X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction.

Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.

Latin-American guidelines of recommendations at discharge from an acute coronary syndrome.

The diagnostic criteria, treatments at the time of admission, and drugs used in patients with acute coronary syndrome are well defined in countless guidelines. However, there is uncertainty about the measures to recommend during patient discharge planning. This document brings together the most recent evidence and the standardized and optimal treatment for patients at the time of discharge from hospitalization for an acute coronary syndrome, for comprehensive and safe care in the patient's transition between care from the acute event to the outpatient care, with the aim of optimizing the recovery of viable myocardium, guaranteeing the most appropriate secondary prevention, reducing the risk of a new coronary event and mortality, as well as the adequate reintegration of patients into daily life.

Los criterios diagnósticos, los tratamientos en el momento de la admisión y los fármacos utilizados en pacientes con síndrome coronario agudo están bien definidos en innumerables guías. Sin embargo, existe incertidumbre acerca de las medidas para recomendar durante la planificación del egreso de los pacientes. Este documento reúne las evidencias más recientes y el tratamiento estandarizado y óptimo para los pacientes al momento del egreso de una hospitalización por un síndrome coronario agudo, para un cuidado integral y seguro en la transición del paciente entre la atención del evento agudo y el cuidado ambulatorio, con el objetivo de optimizar la recuperación de miocardio viable, garantizar la prevención secundaria más adecuada, reducir el riesgo de un nuevo evento coronario y la mortalidad, así como la adecuada reinserción de los pacientes en la vida cotidiana.

A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine.

Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identifies a multi-OMICs pre-vaccination signature and mechanisms predictive of broad antibody responses after immunization with a tetravalent live attenuated DENV vaccine candidate (Butantan-DV/TV003). Anti-inflammatory pathways, including TGF-ß signaling expressed by CD68low monocytes, and the metabolites phosphatidylcholine (PC) and phosphatidylethanolamine (PE) positively correlate with broadly neutralizing antibody responses against DENV. In contrast, expression of pro-inflammatory pathways and cytokines (IFN and IL-1) in CD68hi monocytes and primary and secondary bile acids negatively correlates with broad DENV-specific antibody responses. Induction of TGF-ß and IFNs is done respectively by PC/PE and bile acids in CD68low and CD68hi monocytes. The inhibition of viral sensing by PC/PE-induced TGF-ß is confirmed in vitro. Our studies show that the balance between metabolites and the pro- or anti-inflammatory state of innate immune cells drives broad and protective B cell response to a live attenuated dengue vaccine.

Strengthening Essential Health Services Recovery Policy after the COVID-19 Pandemic. Evidence from the Mexican Institute of Social Security.

AIM: To evaluate the progress of the Mexican Institute of Social Security Recovery Policy (IMSS-RP) in addressing the decline in essential health services caused by the COVID-19 pandemic. METHODS: We analyzed eleven indicators of essential health services from 35 IMSS state delegations. The assessment included ambulatory and hospital care indicators such as breast and cervical cancer screening, family medicine, dental and specialty visits, diabetes and hypertension visits and health outcomes, deliveries, and elective surgeries. We analyzed the period before (January 2018-March 2021) and during (April 2021-June 2023) the implementation of the IMSS-RP. Statistical analysis to determine the association of the policy with service indicators and the change in their trends included an interrupted time series analysis and Poisson Generalized Estimating Equation models. RESULTS: The volume of services showed substantial declines during the first year of the COVID-19 pandemic, reaching between 11 and 81% of pre-pandemic levels. All services increased significantly during the first 27 months of the IMSS-RP implementation; specialty visits, cervical and breast cancer screening, and diabetes control exceeded pre-pandemic levels (103%,112%,103%, and 138%, respectively). However, only deliveries and the percentage of patients with controlled diabetes and hypertension showed a stable increase following the IMSS-RP implementation, whereas the remaining services showed an initial increase but began to decrease over time. CONCLUSIONS: After 27 months of implementation, IMSS-RP achieved progress in increasing the volume of essential health services and improving chronic disease control. However, declining trends in several services signal the need to focalize the policy.

