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Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru.Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021.From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP.Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP.Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru.For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage C.37 (Lambda) has spread rapidly in Peru and other Latin American countries. However, most studies in Peru have focused on Lima, the capital city, without knowing the dynamics of the spread of the variant in other departments. Cusco, Peru, is one of the most popular departments in the country for tourists, so the introduction of new variants of SARS-CoV-2 might occur despite closure of the borders. Therefore, in this work, we analyzed the variants circulating in Cusco. The aim of this work was to better understand the distribution of SARS-CoV-2 lineages circulating in Cusco and to characterize the genomes of these strains. To this end, 46 SARS-CoV-2 genomes from vaccinated and unvaccinated patients were sequenced in the first half of 2021. The genomes were analyzed using phylogenetic and natural selection methods. Phylogenetic trees from Cusco showed dominance of the Lambda lineage over the variants of concern (VOCs), and there was no clustering of variants by district. Natural selection analysis revealed mutations, mainly in the spike protein, at positions 75, 246, 247, 707, 769, and 1020. In addition, we found that unvaccinated patients accumulated more new mutations than did vaccinated patients, and these included the F101Y mutation in ORF7a, E419A in NSP3, a deletion in S (21,618-22,501), and a deletion in ORF3a (25,437-26,122).

Many professional societies utilize travel awards programs to foster inclusion and facilitate the professional development of underrepresented minority (URM) scientists. All member societies that participate in the Alliance to Catalyze Change for Equity in STEM Success (ACCESS) do so to some degree. Members of this meta-organization recently came together to share their different approaches to URM travel award program assessment. The practices of the Biophysical Society (BPS), one of the ACCESS member societies, is used as a case study to discuss the highlights of our findings. We share and discuss a framework for URM travel award program assessment.

Antecedentes: La prevalencia mundial de discapacidad en adultos mayores oscila entre 29.5% y 43.4% en países de ingreso alto/bajo (OMS 2011). Objetivo: Determinar la prevalencia de discapacidad y factores asociados en adultos mayores, Honduras, 2014-2015. Métodos: Estudio descriptivo transversal con análisis de asociación. Estudiantes de último año, Carrera de Medicina, Universidad Nacional Autónoma de Honduras, realizaron búsqueda activa de 50 participantes ≥60 años de edad. Se aplicaron dos instrumentos, uno para búsqueda activa y otro para caracterizar al participante con/sin discapacidad permanente ≥1 año de evolución. Se evaluó limitación de actividad y restricción de participación ≤30 días utilizando la Clasificación Internacional del Funcionamiento, Discapacidad y Salud (CIF) y cuestionario WHODAS 2.0 (OMS). Se realizó análisis univariado (frecuencias, porcentajes, prevalencias, IC95%) y análisis bivariado (diferencia de proporciones); valor p70 años, escolaridad

El presente trabajo de investigación consistió en hacer un mapeo de preferencias acerca de los néctares de fruta envasados más representativos, de durazno, que existen en nuestro país. Estos fueron Liber, Pulp, Frugos y Watts. Por tal motivo, la idea es analizar a través de la técnica estadística del mapeo, cual es el néctar que puede tener mayor aceptabilidad en el consumidor y que características pueden influir en el mismo; ya que nos permite conocer que propiedades debe tener este producto, si en caso se quiere lanzar uno nuevo al mercado. Así mismo, se encuestó y se le hizo pruebas de análisis sensorial a un cierto grupo de personas (familiares y conocidos de los investigadores, por temas del Covid 19), para determinar y puntuar características básicas a modo de los atributos sensoriales tales como el sabor, olor, claridad, espesor, color, entre otras. Posteriormente, los resultados fueron organizados en un Excel para su posterior uso y/o manejo en el programa RStudio. Donde, se realizó el análisis correspondiente a toda esa data de néctares para poder obtener los diferentes resultados de mapas de preferencia a través de gráficos didácticos y representativos, como elipses de confianza, mapa de individuos, entre otros. Por consiguiente, al final del estudio y el análisis se puede afirmar que uno de los néctares con mayor aceptación y preferencia fue el de la marca Líber según nuestra encuesta de consumo, y con respecto al análisis sensorial el más importante fue el néctar Frugos para los panelistas.

