[Syncope : updates in primary care medicine].

Syncope is a common reason for consultations and hospitali-zations. A diagnosis is established in 50 % of cases with the initial assessment. It can also be used to stratify the risk of cardiovascular events or recurrence, and their potentially fatal consequences.

Development of in silico models to predict viscosity and mouse clearance using a comprehensive analytical data set collected on 83 scaffold-consistent monoclonal antibodies.

Biologic drug discovery pipelines are designed to deliver protein therapeutics that have exquisite functional potency and selectivity while also manifesting biophysical characteristics suitable for manufacturing, storage, and convenient administration to patients. The ability to use computational methods to predict biophysical properties from protein sequence, potentially in combination with high throughput assays, could decrease timelines and increase the success rates for therapeutic developability engineering by eliminating lengthy and expensive cycles of recombinant protein production and testing. To support development of high-quality predictive models for antibody developability, we designed a sequence-diverse panel of 83 effector functionless IgG1 antibodies displaying a range of biophysical properties, produced and formulated each protein under standard platform conditions, and collected a comprehensive package of analytical data, including in vitro assays and in vivo mouse pharmacokinetics.

Greater lifetime stressor exposure is associated with poorer mental health among sexual minority people of color.

Background: Research has shown that sexual minority people of color experience pervasive and sometimes severe life stressors that increase their risk of experiencing mental health problems, and that can contribute to lifelong health disparities. However, no studies in this population have investigated stressor exposure occurring over the entire lifespan. Moreover, it remains unknown whether these stressor-health effects differ based on the timing or types of stressors experienced.

Corporal Punishment Is Uniquely Associated With a Greater Neural Response to Errors and Blunted Neural Response to Rewards in Adolescence.

Background: Although corporal punishment is a common form of punishment with known negative impacts on health and behavior, how such punishment affects neurocognitive systems is relatively unknown.

Methods: To address this issue, we examined how corporal punishment affected neural measures of error and reward processing in 149 adolescent boys and girls of ages 11 to 14 years (mean age [SD] = 11.02 [1.

Prefrontal Cortex Volume Mediates the Relationship Between Lifetime Chronic Stressor Exposure and Cognition in People Living With and Without HIV.

Objective: Despite considerable research documenting how stress affects brain and neurobehavioral outcomes, few studies have assessed stressor exposure occurring over the entire life span, and no studies have investigated these associations in people living with HIV (PLWH), despite the high stress and disease burden experienced by this population. To address this issue, we examined how cumulative lifetime chronic stressor exposure related to cognition and brain integrity (i.e.

Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe.

Chromosomal instability (CIN) is a hallmark of cancer that results from errors in chromosome segregation during mitosis. Targeting of CIN-associated vulnerabilities is an emerging therapeutic strategy in drug development. KIF18A, a mitotic kinesin, has been shown to play a role in maintaining bipolar spindle integrity and promotes viability of CIN cancer cells.

Assessing lifetime stressor exposure in sport performers: Associations with trait stress appraisals, health, well-being, and performance.

Research has found that greater lifetime stressor exposure increases the risk for mental and physical health problems. Despite this, few studies have examined how stressors occurring over the entire lifespan affect sport performers' health, well-being, and performance, partly due to the difficulty of assessing lifetime stressor exposure. To address this issue, we developed a sport-specific stress assessment module (Sport SAM) for the Stress and Adversity Inventory (STRAIN) and then analyzed the instrument's usability, acceptability, validity, and test-retest reliability.

Lifetime and perceived stress, social support, loneliness, and health in autistic adults.

Objectives: Although the health consequences of life stress exposure in the general population are well known, how different stressors occurring over the lifetime cause morbidity and mortality in autism is unclear, as are the factors that moderate and mediate these associations. The few studies that have compared autistic and nonautistic individuals have used instruments that yield few stress exposure indices and assess stressors occurring over short time periods.

Method: To address these issues, we used the Stress and Adversity Inventory to assess lifetime stressor exposure and perceived stressor severity in 127 autistic and 104 nonautistic adults.

How stress, discrimination, acculturation and the gut microbiome affect depression, anxiety and sleep among Chinese and Korean immigrants in the USA: a cross-sectional pilot study protocol.

