Circumstances of falls causing hip fractures in the elderly.
A prospective analysis was performed on 832 patients to determine the circumstances surrounding falls leading to hip fracture within a homogeneous, elderly urban population. Special emphasis was placed on the season of year, time of day, location of fall, and other circumstances in which the fracture occurred. All patients were community dwelling, cognitively intact, previously ambulatory elderly who sustained a femoral neck or intertrochanteric fracture. Most fractures occurred at home, particularly in patients who were older, less healthy, and poorer ambulators. More than 75% of fractures resulted from a fall while the patient was standing or walking. Most falls occurred during daylight hours with a peak seen in the afternoon. No seasonal variation in the incidence of hip fractures was observed.


Studies of epithelial electrolyte transport by marker ions.
The paper reviews several recent studies in which marker ions, such as Rb and Br, were used to identify ion transport pathways and membrane properties in epithelia. In the frog skin epithelium, using Rb as a substitute for K, Cl transport mechanisms across the basolateral membranes of principal cells were studied. The data suggest that intracellular Cl is maintained above electrochemical equilibrium by an Na-K-2Cl cotransport system which, under non-stimulated conditions, is normally quiescent. In toad and frog skins, the route of transepithelial Cl movement was investigated. A subpopulation of mitochondria-rich cells demonstrated a ready exchange of Br with the apical and basal bathing media, consistent with the view that these cells constitute a transcellular anion shunt. Moreover, voltage-activation resulted in an increased Br uptake from the apical bath. Nevertheless, because of the very small number of these cells, it may be questioned whether the mitochondria-rich cell constitutes the only shuntpathway for Cl. In other studies, Rb uptake was employed to measure the Na/K-pump activity. In principal cells of the frog skin epithelium, amiloride inhibited Rb uptake and lowered Na concentration, supporting the view that this cell type is engaged in amiloride-sensitive Na transport. In contrast, no significant changes in the Rb, Na, and Cl concentration of mitochondria-rich cells were detectable. Studies with Rb as marker ion in the rabbit urinary bladder revealed that the epithelium behaves like a functional syncytium with regard to transepithelial ion transport.


Novel symptomatology and changing epidemiology of domoic acid toxicosis in California sea lions (Zalophus californianus): an increasing risk to marine mammal health.
Harmful algal blooms are increasing worldwide, including those of Pseudo-nitzschia spp. producing domoic acid off the California coast. This neurotoxin was first shown to cause mortality of marine mammals in 1998. A decade of monitoring California sea lion (Zalophus californianus) health since then has indicated that changes in the symptomatology and epidemiology of domoic acid toxicosis in this species are associated with the increase in toxigenic blooms. Two separate clinical syndromes now exist: acute domoic acid toxicosis as has been previously documented, and a second novel neurological syndrome characterized by epilepsy described here associated with chronic consequences of previous sub-lethal exposure to the toxin. This study indicates that domoic acid causes chronic damage to California sea lions and that these health effects are increasing.


Dupilumab sustains efficacy in patients with moderate-to-severe type 2 asthma regardless of inhaled corticosteroids dose.
Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins-4/13, key and central drivers of type 2 inflammation. The TRAVERSE (NCT02134028) open-label extension study demonstrated the long-term safety and efficacy of dupilumab in patients ≥12 years who completed a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Here, we assess whether dupilumab sustains long-term efficacy in patients regardless of inhaled corticosteroid (ICS) dose at parent study baseline (PSBL). Patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high- or medium-dose ICS at PSBL and enrolled in TRAVERSE were included. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1 ), 5-item asthma control questionnaire, and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO. Of patients with type 2 asthma (n = 1666), 891 (53.5%) were receiving high-dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab versus placebo were 0.517 versus 1.883 (phase 2b) and 0.571 versus 1.300 (QUEST) over the parent study (52 weeks) and remained low throughout TRAVERSE (0.313-0.494). Improvements in pre-BD FEV1 were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium-dose ICS at PSBL and biomarker subgroups. Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma on high- or medium-dose ICS.


Calcium uptake by brush-border membrane vesicles from the rat intestine.
Uptake of calcium by brush-border membrane vesicles from rat small intestine is composed of saturable and nonsaturable components. We studied regulation of calcium uptake using the divalent cations strontium, a foreign ion that mimics calcium biologically and magnesium, a physiologically important ion that resembles calcium physically, although not biologically. Strontium present outside the vesicle inhibited saturable calcium uptake competitively, consistent with binding to the transporter at the same site as calcium. Strontium inside the vesicle accelerated saturable calcium uptake from the outside (countertransport), also consistent with binding to the same transporter site as calcium. Thus the calcium transporter shows functional characteristics of a mobile carrier. In the uptake medium (extracellular), magnesium was a noncompetitive inhibitor of saturable calcium transport, consistent with a regulatory role in calcium uptake by binding to the transporter at a locus other than that for calcium. Magnesium at 1 mM concentration inside the vesicle had no effect on saturable calcium uptake and a high concentrations functioned as a week uncompetitive inhibitor. Thus intracellular magnesium appears to have no major role in regulating saturable calcium uptake at the brush border of the enterocyte.


Factors predicting treatment adherence in patients with adult attention-deficit/hyperactivity disorder: a preliminary study.
This study aimed to elicit patient- and treatment-related factors that can potentially predict treatment adherence in adult ADHD. Subjects who were over 18 and received a diagnosis of ADHD were included in the study. Chart review data of 102 subjects regarding demographics, medications, comorbidities, concomitant medications and domains of functional impairment were collected, and predictors were assessed using a binominal logistical regression model. One hundred and two patients (78.4 % male) with a mean age of 28.8 (SD = 9.8, range = 18-55) years were enrolled in the study. Childhood diagnosis of ADHD, agents used for treatment (MPH or atomoxetine), individual domains of dysfunction and use of additional psychotropic drugs were not found to be related to treatment adherence. Patients with a university education and those referred for family history of ADHD were more likely to adhere to treatment (p = 0.05 and 0.03, respectively). On the other hand, reasons for referral other than ADHD were significantly more frequently related to non-adherence (p = 0.02). Treatment noncompliance remains a significant problem despite therapeutic effects of medications. Identification of predictors of non-adherence can lead to heightened awareness of special populations at risk. We have found that prior awareness on ADHD (via past history/media/friends) leading to self/clinician referral to rule out ADHD and pervasiveness of symptoms across functional domains led to better compliance in our sample. Future research with prospective design utilizing objective tools for adherence is required.


Distinguishing failure modes in oligomeric polymer nanopillars.
Brittle failure is ubiquitous in amorphous materials that are sufficiently cooled below their glass transition temperature, Tg. This catastrophic failure mode is limiting for amorphous materials in many applications, and many fundamental questions surrounding it remain poorly understood. Two challenges that prevent a more fundamental understanding of the transition between a ductile response at temperatures near Tg to brittle failure at lower temperatures are (i) a lack of computationally inexpensive molecular models that capture the failure modes observed in experiments and (ii) the lack of quantitative metrics that can distinguish various failure mechanisms. In this work, we use molecular dynamics simulations to capture ductile-to-brittle transition in glass-forming oligomeric polymer systems where we systematically vary both the temperature relative to Tg and the form of the interaction potential to induce a variety of failure modes. We characterized the effects of this new potential on macroscopic mechanical properties as well as microscopic structural and dynamical response during deformation. Finally, we develop several quantitative metrics to distinguish between different failure modes, and we find that the transition between catastrophic brittle failure, necking, and homogeneous plastic flow is gradual as the temperature is increased.


Perfect prosthetic heart valve: generative design with machine learning, modeling, and optimization.
Majority of modern techniques for creating and optimizing the geometry of medical devices are based on a combination of computer-aided designs and the utility of the finite element method This approach, however, is limited by the number of geometries that can be investigated and by the time required for design optimization. To address this issue, we propose a generative design approach that combines machine learning (ML) methods and optimization algorithms. We evaluate eight different machine learning methods, including decision tree-based and boosting algorithms, neural networks, and ensembles. For optimal design, we investigate six state-of-the-art optimization algorithms, including Random Search, Tree-structured Parzen Estimator, CMA-ES-based algorithm, Nondominated Sorting Genetic Algorithm, Multiobjective Tree-structured Parzen Estimator, and Quasi-Monte Carlo Algorithm. In our study, we apply the proposed approach to study the generative design of a prosthetic heart valve (PHV). The design constraints of the prosthetic heart valve, including spatial requirements, materials, and manufacturing methods, are used as inputs, and the proposed approach produces a final design and a corresponding score to determine if the design is effective. Extensive testing leads to the conclusion that utilizing a combination of ensemble methods in conjunction with a Tree-structured Parzen Estimator or a Nondominated Sorting Genetic Algorithm is the most effective method in generating new designs with a relatively low error rate. Specifically, the Mean Absolute Percentage Error was found to be 11.8% and 10.2% for lumen and peak stress prediction respectively. Furthermore, it was observed that both optimization techniques result in design scores of approximately 95%. From both a scientific and applied perspective, this approach aims to select the most efficient geometry with given input parameters, which can then be prototyped and used for subsequent in vitro experiments. By proposing this approach, we believe it will replace or complement CAD-FEM-based modeling, thereby accelerating the design process and finding better designs within given constraints. The repository, which contains the essential components of the study, including curated source code, dataset, and trained models, is publicly available at https://github.com/ViacheslavDanilov/generative_design.


Challenges for undergraduate speech pathology students undertaking cross-cultural clinical placements.
Two Australian undergraduate speech pathology students completed a series of clinical placements working with people with complex communication needs in cross-cultural contexts. To describe the challenges that the students faced and how best to prepare future students for such experiences. The students completed the placements in Thailand, Nepal, Bangladesh, India and South Africa. They used personal journaling to record their experiences. The students used the journals as the basis for reflective discussion when considering the challenges they experienced in applying their knowledge and skills. The challenges were (1) to prepare adequately ahead of the placements; (2) to select appropriate models of service delivery; (3) to use existing service approaches, resources and infrastructure appropriately; (4) to access professional support; (5) to define their professional role; (6) to manage variable shared language proficiency; (7) to adapt personally; and (8) to work using an undergraduate level of knowledge, skills and experience. The students encountered challenges related to their clinical preparation and their capacity to adapt in both a professional and personal sense. Future students preparing to undertake such placements need to attain at least minimum clinical competencies before placements. They will be helped if they have some clinical experience in working with people with complex communication needs in cross-cultural contexts, information about the cultures they will visit, and if they set professional and personal learning goals for each clinical placement. This preparation will aid students in maximizing their learning experience.


