Site-specific ubiquitination of the E3 ligase HOIP regulates apoptosis and immune signaling.

HOIP, the catalytic component of the linear ubiquitin chain assembly complex (LUBAC), is a critical regulator of inflammation. However, how HOIP itself is regulated to control inflammatory responses is unclear. Here, we discover that site-specific ubiquitination of K784 within human HOIP promotes tumor necrosis factor (TNF)-induced inflammatory signaling. A HOIP K784R mutant is catalytically active but shows reduced induction of an NF-κB reporter relative to wild-type HOIP. HOIP K784 is evolutionarily conserved, equivalent to HOIP K778 in mice. We generated HoipK778R/K778R knock-in mice, which show no overt developmental phenotypes; however, in response to TNF, HoipK778R/K778R mouse embryonic fibroblasts display mildly suppressed NF-κB activation and increased apoptotic markers. On the other hand, HOIP K778R enhances the TNF-induced formation of TNFR complex II and an interaction between TNFR complex II and LUBAC. Loss of the LUBAC component SHARPIN leads to embryonic lethality in HoipK778R/K778R mice, which is rescued by knockout of TNFR1. We propose that site-specific ubiquitination of HOIP regulates a LUBAC-dependent switch between survival and apoptosis in TNF signaling.

A close-up view of the Hunter syndrome.

The Lysosomal Storage disease known as Mucopolysaccharidosis type II, is caused by mutations affecting the iduronate-2-sulfatase required for heparan and dermatan sulfate catabolism. The central nervous system (CNS) is mostly and severely affected by the accumulation of both substrates. The complexity of the CNS damage observed in MPS II patients has been limitedly explored. The use of mass spectrometry (MS)-based proteomics tools to identify protein profiles may yield valuable information about the pathological mechanisms of Hunter syndrome. In this further study, we provide a new comparative proteomic analysis of MPS II models by using a pipeline consisting of the identification of native protein complexes positioned selectively by using a specific antibody, coupled with mass spectrometry analysis, allowing us to identify changes involving in a significant number of new biological functions, including a specific brain antioxidant response, a down-regulated autophagic, the suppression of sulfur catabolic process, a prominent liver immune response and the stimulation of phagocytosis among others.

Identification of Orthosteric and Allosteric Pharmacological Chaperones for Mucopolysaccharidosis type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal inherited disease caused by mutations in gene encoding the lysosomal enzyme N-acetyl-alpha-glucosaminidase (NAGLU). These mutations result in reduced NAGLU activity, preventing it from catalyzing the hydrolysis of the glycosaminoglycan heparan sulfate (HS). There are currently no approved treatments for MPS IIIB. A novel approach in the treatment of lysosomal storage diseases is the use of pharmacological chaperones (PC). In this study, we used a drug repurposing approach to identify and characterize novel potential PCs for NAGLU enzyme. We modeled the interaction of natural and artificial substrates within the active cavity of NAGLU (orthosteric site) and predicted potential allosteric sites. We performed a virtual screening for both the orthosteric and the predicted allosteric site against a curated database of human tested molecules. Considering the binding affinity and predicted blood-brain barrier permeability and gastrointestinal absorption, we selected atovaquone and piperaquine as orthosteric and allosteric PCs. The PCs were evaluated by their capacity to bind NAGLU and the ability to restore the enzymatic activity in human MPS IIIB fibroblasts These results represent novel PCs described for MPS IIIB and demonstrate the potential to develop novel therapeutic alternatives for this and other protein deficiency diseases.

Epilepsy Care in Latin America and the Caribbean: Overcoming Challenges and Embracing Opportunities.

The burden of epilepsy in the Latin America and the Caribbean (LAC) region causes a profound regional impact on the health care system and significantly contributes to the global epilepsy burden. As in many other resource-limited settings worldwide, health care professionals and patients with epilepsy in LAC countries face profound challenges due to a combination of factors, including high disease prevalence, stigmatization of epilepsy, disparities in access to care, limited resources, substantial treatment gaps, insufficient training opportunities for health care providers, and a diverse patient population with varying needs. This article presents an overview of the epidemiology of epilepsy and discusses the principal obstacles to epilepsy care and key contributors to the epilepsy diagnosis and treatment gap in the LAC region. We conclude by highlighting various initiatives across different LAC countries to improve epilepsy care in marginalized communities, listing strategies to mitigate treatment gaps and facilitate better health care access for patients with epilepsy by enhancing the epilepsy workforce.

