Effects of Wearing a Jaw-repositioning Intra-oral Device in Synchronized Swimming Athletes.
The effects of wearing an intra-oral device on several ventilatory and fatigue markers have been reported for a variety of sports. The quality of the figures performed in synchronized swimming is directly affected by fatigue, and can be monitored during training sessions (TS). The aim of the study was to investigate the acute effects of wearing customized intra-oral devices on heart rate variability, rating of perceived exertion, blood lactate accumulation, and salivary cortisol production during a competitive training session. Twelve highly trained elite female athletes (age: 21.0±3.6 years) participated in the study. Fatigue markers were assessed at the beginning and at the end of the 3rd and 5th afternoon TS for that week, once with and once without an intra-oral device, in random order. Salivary cortisol levels were higher in relation to the baseline in the intra-oral device condition (P<0.05) but not in athletes without an intra-oral device. No differences between conditions were found in rating of perceived exertion (P=0.465) and blood lactate (P=0.711). No time or condition interactions or main effects were shown for heart rate variability. Thus, there is no evidence that wearing a low-arch intra-oral device is a good recommendation for high-standard athletes performing long and stressful routines.


Neuroprotective attributes of L-theanine, a bioactive amino acid of tea, and its potential role in Parkinson's disease therapeutics.
Meta-analyses of tea consumption and reduced risk of Parkinson's disease have thrown light in the pathway of exploring beneficial properties of tea components. On the basis of dry mass, a typical black or green tea beverage contains approximately 6% of free amino acids, which impart high quality, taste and distinctive aroma to the tea infusion. L-theanine (chemically known as γ-glutamylethylamide) is a non-proteinogenic amino acid of tea that takes part in the biosynthesis of its polyphenols. Recently discovered neuroprotective effects of L-theanine can be attributed to its structural analogy with glutamate, the principal excitatory neurotransmitter in brain. This unique amino acid also bears a potential to ameliorate the pathophysiological changes associated with Parkinson's disease as it displays antioxidant and anti-inflammatory properties, improves motor behavioral abnormalities, increases dopamine availability and may cause a favorable downshift in neurodegeneration due to glutamate excitotoxicity. To gain an explicit understanding of the role of L-theanine, this review article is the first one to focus on its mechanism of neuromodulatory action and to critically evaluate the possibilities of employing this bioactive amide in the forage of anti-Parkinsonian medication. We also hypothesize the idea of L-theanine being a potent natural agent against L-DOPA induced dyskinesia, since long-term reliance on dopamine replacement therapy is linked with elevation in glutamate receptor activity.


Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.
Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care.


[Prolactin producing hypophyseal adenoma: diagnosis and therapeutic possibilities].
The introduction of radioimmunoassay for prolactin concentrated interest in infertility research on prolactin-producing pituitary adenomas (prolactinomas). In women in the fertile age group these tumors cause amenorrhea and galactorrhea, and in men loss of libido, impotence and occasionally gynecomastia. Microprolactinomas (diameter 10 mm and less) and macroprolactinomas (diameter more than 10 mm) differ in growth characteristics, symptomatology and prognosis. Different therapeutic approaches may be used. Both bromocriptine treatment and selective microsurgical tumor extirpation are successful. Both have advantages and disadvantages, thus rendering the decision as to appropriate treatment increasingly difficult. Recent findings demonstrate that bromocriptine may cause irreversible tumor fibrosis, which decreases the chances of prolactin normalization by subsequent surgery.


[Coronary bypass surgery in octogenarians].
The age of the patients referred for coronary bypass surgery is getting older progressively. Early and late postoperative outcome of octogenarians were evaluated and compared with younger age group in this study. Records of 55 patients aged 80 years or older (mean age 82.7 +/- 2.8) among 3834 patients, who had coronary bypass graft procedure, operated between 1995 and 2001 were reviewed retrospectively. There were 39 men (70.9%) and 16 women (29.1%). Three patients had aortic valve replacement, 1 had left ventricular aneurysm repair, 1 had carotid endarterectomy additionally. Atrial fibrillation (21.8%), renal dysfunction (16.4%), and prolonged ventilation (10.9%) were the prominent complications. The hospital mortality rate was 7.27% (4 patients). Kaplan Meier Survival Analysis estimated that at the end of 5 years 83.1 + 5.2% of patients were still alive. Coronary bypass operations can be performed in octogenarians with slightly increased but acceptable hospital mortality and longer hospital stay. Early intervention and individual modifications in cardiopulmonary bypass techniques may improve the results in this patient population.


Sharpening bounds on principal effects with covariates.
Estimation of treatment effects in randomized studies is often hampered by possible selection bias induced by conditioning on or adjusting for a variable measured post-randomization. One approach to obviate such selection bias is to consider inference about treatment effects within principal strata, that is, principal effects. A challenge with this approach is that without strong assumptions principal effects are not identifiable from the observable data. In settings where such assumptions are dubious, identifiable large sample bounds may be the preferred target of inference. In practice these bounds may be wide and not particularly informative. In this work we consider whether bounds on principal effects can be improved by adjusting for a categorical baseline covariate. Adjusted bounds are considered which are shown to never be wider than the unadjusted bounds. Necessary and sufficient conditions are given for which the adjusted bounds will be sharper (i.e., narrower) than the unadjusted bounds. The methods are illustrated using data from a recent, large study of interventions to prevent mother-to-child transmission of HIV through breastfeeding. Using a baseline covariate indicating low birth weight, the estimated adjusted bounds for the principal effect of interest are 63% narrower than the estimated unadjusted bounds.


Hygiene of housing conditions and proinflammatory signals alter gene expressions in porcine adipose tissues and blood cells.
Adipose tissue is an organ with metabolic, endocrine and immune functions. In this tissue, the expressions of genes associated with several metabolic pathways, including lipid metabolism, have been shown to be affected by genetic selection for feed efficiency, an important trait to consider in livestock. We hypothesized that the stimulation of immune system caused by poor hygiene conditions of housing impacts the molecular and cellular features of adipose tissue and that the impact may differ between pigs that diverge in feed efficiency. At the age of 12 weeks, Large White pigs from two genetic lines divergent for residual feed intake (RFI) were housed in two contrasting hygiene conditions (good vs poor). After six weeks of exposure, pigs were slaughtered (n = 36). Samples of blood, subcutaneous (SCAT) and perirenal (PRAT) adipose tissues were collected for cell response and gene expression investigations. The decrease in the relative weight of PRAT was associated with a decline in mRNA levels of FASN, ME, LCN2 and TLR4 (P < 0.05) in pigs housed in poor conditions compared with pigs housed in good conditions for both RFI lines. In SCAT, the expressions of only two key genes (PPARG and TLR4) were significantly affected by the hygiene of housing conditions. Besides, the mRNA levels of both LCN2 and GPX3 were influenced by the RFI line (P < 0.05). Because we suspected an effect of poor hygiene at the cellular levels, we investigated the differentiation of stromal vascular cells isolated from SCAT in vitro in the absence or presence of a pro-inflammatory cytokine, Tumor Necrosis Factor-α (TNF-α). The ability of these cells to differentiate in the absence or presence of TNF-α did not differ among the four groups of animals (P > 0.05). We also investigated the expressions of genes involved in the immune response and lipid metabolism in whole blood cells cultured in the absence and presence of LPS. The hygiene conditions had no effect but, the relative expression of the GPX3 gene was higher (P < 0.001) in high RFI than in low RFI pigs while the expressions of IL-10 (P = 0.027), TGFβ1 (P = 0.023) and ADIPOR2 (P = 0.05) genes were lower in high RFI than in low RFI pigs. Overall, the current study indicates that the hygiene of housing had similar effects on both RFI lines on the expression of genes in adipose tissues and on the features of SCAT adipose cells and whole blood cells in response to TNF-α and LPS. It further demonstrates that the number of genes with expression impacted by housing conditions was higher in PRAT than in SCAT. It suggests a depot-specific response of adipose tissue to the current challenge.


Dietary soy protein and isoflavones: minimal beneficial effects on bone and no effect on the reproductive tract of sexually mature ovariectomized Sprague-Dawley rats.
The present study was conducted to determine the effects of dietary soy protein and isoflavones on bone and the reproductive tract in the absence of the ovary. Three-month-old Sprague-Dawley rats (n = 56) were either sham-operated or ovariectomized and then fed diets containing casein or soy protein +/- isoflavone extract for 12 weeks. The amounts of casein, soy protein, and extract (per kg diet) in each group were as follows: (1) Ovariectomy, 200 g of casein; (2) Ovariectomy+low soy, 100 g of casein + 100 g of soy protein; (3) Ovariectomy+high soy, 200 g of soy protein; (4) Ovariectomy+low extract, 200 g of casein + 17.2 g of extract; (5) Ovariectomy+high extract, 200 g of casein + 34.4 g of extract; (6) Ovary intact, 200 g of casein; (7) Ovariectomy+estradiol-17beta, 200 g of casein. Diet consumption, body weight, uterine weight, urine deoxypyridinoline, and bone mineral density of the femur and lumbar vertebrae were measured. The femur rigidity was evaluated by histomorphometry. The reproductive tract (uterus, vagina, and cervix) was studied histologically. The Ovariectomy group showed significant increases in body weight, diet consumption, and deoxypyridinoline, decreases in uterine weight and bone mineral density, and negative changes in histomorphometry compared with the Ovary intact group. Neither soy protein nor extract diets abrogated these alterations, except for the Ovariectomy+high extract group that showed statistically significant positive changes in histomorphometric parameters. There were no histological differences in the reproductive tract among Ovariectomy, Ovariectomy+soy, and Ovariectomy+extract groups. The estradiol-17beta replacement abrogated ovariectomy-induced alterations. Dietary intake of isoflavones by sexually mature ovariectomized rats has a minimal beneficial effect on bone with no effect on the reproductive tract.


