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.

Utilidad de la telemedicina en la atención pediátrica urgente durante la pandemia por COVID-19 / Usefulness of telemedicine in urgent pediatric care during the COVID-19 pandemic

Introducción: nuestro sistema sanitario ha sufrido una reorganización sin precedentes priorizando la atención de los pacientes con sintomatología COVID-19. El uso de telemedicina se presenta como una alternativa útil en la era pos-COVID. El objetivo del estudio fue valorar la utilidad del servicio de mensajería de Twitter como herramienta de telemedicina para el cribado de patología urgente. Material y métodos: estudio descriptivo, retrospectivo y transversal de un programa de telemedicina desarrollado por un equipo de especialistas en Pediatría y sus Áreas Específicas durante el estado de alarma. Se recogieron datos demográficos, número y motivos de consultas según signos, síntomas y su forma de presentación (texto, foto o vídeo). Se analizó el número de consultas resueltas, derivaciones y el grado de satisfacción. Resultados: se atendió un total de 182 consultas realizadas en su mayoría por mujeres (71%), durante las primeras semanas del confinamiento (70%). El 100% fueron mensajes de texto, acompañados casi en un tercio de los casos de material audiovisual (27,2% fotos, 4,6% vídeos). La edad media de los pacientes atendidos fue de 2,72 ± 2,74 y los principales motivos de consulta: fiebre, exantemas y dificultad respiratoria. El 18,13% tuvo relación con la COVID-19, y solamente el 8,24% fue derivado. Conclusiones: aunque la telemedicina no puede reemplazar la valoración presencial y todavía existen limitaciones técnicas y legales, nuestros resultados sugieren que podría ser una alternativa prometedora para mejorar el acceso, reducir los tiempos de triaje, coordinar los recursos disponibles, y disminuir el riesgo de contagio y saturación de las instalaciones sanitarias (AU)

Introduction: our healthcare system has undergone an unprecedented reorganization, prioritizing the care of patients with COVID-19 symptoms. Telemedicine has emerged as a useful alternative in the post-COVID era. The aim of the study was to assess the usefulness of the Twitter® messaging service as a telemedicine tool for the screening of urgent pathology.Material and methods: cross-sectional, retrospective and descriptive study of a telemedicine programme developed by a team of specialists in paediatrics and its subspecialities during the state of alarm. We collected demographic data and the number and reasons for consultations based on the presenting signs and symptoms and how they were conveyed (text, photo and/or video). We analysed the number of resolved concerns, referrals and the degree of user satisfaction.Results: the service managed a total of 182 consultations, mostly made by women (71%) and during the first weeks of the survey (70%). All consultations included text, accompanied in almost 1/3 of the cases by audiovisual content (27.2% photo, 4.6% video). The average age of the managed patients was 2.72 ± 2.74 years and the main reasons for consultation were fever, exanthema and respiratory difficulty. Of all consultations, 18.13% were related to COVID-19, and only 8.24% led to referral.Conclusions: although telemedicine cannot replace face-to-face assessment and there are still technical and legal limitations, our results suggest that it could be a promising alternative to improve access, reduce triage times, coordinate available resources, and decrease the risk of contagion and the saturation of health care facilities. (AU)

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.

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.