Factors Associated with HIV Testing Among Spanish and English-Speaking Latino Adolescents Aged 13-18.

Adolescent Latino men who have sex with men (LMSM) in the U.S. are disproportionately impacted by HIV. However, there has been limited focus on their HIV prevention and risk behaviors. In this study, we examine the rates of HIV testing and explore the significant demographic and healthcare factors that influence HIV prevention among adolescent LMSM. The analysis for this study utilized data collected during the baseline assessment of SMART, a pragmatic trial aimed at evaluating the effectiveness of an online HIV prevention intervention for adolescent LMSM (N = 524). Only 35.5% of participants had ever had an HIV test in their lifetime. Rates of testing increased among adolescent LMSM who had a doctor with whom they spoke about their sexual health (odds ratio: 4.0; 95% confidence interval: 2.1-8.4; P < 0.001) or HIV testing (odds ratio: 5.8; 95% confidence interval: 3.1-10.7; P < 0.001). Out of the 61 participants who took part in the survey conducted in Spanish, only 26% reported ever having an HIV test. Additionally, 24.5% stated that they had discussed their sexual orientation with a doctor, and only 8.2% had undergone HIV testing. Spanish-speaking adolescents who completed the SMART survey were less likely to openly discuss their sexual orientation or sexual health with most people or have a doctor with whom they discussed these topics, compared to those who completed the survey in English. These findings suggest that Spanish-speaking adolescent LMSM may face obstacles in accessing HIV prevention services in the U.S.

RESUMEN: Los adolescentes latinos hombres que tienen sexo con otros hombres (LHSH) tienen mayor probabilidad de recibir tratamiento para el VIH más tarde en comparación con todos los casos nuevos del VIH en los Estados Unidos. Sin embargo, se ha estudiado muy poco sus prácticas de prevención de VIH o prácticas de riesgo, que similar a la de jóvenes no latinos, es determinada por múltiples factores. En este estudio describimos las tasas de pruebas para el VIH e identificamos los factores lingüísticos, individuales, familiares, escolares y de cuidado de salud que influencian a los adolescentes LHSH. Los datos provinieron de la evaluación inicial para SMART, un ensayo práctico de una intervención en línea para prevenir el VIH entre adolescentes LHSH (N = 524). Las medidas incluían la experiencia de hacerse la prueba del VIH a lo largo de la vida, factores de aculturación, datos demográficos, prácticas sexuales, educación sobre el VIH en la escuela y el hogar, comunicación sobre salud sexual con los médicos, conocimiento sobre el VIH y actitudes de riesgo. Solo 35.5% de los participantes se han realizado la prueba de VIH al menos una vez en su vida. La tasa de pruebas del VIH fue más alta entre los adolescentes LHSH que indicaron haber hablado con su médico sobre su salud sexual (odds ratio: 4.0; intervalo de confianza del 95%: 2.1­8.4; P < 0.001) o de la prueba del VIH (odds ratio: 5.8; intervalo de confianza del 95%: 3.1­10.7; P < 0.001). Más de 60 participantes completaron la encuesta en español. De estos, pocos reportaron alguna vez haberse hecho la prueba del HIV (26%), tener un médico con quien hablar sobre su orientación sexual (24.5%) o hablar sobre la prueba del VIH (8.2%). Estas cifras son significativamente más bajas que las obtenidas en la encuesta en inglés. Este estudio es uno de los primeros en evaluar los factores para hacerse la prueba del VIH entre adolescentes latinos que hablan inglés y español con edades entre 13 y 18 años. Los adolescentes latinos que completaron SMART en español tuvieron menos probabilidad de haber compartido sobre su orientación sexual con la mayoría de las personas o tener un médico con quien hablar sobre su orientación sexual o su salud sexual, en comparación con aquellos que completaron SMART en inglés, lo que sugiere que los jóvenes latinos que prefieren comunicarse en español pueden experimentar mayores barreras para acceder a los servicios de prevención del VIH en los Estados Unidos.

Factors Influencing Engagement Across the Motivational PrEP Cascade Among Latino SMM: A Mixed-Methods Analysis from the Perspectives of Community Providers and Latino SMM.

