the names Agromyces iriomotensis sp. nov. and Agromyces subtropica sp. nov. are proposed; the type strains are IY07-20(T) ( = NBRC 106452(T) = DSM 26155(T)) and IY07-56(T) ( = NBRC 106454(T) = DSM 26153(T)), respectively.


Resources for Middle Eastern patients: online resources for culturally and linguistically appropriate services in home healthcare and hospice, part 3.
As the population of patients for whom English is not their primary language grows, home care and hospice clinicians are challenged to provide culturally respectful and acceptable patient-centered care for cultures and languages unfamiliar to them. This article identifies resources for understanding the culture of Middle Eastern-born patients and appropriate patient education materials in most of the languages spoken by this population. The resources have been made available for free on the Web by healthcare professionals, government agencies, and support organizations from around the world.


Modulation of Exercise-Induced Hypoalgesia Following an Exercise Intervention in Healthy Subjects.
Exercise is recommended to promote and maintain health and as treatment for more than 25 diseases and pain conditions. Exercise-induced hypoalgesia (EIH), a measure of descending pain inhibitory control, has been found to be impaired in some chronic pain conditions, but it is currently unclear if EIH is modifiable. This study investigated whether a long-term exercise intervention could modulate EIH in healthy subjects. In 38 healthy subjects, EIH was assessed as change in pressure pain threshold (PPT) after a three-minute isometric wall squat within the first week and after approximately seven weeks of military training (MT). Further, temporal summation of pain (TSP) and Knee injury and Osteoarthritis Outcome Score (KOOS) were assessed. Physical performance capacity was assessed using the Endurance 20-m shuttle run fitness test (20MSR). Hypoalgesic (EIH > 0.0 kPa) and hyperalgesic (EIH ≤ 0.0 kPa) subgroups were defined based on baseline EIH. Change in EIH following MT was used as the primary outcome. Increased EIH (P = 0.008), PPT (P < 0.003), and 20MSR (P < 0.001) were found following MT, with no changes in TSP and KOOS (P > 0.05). Subjects with a hyperalgesic EIH response at baseline (26% of the participants) presented significantly improved EIH following MT (P = 0.010). Finally, an association between 20MRS change and EIH change was found (r = 0.369, P = 0.023). MT increased EIH, especially in subjects who demonstrated a hyperalgesic response at baseline. Improvement in physical performance capacity was associated with an improvement in EIH, indicating that improvement in physical performance capacity may improve central pain mechanisms.


Computational analysis of high-risk SNPs in human CHK2 gene responsible for hereditary breast cancer: A functional and structural impact.
Nowadays CHK2 mutation is studied frequently in hereditary breast and ovarian cancer patients in addition to BRCA1/BRCA2. CHK2 is a tumor suppressor gene that encodes a serine/threonine kinase, also involved in pathways such as DNA repair, cell cycle regulation and apoptosis in response to DNA damage. CHK2 is a well-studied moderate penetrance gene that correlates with third high risk susceptibility gene with an increased risk for breast cancer. Hence before planning large population study, it is better to scrutinize putative functional SNPs of CHK2 using different computational tools. In this study, we have used various computational approaches to identify nsSNPs which are deleterious to the structure and/or function of CHK2 protein that might be causing this disease. Computational analysis was performed by different in silico tools including SIFT, Align GVGD, SNAP-2, PROVEAN, Poly-Phen-2, PANTHER, PhD-SNP, MUpro, iPTREE-STAB, Consurf, InterPro, NCBI Conserved Domain Search tool, ModPred, SPARKS-X, RAMPAGE, Verify-3D, FT Site, COACH and PyMol. Out of 78 nsSNP of human CHK2 gene, seven nsSNPs were predicted functionally most significant SNPs. Among these seven nsSNP, p.Arg160Gly, p.Gly210Arg and p.Ser415Phe are highly conserved residues with conservation score of 9 and three nsSNP were predicted to be involved in post translational modification. The p.Arg160Gly and p.Gly210Arg may interfere in phosphopeptide binding site on FHA conserved domain. The p.Ser415Phe may interfere in formation of activation loop of protein-kinase domain and might interfere in interactions of CHK2 with ligand. The study concludes that mutation of serine to phenylalanine at position 415 is a major mutation in native CHK2 protein which might contribute to its malfunction, ultimately causing disease. This is the first comprehensive study, where CHK2 gene variants are analyzed using in silico tools hence it will be of great help while considering large scale studies and also in developing precision medicines related to these polymorphisms in the era of personalized medicine.


Transvenous Implantation of a Stent Valve in Patients With Degenerated Mitral Prostheses and Native Mitral Stenosis.
The purpose of this study was to report the use of a transvenous transseptal approach using a stent valve in patients with degenerated biological mitral valve prostheses, regurgitation after mitral repair, and native mitral stenosis. Ten patients (median age, 74 years; range, 20-89 years; 5 men and 5 women) with degenerated mitral bioprosthetic valves (n = 7), failed mitral repair (n = 1), or calcified native stenotic valves (n = 2) underwent transvenous implantation of a stent valve. The procedure was initially successful in all patients. Predilation was performed for balloon sizing only in the 2 patients with native mitral stenosis. The stent valve was deployed during 1 period of rapid pacing. A guidewire, as a loop from the right femoral vein and through the left ventricular apex, facilitated a good angle and secure positioning of the stent valve. An ultrasonographically guided puncture of the apex was carried out in 6 patients, and in the other 4 we performed a minithoracotomy before apical puncture. All valves were implanted in a good position with improved function and without significant paravalvular leakage (PVL). There were no periprocedural deaths. The 30-day survival was 80% (8 of 10 patients), and 60% (6 of 10) of patients were still alive a median time of 290 days after the procedure. Transvenous transseptal implantation of a stent valve was performed in 10 patients with mitral valve disease, with good early functional results. These high-risk patients must be carefully selected by a multidisciplinary team because the procedure carries a high mortality.


