Metformin to treat Huntington disease: A pleiotropic drug against a multi-system disorder.

Huntington disease (HD) is a neurodegenerative disorder produced by an expansion of CAG repeats in the HTT gene. Patients of HD show involuntary movements, cognitive decline and psychiatric impairment. People carrying abnormally long expansions of CAGs (more than 35 CAG repeats) produce mutant huntingtin (mHtt), which encodes tracks of polyglutamines (polyQs). These polyQs make the protein prone to aggregate and cause it to acquire a toxic gain of function. Principally affecting the frontal cortex and the striatum, mHtt disrupts many cellular functions. In addition, this protein is expressed ubiquitously, and some reports show that many other cell types are affected by the toxicity of mHtt. Several studies reported that metformin, a widely-used anti-diabetic drug, is neuroprotective in models of HD. Here, we provide a review of the benefits of this substance to treat HD. Metformin is a pleiotropic drug, modulating different targets such as AMPK, insulin signalling and many others. These molecules regulate autophagy, chaperone expression, and more, which in turn reduce mHtt toxicity. Moreover, metformin alters gut microbiome and its metabolic processes. The study of potential targets, interactions between the drug, host and microbiome, or genomic and pharmacogenomic approaches may allow us to design personalised medicine to treat HD.

Individual and poly-substance use and condomless sex among HIV-uninfected adults reporting heterosexual sex in a multi-site cohort.

BACKGROUND: We analyzed the association between substance use (SU) and condomless sex (CS) among HIV-negative adults reporting heterosexual sex in the Seek, Test, Treat, and Retain (STTR) consortium. We describe the impact of SU as well as person/partner and context-related factors on CS, identifying combinations of factors that indicate the highest likelihood of CS. METHODS: We analyzed data from four US-based STTR studies to examine the effect of SU on CS using two SU exposures: 1) recent SU (within 3 months) and 2) SU before/during sex. Behavioral data were collected via 1:1 or self-administered computerized interviews. Adjusted individual-study, multivariable relative risk regression was used to examine the relationship between CS and SU. We also examined interactions with type of sex and partner HIV status. Pooled effect estimates were calculated using traditional fixed-effects meta-analysis. We analyzed data for recent SU (n = 6781; 82% men, median age = 33 years) and SU before/during sex (n = 2915; 69% men, median age = 40 years). RESULTS: For both exposure classifications, any SU other than cannabis increased the likelihood of CS relative to non-SU (8-16%, p-values< 0.001). In the recent SU group, however, polysubstance use did not increase the likelihood of CS compared to single-substance use. Cannabis use did not increase the likelihood of CS, regardless of frequency of use. Type of sex was associated with CS; those reporting vaginal and anal sex had a higher likelihood of CS compared to vaginal sex only for both exposure classifications (18-21%, p < 0.001). Recent SU increased likelihood of CS among those reporting vaginal sex only (9-10%, p < 0.001); results were similar for those reporting vaginal and anal sex (5-8%, p < 0.01). SU before/during sex increased the likelihood of CS among those reporting vaginal sex only (20%; p < 0.001) and among those reporting vaginal and anal sex (7%; p = 0.002). Single- and poly-SU before/during sex increased the likelihood of CS for those with exclusively HIV-negative partners (7-8%, p ≤ 0.02), and for those reporting HIV-negative and HIV-status unknown partners (9-13%, p ≤ 0.03). CONCLUSION: Except for cannabis, any SU increased the likelihood of CS. CS was associated with having perceived HIV-negative partners and with having had both anal/vaginal sex.

Correlates of psychological intimate partner violence with HIV care outcomes on patients in HIV care.