Antecedentes. Cobertura Universal en Salud es uno de los Objetivos de Desarrollo Sostenible. Las personas con discapacidad suelen tener mayores dificultades de acceso a la salud que el resto de la población. Factores del entorno como el diseño y las construcciones pueden ser una barrera o un facilitador. Objetivo. Evaluar las características de accesibilidad en el diseño y las ayudas técnicas para la movilidad en los establecimientos de salud en zonas de realización del servicio médico social, Carrera de Medicina UNAH, cohorte 2013-2014. Métodos. En base a principios de diseño universal se evaluaron barreras y facilitadores para el acceso a la salud en establecimientos de salud, incluyendo centros de atención primaria y hospitales. Resultados. Se evaluaron 176 establecimientos en 17 departamentos, 154 unidades de atención primaria (UAP) y 22 hospitales. Las mayores barreras fueron la señalización inadecuada de rutas: 150 (97.4%) UAP y 20 (90.9%) hospitales; la carencia de soportes en los baños: 152 (98.7%) UAP y 20 (90.9%) hospitales; la inaccesibilidad a personas en sillas de ruedas: 129 (83.8%) UAP y 9 (40.9%) hospitales. Discusión. Mejorar el acceso y la calidad de los servicios de salud para las personas con discapacidad es imprescindible para reducir las inequidades. Nuestro estudio indica que el diseño de los establecimientos de salud en Honduras supone una barrera para el acceso y calidad de salud de las personas con discapacidad. Se exhorta al Estado a regular y supervisar el diseño y construcción de edificios accesibles para todos, a fin de reducir las brechas en salud.

Antecedentes: La Revista Médica Hondureña (RMH) se ha caracterizado durante más de 90 años por ser el principal medio de difusión médico-científico en Honduras. Objetivo: Identificar si el manejo rehabilitador es considerado como opción terapéutica de acuerdo a la discapacidad de los casos clínicos publicados en la RMH en el periodo 1995-2019 y revisar algunas condiciones que generan discapacidad cuando no son atendidas oportunamente. Métodos: Revisión bibliométrica de los artículos de la sección Casos Clínicos, desde el Volumen 63 Número 1 Año 1995 al Volumen 87 Número 2 Año 2019, 98 números en total. En cada artículo se revisó si se había incluido la rehabilitación dentro del manejo terapéutico, y/o si había sido mencionado como parte integral del manejo de los pacientes. Resultados: De 206 artículos revisados, 11 (5.3%) describieron la rehabilitación como parte del manejo recibido; en 8 publicaciones el autor describió en la revisión de literatura que el manejo ideal en tales casos incluye la rehabilitación. De acuerdo a parámetros ya establecidos en Medicina Física y Rehabilitación, los casos informados en 106 (51.4%) artículos se habrían beneficiado de recibir manejo de rehabilitación. Discusión: A través de esta revisión bibliométrica de veinticinco años, se ha podido documentar que en Honduras aún no se reconoce el beneficio de la rehabilitación en las distintas patologías, tanto en el manejo hospitalario como ambulatorio. La Medicina Física y Rehabilitación contribuye a disminuir y/o evitar complicaciones en los pacientes, por lo que exhortamos a médicos generales y de otras especialidades a tomar conciencia de ello.

Trifluoroselenomethionine (TFSeM), a new unnatural amino acid, was synthesized in seven steps from N-(tert-butoxycarbonyl)-l-aspartic acid tert-butyl ester. TFSeM shows enhanced methioninase-induced cytotoxicity, relative to selenomethionine (SeM), toward HCT-116 cells derived from human colon cancer. Mechanistic explanations for this enhanced activity are computationally and experimentally examined. Comparison of TFSeM and SeM by selenium EXAFS and DFT calculations showed them to be spectroscopically and structurally very similar. Nonetheless, when two different variants of the protein GB1 were expressed in an Escherichia coli methionine auxotroph cell line in the presence of TFSeM and methionine (Met) in a 9:1 molar ratio, it was found that, surprisingly, 85 % of the proteins contained SeM residues, even though no SeM had been added, thus implying loss of the trifluoromethyl group from TFSeM. The transformation of TFSeM into SeM is enzymatically catalyzed by E. coli extracts, but TFSeM is not a substrate of E. coli methionine adenosyltransferase.