Controlled hypotension during middle ear surgery: hemodynamic effects of remifentanil vs nitroglycerin.
Controlled hypotension is a well-known technique used by anesthesiologists to limit intraoperative bleeding in patients undergoing middle ear surgery and improve visibility of the surgical field. Nitroglycerin and remifentanil are among the drugs used to induce controlled hypotension.The aim of our study was to compare the hemodynamic effects of remifentanil and nitroglycerin in this patient population. All consecutive patients who underwent middle ear surgery between January and December 2016, at the University Hospital Vittorio Emanuele in Catania were included in a retrospective study. Patients who were given nitroglycerin to induce controlled hypotension were compared to those given remifentanil. The following parameters were measured systolic and diastolic blood pressure, heart rate, peripheral (capillary) oxygen saturation, and fraction of expired carbon dioxide. A mean arterial pressure of 50-70 mmHg was considered optimal. Thirty patients who underwent stapedioplasty and tympanoplasty, 25 men and 5 women,with a mean age of 43 years (range 32-58 years) were included in the study. Fifteen patients had received nitroglycerin (group A) and 15 patients remifentanil (group B). The target blood pressure was reached in all patients and no significant difference was found between the groups with regard to the level of systolic and diastolic blood pressure, heart rate, peripheral (capillary) oxygen saturation, and fraction of expired carbon dioxide. However the heart rate of 2 younger patients in group A rose to > 100 bpm after the administration of nitroglycerin. Both remifentanil and nitroglycerin are effective in inducing controlled hypotension. In younger patients administration of nitroglycerin is associated with an increase in heart rate. Controlled hypotension, Middle ear surgery, Nitroglycerin, Remifentanil.


Development of the olfactory nerve in the clawed frog, Xenopus laevis: II. Effects of hypothyroidism.
Quantitative and morphological data were obtained on developing olfactory axons in normal and hypothyroid larvae of the African clawed frog Xenopus laevis. Hypothyroid larvae were produced by rearing the animals, beginning at stage 48, in a 0.01% solution of propylthiouracil (PTU), a treatment that blocks synthesis of thyroid hormone. These PTU-treated larvae were compared to their age-matched siblings when these siblings reached stage 52 (premetamorphic larvae; prior to synthesis of thyroid hormone), stage 57 (late premetamorphic larvae; after the onset of thyroid hormone synthesis), or stage 58 (larvae at the onset of metamorphic climax; thyroid hormone levels continue to rise). The number of olfactory axons did not differ between stage 52 control animals and the age-matched, PTU-treated animals, but there were only about half the number of axons in the PTU-treated animals that were age-matched to the stage 57 or 58 controls. Thus, PTU had no effect on olfactory axon number prior to the normal rise in thyroid hormone levels. But PTU significantly reduced the normal increase in olfactory axon number compared to stage 58 control larvae, whose thyroid hormone levels are high. While PTU also produced some changes in several other body measurements, the effect on the olfactory axons was the most consistent and prominent. The results presented here support our previous findings that thyroid hormone plays a significant role in the development of the olfactory system in Xenopus.


Clinical aspects and outcomes in osteoarthritis.
Osteoarthritis (OA) is the most prevalent type of arthritis worldwide, and its incidence significantly increases with age. It commonly affects the knees, hips, spine, big toes, and hands. OA can be identified through clinical examination, symptoms, and imaging methods. Its main symptoms include pain, stiffness, and limitations in joint movement. Examinations may reveal coarse crepitus, bony enlargement, and tenderness at the joint line. In severe cases of OA, rest pain, night pain, and deformity may occur. OA can lead to decreased physical activity, function, and quality of life due to symptoms such as pain and stiffness. To evaluate these impacts, patient-reported outcome measures (PROMs) are necessary. Various generic, disease-specific, and joint-specific PROMs have been developed and used in clinical practice to assess the outcomes of OA.


Sensitization of nociceptive spinal neurons contributes to pain in a transgenic model of sickle cell disease.
Chronic pain is a major characteristic feature of sickle cell disease (SCD). The refractory nature of pain and the development of chronic pain syndromes in many patients with SCD suggest that central neural mechanisms contribute to pain in this disease. We used HbSS-BERK sickle mice, which show chronic features of pain similar to those observed in SCD, and determined whether sensitization of nociceptive neurons in the spinal cord contributes to pain and hyperalgesia in SCD. Electrophysiological recordings of action potential activity were obtained from single identified dorsal horn neurons of the spinal cord in anesthetized mice. Compared with control HbAA-BERK mice, nociceptive dorsal horn neurons in sickle mice exhibited enhanced excitability as evidenced by enlarged receptive fields, increased rate of spontaneous activity, lower mechanical thresholds, enhanced responses to mechanical stimuli, and prolonged afterdischarges following mechanical stimulation. These changes were accompanied by increased phosphorylation of mitogen-activated protein kinases (MAPKs) in the spinal cord that are known to contribute to neuronal hyperexcitability, including c-Jun N-terminal kinase (JNK), p44/p42 extracellular signaling-regulated kinase (ERK), and p38. These findings demonstrate that central sensitization contributes to pain in SCD.


Evaluation of genetic variation contributing to differences in gene expression between populations.
Gene expression is a complex quantitative trait partially regulated by genetic variation in DNA sequence. Population differences in gene expression could contribute to some of the observed differences in susceptibility to common diseases and response to drug treatments. We characterized gene expression in the full set of HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry for 9156 transcript clusters (gene-level) evaluated with the Affymetrix GeneChip Human Exon 1.0 ST Array. Gene expression was found to differ significantly between these samples for 383 transcript clusters. Biological processes including ribosome biogenesis and antimicrobial humoral response were found to be enriched in these differential genes, suggesting their possible roles in contributing to the population differences at a higher level than that of mRNA expression and in response to environmental information. Genome-wide association studies for local or distant genetic variants that correlate with the differentially expressed genes enabled identification of significant associations with one or more single-nucleotide polymorphisms (SNPs), consistent with the hypothesis that genetic factors and not simply population identity or other characteristics (age of cell lines, length of culture, etc.) contribute to differences in gene expression in these samples. Our results provide a comprehensive view of the genes differentially expressed between populations and the enriched biological processes involved in these genes. We also provide an evaluation of the contributions of genetic variation and nongenetic factors to the population differences in gene expression.