Introduction: Although a considerable proportion of Asians in the USA experience depression, anxiety and poor sleep, these health issues have been underestimated due to the model minority myth about Asians, the stigma associated with mental illness, lower rates of treatment seeking and a shortage of culturally tailored mental health services. Indeed, despite emerging evidence of links between psychosocial risk factors, the gut microbiome and depression, anxiety and sleep quality, very few studies have examined how these factors are related in Chinese and Korean immigrants in the USA. The purpose of this pilot study was to address this issue by (a) testing the usability and feasibility of the study's multilingual survey measures and biospecimen collection procedure among Chinese and Korean immigrants in the USA and (b) examining how stress, discrimination, acculturation and the gut microbiome are associated with depression, anxiety and sleep quality in this population.

Beyond WEIRD: Associations between socioeconomic status, gender, lifetime stress exposure, and depression in Madagascar.

Objective: Although research has examined associations between socioeconomic status (SES), gender, and acute and chronic life stressors in depression, most studies have been conducted in Western, educated, industrialized, rich, democratic (WEIRD) populations.

Method: We addressed this issue by interviewing 65 adults (55 women, M  = 37) living in Madagascar, a typical low- and middle-income country.

Results: As hypothesized, women experienced more life stressors and depressive symptoms, on average, than men, as did those from lower (vs.

Rational selection of building blocks for the assembly of bispecific antibodies.

Bispecific antibodies, engineered to recognize two targets simultaneously, demonstrate exceptional clinical potential for the therapeutic intervention of complex diseases. However, these molecules are often composed of multiple polypeptide chains of differing sequences. To meet industrial scale productivity, enforcing the correct quaternary assembly of these chains is critical.

Complex assessment of relationship quality within dyads.

Higher quality relationships have been linked to improved outcomes; however, the measurement of relationship quality often ignores its complexity and the possibility of co-occurring positivity and negativity across different contexts. The goal of this study is to test the added benefit of including multiple dimensions, contexts, and perspectives of relationship quality from both individuals in predicting marital functioning. The Social Relationships Index assessed positive and negative dimensions of relationship quality under neutral, positive, and support-seeking contexts for 183 heterosexual married couples.

Psychosocial Interventions and Immune System Function: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Importance: Recent estimates suggest that more than 50% of all deaths worldwide are currently attributable to inflammation-related diseases. Psychosocial interventions may represent a potentially useful strategy for addressing this global public health problem, but which types of interventions reliably improve immune system function, under what conditions, and for whom are unknown.

Objective: To address this issue, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) in which we estimated associations between 8 different psychosocial interventions and 7 markers of immune system function, and examined 9 potential moderating factors.

High Mass Analysis with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: From Inorganic Salt Clusters to Antibody Conjugates and Beyond.

Analysis of proteins and complexes under native mass spectrometric (MS) and solution conditions was typically performed using time-of-flight (ToF) analyzers, due to their routine high / transmission and detection capabilities. However, over recent years, the ability of Orbitrap-based mass spectrometers to transmit and detect a range of high molecular weight species is well documented. Herein, we describe how a 15 Tesla Fourier transform ion cyclotron resonance mass spectrometer (15 T FT-ICR MS) is more than capable of analyzing a wide range of ions in the high / scale (>5000), in both positive and negative instrument polarities, ranging from the inorganic cesium iodide salt clusters; a humanized IgG1 monoclonal antibody (mAb; 148.

The Stress and Adversity Inventory for Adults (Adult STRAIN) in Brazilian Portuguese: Initial Validation and Links With Executive Function, Sleep, and Mental and Physical Health.

It has been widely hypothesized that stressors occurring over the lifespan exert a cumulative impact on health, but little work has directly tested these theories given the difficulty associated with measuring cumulative stress exposure over the lifespan. We addressed this issue in Brazil by translating the Stress and Adversity Inventory for Adults (Adult STRAIN) into Brazilian Portuguese. We then examined the instrument's usability and acceptability; concurrent, discriminant, predictive, and incremental validity; and test-retest reliability.

Effects of Buffer Composition on Site-Specific Glycation of Lysine Residues in Monoclonal Antibodies.