Macrolitter and microplastics along the East Pacific coasts - A homemade problem needing local solutions.

The East Pacific (EP) region, especially the central and southern EP, has been fairly less studied than other world's regions with respect to marine litter pollution. This comprehensive literature review (257 peer-reviewed publications) showed that both macrolitter (mostly plastics) and microplastics tend to accumulate on EP shorelines. Moreover, they were also reported in all the other compartments investigated: sea surface, water column, seafloor and 'others'. Mostly local, land-based sources (e.g., tourism, poor waste management) were identified across the region, especially at continental sites from low and mid latitudes. Some sea-based sources (e.g., fisheries, long-distance drifting) were also identified at high latitudes and on oceanic islands, likely enhanced by the oceanographic dynamics of the EP that affect transport of floating litter. Our results suggest that effective solutions to the problem require local and preventive strategies to significantly reduce the levels of litter along the EP coasts.

Prior acupuncture experience among elderly participants enrolled in a clinical trial of acupuncture for chronic low back pain: Implications for future trials.

Background: The effectiveness of acupuncture for chronic low back pain (cLBP) has not been studied specifically in the 65-and-older population. To inform the validity and generalizability of future acupuncture studies among older adults, we characterized elderly participants' prior experience with and views toward acupuncture and tested for clinical and sociodemographic differences between acupuncture-naïve and non-naïve participants. Methods: Data for this study were collected during the baseline telephone interview from the participants enrolled in the Kaiser Permanente Northern California site of an NIH-funded, multicenter clinical trial of acupuncture for cLBP in older adults. Results: Nearly two-thirds (65.6 %) of participants surveyed reported they had previously received acupuncture treatment with the vast majority seeking acupuncture treatment for pain-related issues (84.8 %). The majority of these participants reported relatively modest levels of exposure to acupuncture with most participants (63.1 %) reporting fewer than 10 treatment sessions over their lifetimes. There were no significant differences in age, sex, race, ethnicity, disability scores, income levels, or pain levels between the acupuncture-naïve and non-naïve groups. Conclusion: Contextual consideration for prior acupuncture utilization rates is warranted and may be higher than expected or previously reported. We found few differences in baseline characteristics between participants who were acupuncture-naïve and those with prior acupuncture experience; thus, future pragmatic clinical trials might relax previous acupuncture-use considerations in their recruitment criteria. For trials focused on acupuncture-naive patients, it may be more feasible to expand the definition of "acupuncture-naive" based on lifetime acupuncture visits or time since last treatment. Trial registration: The protocol was registered at clinicaltrials.gov (#NCT04982315).

Hearing Difficulties Among Farmworkers in the México-US Southwest Border Region.

Migrant and seasonal farmworkers are a vulnerable population with a potentially high risk for hearing loss due to farm-related noise exposures. Occupational noise-induced hearing loss (NIHL) is permanent, and it is associated with an increased risk for injuries on the job, as well as communication difficulties, isolation, and depression. The México/US border region is one of the most productive agricultural regions in the country, however, no known studies have explored hearing loss among farmworkers in this area. This pilot study was a first step toward measuring and addressing hearing loss and noise exposure among this region's farmworkers. We conducted a cross-sectional survey to estimate the prevalence of subjective hearing difficulties among Yuma County, Arizona farmworkers. Survey interviews took place during a late-night farmworker health fair from 2 am to 6 am to accommodate local farms' labor schedules. Multivariable regression adjusted for demographic and work covariates estimated subjective hearing loss prevalence ratios. Among 132 farmworker participants, 36% reported they have or might have hearing loss, and 62% reported no hearing loss. Subjective hearing loss prevalence was lower in farmworkers who report not working in noise compared to prevalence in farmworkers who work in noise [prevalence ratio, 0.44 (95% CI 0.23-0.82)]. This report contributes to understanding the perception of hearing-related health and occupational exposures among farmworkers in the México-US Southwest border region. The information from this line of research will inform appropriate safety measures known to lower the risk of experiencing occupational NIHL.