Malic Enzyme is a Major Source of NADPH for Lipid Accumulation by Aspergillus Nidulans.
Malic enzyme was shown to be a major source of NADPH for the synthesis of storage lipid by Aspergillus nidulans. A previously produced mutant lacking malic enzyme activity (acuK248) accumulated only half the lipid (12%, w/w, of cell dry weight) accumulated by strains of A. nidulans possessing malic enzyme. When cultivated under conditions designed not to promote the production of storage lipid all three strains of A. nidulans studied contained equivalent amounts of lipid (5%, w/w, of cell dry weight). Thus malic enzyme did not appear to be limiting the synthesis of metabolically active lipid (e.g. membrane lipids). No evidence of a role for malic enzyme in the desaturation of fatty acids was found.


Precarious employment and health: analysis of the Comprehensive National Survey in Japan.
Recent studies suggest that unstable employment contracts may affect the health of workers. Many Japanese workers working full time in ostensibly permanent positions actually operate within unstable and precarious employment conditions. We compared the health status of Japanese workers with precarious employment contracts with that of permanent workers using the 2007 Comprehensive Survey of Living Conditions of the People on Health and Welfare (n=205,994). We classified their employment status as 'permanent' vs. 'precarious' (part-time, dispatch, or contract/non-regular) and compared their health conditions. Among both sexes, precarious workers were more likely than permanent workers to have poor self-rated health or more subjective symptoms, with more workers in full-time employment suffering from serious psychological distress (SPD) and more female workers who smoke. Using logistic regression, we identified a positive association between precarious employment and SPD and current smoking among workers engaged in full-time employment after adjusting for age, marital status, and work-related conditions. This study demonstrates that precarious employment contracts are associated with poor self-rated health, psychological distress, and tobacco use, especially among people working full-time jobs. These results suggest that engagement in full-time work under unstable employment status impairs workers' health.


SYNAPSE, Symposium for Young Neuroscientists and Professors of the Southeast: A One-day, Regional Neuroscience Meeting Focusing on Undergraduate Research.
The Symposium for Young Neuroscientists and Professors of the Southeast (SYNAPSE; synapse.cofc.edu) was designed to encourage contacts among faculty and students interested in neuroscience. Since its inception in 2003, the SYNAPSE conference has consistently drawn faculty and undergraduate interest from the region. This unique meeting provides undergraduates with a valuable opportunity for neuroscience education; students interact with noted neuroscience faculty, present research results, obtain feedback from neuroscientists at other institutions, and form connections with other neuroscientists in the region. Additionally, SYNAPSE allows undergraduate students and faculty to attend workshops and panel discussions about issues related to professional skills and career options. The SYNAPSE conference currently travels among host institutions in the southeastern United States in two-year cycles. This article briefly describes the genesis of SYNAPSE and reviews SYNAPSE conferences from 2006 through 2010. The goal of this paper is to highlight key issues organizers have experienced launching, sustaining, and hosting this regional undergraduate neuroscience conference as well as assist faculty to develop similar conferences.


Infrared emission spectra from a heterogeneous catalyst system in reaction conditions. 2: Infrared spectroscopic aspects.
Infrared spectroscopic aspects of IR emission investigations of a heterogeneous catalytic system in reaction conditions are outlined. A brief theoretical review of emission spectroscopy is given. In addition, experimental problems especially related to the microreactor designed for in situ IR emission investigations of catalytic reactions are discussed. It can be concluded that most experimental problems are not prohibitive. Infrared emission spectroscopy turns out to be a feasible technique over both a wide frequency range and a large temperature range. This is illustrated by a few experimental results.


The overlapping geography of cognitive ability and chronotype.
Chronotype and cognitive ability are two human phenotypes with an uneven geographic distribution due to both selective migration and causal environmental effects. In our study, we aimed to examine the relationship between geographic variables, cognitive ability and chronotype. We used a large anonymized sample (n = 25,700, mostly from the USA, UK, Canada and Australia) of dating site users to estimate chronotype and cognitive ability from questionnaire responses using item response theory. We matched each user to geographic coordinates and city size using the reported locations and geographic databases. In line with previous research we found that male sex, younger age, residence in a more populous locale, higher cognitive ability and more westward position within the same time zone were associated with later chronotype. Male sex, younger age, residence in a more populous locale, later chronotype and higher latitude were associated with higher cognitive ability, but the effect of population on chronotype and latitude on cognitive ability was only present in the USA. The relationship between age and chronotype was stronger in males, and the relationship between chronotype and cognitive ability was stronger in males and in older participants. Population density had an independent association with cognitive ability, but not chronotype. Our results confirm the uneven geographic distribution of chronotype and cognitive ability. These findings generalize across countries, but they are moderated by age and sex, suggesting both biological and cultural effects.


Effect of silver nanoparticles on Mediterranean sea urchin embryonal development is species specific and depends on moment of first exposure.
With the ever growing use of nanoparticles in a broad range of industrial and consumer applications there is increasing likelihood that such nanoparticles will enter the aquatic environment and be transported through freshwater systems, eventually reaching estuarine or marine waters. Due to silver's known antimicrobial properties and widespread use of silver nanoparticles (AgNP), their environmental fate and impact is therefore of particular concern. In this context we have investigated the species-specific effects of low concentrations of 60 nm AgNP on embryonal development in Mediterranean sea urchins Arbacia lixula, Paracentrotus lividus and Sphaerechinus granularis. The sensitivity of urchin embryos was tested by exposing embryos to nanoparticle concentrations in the 1-100 μg L(-1) range, with times of exposure varying from 30 min to 24 h (1 h-48 h for S. granularis) post-fertilisation which corresponded with fertilized egg, 4 cell, blastula and gastrula development phases. The most sensitive species to AgNP was A. lixula with significant modulation of embryonal development at the lowest AgNP concentrations of 1-10 μg L(-1) with high numbers of malformed embryos or arrested development. The greatest impact on development was noted for those embryos first exposed to nanoparticles at 6 and 24 h post fertilisation. For P. lividus, similar effects were noted at higher concentrations of 50 μg L(-1) and 100 μg L(-1) for all times of first exposure. The S. granularis embryos indicated a moderate AgNP impact, and significant developmental abnormalities were recorded in the concentration range of 10-50 μg L(-1). As later post-fertilisation exposure times to AgNP caused greater developmental changes in spite of a shorter total exposure time led us to postulate on additional mechanisms of AgNP toxicity. The results herein indicate that toxic effects of AgNP are species-specific. The moment at which embryos first encounter AgNP is also shown to be an important factor in the development of abnormalities, and future applications of the sea urchin embryo development test for nanoparticle toxicity testing should carefully address the specific phase of development of embryos when nanoparticles are first introduced.