Long-term outcomes of renal tumor radio frequency ablation stratified by tumor diameter: size matters.
Renal tumor size influences the efficacy of radio frequency ablation but identification of confident size cutoffs has been limited by small numbers and short followup. We evaluated tumor size related outcomes after radio frequency ablation for patients with adequate (greater than 3 years) followup. We identified 159 tumors treated with radio frequency ablation as primary treatment. Disease-free survival was defined as the time from definitive treatment to local recurrence, detection of metastasis or the most recent imaging showing no evidence of disease. Patients were evaluated with contrast enhancing imaging preoperatively, and at 6 weeks, 6 months and at least annually thereafter. Median tumor size was 2.4 cm (range 0.9 to 5.4) with a median followup of 54 months (range 1.5 to 120). Renal cell carcinoma was confirmed in 72% of the 150 tumors that had pre-ablation biopsy (94%). The 3 and 5-year disease-free survival was comparable at 92% and 91% overall, and was dependent on tumor size, being 96% and 95% for tumors smaller than 3.0 cm and 79% and 79%, respectively, for tumors 3 cm or larger (p=0.001). Most failures (14 of 18) were local, either incomplete ablations or local recurrences. This is an intent to treat analysis and, therefore, includes patients ultimately found to have benign tumors, although outcomes were comparable in patients with cancer. Radio frequency ablation treatment success of the small renal mass is strongly correlated with tumor size. Radio frequency ablation provides excellent and durable outcomes, particularly in tumors smaller than 3 cm. Of tumors 3 cm or larger, approximately 20% will recur such that alternative treatment techniques should be considered. However, most treatment failures are local and are often successfully treated with another ablation session.


Differences in human macrophage receptor usage, lysosomal fusion kinetics and survival between logarithmic and metacyclic Leishmania infantum chagasi promastigotes.
The obligate intracellular protozoan, Leishmania infantum chagasi (Lic) undergoes receptor-mediated phagocytosis by macrophages followed by a transient delay in phagolysosome maturation. We found differences in the pathway through which virulent Lic metacyclic promastigotes or avirulent logarithmic promastigotes are phagocytosed by human monocyte-derived macrophages (MDMs). Both logarithmic and metacyclic promastigotes entered MDMs through a compartment lined by the third complement receptor (CR3). In contrast, many logarithmic promastigotes entered through vacuoles lined by mannose receptors (MR) whereas most metacyclic promastigotes did not (P < 0.005). CR3-positive vacuoles containing metacyclic promastigotes stained for caveolin-1 protein, suggesting CR3 localizes in caveolae during phagocytosis. Following entry, the kinetics of phagolysosomal maturation and intracellular survival also differed. Vacuoles containing metacyclic parasites did not accumulate lysosome-associated membrane protein-1 (LAMP-1) at early times after phagocytosis, whereas vacuoles with logarithmic promastigotes did. MDMs phagocytosed greater numbers of logarithmic than metacyclic promastigotes, yet metacyclics ultimately replicated intracellularly with greater efficiency. These data suggest that virulent metacyclic Leishmania promastigotes fail to ligate macrophage MR, and enter through a path that ultimately enhances intracellular survival. The relatively quiescent entry of virulent Leishmania spp. into macrophages may be accounted for by the ability of metacyclic promastigotes to selectively bypass deleterious entry pathways.


MD simulations explain the excess molar enthalpies in pseudo-binary mixtures of a choline chloride-based deep eutectic solvent with water or methanol.
The addition of molecular liquid cosolvents to choline chloride (ChCl)-based deep eutectic solvents (DESs) is increasingly investigated for reducing the inherently high bulk viscosities of the latter, which represent a major obstacle for potential industrial applications. The molar enthalpy of mixing, often referred to as excess molar enthalpy H E-a property reflecting changes in intermolecular interactions upon mixing-of the well-known ChCl/ethylene glycol (1:2 molar ratio) DES mixed with either water or methanol was recently found to be of opposite sign at 308.15 K: Mixing of the DES with water is strongly exothermic, while methanol mixtures are endothermic over the entire mixture composition range. Knowledge of molecular-level liquid structural changes in the DES following cosolvent addition is expected to be important when selecting such "pseudo-binary" mixtures for specific applications, e.g., solvents. With the aim of understanding the reason for the different behavior of selected DES/water or methanol mixtures, we performed classical MD computer simulations to study the changes in intermolecular interactions thought to be responsible for the observed H E sign difference. Excess molar enthalpies computed from our simulations reproduce, for the first time, the experimental sign difference and composition dependence of the property. We performed a structural analysis of simulation configurations, revealing an intriguing difference in the interaction modes of the two cosolvents with the DES chloride anion: water molecules insert between neighboring chloride anions, forming ionic hydrogen-bonded bridges that draw the anions closer, whereas dilution of the DES with methanol results in increased interionic separation. Moreover, the simulated DES/water mixtures were found to contain extended hydrogen-bonded structures containing water-bridged chloride pair arrangements, the presence of which may have important implications for solvent applications.


Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells.
Development of clinical stem cell interventions are hampered by immature cell progeny under current protocols. Human mesenchymal stem cells (hMSCs) are characterized by their ability to self-renew and differentiate into multiple lineages. Generating hMSCs from pluripotent stem cells (iPSCs) is an attractive avenue for cost-efficient and scalable production of cellular material. In this study we generate mature osteoblasts from iPSCs using a stable expandable MSC intermediate, refining established protocols. We investigated the timeframe and phenotype of cells under osteogenic conditions as well as the effect of menaquinone-7 (MK-7) on differentiation. From day 2 we noted a significant increase in RUNX2 expression under osteogenic conditions with MK-7, as well as decreases in ROS species production, increased cellular migration and changes to dynamics of collagen deposition when compared to differentiated cells that were not treated with MK-7. At day 21 OsteoMK-7 increased alkaline phosphatase activity and collagen deposition, as well as downregulated RUNX2 expression, suggesting to a mature cellular phenotype. Throughout we note no changes to expression of osteocalcin suggesting a non-canonical function of MK-7 in osteoblast differentiation. Together our data provide further mechanistic insight between basic and clinical studies on extrahepatic activity of MK-7. Our findings show that MK-7 promotes osteoblast maturation thereby increasing osteogenic differentiation.


Linearity and shift invariance for quantitative magnetic particle imaging.
Magnetic Particle Imaging (MPI) is a promising tracer imaging modality that employs a kidney-safe contrast agent and does not use ionizing radiation. MPI already shows high contrast and sensitivity in small animal imaging, with great potential for many clinical applications, including angiography, cancer detection, inflammation imaging, and treatment monitoring. Currently, almost all clinically relevant imaging techniques can be modeled as systems with linearity and shift invariance (LSI), characteristics crucial for quantification and diagnostic utility. In theory, MPI has been proven to be LSI. However, in practice, high-pass filters designed to remove unavoidable direct feedthrough interference also remove information crucial to ensuring LSI in MPI scans. In this work, we present a complete theoretical and experimental description of the image artifacts from filtering. We then propose and validate a robust algorithm to completely restore the lost information for the x-space MPI method. We provide the theoretical, simulated, and experimental proof that our algorithm indeed restores the LSI properties of MPI.


Elbow flexion response as another primitive reflex.
In daily clinical practice we noticed that patients with intellectual impairment spontaneously flex the elbow within a few seconds of the forearm being manipulated during routine examination of spasticity of the muscles in the upper extremities. We termed this phenomenon elbow flexion response (EFR), and prospectively studied it in 229 patients who underwent in-hospital rehabilitation following brain damage. Evaluation of each patient included EFR, patient profile, ability to communicate, scores on three parameters from various intelligence tests, scores on seven parameters testing primitive reflexes, and scores on three parameters describing personality. We investigated for relationships among these parameters. Consequently, although EFR rarely have a statistical association with the varied profiles of patients, patients with bilateral lesion or bilateral paresis demonstrated significantly more marked EFR than those with unilateral lesion or unilateral paresis. Patients with involvement of the frontal lobe showed significantly more marked EFR than those without damage in this area. Elbow flexion responses occurred significantly more frequently in relation with lower scores on intelligence and occurred with significantly higher frequency in conjunction with the more marked appearance of conventional primitive reflexes. Therefore, we conclude that EFR have a strong association with intelligence and with the existence of frontal lobe lesion, and their mode of clinical presentation parallels that of primitive reflexes particularly that of the grasp reflex. We propose that EFR could be referred as a variation of the grasp reflex occurring in the more proximal or axial part of the body.


Association of hormonal contraceptive use with reduced levels of depressive symptoms: a national study of sexually active women in the United States.
An estimated 80% of sexually active young women in the United States use hormonal contraceptives during their reproductive years. Associations between hormonal contraceptive use and mood disturbances remain understudied, despite the hypothesis that estrogen and progesterone play a role in mood problems. In this study, we used data from 6,654 sexually active nonpregnant women across 4 waves of the National Longitudinal Study of Adolescent Health (1994-2008), focusing on women aged 25-34 years. Women were asked about hormonal contraceptive use in the context of a current sexual partnership; thus, contraceptive users were compared with other sexually active women who were using either nonhormonal contraception or no contraception. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. At ages 25-34 years, hormonal contraceptive users had lower mean levels of concurrent depressive symptoms (β = -1.04, 95% confidence interval: -1.73, -0.35) and were less likely to report a past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using low-efficacy contraception or no contraception, in models adjusted for propensity scores for hormonal contraceptive use. Longitudinal analyses indicated that associations between hormonal contraception and depressive symptoms were stable. Hormonal contraception may reduce levels of depressive symptoms among young women. Systematic investigation of exogenous hormones as a potential preventive factor in psychiatric epidemiology is warranted.