Plastic pollution transcends marine protected area boundaries in the eastern tropical and south-eastern Pacific.

The Eastern Tropical and South-Eastern Pacific region is of global biodiversity importance. At COP26, the governments of Costa Rica, Panama, Colombia, and Ecuador committed to the expansion of existing MPAs to create a new Mega MPA, safeguarding the Eastern Tropical Pacific Marine Corridor. It offers a profound step forward in conservation efforts but is not specifically designed to protect against the more diffuse anthropogenic threats, such as plastic pollution. We combine published data with our own unpublished records to assess the abundance and distribution of plastic pollution in the region. Macro- and microplastic concentrations varied markedly and were not significantly different when comparing areas inside and outside existing MPA boundaries. These findings highlight the diffuse and complex nature of plastic pollution and its ubiquitous presence across MPA boundaries. Understanding the sources and drivers of plastic pollution in the region is key to developing effective solutions.

[Lifestyle modification and risk factor control in the prevention and treatment of atrial fibrillation]. / Modificaciones en el estilo de vida y control de los factores de riesgo en la prevención y el tratamiento de la fibrilación auricular.

Atrial fibrillation (AF) is the most prevalent arrhythmia and is related with significant morbidity, mortality and costs. In spite of relevant advances in the prevention of embolic events and rhythm control, little has been done to reduce its prevalence, progression and impact, since it increases with ageing as well as with common risk factors such as alcohol intake, tobacco use and stress as well as with arterial hypertension, diabetes mellitus, heart failure, sleep apnea, kidney failure, chronic pulmonary obstructive disease, ischemic heart disease and stroke, among other important comorbidities. Fortunately, new evidence suggests that lifestyle modifications and adequate risk factors and comorbidities control could be effective in primary and secondary AF prevention, especially in its paroxysmal presentations. This is why a multidisciplinary approach integrating lifestyle modifications, risk factors and comorbidities control, is necessary in conjunction with rhythm or rate control and anticoagulation. Unfortunately, that holistic approach strategy is not considered, is scarcely studied or is subtilized in general clinical practice. The present statement's objectives are to: 1) review the relationship between habits, risk factors and illnesses with AF, 2) review the individual and common physiopathology mechanisms of each one of those conditions that may lead to AF, 3) review the effect of control of habits, risk factors and co-morbidities on the control and impact of AF, and 4) supply guidelines and recommendations to start multidisciplinary and integrative AF treatment.

La fibrilación auricular (FA) es la arritmia más frecuente y se asocia con importante morbilidad, mortalidad y costos. A pesar de los grandes avances en la prevención de eventos embólicos y en el control del ritmo, poco se ha realizado para reducir su prevalencia, progresión e impacto, debido a que incrementa con la edad y con la presencia de múltiples factores de riesgo muy comunes en la población, como obesidad, sedentarismo, alcoholismo, tabaquismo y estrés, así como con hipertensión arterial sistémica, diabetes mellitus, insuficiencia cardiaca, apnea del sueño, enfermedad renal crónica, enfermedad pulmonar obstructiva crónica, cardiopatía isquémica y enfermedad vascular cerebral, entre otra comorbilidad importante. Afortunadamente, nuevas evidencias demuestran que las modificaciones en el estilo de vida y el control adecuado de los factores de riesgo y de la comorbilidad pueden ser efectivos en la prevención primaria y secundaria de la FA, en especial en sus formas paroxísticas; para ello, es necesario un manejo multidisciplinario que integre las modificaciones en el estilo de vida, el manejo de los factores de riesgo y el control de la comorbilidad en el tratamiento de la FA en conjunto con el control del ritmo o de la frecuencia y la anticoagulación. Por desgracia, en la práctica clínica estas estrategias a menudo no se tienen en cuenta, son infrautilizadas y poco estudiadas. Los objetivos del presente posicionamiento son: 1) revisar la relación de los factores de riesgo y la comorbilidad con la FA, 2) revisar los mecanismos fisiopatológicos de cada una de estas condiciones, 3) revisar el impacto del control de los factores de riesgo y de la comorbilidad en el control y en el impacto de la FA, y 4) proporcionar guías y recomendaciones para la puesta en práctica de programas de tratamiento multidisciplinario e integral en pacientes con FA.