Florence Nightingale: statistician and consultant epidemiologist.
Florence Nightingale became a legend in her own lifetime and the image of the lady with the lamp still influences public thinking about the practice of nursing and its practitioners. Like many legends, her story has been adapted to suit changing circumstances and purposes. One could speculate why it is that particular aspects have come into greater prominence at particular times in history. This article explores a less-known aspect of her work, her expertise and use of statistics and epidemiology. And it illustrates how that expertise was called upon to address a major health problem in New Zealand in 1860.


Synthesis of free-standing Ta3N5 nanotube membranes and flow-through visible light photocatalytic applications.
We report on free-standing Ta3N5 nanotubular membranes with open top and bottom, used as visible-light-active, flow-through photocatalytic micro-reactors. We grow first a robust anodic Ta2O5 layer, lift-off a membrane and convert to Ta3N5. Such membranes can easily, in a flow-through mode, degrade methylene blue under visible light (wavelength >400 nm) or solar illumination.


NMR structure of the haem core of a novel tetrahaem cytochrome isolated from Shewanella frigidimarina: identification of the haem-specific axial ligands and order of oxidation.
The tetrahaem cytochrome isolated during anaerobic growth of Shewanella frigidimarina NCIMB400 is a small protein (86 residues) involved in electron transfer to Fe(III), which can be used as a terminal respiratory oxidant by this bacterium. A 3D solution structure model of the reduced form of the cytochrome has been determined using NMR data in order to determine the relative orientation of the haems. The haem core architecture of S. frigidimarina tetrahaem cytochrome differs from that found in all small tetrahaem cytochromes c(3) so far isolated from strict anaerobes, but has some similarity to the N-terminal cytochrome domain of flavocytochrome c(3) isolated from the same bacterium. NMR signals obtained for the four haems of S. frigidimarina tetrahaem cytochrome at all stages of oxidation were cross-assigned to the solution structure using the complete network of chemical exchange connectivities. Thus, the order in which each haem in the structure becomes oxidised was determined.


Elastolytic activity of human blood monocytes characterized by a new monoclonal antibody against human leucocyte elastase. Relationship to rheumatoid arthritis.
The leucocyte elastase of human blood monocytes was investigated by applying a new monoclonal antibody which did not block the enzyme activity against elastin. In a fixed population of mononuclear cells (MNC) and using fluorescence activated cell sorting (FACS), the human leucocyte elastase (HLE) antibody identified a subgroup of CD14+ cells which contained all the elastase activity and which could be blocked by a specific chloromethylketone elastase inhibitor. By anti-CD14 labelling the HLE positive cells were identified as monocytes and amounted to 88% of this cell type (median: range 72-96%). In a parallel study of patients with active rheumatoid arthritis (RA) and control donors the elastolytic capacity of PMA-stimulated live MNC was higher for RA patients than for controls (p less than 0.02). For control donors the number of HLE+ cells correlated well to the elastolysis in the same MNC sample (Spearman's rho:0.83, p less than 0.05); in the samples from RA patients no correlation was found between the normal number of HLE+ cells and the increased elastolysis (rho: 0.54, p greater than 0.20).


The relative contribution of physical and cognitive fall risk factors in people with Parkinson's disease: a large prospective cohort study.
In order to develop multifaceted fall prevention strategies for people with Parkinson's disease (PD), greater understanding of the impact of physical and cognitive performance on falls is required. We aimed to identify the relative contribution of a comprehensive range of physical and cognitive risk factors to prospectively-measured falls in a large sample of people with PD and develop an explanatory multivariate fall risk model in this group. METHODS MEASURES: of PD signs and symptoms, freezing of gait, balance, mobility, proprioception, leg muscle strength, and cognition were collected on 205 community-dwelling people with PD. Falls were monitored prospectively for 6 months using falls diaries. A total of 120 participants (59%) fell during follow-up. Freezing of gait (P < .001), dyskinesia (P = .02), impaired anticipatory and reactive balance (P < .001), impaired cognition (P = .002), reduced leg muscle strength (P = .006), and reduced proprioception (P = .04) were significantly associated with future falls in univariate analyses. Freezing of gait (risk ratio [RR] = 1.03, 95% confidence interval [CI] = 1.00-1.05, P = .02), impaired anticipatory (RR = 1.01, 95% CI = 1.00-1.02, P = .03) and reactive (RR = 1.26, 95% CI = 1.01-1.58, P = .04) balance, and impaired orientation (RR = 1.28, 95% CI = 1.01-1.62, P = .04) maintained significant associations with falls in multivariate analysis. The study findings elucidate important physical and cognitive determinants of falls in people with PD and may assist in developing efficacious fall prevention strategies for this high-risk group.


