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Abstract Background Mobile health is gradually revolutionizing the way medical care is delivered worldwide. In Mozambique, a country with a high human immunodeficiency virus prevalence, where antiretroviral treatment coverage is 77% accompanied by a 67% of retention rate, the use of mobile health technology may boost the antiretroviral treatment, by delivering care beyond health facilities and reaching underrepresented groups. Leveraging new technologies is crucial to reach the 95–95-95 United Nations target by 2030. The design, development, implementation, and evaluation of a mobile health platform called Infomóvel were covered in this article. Its intended use involves collaboration with community health workers and aims to increase human immunodeficiency virus patient access, adherence, and retention to care. Methods Using the Design Science Research Methodology, Infomóvel was created, as well as this publication. The explanation of various actions includes everything from problem description to observational study and goal-following for a solution, which results in the design and development of a platform proposal. Before the utility assessment of Infomóvel was conducted to make adjustments, a demonstration phase was conducted in one region of Mozambique. Results The initial subjects of the Infomóvel flowchart and physical process design were patients receiving antiretroviral medication who were enrolled in the patients tracking system and who had consented to home visits. The case manager examines the file before importing it into the Infomóvel database stored on a cloud server using the website www.commcarehq.org . The case manager application synchronises with the Infomóvel server database, enabling the import of latest data and access to the lists of new patients and community health workers. The community health worker uses his phone to access his application, which allows him to record the geographic coordinates and sort the list of patients by priority and type of visit. Conclusion Results from Infomóvel add to the growing body of data showing that mobile health techniques are beneficial for managing stable individuals with chronic conditions in Mozambique. These approaches can be scaled up and better utilised. However, additional studies should be conducted to quantify the resources needed to implement on a larger scale.

Antiviral agents are needed for the treatment of SARS-CoV-2 infections and to control other coronavirus outbreaks that may occur in the future. Here we report the identification and characterization of RNA-binding compounds that inhibit SARS-CoV-2 replication. The compounds were detected by screening a small library of antiviral compounds previously shown to bind HIV-1 or HCV RNA elements with a live-virus cellular assay detecting inhibition of SARS-CoV-2 replication. These experiments allowed detection of eight compounds with promising anti-SARS-CoV-2 activity in the sub-micromolar to micromolar range and wide selectivity indexes. Examination of the mechanism of action of three selected hit compounds excluded action on the entry or egress stages of the virus replication cycle and confirmed recognition by two of the molecules of conserved RNA elements of the SARS-CoV-2 genome, including the highly conserved S2m hairpin located in the 3’-untranslated region of the virus. While further studies are needed to clarify the mechanism of action responsible for antiviral activity, these results facilitate the discovery of RNA-targeted antivirals and provide new chemical scaffolds for developing therapeutic agents against coronaviruses.

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.

An under-explored target for SARS-CoV-2 is the S-adenosyl methionine (SAM)-dependent methyltransferase Nsp14, which methylates the N7-guanosine of viral RNA at the 5'-end, allowing the virus to evade host immune response. We sought new Nsp14 inhibitors with three large library docking strategies. First, up to 1.1 billion lead-like molecules were docked against the enzyme's SAM site, leading to three inhibitors with IC50 values from 6 to 50 μM. Second, docking a library of 16 million fragments revealed 9 new inhibitors with IC50 values from 12 to 341 μM. Third, docking a library of 25 million electrophiles to covalently modify Cys387 revealed 7 inhibitors with IC50 values from 3.5 to 39 μM. Overall, 32 inhibitors encompassing 11 chemotypes had IC50 values < 50 μM and 5 inhibitors in 4 chemotypes had IC50 values < 10 μM. These molecules are among the first non-SAM-like inhibitors of Nsp14, providing starting points for future optimization.

