Polygenic Risk and Social Support in Predicting Depression Under Stress.

Objective: Despite substantial progress in identifying genomic variation associated with major depression, the mechanisms by which genomic and environmental factors jointly influence depression risk remain unclear. Genomically conferred sensitivity to the social environment may be one mechanism linking genomic variation and depressive symptoms. The authors assessed whether social support affects the likelihood of depression development differently across the spectrum of genomic risk in two samples that experienced substantial life stress: 1,011 first-year training physicians (interns) in the Intern Health Study (IHS) and 435 recently widowed Health and Retirement Study (HRS) participants.

A caveat to using wearable sensor data for COVID-19 detection: The role of behavioral change after receipt of test results.

Background: Recent studies indicate that wearable sensors can capture subtle within-person changes caused by SARS-CoV-2 infection and play a role in detecting COVID-19 infections. However, in addition to direct effects of infection, wearable sensor data may capture changes in behavior after the receipt of COVID test results. At present, it remains unclear to what extent the observed discriminative performance of the wearable sensor data is affected by behavioral changes upon receipt of the test results.

Assessment of the Prevalence and Trajectory of Depressive Symptoms by Sexual Orientation During Physician Training.

This cohort study uses survey data to assess the prevalence and development of depressive symptoms among sexual minority and heterosexual physicians during residency training.

Patterns in Actions Against Physician Licenses Related to Substance Use and Psychological or Physical Impairment in the US From 2004 to 2020.

This cross-sectional study examines the frequency of actions taken against physician licenses in the US because of substance use and psychological or physical impairment from 2004 to 2020.

Motor Unit Recruitment is Altered When Acute Experimental Pain is Induced at a Site Distant to the Contracting Muscle.

Acute pain alters motor unit discharge properties in muscles that are painful or influence loading of painful structures. Less is known about the changes in discharge when pain is induced in distant tissues that are unable or have limited capacity to modify the load of the contracting muscle. We aimed to determine whether acute experimental pain alters quadriceps motor unit discharge when pain is induced in; (i) a muscle that is unlikely to be mechanically influenced by modified quadriceps activity (tibialis anterior: TA), or (ii) the antagonist muscle (biceps femoris: BF).

Trends in Depressive Symptoms and Associated Factors During Residency, 2007 to 2019 : A Repeated Annual Cohort Study.

Background: Efforts to address the high depression rates among training physicians have been implemented at various levels of the U.S. medical education system.

Interpersonal Correlates of Dementia Caregivers' Emotional Support Networks: Considering Family History.

Caregiving networks of individuals with Alzheimer's disease and related dementias (ADRD) are comprised of family and friends directly involved in caregiving activities and those supporting these activities. The purpose of this study was to investigate whether caregiving-related behaviors and interactions (i.e.

A Caveat to Using Wearable Sensor Data for COVID-19 Detection: The Role of Behavioral Change after Receipt of Test Results.

Recent studies indicate that wearable sensors have the potential to capture subtle within-person changes that signal SARS-CoV-2 infection. However, it remains unclear the extent to which observed discriminative performance is attributable to behavioral change after receiving test results. We conducted a retrospective study in a sample of medical interns who received COVID-19 test results from March to December 2020.

Efficacy of a Stress Management Intervention for Mothers of Children with Cancer.

Objective: Mothers of children with cancer confront life stress that can impact their psychological and physical health and, in turn, the health of the family. Recommendations advocate preemptive stress-management interventions; however, few studies have investigated their efficacy. Here, we report results of a parallel randomized pilot trial examining health benefits of a stress management intervention designed to teach coping skills.

Dietary Management of Propionic Acidemia: Parent Caregiver Perspectives and Practices.

Background: Propionic acidemia (PA), an autosomal recessive metabolic disorder, has an estimated incidence of 1:105,000-130,000 in the United States. Nutrition management is a main intervention for PA. Research in inborn errors of metabolism such as phenylketonuria has identified association of parental perceptions and practices with dietary outcomes.

Development of glucocorticoid resistance over one year among mothers of children newly diagnosed with cancer.

Chronic distress associates with peripheral release of cortisol and a parallel upregulation of innate inflammation. Typically, cortisol functions to down-regulate inflammatory processes. However, in the context of chronic stress, it is hypothesized that glucocorticoid receptors within immune cells become less sensitive to the anti-inflammatory effects of cortisol, resulting in increased systemic inflammation.

A new lysine derived glyoxal inhibitor of trypsin, its properties and utilization for studying the stabilization of tetrahedral adducts by trypsin.

