Search

The aggregation of β‐amyloid peptide (Aβ) is associated with neurodegenerative diseases such as Alzheimer's disease (AD). Several therapies aimed at reducing the aggregation of this peptide have emerged as potential strategies for the treatment of AD. This paper describes the design and preparation of new hybrid molecules based on steroids, selenosugars, and [60]fullerene as potential inhibitors of Aβ oligomerization. These moieties were selected based on their antioxidant properties and possible areas of interaction with the Aβ. Cyclopropanations between C60 and malonates bearing different steroid and selenosugar moieties using the Bingel–Hirsch protocol have enabled the synthesis of functionalized molecular hybrids. The obtained derivatives were characterized by physical and spectroscopic techniques. Theoretical calculations for all the selenium compounds were performed using the density functional theory DFT/B3LYP‐D3(BJ)/6‐311G(2d,p) predicting the most stable conformations of the synthesized derivatives. Relevant geometrical parameters were investigated to relate the stereochemical behavior and the spectroscopic data obtained. The affinity of the compounds for Aβ‐peptide was estimated by molecular docking simulation, which predicted an increase in affinity and interactions for Aβ for the hybrids containing the C60 core. In addition, parameters such as lipophilicity, polar surface area, and dipole moment were calculated to predict their potential interaction with membrane cells. [ABSTRACT FROM AUTHOR]

The MCM2-7 complex is a highly conserved hetero-hexameric protein complex, critical for DNA unwinding at the replicative fork during DNA replication. Overexpression or mutation in MCM2-7 genes is linked to and may drive several cancer types in humans. In mice, mutations in MCM2-7 genes result in growth retardation and mortality. All six MCM2-7 genes are also expressed in the developing mouse CNS, but their role in the CNS is not clear. Here, we use the central nervous system (CNS) of Drosophila melanogaster to begin addressing the role of the MCM complex during development, focusing on the specification of a well-studied neuropeptide expressing neuron: the Tv4/FMRFa neuron. In a search for genes involved in the specification of the Tv4/FMRFa neuron we identified Mcm5 and find that it plays a highly specific role in the specification of the Tv4/FMRFa neuron. We find that other components of the MCM2-7 complex phenocopies Mcm5, indicating that the role of Mcm5 in neuronal subtype specification involves the MCM2-7 complex. Surprisingly, we find no evidence of reduced progenitor proliferation, and instead find that Mcm5 is required for the expression of the type I BMP receptor Tkv, which is critical for the FMRFa expression. These results suggest that the MCM2-7 complex may play roles during CNS development outside of its well-established role during DNA replication.

Abstract Preeclampsia (PE) is a prevalent pregnancy disorder that leads to high maternal and fetal morbidity and mortality. While defective vascular development and angiogenesis in placenta are known as crucial pathological findings, its pathophysiological mechanism remains elusive. To better understand the effects of PE on angio-vasculogenesis and inflammatory networks in the fetus and to identify their biological signatures, we investigated the quantitative and functional characteristics of cord blood-derived mononuclear cells (CB-MNCs) and CD31-positive MNCs. Flow cytometry analysis demonstrated that the CB-MNCs from the severe PE group had significantly decreased number of cells expressing CD3, CD11b, CD14, CD19, KDR, and CD31 compared with the normal group. Quantitative real time PCR (qRT-PCR) shows down-regulation of the major angiogenic factor VEGFA in MNCs and CD31+ MNCs in severe PE. The major inflammatory cytokines IL1 was highly upregulated in CD31+ CB-MNCs in the severe PE patients. Mild PE patients, however, did not display any significant difference in expression of all measured angiogenic genes and most inflammatory genes. These findings show distinct angiogenic and inflammatory signatures from severe PE, and they may play a significant role in the pathogenesis of vascular defects in placenta of severe PE.

ABSTRACT We report a case with a broad spectrum of symptoms, related to GATA2 deficiency syndrome, which emerged as early as at 6 months of age. They ranged from lymphedema, deafness to myelodysplastic syndrome (MDS).