BACKGROUND: Among people living with HIV (PLWH), physical intimate partner violence (IPV) is associated with poor virologic, psychiatric, and behavioral outcomes. We examined non-physical, psychological intimate partner violence (psy-IPV) and HIV care outcomes using data from two U.S. consortia. METHODS: We conducted multivariable analyses with robust standard errors to compare patients indicating/not indicating psy-IPV. RESULTS: Among PLWH (n = 5950), 9.5% indicated psy-IPV; these individuals were younger (- 3; 95% CI [- 2,-4], p-value < 0.001), less likely to be on antiretroviral treatment (ART) (0.73 [0.55,0.97], p = 0.03), less adherent to ART (- 4.2 [- 5.9,-2.4], p < 0.001), had higher odds of detectable viral load (1.43 [1.15,1.78], p = 0.001) and depression (2.63 [2.18,3.18], p < 0.001), and greater use of methamphetamines/crystal [2.98 (2.30,3.87),p < 0.001], cocaine/crack [1.57 (1.24,1.99),p < 0.001], illicit opioids [1.56 (1.13,2.16),p = 0.007], and marijuana [1.40 (1.15,1.70), p < 0.001]. CONCLUSION: Psychological IPV, even in the absence of physical or sexual IPV, appears to be associated with HIV care outcomes and should be included in IPV measures integrated into routine HIV care.

From Silos to Solidarity: Case Study of a Patient-Centered, Integrative Approach to Opioid Tapering and Chronic Pain Mitigation in a Multidisciplinary AIDS Clinic.

BACKGROUND: People with HIV (PWH) are at a disproportionate risk for experiencing both chronic pain and opioid use disorder (OUD). Prescription opioid tapering is typically addressed within the "silo model" of medical care, whereby attention is focused solely on opioid addiction rather than also addressing chronic pain management, and limited communication occurs between patient and providers. OBJECTIVE: This descriptive case study examined an integrative, collaborative care model consisting of Provider, Physical Therapist (PT), and Patient aimed at decreasing chronic pain and opioid use within a multidisciplinary HIV/AIDS clinic. METHOD: A physical-therapy based model of chronic pain mitigation and physician-driven opioid tapering was implemented. The Provider, PT, and Patient worked collaboratively to address physiological pain, pain coping skills and opioid tapering. A patient case example was used to illustrate the implementation of the model for a future, larger study in the same patient population. RESULTS: This model was feasible in this case example in terms of clinic workflow and acceptability to both the Patient and Providers in this clinic. After the intervention, the Patient's pain was fully eliminated, and he had ceased all opioid use. CONCLUSION: Results of this case study suggest that utilizing an integrative, patient-centered approach to both chronic pain management and opioid tapering may be feasible within the context of a multidisciplinary HIV/AIDS clinic. Generalizability is limited by case study model; however, this gives insight into the value of a collaborative alternative compared to a "silo" model of opioid tapering and chronic pain management in preparation for a larger study.

Checklist of decapod crustaceans from the coast of the São Paulo state (Brazil) supported by integrative molecular and morphological data: IV. Infraorder Anomura: Superfamilies Chirostyloidea, Galatheoidea, Hippoidea and Paguroidea.

This checklist is the fourth contribution resulting from a long-term multidisciplinary project which combined morphological analyses and molecular techniques (mitochondrial DNA markers) for accurate identification of marine and coastal decapod crustaceans of São Paulo State (Brazil). We provide a list of 63 species of the following 11 families of 4 superfamilies of Anomura: Albuneidae (4 spp.), Blepharipodidae (1 sp.), Chirostylidae (1 sp.), Diogenidae (18 spp.), Hippidae (1 sp.), Munididae (8 spp.), Munidopsidae (1 sp.), Paguridae (13 spp.), Parapaguridae (2 spp.), Porcellanidae (13 spp.), and Pylochelidae (1 sp.). Seven species previously reported from the region were neither collected nor found in museum collections during our study, including one (Sympagurus dimorphus) that we suggest to be removed from São Paulo coast fauna lists. We generated new sequences of cytochrome oxidase subunit I (barcode region) and 16S genes of 44 species. This anomuran inventory may serve as guideline for future studies on taxonomy, conservation, population genetics, biogeography, and phylogenetics, which might flag species that deserve further investigations and concerns.

Manifestaciones dermatológicas de COVID-19: ¿casualidad o causalidad? / Cutaneous manifestations of COVID-19: ¿chance or causality?

Resumen En esta revisión narrativa de la literatura se describen las manifestaciones en piel del SARS-CoV-2 en todas las edades reportadas hasta hoy. El objetivo es entender la presentación clínica y el tiempo de aparición en el curso de la enfermedad, para aumentar el rendimiento de las pruebas diagnósticas y mejorar la identificación de pacientes asintomáticos. Para la descripción se clasifican en cinco grupos: relacionadas directa o indirectamente con el virus, toxicodermias, dermatitis de contacto y trauma por presión. Hasta ahora no se ha comprobado si estas lesiones son por una manifestación directa del virus, por una reacción inmunitaria inespecífica o secundarias a los tratamientos usados.