The canonical pathogenesis of Alzheimer's disease links the expression of apolipoprotein E ε4 allele (ApoE) to amyloid precursor protein (APP) processing and Aβ peptide accumulation by a set of mechanisms that is incompletely defined. The development of a simple system that focuses not on a single variable but on multiple factors and pathways would be valuable both for dissecting the underlying mechanisms and for identifying candidate therapeutics. Here we show that, although both ApoE3 and ApoE4 associate with APP with nanomolar affinities, only ApoE4 significantly (i) reduces the ratio of soluble amyloid precursor protein alpha (sAPPα) to Aβ; (ii) reduces Sirtuin T1 (SirT1) expression, resulting in markedly differing ratios of neuroprotective SirT1 to neurotoxic SirT2; (iii) triggers Tau phosphorylation and APP phosphorylation; and (iv) induces programmed cell death. We describe a subset of drug candidates that interferes with the APP-ApoE interaction and returns the parameters noted above to normal. Our data support the hypothesis that neuronal connectivity, as reflected in the ratios of critical mediators such as sAPPα:Aβ, SirT1:SirT2, APP:phosphorylated (p)-APP, and Tau:p-Tau, is programmatically altered by ApoE4 and offer a simple system for the identification of program mediators and therapeutic candidates.

A new synthesis of fluorinated allylamines through the reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides (as vinyl anion equivalents) with imines and imino esters has been described. The process includes a TBAF-mediated fragmentation of 2-(trimethylsilyl)ethyl sulfones to afford the desired allylic amines. When the reaction is performed with the corresponding sulfoxides, the fragmentation takes place under the addition conditions, affording the final products in a single step. (C) 2007 Elsevier B.V. All rights reserved.

This paper describes a novel fluorous synthesis of fluorinated uracils 4. In this new protocol, fluorous alcohols 1, which are used as fluorous tags, are acetylated to yield acetates 2, which in turn are treated with a base to form their enolates. These are then reacted with fluorinated nitriles to furnish tagged β-enamino esters 3. Although this condensation step had been performed easily in previous solution and solid-phase syntheses, it proved to be very elusive in the fluorous version. Meticulous control of the reaction conditions was thus essential in order to achieve satisfactory yields of β-enamino esters 3. The final treatment of compounds 3 with isocyanates or isothiocyanates efficiently afforded uracils 4 with concomitant elimination of the fluorous tag, thereby facilitating the preparation of a small library of these derivatives.

Resumen: Streptococo pneumoniae (Neumococo), Neisseria meningitidis y Haemophilus influenzae producen meningitis bacterianas. Este trabajo describe las caracteristicas del aumento de casos de meningitis bacterianas en la Provincia de la Rioja, Argentina. Se realizó un estudio descriptivo retrospectivo de las meningitis desde 1997 hasta 2001. Se estudió la circulación de los agentes etiologicos; la distribución de las neumonías y bacteriemias producidas por neumococo; las variaciones de la humedad relativa y de las temperaturas promedios (aportadas por el Servicio Meteorológico Nacional). Los casos se estudiaron desde fichas epidemiológicas de la Dirección de epidemiología y de historias clínicas del Hospital "Dr. E. Vera Barros". Los liquidos cefalorraquideos y lavados pleurales o bronquiales se procesaron en el laboratorio de bacteriología. Los aislamientos se remitieron para su serotipificación al laboratorio de referencia nacional. Durante el año 2000, la tasa de incidencia de meningitis fue mayor y la tasa de meningitis por neumococo fue mayor en el periodo estudiado. En ese año, el neumococo aumenta la circulación presentandose aumento de meningitis, neumonias mientras que las infecciones neumococcicas invasivas fueron simirales a otros años. La circulación de los otros agentes etiológico se mantienen constante en el periodo estudiado. Los serotipos circulantes fueron sensibles penicilina. Durante el año 2000 aumenta en la humedad (2-6 puntos) y disminuye la amplitud térmica en los meses simultáneamente a la presencia de los casos de infecciones por neumococo. Los resultados sugieren que la circulación del neumococo en una población estaría relacionada con la alta humedad relativa y la poca amplitud térmica.