The E1A products of oncogenic adenovirus serotype 12 include amino-terminally modified forms able to bind the retinoblastoma protein but not p300.
The cell growth-regulating properties of the adenovirus type 5 (Ad5) E1A oncogene correlate closely with the binding of the E1A products to specific cellular proteins. These proteins include the products of the retinoblastoma tumor susceptibility gene and a 300-kDa product, p300. pRB binds to E1A sequences that are highly conserved among the E1A products of various serotypes, while p300 binding requires sequences in the E1A amino terminus, a region that is not highly conserved. To help evaluate the roles of the E1A-associated proteins in cell growth control, we have compared the p300-binding abilities of the E1A products of Ad5 and of the more oncogenic Ad12 serotype. We show here that despite encoding a sequence that varies somewhat from the p300-binding sequences of Ad5 E1A, the Ad12 E1A products associate with p300 with an affinity similar to that of the Ad5 E1A products. Both the 12S and 13S splice products of Ad12 E1A, like those of Ad5 E1A, encode proteins able to associate with p300. Interestingly, though, both also give rise to prominent forms that are amino terminally modified and unable to associate with p300. This modification, at least in the 13S product, does not appear to diminish the affinity of this product for the retinoblastoma protein.


Improved detection of salicylic acids using terbium-sensitized luminescence in aqueous micellar solutions of cetyltrimethylammonium chloride.
The determination of salicylic, p-aminosalicylic and 5-fluorosalicylic acids was investigated using terbium-sensitized luminescence in aqueous solutions. Formation of a ternary chelate between terbium, EDTA and the salicylic acid requires dissociation of the phenol group which is adjacent to the dissociated carboxylic group. The reaction is obtained in alkaline solutions and is enhanced in the presence of cetyltrimethylammonium chloride. As evidenced by absorbance and fluorescence measurements, the cationic surfactant plays an important role in the formation of the ternary chelate and then terbium luminescence depends mainly on the extent of chelate formation. Linearity is found over more than four orders of magnitude and detection limits are in the range (2-4) x 10(-10) mol l-1 for the three acids.


Machine learning in oncology: a review.
Machine learning is a set of techniques that promise to greatly enhance our data-processing capability. In the field of oncology, ML presents itself with a wealth of possible applications to the research and the clinical context, such as automated diagnosis and precise treatment modulation. In this paper, we will review the principal applications of ML techniques in oncology and explore in detail how they work. This will allow us to discuss the issues and challenges that ML faces in this field, and ultimately gain a greater understanding of ML techniques and how they can improve oncological research and practice.


Modes of alcohol administration appropriate for the study of the role of alcohol in carcinogenesis.
The route of alcohol administration used in the experimental study of the role of alcohol in carcinogenesis should mimic the human condition: the p.o. route should, therefore, have major attention. This route appears in concord with epidemiological evidence of alcohol involvement in cancers of the upper digestive tract. The relative advantages of schedule-induced polydipsia, an alcohol solution as the sole fluid source, and an alcohol-containing fluid diet are assessed, as well as the intake of alcohol via the respired air. These routes allow a wide range of daily alcohol doses to be ingested, the largest resulting in continuous intoxication and the development of physical dependence. The equivocal resulta from various already published typical experiments are discussed, indicating the necessity of using a variety of appropriate dosages, dosage routes, and dosage forms in appropriate controls, as well as indicating the necessity of investigating the role of concentration and kind of alcoholic beverage in a variety of strains and species in both sexes and at various ages.


The metabolic syndrome of omega3-depleted rats. IV. Intestinal phospholipid omega3 fatty acids.
A dietary deprivation in long-chain polyunsaturated omega3 fatty acids initiated in 7-week old normal rats provokes within 3 to 7 months the appearance of several features of the metabolic syndrome. Likewise, within 2 to 4-5 weeks exposure to a flaxseed oil-enriched diet, these anomalies are rapidly corrected. The present study deals with the omega3 fatty acid content of intestinal phospholipids under the same experimental conditions. For the sake of comparison, the control rats were given access during the last 4-5 weeks to either a soybean or flaxseed oil-enriched diet. In control rats, the relative weight content of omega3 fatty acids as well as their product/precursor ratio differed in distinct segments of the intestinal tract (duodenum, jejunum, caecum, colon). Within 3 months of omega3-deprivation, the intestinal content of C18:3omega3, C20:5omega3 and C22:5omega3 reached values below the limit of detection, whilst the C22:6omega3 content progressively decreased down to 10-20% of control values. Within 2 weeks of exposure to the omega3-rich diet, the C18:3omega3, C20:5omega3 and C22:5omega3 content of intestinal phospholipids were higher than control values, whilst that of C22:6omega3 progressively returned to a normal level during the 2 to 4-5 weeks exposure to the flaxseed oil-enriched diet. The results collected in the intestinal cells, which are the first cells exposed to each given diet, reinforce the view that the present animal model is quite suitable to assess the metabolic consequences of both omega3 fatty acid deprivation and replenishment.


Insights into the COVID-19 pandemic: Origin, pathogenesis, diagnosis, and therapeutic interventions.
Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the human coronavirus (HCoV) family that targets the lower part of the respiratory tract and causes severe acute respiratory syndrome (SARS). In a short span of time, this infection has led to a global pandemic and has become a significant threat to the existence of present human society. Currently, there are no treatments for this infection and the measures established across various countries such as social distancing, usage of mask to prevent entry of the virus into the respiratory tract, quarantine, and containment together have reduced the prevalence of this disease and mortality in highly susceptible individuals. Here, we examine the structure, replication cycle, phylogeny and genomic organization of this virus and discuss the role of spike (S) protein of the virus, an important structure that interacts with the host ACE2 receptor facilitating viral entry. Further, we explore the epidemiology, symptoms of the disease, describe the reverse transcriptase-polymerase chain reaction (RT-PCR) that establishes the diagnosis of the disease and also review its unique diagnostic features in the chest CT-Scan. Finally, we review the current approaches to develop therapies and vaccines as a measure for disease prevention and control.


Inference of signal transduction networks from double causal evidence.
Here, we present a novel computational method, and related software, to synthesize signal transduction networks from single and double causal evidences. This is a significant and topical problem because there are currently no high-throughput experimental methods for constructing signal transduction networks, and because the understanding of many signaling processes is limited to the knowledge of the signal(s) and of key mediators' positive or negative effects on the whole process. Our software NET-SYNTHESIS is freely downloadable from http://www.cs.uic.edu/∼dasgupta/network-synthesis/ .Our methodology serves as an important first step in formalizing the logical substrate of a signal transduction network, allowing biologists to simultaneously synthesize their knowledge and formalize their hypotheses regarding a signal transduction network. Therefore, we expect that our work will appeal to a broad audience of biologists. The novelty of our algorithmic methodology based on nontrivial combinatorial optimization techniques makes it appealing to computational biologists as well.


Measuring radioactive methane with the liquid scintillation counter.
Although a gas proportional counter is the most convenient method of measuring the radioactivity of fixed gases such as methane, it cannot be used when high nonradioactive concentrations of methane are present in the gas phase, due to quenching. If only methane and carbon dioxide are present in radioactive form in the gas phase, a liquid scintillation method for measuring these substances can be used. The procedure is described in detail, and the solubility of methane in liquid scintillation cocktails is determined.


Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function.
The present study was designed to evaluate the therapeutic efficacy of melatonin and insulin coadministration in diabetes-induced renal injury in rats. Diabetes was achieved by giving streptozotocin (15 mg/kg) for 6 consecutive days. The diabetic condition was confirmed by assessing the blood glucose level; animals having blood glucose levels above 250 mg were considered as diabetic. Following the confirmation, animals were randomly divided into different experimental groups, viz group I served as the control (CON), group II diabetic (D), group III D+melatonin (MEL), group IV D+insulin (INS), group V D+MEL+INS, group VI D+glibenclamide (GB), group VII CON+MEL, group VIII CON+INS, and group IX CON+GB. Following the completion of the experimental period, animals were sacrificed, blood was collected via a retro-orbital puncture, and kidneys were harvested. Diabetic rats exhibited a significant increment in blood glucose and biochemical indexes of renal injury (tubular disruption, swollen glomeruli with loss of glomerular spaces, and distortion of the endothelial lining) including augmented levels of serum creatinine, urea, uric acid, Na+, and K+, and inhibition/suppression of the activity of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and GSH-S-transferase in the renal cortex. By examining thiobarbiturate reactive substances, reduced GSH, superoxide dismutase activity, and catalase activity in the renal cortex of control and diabetic rats, it was documented that treatment with melatonin or insulin alone or in combination showed a significant ad integrum recovery of GSH-dependent antioxidative enzymatic activities. Melatonin and insulin coadministration caused greater reductions in circulating tumor necrosis factor-α, tumor growth factor-β1, interleukin (IL)-1β, and IL-6 levels in diabetic rats, whereas IL-10 levels increased, as compared to each treatment alone. Diabetic rats showed a significant increase in the expression of both MT1 and MT2 melatonin receptor genes. Melatonin or insulin treatment alone or in combination resulted in significant restoration of the relative expression of both melatonin receptors in the renal cortex. The coadministration of exogenous melatonin and insulin abolished many of the deleterious effects of type 1 diabetes on rat renal function.