Latino sexual minority men (SMM) are a highly vulnerable population to HIV, and while pre-exposure prophylaxis (PrEP) has emerged as a promising biomedical tool for HIV prevention among them, its utilization remains disproportionately low in this community despite its potential. Understanding the barriers along the PrEP continuum of care, known as the "PrEP cascade," is crucial for effectively implementing PrEP interventions. Therefore, the objective of our study was twofold: first, to explore the stage of Latino SMM in the PrEP cascade by examining disparities in demographics, social factors, and healthcare aspects; second, to gain insights from healthcare providers who have direct clinical experience with our population regarding the challenges faced by Latino SMM in accessing and adhering to PrEP. Based on the study findings, the majority of participants (n = 74; 49%) were in the contemplation stage, and only one in ten Latino SMM (10.6%) were currently adherent to PrEP. Compared to those who were at least second-generation, first-generation status had a positive association (B = 0.699, SE = 0.208, ß = 0.351, p < .001) with engagement along the PrEP Contemplation Ladder. Conversely, having at least one parent who did not have legal residency, relative to those whose parents were both U.S. citizens or held legal residency documentation, was found to have a negative association (B = - 0.689, SE = 0.245, ß = 0.245, p = .006) with engagement along the PrEP Contemplation Ladder. Additionally, discussing PrEP with a healthcare provider had a positive association (B = 0.374, SE = 0.179, ß = 0.185, p = .038) with engagement along the PrEP Contemplation Ladder. Qualitative results from our study suggest that some Latinos who initially agreed to start using PrEP ended up getting lost in the care pipeline and failed to attend their scheduled appointments. Providers also noted that many patients lacked access to a pharmacy where they felt comfortable obtaining their PrEP prescription, leading them to discontinue use after only a few months. These findings emphasize the importance of considering the unique needs, culture, and background of Latinos, including care delivery and provider attitudes that can facilitate progress through the PrEP cascade.

Comamonas testosteroni as the cause of mortality in embryonated chicken eggs of breeding broiler hens in Costa Rica.

Mortality of chicken embryos and first-week chickens was reported in a commercial incubator company in Costa Rica. Six 1-day-old Cobb chickens and twenty-four embryonated chicken eggs were examined in the Laboratory of Avian Pathology and the Laboratory of Bacteriology of the National University of Costa Rica. Twelve dead-in-shell embryos showed maceration and were immersed in a putrid, turbid, slightly thick brown liquid. Additionally, the other 12 embryonated eggs had milky yellow-orange content. The livers of those embryos had congestion, haemorrhages and multifocal cream foci of necrosis. Granulocytic infiltration was observed in the bursa of Fabricius, myocardium, liver, lung and kidney. Livers and egg yolks from six embryonated chickens and all 1-day-old chickens were aseptically collected and cultured. In addition, tissues from six better conserved embryos and all 1-day-old chickens were fixed in buffered formalin and embedded in paraffin. Biochemical and molecular tests identified Comamonas testosteroni as the cause of the early, middle and late embryo mortality. As all the eggshells from the sampled embryonated eggs were dirty with soiled a fecal matter, contamination after manipulating the eggs was considered the source of infection. C. testosteroni is an environmental microorganism that has rarely been reported to cause human disease. To our knowledge, this is the first report of C. testosteroni causing mortality in a hatchery. Cleaning and disinfection using ozone were implemented in the hatchery to eliminate the embryo mortality associated with C. testosteroni.

Factors that indicate performance on the MoCA 7.3 in healthy adults over 50 years old.

Human aging is a physiological, progressive, heterogeneous global process that causes a decline of all body systems, functions, and organs. Throughout this process, cognitive function suffers an incremental decline with broad interindividual variability.The first objective of this study was to examine the differences in the performance on the MoCA test (v. 7.3) per gender and the relationship between the performance and the variables age, years of schooling, and depressive symptoms .The second objective was to identify factors that may influence the global performance on the MoCA test (v. 7.3) and of the domains orientation, language, memory, attention/calculation, visuospatial and executive function, abstraction, and identification.A cross-sectional study was carried out in which five hundred seventy-three (573) cognitively healthy adults ≥ 50 years old were included in the study. A sociodemographic questionnaire, the GDS-15 questionnaire to assess depression symptoms and the Spanish version of the MoCA Test (v 7.3) were administered. The evaluations were carried out between the months of January and June 2022. Differences in the MoCA test performance per gender was assessed with Student's t-test for independent samples. The bivariate Pearson correlation was applied to examine the relationship between total scoring of the MoCA test performance and the variables age, years of schooling, and depressive symptoms. Different linear multiple regression analyses were performed to determine variables that could influence the MoCA test performance.We found gender-related MoCA Test performance differences. An association between age, years of schooling, and severity of depressive symptoms was observed. Age, years of schooling, and severity of depressive symptoms influence the MoCA Test performance, while gender does not.