Identifying locally actionable strategies to increase participant acceptability and feasibility to participate in Phase I cancer clinical trials.

BACKGROUND: Recruitment of cancer clinical trial (CCT) participants, especially participants representing the diversity of the US population, is necessary to create successful medications and a continual challenge. These challenges are amplified in Phase I cancer trials that focus on evaluating the safety of new treatments and are the gateway to treatment development. In preparation for recruitment to a Phase I recurrent head and neck cancer (HNC) trial, we assessed perceived barriers to participation or referral and suggestions for recruitment among people with HNC and community physicians (oncologist, otolaryngologist or surgeon). METHODS: Between December 2020 and February 2022, we conducted a qualitative needs assessment via semistructured interviews with a race and ethnicity-stratified sample of people with HNC (n = 30: 12 non-Hispanic White, 9 non-Hispanic African American, 8 Hispanic and 1 non-Hispanic Pacific Islander) and community physicians (n = 16) within the University of Florida Health Cancer Center catchment area. Interviews were analyzed using a qualitative content analysis approach to describe perspectives and identify relevant themes. RESULTS: People with HNC reported thematic barriers included: concerns about side effects, safety and efficacy; lack of knowledge and systemic and environmental obstacles. Physicians identified thematic barriers of limited physician knowledge; clinic and physician barriers and structural barriers. People with HNC and physicians recommended themes included: improved patient education, dissemination of trial information and interpersonal communication between community physicians and CCT staff. CONCLUSIONS: The themes identified by people with HNC and community physicians are consistent with research efforts and recommendations on how to increase the participation of people from minoritized populations in CCTs. This community needs assessment provides direction on the selection of strategies to increase CCT participation and referral. PATIENT OR PUBLIC CONTRIBUTION: This study focused on people with HNC and community physicians' lived experience and their interpretations of how they would consider a future Phase I clinical trial. In addition to our qualitative data reflecting community voices, a community member reviewed the draft interview guide before data collection and both people with HNC and physicians aided interpretation of the findings.

Expansion of endogenous T cells in CSF of pediatric CNS tumor patients undergoing locoregional delivery of IL13R〿2-targeting CAR T cells: an interim analysis.

Outcomes for pediatric brain tumor patients remain poor, and there is optimism that chimeric antigen receptor (CAR) T cell therapy can improve prognosis. Here, we present interim results from the first six pediatric patients treated on an ongoing phase I clinical trial (NCT04510051) of IL13BBζ-CAR T cells delivered weekly into the lateral cerebral ventricles, identifying clonal expansion of endogenous CAR-negative CD8+ T cells in the cerebrospinal fluid (CSF) over time. Additionally, of the five patients evaluable for disease response, three experienced transient radiographic and/or clinical benefit not meeting protocol criteria for response. The first three patients received CAR T cells alone; later patients received lymphodepletion before the first infusion. There were no dose limiting toxicities (DLTs). Aside from expected cytopenias in patients receiving lymphodepletion, serious adverse events possibly attributed to CAR T cell infusion were limited to one episode of headache and one of liver enzyme elevation. One patient withdrew from treatment during the DLT period due to a Grade 3 catheter-related infection and was not evaluable for disease response, although this was not attributed to CAR T cell infusion. Importantly, scRNA- and scTCR-sequence analyses provided insights into CAR T cell interaction with the endogenous immune system. In particular, clonally expanded endogenous CAR- T cells were recovered from the CSF, but not the peripheral blood, of patients who received intraventricular IL13BBζ-CAR T cell therapy. Additionally, although immune infiltrates in CSF and post-therapy tumor did not generally correlate, a fraction of expanded T cell receptors (TCRs) was seen to overlap between CSF and tumor. This has important implications for what samples are collected on these trials and how they are analyzed. These initial findings provide support for continued investigation into locoregionally-delivered IL13BBζ-CAR T cells for children with brain tumors.

