Food access, domestic environments, and dietary quality of low-middle income Chilean children during the COVID-19 pandemic.

Introduction: Food access is associated with dietary quality; however, people living in similar physical environments can have different food access profiles. Domestic environments may also influence how food access relates to dietary quality. We studied food access profiles of 999 low-middle income Chilean families with children during the COVID-19 lockdown and how these profiles relate to dietary quality; secondarily, we also explore the role of the domestic environment in this relationship. Materials and methods: Participants of two longitudinal studies conducted in the southeast of Santiago, Chile, answered online surveys at the beginning and end of the COVID-19 pandemic lockdown. Food access profiles were developed by a latent class analysis considering food outlets and government food transfers. Children's dietary quality was estimated by self-reported compliance with the Chilean Dietary Guidelines of Americans (DGA) and daily ultra-processed food (UPF) consumption. Logistic and linear regressions were used to assess the association between food access profiles and dietary quality. Domestic environment data (i.e., the sex of the person who buys food and cooks, meal frequency, cooking skills, etc.) were incorporated in the models to assess their influence on the relationship between food access and dietary quality. Results: We have categorized three food access profiles: Classic (70.2%), Multiple (17.9%), and Supermarket-Restaurant (11.9%). Households led by women are concentrated in the Multiple profile, while families from higher income or education levels are focused on the Supermarket-Restaurant profile. On average, children presented poor dietary quality, with a high daily UPF consumption (median = 4.4; IQR: 3) and low compliance with national DGA recommendations (median = 1.2; IQR: 2). Except for the fish recommendation (OR = 1.77, 95% CI:1.00-3.12; p: 0.048 for the Supermarket-Restaurant profile), the food access profiles were poorly associated with children's dietary quality. However, further analyses showed that domestic environment variables related to routine and time use influenced the association between food access profiles and dietary quality. Conclusion: In a sample of low-middle income Chilean families, we identified three different food access profiles that presented a socioeconomic gradient; however, these profiles did not significantly explain children's dietary quality. Studies diving deeper into household dynamics might give us some clues on intra-household behaviors and roles that could be influencing how food access relates to dietary quality.

Cephalopod-omics: Emerging Fields and Technologies in Cephalopod Biology.

Few animal groups can claim the level of wonder that cephalopods instill in the minds of researchers and the general public. Much of cephalopod biology, however, remains unexplored: the largest invertebrate brain, difficult husbandry conditions, and complex (meta-)genomes, among many other things, have hindered progress in addressing key questions. However, recent technological advancements in sequencing, imaging, and genetic manipulation have opened new avenues for exploring the biology of these extraordinary animals. The cephalopod molecular biology community is thus experiencing a large influx of researchers, emerging from different fields, accelerating the pace of research in this clade. In the first post-pandemic event at the Cephalopod International Advisory Council (CIAC) conference in April 2022, over 40 participants from all over the world met and discussed key challenges and perspectives for current cephalopod molecular biology and evolution. Our particular focus was on the fields of comparative and regulatory genomics, gene manipulation, single-cell transcriptomics, metagenomics, and microbial interactions. This article is a result of this joint effort, summarizing the latest insights from these emerging fields, their bottlenecks, and potential solutions. The article highlights the interdisciplinary nature of the cephalopod-omics community and provides an emphasis on continuous consolidation of efforts and collaboration in this rapidly evolving field.

Association Between Markers of Adiposity During Childhood and Puberty Onset in Latino Girls.

CONTEXT: Prepubertal adiposity is associated with earlier puberty. It is unclear when this association starts, if all adiposity markers are similarly associated, and whether all pubertal milestones are similarly affected. OBJECTIVE: To evaluate the association between different adiposity markers during childhood and the timing of different pubertal milestones in Latino girls. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal follow-up of 539 female participants of the Chilean Growth and Obesity Cohort recruited from childcare centers (mean age 3.5 years) from the southeast area of Santiago, Chile. Participants were singletons born between 2002 and 2003 within the normal birthweight range. Since 2006, a trained dietitian measured weight, height, waist circumference (WC) and skinfolds to estimate body mass index (BMI) Centers for Disease Control and Prevention percentiles, central obesity, percentage of fat mass (%FM), and fat mass index (FMI, fat mass/height2). MAIN OUTCOME: Since 2009, sexual maturation was assessed every 6 months to assess age at (1) thelarche, (2) pubarche, (3) menarche, and (4) peak height velocity (PHV). RESULTS: At thelarche, 12.5% were obese and 2% had central obesity. The median age of pubarche, menarche, and PHV were all associated with markers of adiposity at different time points during childhood whereas thelarche only with %FM and FMI. Adiposity clusters models showed that children with trajectories of high WC, %FM, and FMI during childhood were related with earlier thelarche, pubarche, menarche, and PHV but BMI trajectories only with menarche and PHV. CONCLUSIONS: Higher WC, %FM, and FMI were associated with earlier age at thelarche, pubarche, menarche, and PHV. The effect of BMI was less consistent.