First principles density functional theory is utilized to describe electronic structure and magnetic interactions between Cr(III) ions in linear and bent geometry of [cis-[hydroxotetramminechromium-μ-hydroxopentamminechromium]4+. The effective exchange parameter J is extracted and compared with empirical values fitted to experimental data. The calculated value J = 48 K for bent geometry compares well with the 30 K experimental value; the magnetic interaction is an order of magnitude larger in the linear configuration. Low-lying optical transitions are analyzed, making use of the transition state scheme, and are in semiquantitative agreement with experimental absorption.

Condensation of unsaturated esters (I) and (VII) with 1,2-diamines proceeds in the presence of trimethylaluminum providing imidazolines (III) and (VIII) which are further allylated giving suitable dienes (V) and (IX).

[EN] An efficient method for the synthesis of fluorinated and non-fluorinated imidazoazepines by a ring-closing metathesis reaction as the key step is described. The influence of the fluorine atoms on the preparation of these bicyclic systems is also studied., We would like to thank the Ministerio de Ciencia e Innovacion (MICINN) (CTQ2010-19774) of Spain and the Generalitat Valenciana (PROMETEO/2010/061) for financial support. S. F. expresses her thanks for a predoctoral fellowship (FPU Programme).

The preparation of novel fluorinated allylamines and their use as key fragments for the stereoselective synthesis of hydroxyethyl secondary amine (HEA)-type peptidomimetics is described. Our strategy employs chiral sulfinyl imines as synthesis intermediates, by treatment of hemiaminal precursors with two equivalents of vinylmagnesium bromide. The subsequent oxidation of the allylic amines to the corresponding epoxides was achieved by treatment with methyl(trifluoromethyl)dioxirane. Finally, epoxide ring opening with a range of nitrogen nucleophiles provided a library of HEA-derived peptidomimetics with a phenyldifluoromethylene moiety. The biological evaluation of these derivatives revealed compounds with remarkable BACE1 inhibitory activity. Docking studies revealed the influence of the fluorine atoms in the binding mode of the synthesized ligands. Furthermore, the biological evaluation of our final products and synthesis intermediates led to the discovery of compounds with antimicrobial activity against Mycobacterium and Nocardia species.

N-Sulfinyl amines have been successfully employed as nitrogen nucleophiles for the asymmetric intramolecular aza-Michael reaction. The synthetic strategy involves a cross-metathesis reaction followed by the Michael-type cyclization, either in a base-catalyzed two-step procedure or in a tandem fashion. The developed methodology allows access to chiral substituted pyrrolidines and piperidines bearing one or two stereocenters and it has been applied to the synthesis of the piperidine alkaloid (-)-pinidinol.

A new synthesis of fluorinated allylamines through the reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides (as vinyl anion equivalents) with imines and imino esters has been described. The process includes a TBAF-mediated fragmentation of 2-(trimethylsilyl)ethyl sulfones to afford the desired allylic amines. When the reaction is performed with the corresponding sulfoxides, the fragmentation takes place under the addition conditions, affording the final products in a single step.

The benefits of hepatic transplantation (HT) compared with hepatic resection (HR) in treating hepatocellular carcinoma (HCC) in patients with cirrhosis are controversial. The aim of this study was to compare the results of these therapeutic options. The charts of all patients with cirrhosis who underwent HR or HT for HCC between 1997 and 2000 were analyzed. The cohort included 44 patients who underwent HR compared with 65 with HT. All patients in the HR group had Child's A disease, in contrast to the HT group, which included 23% Child's A and 77% Child's B and C patients. Whereas all HT patients spent at least three nights in the intensive care unit, 41% of the HR group never required critical care. Perioperative mortality was 7% in both groups. Pathologic analysis revealed T1/T2 disease in 43% of the HR group compared with 75% of the HT group. After 36 months of follow-up, there was no significant difference in overall survival (57% vs. 66%) or disease-free survival (36% vs. 66%) between the two groups. With overall survival and disease-free survival as the main outcomes, the results of HR versus HT are comparable in Child's A patients with HCC. In this patient subset, HR not only is an effective form of therapy, but is also associated with quicker recovery.