Promotive role of IRF7 in ferroptosis of colonic epithelial cells in ulcerative colitis by the miR-375-3p/SLC11A2 axis.
Ferroptosis is implicated in the progression of ulcerative colitis (UC), and interferon regulatory factor 7 (IRF7) contributes to cell death. This study probed the mechanism of IRF7 in ferroptosis of colonic epithelial cells (ECs) in mice with dextran sodium sulfate (DSS)-induced UC. The UC mouse model and the in vitro ferroptosis model were respectively established by DSS feeding and the treatment with FIN56 (a ferroptosis inducer). Results of quantitative real-time polymerase chain reaction and western blotting revealed the upregulation of IRF7 and solute carrier family 11 member 2 (SLC11A2/NRAMP2/DMT1) and the downregulation of microRNA (miR)-375-3p in DSS-treated mice and FIN56-treated ECs. Silencing of IRF7 improved the symptoms of UC in DSS-induced mice and decreased the levels of tumor necrosis factor α, interleukin 6, monocyte chemoattractant protein 1, and interleukin 1β, reactive oxygen species, iron ions, lipid peroxidation, and increased glutathione and glutathione peroxidase 4. Chromatin immunoprecipitation and dual-luciferase assays showed that binding of IRF7 to the miR-375-3p promoter inhibited miR-375-3p expression, and miR-375-3p suppressed SLC11A2 transcription. The rescue experiments revealed that knockdown of miR-375-3p neutralized the role of silencing IRF7 in alleviating ferroptosis of colonic ECs. Overall, IRF7 upregulated SLC11A2 transcription by inhibiting miR-375-3p expression, thereby prompting ferroptosis of colonic ECs and UC progression in DSS-treated mice.


Soybean diacylglycerol regulates lipid metabolism in D-galactose-induced aging rats by altering gut microbiota and gene expression of colonic epithelial cells.
Lipid metabolism is closely related to the health of aging bodies and its disorder often leads to cardiovascular diseases and chronic diseases. Dietary fat is one of the important sources of body fat, which affects the body's lipid metabolism. However, how dietary fat affects lipid metabolism in aging bodies has not been reported. Thus, the effects of soybean diacylglycerol (DAG) on lipid metabolism in D-galactose-induced aging rats were investigated by detecting the serum biochemical indexes, hepatocyte morphology, gut microbiota changes, and gene expression of colonic epithelial cells. The results showed that DAG alleviated the lipid metabolism disorders, and the hepatocyte morphology of aging rats fed DAG was normal. 16S rDNA analysis showed that DAG restored Eisenbergiella and Veillonella that were missing in aging rats. The relative abundances of Romboutsia and Ruminococcus_2 decreased and the relative abundance of Lachnospiraceae NK4A136 group increased significantly with the influence of DAG (P < 0.05). Gene expression profiles showed that the gene expression of colon epithelial cells was altered by DAG and DAG downregulated the genes Lipe and Fabp4 related to the lipolysis of adipocytes. In conclusion, DAG regulated the lipid metabolism of aging rats by regulating gut microbiota and gene expression of colonic epithelial cells.


Immature CD45RA(low)RO(low) T cells in the human cord blood. I. Antecedents of CD45RA+ unprimed T cells.
A subset of resting T cells expressing low levels CD45RA and CD45RO molecules (< 1 x 10(3)/cell; CD45RA(low)CD45RO(low)) but high levels of CD45RB and CD38 (5 to 25 x 10(3)/cell) were identified in human cord blood. When these CD45RA(low)RO(low) cells were isolated, they failed to survive in culture (< 10% viability at day 3) unless they were co-cultured on fibroblast monolayers. During the co-culture with fibroblasts, these lymphocytes acquired high levels of cytoplasmic and then membrane CD45RA by day 3 without signs of activation. When stimulated with PHA in the absence of fibroblasts the CD45RA(low)RO(low) cells required monocytes or IL-1 to respond; they rapidly perished if neither were present. On optimal mitogenic stimulation for 48 h in the presence of monocytes, > 90% of CD45RA(low)RO(low) T cells showed only transient CD45RA expression and rapidly acquired CD45RO reactivity. After activation for 48 h the stimulated CD45RA(low)RO(low) subset synthesized high levels of IL-2, comparable to mature peripheral T cells. No IL-4 was detected in these stimulated cultures of cord blood T cells. These data taken together suggest that CD45RA(low)RO(low) T cells in the cord blood are the relatively immature antecedents of CD45RA+RO T cells that require stromal factors for survival in a resting state. The same cells need monocytes or IL-1 for their activation to develop after a short CD45RA+ stage into activated CD45RO+RA(low) T cells with potent IL-2 biosynthetic capacity. An additional study of these cells is warranted to confirm that they are in fact the recent emigrants from the thymus, as suggested by similar observations in animal models.


Automated identification and quantitative morphometry of the senile plaques of Alzheimer's disease.
Senile plaques (SP) are one of the characteristic neuropathologic lesions of Alzheimer's Disease (AD), and studies of SP cortical distribution, density and morphology may lead to new information about the mechanism and pathogenesis of AD. We used an automated, digital image analysis program to detect and measure SP size, shape and total fractional area in digital images of silver-stained tissue sections. The program observed 94,000 SP in 2,800 digitized microscope fields from tissue sections from 42 postmortem cases ranging from healthy aged to severely demented subjects, studied prospectively before death. Automated pattern recognition can measure SP densities in excellent agreement with an expert and can generate morphometric information not obtainable by conventional microscopy. SP densities (number of SPs/mm2) strongly correlate with tissue load (fraction of tissue area occupied by lesions). SP densities strongly correlate between cortical regions within the same subjects. SP densities, while correlating with the occurrence of AD, do not display a significant trend with respect to dementia severity; likewise, mean SP area and shape properties do not vary significantly with dementia severity. Finally, all the computed SP densities would have produced the same diagnoses of AD in these subjects as the manual SP densities according to the consensus criteria. This is the first fully automated program to identify SPs and measure SP morphometry; it uses well-established digital image analysis and statistical pattern recognition methods. The computed SP densities correlate highly with expert results, and the systematic differences are smaller than the interrater differences reported in several multicenter Alzheimer's disease neuropathology studies. The program measures morphometric properties that would be impractical to measure by manual means and, with program-controlled, scanning stage microscopy, can measure lesion densities exhaustively across large cortical areas without stereologic sampling. SP densities rise from near zero to significant values at the mildest diagnosed stage of AD, but beyond this point, there is no demonstrable correlation of density, or any other SP property, with dementia severity. Computed SP densities for even the mildest dementia satisfy the consensus diagnostic criteria.


The transcriptional corepressor CBFA2T3 inhibits all-trans-retinoic acid-induced myeloid gene expression and differentiation in acute myeloid leukemia.
CBFA2/RUNX1 partner transcriptional co-repressor 3 (CBFA2T3, also known as MTG16 or ETO2) is a myeloid translocation gene family protein that functions as a master transcriptional corepressor in hematopoiesis. Recently, it has been shown that CBFA2T3 maintains leukemia stem cell gene expression and promotes relapse in acute myeloid leukemia (AML). However, a role for CBFA2T3 in myeloid differentiation of AML has not been reported. Here, we show that CBFA2T3 represses retinoic acid receptor (RAR) target gene expression and inhibits all-trans-retinoic acid (ATRA)-induced myeloid differentiation of AML cells. ChIP-Seq revealed that CBFA2T3 targets the RARα/RXRα cistrome in U937 AML cells, predominantly at myeloid-specific enhancers associated with terminal differentiation. CRISPR/Cas9-mediated abrogation of CBFA2T3 resulted in spontaneous and ATRA-induced activation of myeloid-specific genes in a manner correlated with myeloid differentiation. Importantly, these effects were reversed by CBFA2T3 re-expression. Mechanistic studies showed that CBFA2T3 inhibits RAR target gene transcription by acting at an early step to regulate histone acetyltransferase recruitment, histone acetylation, and chromatin accessibility at RARα target sites, independently of the downstream, RAR-mediated steps of transcription. Finally, we validated the inhibitory effect of CBFA2T3 on RAR in multiple AML subtypes and patient samples. To our knowledge, this is the first study to show that CBFA2T3 down-regulation is both necessary and sufficient for enhancing ATRA-induced myeloid gene expression and differentiation of AML cells. Our findings suggest that CBFA2T3 can serve as a potential target for enhancing AML responsiveness to ATRA differentiation therapies.


The mechanism of electroforming of metal oxide memristive switches.
Metal and semiconductor oxides are ubiquitous electronic materials. Normally insulating, oxides can change behavior under high electric fields--through 'electroforming' or 'breakdown'--critically affecting CMOS (complementary metal-oxide-semiconductor) logic, DRAM (dynamic random access memory) and flash memory, and tunnel barrier oxides. An initial irreversible electroforming process has been invariably required for obtaining metal oxide resistance switches, which may open urgently needed new avenues for advanced computer memory and logic circuits including ultra-dense non-volatile random access memory (NVRAM) and adaptive neuromorphic logic circuits. This electrical switching arises from the coupled motion of electrons and ions within the oxide material, as one of the first recognized examples of a memristor (memory-resistor) device, the fourth fundamental passive circuit element originally predicted in 1971 by Chua. A lack of device repeatability has limited technological implementation of oxide switches, however. Here we explain the nature of the oxide electroforming as an electro-reduction and vacancy creation process caused by high electric fields and enhanced by electrical Joule heating with direct experimental evidence. Oxygen vacancies are created and drift towards the cathode, forming localized conducting channels in the oxide. Simultaneously, O(2-) ions drift towards the anode where they evolve O(2) gas, causing physical deformation of the junction. The problematic gas eruption and physical deformation are mitigated by shrinking to the nanoscale and controlling the electroforming voltage polarity. Better yet, electroforming problems can be largely eliminated by engineering the device structure to remove 'bulk' oxide effects in favor of interface-controlled electronic switching.


The use of imagery in global health: an analysis of infectious disease documents and a framework to guide practice.
We report an empirical analysis of the use of imagery by the key actors in global health who set policy and strategy, and we provide a comprehensive overview, particularly related to images used in reports on vaccination and antimicrobial resistance. The narrative currently depicted in imagery is one of power imbalances, depicting women and children from low-income and middle-income countries (LMICs) with less dignity, respect, and power than those from high-income countries. The absence of any evidence of consent for using intrusive and out-of-context images, particularly of children in LMICs, is concerning. The framework we have developed provides a platform for global health actors to redefine their intentions and recommission appropriate images that are relevant to the topic, respect the integrity of all individuals depicted, are accompanied by evidence of consent, and are equitable in representation. Adhering to these standards will help to avoid inherent biases that lead to insensitive content and misrepresentation, stigmatisation, and racial stereotyping.


