Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia.

Background: This is a placebo-controlled multi-national trial of roluperidone, a compound with antagonist properties for 5-HT2A, sigma2, and α1A-adrenergic receptors, targeting negative symptoms in patients with schizophrenia. This trial follows a previous trial that demonstrated roluperidone superiority over placebo in a similar patient population.

Methods: Roluperidone 32 mg/day, roluperidone 64 mg/day, or placebo was administered for 12 weeks to 513 patients with schizophrenia with moderate to severe negative symptoms.

Overcoming barriers to promotion for women and underrepresented in medicine faculty in academic emergency medicine.

Equity in the promotion of women and underrepresented minorities (URiM) is essential for the advancement of academic emergency medicine and the specialty as a whole. Forward-thinking healthcare organizations can best position themselves to optimally care for an increasingly diverse patient population and mentor trainees by championing increased diversity in senior faculty ranks, leadership, and governance roles. This article explores several potential solutions to addressing inequities that hinder the advancement of women and URiM faculty.

Equal Performance, Different Grade: Women's Performance in Discussion Perceived Worse Than Men's.

We investigate how men and women are evaluated in group discussions. In five studies ( = 761) using a variant of a , we find that, when experimentally and/or statistically controlling for gender differences in behavior, the female performance in a group discussion is devalued in comparison to male performance. This was observed for fellow group members (Study 1) and outside observers (Studies 2-5), in both primarily student (Studies 1, 4, and 5) and mixed samples (Studies 2 and 3), for different measures of performance (perceived helpfulness of the contribution, for work-related competence), across different discussion formats (preformulated chat messages, open chat), and when controlling for the number of female group members (Study 5).

Zoonosis: Update on Existing and Emerging Vector-Borne Illnesses in the USA.

Purpose Of Review: This review describes mosquito- and tick-borne diseases found in the Western Hemisphere. It focuses on emerging diseases and recent geographic shifts in the presence of disease vectors.

Recent Findings: Mosquito and tick vectors have become more widespread as environmental conditions have become more favorable.

Efficacy and Safety of MIN-101: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial of a New Drug in Development for the Treatment of Negative Symptoms in Schizophrenia.

Objective: The authors assessed the efficacy, safety, and tolerability of MIN-101, a compound with affinities for sigma-2 and 5-HT receptors and no direct dopamine affinities, in comparison with placebo in treating negative symptoms in stabilized patients with schizophrenia.

Method: The trial enrolled 244 patients who had been symptomatically stable for at least 3 months and had scores of at least 20 on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). After at least 5 days' withdrawal from all antipsychotic medication, patients were randomly assigned to receive placebo or 32 mg/day or 64 mg/day of MIN-101 for 12 weeks.

Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4 Foxp3 Regulatory T Cells.

Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4 conventional (CD4CD25Foxp3, Tconv) and regulatory (CD4CD25Foxp3, Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4 Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4 Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice.

Direct Binding of the pH-Regulated Protein 1 (Pra1) from Inhibits Cytokine Secretion by Mouse CD4 T Cells.

Opportunistic infections with the saprophytic yeast are a major cause of morbidity in immunocompromised patients. While the interaction of cells and molecules of innate immunity with has been studied to great depth, comparatively little is known about the modulation of adaptive immunity by . In particular, direct interaction of proteins secreted by with CD4 T cells has not been studied in detail.

Hsp90 inhibition ameliorates CD4 T cell-mediated acute Graft versus Host disease in mice.

Introduction: For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co-transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)-a potentially life-threatening complication.

Inhibition of Acid Sphingomyelinase Allows for Selective Targeting of CD4+ Conventional versus Foxp3+ Regulatory T Cells.

CD4 Foxp3 regulatory T cells (Tregs) depend on CD28 signaling for their survival and function, a receptor that has been previously shown to activate the acid sphingomyelinase (Asm)/ceramide system. In this article, we show that the basal and CD28-induced Asm activity is higher in Tregs than in conventional CD4 T cells (Tconvs) of wild-type (wt) mice. In Asm-deficient (Smpd1; Asm) mice, as compared with wt mice, the frequency of Tregs among CD4 T cells, turnover of the effector molecule CTLA-4, and their suppressive activity in vitro were increased.

Assessing sleep architecture and continuity measures through the analysis of heart rate and wrist movement recordings in healthy subjects: comparison with results based on polysomnography.

Objective: The objective of the study was to evaluate the reliability of a new methodology for assessing sleep architecture descriptors based on heart rate and body movement recordings.

Methods: Twelve healthy male and female subjects between 18 and 40 years of age, without sleep disorders and not taking any drug or medication that could affect sleep, were recorded continuously during five consecutive nights. Together with the standard polysomnography, heart rate was recorded with a Holter and wrist movements by actimetry.

In vitro polyclonal activation of conventional T cells with a CD28 superagonist protects mice from acute graft versus host disease.

Upon transplantation of T cells from a CD28 superagonist (CD28-SA) treated donor into an irradiated allogeneic host, the CD28-SA-induced activation and expansion of Treg cells inhibits acute graft versus host disease (aGvHD), while not abrogating the desired graft versus tumor effect. Human peripheral blood CD4(+) T cells, however, harbor only very few Treg cells. Therefore, we studied whether polyclonal in vitro prestimulation of conventional, that is Treg -cell-depleted, CD4(+) T cells of C57BL/6 mice with CD28-SA-coated paramagnetic beads is sufficient to protect recipient BALB/c mice from aGvHD.