Cytodiagnosis of malignant lesions in cerebrospinal fluid. Review and cytohistologic correlation.
In an evaluation of the efficacy of cerebrospinal fluid (CSF) examination in our laboratory, 1,635 CSF specimens received between March 1, 1975, and December 31, 1982, were reviewed. All 111 positive samples (from 77 cases) and all 141 suspicious samples (from 83 cases) were reviewed microscopically, and the clinical records in the cases were rechecked. The 77 positive cases were confirmed by tissue and other studies: 23 as primary brain tumors, 26 as secondary carcinomas, 14 as leukemias, 12 as lymphomas and 2 as multiple myelomas. The 83 suspicious cases were similarly confirmed: 31 as primary brain tumors, 14 as secondary carcinomas, 22 as leukemias and 7 as lymphomas-with 9 found to be "benign." There were no false positives in the positive group. This study suggests that the identification of malignant cells in CSF samples constitutes a reliable method of diagnosis and lessens the need for further biopsies.


Copolymerization kinetics of methyl methacrylate-styrene obtained by PLP-MALDI-ToF-MS.
The combination of MALDI-ToF-MS and pulsed laser polymerization has been used to study the propagation rate coefficients for the copolymer system styrene-methyl methacrylate. For the first time, complete information regarding mode of termination, reactivity of photoinitiator-derived radicals, copolymer molecular mass, chemical composition, and copolymerization rates is obtained interrelated. The polymerizations were carried out in bulk with varying styrene concentrations at a temperature of 15.2 degrees C by an excimer pulsed laser with varying frequencies. Both chemical composition distributions and molecular weight distributions were determined by MALDI-ToF-MS. The data were fitted to the implicit penultimate unit model and have resulted in new point estimates of the monomer and radical reactivity ratios for the copolymer system styrene-methyl methacrylate: r(St) = 0.517, r(MMA) = 0.420, s(St) = 0.296, s(MMA) = 0.262. Comparison between Monte Carlo simulations and the obtained results further confirmed the very successful combination of pulsed laser copolymerization experiments with MALDI-ToF-MS. The obtained results are believed to be the most accurate and complete set of copolymerization parameters to date.


Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era.
Cerebral atrophy is a well-described, but poorly understood complication of human immunodeficiency virus (HIV) infection. Despite reduced prevalence of HIV-associated dementia in the highly active antiretroviral therapy (HAART) era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV-infected patients on HAART, and demographic and clinical factors contributing to brain volume loss. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection, and age would be associated with reduced cortical volumes. Volumes of cortical and subcortical regions in 69 HIV-infected neuroasymptomatic (NA) individuals and 13 with at least mild acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) were measured using voxel-based morphometry. Demographic and clinical factors (age, plasma HIV RNA level, current and nadir CD4 counts, duration of infection, central nervous system [CNS] penetration of antiretroviral regimen) along with their interactions were entered into a regression model selection algorithm to determine the final models that best described regional brain volumes. Relative to NA, individuals with ADC exhibited decreased total gray matter and parietal cortex volumes and increased total ventricular volumes. Final regression models showed overall cerebral volume, including gray and white matter volume and volumes of the parietal, temporal, and frontal lobes and the hippocampus, were most strongly associated with disease history factors (nadir CD4 and duration of infection). In contrast, basal ganglia volumes were related most strongly to current disease factors, most notably plasma HIV RNA. These findings indicate that individuals with a history of chronic HIV infection with previous episodes of severely impaired immune function, as reflected by reduced nadir CD4+ lymphocyte count, may be at greatest risk for cerebral atrophy. The pattern of HIV-associated brain loss may be changing from a subcortical to a cortical disease among patients who are largely asymptomatic on HAART.


A Golgi and tonoplast localized S-acyl transferase is involved in cell expansion, cell division, vascular patterning and fertility in Arabidopsis.
S-acylation of eukaryotic proteins is the reversible attachment of palmitic or stearic acid to cysteine residues, catalysed by protein S-acyl transferases that share an Asp-His-His-Cys (DHHC) motif. Previous evidence suggests that in Arabidopsis S-acylation is involved in the control of cell size, polarity and the growth of pollen tubes and root hairs. Using a combination of yeast genetics, biochemistry, cell biology and loss of function genetics the roles of a member of the protein S-acyl transferase PAT family, AtPAT10 (At3g51390), have been explored. In keeping with its role as a PAT, AtPAT10 auto-S-acylates, and partially complements the yeast akr1 PAT mutant, and this requires Cys(192) of the DHHC motif. In Arabidopsis AtPAT10 is localized in the Golgi stack, trans-Golgi network/early endosome and tonoplast. Loss-of-function mutants have a pleiotropic phenotype involving cell expansion and division, vascular patterning, and fertility that is rescued by wild-type AtPAT10 but not by catalytically inactive AtPAT10C(192) A. This supports the hypothesis that AtPAT10 is functionally independent of the other Arabidopsis PATs. Our findings demonstrate a growing importance of protein S-acylation in plants, and reveal a Golgi and tonoplast located S-acylation mechanism that affects a range of events during growth and development in Arabidopsis.


Comparing quantum-chemical calculation methods for structural investigation of zeolite crystal structures by solid-state NMR spectroscopy.
Combining quantum-chemical calculations and ultrahigh-field NMR measurements of (29)Si chemical shielding (CS) tensors has provided a powerful approach for probing the fine details of zeolite crystal structures. In previous work, the quantum-chemical calculations have been performed on 'molecular fragments' extracted from the zeolite crystal structure using Hartree-Fock methods (as implemented in Gaussian). Using recently acquired ultrahigh-field (29) Si NMR data for the pure silica zeolite ITQ-4, we report the results of calculations using recently developed quantum-chemical calculation methods for periodic crystalline solids (as implemented in CAmbridge Serial Total Energy Package (CASTEP) and compare these calculations to those calculated with Gaussian. Furthermore, in the context of NMR crystallography of zeolites, we report the completion of the NMR crystallography of the zeolite ITQ-4, which was previously solved from NMR data. We compare three options for the 'refinement' of zeolite crystal structures from 'NMR-solved' structures: (i) a simple target-distance based geometry optimization, (ii) refinement of atomic coordinates in which the differences between experimental and calculated (29)Si CS tensors are minimized, and (iii) refinement of atomic coordinates to minimize the total energy of the lattice using CASTEP quantum-chemical calculations. All three refinement approaches give structures that are in remarkably good agreement with the single-crystal X-ray diffraction structure of ITQ-4.