Sensitivity of pyruvate dehydrogenase to insulin in activated T lymphocytes. Lack of responsiveness to insulin in patients with polycystic ovarian disease and diabetes.
Using phytohemagglutinin-activated T lymphocytes, we studied possible mechanisms responsible for insulin resistance in patients with polycystic ovarian disease (PCO) and acanthosis nigricans (AN) by examining insulin binding to erythrocytes and activated T lymphocytes and T-lymphocyte pyruvate dehydrogenase (PDH) responsiveness to insulin in three groups. These groups of subjects consisted of six PCO-AN patients with normal glucose tolerance, six PCO-AN patients with mild non-insulin-dependent diabetes mellitus (NIDDM), and six weight-matched control subjects. We found that insulin binding to both erythrocytes and activated T lymphocytes was significantly lower in PCO and PCO-NIDDM patients than control subjects but did not differ between the PCO groups. Insulin binding to erythrocytes and T lymphocytes varied inversely with basal insulin. In activated T lymphocytes of PCO-NIDDM patients, PDH responsiveness to both submaximal and maximal insulin concentrations was impaired, the extent of which varied in proportion to their degree of carbohydrate intolerance. In contrast, PDH responsiveness to maximal amounts of insulin in T lymphocytes of PCO patients without NIDDM was similar to the weight-matched control subjects. These data may suggest that lesions at the level of the receptor are primarily responsible for insulin resistance in patients with PCO but that both receptor and postreceptor defects (i.e., PDH responsiveness to insulin) contribute to the insulin-resistant state of PCO patients with NIDDM.


Redisplaced unstable fractures of the distal radius. A randomised, prospective study of bridging versus non-bridging external fixation.
A randomised, prospective study was carried out on 60 patients with unstable fractures of the distal radius to compare bridging with non-bridging external fixation using pins placed in the distal fragment of the radius. The radiological results showed significant improvement in the non-bridging group at all stages of review. In particular, normal volar tilt and carpal alignment were regained and maintained. The functional results at six weeks, three months, six months and one year showed statistically better grip strength and flexion in the non-bridging group at all stages of review. Other ranges of movement showed an early advantage in the non-bridging group. Non-bridging external fixation is the treatment of choice for unstable fractures of the distal radius which have sufficient space for the placement of pins in the distal fragment.


Sacral Neuromodulation in a Patient with Wolff-Parkinson-White Syndrome: A Case Report.
Sacral neuromodulation has gained widespread use for bladder overactivity, frequency, urgency, fecal incontinence, and nonobstructive urinary retention; hence, implantations of this device in patients with comorbid cardiac conduction diseases have increased. Theoretically, there are some concerns regarding the use of sacral neuromodulation implants in patients with Wolf-Parkinson-White syndrome and cardiac conduction diseases because of the risk of interference with electrical impulses. This study aimed to describe the safety of using sacral neuromodulation to treat nonobstructive urinary retention in patients with a cardiac conduction disease. We report a case in which sacral neuromodulation was performed to treat nonobstructive urinary retention in a 25-year-old woman with Wolf-Parkinson-White syndrome who was receiving antiarrhythmic medication. The patient underwent magnetic resonance imaging of the spine and urodynamic studies after presenting with urinary symptoms at a urology clinic. She was then diagnosed with nonobstructive urinary retention. She underwent two-staged InterStim therapy, which involved implanting a permanent tined lead through the S3 foramen in the first stage and an implantable pulse generator in the second stage. The patient responded well to the therapy, and the frequency of clean intermittent catheterization was reduced from 6 times a day to once daily with only 250 mL drained per day. The cardiology team recommended intraoperative cardiac monitoring and postoperative electrocardiogram monitoring. No interference was observed between the implantable pulse generator and the cardiac rhythm on electrocardiography. She experienced no exacerbation of her cardiac symptoms. Sacral neuromodulation in a patient with Wolf-Parkinson-White syndrome appears to have been safe. Further, prospective and randomized studies with larger study samples are required to investigate the safety of these implants in WPW patients.


Tobacco-induced contact dermatitis.
Tobacco and tobacco smoke are strongly associated with various skin conditions, among which contact dermatitis is of prime importance. The aetiological and clinical aspects vary according to the different tobacco production and processing steps. Contact dermatitis is frequent in tobacco harvesters, curers and cigar makers, whereas it rarely affects smokers and, only exceptionally, cigarette packaging workers. The skin sites involved also vary, according to whether the exposure is occupational or non-occupational. Tobacco contact irritation is far more frequent than contact allergy. The sensitizing compound in tobacco is unknown; nicotine, while highly toxic, does not seem to cause sensitization, except in rare cases. Besides natural substances, several compounds are added to tobacco during processing and manufacturing. For this reason, identifying the aetiological factors is exceedingly difficult. Another important aspect to take into account is the co-causative role of tobacco in eliciting or exacerbating contact dermatitis in response to other agents, occupational or extra-occupational.


The evolutionary fate of heterogeneous gene duplications: A precarious overdominant equilibrium between environment, sublethality and complementation.
Gene duplications occur at a high rate. Although most appear detrimental, some homogeneous duplications (identical gene copies) can be selected for beneficial increase in produced proteins. Heterogeneous duplications, which combine divergent alleles of a single locus, are seldom studied due to the paucity of empirical data. We investigated their role in an ongoing adaptive process at the ace-1 locus in Culex pipiens mosquitoes. We assessed the worldwide diversity of the ace-1 alleles (single-copy, susceptible S and insecticide-resistant R, and duplicated D that pair one S and one R copy), analysed their phylogeography and measured their fitness to understand their early dynamics using population genetics models. It provides a coherent and comprehensive evolutionary scenario. We show that D alleles are present in most resistant populations and display a higher diversity than R alleles (27 vs. 4). Most appear to result from independent unequal crossing-overs between local single-copy alleles, suggesting a recurrent process. Most duplicated alleles have a limited geographic distribution, probably resulting from their homozygous sublethality (HS phenotype). In addition, heterozygotes carrying different HS D alleles showed complementation, indicating different recessive lethal mutations. Due to mosaic insecticide control practices, balancing selection (overdominance) plays a key role in the early dynamics of heterogeneous duplicated alleles; it also favours a high local polymorphism of HS D alleles in natural populations (overdominance reinforced by complementation). Overall, our study shows that the evolutionary fate of heterogeneous duplications (and their long-term role) depends on finely balanced selective pressures due to the environment and to their genomic structure.


Estimating net anthropogenic nitrogen inputs to U.S. watersheds: comparison of methodologies.
The net anthropogenic nitrogen input (NANI) approach is a simple quasi-mass-balance that estimates the human-induced nitrogen inputs to a watershed. Across a wide range of watersheds, NANI has been shown to be a good predictor of riverine nitrogen export. In this paper, we review various methodologies proposed for NANI estimation since its first introduction and evaluate alternative calculations suggested by previous literature. Our work is the first study in which a consistent NANI calculation method is applied across the U.S. watersheds and tested against available riverine N flux estimates. Among the tested methodologies, yield-based estimation of agricultural N fixation (instead of crop area-based) made the largest difference, especially in some Mississippi watersheds where the tile drainage was a significant factor reducing watershed N retention. Across the U.S. watersheds, NANI was particularly sensitive to farm N fertilizer application, cattle N consumption, N fixation by soybeans and alfalfa, and N yield by corn, soybeans, and pasture, although their relative importance varied among different regions.


Need for sedation in a patient undergoing active compression--decompression cardiopulmonary resuscitation.
The authors report the case of a 57-year-old man with a history of ischemic heart disease who presented to the emergency department with an acute myocardial infarction and hypotension. Despite aggressive pharmacotherapy, the patient's heart rate decreased, and he developed pulseless electrical activity within 15 minutes of his arrival. Cardiopulmonary resuscitation (CPR) was begun with an active compression-decompression (ACD) device, and the patient became agitated, making purposeful movements. When ACD-CPR was discontinued for a rhythm check, the patient had no pulse and became motionless. Agitation and purposeful movements occurred on two subsequent occasions with the initiation of ACD-CPR. The patient required physical restraints, sedation, and paralysis for personnel to perform endotracheal intubation and facilitate treatment. The implications of this case are discussed.


A Systematic Review of Psychosocial-Based Outcomes in Peer-Support Services.
Purpose: In determining whether peer support interventions are effective, an examination of the measures used to assess outcomes is essential. Prior reviews often do not account for validly and reliability of measures used in studies, which may lead to conflicting conclusions. Method: Explicit criteria to identify articles of psychosocial based outcomes in peer support services was used. Outcome measures were categorized along broad dimensions, examined for validity and reliability and reviewed for major findings. Results: Thirteen domains of psychosocial based outcomes emerged. Most domains had at least one outcome measure that was valid and reliable. Articles that included valid and reliable outcomes suggests peer support services may be associated with multiple domains. Conclusion: From an examination of the validity and reliability of measures used to evaluate peer support services, a stronger evidence base for services is established. Future directions for both social work research and practice are identified.


Distribution of ultramicrobacteria in a gulf coast estuary and induction of ultramicrobacteria.
The abundance of ultramicrobacteria (i.e., bacteria that pass through a 0.2μm filter) in a subtropical Alabama estuary was determined during a 1-year period. Although phenotypic and molecular characterization indicated that the population of ultramicrobacteria was dominated byVibrio species, species ofListonella andPseudomonas were also abundant. Vibrios occurred with the greatest frequency in waters whose salinities were less than 14‰, and were the most abundant species of the total ultramicrobacterial population year-round, whilePseudomonas species were absent or considerably reduced during the winter months. The total number of ultramicrobacteria showed an inverse relationship to total heterotrophic bacteria as measured by colony-forming units (CFU)/ml and to water quality as measured by several parameters. Analysis by generic composition indicated that both salinity and temperature significantly affected the distribution of these organisms. Laboratory studies revealed that strains of vibrios under starvation in both static and continuous-flow microcosms could be induced to form cells that passed through 0.2 and/or 0.4μm filters. Cells exposed to low nutrients became very small; some grew on both oligotrophic (5.5 mg carbon/liter) and eutrophic (5.5 g carbon/liter) media; and some few cells grew only on oligotrophic media. By passing selected vibrio strains on progressively diluted nutrient media, cells were also obtained that were small, that passed through 0.4μm filters, and that could grow in oligotrophic media. These results suggest that ultramicrobacteria in estuaries (at least some portion of the population) may be nutrientstarved or low nutrient-induced forms of certain heterotrophic, eutrophic, autochthonous, estuarine bacteria.