[Atherogenic index and its association with acute coronary ischemic syndrome mortality]. / Índice aterogénico y su relación con la mortalidad del síndrome isquémico coronario agudo.

Background: Several indexes have been developed to define the risk attributable to lipid metabolism with a single value. The total cholesterol/high-density lipoprotein (TC/HDL-C) and low-density lipoprotein/high-density lipoprotein (LDL-C/HDL-C) ratios are the most used. The higher the value of these ratios, the greater the probability of cardiovascular events. Objective: To identify whether the TC/HDL-C and LDL-C/HDL-C ratios are early prognostic markers of mortality and major cardiovascular events in patients with ST-elevation acute coronary syndrome. Material and methods: 265 patients with ST-segment elevation acute coronary ischemic syndrome were included, divided into 4 groups according to the values of the atherogenic indices. Mortality and major cardiovascular events at 30-day follow-up were analyzed. Comparison of the groups was performed using the chi-squared test or ANOVA, depending on the case (p < 0.05). Results: The cut-off point for the TC/HDL-C index was 6.9 and for the LDL-C/HDL-C it was 2.7. The comparative analysis of groups showed that cardiovascular death and arrhythmia were higher in group 3 (p = 0.006 and p = 0.003, respectively). Conclusions: TC/HDL-C and LDL-C/HDL-C indexes can be used as prognostic markers of cardiovascular mortality in the first 30 days of follow-up.

Introducción: se han elaborado diferentes índices para definir el riesgo atribuible al metabolismo lipídico con un solo valor. Los coeficientes colesterol total/lipoproteínas de alta densidad (CT/C-HDL) y lipoproteínas de baja densidad/lipoproteínas de alta densidad (C-LDL/C-HDL) son los más utilizados. A mayor valor de estos cocientes, la probabilidad de eventos cardiovasculares es mayor. Objetivo: identificar si los índices CT/C-HDL y C-LDL/C-HDL son marcadores pronósticos tempranos de mortalidad y evento cardiovascular mayor en pacientes con síndrome isquémico coronario agudo con elevación del ST. Material y métodos: se incluyeron 265 pacientes con síndrome isquémico coronario agudo con elevación del segmento ST, divididos en 4 grupos según los valores de los índices aterogénicos. Se analizó la mortalidad y el evento cardiovascular mayor en los 30 días de seguimiento. Se identificó el punto de corte de cada índice mediante un análisis de curva ROC. La comparación de los grupos se hizo con chi cuadrada o ANOVA, según fuera el caso (p < 0.05). Resultados: el punto de corte para el índice CT/C-HDL fue de 6.9 y para el C-LDL/C-HDL de 2.7. El análisis comparativo de los grupos demostró que la muerte cardiovascular y arritmia fue mayor en el grupo 3 (p = 0.006 y p = 0.003, respectivamente). Conclusiones: los índices CT/C-HDL y C-LDL/C-HDL pueden ser utilizados como marcadores pronósticos de mortalidad cardiovascular en los primeros 30 días de seguimiento.

Vaginal Approach to Cesarean Section Scar Pregnancies: A Standardized Ten-step Surgical Procedure.