Atypical meningioma with large cyst. Case report.
A 29-year-old male presented with loss of consciousness and generalized seizure, followed by right hemiparesis and speech disturbance. Computed tomography and magnetic resonance imaging showed a solid, enhanced tumor with a cyst in the left frontal area with surrounding edema and mild mass effect. The cyst wall was also enhanced. The preoperative diagnosis was cystic falx meningioma. The tumor was totally resected, but most of the cyst wall adhered tightly to the surrounding brain and could not be removed. Histological examination revealed atypical meningioma and tumor cells in the cyst wall. The patient received local radiotherapy to the residual cyst wall with a total dose of 50 Gy.


Short-term outcome trapeziectomy with ligament reconstruction and tendon interposition versus trapeziometacarpal prosthesis : a literature review.
Trapeziectomy with ligament reconstruction and tendon interposition and trapeziometacarpal prosthesis are two commonly used procedures for first carpometacarpal joint osteoarthritis. The purpose of this study is to compare the short-term outcome of trapeziectomy with ligament reconstruction and tendon interposition to trapeziometacarpal prosthesis. Pubmed, Cochrane library and science direct database were searched with adequate search terms. Used parameters were force, pain, mobility, functionality and complication. All papers describing short-term outcome of ligament reconstruction and tendon interposition or trapeziometacarpal prosthesis were included in this review. Trapeziometacarpal prostheses showed faster pain relief compared with trapeziectomy and ligament reconstruction and tendon interposition. Overall, there was a better strength in the trapeziometacarpal prosthesis group. A lack of information was found about the short- term functionality. The mobility recovers faster in the prosthesis group, although different scoring scales were used for measurement. We could confirm the faster pain relief in the prosthesis group and generally a faster recovery of strength and mobility. In the prosthesis group were more short-term complications. More studies are required to evaluate the short-term recovery of strength, the mobility, functionality and satisfaction.


Effectiveness of patiromer in the treatment of hyperkalemia in chronic kidney disease patients with hypertension on diuretics.
Recurrent hyperkalemia frequently limits use of renin-angiotensin-aldosterone system inhibitors (RAASi) in chronic kidney disease (CKD) patients with hypertension, diabetes, and/or heart failure. Patiromer is a sodium-free, nonabsorbed potassium (K)-binding polymer approved by the US Food and Drug Administration for the treatment of hyperkalemia. This post-hoc analysis of OPAL-HK examined the effectiveness and safety of patiromer in reducing serum K in hyperkalemic CKD patients on RAASi, with hypertension, receiving diuretic therapy versus those not on diuretics. Depending on the degree of hyperkalemia at baseline, CKD patients with serum K from 5.1 to less than 6.5 mmol/l on RAASi (n = 243) were assigned to a patiromer of total dose 8.4 or 16.8 g, divided twice daily. Changes in serum K, and tolerability and safety were assessed over 4 weeks in patients on and not on diuretics. At baseline, 132 patients used diuretics and 111 were not on diuretics, mean age was 64.3 and 64.0 years, respectively, and 63 and 51% were men. Similar reductions in serum K were seen over 4 weeks in both subgroups. At week 4, serum K fell by -0.95 ± 0.04 mmol/l with any diuretic and -1.04 ± 0.05 mmol/l with no diuretic. Patiromer was well tolerated, with mild-to-moderate constipation reported as the most common adverse event (7.6 and 14.4% of patients on any diuretic or no diuretic, respectively). Hypokalemia (s-K <3.5 mEq/l) was reported in 2.3% of patients on any diuretic and in 3.7% not on diuretics. The serum K-lowering efficacy and safety profile of patiromer in hyperkalemia patients with CKD was not compromised by diuretic therapy.


Phylogeny and patterns of diversity of goat mtDNA haplogroup A revealed by resequencing complete mitogenomes.
We sequenced to near completion the entire mtDNA of 28 Sardinian goats, selected to represent the widest possible diversity of the most widespread mitochondrial evolutionary lineage, haplogroup (Hg) A. These specimens were reporters of the diversity in the island but also elsewhere, as inferred from their affiliation to each of 11 clades defined by D-loop variation. Two reference sequences completed the dataset. Overall, 206 variations were found in the full set of 30 sequences, of which 23 were protein-coding non-synonymous single nucleotide substitutions. Many polymorphic sites within Hg A were informative for the reconstruction of its internal phylogeny. Bayesian and network clustering revealed a general similarity over the entire molecule of sequences previously assigned to the same D-loop clade, indicating evolutionarily meaningful lineages. Two major sister groupings emerged within Hg A, which parallel distinct geographical distributions of D-loop clades in extant stocks. The pattern of variation in protein-coding genes revealed an overwhelming role of purifying selection, with the quota of surviving variants approaching neutrality. However, a simple model of relaxation of selection for the bulk of variants here reported should be rejected. Non-synonymous diversity of Hg's A, B and C denoted that a proportion of variants not greater than that allowed in the wild was given the opportunity to spread into domesticated stocks. Our results also confirmed that a remarkable proportion of pre-existing Hg A diversity became incorporated into domestic stocks. Our results confirm clade A11 as a well differentiated and ancient lineage peculiar of Sardinia.


A comparison of the uterine beta2-adrenoreceptor selectivity of fenoterol, hexoprenaline, ritodrine and salbutamol.
A study was undertaken to compare the uterine beta2-adrenoreceptor selectivity of fenoterol, hexoprenaline, ritodrine and salbutamol. The drugs in doses having an equivalent effect on uterine activity, were randomly administered as an intravenous bolus to 10 patients who had been induced at term. The cardiovascular and uterine effects of the drugs were recorded. The rise in maternal pulse rate was significantly less (P less than 0,001) after the administration of hexoprenaline when it was compared with fenoterol, ritodrine, and salbutamol. Hexoprenaline proved to be the most chronotropically beta2-selective drug, having the least effect on the beta1-adrenoreceptors of the heart, for an equivalent effect on the uterus. Blood pressure changes were less significantly different between the drugs. The clinical use in obstetrics of a highly beta2-selective sympathomimetic drug is discussed.