The T cell-selective IL-2 mutant AIC284 mediates protection in a rat model of Multiple Sclerosis.

Targeting regulatory T cells (Treg cells) with interleukin-2 (IL-2) constitutes a novel therapeutic approach for autoimmunity. As anti-cancer therapy with IL-2 has revealed substantial toxicities a mutated human IL-2 molecule, termed AIC284 (formerly BAY 50-4798), has been developed to reduce these side effects. To assess whether AIC284 is efficacious in autoimmunity, we studied its therapeutic potential in an animal model for Multiple Sclerosis.

Clinical state assessment in bipolar patients by means of HRV features obtained with a sensorized T-shirt.

The aim of this study is to identify parameters extracted from the Heart Rate Variability (HRV) signal that correlate to the clinical state in patients affected by bipolar disorder. 25 ECG and activity recordings from 12 patients were obtained by means of a sensorized T-shirt and the clinical state of the subjects was assessed by a psychiatrist. Features in the time and frequency domain were extracted from each signal.

Speech analysis for mood state characterization in bipolar patients.

Bipolar disorders are characterized by an unpredictable behavior, resulting in depressive, hypomanic or manic episodes alternating with euthymic states. A multi-parametric approach can be followed to estimate mood states by integrating information coming from different physiological signals and from the analysis of voice. In this work we propose an algorithm to estimate speech features from running speech with the aim of characterizing the mood state in bipolar patients.

Modulation of the Sympatho-Vagal Balance during Sleep: Frequency Domain Study of Heart Rate Variability and Respiration.

Sleep is a complex state characterized by important changes in the autonomic modulation of the cardiovascular activity. Heart rate variability (HRV) greatly changes during different sleep stages, showing a predominant parasympathetic drive to the heart during non-rapid eye movement (NREM) sleep and an increased sympathetic activity during rapid eye movement (REM) sleep. Respiration undergoes important modifications as well, becoming deeper and more regular with deep sleep and shallower and more frequent during REM sleep.

Characterization of a new mouse model for peripheral T cell lymphoma in humans.

Peripheral T cell lymphomas (PTCLs) are associated with a poor prognosis due to often advanced disease at the time of diagnosis and due to a lack of efficient therapeutic options. Therefore, appropriate animal models of PTCL are vital to improve clinical management of this disease. Here, we describe a monoclonal CD8(+) CD4(-) αβ T cell receptor Vβ2(+) CD28(+) T cell lymphoma line, termed T8-28.

Fibroblast growth factor-2 deficiency causes defects in adult hippocampal neurogenesis, which are not rescued by exogenous fibroblast growth factor-2.

Neurogenesis within the adult brain is restricted to selected areas, one of which is the dentate gyrus (DG). Several growth factors have been reported to affect neurogenesis in the adult DG. However, a role of fibroblast growth factor-2 (FGF-2) in adult hippocampal neurogenesis has not been firmly established.

Evaluating infant positioning for lumbar puncture using sonographic measurements.

Objectives: Hypoxia has been observed when infants undergo lumbar puncture in a tight flexed lateral recumbent position. This study used sonographic measurements of lumbar interspinous spaces to investigate the anatomic necessity and advantage derived from this tight flexed positioning in infants.

Methods: This was a brief, prospective, observational study of a convenience sample of patients.

Expression and functions of fibroblast growth factor 2 (FGF-2) in hippocampal formation.

Among the 23 members of the fibroblast growth factor (FGF) family, FGF-2 is the most abundant one in the central nervous system. Its impact on neural cells has been profoundly investigated by in vitro and in vivo studies as well as by gene knockout analyses during the past 2 decades. Key functions of FGF-2 in the nervous system include roles in neurogenesis, promotion of axonal growth, differentiation in development, and maintenance and plasticity in adulthood.

The effect of microstructured surfaces and laminin-derived peptide coatings on soft tissue interactions with titanium dental implants.

In the present study, we investigated the dental implant protection from peri-implant inflammation by improving the soft tissue adhesion on the titanium surface. Porous titanium was used to create, at the level of the transmucosal part of the implants (the "neck"), a microstructured 3-dimensional surface that would tightly seal the interface between the implant and soft tissue. Cell-specific adhesion properties were induced via an adhesion peptide derived from laminin-5 coupled to native or cross-linked PLL/PGA multilayered polyelectrolyte films (MPFs), which are used for biomedical device coatings.

Pediatric hemoptysis with pulmonary hemorrhage and respiratory failure.

Hemoptysis is a rare complaint in the pediatric population. It is most commonly of infectious etiology and is rarely life threatening. However, there are rare life-threatening causes of pediatric hemoptysis, which should be included in the differential diagnoses of children presenting to the emergency department (ED) with this complaint.

Effect of hip abduction and external rotation on femoral vein exposure for possible cannulation.

Femoral vein access is often required during resuscitation efforts and when other routes of intravenous access are difficult. This study evaluated by ultrasound the effect of abduction/external rotation of the hip on venous accessibility. This was a prospective repeated measurement study.