Efficient CRISPR/Cas9 nickase-mediated genome editing in an in vitro model of mucopolysaccharidosis IVA.

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder (LSD) caused by mutations in gene encoding for GALNS enzyme. Lack of GALNS activity leads to the accumulation of glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate. Although enzyme replacement therapy has been approved since 2014 for MPS IVA, still there is an unmet medical need to have improved therapies for this disorder. CRISPR/Cas9-based gene therapy has been tested for several LSDs with encouraging findings, but to date it has not been assayed on MPS IVA. In this work, we validated for the first time the use of CRISPR/Cas9, using a Cas9 nickase, for the knock-in of an expression cassette containing GALNS cDNA in an in vitro model of MPS IVA. The results showed the successful homologous recombination of the expression cassette into the AAVS1 locus, as well as a long-term increase in GALNS activity reaching up to 40% of wild-type levels. We also observed normalization of lysosomal mass, total GAGs, and oxidative stress, which are some of the major findings regarding the pathophysiological events in MPS IVA. These results represent a proof-of-concept of the use of CRISPR/Cas9 nickase strategy for the development of a novel therapeutic alternative for MPS IVA.

If You're Not Confused, You're Not Paying Attention: Ochrobactrum Is Not Brucella.

Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged the brucellae with the primarily free-living, phylogenetically related Ochrobactrum spp. in the genus Brucella. This change, founded only on global genomic analysis and the fortuitous isolation of some opportunistic Ochrobactrum spp. from medically compromised patients, has been automatically included in culture collections and databases. We argue that clinical and environmental microbiologists should not accept this nomenclature, and we advise against its use because (i) it was presented without in-depth phylogenetic analyses and did not consider alternative taxonomic solutions; (ii) it was launched without the input of experts in brucellosis or Ochrobactrum; (iii) it applies a non-consensus genus concept that disregards taxonomically relevant differences in structure, physiology, population structure, core-pangenome assemblies, genome structure, genomic traits, clinical features, treatment, prevention, diagnosis, genus description rules, and, above all, pathogenicity; and (iv) placing these two bacterial groups in the same genus creates risks for veterinarians, medical doctors, clinical laboratories, health authorities, and legislators who deal with brucellosis, a disease that is particularly relevant in low- and middle-income countries. Based on all this information, we urge microbiologists, bacterial collections, genomic databases, journals, and public health boards to keep the Brucella and Ochrobactrum genera separate to avoid further bewilderment and harm.

The landscape of CRISPR/Cas9 for inborn errors of metabolism.

Since its discovery as a genome editing tool, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) system has opened new horizons in the diagnosis, research, and treatment of genetic diseases. CRISPR/Cas9 can rewrite the genome at any region with outstanding precision to modify it and further instructions for gene expression. Inborn Errors of Metabolism (IEM) are a group of more than 1500 diseases produced by mutations in genes encoding for proteins that participate in metabolic pathways. IEM involves small molecules, energetic deficits, or complex molecules diseases, which may be susceptible to be treated with this novel tool. In recent years, potential therapeutic approaches have been attempted, and new models have been developed using CRISPR/Cas9. In this review, we summarize the most relevant findings in the scientific literature about the implementation of CRISPR/Cas9 in IEM and discuss the future use of CRISPR/Cas9 to modify epigenetic markers, which seem to play a critical role in the context of IEM. The current delivery strategies of CRISPR/Cas9 are also discussed.

Molecular Trojan Horses for treating lysosomal storage diseases.