Abstract This narrative review describes the manifestations of SARS-CoV-2 in skin at all ages reported to date. The objective is to understand the clinical presentation and time of onset in the course of the disease, to increase the performance of diagnostic tests and improve the identification of asymptomatic patients. They are classified into five groups: directly or indirectly related to the virus, toxicoderma, contact dermatitis and pressure trauma. Until now it has not been verified whether these lesions are due to a direct manifestation of the virus or due to an immune, nonspecific reaction or the treatments used.

Disrupted inhibitory plasticity and homeostasis in Fragile X syndrome.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder instigated by the absence of a key translation regulating protein, Fragile X Mental Retardation Protein (FMRP). The loss of FMRP in the CNS leads to abnormal synaptic development, disruption of critical periods of plasticity, and an overall deficiency in proper sensory circuit coding leading to hyperexcitable sensory networks. However, little is known about how this hyperexcitable environment affects inhibitory synaptic plasticity. Here, we show that in vivo layer 2/3 of the primary somatosensory cortex of the Fmr1 KO mouse exhibits basal hyperexcitability and an increase in neuronal firing rate suppression during whisker activation. This aligns with our in vitro data that indicate an increase in GABAergic spontaneous activity, a faulty mGluR-mediated inhibitory input and impaired inhibitory plasticity processes. Specifically, we find that mGluR activation sensitivity is overall diminished in the Fmr1 KO mouse leading to both a decreased spontaneous inhibitory postsynaptic input to principal cells and a disrupted form of inhibitory long-term depression (I-LTD). These data suggest an adaptive mechanism that acts to homeostatically counterbalance the cortical hyperexcitability observed in FXS.

Spanish multidisciplinary clinical practice guidelines for Anderson-Fabry Disease in Adults. I. Method and recommendations. / Guía de práctica clínica multidisciplinar española sobre la enfermedad de Anderson-Fabry en adultos. I: Método y recomendaciones.

Anderson-Fabry disease is a severe progressive multisystem condition of genetic origin that affects men and women, reducing their life expectancy and quality of life. The considerable variability in its clinical expression, the difficulties in diagnosing the condition and the current availability of several alternatives for its treatment represent a considerable challenge that justifies the development of evidence-based clinical practice guidelines that can help health professionals in the decision-making process for managing these patients. To develop these guidelines, we conducted a systematic search of the main reference databases using strategies adapted to each of the 32 clinical questions considered. We prepared documents to synthesise the evidence and assess its quality for each of the questions. The methodology employed is based on the Spanish methodology manual for preparing clinical practice guidelines, incorporating the GRADE methodology in the assessment of the scientific evidence and the preparation of the recommendations, considering the quality of the evidence, the risk-benefit balance, patient values and preferences, equity and use of resources. For the definitive preparation of the recommendations, we conducted a structured consensus process based on the Delphi-RAND methodology in 2 rounds, with an expert panel proposed by various scientific societies, research centres and patient associations. Ultimately, we developed 92 specific recommendations for managing Fabry disease.

GROW: a model for mentorship to advance women's leadership in global health.

In this essay, we discuss the under-representation of women in leadership positions in global health (GH) and the importance of mentorship to advance women's standing in the field. We then describe the mentorship model of GROW, Global Research for Women. We describe the theoretical origins of the model and an adapted theory of change explaining how the GROW model for mentorship advances women's careers in GH. We present testimonials from a range of mentees who participated in a pilot of the GROW model since 2015. These mentees describe the capability-enhancing benefits of their mentorship experience with GROW. Thus, preliminary findings suggest that the GROW mentorship model is a promising strategy to build women's leadership in GH. We discuss supplemental strategies under consideration and next steps to assess the impact of GROW, providing the evidence to inform best practices for curricula elsewhere to build women's leadership in GH.

Building the Case for Localized Approaches to HIV: Structural Conditions and Health System Capacity to Address the HIV/AIDS Epidemic in Six US Cities.