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

La enfermedad de Anderson-Fabry es una afección multisistémica progresiva y grave de origen genético que afecta tanto a hombres como a mujeres y que reduce sus expectativas y calidad de vida. La gran variabilidad en su expresión clínica, las dificultades para su diagnóstico y la disponibilidad actual de varias alternativas para su tratamiento suponen un gran reto que justifica la realización de una guía de práctica clínica basada en la evidencia que pueda ayudar a los profesionales sanitarios en la toma de decisiones en el manejo de estos pacientes. Para elaborarla se ha realizado una búsqueda sistemática en las principales bases de datos bibliográficas mediante estrategias adaptadas a cada una de las 32 preguntas clínicas consideradas. Se confeccionaron fichas para la síntesis y evaluación de la calidad de las evidencias para cada una de las preguntas. La metodología empleada se basa en el Manual metodológico español para la elaboración de guías de práctica clínica e incorpora en la evaluación de la evidencia científica y en la elaboración de las recomendaciones la metodología GRADE, considerando la calidad de la evidencia, el balance entre beneficios y riesgos, valores y preferencias de los pacientes, equidad y uso de recursos. Para la elaboración definitiva de las recomendaciones se llevó a cabo un proceso de consenso estructurado basado en la metodología Delphi-RAND en 2 rondas, con un panel de expertos propuesto por diferentes sociedades científicas, centros de investigación y asociaciones de pacientes. Finalmente, se han elaborado 92 recomendaciones específicas para el manejo de la enfermedad de Fabry

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

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.

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) / 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)

El objetivo de este estudio ha sido conocer la opinión de los internistas sobre el manejo de la anticoagulación y profilaxis tromboembólica en escenarios clínicos complejos en los que el balance riesgo/beneficio de la intervención es estrecho y elaborar un documento de consenso sobre el uso de fármacos anticoagulantes en este grupo de pacientes. Para ello, se identificaron por consenso las áreas clínicas de mayor incertidumbre, se elaboró una encuesta con 20 escenarios desplegados en 40 preguntas clínicas y se realizó una revisión bibliográfica específica. La encuesta se distribuyó entre los internistas de la Sociedad Española de Medicina Interna (SEMI) y fue cumplimentada por 290 de sus miembros. El proceso de consenso se desarrolló mediante una modificación del método Delphi-RAND de adecuación en un proceso anonimizado de doble ronda que permite al panel de expertos identificar áreas de acuerdo y de incertidumbre. En nuestro caso, además, se incorporaron al panel los resultados de la encuesta, innovación metodológica que permite aportar información adicional de la práctica clínica habitual. El resultado del proceso es un conjunto de 19 recomendaciones formuladas por expertos de la SEMI que permite establecer pautas de actuación sobre el tratamiento anticoagulante en escenarios complejos (alto riesgo o hemorragia activa, corta expectativa vital, coexistencia de tratamiento antiagregante o comorbilidades como enfermedad renal, hepática, etc.), que no son infrecuentes en la práctica clínica habitual

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

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.

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.

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.

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.

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.

Fiebre Q y gestación / Q fever and pregnancy

La fiebre Q es una zoonosis de distribución mundial causada por la bacteria Coxiella Burnetii. En la evolución de la enfermedad se diferencia una fase aguda tras la exposición inicial, y otra crónica, meses o años después de la primoinfección. Su prevalencia es desconocida, al tratarse de una patología frecuentemente subclínica, el número de casos en embarazadas se subestima. Esta entidad provoca un incremento de la morbilidad fetal, incluyendo abortos espontáneos, retraso de crecimiento intrauterino (RCIU), oligoamnios, muerte fetal intraútero y amenaza de parto prematuro. Las complicaciones obstétricas son más frecuentes y severas si la infección se contrae durante el primer trimestre de gestación. El embarazo puede actuar como desencadenante para la cronificación del proceso, siendo la endocarditis materna el diagnóstico más común. La terapia prolongada con cotrimoxazol previene la infección placentaria evitando posibles repercusiones fetales, así como protege a la paciente embarazada del desarrollo de fiebre Q crónica (AU)

Q fever is a zoonosis with worldwide distribution caused by Coxiella burnetii. There are two phases of the disease: an acute phase after the initial exposure and another chronic phase, months or years after the primary infection. The prevalence is unknown, since the signs are often subclinical, leading to underestimation of the number of cases in pregnant women. Q fever during pregnancy increases fetal morbidity and mortality and can cause spontaneous abortions, intrauterine growth restriction, oligohydramnios, intrauterine fetal death and threatened preterm birth. Obstetric complications are more frequent and severe if the disease is contracted during the first trimester of gestation. Pregnancy could be a risk factor for chronic Q fever, with maternal endocarditis being the most common diagnosis. Long-term cotrimoxazole therapy avoids placental infection and possible fetal effects, and protects the pregnant patient from chronic Q fever (AU)