Strong and weak hydrogen bonds in drug-DNA complexes: a statistical analysis.
A statistical analysis of strong and weak hydrogen bonds in the minor groove of DNA was carried out for a set of 70 drug-DNA complexes. The terms 'strong' and 'weak' pertain to the inherent strengths and weakness of the donor and acceptor fragments rather than to any energy considerations. The dataset was extracted from the protein data bank (PDB). The analysis was performed with an in-house software, hydrogen bond analysis tool (HBAT). In addition to strong hydrogen bonds such as O-H...O and N-H...O, the ubiquitous presence of weak hydrogen bonds such as C-H...O is implicated in molecular recognition. On an average, there are 1.4 weak hydrogen bonds for every strong hydrogen bond. For both categories of interaction, the N3 of purine and the O2 of pyrimidine are favoured acceptors. Donor multifurcation is common with the donors generally present in the drug molecules, and shared by hydrogen bond acceptors in the minor groove. Bifurcation and trifurcation are most commonly observed. The metrics for strong hydrogen bonds are consistent with established trends. The geometries are variable for weak hydrogen bonds. A database of recognition geometries for 26 literature amidinium-based inhibitors of Human African Trypanosomes (HAT) was generated with a docking study using seven inhibitors which occur in published crystal structures included in the list of 70 complexes mentioned above, and 19 inhibitors for which the drug-DNA complex crystal structures are unknown. The virtual geometries so generated correlate well with published activities for these 26 inhibitors, justifying our assumption that strong and weak hydrogen bonds are optimized in the active site.


Gravimetrically controlled efficacy of subcorial curettage: a prospective study for treatment of axillary hyperhidrosis.
Botulinum toxin A (BTX-A) proved to be effective for the treatment of axillary hyperhidrosis by means of gravimetry. Quantitatively controlled studies for surgical treatment are lacking so far. To prospectively test the efficacy of subcorial axillary curettage by gravimetric evaluation of pre- and postsurgical sweat rates. Conservatively pretreated patients received subcorial curettage under tumescent local anesthesia using a sharp spoon. Sweat rates of each axilla were determined gravimetrically before and 4-8 weeks after surgery. Evaluation was performed with respect to baseline sweat rates greater than 50 mg/min (group A), greater than 25 and less than 50 mg/min (group B), and less than 25 mg/min (group C). Side effects and patients' ratings were also recorded. Of 42 treated patients, 38 could be evaluated completely. In 29 axillae of group A (high sweat rates), an average reduction from the baseline of 85.6 mg/min to 21.6 mg/min could be achieved (P <.0001). Corresponding values for 22 axillae of group B (medium sweat rates) were 36.8 mg/min and 16.5 mg/min (P <.0001). In 25 axillae with low sweat rates (group C), a significant reduction in sweat rates could not be achieved. The results remained almost stable during a median follow-up of 11 months (range 4-24 months). Only minor side effects were observed and patient satisfaction was high in groups A and B. Subcorial curettage is an effective treatment of axillary hyperhidrosis for patients with baseline sweat rates greater than 25 mg/min.


Changes in synaptic plasticity are associated with electroconvulsive shock-induced learning and memory impairment in rats with depression-like behavior.
Accompanied with the effective antidepressant effect, electroconvulsive shock (ECS) can induce cognitive impairment, but the mechanism is unclear. Synaptic plasticity is the fundamental mechanism of learning and memory. This study aimed to investigate the effect of ECS on synaptic plasticity changes in rats with depression-like behavior. Chronic unpredictable mild stress procedure was conducted to establish a model of depression-like behavior. Rats were randomly divided into the following three groups: control group with healthy rats (group C), rats with depression-like behavior (group D), and rats with depression-like behavior undergoing ECS (group DE). Depression-like behavior and spatial learning and memory function were assessed by sucrose preference test and Morris water test, respectively. Synaptic plasticity changes in long-term potentiation (LTP), long-term depression (LTD), depotentiation, and post-tetanic potentiation (PTP) were tested by electrophysiological experiment. ECS could exert antidepressant effect and also induced spatial learning and memory impairment in rats with depression-like behavior. And, data on electrophysiological experiment showed that ECS induced lower magnitude of LTP, higher magnitude of LTD, higher magnitude of depotentiation, and lower magnitude of PTP. ECS-induced learning and memory impairment may be attributed to postsynaptic mechanism of LTP impairment, LTD and depotentiation enhancement, and presynaptic mechanism of PTP impairment.


Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity.
Insulin resistance in skeletal muscle in obesity and T2DM is associated with reduced muscle oxidative capacity, reduced expression in nuclear genes responsible for oxidative metabolism, and reduced activity of mitochondrial electron transport chain. The presented study was undertaken to analyze mitochondrial content and mitochondrial enzyme profile in skeletal muscle of sedentary lean individuals and to compare that with our previous data on obese or obese T2DM group. Frozen skeletal muscle biopsies obtained from lean volunteers were used to estimate cardiolipin content, mtDNA (markers of mitochondrial mass), NADH oxidase activity of mitochondrial electron transport chain (ETC), and activity of citrate synthase and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD), key enzymes of TCA cycle and beta-oxidation pathway, respectively. Frozen biopsies collected from obese or T2DM individuals in our previous studies were used to estimate activity of beta-HAD. The obtained data were complemented by data from our previous studies and statistically analyzed to compare mitochondrial content and mitochondrial enzyme profile in lean, obese, or T2DM cohort. The total activity of NADH oxidase was reduced significantly in obese or T2DM subjects. The cardiolipin content for lean or obese group was similar, and although for T2DM group cardiolipin showed a tendency to decline, it was statistically insignificant. The total activity of citrate synthase for lean and T2DM group was similar; however, it was increased significantly in the obese group. Activity of beta-HAD and mtDNA content was similar for all three groups. We conclude that the total activity of NADH oxidase in biopsy for lean group is significantly higher than corresponding activity for obese or T2DM cohort. The specific activity of NADH oxidase (per mg cardiolipin) and NADH oxidase/citrate synthase and NADH oxidase/beta-HAD ratios are reduced two- to threefold in both T2DM and obesity.


Development of an initiatives package to increase children's vegetable intake in long day care centres using the Multiphase Optimisation Strategy (MOST) randomised factorial experiment.
To inform a package of initiatives to increase children's vegetable intake while in long day care (LDC) by evaluating the independent and combined effects of three initiatives targeting food provision, the mealtime environment and the curriculum. Using the Multiphase Optimisation Strategy (MOST) framework, a 12-week, eight-condition (n 7 intervention, n 1 control) randomised factorial experiment was conducted. Children's dietary intake data were measured pre- and post-initiative implementation using the weighed plate waste method (1× meal and 2× between-meal snacks). Vegetable intake (g/d) was calculated from vegetable provision and waste. The optimal combination of initiatives was determined using a linear mixed-effects model comparing between-group vegetable intake at follow-up, while considering initiative fidelity and acceptability. LDC centres in metropolitan Adelaide, South Australia. 32 centres, 276 staff and 1039 children aged 2-5 years. There were no statistically significant differences between any of the intervention groups and the control group for vegetable intake (all P > 0·05). The curriculum with mealtime environment group consumed 26·7 g more vegetables/child/day than control (ratio of geometric mean 3·29 (95 % CI 0·96, 11·27), P = 0·06). Completion rates for the curriculum (> 93 %) and mealtime environment (61 %) initiatives were high, and acceptability was good (4/5 would recommend), compared with the food provision initiative (0-50 % completed the menu assessment, 3/5 would recommend). A programme targeting the curriculum and mealtime environment in LDC may be useful to increase children's vegetable intake. Determining the effectiveness of this optimised package in a randomised controlled trial is required, as per the evaluation phase of the MOST framework.


A micelle inhibition model for the bioavailability of polycyclic aromatic hydrocarbons in aquatic systems.
A mathematical model was developed to quantify micelle suppression on the bioavailability of hydrophobic organic compounds in aquatic systems. The model was based on a three-compartment dynamic system in which the hydrophobic compounds are taken up and eliminated by organisms with an equilibrium partitioning between water and micelle. The model was validated against data obtained from in vitro studies of the bioaccumulation of naphthalene, anthracene, and chrysene into the gills of the freshwater mussel (Ellipto complanata) in the presence of a surfactant (Tween 80). The model predictions agreed well with the experimental results for all three chemicals. Sensitivity analyses were performed to examine model responses to the surfactant parameters. From the model, we derive an equation for a bioconcentration factor in aquatic surfactant systems to predict the maximum concentration of polycyclic aromatic hydrocarbons (PAHs) in aquatic organisms. From these results, we also propose a micelle inhibition factor for bioconcentration that is a function of the surfactant concentration, critical micelle concentration, and partition coefficient of hydrophobic compounds between water and micelle. Knowledge of these parameters may improve understanding of the partitioning of PAHs into organisms in the presence of surfactants.


Fluorescence Polarization Anisotropy in Microdroplets.
Chemical reactions can be greatly accelerated in microdroplets, but the factors that lead to acceleration are still being elucidated. Using rhodamine 6G (R6G) as a model compound, we studied the density distribution and fluorescence polarization anisotropy of this dye in water-in-oil microdroplets. We found the density of R6G is higher on the surface of the microdroplets, and the ratio of the surface density to that of the center grows with increasing microdroplet radius or with decreasing R6G concentration. The measured fluorescence polarization anisotropy at the surface is almost the same for droplets of different sizes but becomes larger when the concentration is lowered. We also performed three-dimensional simulations by treating R6G+ and its associated anion as a dipole of fixed length and magnitude. The simulation results match quite well the experimental measurements, showing that the density distribution and fluorescence polarization anisotropy can be largely explained by a simple electrostatic model.