Since the discovery of the secondary preventive benefits of antiretroviral therapy, national and international governing bodies have called for countries to reach 90% diagnosis, ART engagement and viral suppression among people living with HIV/AIDS. The US HIV epidemic is dispersed primarily across large urban centers, each with different underlying epidemiological and structural features. We selected six US cities, including Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle, with the objective of demonstrating the breadth of epidemiological and structural differences affecting the HIV/AIDS response across the US. We synthesized current and publicly-available surveillance, legal statutes, entitlement and discretionary funding, and service location data for each city. The vast differences we observed in each domain reinforce disparities in access to HIV treatment and prevention, and necessitate targeted, localized strategies to optimize the limited resources available for each city's HIV/AIDS response.

Delphi-RAND consensus of the Spanish Society of Internal Medicine on the controversies in anticoagulant therapy and prophylaxis in medical diseases. INTROMBIN Project (Uncertainty in thromboprophylaxis in internal medicine). / Consenso Delphi-RAND de la Sociedad Española de Medicina Interna sobre controversias en terapia y profilaxis anticoagulante en enfermedades médicas. Proyecto INTROMBIN (INcertidumbre en TROMBoprofilaxis en Medicina INterna).

The aim of this study was to determine the opinion of internists on the management of anticoagulation and thromboembolism prophylaxis in complex clinical scenarios in which the risk-benefit ratio of surgery is narrow and to develop a consensus document on the use of drugs anticoagulant therapy in this patient group. To this end, we identified by consensus the clinical areas of greatest uncertainty, a survey was created with 20 scenarios laid out in 40 clinical questions, and we reviewed the specific literature. The survey was distributed among the internists of the Spanish Society of Internal Medicine (SEMI) and was completed by 290 of its members. The consensus process was implemented by changing the Delphi-RAND appropriateness method in an anonymous, double-round process that enabled an expert panel to identify the areas of agreement and uncertainty. In our case, we also added the survey results to the panel, a methodological innovation that helps provide additional information on the standard clinical practice. The result of the process is a set of 19 recommendations formulated by SEMI experts, which helps establish guidelines for action on anticoagulant therapy in complex scenarios (high risk or active haemorrhage, short life expectancy, coexistence of antiplatelet therapy or comorbidities such as kidney disease and liver disease), which are not uncommon in standard clinical practice.

[Autism spectrum disorder and prematurity: towards a prospective screening program]. / Trastorno del espectro autista y prematuridad: hacia un programa de cribado prospectivo.

INTRODUCTION: The prevalence of autism spectrum disorders (ASD) reported in current studies in risk groups such as preterm or low birth weight infants is higher than in the normal population. This fact has led to the increase in recent years of screening studies that investigate possible risk factors for ASD in preterm newborns and their developmental trajectory. AIM: To present the results of the main screening studies of preterm newborns in order to propose screening recommendations for this population at risk. DEVELOPMENT: The results of the studies presented suggest the possibility that the trajectory of socio-communicative and behavioral development of preterm infants differed from what was expected if their birth had occurred at term. This supports the fact that screening programs are carried out based on developmental surveillance and that it is advisable to use screening tools adapted to this population at risk. CONCLUSION: Premature children are a risk group that shows differential characteristics for the screening of ASD.

TITLE: Trastorno del espectro autista y prematuridad: hacia un programa de cribado prospectivo.Introduccion. La prevalencia de trastornos del espectro autista (TEA) comunicada en estudios actuales en grupos de riesgo como son los recien nacidos pretermino o con bajo peso al nacer, es mas alta que en la poblacion normal. Este hecho ha supuesto el incremento en los ultimos años de estudios de cribado que investigan posibles factores de riesgo de TEA en los recien nacidos pretermino y su trayectoria evolutiva. Objetivo. Exponer los resultados de los principales estudios de cribado de recien nacidos pretermino a fin de presentar recomendaciones de cribado en esta poblacion de riesgo. Desarrollo. Los resultados de los estudios presentados sugieren la posibilidad de que la trayectoria del desarrollo sociocomunicativo y conductual de los recien nacidos pretermino difiera de lo esperado si su nacimiento se hubiera producido a termino, lo que apoya el hecho de que se realicen programas de cribado basados en una monitorizacion evolutiva del desarrollo y se utilicen herramientas de cribado adaptadas a esta poblacion de riesgo. Conclusion. Los menores prematuros son un grupo de riesgo que muestra caracteristicas diferenciales para el cribado de TEA.