Fundamento: la lepra es una enfermedad curable. Si es tratada en su primera fase, se puede evitar la discapacidad que genera. Objetivo: describir aspectos clínicos-epidemiológicos de pacientes diagnosticados con lepra.Métodos: estudio de serie de casos realizado en el municipio Cumanayagua, de Cienfuegos, que incluyó los 15 pacientes diagnosticados con lepra desde 2009 hasta 2019, según base de datos de la Unidad Municipal de Higiene y Epidemiología de dicho municipio. Las principales variables fueron: edad, sexo, consejos populares, clasificación clínica, operacional, tipo de contacto, tratamiento aplicado.Resultados: el grupo de 50-79 años representó el 53,3 %; las féminas constituyeron el 70,0 % de los casos; los consejos populares de mayores riesgos fueron Brisas con el 46,6 % y Vila con 20,0 %; el 73,3 % eran enfermos de lepra multibacilar; más del 40,0 % presentaron anestesia cutánea e infiltraciones; la detección fue espontánea en el 46,6 % de los pacientes. Al 73,3 % se les aplicó tratamiento multibacilar.Conclusiones: la lepra no constituye actualmente un problema grave de salud en el municipio Cumanayagua, pero no es una enfermedad totalmente eliminada, por lo que el conocimiento de las características clínicas y epidemiológicas de los pacientes diagnosticados es importante para su mejor tratamiento y seguimiento médico.

Abstract Background Corynebacterium diphtheriae, the agent of diphtheria, is a genetically diverse bacterial species. Although antimicrobial resistance has emerged against several drugs including first-line penicillin, the genomic determinants and population dynamics of resistance are largely unknown for this neglected human pathogen. Methods Here, we analyzed the associations of antimicrobial susceptibility phenotypes, diphtheria toxin production, and genomic features in C. diphtheriae. We used 247 strains collected over several decades in multiple world regions, including the 163 clinical isolates collected prospectively from 2008 to 2017 in France mainland and overseas territories. Results Phylogenetic analysis revealed multiple deep-branching sublineages, grouped into a Mitis lineage strongly associated with diphtheria toxin production and a largely toxin gene-negative Gravis lineage with few toxin-producing isolates including the 1990s ex-Soviet Union outbreak strain. The distribution of susceptibility phenotypes allowed proposing ecological cutoffs for most of the 19 agents tested, thereby defining acquired antimicrobial resistance. Penicillin resistance was found in 17.2% of prospective isolates. Seventeen (10.4%) prospective isolates were multidrug-resistant (≥ 3 antimicrobial categories), including four isolates resistant to penicillin and macrolides. Homologous recombination was frequent (r/m = 5), and horizontal gene transfer contributed to the emergence of antimicrobial resistance in multiple sublineages. Genome-wide association mapping uncovered genetic factors of resistance, including an accessory penicillin-binding protein (PBP2m) located in diverse genomic contexts. Gene pbp2m is widespread in other Corynebacterium species, and its expression in C. glutamicum demonstrated its effect against several beta-lactams. A novel 73-kb C. diphtheriae multiresistance plasmid was discovered. Conclusions This work uncovers the dynamics of antimicrobial resistance in C. diphtheriae in the context of phylogenetic structure, biovar, and diphtheria toxin production and provides a blueprint to analyze re-emerging diphtheria.

Diferentes estudios evidencian que en la enfermedad COVID-19 se producen, constantemente, rebrotes. El objetivo de este trabajo es presentar las acciones de vigilancia y control en un foco de COVID-19 en el municipio de Cumanayagua, Cienfuegos. El caso índice fue un viajero procedente de Estados Unidos, que se alojó en la comunidad y se relacionó con el primer caso encontrado en el Municipio, paciente masculino, de 67 años, jubilado y sin antecedentes de enfermedades concomitantes, cuya sintomatología fue tos, cinco días después de contacto con dicho viajero. Se identificaron 27 contactos, dos de ellos menores de 15 años, todos asintomáticos. Los otros casos secundarios fueron, el esposo de la sobrina, masculino de 22 años, trabajador como Agente de Seguridad, con un total de 14 contactos, todos asintomáticos y la nuera, de 38 años, ama de casa, con cinco contactos, también asintomáticos. A todos los contactos se les trasladó a centro de aislamiento. El tiempo transcurrido entre el contacto directo del caso índice y el diagnóstico de positividad fue entre tres y cinco días. Los casos secundarios, a la semana resultaron positivos. Las medidas epidemiológicas estuvieron encaminadas a detener la transmisión y prevenir el contagio.