Career Transitions for Faculty Members committed to Undergraduate Neuroscience Education.
This article highlights some of the critical issues that were discussed during a breakout session on career transitions at the 2014 Faculty for Undergraduate Neuroscience (FUN) Workshop at Ithaca College on Undergraduate Neuroscience Education: Challenges and Solutions in Creating and Sustaining Programs. Topics included: (1) transitioning from graduate school or a postdoc position to an assistant professor position; (2) preparing for promotion and tenure decisions; (3) balancing teaching, research, and service during a career in academics; (4) exploring alternative career options, including moving to another institution, taking on an administrative position, and working in industry; and (5) deciding when and how to retire. Much of the discussion focused on special challenges that women and minorities face in the academic environment. Participants offered valuable insights and suggestions for helping new faculty members prepare for reappointment, promotion, and tenure decisions, including utilizing networking connections within FUN for letters of support and collaborative opportunities. These networking opportunities were also valued by participants who were in rather unique positions, such as transitioning from a purely administrative role back to a regular faculty position or handling the extra burden of being a chair or program director with essentially the same research and grant-writing expectations of a regular faculty member. The session proved to be enlightening for most participants and though several questions and concerns remained unanswered, several ideas and insights were shared by the participants and a sense of empathy for the unique circumstances many of the participants were experiencing provided an atmosphere of comradery and support that often emanates from these FUN workshop sessions.


Description of a new Brazilian Paraportanus and key to the species of the genus (Insecta, Hemiptera, Cicadellidae, Portanini).
Paraportanus longispinus,, a new leafhopper species from Roraima and Amazonas States, North Brazil, is described and illustrated. The new species can be recognized by the male genital features, especially the distal third of ventral margin of the pygofer with a dentiform short process; plates distinctly longer than pygofer, extending posteriorly beyond pygofer by approximately 1/3 of their length and aedeagus with one pair of spiniform process long crossed and directed ventrally. A checklist and key to males of all known Paraportanus species is provided.


The Gram-Positive Bacterium Leuconostoc pseudomesenteroides Shows Insecticidal Activity against Drosophilid and Aphid Pests.
Insect pests reduce global crop yields by up to 20%, but the most effective control measures are currently based on environmentally hazardous chemical pesticides. An alternative, ecologically beneficial pest-management strategy involves the use of microbial pathogens (or active compounds and extracts derived from them) that naturally target selected insect pests. A novel strain of the bacterium Leuconostoc pseudomesenteroides showed promising activity in our preliminary tests. Here, we investigated its effects in more detail, focusing on drosophilid and aphid pests by testing the survival of two species representing the family Drosophilidae (Drosophila suzukii and D. melanogaster) and one representing the family Aphididae (Acyrthosiphon pisum). We used oral and septic infection models to administer living bacteria or cell-free extracts to adult flies and aphid nymphs. We found that infection with living bacteria significantly reduced the survival of our insect models, whereas the administration of cell-free extracts had a significant effect only in aphids. These results confirm that L. pseudomesenteroides has potential as a new biocontrol agent for sustainable pest management.


Cholesterol mediates chitosan activity on phospholipid monolayers and Langmuir-Blodgett films.
The polysaccharide chitosan has been largely used in many biological applications as a fat and cholesterol reducer, bactericide agent, and wound healing material. While the efficacy for some of such uses is proven, little is known about the molecular-level interactions involved in these applications. In this study, we employ mixed Langmuir and Langmuir-Blodgett (LB) films of negatively charged dimyristoyl phosphatidic acid (DMPA) and cholesterol as cell membrane models to investigate the role of cholesterol in the molecular-level action of chitosan. Chitosan does not remove cholesterol from the monolayer. The interaction with chitosan tends to expand the DMPA monolayer due to its interpenetration within the film. On the other hand, cholesterol induces condensation of the DMPA monolayer. The competing effects cause the surface pressure isotherms of mixed DMPA-cholesterol films on a chitosan subphase to be unaffected by the cholesterol mole fraction, due to distinct degrees of chitosan penetration into the film in the presence of cholesterol. By combining polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) and sum-frequency generation spectroscopy (SFG), we showed that chitosan induces order into negatively charged phospholipid layers, whereas the opposite occurs for cholesterol. In conclusion, chitosan has its penetration in the film modulated by cholesterol, and electrostatic interactions with negatively charged phospholipids, such as DMPA, are crucial for the action of chitosan.


Cultural diversity broadens social networks.
Migration and mobility increase the cultural diversity of a society. Does this diversity have consequences for how people interact and form social ties, even when they join a new community? We hypothesized that people from regions with greater cultural diversity would forge more diversified social ties in a newly formed community, connecting otherwise unconnected groups. In other words, they would become social brokers. We tested this prediction by characterizing the social networks of eight Master of Business Administration cohorts (N = 2,257) at a business school in the U.S. International students (N = 773) from populations with both greater present day ethnic diversity and a history of extensive cultural intermingling were more likely to become social brokers than international students from less diverse nations. Domestic students' (N = 1,461) brokerage scores were also positively related to the ancestral diversity of the U.S. county they identified as "home." The results of this study suggest that more culturally diverse social environments-defined here at multiple geographic and temporal scales-endow people with socially adaptable behaviors that help them connect broadly within new, heterogeneous communities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Docetaxel Inhibits Epithelial-Mesenchymal Transition in Human Mammary Cells.
Epithelial-mesenchymal transition (EMT) is a reversible and dynamic biological process in which epithelial cells acquire mesenchymal characteristics including enhanced stemness and migratory ability. EMT can facilitate cancer metastasis and is a known driver of cellular resistance to common chemotherapeutic drugs, such as docetaxel. Current chemotherapeutic practices such as docetaxel treatment can promote EMT and increase the chance of tumor recurrence and resistance, calling for new approaches in cancer treatment. Here we show that prolonged docetaxel treatment at a sub-IC50 concentration inhibits EMT in immortalized human mammary epithelial (HMLE) cells. Using immunofluorescence, flow cytometry, and bulk transcriptomic sequencing to assess EMT progression, we analyzed a range of cellular markers of EMT in docetaxel-treated cells and observed an upregulation of epithelial markers and downregulation of mesenchymal markers in the presence of docetaxel. This finding suggests that docetaxel may have clinical applications not only as a cytotoxic drug but also as an inhibitor of EMT-driven metastasis and multidrug resistance depending on the concentration of its use.


Pyvolve: A Flexible Python Module for Simulating Sequences along Phylogenies.
We introduce Pyvolve, a flexible Python module for simulating genetic data along a phylogeny using continuous-time Markov models of sequence evolution. Easily incorporated into Python bioinformatics pipelines, Pyvolve can simulate sequences according to most standard models of nucleotide, amino-acid, and codon sequence evolution. All model parameters are fully customizable. Users can additionally specify custom evolutionary models, with custom rate matrices and/or states to evolve. This flexibility makes Pyvolve a convenient framework not only for simulating sequences under a wide variety of conditions, but also for developing and testing new evolutionary models. Pyvolve is an open-source project under a FreeBSD license, and it is available for download, along with a detailed user-manual and example scripts, from http://github.com/sjspielman/pyvolve.


CD55 costimulation induces differentiation of a discrete T regulatory type 1 cell population with a stable phenotype.
Unlike other helper T cells, the costimulatory ligands responsible for T regulatory type 1 (Tr1) cell differentiation remain undefined. Understanding the molecular interactions driving peripheral Tr1 differentiation is important because Tr1s potently regulate immune responses by IL-10 production. In this study, we show that costimulation of human naive CD4(+) cells through CD97/CD55 interaction drives Tr1 activation, expansion, and function. T cell activation and expansion was equipotent with CD55 or CD28 costimulation; however, CD55 costimulation resulted in two IL-10-secreting populations. Most IL-10 was secreted by the minor Tr1 population (IL-10(high)IFN-γ(-)IL-4(-), <5% cells) that expresses Tr1 markers CD49b, LAG-3, and CD226. This Tr1 phenotype was not restimulated by CD28. However, on CD55 restimulation, Tr1s proliferated and maintained their differentiated IL-10(high) phenotype. The Tr1s significantly suppressed effector T cell function in an IL-10-dependent manner. The remaining (>95%) cells adopted a Th1-like IFN-γ(+) phenotype. However, in contrast to CD28-derived Th1s, CD55-derived Th1s demonstrated increased plasticity with the ability to coexpress IL-10 when restimulated through CD55 or CD28. These data identify CD55 as a novel costimulator of human Tr1s and support a role for alternative costimulatory pathways in determining the fate of the growing number of T helper populations. This study demonstrates that CD55 acts as a potent costimulator and activator of human naive CD4(+) cells, resulting in the differentiation of a discrete Tr1 population that inhibits T cell function in an IL-10-dependent manner and maintains the Tr1 phenotype upon restimulation.


Expression of equine glucose transporter type 4 in skeletal muscle after glycogen-depleting exercise.
To clone and sequence cDNA for equine insulin-responsive glucose transporter (glucose transporter type 4 [GLUT-4]) and determine effects of glycogen-depleting exercise and meal type after exercise on GLUT-4 gene expression in skeletal muscle of horses. Muscle biopsy specimens from 7 healthy adult horses. Total RNA was extracted from specimens, and GLUT-4 cDNA was synthesized and sequenced. Horses were exercised on 3 consecutive days. On the third day of exercise, for 8 hours after exercise, horses were either not fed, fed half of daily energy requirements as hay, or fed an isocaloric amount of corn. The GLUT-4 mRNA was determined by use of real-time reverse transcriptase-polymerase chain reaction in muscle biopsy specimens obtained before 3 consecutive days of exercise and within 10 minutes and 4, 8, and 24 hours after the third exercise bout. A 1,629-bp segment was sequenced, of which 1,530 bp corresponded to the coding region end encoded a protein of 509 amino acids. Expression of GLUT-4 gene increased by 2.3, 4.3, 3.3, and 2.6 times 10 minutes and 4, 8, and 24 hours after exercise, respectively, compared with that prior to exercise. No differences were observed in GLUT-4 gene expression among conditions of feed withholding, corn feeding, and hay feeding during the 8 hours postexercise. Lack of increase of GLUT-4 gene expression after grain feeding and exercise may explain the apparently slower rate of glycogen synthesis after exercise in horses relative to that of other species.