Higher Prepubertal IGF-1 Concentrations Associate to Earlier Pubertal Tempo in Both Sexes.

INTRODUCTION: Pubertal onset is triggered by multiple neuroendocrine interactions. The role of prepubertal IGF-1 in this process has not been explored in both sexes. Our objective was to analyze the association of prepubertal IGF-1 concentration with age at thelarche (B2) and menarche (M) in girls and age at gonadarche (G2) in boys. METHODS: This is a longitudinal study (n = 1,196 boys and girls) within the Growth and Obesity Chilean Cohort Study (GOCS). At age ≈ 6.7 years, blood sample was taken for IGF-1. Subjects were divided into 4 groups according to the onset age of the pubertal event. RESULTS: Higher prepubertal IGF-1 levels were observed at earlier ages of B2 (p = 0.003) and M onset (p = 0.041). A taller prepubertal height was observed at younger ages of B2 and M (p=<0.001 and 0.002, respectively). The hazard proportional regression models (HR) showed that with an increase of 1 SD in IGF-1, the HR of presenting B2 at younger ages was 1.25, and this association was maintained when adjusted for confounding variables. Similarly, the HR of presenting M at earlier ages was 1.21. This association was maintained only when adjusting for body mass index but not using further confounders. In boys, prepubertal IGF-1 showed a tendency to be significantly higher in children with earlier G2 and taller height (both p < 0.001). The HR of presenting G2 at younger ages was 1.22, and this association was maintained after adjusting for confounders. CONCLUSIONS: Higher IGF-1 levels in mid-childhood are associated with earlier puberty onset. The role of IGF-1 in the onset of puberty requires further investigation.

Analysis of surgical and histopathological results of robot-assisted partial nephrectomy with use of three or four robotic arms: an early series results

ABSTRACT Objectives: The aim of this study was to evaluate whether criteria exist to guide election between the use the three- or four-arm technique in robotic partial nephrectomy (RPN) instead of just the surgeon's preference. Material and Methods: We performed a retrospective review of 80 patients submitted to RPN from May 2016 to February 2020. The patients were divided into two groups of 40, the first submitted to the surgical procedure with use of three robotic arms and the second with four arms. The group division was performed independently of the complexity of the cases, age or gender of the patients and laterality of the renal lesions. Peri- and postoperative data were analyzed for comparison between the two groups. Results: Both techniques had similar oncological outcomes (positive tumor margins), renal function preservation (warm ischemia time) and hemorrhagic complications (estimated blood loss and renal artery pseudoaneurysm), with a small difference in the need for blood transfusion, favoring the technique with three arms. Conclusions: The two robotic partial nephrectomy techniques had similar oncological and postoperative outcomes, with minimal perioperative complications. The three-arm technique is safe and feasible regardless of the complexity and size of the tumor. Additionally, the use of the three-arm technique reduced surgery costs by US$ 413.00 per patient.

Analysis of surgical and histopathological results of robot-assisted partial nephrectomy with use of three or four robotic arms: an early series results.

OBJECTIVES: The aim of this study was to evaluate whether criteria exist to guide election between the use the three- or four-arm technique in robotic partial nephrectomy (RPN) instead of just the surgeon's preference. MATERIAL AND METHODS: We performed a retrospective review of 80 patients submitted to RPN from May 2016 to February 2020. The patients were divided into two groups of 40, the first submitted to the surgical procedure with use of three robotic arms and the second with four arms. The group division was performed independently of the complexity of the cases, age or gender of the patients and laterality of the renal lesions. Peri- and postoperative data were analyzed for comparison between the two groups. RESULTS: Both techniques had similar oncological outcomes (positive tumor margins), renal function preservation (warm ischemia time) and hemorrhagic complications (estimated blood loss and renal artery pseudoaneurysm), with a small difference in the need for blood transfusion, favoring the technique with three arms. CONCLUSIONS: The two robotic partial nephrectomy techniques had similar oncological and postoperative outcomes, with minimal perioperative complications. The three-arm technique is safe and feasible regardless of the complexity and size of the tumor. Additionally, the use of the three-arm technique reduced surgery costs by US$ 413.00 per patient.