Fundamento: la formación sobre higiene de manos es la estrategia más utilizada para mejorar el porcentaje de cumplimiento de las indicaciones al respecto.Objetivo: describir los resultados de la formación en higiene de manos desarrollada por el proyecto Manos Seguras, previo a la COVID-19 en el municipio de Cienfuegos.Métodos: estudio descriptivo retrospectivo que recoge las actividades de capacitación sobre higiene de manos desarrollada en círculos infantiles y escuelas del municipio Cienfuegos como parte del proyecto Manos Seguras.Resultados: la formación en higiene de manos en el municipio Cienfuegos permitió llevar el conocimiento de la técnica correcta a 120 niños (as) de los círculos infantiles, 169 niños (as) de las escuelas primarias y 140 adolescentes de la enseñanza secundaria básica. Se capacitaron un total de 1356 trabajadores de diferentes sectores, y 411 trabajadores de la salud.Conclusiones: la capacitación desarrollada mejoró los conocimientos y habilidades sobre higiene de manos entre los participantes, hecho sumamente importante para enfrentar los acontecimientos posteriores, pues el lavado de manos ha sido una de las principales medidas para evitar propagar la COVID-19 a otras personas.

Foundation: due to the current pandemic of COVID 19, it is important to know the categorizing essentialities of acute respiratory infections in general for future studies in which COVID 19 will constitute a category of the taxonomy of those to be taken into account.Objective: to characterize acute respiratory infections in the Cienfuegos province from January 1 to March 31, 2020.Methods: the population studied was the population of the Cienfuegos province. The main study variables considered were: age groups, municipalities of residence, demand for medical consultations, statistical weeks, rates temporal variation, their trend, severity of clinical evolution, admissions and deaths from severe respiratory infections, outbreaks and epidemiological surveillance. Statistical methods and techniques used were, from descriptive statistics: absolute and relative frequencies, means, rates, increases and decreases in rates, the endemic corridor and its trend.Results: the characterizing essentialities were: its highest incidence in children under five years of age and adults 60 years and over; the leading cause of death was from community-acquired pneumonia; the identified circulating viruses were respiratory syncytial, parainfluenza, unsubtyped influenza A, and coronavirus. The trend is upward.Conclusions: the behavior of acute respiratory infections was within the expected parameters, except that from week eleven there was an increase in medical care, which could be related to the inquiring and surveillance actions.

Fundamento: a nivel mundial se ha adoptado un conjunto de objetivos para erradicar la pobreza, proteger el planeta y asegurar la prosperidad para todas las personas. Se establecieron 17 objetivos de desarrollo sostenible.Objetivo: caracterizar al personal de enfermería para su contribución al cumplimiento de los objetivos de desarrollo sostenible. Métodos: estudio descriptivo de corte transversal sobre las características del personal de enfermería del municipio de Cumanayagua en la provincia de Cienfuegos. De un universo de 235 enfermeros/eras, se escogió una muestra a conveniencia conformada por 78 enfermeros/eras. Se analizó sexo, edad, años de experiencia (de graduados y en la labor actual), actividades que realizan.Resultados: la cobertura del municipio con personal de enfermería está sustentada en profesionales del sexo femenino, edades entre los 40 y 49 años y tiempo de experiencia en la práctica entre los 20 y 29 años. Entre las principales actividades que realizan están audiencias sanitarias para toda la comunidad, en especial para los grupos de personas mayores de 60 años y la población menor de 15 años; atención a círculos de abuelos, cobertura total del programa de vacunación, seguimiento a mujeres en edad fértil, intervención directa en los programas de salud establecidos, participación activa en la identificación, priorización y análisis causal de los principales problemas de salud. Poseen un largo período de actividad laboral en consultorios.Conclusiones: el personal de enfermería en el municipio de Cumanayagua se caracteriza por ejecutar acciones integrales que favorecen el cumplimiento de los objetivos de desarrollo sostenible y poseer suficiente experiencia para hacerlo con calidad.