Se trata de una paciente de 58 años, sexo femenino, que se presenta con hematuria, proteinuria severa y función renal normal. Pocas semanas después, ella desarrolla una trombosis de vena renal, embolia pulmonar secundaria y un episodio de insuficiencia renal aguda. Este caso clínico ilustra las distintas presentaciones clínicas de una nefropatía por IgA grave, incluyendo hematuria, síndrome nefrótico y trombosis de vena renal. Además muestra otras complicaciones serias, como embolia pulmonar y falla renal aguda. La paciente fue sometida a 2 biopsias renales, que permitieron una correlación adecuada entre las manifestaciones clínicas y la patología renal.

Se presenta el caso de una paciente de 41 años portadora de mamas axilares bilaterales que consulta por dolor más masa palpable en una de ellas. La paciente es sometida a resección quirúrgica que mostró que el tumor era un fibroadenoma.

El siguiente trabajo tiene la finalidad de aplicar algunas de las generalidades que involucra el procesamiento estadístico deorden superior al monitoreo del estado de las máquinas rotatorias, a partir del sensado de las vibraciones que esta genera.Básicamente se trabajó en la detección del desequilibrio presente, así como en la estimación de la magnitud del mismo.Como elementos estadísticos que se procesaron figuran los momentos y cumulantes de orden superior (hasta orden cuarto)de las vibraciones medidas tanto en el eje horizontal, como el vertical.Finalmente, se constató como resultado, la efectividad de tal método para detectar un fallo específico, en este caso, eldesequilibrio y que podría ser extendido para otros tipos de fallos.Palabras claves: Análisis de vibraciones, procesamiento estadístico de orden superior, diagnóstico demaquinarias rotatorias.___________________________________________________________________________Abstract.The aim of this work is to apply higher-order statistics foundations on machine condition monitoring via vibration analysis.Specifically, shaft unbalance was the defect under study, and tasks for detection and magnitude estimation of thismechanical problem were accomplish.Higher-order (up to fourth-order) moments and cumulants of vertical and horizontalvibrations were estimated and analyzed.It was probed the method effectiveness when it is applied on unbalance detection.Passwords: Vibration analysis, higher-order estatistics processing, rotating machine diagnosis.

Los marcadores del cromosoma X se han utilizado en identificación humana y en pruebas de paternidad desde la década de los setenta, entre los más conocidos está el antígeno de los eritrocitos "Xgª", codificado por el gen del locus Xp22.32, y algunas enzimas de los eritrocitos, la más conocida es la Glucosa 6-fosfato Deshidrogenasa. Los marcadores moleculares ligados al Cromosoma X que se utilizan en genética forense son los STR, se han identificado más de 200 loci, entre trinucleótidos y tetranucleótidos. Sin embargo, solo en los últimos años se ha evaluado el poder informativo de los STR ligados al cromosoma X para su utilización en identificación humana y en investigaciones de paternidad, lo que ha estimulado su estudio en las diferentes poblaciones del mundo. Presentamos los resultados de una investigación genético-poblacional en una muestra poblacional del Departamento de Bolívar - Colombia, con 10 microsatélites ligados al Cromosoma X. Se analizaron 279 cromosomas, de 101 hombres y 89 mujeres, no relacionados biológicamente, mediante PCR multiplex con los marcadores DXS6809, DXS7423, GATA172D05, DXS6789, DXS9902, DXS7132, GATA31E08, DXS7133, DXS9898 y DXS8378. Se reportan las frecuencias alélicas para los 10 marcadores estudiados. Ninguno de los loci estudiados presentó desviación del equilibrio de Hardy - Weinberg, tampoco se observó asociación entre los loci al ser evaluado el desequilibrio de ligamiento. Arrojaron un poder de discriminación acumulado para hombres y mujeres de 99.9999% y 99.9999999%, respectivamente, y un poder de exclusión acumulado mayor del 99.9%, tanto para tríos padre-madre-hija como para dúos padre-hija. Estos hallazgos los validan para ser usados en casos de de identificación y establecimiento de relaciones biológicas en el Departamento de Bolívar, creándose así una nueva base de datos para la región.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