Straightforward N-Acyl Homoserine Lactone Discovery and Annotation by LC-MS/MS-based Molecular Networking.

N-Acyl-l-homoserine lactones (AHLs) are a large family of signaling molecules in "quorum sensing" communication. This mechanism is present in a number of bacterial physiological phenomena, including pathogenic phenomena. In this study, we described a simple and accessible way to detect, annotate, and quantify these compounds from bacterial culture media. Analytical standards and ethyl acetate bacterial extracts containing AHLs were analyzed by an ultra-high-performance liquid chromatography system coupled to a mass spectrometer using a nontargeted FullMS data-dependent MS2 method. The results were processed in MZmine2 and then analyzed by a Feature-Based Molecular Networking (FBMN) workflow in the Global Natural Products Social Networking (GNPS) platform for the discovery and annotation of known and unknown AHLs. Our group analyzed 31 AHL standards and included the MS2 spectra in the spectral library of the GNPS platform. We also provide the 31 standard AHL spectrum list for inclusion in molecular networking analyses. FBMN analysis annotated 30 out of 31 standards correctly. Then, as an example, a set of five bacterial extracts was prepared for AHL annotation. Following the method described in this Article, 5 known and 11 unknown AHLs were properly annotated using the FBMN-based molecular network approach. This study offers the possibility for the automatic annotation of known AHLs and the search for nonreferenced AHLs in bacterial extracts in a somewhat straightforward approach even without acquiring analytical standards. The method also provides relative quantification information.

Pilot Study of the Influence of Equine Assisted Therapy on Physiological and Behavioral Parameters Related to Welfare of Horses and Patients.

Different welfare indicators were studied in three patients with psychomotor alterations and in two horses throughout 9-10 equine assisted therapy sessions in each patient. In horses, heart and respiratory rates, blood pressure, temperature and behavioral signs were studied. In patients, heart rate, oxygen saturation, temperature, sleep quality, psychomotor and emotional parameters were analyzed. Data collection was recorded in the anticipatory phase (15 min before the start of the session), two interaction phases (after 30 min of horse-patient interaction on the ground and on horseback, respectively) and the recovery phase (15 min after the end of the session). During the anticipatory phase, most of physiological parameters of patients and horses and the stress behavioral signs of horses increased, followed by a relaxing phase during the horse-patient interaction on the ground. In horse-patient riding phase the heart and respiratory rates of the horses again increased. These results showed that the horses did not seem to suffer stress attributable to the therapy sessions, but only an increase in their parameters associated with activity and external stimuli. The patients improved their gross and fine motor skills, their cognitive and perceptual-sensitive parameters and it led to an improvement in the life quality of their families.

Clinical characterization and treatment of head and neck mucosal melanoma: a Chilean experience.

OBJECTIVES: Head and neck mucosal melanoma (HNMM) is a rare disease with a poor prognosis. The aim of this research was to analyze clinical characteristics and prognostic factors in a Latin American cohort. STUDY DESIGN: A retrospective chart review of patients with HNMM treated between 2008 and 2019 was conducted. Demographic characteristics, tumor characteristics, surgical treatment, adjuvant therapy, and oncologic outcomes were recorded. RESULTS: Twenty HNMMs were identified; 60% were in men. The most frequent primary location was the nasal cavity (10; 50%). Regional disease was uncommon and limited to the oral cavity. The median overall survival was 29 months; the 3- and 5-year overall survival rates were 37.2% and 26.6%, respectively. Univariate analysis revealed that predictors of a worse overall survival were paranasal location (hazard ratio [HR], 4.61; 95% confidence interval [CI], 1.61-18.40; P = .030), positive lymph nodes (HR, 6.00; 95% CI, 1.30-27.7; P = .022), positive margins (HR, 4.32; 95% CI, 1.08-17.2; P = .039), bone invasion (HR, 3.27;95% CI, 1.05-10.1; P = .041), and lymphovascular invasion (HR, 3.82; CI, 1.03-14.2; P = .045). Three-year recurrence-free survival was 17.3%, and most of the recurrences were with distant disease. CONCLUSIONS: HNMM is an infrequent disease with an aggressive behavior. Survival outcomes are related to location of the primary disease, regional spread, lymphovascular invasion, and bone invasion.