Lysosomal storage diseases (LSDs) are caused by monogenic mutations in genes encoding for proteins related to the lysosomal function. Lysosome plays critical roles in molecule degradation and cell signaling through interplay with many other cell organelles, such as mitochondria, endoplasmic reticulum, and peroxisomes. Even though several strategies (i.e., protein replacement and gene therapy) have been attempted for LSDs with promising results, there are still some challenges when hard-to-treat tissues such as bone (i.e., cartilages, ligaments, meniscus, etc.), the central nervous system (mostly neurons), and the eye (i.e., cornea, retina) are affected. Consistently, searching for novel strategies to reach those tissues remains a priority. Molecular Trojan Horses have been well-recognized as a potential alternative in several pathological scenarios for drug delivery, including LSDs. Even though molecular Trojan Horses refer to genetically engineered proteins to overcome the blood-brain barrier, such strategy can be extended to strategies able to transport and deliver drugs to specific tissues or cells using cell-penetrating peptides, monoclonal antibodies, vesicles, extracellular vesicles, and patient-derived cells. Only some of those platforms have been attempted in LSDs. In this paper, we review the most recent efforts to develop molecular Trojan Horses and discuss how this strategy could be implemented to enhance the current efficacy of strategies such as protein replacement and gene therapy in the context of LSDs.

Primary headache disorders in Latin America and the Caribbean: A meta-analysis of population-based studies.

BACKGROUND: In this manuscript, we aim to systematically estimate the pooled prevalence and incidence of primary headaches and its subtypes (migraine, tension-type headache, and chronic headaches) in Latin America and the Caribbean, describing its epidemiological profile and associated factors. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and LILACS (From conception to March 2021), for populational studies reporting the epidemiology of primary headaches and their associated factors in Latin America and the Caribbean. The data extraction was conducted independently. We performed random-effect model meta-analysis of prevalence (overall primary headaches and by subtypes) and associated factors, assessed potential sources of heterogeneity, the risk of bias, publication bias, and the evidence certainty (GRADE methodology). RESULTS: We included 32 populational studies (38 subpopulations, n = 63,813). The prevalence of primary headaches was 41.4% (95% CI 31.1-52.2%; n = 54,357), 15% for migraine (95% CI 12.0-18.3; n = 53,658 individuals), 20.6% for tension-type headache (95% CI 12.4-30.2; n = 25,840), and 6% for chronic headaches (95% CI 3.3-9.6; n = 21,720), with high between-study heterogeneity. No incidence data was found. Female sex, white ethnicity, high BMI, comorbid mental health disorders, and low-back pain were associated with higher prevalence of primary headaches. The prevalence was less in rural areas. CONCLUSION: In Latin America and the Caribbean, primary headaches are highly prevalent affecting young females disproportionally. The prevalence of chronic headaches is higher than in other systematic global and regional estimations. The presence of comorbidities as modifiable risk factors should encourage their integration as targets for community-based preventive and therapeutic interventions. PROTOCOL REGISTRATION NUMBER: CRD42018105116.

Assessment of predation risk through conspecific cues by anuran larvae.

Accurate assessment of predation risk is critical for prey survival during predator-prey interactions. Prey can assess predation risk by the presence of cues dropped by predators themselves, but they can also gather information about risk level through cues released by other prey, avoiding the hazard of being in close proximity to predators. In this study, we examine the ability of anuran larvae (Pelobates cultripes) to detect predation risk indirectly when they are in contact with conspecifics that have been recently exposed to chemical stimuli from natural predators (larvae of aquatic beetles). In a first experiment, we confirmed that larvae exposed to predator cues exhibited innate defensive behavior, indicating that they perceived the risk of predation and, thus, could potentially act as risk indicators for naïve conspecifics. In a second experiment, we observed that unexposed larvae paired with a startled conspecific adjusted their antipredator behavior, presumably by mirroring conspecifics' behavior and/or using chemical cues from their partners as a risk information source. This cognitive ability of tadpoles to assess predation risk through conspecific cues might play an important role in their interaction with predators, facilitating the early detection of potential threats to elicit appropriate antipredator responses and increase the chances of survival.

Advances in the control of lipid peroxidation in oil-in-water emulsions: kinetic approaches†.