New trypsin inhibitors Z-Lys-COCHO and Z-Lys-H have been synthesised. values for Z-Lys-COCHO, Z-Lys-COOH, Z-Lys-H and Z-Arg-COOH have been determined. The glyoxal group (-COCHO) of Z-Lys-COCHO increases binding ~300 fold compared to Z-Lys-H.

Quantifying tetrahedral adduct formation and stabilization in the cysteine and the serine proteases.

Two new papain inhibitors have been synthesized where the terminal α-carboxyl groups of Z-Phe-Ala-COOH and Ac-Phe-Gly-COOH have been replaced by a proton to give Z-Phe-Ala-H and Ac-Phe-Gly-H. We show that for papain, replacing the terminal carboxylate group of a peptide inhibitor with a hydrogen atom decreases binding 3-4 fold while replacing an aldehyde or glyoxal group with a hydrogen atom decreases binding by 300,000-1,000,000 fold. Thiohemiacetal formation by papain with aldehyde or glyoxal inhibitors is shown to be ~10,000 times more effective than hemiacetal or hemiketal formation with chymotrypsin.

Hemiacetal stabilization in a chymotrypsin inhibitor complex and the reactivity of the hydroxyl group of the catalytic serine residue of chymotrypsin.

The aldehyde inhibitor Z-Ala-Ala-Phe-CHO has been synthesized and shown by (13)C-NMR to react with the active site serine hydroxyl group of alpha-chymotrypsin to form two diastereomeric hemiacetals. For both hemiacetals oxyanion formation occurs with a pKa value of ~7 showing that chymotrypsin reduces the oxyanion pKa values by ~5.6 pKa units and stabilizes the oxyanions of both diastereoisomers by ~32kJmol(-1).

Enteropathogenic Escherichia coli type III effectors EspG and EspG2 disrupt the microtubule network of intestinal epithelial cells.

Enteropathogenic Escherichia coli infection of intestinal epithelial cells leads to localized depletion of the microtubule cytoskeleton, an effect that is dependent on delivery of type III translocated effector proteins EspG and Orf3 (designated EspG2) to the site of depletion. Microtubule depletion involved disruption rather than displacement of microtubules.

Interaction of enteropathogenic Escherichia coli with human intestinal mucosa: role of effector proteins in brush border remodeling and formation of attaching and effacing lesions.

Enteropathogenic Escherichia coli (EPEC) strains deliver effector proteins Tir, EspB, Map, EspF, EspH, and EspG into host cells to induce brush border remodeling and produce attaching and effacing (A/E) lesions on small intestinal enterocytes. In this study, the role of individual EPEC effectors in brush border remodeling and A/E lesion formation was investigated with an in vitro human small intestinal organ culture model of EPEC infection and specific effector mutants. tir, map, espB, and espH mutants produced "footprint" phenotypes due to close bacterial adhesion but subsequent loss of bacteria; an espB mutant and other type III secretion system mutants induced a "noneffacing footprint" associated with intact brush border microvilli, whereas a tir mutant was able to efface microvilli resulting in an "effacing footprint"; map and espH mutants produced A/E lesions, but loss of bacteria resulted in a "pedestal footprint.

Enteropathogenic Escherichia coli (EPEC) adhesion to intestinal epithelial cells: role of bundle-forming pili (BFP), EspA filaments and intimin.

Enteropathogenic Escherichia coli (EPEC), an important paediatric diarrhoeal pathogen, employs multiple adhesins to colonize the small bowel and produces characteristic 'attaching and effacing' (A/E) lesions on small intestinal enterocytes. EPEC adhesins that have been associated with A/E adhesion and intestinal colonization include bundle-forming pili (BFP), EspA filaments and intimin. BFP are involved in bacteria-bacteria interaction and microcolony formation but their role in cell adhesion remains unclear; EspA filaments are components of the EPEC type III secretion system but since they interact directly with host cells they may also function as adhesins; intimin is the well characterized intimate EPEC adhesin which binds the translocated intimin receptor, Tir.

Involvement of the intermediate filament protein cytokeratin-18 in actin pedestal formation during EPEC infection.

While remaining extracellular, enteropathogenic Escherichia coli (EPEC) establish direct links with the cytoskeleton of the target epithelial cell leading to the formation of actin-rich pedestals underneath attached bacteria. The translocated adaptor protein Tir forms the transmembrane bridge between the cytoskeleton and the bacterium; the extracellular domain of Tir functions as a receptor for the bacterial adhesin intimin, while the intracellular amino and carboxy termini interact with a number of focal adhesion and other cytoskeletal proteins; and recruitment of some is dependent on phosphorylation of Tyr 474. Using Tir as bait and HeLa cell cDNA library as prey in a yeast two-hybrid screen, we identified cytokeratin 18 as a novel Tir partner protein.