Empleo del ecocardiograma transtorácico en salas de emergencias / Use of the transthoracic echocardiography in emergency rooms

RESUMEN Introducción: la ecocardiografía ha significado una de las más espectaculares revoluciones en el campo de las ciencias médicas de los últimos cien años. Objetivo: describir algunas indicaciones del ecocardiograma transtorácico en enfermos críticos así como de los cambios terapéuticos inducidos por su resultado. Métodos: se realizó un estudio descriptivo y transversal, entre el 1 de noviembre de 2018 hasta el 31 de enero de 2020 en los servicios de emergencia del Hospital Docente Clínico-Quirúrgico Joaquín Albarrán, en la provincia de La Habana, Cuba. El universo de estudio estuvo constituido por los pacientes (89 en total) que arribaron al servicio de emergencia con inestabilidad hemodinámica en el período señalado; a todos se les realizó un ecocardiograma transtorácico. Resultados: se realizaron 106 ecocardiogramas transtorácicos, y la mayor parte de los pacientes presentaron enfermedades clínicas. En el 100 % de los pacientes fue posible adquirir imágenes útiles para el diagnóstico. En promedio, fueron utilizadas 1,9±1 ventanas acústicas por pacientes; después de la realización del ecocardiograma se realizaron 44 modificaciones terapéuticas (41,5 %). Los cambios más importantes estuvieron relacionados con el aporte de fluidos y el uso de dobutamina. Conclusiones: el ecocardiograma transtorácico, en el contexto de la emergencia, puede ofrecer información clave que conlleve a cambios importantes en la terapéutica.

ABSTRACT Introduction: echocardiography has meant one of the most spectacular revolutions in the field of medical sciences in the last hundred years. Objective: to describe some indications of the transthoracic echocardiography in critically ill patients as well as the therapeutic changes induced by its result. Methods: a descriptive and cross-sectional study was carried out between November 1, 2018 and January 31, 2020 in the emergency services at "Joaquín Albarrán" Clinical and Surgical Teaching Hospital, Havana province, Cuba. The study universe consisted of patients (89 in total) who arrived at the emergency service with hemodynamic instability in the indicated period; all underwent a transthoracic echocardiography. Results: 106 transthoracic echocardiograms were performed, and most of the patients had clinical diseases. It was possible to acquire useful images for the diagnosis in 100% of the patients. On average, 1.9 ± 1 acoustic windows were used per patient; 44 therapeutic modifications were made (41.5%) after performing the echocardiogram. The most important changes were related to fluid intake and the use of dobutamine. Conclusions: the transthoracic echocardiography, in the emergency context, can offer key information that leads to important changes in therapy.

The Association Between Social Support and Psychological Distress in Latina Mothers Living in Miami-Dade County, Florida.

BACKGROUND: This study analysed the relationship between social support and psychological distress in Latina women in Miami-Dade County. Acculturation was examined as a modifying factor. METHODS: A 2005 data set from interviews of 155 Latina mothers in Miami-Dade County, from mother-daughter dyads, was analysed. Social support was measured using the Interpersonal Support Evaluation List (ISEL) score. Psychological distress was based on self-reporting symptoms of depression, anxiety, or suicidality. Acculturation was based on English proficiency and length of U.S. residency. RESULTS: Compared to those with high social support, women with low social support had greater odds of reporting psychological distress (odds ratio = 7.8 [95% CI 2.70-22.10]). Acculturation did not modify the association (p=0.74). CONCLUSIONS: Social support was inversely associated with psychological distress among Latina women. Acculturation was not an effect modifier, likely due to inadequate power. The study has clinical implications for mental illness prevention in this population.