Presentamos una nueva forma de drenaje venoso pulmonar anómalo parcial: una comunicación laterolateral entre vena pulmonar derecha única y vena cava superior (VCS). Material y método: Técnica quirúrgica: decúbito lateral izquierdo. Minitoracotomía axilar izquierda entre el pectoral mayor y el dorsal ancho, se aborda el tórax por el cuarto espacio intercostal. Visión combinada con toracoscopio de 5 mm. Se diseca y moviliza la VCS y la vena pulmonar derecha, que es una gran vena única conectada a la aurícula izquierda. Se encontró una gran comunicación laterolateral entre la vena pulmonar única y la VCS. Se procedió al clampaje parcial de ambas venas seccionándolas y resuturándolas con sutura reabsorbale PDS 6/0. Cierre según la técnica habitual. El paciente se extubó en quirófano. Resultados: Varón de 16 años de edad con disnea de grandes esfuerzos, diagnosticado inicialmente por ecocardiograma y cateterismo de drenaje venoso pulmonar anómalo parcial de vena pulmonar superior derecha a VCS en ausencia de comunicación interauricular (CIA) con Qp/Qs de 1.84/1 y dilatación de cavidades derechas. En quirófano se apreció una conexión normal de una vena pulmonar derecha única a la aurícula izquierda (AI) pero con un drenaje anómalo a VCS debido a la presencia de una ventana cavopulmonar. El paciente no precisó hemoderivados. Estancia en unidad de cuidados intensivos (UCI) de 24 h. Ecocardiograma de control: ausencia de cortocircuito, ventrículo derecho (VD) ligeramente dilatado de 2,9 cm, normotensión pulmonar. Conclusiones: La ventana cavopulmonar es una nueva forma de drenaje venoso anómalo parcial que puede ser corregida de manera sencilla, segura y reproducible. Esta lesión no había sido descrita con anterioridad.

El síndrome de Beals, o aracnodactilia contractural congénita, produce cardiopatía, esencialmente ectasia anuloaórtica, en un 30% de los casos. Materiales y métodos: Varón de 18 años intervenido en la infancia de coartación aórtica, comunicación interventricular (CIV) perimembranosa y reparación aórtica por perforación de velo no coronariano. Presenta en su evolución una ectasia anuloaórtica de 5,5 cm de diámetro con insuficiencia aórtica ligera. Técnica quirúrgica: Estereotomía media e instauración de circulación extracorpórea (CEC) convencional. Se encontró un aneurisma de 5,5 cm a nivel de los senos de Valsalva con anillo aórtico de 3,1 cm y la parte tubular de la aorta ascendente y resto de la aorta normales. Insuficiencia aórtica ligera. Se resecó el aneurisma de los senos de Valsalva dejando los dos botones coronarios y se implantó un anillo subaórtico de Lansac de 27 mm en posición extracardíaca. La raíz se sustituyó con tubo de dacrón de 30 mm según técnica de Yacoub, conservando la válvula nativa. Se corrigió un prolapso del velo no coronariano con puntos centrales en el borde libre. Se reimplantaron las coronarias al tubo de dacrón. Resultados: T de CEC 264’ T de isquemia 182’. Postoperatorio favorable salvo bloqueo auriculoventricular (AV) que requirió el implante de marcapasos. Ecocardiograma postoperatorio: raíz aórtica normal. Insuficiencia aórtica ligera. Conclusiones: La dilatación de la raíz aórtica en el síndrome de Beals puede ser corregida de manera eficaz con la implantación de un anillo subaórtico que remodela la raíz y evita su dilatación posterior. Esta técnica puede ser utilizada en el Marfan y otras lesiones con dilatación del anillo aórtico.

The present research aims to analyze the Panamanian State Budget for Education according to the allocations approved by the government over the last 26 years. In the overall state budget, it is striking that the percentage allocated to education is far below the amount required. Education must be a priority for any state agenda if access is to be ensured to quality education that is equitable, inclusive, pertinent and comprehensive. The United Nations Educational Scientific and Cultural Organization (UNESCO) recommend that countries allocate 20% of overall state budgets to education. If a nation aims to develop, it must demonstrate a real and firm commitment to education by the political class and society as a whole; this commitment is embodied in the state budget designations for education.