Poliomyelitis era in Trinidad from 1940 to 1972 and beyond: Implications for effective global health governance for its eradication.
Acute poliomyelitis (APM/polio) is a viral infection caused by the polio virus that continues to have a fascinating social and economic impact on countries throughout the world. Humans acquire the virus by close personal contact with transmission occurring through the fecal-oral route. The majority of poliovirus infections results in no illness or produces only self-limited symptoms, however in approximately 5% of infected patients flaccid paralysis of the limbs can occur and 1% can die. Although APM is no longer a feared disease mainly due to the development of effective vaccines, its eradication remains elusive. The aim of this study is to review the historical impact of APM in Trinidad. A retrospective analysis of all cases occurring from 1939 to 1972 was undertaken. Data for the study were derived from two sources the Annual Statistical Reports of the Ministry of Health 1972-2000 and the epidemiological publications of the League of Nations Health Organization and the World Health Organization. There were four outbreaks of APM in Trinidad 1941, 1942, 1954, and 1972. After the final outbreak in 1972, APM was eradicated not only from Trinidad but also all the countries of the Americas mainly through the effective use of the oral polio vaccine. Polio has brought together international agencies, governments, and the people to build an effective public health system around a common vision for health and wellbeing. The polio eradication and endgame strategic plan represents a major milestone in polio eradication developed by global polio eradication initiative. The initiative would still benefit from adopting some of the best practices in governance from other organizations in the global health sector.


Idiosyncratic Drug Induced Liver Injury in African-Americans Is Associated With Greater Morbidity and Mortality Compared to Caucasians.
Idiosyncratic drug induced liver injury (DILI) is a rare but potentially serious liver disorder and a major cause of significant liver injury. Limited data exist on racial differences in DILI incidence, presentation, and course. We compared the causative agents, clinical features, and outcomes of DILI among self-described African-Americans and non-Hispanic whites (Caucasians) enrolled in the DILIN Prospective Study. Individuals with definite, highly likely, or probable DILI enrolled between September 2004 and February 2016 were included in this analysis. 144 African-Americans and 841 Caucasian patients met the eligibility criteria. Causal medications varied by race: trimethoprim/sulfamethoxazole being the most common cause among African-Americans (7.6 vs. 3.6%) followed by methyldopa (4 vs. <1%), phenytoin (5 vs. <1%), isoniazid (4 vs. 4%), and amoxicillin/clavulanate (4.1 vs. 13.4%). The severity of illness, however, tended to be greater in African-Americans than Caucasians as determined by peak mean bilirubin (14.3 vs. 12.8 mg/dl), INR (1.9 vs. 1.6), and DILIN severity score (3.0 vs. 2.6). The frequency of severe cutaneous reactions was significantly higher in African-Americans (2.1 vs. 0.36% in Caucasians, P=0.048). African-Americans also had higher rates of hospitalization (76.7 vs. 57.6%, P<0.001), liver transplantation or liver related death by 6 months (10.2 vs. 5.8%, P=0.02 after controlling for selected covariates), and chronic DILI (24 vs. 16%, P=0.06). The most common DILI causative agents differ between African-Americans and Caucasians. African-Americans are more likely to have severe cutaneous reactions and more severe liver injury leading to worse outcomes, including death and liver transplant.


Glycerol tributylate (Triacylglycerol tributanoate) promoted the liver lipid metabolism by cultivating the intestinal flora of grass carp (Ctenopharyngodon idellus).
To investigate the effects of glycerol tributyrin (TB) (Triacylglycerol tributanoate) on the regulation of liver lipid metabolism by intestinal flora of grass carp (Ctenopharyngodon idellus). The compound feed with soybean oil 2.8% + fish oil 1.8%, soybean oil 6.3% + fish oil 1.8%, and soybean oil 6.2% + fish oil 1.8% + TB 0.1% was added to the basal diet as a fat source and fed to the basal (control) group, high lipid (HL) group, and tributyrin (TB) group for 12 weeks. We tested the growth performance, fat content, diversity, and abundance of gut flora and other related indexes of grass carp by Soxhlet extraction, liver tissue enzyme activity, oil red O staining, and 16S rRNA high-throughput sequencing. The results showed that the liver fat number and liver fat content of grass carp in the TB group were lower than those in the HL group, while the fattening degree was significantly higher than those in the other two groups; according to the indices such as Shannon, Ace, and Coverage, it was found that the grass carp in the TB group had the highest abundance and diversity of intestinal microflora; at the portal level, Proteobacteria and Fusobacteria were the main dominant flora in the TB group, with the number of unique OUTs accounting for about 59. 9% of the total number measured; at the genus level, the relative abundance of lipase-producing, short-chain fatty acid-associated bacteria, such as Bacillus-Lactobacillus and Bifidobacterium, was significantly lower (p < 0.05). Thus, we conclude that the addition of TB to high-fat diets can alter the structure of the intestinal microbial community and promote hepatic lipid metabolism in grass carp. TB can alleviate fatty liver in grass carp by increasing the relative abundance of short-chain fatty acids in the intestine. Meanwhile, TB inhibits the conversion of primary bile acids to secondary bile acids in the host, which can block intestinal FXR signaling and the hepatic FXR-SHP pathway, thus slowing down fat synthesis and alleviating the accumulation of liver lipids in grass carp.


Correlation between Cancer Stem Cells and Circulating Tumor Cells and Their Value.
The scientific community has proven the value of circulating tumor cells (CTCs) as a prognostic factor in the development of cancer and progress to metastases [1, 2, 3, 4]. Simultaneously, a new type of cancer stem cell-like (CSC-like) cells has also been established as a progenitor of metastases and relapses in cancer patients [5, 6]. The present research attempts to support the hypothesis that CTCs have all the cellular hallmarks of CSC-like cells which play a crucial role in cancer spreading. TWO METHODS HAVE BEEN CHOSEN: a cellular-based and a molecular-based method. The first method is based on the fact that CSCs form microspheres in culture. In the second method, microspheres develop in the presence of specific markers that define the CSC phenotype [6]. In cellular-based assays, it has been shown that microspheres form in semi-suspension in a culture flask. In the second panel of the test, Nanog was chosen as a marker and the tested sample was positive when grown under specific conditions. Our analysis has demonstrated that in this particular case, CSCs-like cells are included in the vast majority of CTCs.