OBJECTIVE: To show a 10-step standardized vaginal surgical technique to treat first-trimester cesarean section scar pregnancies. DESIGN: A video article with a stepwise demonstration captured in an operation room of a tertiary medical center of a low-income country (Bolivia). SETTING: Cesarean section scar pregnancies have a wide variety of management options. We present a vaginal surgical approach that has been developed by our group with no observed complications in 6 consecutive cases at the time of this publication. INTERVENTIONS: A 10-step technique: (1) patient positioning, (2) cervical exposure and traction, (3) cervical infiltration with vasoconstrictor solution, (4) anterior mucosal incision and dissection of vesicovaginal space, (5) identification of vascular pedicle and ligation, (6) cold-knife isthmocele incision and ectopic pregnancy evacuation, (7) uterine cavity curettage, (8) hysterorrhaphy with interrupted suture, (9) cystoscopy, and (10) vaginal mucosa closure with running suture. We have used this technique in 6 consecutive patients. Operating time ranged between 20 and 25 minutes. All patients were discharged in postoperative day 1. CONCLUSION: We prefer surgical options for these patients because it provides both a complete removal of the ectopic pregnancy and repair of the isthmocele. A vaginal approach to such cases has proven to be a safe, simple, and fully reproductible technique. We find it applicable for any patient with this pathology but especially suitable for low-resource or somehow financially challenged hospitals.

Infectious endocarditis without intracardiac devices or underlying structural heart disease.

OBJECTIVE: To describe clinical, microbiological and echocardiographic aspects of endocarditis in a specific group of patients without intracardiac devices or underlying structural heart disease. METHOD: Retrospective study, clinical records and echocardiographic reports were reviewed during the period 1997 to 2020. Duke's modified criteria were applied. Statistical analysis: univariate expressed in frequencies, using measures of dispersion and central tendency. RESULTS: 30,000 echocardiographic reports were reviewed, only 1350 had infectious endocarditis as a reason for sending, of which 248 cases were selected. The mean age was 48.1 ± 16.7 years. 140 men (56%) and 108 women (44%). The most frequent echocardiographic sign was vegetation, in 278 (93.60%), and most common location was mitral (35.55%), with a higher number of cases in the right ventricle than expected. The most common systemic disease was kidney disease, in 135 (41.08%). A case of Streptococcus thoraltensis not previously reported in Mexico was identified. CONCLUSIONS: The presence of infectious endocarditis has increased due to invasive in-hospital and drug procedures. Due to their complexity, multidisciplinary teams are indispensable.

OBJETIVO: Describir aspectos clínicos, microbiológicos y ecocardiográficos de endocarditis en un grupo específico de pacientes sin dispositivos intracardiacos ni cardiopatía estructural subyacente. MÉTODO: Estudio retrospectivo en el que se revisaron expedientes clínicos y reportes ecocardiográficos durante el periodo de 1997 a 2020. Se aplicaron los criterios modificados de Duke. Se describió la muestra por edad, sexo, enfermedad sistémica, vegetaciones y agente microbiológico. Se excluyeron pacientes con cardiopatía estructural o Libman-Sacks. Análisis estadístico: univariado expresado en frecuencias, utilizando medidas de dispersión y tendencia central. RESULTADOS: Se revisaron 30,000 reportes ecocardiográficos, de los cuales solo 1350 tenían como motivo de envío endocarditis infecciosa, y de estos se seleccionaron 248 casos. La edad promedio fue de 48.1 ± 16.7 años. Hubo 140 hombres (56%) y 108 mujeres (44%). El signo ecocardiográfico más frecuente fue la vegetación, en 278 (93.60%), y la ubicación más común fue mitral (35.55%), con un número mayor de casos en el ventrículo derecho de lo esperado. La enfermedad sistémica más común fue la enfermedad renal, en 135 (41.08%). Se identificó un caso de Streptococcus thoraltensis no reportado previamente en México. CONCLUSIONES: La presencia de endocarditis infecciosa ha aumentado debido a procedimientos invasivos intrahospitalarios y fármacos. Por su complejidad, los equipos multidisciplinarios son indispensables.

A Geospatial Model to Identify Areas Associated with Late- Stage Breast Cancer: A Spatial Epidemiology Approach.