Heterothermy is considered to be the most effective energy-saving strategy improving survival under natural conditions. Interspecific studies suggest that this strategy is also associated with reduced reproductive output. Yet little is known about the reproductive consequences of heterothermy use at the intraspecific level and thus its repercussions for microevolutionary processes. Moreover, as yet no study has aimed to test if litter size and juvenile mass are affected by torpor use in wild captured animals under undemanding laboratory conditions. Here we tested the hypothesis that intraspecific variation in heterothermy use is associated with different reproductive successes, being the result of the evolution of distinct life histories. We predicted that heterothermy use in winter negatively correlates with litter size and juvenile body mass during the subsequent breeding season. To test this prediction, we used yellow-necked mice from a population in which individuals consistently differ in their use of heterothermy in winter. We measured body size (head width) and body mass, basal metabolic rate, as well as metabolism and body temperature during fasting-induced torpor in wild caught mice in winter. Phenotyped mice were bred in the subsequent summer selectively - males and females with similar heterothermy characteristics were paired, the most to the least heterothermic. Dam body size, but not basal metabolism, was positively correlated with litter size (but not juvenile mass). However, when accounting for this relationship, litter size was negatively while juvenile mass was positively correlated with the average heterothermy use of a given couple. Our study indicates that heterothermy use correlates with specific life-history strategies arising from a fundamental evolutionary trade-off between survival and reproduction. [ABSTRACT FROM AUTHOR]

Parasitic infections have the potential to impact the hosts' body condition, elevate physiological responses, and ultimately lead to increased mortality. Host-parasite interactions are tied to the ecological and life-history traits of the hosts. While montane birds are susceptible to avian blood parasites, few studies have simultaneously assessed how inter- and intra-specific traits of hosts influence their probability of parasite infection. In this study, we screened for avian blood parasites across 214 individuals from 51 species at two sites, including a lowland farmland at 700 m and a highland forest at 2,500 m, in the Gaoligong Mountains in southwestern China. Overall blood parasite prevalence was 53.74%, with divergent species-specific prevalence ranging from 6.25% to 66.67%. We also measured traits indicative of body condition and physiological responses of each sampled individual. Using Bayesian phylogenetic logistic models, we assessed whether parasite infection probability is associated with ecological and life history traits of host species. Larger bird species were more likely to be infected than smaller bird species, and omnivore species showed lower susceptibility than those with other diets such as insectivores and herbivores. In contrast, foraging strata, nest type, and participation in mixed-species flocks of host species did not affect infection probability. We then used a reduced sample of eight species with more than five individuals, to assess the associations between intra-specific infection probability and host body condition, represented by fat and muscle reserves, and acute stress responses measured through breath rate. While infected individuals were likely to have more fat reserves than non-infected individuals, we did not find any association between infection probability and muscle reserve and body mass, nor with breath rate. Our results revealed that at the species level, specific traits (body mass and diet) of host species predict infection probability and implied a potential link at the individual level between enhanced body condition and increased resilience to parasite infection. [ABSTRACT FROM AUTHOR]

The ingress of carbon dioxide CO2 into concrete is an issue that, unfortunately, does not have sufficient precedents at the national level for the execution of the Residual Service Life analysis of concrete structures. As a precursor element of steel corrosion, it is necessary to count on information on the behavior that concrete could have in Chile, according to the levels of aggressiveness expected for specific project locations. It was only in 2016 that the NCh170 Concrete Standard included this type of Exposure with Grade C1 as Mild Aggressiveness. This work presents a review of background information collected from various third-party and own works, along with measurements of Carbonation Rates in 20-year-old concretes made in the city of Santiago, relating them to Air Permeability measured in a non-destructive way, which allowed generating a proposal for the Classification of the Degree of Exposure to Carbonation. [ABSTRACT FROM AUTHOR]