Epidemiological profile of patients on renal replacement therapy in Brazil, 2000-2004.
To describe the clinical and epidemiological profile of patients under renal replacement therapies, identifying risk factors for death. This is a non-concurrent cohort study of data for 90,356 patients in the National Renal Replacement Therapies Database. A deterministic-probabilistic linkage was performed using the Authorization System for High Complexity/Cost Procedures and the Mortality Information System databases. All patients who started dialysis between 1/1/2000 and 12/31/2004 were included and followed until death or the end of 2004. Age, sex, region of residence, primary renal disease and causes of death were analyzed. A proportional hazards model was used to identify factors associated with risk of death. The prevalence of patients under renal replacement therapies increased an average of 5.5%, while incidence remained stable during the period. Hemodialysis was the predominant initial modality (89%). The patients were majority male with mean age 53 years, residents of the Southeast region and presented unknown causes as the main cause of chronic renal disease, followed by hypertension, diabetes and glomerulonephritis. Of these patients, 42% progressed to death and 7% underwent kidney transplantation. The patients on peritoneal dialysis were older and had higher prevalence of diabetes. The death rate varied from 7% among transplanted patients to 45% among non-transplanted patients. In the final Cox proportional hazards model, the risk of mortality was associated with increasing age, female sex, having diabetes, living in the North and Northeast region, peritoneal dialysis as a first modality and not having renal transplantation. There was an increased prevalence of patients on renal therapy in Brazil. Increased risk of death was associated with advanced age, diabetes, the female sex, residents of the North and Northeast region and lack of renal transplant.


Host genetics in immune-mediated hepatitis C virus clearance.
Upon infection with hepatitis C virus (HCV), only few patients spontaneously clear the virus, while most patients develop chronic HCV infection. The host innate and adaptive immune response is believed to be the key determinant of viral clearance or persistence. Several host factors have been demonstrated to influence the efficiency of the antiviral immune response, including IL-28B polymorphisms, inhibitory natural killer cell receptors, as well as HLA class I and II alleles presenting viral antigens to CD8(+) and CD4(+) T cells. The understanding of the respective mechanisms is essential for the development of successful vaccination strategies against HCV.


The abrogation of condensin function provides independent evidence for defining the self-renewing population of pluripotent stem cells.
Heterogeneity of planarian stem cells has been categorised on the basis of single cell expression analyses and subsequent experiments to demonstrate lineage relationships. Some data suggest that despite heterogeneity in gene expression amongst cells in the cell cycle, in fact only one sub-population, known as sigma neoblasts, can self-renew. Without the tools to perform live in vivo lineage analysis, we instead took an alternative approach to provide independent evidence for defining the self-renewing stem cell population. We exploited the role of highly conserved condensin family genes to functionally assay neoblast self-renewal properties. Condensins are involved in forming properly condensed chromosomes to allow cell division to proceed during mitosis, and their abrogation inhibits mitosis and can lead to repeated endoreplication of the genome in cells that make repeated attempts to divide. We find that planarians possess only the condensin I complex, and that this is required for normal stem cell function. Abrogation of condensin function led to rapid stem cell depletion accompanied by the appearance of 'giant' cells with increased DNA content. Using previously discovered markers of heterogeneity we show that enlarged cells are always from the sigma-class of the neoblast population and we never observe evidence for endoreplication for the other neoblast subclasses. Overall, our data establish that condensins are essential for stem cell maintenance and provide independent evidence that only sigma-neoblasts are capable of multiple rounds of cell division and hence self-renewal.


Inhibition of phenylamide hydrolysis by Bacillus sphaericus with methylcarbamate and organophosphorus insecticides.
The degradation of the phenylamide herbicides monolinuron, linuron, and solan by cultures of Bacillus sphaericus ATCC 12123 was inhibited by the methylcarbamate insecticides metmercapturon, aldicarb, propoxur, and carbaryl and by the organophosphorus insecticides fenthion and parathion. The extent of inhibition was largest with metmercapturon and smallest with parathion inhibition of hydrolysis of the two phenylurea herbicides was greater than of the acylanilide compound. Tests with crude enzyme preparations of aryl acylamidase derived from B. sphaericus showed that the inhibition of the hydrolysis of linuron with methylcarbamates is a competitive one. The insecticides tested did induce the enzyme, nor could they serve as its substrate.


Analysis of the gap in PCR monitoring availability for patients with chronic myeloid leukemia in 60 low- and middle-income countries.
To estimate the resource gap in the polymerase chain reaction (PCR) monitoring for patients with chronic myeloid leukemia (CML) in low- and middle-income countries (LMICs). We developed a model of demand and supply of PCR monitoring of CML patients in 60 LMICs. PCR testing was assumed to use Cepheid's GeneXpert® IV system. We included costs of GeneXpert® instruments, uninterrupted power supplies, warranties, calibration kits, test cartridges, and shipping. We calculated the country-specific monetary gap in PCR monitoring, stratified by country priority defined as the availability of tyrosine kinase inhibitors (TKIs) through The Max Foundation initiatives. The 5-year gap in PCR monitoring was $29.1 million across all countries, 22% ($6.4 million) in countries with all five TKIs available, 20% ($5.7 million) in countries with four TKIs available, 50% ($14.5 million) in countries with three TKIs available, 8% ($2.2 million) in countries with two TKIs available, and 1% ($0.3 million) in countries with one TKI available. The gap was highest in South Asia (52%; $15.1 million) and lowest in Latin America (6%; $1.9 million). Excluding labor costs, the bulk of the resource needs (86%; $25.2 million) were for procurement of BCR-ABL cartridges. Removing the 5-year gap in PCR monitoring capacity for CML in LMICs will require the mobilization of significant resources and will likely lead to better treatment outcomes and reduced treatment costs through optimization of treatment, discontinuation of therapy in appropriate patients, and facilitation of clinical research. Development of streamlined monitoring guidelines for resource-limited countries should be considered.


Irregular recurrence of large earthquakes along the san andreas fault: evidence from trees.
Old trees growing along the San Andreas fault near Wrightwood, California, record in their annual ring-width patterns the effects of a major earthquake in the fall or winter of 1812 to 1813. Paleoseismic data and historical information indicate that this event was the "San Juan Capistrano" earthquake of 8 December 1812, with a magnitude of 7.5. The discovery that at least 12 kilometers of the Mojave segment of the San Andreas fault ruptured in 1812, only 44 years before the great January 1857 rupture, demonstrates that intervals between large earthquakes on this part of the fault are highly variable. This variability increases the uncertainty of forecasting destructive earthquakes on the basis of past behavior and accentuates the need for a more fundamental knowledge of San Andreas fault dynamics.


Sensitizing mothers of children with microcephaly in promoting the health of their children.
To report the educational experiences of mothers or caregivers of children with microcephaly, as developed by an academic team with the theme of promoting these children's health. This is an experience report by undergraduate nursing students and Health and Environment Post-Graduation students and professors of Tiradentes University on educational interventions carried out in three reference units for the care of children with microcephaly in the state of Sergipe. The study sample was taken by convenience. A total of 70 mothers or primary caregivers of children with a confirmed diagnosis of microcephaly during the months of September to December participated in the study. The thematic-theoretical axes selected to describe the activities were promotion of healthy eating, importance of the mother and child bond, and early stimulation of children with microcephaly. The experience reported demonstrates the importance of educational strategies in promoting the health of children with microcephaly, providing additional training to mothers/caregivers to provide holistic and humanized care to these children.


Neighborhood Racial Diversity, Socioeconomic Status, and Perceptions of HIV-Related Discrimination and Internalized HIV Stigma Among Women Living with HIV in the United States.
Relationships that traverse sociodemographic categories may improve community attitudes toward marginalized groups and potentially protect members of those groups from stigma and discrimination. The present study evaluated whether internalized HIV stigma and perceived HIV-related discrimination in health care settings differ based on individual- and neighborhood-level characteristics of women living with HIV (WLHIV). We also sought to extend previous conceptual and empirical work to explore whether perceived HIV-related discrimination mediated the association between neighborhood racial diversity and internalized HIV stigma. A total of 1256 WLHIV in the Women's Interagency HIV Study (WIHS) attending 10 sites in metropolitan areas across the United States completed measures of internalized HIV stigma and perceived HIV-related discrimination in health care settings. Participants also provided residential information that was geocoded into Federal Information Processing Standard (FIPS) codes and linked with census-tract level indicators. In cross-sectional analyses, greater neighborhood racial diversity was associated with less internalized HIV stigma and less perceived HIV-related discrimination regardless of individual race. Neighborhood median income was positively associated with internalized HIV stigma and perceived discrimination, while individual income was negatively associated with perceptions of stigma and discrimination. In an exploratory mediation analysis, neighborhood racial diversity had a significant indirect effect on internalized HIV stigma through perceived HIV-related discrimination. An indirect effect between neighborhood income and internalized stigma was not supported. These findings suggest that greater neighborhood racial diversity may lessen HIV stigma processes at the individual level and that HIV stigma-reduction interventions may be most needed in communities that lack racial diversity.


Use of streptavidin bound to biotinylated DNA structures as model substrates for analysis of nucleoprotein complex disruption by helicases.
Helicases are a subfamily of translocases that couple the directional translocation along a nucleic acid lattice to the separation of nucleic acid duplexes using the energy derived from nucleoside triphosphate hydrolysis. These enzymes perform essential functions in all aspects of nucleic acid metabolism by unwinding and remodelling DNA or RNA in DNA replication, repair, recombination, transcription and translation. Most classical biochemical studies assay the ability of these enzymes to separate naked nucleic acids. However, many different types of proteins form non-covalent interactions with nucleic acids in vivo and so the true substrates of helicases are protein-nucleic acid complexes rather than naked DNA and RNA. Studies over the last decade have revealed that bound proteins can have substantial inhibitory effects on the ability of helicases to unwind nucleic acids. Any analysis of helicase mechanisms in vitro must therefore consider helicase function within the context of nucleoprotein substrates rather than just DNA or RNA. Here we discuss how to analyse the impact of bound proteins on the ability of helicases to unwind DNA substrates in vitro.