Liderazgo en tiempos de crisis sanitaria por covid-19 / Leadership in times of healthcare crisis due to COVID-19

La pandemia causada por el coronavirus SARS-Cov2 ha puesto a prueba a las organizaciones sanitarias, sus equipos directivos y gestores, y por supuesto a todos los profesionales que las integran, así como a los equipos de soporte. Una crisis sanitaria de estas dimensiones se podría considerar inimaginable, pero cuando acontece con esta magnitud es fundamental que emerja un liderazgo efectivo, un liderazgo capaz de resolver con inmediatez e imaginación todos los problemas no previstos que se originan. En esas circunstancias es preciso contar con un liderazgo ágil, coherente y adaptado a las necesidades más inmediatas que se producen para dar respuesta al gran impacto sociosanitario en la población, al aumento desmedido de pacientes que requieren atención inmediata de forma simultánea, con la gravedad de un proceso desconocido para muchos de ellos, alta demanda de camas en Cuidados Intensivos y Hospitalización específica, hiperdemanda de atención en la Urgencia, así como enfrentarse a situaciones de miedo al tener que manejar una enfermedad provocada por un virus desconocido con alta tasa de infectividad y mortalidad no habitual en nuestro entorno. Los profesionales necesitan establecer vías de comunicación fiable, constante y adaptada a la nueva situación. Los líderes durante la pandemia han de adaptarse rápidamente a la mayor crisis sanitaria conocida en el sistema sanitario español desde hace muchos años y tienen que asumir retos constantes para dar respuestas rápidas y eficientes a las situaciones críticas que se viven en el día a día

The pandemic caused by the SARS-Cov2 coronavirus has represented a test for healthcare organizations, their executive and management teams, and of course all professionals included, as well as their support teams. A healthcare crisis of these dimensions could be considered unimaginable; but when it occurs at such an extent, the emergence of an effective leadership becomes essential: a leadership able to solve immediately and with imagination all those non-foreseen problems that might arise. In these circumstances, it is necessary to have an agile and consistent leadership, adapted to the more immediate needs that appear, in order to address the major sociosanitary impact on the society, the disproportionate increase in patients requiring immediate care simultaneously, with the severity of a condition unknown for many of them, high demand on beds in Intensive Care and specific Hospitalization, hyper demand of Emergency care, as well as to face frightening situations when having to manage a disease caused by an unknown virus with a high infectivity and mortality rate, not usual in our setting. Professionals need to establish reliable communication routes, which are constant and adapted to the new situation. During the pandemic, leaders must adapt in a fast way to the greater healthcare crisis known in the Spanish Health System for many years, and they must accept constant challenges in order to give fast and efficient answers to the critical situations occurring in daily life

Difference in toxicity between HIV-positive and HIV-negative patients with squamous-cell cancer of the anal canal treated with concomitant radio-chemotherapy.

BACKGROUND: The incidence of squamous cell carcinoma of the anal canal has been increasing over the last 30 years. HIV has been found to be a risk factor for the development of this disease; radio-chemotherapy (RTCT) may also be more toxic than in HIV-negative patients. The study aims at assessing whether there are any differences in terms of toxicity between HIV-positive and HIV-negative patients treated with concomitant RTCT. METHODS: Search in MEDLINE, EMBASE, CENTRAL (via Cochrane Library-Wiley), DARE, LILACS bibliographic databases. Experimental and analytical observational studies with at least two comparative arms were included: squamous-cell (SC) anal-canal cancer (ACC) treated with RTCT in HIV-positive vs. HIV-negative patients. RESULTS: Fifteen publications, 14 retrospective studies and 1 systematic review, were found. All radiotherapy (RT) techniques and all chemotherapeutic agents used to manage this disease were included. No differences were found in terms of duration (P=0.67) and dose (P=0.53) of RT, while CT results were contradictory. Acute and hematological toxicities were significantly higher in HIV-positive patients, while gastrointestinal, dermatological and chronic toxicities did not significantly differ between the two groups. Given the high heterogeneity of the studies, no objective comparison could be made between studies that included antiretrovirals and those that did not. CONCLUSIONS: HIV-positive patients may be at higher risk for acute and hematological toxicity than HIV-negative patients. A precise conclusion cannot be drawn on the use of antiretrovirals, given the high heterogeneity of data.

Novel insights into pore-scale dynamics of wettability alteration during low salinity waterflooding.