Intervención cognitivo-conductual para trastornos del sueño en adultos mayores / Cognitive-behavioral intervention on senior adults with sleep disorders / Intervenção cognitivo-comportamental para transtornos do sono em idosos

Los trastornos del sueño en el adulto mayor son un problema manifestado con frecuencia, que afecta la calidad de vida y tiene impacto en los costos y el cuidado de salud. La actual forma de manejo de estos problemas se relaciona con prescripciones de fármacos, los cuales tienen efectos secundarios y aumenta su vulnerabilidad. En este contexto, el objetivo de esta investigación es evaluar la efectividad de una intervención cognitivo y conductual, que pretende mejorar el sueño mediante el cambio de los hábitos deficientes, así como el desafío de los pensamientos, las actitudes y las creencias negativas acerca del mismo. El método incluyó intervenciones cognitivo-conductuales grupales, con evaluaciones pre y post intervención. Los resultados indican una media de 9 (Pittsburgh) al inicio del programa y 4.9 al finalizar. Se concluye que la intervención a corto plazo consigue cambios significativos en hábitos e higiene del sueño. Esta investigación orienta a los profesionales de enfermería en la aplicación de estrategias hacia el bienestar del adulto mayor y el desarrollo de la disciplina en el marco del fortalecimiento de cuidados esenciales y fundamentales en procesos vitales.

Sleep disorders among senior adults are a frequent problem which has important impacts on their quality of life, and the costs of healthcare. The current management of these disorders is based on drug prescriptions, which in turn, have secondary effects and also enhance underlying conditions and vulnerabilities. Within this context, the objective of this study was to assess the effectiveness of a cognitive behavioral intervention aimed at improving the quality of sleep of these persons by modifying negative habits, thoughts, and beliefs. The method included group cognitive-behavioral interventions with pre and post assessments. The corresponding results showed a mean of 9 (Pittsburg) at the beginning of the program, and a mean of 4.9 at the end. It was thus concluded that the intervention, in the short term, helped to achieve significant improvements in relation to the sleep hygiene of these persons. This study can orient nursing professionals to establish strategies aimed at the wellbeing of senior adults; all within the vital processes and essential care strengthening framework.

Os transtornos do sono no idoso são um problema manifestado com frequência e que afeta a qualidade de vida e tem impacto nos custos e no cuidado de saúde. A atual forma de manejo destes problemas relaciona-se com prescrições de fármacos, os quais têm efeitos secundários e aumenta sua vulnerabilidade. Neste contexto, o objetivo desta pesquisa é avaliar a efetividade de uma intervenção cognitivo e comportamental, que pretende melhorar o sono mediante a mudança dos hábitos deficientes, assim como o desafio dos pensamentos, as atitudes e as crenças negativas acerca de si próprio. O método incluiu intervenções cognitivo-comportamentais grupais, com avaliações pre e post intervenção. Os resultados indicam uma média de 9 (Pittsburg) ao início do programa e 4.9 para finalizar. Conclui-se que a intervenção a curto prazo consegue câmbios significativos em hábitos e higiene do sono. Esta pesquisa orienta aos profissionais de enfermagem na aplicação de estratégias para o bem-estar do idoso e do desenvolvimento da disciplina no marco do fortalecimento de cuidados essenciais e fundamentais em processos vitais.

Efficacy of a mephentermine-based product as a vasopressor and a cardiac performance enhancer when given intramuscularly to cattle.