Proteomic changes during experimental de- and remyelination in the corpus callosum.
In the cuprizone model of multiple sclerosis, de- and remyelination can be studied without major interference from the adaptive immune responses. Since previous proteomic studies did not focus on the corpus callosum, where cuprizone causes the most pronounced demyelination, we performed a bottom up proteomic analysis on this brain region. Eight week-old mice treated with 0.2% cuprizone, for 4 weeks and controls (C) were sacrificed after termination of the treatment (4wD), and 2 (2dR) or 14 (2wR) days later. Homogenates of dissected corpus callosum were analysed by quantitative proteomics. For data processing, clustering, gene ontology analysis, and regulatory network prediction, we used Perseus, PANTHER and Ingenuity Pathway Analysis softwares, respectively. We identified 4886 unmodified, single- or multi phosphorylated and/or gycosylated (PTM) proteins. Out of them, 191 proteins were differentially regulated in at least one experimental group. We found 57 proteins specific for demyelination, 27 for early- and 57 for late remyelinationwhile 36 proteins were affected in two, and 23 proteins in all three groups. Phosphorylation represented 92% of the post translational modifications among differentially regulated modified (PTM) proteins with decreased level, while it was only 30% of the PTM proteins with increased level. Gene ontology analysis could not classify the demyelination specific proteins into any biological process category, while allocated the remyelination specific ones to nervous system development and myelination as the most specific subcategory. We also identified a protein network in experimental remyelination, and the gene orthologues of the network were differentially expressed in remyelinating multiple sclerosis brain lesions consistent with an early remyelination pattern. Proteomic analysis seems more informative for remyelination than demyelination in the cuprizone model.


Grr1-dependent inactivation of Mth1 mediates glucose-induced dissociation of Rgt1 from HXT gene promoters.
In budding yeast, HXT genes encoding hexose permeases are induced by glucose via a mechanism in which the F box protein Grr1 antagonizes activity of the transcriptional repressor Rgt1. Neither the mechanism of Rgt1 inactivation nor the role of Grr1 in that process has been understood. We show that glucose promotes phosphorylation of Rgt1 and its dissociation from HXT gene promoters. This cascade of events is dependent upon the F-box protein Grr1. Inactivation of Rgt1 is sufficient to explain the requirement for Grr1 but does not involve Rgt1 proteolysis or ubiquitination. We show that inactivation of Mth1 and Std1, known negative regulators of HXT gene expression, leads to the hyperphosphorylation of Rgt1 and its dissociation from HXT promoters even in the absence of glucose. Furthermore, inactivation of Mth1 and Std1 bypasses the requirement for Grr1 for induction of these events, suggesting they are targets for inactivation by Grr1. Consistent with that proposal, Mth1 is rapidly eliminated in response to glucose via a mechanism that requires Grr1. Based upon these data, we propose that glucose acts via Grr1 to promote the degradation of Mth1. Degradation of Mth1 leads to phosphorylation and dissociation of Rgt1 from HXT promoters, thereby activating HXT gene expression.


MRI measurements of carotid plaque in the atherosclerosis risk in communities (ARIC) study: methods, reliability and descriptive statistics.
To measure carotid plaque components using MRI and estimate reliability in the population-based Atherosclerosis Risk in Communities (ARIC) study. Contrast-enhanced high-resolution (0.51 x 0.58 x 2 mm(3)) MRI images were acquired through internal (ICA) and common carotid arteries (CCA) of 2066 ARIC participants at four sites. Sixty-one exams were repeated and 164 pairs had repeated interpretations. Plaque component thicknesses, areas and volumes over eight slices (1.6-cm segment) were measured. Intraplaque hemorrhage was recorded. Reliability was evaluated by intraclass correlations and kappa statistics. There were 1769 successful MRI exams (mean age 71 years; 57% females; 81% white; 19% African-Americans). Repeat scan reliability was highest for CCA lumen area (0.94) and maximum wall thickness (0.89), ICA lumen area (0.89) and maximum wall thickness (0.77) and total wall volume (0.79), and lowest for small structures-core volume (0.30) and mean cap thickness (0.38). Overall reliability was primarily related to reader variability rather than scan acquisition. K's for presence of core, calcification and hemorrhage were fair to good. White men had the thickest plaques (average maximum ICA wall thickness = 2.3 mm) and the most cores (34%). The most important limiting factor for MRI measurements of plaque components is reader variability. Measurement error depends largely on the analyzed structure's size.


Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with Aspergillus fumigatus Virulence.
Previous work has shown that environmental and clinical isolates of Aspergillus fumigatus represent a diverse population that occupies a variety of niches, has extensive genetic diversity, and exhibits virulence heterogeneity in a number of animal models of invasive pulmonary aspergillosis (IPA). However, mechanisms explaining differences in virulence among A. fumigatus isolates remain enigmatic. Here, we report a significant difference in virulence of two common lab strains, CEA10 and AF293, in the murine triamcinolone immunosuppression model of IPA, in which we previously identified severe low oxygen microenvironments surrounding fungal lesions. Therefore, we hypothesize that the ability to thrive within these lesions of low oxygen promotes virulence of A. fumigatus in this model. To test this hypothesis, we performed in vitro fitness and in vivo virulence analyses in the triamcinolone murine model of IPA with 14 environmental and clinical isolates of A. fumigatus Among these isolates, we observed a strong correlation between fitness in low oxygen in vitro and virulence. In further support of our hypothesis, experimental evolution of AF293, a strain that exhibits reduced fitness in low oxygen and reduced virulence in the triamcinolone model of IPA, results in a strain (EVOL20) that has increased hypoxia fitness and a corresponding increase in virulence. Thus, the ability to thrive in low oxygen correlates with virulence of A. fumigatus isolates in the context of steroid-mediated murine immunosuppression. Aspergillus fumigatus occupies multiple environmental niches, likely contributing to the genotypic and phenotypic heterogeneity among isolates. Despite reports of virulence heterogeneity, pathogenesis studies often utilize a single strain for the identification and characterization of virulence and immunity factors. Here, we describe significant variation between A. fumigatus isolates in hypoxia fitness and virulence, highlighting the advantage of including multiple strains in future studies. We also illustrate that hypoxia fitness correlates strongly with increased virulence exclusively in the nonleukopenic murine triamcinolone immunosuppression model of IPA. Through an experimental evolution experiment, we observe that chronic hypoxia exposure results in increased virulence of A. fumigatus We describe here the first observation of a model-specific virulence phenotype correlative with in vitro fitness in hypoxia and pave the way for identification of hypoxia-mediated mechanisms of virulence in the fungal pathogen A. fumigatus.


MicroRNA: novel modulators of the cholinergic anti-inflammatory pathway.
MicroRNAs (miRNAs) have emerged as key gene regulators controlling the expression of many target mRNAs. The nervous system harbors highest number of miRNAs expressed in a spatially and temporally controlled manner. Neural miRNAs have been accredited with diverse roles like regulation of neural differentiation, synaptogenesis, inflammation, memory and cognition. Their aberrant expression and/or function has been linked to various neurodegenerative, neuroinflammatory and stress related disorders. Recent evidence indicates that miRNAs are essential to the fine tuning of the immune responses. Besides controlling the maturation, proliferation and differentiation of myeloid and lymphoid lineages they participate directly by modulating the signaling pathways through the Toll-like receptors and thus the cytokine response. The miRNAs commuting between the nervous and immune systems and affecting the neuro-immune dialogue are emerging.


Estimation of the half-life of a secretory protein message.
Synthesis of a specific secretory protein was followed in the presence of actinomycin D and cordycepin (3'-deoxyadenosine). The apparent half-life of the messenger RNA for this protein is significantly longer in the presence of actinomycin D than in the presence of cordycepin. These results suggest that actinomycin D studies of half-life in specialized cells may be inaccurate.


The comparability of the universalism value over time and across countries in the European Social Survey: exact vs. approximate measurement invariance.
Over the last decades, large international datasets such as the European Social Survey (ESS), the European Value Study (EVS) and the World Value Survey (WVS) have been collected to compare value means over multiple time points and across many countries. Yet analyzing comparative survey data requires the fulfillment of specific assumptions, i.e., that these values are comparable over time and across countries. Given the large number of groups that can be compared in repeated cross-national datasets, establishing measurement invariance has been, however, considered unrealistic. Indeed, studies which did assess it often failed to establish higher levels of invariance such as scalar invariance. In this paper we first introduce the newly developed approximate approach based on Bayesian structural equation modeling (BSEM) to assess cross-group invariance over countries and time points and contrast the findings with the results from the traditional exact measurement invariance test. BSEM examines whether measurement parameters are approximately (rather than exactly) invariant. We apply BSEM to a subset of items measuring the universalism value from the Portrait Values Questionnaire (PVQ) in the ESS. The invariance of this value is tested simultaneously across 15 ESS countries over six ESS rounds with 173,071 respondents and 90 groups in total. Whereas, the use of the traditional approach only legitimates the comparison of latent means of 37 groups, the Bayesian procedure allows the latent mean comparison of 73 groups. Thus, our empirical application demonstrates for the first time the BSEM test procedure on a particularly large set of groups.


Soft tissue Ilizarov correction of congenital talipes equinovarus--5 to 10 years postsurgery.
The aim of this study was to address concerns regarding maintenance of correction of foot deformity after soft tissue Ilizarov distraction in relapsed clubfeet. We retrospectively reviewed the results of Ilizarov surgery of 19 rigid clubfeet in 14 children. The postoperative follow-up was at least 5 years (range, 5-10 years). All patients were assessed using the International Clubfoot Study Group score. This is a comprehensive scoring system published in 2003, incorporating morphological, functional, and radiological assessments. Patient and parent satisfaction was also assessed. Using the International Clubfoot Study Group score, 14 of the 19 feet managed by the Ilizarov soft tissue distraction technique were graded good or excellent. Only 1 patient experienced recurrence of the deformity. Subjectively, 13 of the 14 children in the study were satisfied with the result of the treatment. The study confirms that the short-term good results reported previously are maintained at least 5 years after the operation. There are no other similar studies with a minimum 5-year follow-up.