OBJECTIVE: The aim of this study was to show how a geospatial model can be used to identify areas with a higher probability for late-stage breast cancer (BC) diagnoses. METHODS: Our study considered an ecological design. Clinical records at a tertiary care hospital were reviewed in order to obtain the place of residence and stage of the disease, which was classified as early (0-IIA) and late (IIB-IV) and whose diagnoses were made during the 2013-2017 period. Then, they were geolocated to identify the distribution and spatial trend. Subsequently, the pattern of location, i.e. scattered, random and concentrated, was statistically assessed and a geospatial model was elaborated to determine the probability of late diagnoses in the state of Jalisco, Mexico. RESULT: There were 1 954 (N) geolocated BC diagnoses: 58.3% were late. During the five-year period, a southwest-northeast trend was identified, nearly 9.5% of the surface of Jalisco, where 6 out of 10 (n= 751) late- stage diagnoses were concentrated. A concentrated and statistically significant pattern was identified in the southern, central and northern Pacific area of Jalisco, where the geospatial model delimited the places with the highest probability of late clinical stages (p <0.05). CONCLUSION: The geographical differences associated with the late diagnoses of BC suggest it is necessary to adapt and focus the strategies for early detection as an alternative to create a major impact on the population. Reproducible analysis tools were used in other contexts where geolocation data are available to complement public policies and strategies aimed to control BC.

Detection of Leishmania spp. in Cats: Analysis of Nasal, Oral and Conjunctival Swabs by PCR and HRM.

BACKGROUND AND OBJECTIVES: Feline leishmaniasis (FeL) is caused by several species of parasites of the genus Leishmania. The disease can occur with the presence or absence of clinical signs, similar to those observed in other common infectious diseases. In endemic regions for FeL, the infection has been associated with dermatological lesions. Therefore, considering the search for less invasive and more effective diagnostic techniques, we aimed to investigate the presence of Leishmania spp. in domestic cats through Polymerase Chain Reaction (PCR) and high-resolution melting (HRM) analyses of conjunctival, oral, and nasal epithelial cells, and we detected the presence of anti-Leishmania IgG antibodies from serological techniques of the Immunofluorescent Antibody Test (IFAT) and ELISA. METHODS: The PCR and HRM for detection of Leishmania spp. were performed on 36 samples of epithelial cells from the conjunctiva of male and female cats, collected using sterile swabs. The serological tests IFAT and ELISA were also performed. RESULTS: The prevalence of Leishmania donovani infection was 11.1% (4/36) by PCR assay, and those results were confirmed for Leishmania species using the HRM technique. Twenty-four cats (24/36 = 66.7%) were reactive to the IFAT and twenty-two cats were reactive by the ELISA technique (22/36 = 61.1%). INTERPRETATION AND CONCLUSIONS: The use of conjunctival swabs was shown to be a non-invasive, practical, and easy-to-perform technique, and in addition to the genetic sequencing and HRM, it was able to identify the parasitic DNA of L. donovani in cats. This technique can be used for screening diagnosis in future epidemiological surveys of FeL and can be used as a complement to clinical and/or serological tests, as well as associating the clinical history of the animal, for the diagnostic conclusion.

Translation and adaptation to Spanish of Aberdeen varicose veins questionnaire.

OBJECTIVE: The purpose of the study is to translate the Aberdeen Varicose Vein Questionnaire (AVVQ) into Spanish and evaluate the feasibility and reliability of the Spanish-translated AVVQ in patients with chronic venous disease. METHODS: Reliability was assessed by test and retest of the Spanish translated AVVQ in a sample of 77 patients. The questionnaires were answered within a 2-week interval. RESULTS: There was a 100% test and retest response. The AVVQ showed 6.5% of missing responses. Cronbach's alpha was 0.71 indicating an adequate level of internal consistency. Spearman's rho showed a significant strong association between test and retest scores (rho = 0.84, p < 0.0001). CONCLUSIONS: The Spanish-translated AVVQ is a reliable tool in our daily clinical practice in order to measure the impact of venous disease in the quality of life.

Breast arterial calcification is associated with incident atrial fibrillation among older but not younger post-menopausal women.