The goal of this study was to confirm the vasopressor and cardiac effects of POTENAY® INJETÁVEL (POT), a mephentermine-based product, given to cattle with induced vascular/cardiac depression. Ten healthy Holstein cattle (206 ± 13 kg) followed a randomized-complete-block design (RCBD) utilizing crossover study design. Each animal randomly received (1 ml/25 kg, IM) of either POT (n = 10) or volume-matched placebo control (0.9%NaCl, CP, n = 10). A subset of animals (n = 5) received POT first (day 0) while the remaining (n = 5) received CP; after a six-day washout period, cattle received the opposite compound. Animals were anesthetized and catheterized for systemic/left ventricular hemodynamic monitoring. Myocardial dysfunction/hypotension was induced by increasing the end-tidal isoflurane concentration until arterial blood pressure was 20% lower than at baseline and remained stable. Once the animal was determined to be hypotensive and hemodynamically stable, steady-state hypotensive baseline data (BL2) were acquired, and treatment with either POT or CP was given. Data were acquired post-treatment at every 15 min for 90 min. POT improved cardiac output (+68 L/min, ±14%, p < 0.05), MAP (+14 mmHg, ±4%, p < 0.05), HR (+22 bpm, ±8%, p < 0.05), and peak rates of ventricular pressure change during both systole (dP/dtmax : +37 mmHg/s ±13%, p < 0.05) and diastole (dP/dtmin : +31 mmHg/s, ±7%, p < 0.05). No improvements were noted following placebo-control administration. Results indicate that POT improves cardiac performance and systemic hemodynamics in cattle with induced cardiovascular depression when given as single intramuscular injection.

mPeriod2 Brdm1 and other single Period mutant mice have normal food anticipatory activity.

Animals anticipate the timing of food availability via the food-entrainable oscillator (FEO). The anatomical location and timekeeping mechanism of the FEO are unknown. Several studies showed the circadian gene, Period 2, is critical for FEO timekeeping. However, other studies concluded that canonical circadian genes are not essential for FEO timekeeping. In this study, we re-examined the effects of the Per2 Brdm1 mutation on food entrainment using methods that have revealed robust food anticipatory activity in other mutant lines. We examined food anticipatory activity, which is the output of the FEO, in single Period mutant mice. Single Per1, Per2, and Per3 mutant mice had robust food anticipatory activity during restricted feeding. In addition, we found that two different lines of Per2 mutant mice (ldc and Brdm1) anticipated restricted food availability. To determine if FEO timekeeping persisted in the absence of the food cue, we assessed activity during fasting. Food anticipatory (wheel-running) activity in all Period mutant mice was also robust during food deprivation. Together, our studies demonstrate that the Period genes are not necessary for the expression of food anticipatory activity.

Insulin-like growth factor 1 prevents diastolic and systolic dysfunction associated with cardiomyopathy and preserves adrenergic sensitivity.

AIMS: Insulin-like growth factor 1 (IGF-1)-dependent signalling promotes exercise-induced physiological cardiac hypertrophy. However, the in vivo therapeutic potential of IGF-1 for heart disease is not well established. Here, we test the potential therapeutic benefits of IGF-1 on cardiac function using an in vivo model of chronic catecholamine-induced cardiomyopathy. METHODS: Rats were perfused with isoproterenol via osmotic pump (1 mg kg(-1) per day) and treated with 2 mg kg(-1) IGF-1 (2 mg kg(-1) per day, 6 days a week) for 2 or 4 weeks. Echocardiography, ECG, and blood pressure were assessed. In vivo pressure-volume loop studies were conducted at 4 weeks. Heart sections were analysed for fibrosis and apoptosis, and relevant biochemical signalling cascades were assessed. RESULTS: After 4 weeks, diastolic function (EDPVR, EDP, tau, E/A ratio), systolic function (PRSW, ESPVR, dP/dtmax) and structural remodelling (LV chamber diameter, wall thickness) were all adversely affected in isoproterenol-treated rats. All these detrimental effects were attenuated in rats treated with Iso+IGF-1. Isoproterenol-dependent effects on BP were attenuated by IGF-1 treatment. Adrenergic sensitivity was blunted in isoproterenol-treated rats but was preserved by IGF-1 treatment. Immunoblots indicate that cardioprotective p110α signalling and activated Akt are selectively upregulated in Iso+IGF-1-treated hearts. Expression of iNOS was significantly increased in both the Iso and Iso+IGF-1 groups; however, tetrahydrobiopterin (BH4) levels were decreased in the Iso group and maintained by IGF-1 treatment. CONCLUSION: IGF-1 treatment attenuates diastolic and systolic dysfunction associated with chronic catecholamine-induced cardiomyopathy while preserving adrenergic sensitivity and promoting BH4 production. These data support the potential use of IGF-1 therapy for clinical applications for cardiomyopathies.