Large efforts have been, and still are, devoted to minimize the harmful effects of lipid peroxidation. Much of the early work focused in understanding both the lipid oxidation mechanisms and the action of antioxidants in bulk solution. However, food-grade oils are mostly present in the form of oil-in-water emulsions, bringing up an increasing complexity because of the three-dimensional interfacial region. This review presents an overview of the kinetic approaches employed in controlling the oxidative stability of edible oil-in-water emulsions and of the main outcomes, with particular emphasis on the role of antioxidants and on the kinetics of the inhibition reaction. Application of physical-organic chemistry methods, such as the pseudophase models to investigate antioxidant partitioning, constitute a remarkable example on how kinetic methodologies contribute to model chemical reactivity in multiphasic systems and to rationalize the role of interfaces, opening new opportunities for designing novel antioxidants with tailored properties and new prospects for modulating environmental conditions in attempting to optimize their efficiency. Here we will summarize the main kinetic features of the inhibition reaction and will discuss on the main factors affecting its rate, including the determination of antioxidant efficiencies from kinetic profiles, structure-reactivity relationships, partitioning of antioxidants and concentration effects.

Reactions to Testing HIV Negative: An Assessment of Measurement Invariance and Associations with Condomless Anal Sex among English and Spanish-speaking Latinx Sexual Minority Men in the United States.

Among the many effective prevention strategies, frequent HIV testing continues to be promoted to reduce the risk of HIV transmission among sexual minority men (SMM). Testing negative for HIV can result in varied reactions that influence subsequent HIV transmission behaviors, yet the extant research has primarily been conducted in English. The current study examined measurement invariance of a Spanish-translated Inventory of Reactions to Testing HIV Negative (IRTHN). The study also examined whether the IRTHN was associated with subsequent condomless anal sex. Data were drawn from 2,170 Latinx SMM subsample of the UNITE Cohort Study. We conducted a multigroup confirmatory factor analysis to test for measurement invariance between participants who opted to take the survey in English (n = 2,024) and those who opted to take it in Spanish (n = 128). We also examined if the IRTHN is associated with subsequent CAS. The results were suggestive of partial invariance. The subscales of Luck and Invulernability were associated with CAS at the 12-month follow-up. Practice and research-based implications are discussed.

Effectiveness of the SMART Sex Ed program among 13-18 year old English and Spanish speaking adolescent men who have sex with men.

Adolescent men who have sex with men (AMSM) have a high HIV incidence and low utilization of testing and prevention services. However, very few HIV prevention programs exist that focus on the unique sexual health needs of AMSM. SMART is a stepped care package of eHealth interventions that comprehensively address the sexual and HIV prevention needs of AMSM. This study examines the impact of the first step of SMART, "SMART Sex Ed," on 13- to 18-year-old AMSM (n = 983) from baseline to three-month follow-up across 18 separate outcomes measuring HIV prevention attitudes, skills, and behaviors. We observed significant change from baseline to three-month post-intervention in nine HIV-related outcomes (e.g., receipt of HIV and STI test, HIV knowledge), as well as largely consistent effects across demographic subgroups (e.g., race, age, rural, low SES). Analyses observed no effects on condom use behaviors. SMART Sex Ed shows promise as an effective sexual health education program for diverse AMSM.

RESUMEN: Los adolescentes hombres que tienen sexo con otros hombres (AHSH) experimentan alta incidencia del VIH y baja utilización de servicios de prueba y prevención. Sin embargo, existen muy pocos programas de prevención del VIH enfocados en las necesidades particulares para la salud sexual de AHSH. SMART es un paquete de intervenciones de cuidado escalonado que usa plataformas electrónicas (eHealth) y que atiende de forma integrada las necesidades de salud sexual y prevención del VIH de AHSH. Este estudio examina el impacto de la primera etapa de SMART, llamada "SMART Sex Ed", entre AHSH (n = 983) entre las edades de 13 a 18 años e integra datos desde el reclutamiento con seguimiento cada 3 meses. Se recopilaron datos de 18 indicadores de actitudes, destrezas y prácticas de prevención del VIH (Ej. Historial de pruebas de VIH o ITS; conocimiento sobre VIH), así como los efectos en diferentes grupos demográficos (Ej. Raza, edad, área rural, y bajo nivel socioeconómico). Los análisis realizados demuestran que las características demográficas no tienen efecto en las prácticas de uso de condón. SMART Sex Ed es una intervención prometedora para educación sexual efectiva para AHSH.

Early start hemodialysis with a catheter may be associated with greater mortality: A propensity score analysis.