In vitro evaluation of proximal carious lesions using digital radiographic systems.
The study aimed to compare the sensitivity and specificity of digital radiographic systems for the diagnosis of proximal carious lesions. Extracted human teeth (3 canines, 3 premolars, and 3 molars) were submitted to one of three types of proximal lesions (demineralized area, cavity affecting the enamel alone, and cavity affecting enamel and dentin). Bitewing radiographs were obtained from each system (Sirona, Kodak, and Schick) and evaluated by 12 raters (4 dental students, 4 radiology specialists, and 4 dentists). The chi-squared test was used to determine the frequency of correct diagnoses among the different systems, raters, teeth, and types of lesion. Sensitivity and specificity regarding demineralized areas were calculated for each system. The frequencies of correct diagnoses were found: Schick (70.8%), Kodak (63.9%), Sirona (59.0%), specialists (69.4%), students (62.5%), dentists (61.8%), premolars (70.1%), canines (65.3%), and molars (58.3%). No significant differences were found among the different systems, raters, or teeth (P > 0.05). Sensitivity and specificity were 0.64 and 0.47 (Schick), 0.56 and 0.50 (Sirona), and 0.48 and 0.58 (Kodak). The most correct diagnoses were achieved using the Schick digital system on premolars and evaluated by specialists in radiology. The systems demonstrated low sensitivity and specificity for the diagnosis of demineralized areas.


[Corneal incision in inverse step (author's transl)].
The author presents a corneal incision similar to that of Charleux, but the "biseau" was replaced by a step. Thus the wound is easier closed by the intraocular pressure because the thin posterior plane is moulded over the irregularities of the superficial plane easier than the short slope of Charleux's incision. As a proof, without reducing the postoperative security, the suture consists only of 3 points -- thus inducing a favourable influence on the cicatrisation --, the knotting force is diminished -- avoiding thus the risk of thread cutting the tissue, and the conjunctival covering is rarely used -- leaving thus the entire draining way of the aqueous humour unaffected. The 80 patients operated on left the hospital in the 4th day (41%), 10th day (50%) or in the 14th-21st day (9%), with satisfactory late results: visual acuity superior to 5/10 (87%) and astigmatism inferior to 1D (89%).


Molecular cloning and expression of a human B-cell growth factor gene in Escherichia coli.
A human B-cell growth factor (BCGF) (12 kilodaltons) supports the clonal proliferation of B lymphocytes. A clone was isolated that contained the proper structural sequence to encode biologically active, 12-kilodalton BCGF in Escherichia coli and to hybridize to a specific messenger RNA, identified by in vitro translation in Xenopus laevis oocytes. A relatively hydrophobic region of 18 amino acids was found at the amino terminal of the 124-amino acid-long polypeptide. The carboxyl terminal is composed of at least 32 amino acids that are derived from nucleotide sequences bearing significant homology to the Alu repeat family.


Use of horseshoe kidneys for transplantation.
Report of a case in which a horseshoe kidney was divided and transplanted into two recipients. The literature on transplantation of horseshoe kidneys is reviewed. This renal anomaly is not a contra-indication to its use for transplantation.


Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women.
To determine the effects of nevirapine (NVP), a nonnucleoside reverse-transcriptase inhibitor of HIV-1 and P450 inducer, on the pharmacokinetics (PK) of ethinyl estradiol (EE)/norethindrone (NET), a widely used oral contraceptive, and to assess the effects of EE/NET on the steady-state PK of NVP. Ten HIV-1-infected women underwent intensive PK sampling after single-dose administration of EE/NET (days 0-1). Oral NVP 200 mg once daily (days 2-15), followed by 200 mg twice daily (days 16-29), was added to background potent antiretroviral therapy. On day 30, intensive PK sampling was performed after concurrent administration of NVP 200 mg and a single dose of EE/NET. Concomitant administration of NVP at steady state with EE/NET resulted in a significant (29%) median reduction in the area under the plasma concentration time curve (AUC(infinity)) and a significant reduction in mean residence time (MRT) and half-life (t(1/2)) of EE. There was a significant (18%) median reduction in the AUC(infinity) for NET that was not associated with a detectable change in NET C(max), MRT, or t(1/2). Oral contraceptives should not be the primary method of birth control in women of child-bearing potential who are treated with NVP.


Orientations of Iron-Sulfur Clusters FA and FB in the Homodimeric Type-I Photosynthetic Reaction Center of Heliobacterium modesticaldum.
Orientations of the FA and FB iron-sulfur (FeS) clusters in a structure-unknown type-I homodimeric heriobacterial reaction center (hRC) were studied in oriented membranes of the thermophilic anaerobic photosynthetic bacterium Heliobacterium modesticaldum by electron paramagnetic resonance (EPR), and compared with those in heterodimeric photosystem I (PS I). The Rieske-type FeS center in the cytochrome b/c complex showed a well-oriented EPR signal. Illumination at 14 K induced an FB(-) signal with g-axes of gz = 2.066, gy = 1.937, and gx = 1.890, tilted at angles of 60°, 60°, and 45°, respectively, with respect to the membrane normal. Chemical reduction with dithionite produced an additional signal of FA(-), which magnetically interacted with FB(-), with gz = 2.046, gy = 1.942, and gx = 1.911 at 30°, 60°, and 90°, respectively. The angles and redox properties of FA(-) and FB(-) in hRC resemble those of FB(-) and FA(-), respectively, in PS I. Therefore, FA and FB in hRC, named after their g-value similarities, seem to be located like FB and FA, not like FA and FB, respectively, in PS I. The reducing side of hRC could resemble those in PS I, if the names of FA and FB are interchanged with each other.


[Isolation of new transforming viruses from "phenotypically transformed" Sirc cells in a medium with a low concentration of serum or calcium ions].
Possibility of rapid generation of highly transforming viruses from rabbit epithelial corneal cells (Sirc) on the basis of SSAV virus is discussed. The results of the study suggested a relationship between the phenomenon of "phenotypic transformation" with expression of cellular genes and a potential transforming activity. Sirc/SSAV phenotypic transformation was induced by cultivating of cells in a medium with low levels of serum or calcium ions. Subsequent infection of mink lung fibroblasts resulted in generation of 2 new transforming SSAV isolates which induced transformation in cellular lines permissive for SSAV replication. The foci of transformation were of various morphological patterns.


Multi-dimensional sensorimotor grounding of concrete and abstract categories.
Semantic categories, and the concepts belonging to them, have commonly been defined by their relative concreteness, that is, their reliance on perception. However, sensorimotor grounding must be regarded as going beyond the basic five senses and incorporate a multi-dimensional variety of perceptual and action experience. We present a series of exploratory analyses examining the sensorimotor grounding of participant-produced member concepts for 117 categories, spanning concrete (e.g. animal and furniture) and highly abstract (e.g. unit of time and science) categories. We found that both concrete and abstract categories are strongly grounded in multi-dimensional sensorimotor experience. Both domains were dominated by vision and, to a lesser extent, head movements, but concrete categories were more grounded in touch and hand-arm action, while abstract categories were more grounded in hearing and interoception. Importantly, this pattern of grounding was not uniform, and subdomains of concrete (e.g. ingestibles, animates, natural categories and artefacts) and abstract (e.g. internal, social and non-social) categories were grounded in different profiles of sensorimotor experience. Overall, these findings suggest that the distinction between abstract and concrete categories is not as clearcut as ontological assumptions might suggest, and that the strength and diversity of sensorimotor grounding in abstract categories must not be underestimated. This article is part of the theme issue 'Concepts in interaction: social engagement and inner experiences'.


[The preparedness of the Italian obstetric surveillance system in the response to the emergency of the SARS-CoV-2 pandemic: methodological aspects of a population-based study].
This paper aims to describe the Italian obstetric surveillance system (ItOSS) preparedness as an element for a timely response to the new Coronavirus pandemic. ItOSS is a surveillance network that has been collecting data on maternal mortality and conducting population studies on obstetric near misses since 2013. At the beginning of the pandemic, ItOSS launched a new population-based project to monitor SARS-CoV-2 infection during pregnancy and post-partum and promptly give back information useful to clinicians and decision-makers. All the regions and autonomous provinces, for a total of 289 birth units (PN), joined the study. Data relating to pregnant or post-partum women with a confirmed SARS-CoV-2 infection diagnosis addressing the maternities for outpatient visits or hospitalization were collected. The project methodology entails that each participating maternity reports the cases to ItOSS uploading data through an open-source platform. The on-line form includes sociodemographic and clinical data and maternal-neonatal outcomes. Biological samples to detect possible vertical transmission are also collected voluntarily. A total of 534 incident cases were reported from February 25th to July 10th 2020; 7 regions also collected biological samples for 227 cases; data collection is still ongoing.A preliminary analysis of the first 146 SARS-CoV-2 positive women who gave birth between February 25th to April 22nd shows an incidence rate of the infection equal to 2.1/1,000 in Italy and 6.9/1,000 in the Lombardy Region (Northern Italy). The brief time needed to setting up and operating the project, the national coverage, the adoption of shared tools for data collection, the quality and completeness of the information collected show how the availability of active networks like ItOSS represents a crucial element to hold a high level of preparedness in case of a health emergency.


Morphologic measurements of anatomic landmarks in pulp chambers of human first molars: a study of bitewing radiographs.
Knowledge of the anatomic location and dimension of the molar pulp chamber may preserve healthy pulp during operative procedure and reduce risk of perforation of chamber during access preparation. A review of literatures regarding the morphology of pulp chamber however revealed very little information; so the aim of this in vivo study was to measure the dimensions of first molar pulp chambers as seen on bitewing (BW) radiographs. In this cross-sectional study molar's BW radiographs of 130 subjects in two age groups were taken under standardized conditions (group of 18-25 years old subjects and group of 50-65 years old subjects). The films were digitized and nine anatomical landmarks were evaluated from the image of each first molar as follow: A; mesial to distal pulp horn distance, B; mesial to distal walls at the middle of pulp chamber, C; mesial to distal orifices, D; mesial cusp tip to its horn, E; distal cusp tip to its horn, F; pulp chamber height, G; pulp chamber floor to furcation, H; pulp chamber ceiling to furcation, I; cusp tips to furcation. The data were evaluated by using AUTOCAD (2007) software with 0.00 precision. Two way ANOVA test (Uni-variant analysis) were used to determine the interaction between restoration and age on pulp chamber dimensions. There was no significant difference in pulp chamber dimensions between the genders. Although there was significant reduction in the size of pulp chamber with advancing age, no significant differences were found in the restored and non restored teeth. The finding of this study showed size reduction and changes of pulp chamber with age so may enhance knowledge to minimize errors during endodontics treatments.