Chemokine-related gene expression in the brain following ischemic stroke: no role for CXCR2 in outcome.
This study sought to identify potential targets for acute stroke therapy that can be exploited pharmacologically beyond the current 4.5h time limit for clinical administration of recombinant tissue-plasminogen activator. We used PCR arrays to initially screen the temporal expression profiles of several chemokine-related genes in the brain at 4, 24 and 72h after stroke. We identified large increases (>10-fold) in mRNA at 24 or 72h for the neutrophil CXCR2 receptor, and for CXCL1 and CXCL2-two chemokine ligands expressed by monocytes and neutrophils with strong neutrophil chemoattractant activity via CXCR2. We then tested the efficacy of a CXCR2 antagonist as a therapeutic. Mice were treated with vehicle (1% DMSO) or SB225002 (2mg/kg per day, ip) commencing at reperfusion, and we evaluated chemokine gene expression, neutrophil infiltration and functional and histological endpoints of stroke outcome. Expression levels of CXCL1, CXCL2 and CXCR2 after 24h were markedly reduced to near normal levels in SB225002-treated mice. Myeloperoxidase-positive cell infiltration was significantly reduced in SB225002-treated mice compared with vehicle-treated mice, and was similar to levels in sham-operated mice. However, although SB225002 evidently antagonised the interaction between CXCR2 and its chemokine ligands in the ischemic brain, mice treated with either SB225002 or vehicle had similar motor impairment and infarct volume at 72h. Thus, the reduced expression of CXC chemokine subfamily genes and neutrophil-related infiltration following SB225002 administration did not improve outcome after cerebral ischemia-reperfusion. CXCR2 antagonists are therefore unlikely to be a potential therapy for ischemic stroke.


Kikuchi's lymphadenitis and carcinoma of the stomach.
A 37 year old male with a poorly differentiated carcinoma of the stomach presented with cervical lymphadenopathy. It was clinically thought to be a metastatic carcinoma, but on biopsy, it exhibited features of Kikuchi's lymphadenitis. Distinguishing the signet ring histiocytes seen in Kikuchi's disease from signet ring carcinoma cells can be a diagnostic problem. To our knowledge this is the first reported case of an association of Kikuchi's disease and carcinoma.


Basic calcium phosphate crystals stimulate the endocytotic activity of cells--inhibition by anti-calcification agents.
Pathological calcifications are associated with many medical conditions including diabetes, breast cancer, and crystals-associated osteoarthritis. The deposition of calcium-containing crystals on cells induces detrimental cellular effects and speeds up the progression of associated diseases. We carried out the present study to test the hypotheses that calcium-containing crystals may stimulate the influx of other molecules existing in the extracellular fluid disturbing normal molecular signaling and that anti-calcification agent will inhibit such endocytotic process. We found that basic calcium phosphate (BCP) crystals greatly stimulated the endocytotic activity of cells by rendering the cells more permeable and that the anti-calcification agent phosphocitrate and several others inhibited the crystals-mediated endocytosis. This is the first study reporting that the endocytotic activity of cells is affected by BCP crystals and that such endocytotic activity can be inhibited by anti-calcification agents. Since calcium-containing crystals are associated with many human diseases and in many circumstances are associated with apoptotic bodies, extracellular and matrix vesicles where DNA fragments, small peptides, and minerals are released into extracellular space, the findings reported here are important for our understanding of the complex biological effects and the potential pathological role of calcium-containing crystals in crystals-associated diseases, and for the development of disease modifying agents as well.


Hematopoietic stem/progenitor involvement in retinal microvascular repair during diabetes: Implications for bone marrow rejuvenation.
The widespread nature of diabetes affects all organ systems of an individual including the bone marrow. Long-term damage to the cellular and extracellular components of the bone marrow leads to a rapid decline in the bone marrow-hematopoietic stem/progenitor cells (HS/PCs) compartment. This review will highlight the importance of bone marrow microenvironment in maintaining bone marrow HS/PC populations and the contribution of these key populations in microvascular repair during the natural history of diabetes. The autonomic nervous system can initiate and propagate bone marrow dysfunction in diabetes. Systemic pharmacological strategies designed to protect the bone marrow-HS/PC population from diabetes induced-oxidative stress and advanced glycation end product accumulation represent a new approach to target diabetic retinopathy progression. Protecting HS/PCs ensures their participation in vascular repair and reduces the risk of vasogdegeneration occurring in the retina.


An in vitro systematic spectroscopic examination of the photostabilities of a random set of commercial sunscreen lotions and their chemical UVB/UVA active agents.
The photostabilities of a random set of commercially available sunscreen lotions and their active ingredients are examined spectroscopically subsequent to simulated sunlight UV exposure. Loss of filtering efficacy can occur because of possible photochemical modifications of the sunscreen active agents. Changes in absorption of UVA/ UVB sunlight by agents in sunscreen lotions also leads to a reduction of the expected photoprotection of human skin and DNA against the harmful UV radiation. The active ingredients were investigated in aqueous media and in organic solvents of various polarities (methanol, acetonitrile, and n-hexane) under aerobic and anaerobic conditions The UV absorption features are affected by the nature of the solvents with properties closely related to oil-in-water (o/w) or water-in-oil (w/o) emulsions actually used in sunscreen formulations, and by the presence of molecular oxygen. The photostabilities of two combined chemical ingredients (oxybenzone and octyl methoxycinnamate) and the combination oxybenzone/titanium dioxide were also explored. In the latter case, oxybenzone undergoes significant photodegradation in the presence of the physical filter TiO2.