INTRODUCTION: Deciding when and how to initiate hemodialysis (HD) is still controversial. An early start (ES) seems to show a lack of benefit. "Lead time bias" and comorbidities have been associated with different outcomes in ES groups. On the other hand, it is well accepted that the impact the type of vascular access (VA) has on patient survival. Our aim was to evaluate survival with early start (ES) versus late start (LS) on HD, taking into account the vascular access (VA) used. METHODS: Between 01/1995 and 06/2018, 503 incidental patients initiated HD at our Dialysis Unit. eGFR was estimated by the CKD-EPI equation. Diabetes mellitus (DM), coronary disease (CD), and peripheral vascular disease (PVD) were considered comorbid conditions. According to eGFR and VA, patients were divided into four groups: G1: ES (eGFR > 7 mL/min) with catheter (ES + C), G2: ES with fistula or graft (F/G) (ES + F/G), G3: LS (eGFR< 7 mL/min) with catheter (LS + C), and G4: LS with F/G (LS + F/G). The cut-off value to define ES or LS was based on median eGFR for these 503 patients. We compared patient's survival rates by Kaplan-Meier and log-rank test. The four groups were compared before and after matching with propensity scores (PS). Cox analysis was performed to determine the impact of predictors of mortality. RESULTS: Median eGFR was 7 (5.3-9.5) mL/min/1.73 m2 , median follow-up time was 30.9 (13-50) months, 52.1% had F/G access at entry, and 46.9% died during the observation period. Among the four groups, the ES + C were significantly older, and there were more diabetics and comorbid conditions, while phosphatemia, iPTH, albumin, and hemoglobin were significantly higher in the LS groups. Before propensity score (PS) matching, the ES + C group had a poor survival rate (p < 0.0001), while LS + F/G access had the best survival. After PS, a total of 180 patients were selected in the same four groups and ES + C kept showing a statistically significant poorer survival. Multivariate analysis revealed that ES + C was an independent predictor of mortality. CONCLUSION: In this retrospective study, ES + C on HD was associated with a higher mortality rate than LS. This association persisted after PS matching.

Characterization and expression of domains of Alphaherpesvirus bovine 1/5 envelope glycoproteins B in Komagataella phaffi.

BACKGROUND: Bovine herpes virus (BoHV 1 and BoHV-5) are the causative agents of infectious bovine rhinotracheitis (IBR). IBR is responsible for important economic losses in the cattle industry. The envelope glycoprotein B (gB) is essential for BoHV infection of cattle's upper respiratory and genital tract. gB is one of the main candidate antigens for a potential recombinant vaccine since it induces a strong and persistent immune response. RESULTS: In this study, gB of BoHV-1 and BoHV-5 was characterized in terms of function, structure, and antigenicity through bioinformatics tools. gB showed conserved sequence and structure, so, both domains named PH Like 1 and 2 domains of each virus were selected for the design of a bivalent vaccine candidate. The immunoinformatic study showed that these two domains have epitopes recognizable by B and T lymphocytes, followed by this, the cDNA domains from BoHV-1/5 gB (Domains-gB) were transformed into the yeast Komagataella phaffii GS115 (previously known as Pichia pastoris). A recombinant protein with molecular weight of about 110 kDa was obtained from the culture media. The vaccine candidate protein (Domains-gB) was recognized by a monoclonal antibody from a commercial ELISA kit used for IBR diagnostic, which may suggest that the epitopes are conserved of the entire infectious virus. CONCLUSION: Overall, it was shown that the recombinant domains of BoHV-1/5 gB have antigenic and immunogenic properties similar to the native gB. This vaccine candidate is promising to be used in future studies to assess its immunogenicity in an animal model.

Genome Editing Tools for Lysosomal Storage Disorders.

Genome editing has multiple applications in the biomedical field. They can be used to modify genomes at specific locations, being able to either delete, reduce, or even enhance gene transcription and protein expression. Here, we summarize applications of genome editing used in the field of lysosomal disorders. We focus on the development of cell lines for study of disease pathogenesis, drug discovery, and pathogenicity of specific variants. Furthermore, we highlight the main studies that use gene editing as a gene therapy platform for these disorders, both in preclinical and clinical studies. We conclude that gene editing has been able to change quickly the scenario of these disorders, allowing the development of new therapies and improving the knowledge on disease pathogenesis. Should they confirm their hype, the first gene editing-based products for lysosomal disorders could be available in the next years.