Candidate antibodies under consideration for development as pharmaceuticals must be screened for potential liabilities. Glycation of lysine side chains is one liability which can significantly alter the efficacy of a therapeutic antibody. Antibody candidates are often subjected to stress-testing after purification to assess liabilities that may arise from variability in the manufacturing process and gauge the manufacturability of the molecule.

Feel free to write this down: Writing about a stressful experience does not impair change detection task performance.

Acute stress impairs working memory (i.e., the ability to update and keep information in mind).

Rapid LC-MS Method for Accurate Molecular Weight Determination of Membrane and Hydrophobic Proteins.

Therapeutic target characterization involves many components, including accurate molecular weight (MW) determination. Knowledge of the accurate MW allows one to detect the presence of post-translational modifications, proteolytic cleavages, and importantly, if the correct construct has been generated and purified. Denaturing liquid chromatography-mass spectrometry (LC-MS) can be an attractive method for obtaining this information.

Discovery, characterization, and remediation of a C-terminal Fc-extension in proteins expressed in CHO cells.

Protein-based biotherapeutics are produced in engineered cells through complex processes and may contain a wide variety of variants and post-translational modifications that must be monitored or controlled to ensure product quality. Recently, a low level (~1-5%) impurity was observed in a number of proteins derived from stably transfected Chinese hamster ovary (CHO) cells using mass spectrometry. These molecules include antibodies and Fc fusion proteins where Fc is on the C-terminus of the construct.

Serological evidence of hepatitis E virus infection in zoo animals and identification of a rodent-borne strain in a Syrian brown bear.

Hepatitis E virus (HEV) is the causative agent of hepatitis E, an emerging infectious disease of humans. HEV infections have also been described in various animal species. Whereas domestic pigs and wild boars are well-known animal reservoirs for HEV, the knowledge on natural HEV infection in zoo animals is scarce so far.

Detection of HEV-specific antibodies in four non-human primate species, including great apes, from different zoos in Germany.

The hepatitis E virus (HEV) has been described in humans and various animal species in different regions of the world. However, the knowledge on natural HEV infection in non-human primates and the corresponding risk of zoonotic transmission is scarce. To determine whether primates in captivity are affected by HEV infection, we investigated 259 individual sera of clinically healthy non-human primates of 14 species from nine German zoos.

Developing a Strategy Menu for Community-Level Obesity Prevention.

Childhood obesity is a complex problem influenced by policies, systems, and environments, and its prevention requires changes across a range of community settings. To address this, we developed an obesity prevention strategy menu and an ongoing study to pilot its use and provide technical support for its implementation. The strategy menu is comprised of a set of effective approaches communities can use to develop tailored, context-specific health interventions based on local community needs and capacity.

Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry as a Platform for Characterizing Multimeric Membrane Protein Complexes.

Membrane protein characterization is consistently hampered by challenges with expression, purification, and solubilization. Among several biophysical techniques employed for their characterization, native-mass spectrometry (MS) has emerged as a powerful tool for the analysis of membrane proteins and complexes. Here, two MS platforms, the FT-ICR and Q-ToF, have been explored to analyze the homotetrameric water channel protein, AquaporinZ (AqpZ), under non-denaturing conditions.

Hepatitis E virus and related viruses in wild, domestic and zoo animals: A review.

Hepatitis E is a human disease mainly characterized by acute liver illness, which is caused by infection with the hepatitis E virus (HEV). Large hepatitis E outbreaks have been described in developing countries; however, the disease is also increasingly recognized in industrialized countries. Mortality rates up to 25% have been described for pregnant women during outbreaks in developing countries.

Detection of rat hepatitis E virus in wild Norway rats (Rattus norvegicus) and Black rats (Rattus rattus) from 11 European countries.

Rat hepatitis E virus (HEV) is genetically only distantly related to hepeviruses found in other mammalian reservoirs and in humans. It was initially detected in Norway rats (Rattus norvegicus) from Germany, and subsequently in rats from Vietnam, the USA, Indonesia, China, Denmark and France. Here, we report on a molecular survey of Norway rats and Black rats (Rattus rattus) from 12 European countries for ratHEV and human pathogenic hepeviruses.