A Bartonella Effector Acts as Signaling Hub for Intrinsic STAT3 Activation to Trigger Anti-inflammatory Responses.
Chronically infecting pathogens avoid clearance by the innate immune system by promoting premature transition from an initial pro-inflammatory response toward an anti-inflammatory tissue-repair response. STAT3, a central regulator of inflammation, controls this transition and thus is targeted by numerous chronic pathogens. Here, we show that BepD, an effector of the chronic bacterial pathogen Bartonella henselae targeted to infected host cells, establishes an exceptional pathway for canonical STAT3 activation, thereby impairing secretion of pro-inflammatory TNF-α and stimulating secretion of anti-inflammatory IL-10. Tyrosine phosphorylation of EPIYA-related motifs in BepD facilitates STAT3 binding and activation via c-Abl-dependent phosphorylation of Y705. The tyrosine-phosphorylated scaffold of BepD thus represents a signaling hub for intrinsic STAT3 activation that is independent from canonical STAT3 activation via transmembrane receptor-associated Janus kinases. We anticipate that our findings on a molecular shortcut to STAT3 activation will inspire new treatment options for chronic infections and inflammatory diseases.


Effect of seminal hyperviscosity on acrosomal integrity and sperm motility before and after cryopreservation.
Semen cryopreservation is a useful tool in assisted reproduction, which may have impact on sperm characteristics during freezing and thawing. The aim of this study was to assess the integrity of the acrosome and motility of cryopreserved and thawed spermatozoos in hyperviscous and no viscous samples. In semen samples spermiogram, glandular markers, acrosome integrity, culture and the levels markers accessory glands were measured. Each aliquot of semen was immersed in cryoprotectant and maintained in a commercial freezer at -196 ° C. After 30 days, these were thawed and in the cell pellet resuspended, spermatic motility and acrosomal integrity were evaluated. In thawed samples, there were significant decreases in progressive motility (p <0.05), vitality (p <0.005) and acrosome integrity (p <0.05) with respect to fresh sperm, this decline was most evident in hyperviscous samples. The viscosity of fresh semen was inversely related to motility and acrosome integrity before and after freezing (p <0.05). Twenty semen samples showed the presence of microorganisms and C. trachomatis IgA antibodies, of which fifteen showed hyperviscosity. Biochemical analysis demonstrated that semen samples with low levels of citric acid had less acrosomal integrity both before and after freezing (p <0.05). The viscoelasticity and citric acid levels are associated with prostate dysfunction, low sperm motility and premature acrosome reaction, which can reduce the fertilizing capacity of sperm. The etiology of hyperviscosity remains complex; however, to preserve motility and acrosome integrity, its causes must be investigated previously in the seminal samples to be subjected to cryopreservation.


Investigation of photobiomodulation potentiality by 635 and 809 nm lasers on human osteoblasts.
Photobiomodulation (PBM) describes light-induced photochemical reactions achieved by the application of red or near infrared lasers/LED light with low energy densities. This noninvasive and painless method has been used in some clinical areas but controversial outcomes demand a skeptical look for its promising and potential effects. In this detailed in vitro study, the osteoblast cells were irradiated with 635 and 809 nm diode lasers at energy densities of 0.5, 1, and 2 J/cm2. Cell viability, proliferation, bone formation, and osteoblast differentiation were evaluated by methylthiazole tetrazolium (MTT) assay, Alamar Blue assay, acridine orange/propidium iodide staining, alkaline phosphatase (ALP) activity, Alizarin red staining, and reverse-transcription polymerase chain reaction (RT-PCR) to test the expression of collagen type I, ALPL, and osteocalcin. The results indicate that studied energy doses have a transient effect (48 h after laser irradiation) on the osteoblast viability and proliferation. Similarly, laser irradiation did not appear to have any effect on ALP activity. These results were confirmed by RT-PCR analysis of osteoblast markers. This study suggests that several irradiation parameters and variations in the methods should be clearly established in the laboratory before laser treatment becomes a postulated application for bone tissue regeneration in clinical level.


A prospective observational study of real-world treatment and outcome in secondary CNS lymphoma.
Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence. Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330). 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23-86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12-27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8-17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25-0·89), p = 0·0197). This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better.


Biological effects of stellar collapse neutrinos
Massive stars in their final stages of collapse radiate most of their binding energy in the form of MeV neutrinos. The recoil atoms that they produce in elastic scattering off nuclei in organic tissue create radiation damage which is highly effective in the production of irreparable DNA harm, leading to cellular mutation, neoplasia, and oncogenesis. Using a conventional model of the galaxy and of the collapse mechanism, the periodicity of nearby stellar collapses and the radiation dose are calculated. The possible contribution of this process to the paleontological record of mass extinctions is examined.


Circulating Sex Hormone Levels and Risk of Esophageal Adenocarcinoma in a Prospective Study in Men.
Sex hormones have been hypothesized to explain the strong male predominance in esophageal adenocarcinoma, but evidence is needed. This study examined how circulating sex hormone levels influence future risk of esophageal adenocarcinoma. This case-control study was nested in a prospective Norwegian cohort (Janus Serum Bank Cohort), including 244 male patients with esophageal adenocarcinoma and 244 male age-matched control participants. Associations between prediagnostic circulating levels of 12 sex hormones and risk of esophageal adenocarcinoma were assessed using conditional logistic regression. In addition, a random-effect meta-analysis combined these data with a similar prospective study for 5 sex hormones. Decreased odds ratios (ORs) of esophageal adenocarcinoma were found comparing the highest with lowest quartiles of testosterone (OR = 0.44, 95% confidence interval [CI] 0.22-0.88), testosterone:estradiol ratio (OR = 0.37, 95% CI 0.19-0.72), and luteinizing hormone (OR = 0.50, 95% CI 0.30-0.98), after adjustment for tobacco smoking and physical activity. These associations were attenuated after further adjustment for body mass index (OR = 0.56, 95% CI 0.27-1.13 for testosterone; OR = 0.46, 95% CI 0.23-0.91 for testosterone:estradiol ratio; OR = 0.55, 95% CI 0.29-1.08 for luteinizing hormone). No associations were observed for sex hormone-binding globulin, dehydroepiandrosterone sulfate, follicle-stimulating hormone, prolactin, 17-OH progesterone, progesterone, androstenedione, or free testosterone index. The meta-analysis showed an inverse association between testosterone levels and risk of esophageal adenocarcinoma (pooled OR for the highest vs lowest quartile = 0.60, 95% CI 0.38-0.97), whereas no associations were identified for androstenedione, sex hormone-binding globulin, estradiol, or testosterone:estradiol ratio. Higher circulating testosterone levels may decrease the risk of esophageal adenocarcinoma in men.


An improved protocol for flow cytometry analysis of phytoplankton cultures and natural samples.
Preservation of cells, choice of fixative, storage, and thawing conditions are recurrent issues for the analysis of phytoplankton by flow cytometry. We examined the effects of addition of the surfactant Pluronic F68 to glutaraldehyde-fixed photosynthetic organisms in cultures and natural samples. In particular, we examined cell losses and modifications of side scatter (a proxy of cell size) and fluorescence of natural pigments. We found that different marine phytoplankton species react differently to the action of Pluronic F68. In particular, photosynthetic prokaryotes are less sensitive than eukaryotes. Observed cell losses may result from cell lysis or from cell adhesion to the walls of plastic tubes that are commonly used for flow cytometry analysis. The addition of the surfactant, Pluronic F68, has a positive effect on cells for long-term storage. We recommend to modify current protocols for preservation of natural marine planktonic samples, by fixing them with glutaraldehyde 0.25% (final concentration) and adding Pluronic F68 at a final concentration of 0.01% in the samples before preservation. Pluronic F68 also appears effective for preserving samples without fixation for subsequent sorting, e.g. for molecular biology analyses. © 2014 International Society for Advancement of Cytometry.


A conceptual framework for interprofessional and co-managed care.
Interprofessional care has been promoted by some policy makers and health professionals as a response to rising health care costs and threats to patient safety. Proponents suggest that interprofessional models of care can reduce fragmentation and lower costs through improved coordination between different health professionals. These models encourage the collaboration of supplementary skills between different health care professionals. Effective collaborative models of interprofessional care may be influenced by several variables germane to the interaction and structure of the team of health professionals--temporality, urgency, and degree of structured authority--and the author examines the importance of each variable in delivering interprofessional care. Co-managed models of care have also been proposed. Recent state health reform efforts have catalyzed the adoption of co-managed care models by expanding the autonomy of alternative providers through the broadening of scope of practice. These scope-of-practice changes are intended to permit greater diagnostic and therapeutic authority of nonphysician providers. This effort seems aimed at enhancing the competition between provider groups in the market and expanding consumer choices. Herein, the author presents a conceptual framework to describe different models of interprofessional and co-managed care. The author also considers interprofessional and co-managed care models in the context of the health reform movement. Some of the challenges are considered, as policy makers consider the options for facilitating further development of interprofessional models of practice and the implications for curricular modifications at academic health centers.


Neuroprotective therapy for HIV dementia.
Despite the development and use of effective antiretroviral therapy, HIV dementia persists and has important socio-economic consequences. Significant progress has been made in our current understanding of the neuropathogenesis of HIV infection, and it is clear that adjunctive neuroprotective therapy in addition to antiretroviral therapy are necessary for prevention and treatment of this entity. In this manuscript, we discuss the rationale and the pathophysiological mechanisms that support the development of neuroprotective therapy for HIV dementia. We review all the placebo controlled clinical trials conducted to date with neuromodulatory/neuroprotective therapy in patients with HIV dementia and discuss their outcomes. We also provide a thorough review of potential new treatments for HIV dementia based on the experimental literature. We hope that this manuscript will serve as an important guide for future approaches for clinical trials and drug development for patients with HIV dementia.


