No door to lock: victimization among homeless and marginally housed persons

BACKGROUND: Homeless persons experience high rates of sexual and physical assault; homeless women are thought to be at highest risk. To determine the prevalence, distribution, and factors associated with sexual and physical assault, we surveyed homeless and marginally housed adults in San Francisco, Calif. METHODS: We interviewed 2577 respondents about their history of recent sexual and physical assault, housing history, sexual practices, substance use, health status, and criminal justice history. The main outcome measures were self-reported sexual and physical assault in the previous 12 months. RESULTS: Overall, 32.3% of women, 27.1% of men, and 38.1% of transgendered persons reported a history of either sexual or physical assault in the previous year; 9.4% of women, 1.4% of men, and 11.9% of transgendered persons reported sexual assault, and 30.6% of women, 26.6% of men, and 33.3% of transgendered persons reported physical assault. In multivariate models, being homeless (as opposed to marginally housed) was associated with sexual assault for women, but not for men (adjusted odds ratio for homeless women, 3.4 [1.2-9.7]). Housing status was not associated with physical assault for women or men. Mental illness and sex work were both common and associated with high rates of assault in multivariate analyses. CONCLUSIONS: Sexual and physical assault are common experiences for homeless and marginally housed persons. Housing is associated with lower rates of sexual assault among women. Strategies to decrease sexual and physical assault and its consequences are needed in this population.     

Phenotypes and distribution of mucosal memory B-cell populations in the SIV/SHIV rhesus macaque model

As vaccine-elicited antibodies have now been associated with HIV protective efficacy, a thorough understanding of mucosal and systemic B-cell development and maturation is needed. We phenotyped mucosal memory B-cells, investigated isotype expression and homing patterns, and defined plasmablasts and plasma cells at three mucosal sites (duodenum, jejunum and rectum) in rhesus macaques, the commonly used animal model for pre-clinical vaccine studies. Unlike humans, macaque mucosal memory B-cells lacked CD27 expression; only two sub-populations were present: naïve (CD21⁺CD27⁻) and tissue-like (CD21⁻CD27⁻) memory. Similar to humans, IgA was the dominant isotype expressed. The homing markers CXCR4, CCR6, CCR9 and α4β7 were differentially expressed between naïve and tissue-like memory B-cells. Mucosal plasmablasts were identified as CD19⁺CD20^+/−HLA-DR⁺Ki-67⁺IRF4⁺CD138^+/− and mucosal plasma cells as CD19⁺CD20⁻HLA-DR⁻Ki-67⁻IRF4⁺CD138⁺. Both populations were CD39^+/−CD27⁻. Plasma cell phenotype was confirmed by spontaneous IgA secretion by ELISpot of positively-selected cells and J-chain expression by real-time PCR. Duodenal, jejunal and rectal samples were similar in B-cell memory phenotype, isotype expression, homing receptors and plasmablast/plasma cell distribution among the three tissues. Thus rectal biopsies adequately monitor B-cell dynamics in the gut mucosa, and provide a critical view of mucosal B-cell events associated with development of vaccine-elicited protective immune responses and SIV/SHIV pathogenesis and disease control.     

Association of a Common Genetic Factor,PTGER3, With Outcome of Periodontal Therapy and Preterm Birth

Background: Clinical evidence suggests an association between preterm birth and periodontal disease. This study explores whether specific genetic polymorphisms are associated with success of periodontal therapy in pregnant women with periodontal disease and, further, whether any of these same polymorphisms are also associated with spontaneous preterm birth (sPTB). Methods: One hundred sixty high‐risk pregnant women (6 to 20 weeks of gestation) with periodontal disease (≥3 sites with attachment loss ≥4 mm) were studied. All women received scaling and root planing plus oral hygiene instruction. Periodontal examinations were performed before treatment and 20 weeks later. Participants were classified according to two study outcomes: 1) success or failure of periodontal treatment; and 2) presence or absence of sPTB. Maternal DNA samples from mucosal swabs were characterized using a 1536‐SNP (single‐nucleotide polymorphism) custom polymerase chain reaction chip. A probabilistic model of each dichotomous outcome, derived using a stepwise Bayesian procedure, was compared to respective null hypotheses on the basis of Monte Carlo simulations and significance estimates obtained using three measures (z‐test, Welch t‐test, and probability convolution). The models were further confirmed by logistic regression analyses. Results: The models revealed a significant relation between a specific polymorphism of prostaglandin E receptor 3 (a gene associated with inflammatory response) and both periodontal treatment failure (odds ratio 11.09, P <0.0002) and sPTB (odds ratio 6.89, P <0.0032). Conclusions: These results demonstrate that the risk of unsuccessful periodontal treatment is associated with tag SNPs in specific genes that regulate the inflammatory response, one of which is also associated with sPTB.     