Low salinity waterflooding has proven to accelerate oil production at core and field scales. Wettability alteration from a more oil-wetting to a more water-wetting condition has been established as one of the most notable effects of low salinity waterflooding. To induce the wettability alteration, low salinity water should be transported to come in contact with the oil-water interfaces. Transport under two-phase flow conditions can be highly influenced by fluids topology that creates connected pathways as well as dead-end regions. It is known that under two-phase flow conditions, the pore space filled by a fluid can be split into flowing (connected pathways) and stagnant (deadend) regions due to fluids topology. Transport in flowing regions is advection controlled and transport in stagnant regions is predominantly diffusion controlled. To understand the full picture of wettability alteration of a rock by injection of low salinity water, it is important to know i) how the injected low salinity water displaces and mixes with the high salinity water, ii) how continuous wettability alteration impacts the redistribution of two immiscible fluids and (ii) role of hydrodynamic transport and mixing between the low salinity water and the formation brine (high salinity water) in wettability alteration. To address these two issues, computational fluid dynamic simulations of coupled dynamic two-phase flow, hydrodynamic transport and wettability alteration in a 2D domain were carried out using the volume of fluid method. The numerical simulations show that when low salinity water was injected, the formation brine (high salinity water) was swept out from the flowing regions by advection. However, the formation brine residing in stagnant regions was diffused very slowly to the low salinity water. The presence of formation brine in stagnant regions created heterogeneous wettability conditions at the pore scale, which led to remarkable two-phase flow dynamics and internal redistribution of oil, which is referred to as the "pull-push" behaviour and has not been addressed before in the literature. Our simulation results imply that the presence of stagnant regions in the tertiary oil recovery impedes the potential of wettability alteration for additional oil recovery. Hence, it would be favorable to inject low salinity water from the beginning of waterflooding to avoid stagnant saturation. We also observed that oil ganglia size was reduced under tertiary mode of low salinity waterflooding compared to the high salinity waterflooding.

La gestión de proximidad, clave en la estrategia de humanización / Proximity Management as the key to a humanization strategy

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The most effective pollinator principle applies to new invasive pollinators.

G. L. Stebbins' most effective pollinator principle states that when pollinators are not limiting, plants are expected to specialize and adapt to the most abundant and effective pollinator species available. In this study, we quantify the effectiveness of bees, hummingbirds and hawkmoths in a Chilean population of Erythranthe lutea (Phrymaceae), and examine whether flower traits are subject to pollinator-mediated selection by the most effective pollinator species during two consecutive years. Unlike most species in the pollinator community, the visitation rate of the recently arrived Bombus terrestris did not change substantially between years, which together with its high and stable pollen delivery to flower stigmas made this species the most important in the pollinator assemblage, followed by the solitary bee Centris nigerrima Flower traits were under significant selection in the direction expected for short-tongue bees, suggesting that E. lutea is in the initial steps of adaptation to the highly effective exotic bumblebee. Our results illustrate the applicability of Stebbins' principle for new invasive pollinators, and stress their importance in driving flower adaptation of native plant species, a critical issue in the face of biotic exchange and homogenization.

A retrospective clinical audit of general practices in Australia to determine the motivation for switch to dolutegravir/abacavir/lamivudine and clinical outcomes.

The most common reasons for switching HIV-1 therapy in patients with virologic suppression are treatment regimen simplification and resolving tolerability issues. Single-pill regimens that include an integrase inhibitor are recommended options. A retrospective clinical audit was performed to determine the motivations for switching to dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC) at high HIV-caseload general practice clinics in Australia. The most common reasons for switching from a prior suppressive therapy to DTG/ABC/3TC were simplification of regimen, resolving toxicity/intolerance and patient preference (73%, 13% and 12%, respectively). Kaplan-Meier analysis showed that the probability of patients remaining on DTG/ABC/3TC therapy at 12 months was 95.1%. Switching to DTG/ABC/3TC from a range of other regimens was associated with a discontinuation rate of 3.2%, with 2.5% of patients discontinuing due to adverse events and no patients discontinuing due to virologic failure. Switching to DTG/ABC/3TC was a viable treatment strategy in this cohort of Australian patients.

Renal safety of coformulated tenofovir/emtricitabine vs other nucleoside analogues in combination therapy in antiretroviral-naive patients aged 50 years or older in Spain: The TRIP study.