Regional wave travel and reflections along the human aorta: a study with six simultaneous micromanometric pressures.
The human aorta and its terminal branches were investigated in normal subjects during elective cardiac catheterization to evaluate regional wave travel and arterial wave reflections. A specially designed catheter with six micromanometers equally spaced at 10 cm intervals was positioned with the tip sensor in the distal external iliac artery and the proximal sensor in the aortic arch. Simultaneous pressures were obtained and analyzed for foot-to-foot wave velocity, and Fourier analysis was used to derive apparent phase velocity. These quantities were assessed during control (n = 9), during Valsalva (n = 8) and Müller (n = 4) maneuvers, and during femoral artery occlusion by bilateral manual compression (n = 8). During control, regional cross-sectional areas, determined from aortography, and regional foot-to-foot pulse wave velocities were used to calculate the local reflection coefficient in the proximal descending aorta (gamma = 0.05), at the junction of the renal arteries (gamma = 0.43), and at the terminal aortic bifurcation (gamma = 0.13). To test the hypothesis that significant reflections originate in the aorta, at the level of the renal arteries, aortograms were used to design a latex tube model with geometric properties similar to the descending aorta. Velocities and reflection characteristics in the model and in vivo were compared. Inspection of thoracic aortic pressures under control conditions revealed a reflected wave originating from the region of the aorta at the level of the renal arterial branches while abdominal pressures exhibited reflection from a site peripheral to the terminal aortic bifurcation. In the low frequency range, apparent phase velocity was found to be higher proximal to the renal arteries as compared with at the distal sites. In addition, the minimum value occurred at a higher frequency in the lower thoracic aorta than at more distal sites. The effects of reflection on apparent wave velocity in the tube model were consistent with data obtained in vivo. The Valsalva maneuver diminished the reflection from the aortic region of the renal arteries, thus allowing the distal reflected wave to become more evident on the thoracic pressure waveforms. Bilateral femoral artery occlusion usually enhanced the distal reflection and the Müller maneuver usually resulted in small increases in reflections. In conclusion, the geometric and elastic nonuniformity of the aorta results in two major sites of arterial wave reflection that influence the aortic pressure waveforms in man.(ABSTRACT TRUNCATED AT 400 WORDS)


Accuracy of the Depression, Anxiety and Stress Scale (DASS-21) for Screening on Comorbid Internalizing Disorders among Youth in Substance Use Disorder Treatment.
Major depression, anxiety disorders, and post-traumatic stress disorder (PTSD) are among the most prevalent comorbid mental disorders in youth addiction treatment. Hence, screening for these internalizing disorders should be part of the standard routine at intake in substance use disorder treatment. We investigated the usefulness of the Depression, Anxiety and Stress Scale (DASS-21) as a screener for this purpose. A nationally representative sample of 421 treatment-seeking youths aged 16-22 years with a primary cannabis, alcohol, cocaine, or amphetamine use disorder participated in the study. At intake, we administered the DASS-21 and the Mini International Neuropsychiatric Interview (MINI; Sheehan et al., 1998) based on the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), as "gold standard," as part of a broader baseline assessment of the Youth in transition study [Moska et al. BMC Psychiatry. 2021;21(1):1-11]. At comparable sensitivity (0.80-0.84), based on the optimal cut-off value, specificity was higher for the DASS-21 total score detecting any DSM-5 internalizing disorder (0.62) than for the DASS subscales specifically detecting depression, anxiety, or PTSD (0.44, 0.49, and 0.51, respectively). Receiver operating characteristic curve analyses showed an area under the curve (AUC) value of 0.80 for the DASS total score to detect any internalizing disorder ("good discrimination"), compared with AUC values of 0.70-0.75 of the DASS depression and anxiety subscales to detect DSM-5 depression, anxiety, and PTSD ("fair discrimination"). The optimal DASS total score cut-off value of ≥44 for detecting any internalizing disorder resulted in 0.81 sensitivity, 0.62 specificity, 0.80 positive predictive value, and 0.64 negative predictive value. Given the high prevalence of comorbid internalizing disorders in youth addiction care, the need to address these comorbid disorders in treatment, and the favorable accuracy of the DASS to detect these disorders, we recommend to implement the DASS-21 as routine screener in youth addiction treatment in the Netherlands.


Phenotyping of lymphocyte subsets, Th-1/Th-2 cytokines and other parameters in high-risk contacts of SARS-CoV-2.
The information on the pathophysiology of infection in high-risk contacts of SARS-CoV-2 is limited. The aim of the present study was to assess the various factors and their elucidation in the protection of SARS- CoV-2 infection in high-risk contacts. Cross-sectional descriptive clinical study. A total of 136 subjects were recruited in the present study including 100 high-risk subjects and 36 control subjects. Out of 100 high-risk subjects, 44 subjects were found positive for SARS-CoV-2 RNA. Further, absolute blood counts of total T-cells (CD3+), T-helper cells (CD4+), T-cytotoxic cells (CD8+), B lymphocytes (CD19+) Natural Killer (NK) Cells (CD16+, CD56+), cytokines, and other parameters were measured in the samples of study subjects. The continuous variables were analyzed by unpaired 't' test, analysis of variance and 'Tukey test' for multiple comparisons. A significant reduction of total leukocyte counts and absolute lymphocyte count was found in the acute SARS-CoV-2 positive group as compared to control group (<0.05). Interestingly, IL-4 level was significantly elevated in SARS-CoV-2 negative high-risk subjects as compared to control and acute SARS-CoV-2 positive group (p < 0.05). A significant decrease of T-cytotoxic, B-cells, and NK cells were found in acute SARS-CoV-2 positive subjects as compared to control groups. The findings of this study may augment our knowledge about the pathogenesis of SARS-CoV-2 infection that could help in making future strategies to control its infection.


[Cardiac rehabilitation of patients with left ventricular assist device as "destination therapy"].
"End stage" heart failure is unresponsive to conventional pharmacological and non pharmacological treatments and has a bad prognosis either regarding survival or quality-of-life; besides cardiac transplantation is limited by organ shortage. Therefore mechanical devices have been developed, initially as "bridge to transplantation" and, more recently, as "destination therapy": definitive treatment for non-transplantable patients. In these patients instrumental evaluation, treatment and rehabilitation are not yet defined and standardized. This paper reports the initial experience realized, as a part of a regional cooperation project within Florence and Siena University Hospitals activities, with the first three male patients, aged 45 to 70 years, affected by end-stage heart failure (NYHA class IV), non-eligible to transplantation, and implanted with Jarvik Flowmaker 2000, an intraventricular axial-flow VAD generating a continuous blood flow. After clinical stabilization, patients underwent a specific evaluation and treatment purposely designed for these subjects during ICU and post-ICU stay and, subsequently, a formal cardiac rehabilitation program. Hemodynamic, bioumoral and functional parameters were recorded at the beginning, during and at the end of intensive rehabilitation program. All patients completed the program, achieving a remarkable and meaningful functional recovery, such to allow them going home, continuing with a self-activity with weekly follow-up in the Rehabilitation Center. The experience acquired by following these patients longitudinally--from the VAD implantation to hospital discharge--allowed us to develop a flow-chart divided in five phases, identifying the main clinical problems, the rehabilitative treatment goals and the useful indicators to define criteria for shift from every phase to the following one.


The Application Effect of Craniotomy through Transsylvian Rolandic Point-Insular Approach on Hypertensive Intracerebral Hemorrhage in Posterior Basal Ganglia.
To evaluate the hematoma clearance and safety of small bone window craniotomy through the lateral fissure Rolandic point-insular lobe approach for patients with hypertensive intracerebral hemorrhage (HICH) in posterior basal ganglia. This retrospective study enrolled a total of 86 patients with HICH in the posterior basal ganglia region who underwent surgery between January 2020 and December 2021. These patients were divided into two groups: the conventional group and the study group. The intraoperative information, postoperative hematoma clearance rate, increasing rate of cerebral edema and rebleeding occurrence rate, postoperative complication rate, and prognoses were compared between the two groups. Additionally, we observed and compared the rate of postoperative cerebral hematoma increase, as well as the neurological function and activities of daily living (ADL) at admission, 3 months, and 6 months after surgery in both groups. Univariate and multivariate logistic regression analyses were performed to explore factors affecting the prognosis of patients with HICH in the posterior basal ganglia region after small bone window craniotomy through the lateral fissure Rolandic point-insular lobe approach. The study group exhibited significantly shorter automatic eye-opening times and hospital stays compared to the conventional group (P < 0.05). Furthermore, the study group demonstrated better hematoma clearance rates, lower rates of cerebral hematoma at postoperative 48 h and 72 h, and lower rates of rebleeding compared to the conventional group (P < 0.05). At 3 and 6 months postsurgery, the study group exhibited a significantly greater improvement in neurological function and ADL compared to the conventional group (P < 0.05). Additionally, the incidence of postoperative complications in the study group was lower than that in the conventional group (P < 0.05). Furthermore, the prognosis of the study group was significantly better than that of the conventional group at the 6-month follow-up (P < 0.05). A small bone window craniotomy via transsylvian Rolandic point-insular approach has been shown to improve the hematoma clearance rate in patients with HICH in the posterior basal ganglia region while also reducing the incidence of complications. This approach is highly safe and feasible for implementation in clinical practice.