Aims: The goal of this study was to examine the association of breast arterial calcification (BAC) presence and quantity with incident atrial fibrillation (AF) in a large cohort of post-menopausal women. Methods and results: We conducted a longitudinal cohort study among women free of clinically overt cardiovascular disease and AF at baseline (between October 2012 and February 2015) when they attended mammography screening. Atrial fibrillation incidence was ascertained using diagnostic codes and natural language processing. Among 4908 women, 354 incident cases of AF (7%) were ascertained after a mean (standard deviation) of 7 (2) years of follow-up. In Cox regression adjusting for a propensity score for BAC, BAC presence vs. absence was not significantly associated with AF [hazard ratio (HR) = 1.12; 95% confidence interval (CI), 0.89-1.42; P = 0.34]. However, a significant (a priori hypothesized) age by BAC interaction was found (P = 0.02) such that BAC presence was not associated with incident AF in women aged 60-69 years (HR = 0.83; 95% CI, 0.63-1.15; P = 0.26) but was significantly associated with incident AF in women aged 70-79 years (HR = 1.75; 95% CI, 1.21-2.53; P = 0.003). No evidence of dose-response relationship between BAC gradation and AF was noted in the entire cohort or in age groups separately. Conclusion: Our results demonstrate, for the first time, an independent association between BAC and AF in women over age 70 years.

Efficient visual learning by bumble bees in virtual-reality conditions: Size does not matter.

Recent developments allowed establishing virtual-reality (VR) setups to study multiple aspects of visual learning in honey bees under controlled experimental conditions. Here, we adopted a VR environment to investigate the visual learning in the buff-tailed bumble bee Bombus terrestris. Based on responses to appetitive and aversive reinforcements used for conditioning, we show that bumble bees had the proper appetitive motivation to engage in the VR experiments and that they learned efficiently elemental color discriminations. In doing so, they reduced the latency to make a choice, increased the proportion of direct paths toward the virtual stimuli and walked faster toward them. Performance in a short-term retention test showed that bumble bees chose and fixated longer on the correct stimulus in the absence of reinforcement. Body size and weight, although variable across individuals, did not affect cognitive performances and had a mild impact on motor performances. Overall, we show that bumble bees are suitable experimental subjects for experiments on visual learning under VR conditions, which opens important perspectives for invasive studies on the neural and molecular bases of such learning given the robustness of these insects and the accessibility of their brain.

Sodium restriction in patients with chronic heart failure and reduced ejection fraction: A randomized controlled trial.

BACKGROUND: Sodium restriction is recommended for patients with heart failure (HF) despite the lack of solid clinical evidence from randomized controlled trials. Whether or not sodium restrictions provide beneficial cardiac effects is not known. METHODS: The present study is a randomized, double-blind, controlled trial of stable HF patients with ejection fraction ≤ 40%. Patients were allocated to sodium restriction (2 g of sodium/day) vs. control (3 g of sodium/day). The primary outcome was change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 20 weeks. Secondary outcomes included quality of life and adverse safety events (HF readmission, blood pressure or electrolyte abnormalities). RESULTS: Seventy patients were enrolled. Median baseline sodium consumption was 3268 (2225-4537) mg/day. Adherence to the intervention based on 24-hour urinary sodium was 32%. NT-proBNP and quality of life did not significantly change between groups (p > 0.05 for both). Adverse safety events were not significantly different between the arms (p > 0.6 for all). In the per protocol analysis, patients who achieved a sodium intake < 2500 mg/day at the intervention conclusion showed improvements in NT-proBNP levels (between-group difference: -55%, 95% confidence interval -27 to -73%; p = 0.002) and quality of life (between-group difference: -11 ± 5 points; p = 0.04). Blood pressure decreased in patients with lower sodium intake (between-group difference: -9 ± 5 mmHg; p = 0.05) without significant differences in symptomatic hypotension or other safety events (p > 0.3 for all). CONCLUSIONS: Adherence assessed by 24-hour natriuresis and by the nutritionist was poor. The group allocated to sodium restriction did not show improvement in NT-proBNP. However, patients who achieved a sodium intake < 2500 mg/day appeared to have improvements in NT-proBNP and quality of life without any adverse safety signals. CLINICALTRIALS: gov Identifier: NCT03351283.