Sexual Behaviors of US Women at Risk of HIV Acquisition: A Longitudinal Analysis of Findings from HPTN 064.

We describe the sexual behaviors of women at elevated risk of HIV acquisition who reside in areas of high HIV prevalence and poverty in the US. Participants in HPTN 064, a prospective HIV incidence study, provided information about individual sexual behaviors and male sexual partners in the past 6 months at baseline, 6- and 12-months. Independent predictors of consistent or increased temporal patterns for three high-risk sexual behaviors were assessed separately: exchange sex, unprotected anal intercourse (UAI) and concurrent partnerships. The baseline prevalence of each behavior was >30 % among the 2,099 participants, 88 % reported partner(s) with >1 HIV risk characteristic and both individual and partner risk characteristics decreased over time. Less than high school education and food insecurity predicted consistent/increased engagement in exchange sex and UAI, and partner's concurrency predicted participant concurrency. Our results demonstrate how interpersonal and social factors may influence sustained high-risk behavior by individuals and suggest that further study of the economic issues related to HIV risk could inform future prevention interventions.

The cascade of care in the Eastern European country of Georgia.

OBJECTIVES: Individual and public health benefits of antiretroviral therapy (ART) rely on successful engagement of HIV-infected patients in care. We aimed to evaluate the HIV care continuum in the Eastern European country of Georgia. METHODS: The analysis included all adult (age ≥ 18 years) HIV-infected patients diagnosed in Georgia from January 1989 until June 2012. Data were extracted from the national HIV/AIDS database as of 1 October 2012. The following stages of the HIV care continuum were quantified: HIV infected, HIV diagnosed, linked to care, retained in care, eligible for ART and virologically suppressed. RESULTS: Of 3295 cumulative cases of adult HIV infection reported in Georgia, 2545 HIV-infected patients were known to be alive as of 1 October 2012, which is 52% of the estimated 4900 persons living with HIV in the country. Of the 2545 persons diagnosed with HIV infection, 2135 (84%) were linked to care and 1847 (73%) were retained in care. Of 1446 patients eligible for ART, 1273 (88%) were on treatment and 985 (77%) of them had a viral load <400 HIV-1 RNA copies/mL. Overall, 39% of those diagnosed and 20% of those infected had a suppressed viral load. CONCLUSIONS: The findings of our analysis demonstrate that the majority of patients diagnosed with HIV infection are retained in care. Loss of patients occurs at each step of the HIV care continuum, but the major gap is at the stage of HIV diagnosis. Reducing the number of persons living with undiagnosed HIV infection and simultaneously enhancing engagement in continuous care will be critical to achieve maximum individual and public health benefits of ART.

Adverse events in cancer genetic testing: the third case series.

After repeated media attention in 2013 due to the Angelina Jolie disclosure and the Supreme Court decision to ban gene patents, the demand for cancer genetic counseling and testing services has never been greater. Debate has arisen regarding who should provide such services and the quality of genetics services being offered. In this ongoing case series, we document 35 new cases from 7 states (California, Connecticut, Florida, Georgia, Missouri, Pennsylvania, and Utah) and the District of Columbia of adverse outcomes in cancer genetic testing when performed without the involvement of a certified genetic counselor. We identified 3 major themes of errors: wrong genetic tests ordered, genetic test results misinterpreted, and inadequate genetic counseling. Patient morbidity and mortality were an issue in several of these cases. The complexity of cancer genetic testing and counseling has grown exponentially with the advent of multigene panels that include rare genes and the potential for more variants of uncertain significance. We conclude that genetic counseling and testing should be offered by certified genetics providers to minimize the risks, maximize the benefits, and utilize health care dollars most efficiently.

Tamponade a rare cause of shock in patients with pancreatitis: difficulty of diagnostic in patients with positive pressure ventilation.

The causes of hemodynamic instability in acute pancreatitis are numerous. Although pericardial effusion during pancreatitis is common, a cardiac tamponade is rarely reported. The diagnosis of compressive cardiac disorders (CDD) by echocardiography is easily reported when the patient is breathing spontaneously; it becomes difficult when the patient is assisted with positive pressure ventilation.