Dopaminergic effects of caffeine in the human striatum and thalamus.
Epidemiological studies have provided evidence that caffeine, an adenosine receptor antagonist, reduces the risk for Parkinson's disease. There are indications of specific interactions between striatal adenosine A(2A) and dopamine D(2) receptors, but the in vivo effects of caffeine on human dopamine system have not been investigated. In the present study, the dopaminergic effects of caffeine were examined with [(11)C]raclopride positron emission tomography (PET) in eight healthy habitual coffee drinkers after 24 h caffeine abstinence. Compared to oral placebo, 200 mg oral caffeine induced a 12% decrease in midline thalamic binding potential (p < 0.001). A trend-level increase in ventral striatal [(11)C]raclopride binding potential was seen with a correlation between caffeine-related arousal and putaminal dopamine D(2) receptor binding (r = -0.81, p = 0.03). The findings indicate that caffeine has effects on dopaminergic neurotransmission in the human brain, which may be differential in the striatum and the thalamus.


Genetic polymorphisms of the TNF-α-308G/A are associated with metabolic syndrome in asthmatic patients from Hebei province, China.
Asthma is a complex inflammatory disease involving the critical actions of several important cytokines. Epidemiological data show that obesity could increase the risk of asthma, and insulin resistance, or metabolic syndrome are an important risk factor for obesity asthma. Some studies identified that upstream of the transcription start site within the TNF-α gene promoter region-308 polymorphism was associated insulin resistance or metabolic disorders, while this site was closely related to asthma. But no research was performed to evaluate the influence of TNF-α-308G/A polymorphism on metabolic syndrome in asthmatic patients. Here, we recruited 248 asthmatic patients, who were separated into asthma with Mets/asthma without Mets groups and 226 matched healthy controls from Hebei Province to evaluate the influence of TNF-α-308G/A polymorphism on metabolic syndrome in asthmatic patients. Single nucleotide polymorphism of TNF-α-308 locus was genotyped using PCR-RFLP. Some biochemical variables were also determined. Our result showed that the genotypic and allelic frequency of rs1800629 did not show significant difference between asthmatic patients and normal controls. However, the frequency of A allele was significantly higher in asthma group with Mets (22.36%) than in controls (15.71%) (P = 0.02; OR = 0.647; 95% CI = 0.447-0.936). After analyzing the relationship between biochemical features of patients and genotype of TNF-α-308G/A, we found levels of LDL cholesterol, TNF-α and insulin, and HOMA-IR were significantly higher in the asthmatic patients carrying the GA and AA genotypes than in the carriers of GG genotype of rs1800629 (P = 0.029, P = 0.022, P = 0.043, respectively). Thus, our data suggested that TNF-α-308G/A variation was related to metabolic phenotype in asthma patients. Furthermore, we first identified TNF-α-308 A allele was the risk factor for asthmatic patients with Mets in Hebei population, China.


Validation of the neuropathologic criteria of the third consortium for dementia with Lewy bodies for prospectively diagnosed cases.
There is limited information on the validity of the pathologic criteria of the Third Consortium on Dementia with Lewy bodies (CDLB), and none are based on prospectively diagnosed cases. In this study, the core clinical features of dementia with Lewy bodies (DLB) and the suggestive clinical feature of rapid eye movement sleep behavior disorder were assessed using a battery of standardized clinical instruments in 76 patients with the clinical diagnosis of either DLB or Alzheimer disease. At autopsy, 29 patients had high-likelihood, 17 had intermediate-likelihood, and 6 had low-likelihood DLB pathology. The frequency of core clinical features and the accuracy of the clinical diagnosis of probable DLB were significantly greater in high-likelihood than in low-likelihood cases. This is consistent with the concept that the DLB clinical syndrome is directly related to Lewy body pathology and inversely related to Alzheimer pathology. Thus, the Third Consortium on DLB neuropathologic criteria scheme performed reasonably well and are useful for estimating the likelihood of the premortem DLB syndrome based on postmortem findings. In view of differences in the frequency of clinically probable DLB in cases with Braak neurofibrillary tangle stages V (90%) and VI (20%) and diffuse cortical Lewy bodies, a possible modification of the scheme is to consider cases with neurofibrillary tangle stage VI to be low-likelihood DLB.


Motivational interviewing in eHealth and telehealth interventions for weight loss: A systematic review.
The alarming prevalence of adult obesity warrants consideration of treatments with broad reach; digital health interventions meet this need and have demonstrated efficacy for weight loss. One approach that can be delivered remotely is motivational interviewing - a counseling style that helps resolve ambivalence to change unhealthy behavior. This is the first review to systematically examine eHealth and telehealth interventions that incorporate motivational interviewing for weight loss. We searched four electronic databases (PubMed, Embase, PsycInfo, CINAHL) for publications from November 2009-May 2018. Included papers were weight loss RCTs conducted among adults with overweight or obesity that examined eHealth or telehealth interventions with motivational interviewing, compared to any type of treatment arm without it. Results were presented separately by comparison arm (control vs. active comparator). Sixteen papers (15 trials) were included. Twelve used telephone-based counseling to deliver motivational interviewing, two used email and phone, and one used online chats. When compared to a no-treatment control arm, the motivational interviewing arm was associated with greater weight loss on 6 of 11 occasions, but performed better than an active comparator on only 1 of 7 occasions. Retention and engagement were generally high, though few trials examined the relation with weight loss. No trial had high risk of bias, but five lacked power calculations and only two reported fidelity to motivational interviewing. Telephone-based interventions that incorporate motivational interviewing hold promise as effective obesity treatments. There is a dearth of evidence to support the use of motivational interviewing via eHealth, signaling a needed research area.


Direct observation of a widely tunable bandgap in bilayer graphene.
The electronic bandgap is an intrinsic property of semiconductors and insulators that largely determines their transport and optical properties. As such, it has a central role in modern device physics and technology and governs the operation of semiconductor devices such as p-n junctions, transistors, photodiodes and lasers. A tunable bandgap would be highly desirable because it would allow great flexibility in design and optimization of such devices, in particular if it could be tuned by applying a variable external electric field. However, in conventional materials, the bandgap is fixed by their crystalline structure, preventing such bandgap control. Here we demonstrate the realization of a widely tunable electronic bandgap in electrically gated bilayer graphene. Using a dual-gate bilayer graphene field-effect transistor (FET) and infrared microspectroscopy, we demonstrate a gate-controlled, continuously tunable bandgap of up to 250 meV. Our technique avoids uncontrolled chemical doping and provides direct evidence of a widely tunable bandgap-spanning a spectral range from zero to mid-infrared-that has eluded previous attempts. Combined with the remarkable electrical transport properties of such systems, this electrostatic bandgap control suggests novel nanoelectronic and nanophotonic device applications based on graphene.


Integrated breathlessness services for people with chronic conditions.
Optimal management of breathlessness requires generally more than one component. Breathlessness services aim to provide specific interventions and support for patients suffering from breathlessness due to any advanced disease and their carers. This review aims to describe recent studies evaluating the effects of breathlessness services for patients with advanced chronic conditions. Various breathlessness services have been tested and vary regarding structure, duration, frequency and professionals involved. Four randomized controlled trials demonstrated a positive and significant effect on distress due to breathlessness or mastery of breathlessness or breathlessness severity. In the fifth randomized controlled trial, quantitative results were NS, but in the qualitative interviews, patients stressed the positive experience with the breathlessness service and the benefits they gained. The caring, holistic, respectful and integrated approaches were valued by patients. Breathlessness services combine a variety of evidence-based nonpharmacological interventions and some services also pharmacological interventions when physicians are involved. As the prevalence of breathlessness due to advanced disease is high and increasing, more such services should be provided to support patients throughout the course of their disease.


MicroRNA expression profiling defines the impact of electronic cigarettes on human airway epithelial cells.
While all forms of tobacco exposure have negative health effects, the significance of exposure to electronic cigarettes (eCig) is not fully understood. Here, we studied the global effects of eCig on the micro RNA (miRNA) transcriptome in human lung epithelial cells. Primary human bronchial epithelial (NHBE) cells differentiated at air-liquid interface were exposed to eCig liquid. Exposure of NHBE to any eCig liquid resulted in the induction of oxidative stress-response genes including GCLM, GCLC, GPX2, NQO1 and HO-1. Vaporization of, and/or the presence of nicotine in, eCig liquid was associated with a greater response. We identified 578 miRNAs dysregulated by eCig exposure in NHBE, and 125 miRNA affected by vaporization of eCig liquid. Nicotine containing eCig vapor displayed the most profound effects upon miRNA expression. We selected 8 miRNAs (29A, 140, 126, 374A, 26A-2, 147B, 941 and 589) for further study. We validated increased expression of multiple miRNAs, including miR126, following eCig exposure. We also found significant reduction in the expression of two miR126 target genes, MYC and MRGPRX3, following exposure. These data demonstrated that eCig exposure has profound effects upon gene expression in human lung epithelial cells, some of which are epigenetically programmed at the level of miRNA regulation.


Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling.
Ceramide is now recognized as a negative regulator of insulin signaling by impairing protein kinase B (PKB)/Akt activation. In different cells, two distinct mechanisms have been proposed to mediate ceramide inhibition of PKB/Akt: one involving atypical protein kinase C zeta (PKCzeta) and the other the protein phosphatase-2 (PP2A). We hypothesized that ceramide action through PKCzeta or PP2A might depend on plasma membrane (PM) structural organization and especially on caveolin-enriched domain (CEM) abundance. We have used different PKCzeta mutant constructs or the PP2A inhibitor, okadaic acid (OKA), to selectively inhibit PKCzeta- and PP2A-dependent pathways in cells expressing different caveolin-1 levels and evaluated the impact of insulin and ceramide on PKB/Akt activity in different PM subdomains. Although the PKCzeta-mediated negative effect of ceramide on insulin-stimulated PKB/Akt was dominant in adipocytes, a ceramide action through PP2A outside CEMs, prevented by OKA, was also unraveled. To test the importance of CEM to direct ceramide action through the PKCzeta pathway, we treated 3T3-L1 preadipocytes devoid of CEMs with ceramide and we saw a shift of the lipid-negative action on PKB/Akt to a PP2A-mediated mechanism. In fibroblasts with low CEM abundance, the ceramide-activated PP2A pathway dominated, but could be shifted to a ceramide-activated PKCzeta pathway after caveolin-1 overexpression. Our results show that ceramide can switch from a PKCzeta-dependent mechanism to a PP2A pathway, acting negatively on PKB/Akt, and hence revealing a critical role of CEMs of the PM in this process.