Five-year outcome from eating disorders: Relevance of personality disorders

In order to assess the relationship of personality disorder and eating disorder outcome 30 eating disordered patients were followed up 4–5 years after taking part in a study examining the prevalence of personality disorders in eating disordered individuals. Subjects with personality disorders did not differ from those without personality disorders in the amount of symptomatic change over time, although their psychopathology generally remained more severe. The relationship of personality disorder and clinical outcome ratings varied depending on the personality measure. SCID-II personality disorder diagnoses were not significantly associated with outcome ratings, but were related to a greater likelihood to be hospitalized and treated with psychotropic medications. Results with a new personality measure, the Wisconsin Personality Inventory, did display an association between personality disturbance and eating disorder outcome ratings and also suggested that borderline personality was a significant predictor of outcome. © 1994 by John Wiley & Sons, Inc.     

Association between perceived racism and physiological stress indices in Native Hawaiians

The association between racism and the physical health of native U.S. populations has yet to be examined despite their high risk for stress-related disorders and a history of discrimination toward them. We examined the correlation between perceived racism and the two physiological stress indices of cortisol level and blood pressure in 146 adult Native Hawaiians. Attributed and felt racism were assessed with a 10-item shortened version of the Oppression Questionnaire. Height, weight, blood pressure, and salivary cortisol samples (AM and PM) were collected and analyzed along with information on Hawaiian ancestry, BMI, age, sex, marital status, education level, general psychological stress, and ethnic identity. The results indicated that Native Hawaiians reporting more attributed racism had significantly (P < .05) lower average cortisol levels than those reporting less attributed racism, after adjusting for socio-demographic, biological, and psychosocial confounders. Native Hawaiians reporting more felt racism had a significantly higher systolic blood pressure than those reporting less, but this association was not significant after adjusting for the aforementioned confounders. Racism appears to be a chronic stressor that can “get under the skin” of Native Hawaiians by affecting their physical health and risk for stress-related diseases, possibly, through mechanisms of cortisol dysregulation.     

Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex

How G protein-coupled receptor conformational dynamics control G protein coupling to trigger signaling is a key but still open question. We addressed this question with a model system composed of the purified ghrelin receptor assembled into lipid discs. Combining receptor labeling through genetic incorporation of unnatural amino acids, lanthanide resonance energy transfer, and normal mode analyses, we directly demonstrate the occurrence of two distinct receptor:Gq assemblies with different geometries whose relative populations parallel the activation state of the receptor. The first of these assemblies is a preassembled complex with the receptor in its basal conformation. This complex is specific of Gq and is not observed with Gi. The second one is an active assembly in which the receptor in its active conformation triggers G protein activation. The active complex is present even in the absence of agonist, in a direct relationship with the high constitutive activity of the ghrelin receptor. These data provide direct evidence of a mechanism for ghrelin receptor-mediated Gq signaling in which transition of the receptor from an inactive to an active conformation is accompanied by a rearrangement of a preassembled receptor:G protein complex, ultimately leading to G protein activation and signaling.G protein-coupled receptors (GPCRs), one of the largest cell surface receptor families, are involved in many cellular signaling processes (1). Based on this property, as well as their importance as drug targets, the molecular aspects of GPCR functioning have been extensively investigated. In particular, coupling to heterotrimeric G proteins has been the focus of numerous studies. Indeed, delineating the molecular mechanisms responsible for receptor:G protein interaction is absolutely required to better understand how signaling is controlled. Recent years have seen spectacular advances that have culminated in elucidation of the 3D structure of the β₂-adrenergic receptor:Gs complex (2). Nevertheless, the need for further progress remains, in particular to fully understand the dynamics of this interaction. This is a crucial question, given that how the receptor interacts with its G protein partner governs signaling, and thus biological and pathophysiological responses.To date, two different models for GPCR:G protein interaction have been proposed: collision coupling and preassembly. Originally, it was proposed that receptors and G proteins couple by collision (3, 4). One of the main features of this model is that only activated receptors interact with G proteins. Since then, alternative models of signaling have been developed. One of these, the preassembly model, proposes that the receptor and the G protein make a complex even in the absence of agonist (5–8). Discriminating between the two models is crucial. Indeed, signaling outputs, such as the kinetics of G protein activation, will be significantly different depending on whether the ligand-free receptor is always in complex with its G protein or must first be activated by the agonist to recruit the G protein and trigger signaling. Moreover, it has been shown that GPCR conformational dynamics (9–11) and signaling in the absence of ligand are key features of GPCR functioning (12). How receptor constitutive activity and conformational dynamics relate to their coupling to the G protein remains an open question.Here we used the purified ghrelin receptor GHS-R1a to analyze the way in which this GPCR interacts with its G protein partners. Ghrelin is a neuroendocrine peptide hormone that acts through its cognate GPCR to control important biological processes, such as growth hormone secretion, food intake, and reward-seeking behaviors (13). Among the GPCRs, GHS-R1a has been shown to have one of the highest basal Gq activation levels both in vitro (10, 14) and in vivo (15, 16). The physiological relevance of GHS-R1a basal activity is substantiated by the occurrence of a natural human mutation in the GHS-R1a gene (A²⁰⁴E substitution in the second extracellular loop of the receptor) that dramatically decreases constitutive activity and is associated with a short-stature phenotype (17). Along with its importance in drug design, GHS-R1a is a prototype for peptide-activated class A GPCRs.To delineate the way in which the ghrelin receptor interacts with G proteins, we used monomeric GHS-R1a reconstituted in a membrane-mimicking environment, lipid discs, and a combination of innovative biochemical [labeling with unnatural amino acid (UAA)] and biophysical [lanthanide resonance energy transfer (LRET) and normal mode (NM) analyses] approaches. By doing so, we provide the first direct evidence that ghrelin-mediated signaling involves a complex dialogue between the conformational dynamics of the receptor and its ability to interact with the different G protein subtypes to which it is coupled.     

Plant Products as Antimicrobial Agents

The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and "leads" which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.     

PIK3CA‐related overgrowth spectrum (PROS): Diagnostic and testing eligibility criteria,differential diagnosis,and evaluation

Somatic activating mutations in the phosphatidylinositol‐3‐kinase/AKT/mTOR pathway underlie heterogeneous segmental overgrowth phenotypes. Because of the extreme differences among patients, we sought to characterize the phenotypic spectrum associated with different genotypes and mutation burdens, including a better understanding of associated complications and natural history. Historically, the clinical diagnoses in patients with PIK3CA activating mutations have included Fibroadipose hyperplasia or Overgrowth (FAO), Hemihyperplasia Multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal (CLOVES) syndrome, macrodactyly, Fibroadipose Infiltrating Lipomatosis, and the related megalencephaly syndromes, Megalencephaly‐Capillary Malformation (MCAP or M‐CM) and Dysplastic Megalencephaly (DMEG). A workshop was convened at the National Institutes of Health (NIH) to discuss and develop a consensus document regarding diagnosis and treatment of patients with PIK3CA‐associated somatic overgrowth disorders. Participants in the workshop included a group of researchers from several institutions who have been studying these disorders and have published their findings, as well as representatives from patient‐advocacy and support groups. The umbrella term of “PIK3CA‐Related Overgrowth Spectrum (PROS)” was agreed upon to encompass both the known and emerging clinical entities associated with somatic PIK3CA mutations including, macrodactyly, FAO, HHML, CLOVES, and related megalencephaly conditions. Key clinical diagnostic features and criteria for testing were proposed, and testing approaches summarized. Preliminary recommendations for a uniform approach to assessment of overgrowth and molecular diagnostic testing were determined. Future areas to address include the surgical management of overgrowth tissue and vascular anomalies, the optimal approach to thrombosis risk, and the testing of potential pharmacologic therapies. © 2014 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.