Mekuido: intervención en línea para escolares chilenos de apoyo a la prevención del sobrepeso / Mekuido: on line intervention for chilean school children to support prevention of overweight

Se describe la intervención MeKuido disenada para el proyecto "Prevención del sobrepeso y de la obesidad en escolares chilenos: Apuesta a la capacidad emprendedora de los niños" (FONIS SA10I20016). Sujetos y Método: Estudio descriptivo de la intervención realizada a población seleccionada mediante muestreo aleatorio por conglomerado del 50% de los colegios municipalizados de la comuna de La Pintana, conformada por los niños/as que en marzo de 2011, cursaban 5° y 6° año básico, (n=468) y aceptaron participar. Mekuido elemento central de la intervención, es un software con cuatro secciones construidas según marco referencial Orem. Post intervención, se aplicó cuestionario de satisfacción. Resultados: La implementación en el contexto de las actividades escolares demostró ser factible, pero no exenta de dificultades. El cuestionario de satisfacción fue respondido por 355 niños/as (90,8%). En todas las preguntas cerradas más del 80% muestran satisfacción con la intervención y recomendarían su uso. Conclusiones. El marco de referencia de Orem permite diseñar intervenciones para cambio de conductas asociadas a alimentación. Su uso es factible en el contexto escolar, requiere de decisión y compromiso de los profesores. La estrategia puede ser incorporada al curriculum y contribuir al desarrollo de objetivos transversales. La satisfacción con la intervención fue alta.

The MeKuido intervention is described, designed for the project "Prevention of overweight and obesity in Chilean children: Bettinhg on the enterprising capacity of children" (FONIS SA10I20016). Subjects and Method: A descriptive intervention study on a randomly selected population by cluster at 50% of municipal schools in the district of La Pintana, with children enrolled in 5th and 6th grade of primary school who agreed to participate (n = 468). Mekuido, central element is a software with four sections built according to Orem's referential framework. Post intervention, a satisfaction questionnaire was applied. Results: The implementation in the context of school activities proved feasible but not without difficulties. The satisfaction questionnaire was answered by 355 children (90.8%). All closed questions showed over 80% of satisfaction with the intervention and would recommend their use. Conclusion: The Orem framework allows the design of interventions to change behaviors related to feeding. Its use is feasible in the school context, requires determination and commitment of teachers. The strategy can be incorporated into the curriculum and contribute to the development of transversal objectives.

Field Resistance to Verticillium Wilt in Selected Olive Cultivars Grown in Two Naturally Infested Soils.

The resistance of 11 olive cultivars to Verticillium dahliae was assessed in two experimental field trials. One-year-old rooted olive cuttings from the World Olive Germplasm Bank (IFAPA research center, Córdoba, Spain) were planted in a heavily infested field in Utrera (Sevilla province) and in a moderately infested field in Andújar (Jaén province) of southern Spain. Plants were assessed for Verticillium wilt resistance during 22 months based on disease severity and tree growth. Severe disease symptoms were observed 6 months after planting in both trials. Twenty months after planting in the heavily infested soil, V. dahliae had killed nearly all of the trees of 'Bodoquera', 'Cornicabra', 'Manzanilla de Sevilla', and 'Picual', demonstrating the elevated risk of planting susceptible cultivars in a soil heavily infested with V. dahliae. 'Arbequina', 'Koroneiki', 'Sevillenca', and especially 'Frantoio', 'Empeltre', and 'Changlot Real' showed a high level of disease resistance. However, all of them were affected by the disease. Although the field results confirmed the level of resistance previously obtained for these olive genotypes under controlled conditions, there were some discrepancies. This information will be useful in managing the disease and also in selecting new cultivars for the breeding of Verticillium wilt resistance.