Differentiated type II pneumocytes can be reprogrammed by ectopic Sox2 expression.
The adult lung contains several distinct stem cells, although their properties and full potential are still being sorted out. We previously showed that ectopic Sox2 expression in the developing lung manipulated the fate of differentiating cells. Here, we addressed the question whether fully differentiated cells could be redirected towards another cell type. Therefore, we used transgenic mice to express an inducible Sox2 construct in type II pneumocytes, which are situated in the distal, respiratory areas of the lung. Within three days after the induction of the transgene, the type II cells start to proliferate and form clusters of cuboidal cells. Prolonged Sox2 expression resulted in the reversal of the type II cell towards a more embryonic, precursor-like cell, being positive for the stem cell markers Sca1 and Ssea1. Moreover, the cells started to co-express Spc and Cc10, characteristics of bronchioalveolar stem cells. We demonstrated that Sox2 directly regulates the expression of Sca1. Subsequently, these cells expressed Trp63, a marker for basal cells of the trachea. So, we show that the expression of one transcription factor in fully differentiated, distal lung cells changes their fate towards proximal cells through intermediate cell types. This may have implications for regenerative medicine, and repair of diseased and damaged lungs.


Propagation of desert moss Syntrichia caninervis in peat pellet: a method for rapidly obtaining large numbers of cloned gametophytes.
Syntrichia caninervis is a typical desiccation tolerant moss that is a dominant species forming biological soil crusts in the Gurbantunggut Desert. This study investigated the effect of different explants on regeneration potential by propagating them on peat pellet. Juvenile and green leaves can regenerate secondary protonema within one week and shoots in one-half month in peat pellet. Rhizoids have a great ability to regenerate, and similar to leaf regeneration, secondary protonema is the dominant type of regenerant. The process of stem regeneration is similar to that of whole gametophytes. Stems are the most important integral body part during propagation. The whole gametophyte is the best materials for rapidly propagating gametophyte on peat pellet. This article improves the state of our current knowledge of desiccation tolerant moss cultivation, highlighting efforts to effectively obtain a large number of gametophytes through different explant parts. This work provides a useful resource for the study of S. caninervis as well as biocrust restoration.


[Glitazones and the metabolic syndrome: mechanism of action, pathophysiology and therapeutic indications].
Diabetes mellitus (DM) is considered a major public health problem in both developed and developing countries due to its chronic complications, at the macro or microcirculation, with great impact on mortality and morbidity in all patients. The disease is considered the end of a pathophysiologic process involving peripheral and hepatic insulin resistance and reduced insulin secretion that have been started years before the clinical diagnosis. Metabolic syndrome (MS) is a disorder that results from the increasing prevalence of obesity worldwide. DM is frequently associated with clinical and laboratory features of MS, like abdominal obesity, hypertension, dyslipidemia and microalbuminuria that are also risk factors for cardiovascular disease. Populational studies have demonstrated increasing prevalence of all the features of MS from pre-diabetes to clinical DM resulting in a great risk of cardiovascular disease. The prevalence of MS in DM type 2 is estimated to be >80%. Glitazones are PPAR-gamma agonists that improve insulin sensitivity. These drugs induce the transcription of genes related to glucose and lipid metabolism, and expression of inflammatory and endothelial proteins associated with atherosclerosis process resulting in an improvement in endothelial function. However several questions need to be clarified regarding the glitazones, in special those associated with their adverse effects such as weight gain, edema and heart failure.


Bisphenol AF compromises blood-testis barrier integrity and sperm quality in mice.
The profound influence of environmental chemicals on human health including inducing life-threatening gene mutation has been publicly recognized. Being a substitute for the extensively used endocrine-disrupting chemical BPA, Bisphenol AF (BPAF) has been known as teratogen with developmental toxicities and therefore potentially putting human into the risk of biological hazards. Herein, we deciphered the detrimental effects of BPAF on spermatogenesis and spermiotiliosis in sexual maturity of mice exposing to BPAF (5, 20, 50 mg/kg/d) for consecutive 28 days. BPAF exposure significantly compromises blood-testis barrier integrity and sperm quantity and quality in a dose-dependent manner. Sperms from BPAF exposure mice are featured by severe DNA damage, altered SUMOylation and ubiquitination dynamics and interfered epigenetic inheritance with hypermethylation of H3K27me3 presumably due to the aggregation of cellular reactive oxygen species (ROS). Furthermore, BPAF treatment (50 μM for 24 h) compromises cytoskeleton architecture and tight junction permeability in primary cultured Sertoli cells evidenced by dysfunction of actin regulatory proteins (e.g. Arp3 and Palladin) via activation of ERK signaling, thereby perturbing the privilege microenvironment created by Sertoli cells for spermatogenesis. Overall, our study determines BPAF is deleterious for male fertility, leading to a better appreciation of its toxicological features in our life.


Origin and possible roles of the SOX8 transcription factor gene during sexual development.
SOX8 is a member of the SOX family of developmental transcription factor genes and is closely related to SOX9, a critical gene involved in mammalian sex determination and differentiation. Both genes encode proteins with the ability to bind similar DNA target sequences, and to activate transcription in in vitro assays. Expression studies indicate that the two genes have largely overlapping patterns of activity during mammalian embryonic development. A knockout of SOX8 in mice has no obvious developmental phenotype, suggesting that the two genes are able to act redundantly in a variety of developmental contexts. In particular, both genes are expressed in the developing Sertoli cell lineage of the developing testes in mice, and both proteins are able to activate transcription of the gene encoding anti-Müllerian hormone (AMH), through synergistic action with steroidogenic factor 1 (SF1). We have hypothesized that SOX8 may substitute for SOX9 in species where SOX9 is expressed too late to be involved in sex determination or regulation of AMH expression. However, our studies involving the red-eared slider turtle indicate that SOX8 is expressed at similar levels in males and females throughout the sex-determining period, suggesting that SOX8 is neither a transcriptional regulator for AMH, nor responsible for sex determination or gonad differentiation in that species. Similarly, SOX8 is not expressed in a sexually dimorphic pattern during gonadogenesis in the chicken. Since a functional role(s) for SOX8 is implied by its conservation during evolution, the significance of SOX8 for sexual and other aspects of development will need to be uncovered through more directed lines of experimentation. Copyright 2003 S. Karger AG, Basel


In situ quasi-elastic neutron scattering study on the water dynamics and reaction mechanisms in alkali-activated slags.
In this study, in situ quasi-elastic neutron scattering (QENS) has been employed to probe the water dynamics and reaction mechanisms occurring during the formation of NaOH- and Na2SiO3-activated slags, an important class of low-CO2 cements, in conjunction with isothermal conduction calorimetry (ICC), Fourier transform infrared spectroscopy (FTIR) analysis and N2 sorption measurements. We show that the single ICC reaction peak in the NaOH-activated slag is accompanied with a transformation of free water to bound water (from QENS analysis), which directly signals formation of a sodium-containing aluminum-substituted calcium-silicate-hydrate (C-(N)-A-S-H) gel, as confirmed by FTIR. In contrast, the Na2SiO3-activated slag sample exhibits two distinct reaction peaks in the ICC data, where the first reaction peak is associated with conversion of constrained water to bound and free water, and the second peak is accompanied by conversion of free water to bound and constrained water (from QENS analysis). The second conversion is attributed to formation of the main reaction product (i.e., C-(N)-A-S-H gel) as confirmed by FTIR and N2 sorption data. Analysis of the QENS, FTIR and N2 sorption data together with thermodynamic information from the literature explicitly shows that the first reaction peak is associated with the formation of an initial gel (similar to C-(N)-A-S-H gel) that is governed by the Na+ ions and silicate species in Na2SiO3 solution and the dissolved Ca/Al species from slag. Hence, this study exemplifies the power of in situ QENS, when combined with laboratory-based characterization techniques, in elucidating the water dynamics and associated chemical mechanisms occurring in complex materials, and has provided important mechanistic insight on the early-age reactions occurring during formation of two alkali-activated slags.


Asymmetric spin-echo imaging of magnetically inhomogeneous systems: theory, experiment, and numerical studies.
The ability of the asymmetric spin-echo (ASE) pulse sequence to provide different degrees of spin-echo (SE)-type and gradient-echo (GE)-type contrast when imaging media containing magnetic inhomogeneities is investigated. The dependence of the ASE signal on the size of magnetic field perturbers is examined using theory, computer simulations, and experiment. A theoretical prediction of the ASE signal is obtained using the Anderson-Weiss mean field theory, the results of which are qualitatively supported by computer simulations and experimental studies. It is shown that the ASE sequence can be used to tune the range of perturber sizes that provide the largest contributions to susceptibility contrast effects.


Incidence of dementia and association with APOE genotype in older Cubans.
In an admixed population of older Cubans, the incidence and association of APOE and sociodemographic risk factors with dementia incidence was estimated. A single-phase survey (baseline) of all over 65-year-olds residing in seven catchment areas in Cuba (n=2944) was conducted between 2003 and 2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria. APOE genotype was determined in 2520 participants. An incidence wave was conducted 4.5 years after cohort inception in order to estimate incidence and associations with sociodemographic risk factors of the APOE ε4 genotype. The incidence rate of DSM IV dementia was 9.0 per 1000 person-years (95% CI 7.2-11.3) and of 10/66 dementia was 20.5 per 1000 person-years (95% CI, 17.6-23.5). Older age, a family history of dementia and APOE ε4 genotype were independent risk factors for incident 10/66 dementia. APOE genotype was associated cross-sectionally with dementia prevalence, but the effect on the incidence of dementia was attenuated, and only apparent among those in the youngest age group. The incidence of dementia in the older Cuban population is relatively high and similar to levels reported in Europe and North-America. The study showed that the relationship between APOE ε4 and incident dementia is stronger in the younger-old than the older-old and that this change must be taken into account in models of dementia.