OBJECTIVES: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naïve patients >50 years old who started combination antiretroviral therapy (cART). DESIGN: National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009). METHODS: We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non-nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz. RESULTS: We included 103 patients: median age: 54.9 years, 84% males, median CD4 count 247 cells/µl, median viral load 4.7 log; median follow up 18 months (max: 48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV) users in the FTC/TDF group (71.2 vs 98.9 ml/min/1.73 m(2) at month 12, P < 0.05). The risk of renal events (progression to an Chronic Kidney Disease Epidemiology Collaboration value < 60 ml/min/1.73 m(2) in subjects with baseline values >60) was comparable for FTC/TDF users and non users, but was higher and almost significant for LPV/r as compared to EFV users in the FTC/TDF group (adjusted hazard ratio 6.1, 95% CI 0.8-45.5). CONCLUSIONS: In our study with a population of HIV infected subjects ≥ 50 years old, renal safety was similar for FTC/TDF and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.

Safety, efficacy, and persistence of emtricitabine/tenofovir versus other nucleoside analogues in naive subjects aged 50 years or older in Spain: the TRIP study.

OBJECTIVES: Current antiretroviral guidelines state that being older than 50 to 55 years of age is an indication to start antiretroviral therapy (ART), regardless of CD4 status. However, no references to the preferred combination ART (cART) for these patients have been described. Our study compares emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) versus other nucleoside reverse transcriptase inhibitor (NNRTI) regimens in HIV ART-naïve patients who are ≥50 years. DESIGN: National, retrospective cohort analysis of patients who were ≥50 years old when they began the first cART (January 1, 2006 to December 31, 2009). METHODS: We compared safety, effectiveness, and persistence of treatment in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitor (PI) versus NNRTI users and lopinavir/r versus efavirenz users. RESULTS: We included 161 patients: median age was 54.6 years, 83% were men, median CD4 count was 191 cells/µL, median viral load was 4.7 log, and median follow-up was 19 months (maximum, 48 months). Of these participants, 112 started with FTC/TDF and 49 with other nucleotide reverse transcriptase inhibitors (NRTIs). During follow-up, 21.9% of subjects developed at least one laboratory event ≥grade 3, 5.6% interrupted cART due to adverse events,19.3% had virologic failure, and 49.1% modified cART. There were no statistically significant differences between FTC/TDF and non-FTC/TDF users for any output except for persistence: The proportion of subjects who changed cART was 71.4% for non-FTC/TDF users and 38.6% for FTC/TDF users (log rank 0.001; adjusted hazard ratio, 2.10; 95% CI, 1.34-3.29). CONCLUSIONS: In a population of HIV-infected subjects who were ≥50 years old, our study suggests that the use of FTC/TDF is generally safe and effective, with a longer persistence as compared to other regimens.

Translocation of a Bak C-terminus mutant from cytosol to mitochondria to mediate cytochrome C release: implications for Bak and Bax apoptotic function.

BACKGROUND: One of two proapoptotic Bcl-2 proteins, Bak or Bax, is required to permeabilize the mitochondrial outer membrane during apoptosis. While Bax is mostly cytosolic and translocates to mitochondria following an apoptotic stimulus, Bak is constitutively integrated within the outer membrane. Membrane anchorage occurs via a C-terminal transmembrane domain that has been studied in Bax but not in Bak, therefore what governs their distinct subcellular distribution is uncertain. In addition, whether the distinct subcellular distributions of Bak and Bax contributes to their differential regulation during apoptosis remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: To gain insight into Bak and Bax targeting to mitochondria, elements of the Bak C-terminus were mutated, or swapped with those of Bax. Truncation of the C-terminal six residues (C-segment) or substitution of three basic residues within the C-segment destabilized Bak. Replacing the Bak C-segment with that from Bax rescued stability and function, but unexpectedly resulted in a semi-cytosolic protein, termed Bak/BaxCS. When in the cytosol, both Bax and Bak/BaxCS sequestered their hydrophobic transmembrane domains in their hydrophobic surface groove. Upon apoptotic signalling, Bak/BaxCS translocated to the mitochondrial outer membrane, inserted its transmembrane domain, oligomerized, and released cytochrome c. Despite this Bax-like subcellular distribution, Bak/BaxCS retained Bak-like regulation following targeting of Mcl-1. CONCLUSIONS/SIGNIFICANCE: Residues in the C-segment of Bak and of Bax contribute to their distinct subcellular localizations. That a semi-cytosolic form of Bak, Bak/BaxCS, could translocate to mitochondria and release cytochrome c indicates that Bak and Bax share a conserved mode of activation. In addition, the differential regulation of Bak and Bax by Mcl-1 is predominantly independent of the initial subcellular localizations of Bak and Bax.