Selective decreased grey matter volume of the pain-matrix network in cluster headache.
We assessed the pattern of regional white matter and grey matter abnormalities in patients with cluster headache (CH), using tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM). Using a 3.0 Tesla scanner, dual-echo, diffusion tensor and 3D T1-weighted scan were acquired from 15 patients with episodic CH and 19 healthy controls. TBSS analysis was performed using the FMRIB's Diffusion Toolbox. VBM was performed on the 3D T1-weighted images using SPM8. No diffusivity and volumetry abnormalities of brain white matter were detected in CH patients. Compared with controls, CH patients showed decreased grey matter volume in the right thalamus, head of the right caudate nucleus, right precentral gyrus, right posterior cingulate cortex, bilateral middle frontal gyrus, right middle temporal gyrus, left inferior parietal lobule and left insula (p < 0.001). They also had increased grey matter volume of the right cuneus. The results did not change after hemisphere mirroring in the five patients with left lateralized attacks. The decreased left middle frontal gyrus volume was significantly correlated with disease duration (r = -0.79, p < 0.001). CH patients experience tissue abnormalities of grey matter regions that are part of the antinociceptive system, which is shared with other chronic pain conditions.


Survival and cardioprotective benefits of long-term blueberry enriched diet in dilated cardiomyopathy following myocardial infarction in rats.
Despite remarkable progress in treatment of chronic heart failure (CHF) over the last two decades, mortality, personal suffering and cost remain staggering, and effective interventions are still a challenge. Previously we reported that a blueberry-enriched diet (BD) attenuated necroapoptosis and inflammation in periinfarct area in a rat model of myocardial infarction (MI). To test the hypothesis that BD will attenuate the course of CHF, including mortality and cardiac remodeling during the first year after induction of MI in rats. Two weeks after coronary artery ligation, rats were divided into two groups of similar average MI size, measured by echocardiography, and then 12-mo dietary regimens were initiated as follows: ad libitum regular diet (control, CD, n = 27) and isocaloric food with 2% blueberry supplement (BD, n = 27) also available ad libitum. These dietary groups were compared to each other and to sham group (SH). Mortality over the 12 mo was reduced by 22% in BD compared with CD (p<0.01). In the course of developing CHF, BD had no effect on the body weight, heart rate or blood pressure. Bi-monthly Echo revealed significant attenuation of the LV chamber remodeling, LV posterior wall thinning, and MI expansion in BD compared with CD. In fact, BD arrested the MI expansion. This is the first experimental evidence that a blueberry-enriched diet has positive effects on the course of CHF and thus warrants consideration for clinical evaluation.


Inflammation in muscular dystrophy and the beneficial effects of non-steroidal anti-inflammatory drugs.
Glucocorticoids are the only drugs available for the treatment of Duchenne muscular dystrophy (DMD), but it is unclear whether their efficacy is dependent on their anti-inflammatory activity. To address this issue, mdx mice were treated daily with methylprednisolone and non-steroidal anti-inflammatory drugs (NSAIDs: aspirin, ibuprofen, parecoxib). NSAID treatment was effective in ameliorating muscle morphology and reducing macrophage infiltration and necrosis. The percentage of regenerating myofibers was not modified by the treatments. The drugs were effective in reducing COX-2 expression and inflammatory cytokines, but they did not affect utrophin levels. The effects of the treatments on contractile performance were analyzed. Isometric tension did not differ in treated and untreated muscle, but the resistance to fatigue was decreased by treatment with methylprednisolone and aspirin. NSAIDs have a beneficial effect on mdx muscle morphology, pointing to a crucial role of inflammation in the progression of DMD.


Patient, tumor and therapeutic features related to recurrence of ductal carcinoma in situ (DCIS).
To evaluate the correlations between patient, tumor and therapeutic features and DCIS recurrence after primary treatment, a cohort of 132 cases of DCISs, treated at "Prof. Dr. Ion Chiricuta" Oncology Institute, Cluj-Napoca, Romania, between 1999 and 2010, were studied. Present study showed that age <45 years at diagnosis and presence of the necrosis were significantly correlated with recurrence, meanwhile nuclear grade is significantly correlated with quicker relapse meaning that for high-grade lesions recurrence occurs usually during the first 36 months of follow-up, meanwhile for non-high-grade lesions recurrence usually occurs after 36 months of follow-up. Also, the study showed that a important factor correlated with recurrence (both local and overall) for patients treated with breast conservative surgery (BCS) was the status of the resection margins as well as the association of adjuvant radiotherapy. Overall recurrence rate was 9.(84)% and during a mean follow-up of 62.99 months with limits between 24 (imposed by study) and 153 months, standard deviation 29.28.


Neuropsychological deficits in adults age 60 and above with attention deficit hyperactivity disorder.
Neuropsychological deficits are of major importance in ADHD, yet no previous studies have assessed clinically referred samples of older adults. The authors compared older adults with ADHD (60-75years) with both younger adults with ADHD (18-45years) and older healthy controls with regard to various neuropsychological deficits. Well-established tests were used to investigate working memory, inhibition, switching, planning, fluency, and speed of processing. Self-ratings of executive functioning and delay-related behaviors were also included. Both variable-oriented and person-oriented analyses were conducted. Older adults with ADHD differed from controls with regard to working memory, inhibition, switching, and delay-related behaviors. In comparison to younger adults with ADHD, they performed at a similar level with regard to working memory and planning, but significantly better with regard to inhibition, switching, fluency, speed of processing, and delay aversion. Despite several significant group differences relative to controls, person-oriented analyses demonstrated that a majority of older adults with ADHD performed within the average range on each test and 20% showed no clear deficit within any neuropsychological domain. The results are in line with models of heterogeneity that have identified different neuropsychological subtypes in ADHD as well as a subgroup of patients without any clear neuropsychological deficits. For older adults with ADHD, it will be important to assess their functioning across time as normal aging is related to memory decline and these patients could therefore end up with severe deficits as they grow older, which in turn could have serious negative effects on daily life functioning.


Avian sarcoma virus and human immunodeficiency virus, type 1 use different subsets of ESCRT proteins to facilitate the budding process.
Members of the Nedd4 family of E3 ubiquitin ligases bind the L domain in avian sarcoma virus (ASV) Gag and facilitate viral particle release. Translational fusion of ASV Gag with an L domain deletion (Deltap2b) to proteins that comprise ESCRT-I, -II, and -III (the endocytic sorting complexes required for transport) rescued both Gag ubiquitination and particle release from cells. The ESCRT-I factors Vps37C or Tsg101 were more effective in rescue of Gag/Deltap2b budding than the ESCRT-II factor Eap20 or the ESCRT-III component CHMP6. Thus ESCRT components can substitute for Nedd4 family members in ASV Gag release. Unlike wild type, ASV Gag/Deltap2b -ESCRT chimeras failed to co-immunoprecipitate with co-expressed hemagglutinin-tagged Nedd4, indicating that Nedd4 was not stably associated with these Gag fusions. Release of the Gag-ESCRT-I or -II fusions was inhibited by a dominant negative mutant of Vps4 ATPase similar to wild type ASV Gag. In contrast to ASV Gag, HIV-1 Gag containing an L domain inactivating mutation (P7L) was efficiently rescued by fusion to a component of ESCRT-III (Chmp6) but not ESCRT-II (Eap20). Depletion of the endogenous pool of Eap20 (ESCRT-II) had little effect on HIV-1 Gag release but blocked ASV Gag release. In contrast, depletion of the endogenous pool of Vps37C (ESCRT-I) had little effect on ASV but blocked HIV-1 Gag release. Furthermore, an N-terminal fragment of Chmp6 inhibited both HIV-1 and ASV Gag release in a dominant negative manner. Taken together, these results indicate that ASV and HIV-1 Gag utilize different combinations of ESCRT proteins to facilitate the budding process, although they share some common elements.


Breast Cancers Detected at Screening MR Imaging and Mammography in Patients at High Risk: Method of Detection Reflects Tumor Histopathologic Results.
Purpose To compare the clinical, imaging, and histopathologic features of breast cancers detected at screening magnetic resonance (MR) imaging, screening mammography, and those detected between screening examinations (interval cancers) in women at high risk. Materials and Methods This retrospective institutional review board-approved, HIPAA-compliant review of 7519 women at high risk for breast cancer who underwent screening with MR imaging and mammography between January 2005 and December 2010 was performed to determine the number of screening-detected and interval cancers diagnosed. The need for informed consent was waived. Medical records were reviewed for age, risk factors (family or personal history of breast cancer, BRCA mutation status, history of high-risk lesion or mantle radiation), tumor histopathologic results, and time between diagnosis of interval cancer and most recent screening examination. The χ(2) test and logistic regression methods were used to compare the features of screening MR imaging, screening mammography, and interval cancers. The Wilcoxon signed-rank test was used to calculate P values. Results A total of 18 064 screening MR imaging examinations and 26 866 screening mammographic examinations were performed. Two hundred twenty-two cancers were diagnosed in 219 women, 167 (75%) at MR imaging, 43 (19%) at mammography, and 12 (5%) interval cancers. Median age at diagnosis was 52 years. No risk factors were associated with screening MR imaging, screening mammography, or interval cancer (P > .06). Cancers found at screening MR imaging were more likely to be invasive cancer (118 of 167 [71%]; P < .0001). Of the 43 cancers found at screening mammography, 38 (88%) manifested as calcifications and 28 (65%) were ductal carcinoma in situ. Interval cancers were associated with nodal involvement (P = .005) and the triple-negative subtype (P = .03). Conclusion In women at high risk for breast cancer who underwent screening with mammography and MR imaging, invasive cancers were more likely to be detected at MR imaging, whereas most cancers detected at screening mammography were ductal carcinoma in situ. Interval cancers were found infrequently and were more likely to be node positive and of the triple-negative subtype. (©) RSNA, 2016.