En el terreno de la salud pública, la Bioética se hizo necesaria por el acelerado ritmo de los avances científicos y tecnológicos, la comercialización de la medicina, el peligro creciente de la deshumanización, la injusticia social y el acceso desigual a los servicios de salud. Actualmente, la nefasta repercusión social del neoliberalismo y la catastrófica tendencia a la deshumanización de la Medicina es un peligro que azota a los países subdesarrollados. La revisión bibliografía tuvo como propósito valorar los rasgos de deshumanización de los servicios de salud y su implicación en la formación de recursos humanos. Se revisaron conceptos, tendencias y retos presentes en la profesión de enfermería y en el trabajo de sus profesionales. Se encontró una estrecha relación entre el humanismo, ética, bioética y espiritualidad y su significado para mejorar cada vez más la labor como profesionales y técnicos de la salud. La enfermería moderna tiene la obligación de mantener los cuidados que han acompañado a la humanidad desde sus albores, pero hoy, constituida en una profesión con basamento científico, posee las suficientes potencialidades para brindar cuidados de más calidad y eficiencia al individuo sano o enfermo, a la comunidad y al entorno medio ambiental natural.

BackgroundSince the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the main concern is whether reinfections are possible, and which are the associated risk factors. This study aims to describe the clinical and molecular characteristics of 24 sequence-confirmed reinfection SARS-CoV-2 cases over 1 year in Barcelona (Catalonia, Spain).MethodsPatients with > 45 days between two positive PCR tests regardless of symptoms and negative tests between episodes were initially considered as suspected reinfection cases from November 2020 to May 2021. Whole-genome sequencing (WGS) was performed to confirm genetic differences between consensus sequences and for phylogenetic studies based on PANGOLIN nomenclature. Reinfections were confirmed by the number of mutations, change in lineage, or epidemiological criteria.ResultsFrom 39 reported suspected reinfection cases, complete viral genomes could be sequenced from both episodes of 24 patients, all were confirmed as true reinfections. With a median age of 44 years (interquartile range [IQR] 32–65), 66% were women and 58% were healthcare workers (HCWs). The median days between episodes were 122 (IQR 72–199), occurring one-third within 3 months. Reinfection episodes were frequently asymptomatic and less severe than primary infections. The absence of seroconversion was associated with symptomatic reinfections. Only one case was reinfected with a variant of concern (VOC).ConclusionSevere acute respiratory syndrome coronavirus 2 reinfections can occur in a shorter time than previously reported and are mainly found in immunocompetent patients. Surveillance through WGS is useful to identify viral mutations associated with immune evasion.

Background. Donor-specific antibodies (DSA) are a recognized cause of allograft injury, yet biomarkers that indicate their development posttransplant or guide management are not available. CXCL13 (chemokine [C-X-C motif] ligand 1) is a chemoattractant produced within secondary lymphoid organs necessary for germinal center (GC) and alloantibody formation. Perturbations in serum CXCL13 levels have been associated with humoral immune activity. Therefore, CXCL13 may correlate with the formation of HLA antibodies following transplantation. Methods. A murine skin graft model was utilized to define the production and kinetics of CXCL13 in response to alloantigen. Human Tfh:B-cell in vitro cocultures were performed to evaluate CXCL13 production by human lymphocytes, and serum from healthy controls and human transplant recipients with and without de novo DSA was tested for CXCL13. Results. CXCL13 was detectable in the blood of allografted mice and correlated with Tfh and GC B-cell responses. Greater CXCL13 expression was observed in the draining lymph nodes of allografted mice as compared with naïve or syngeneic graft recipients, and serum levels preceded the detection of DSA posttransplant. Similarly, productive human Tfh:B-cell interactions that led to plasmablast differentiation and IgG formation also exhibited CXCL13 expression. CXCL13 levels in human transplant recipients with de novo DSA were greater than in healthy controls and stable transplant patients and also correlated with the development of alloantibodies in a small cohort of serially monitored recipients. Conclusions. CXCL13 indicates GC alloreactivity and alloantibody formation and correlated with DSA formation in kidney transplant recipients, thereby introducing CXCL13 as a potential biomarker for HLA antibodies.

Background. Costimulatory blockade with belatacept has demonstrated long-term benefits in renal transplantation, but de novo use in liver transplant recipients has resulted in increased rejection, graft loss, and death. However, belatacept conversion as a calcineurin inhibitor (CNI) avoidance strategy has not been studied and may be of benefit in liver transplantation where CNI-induced renal dysfunction and toxicity are barriers to improved outcomes. Methods. Using clinical data extracted from our institutional medical record, we report on 8 patients who underwent kidney after liver transplantation and were treated with belatacept-based immunosuppression and transient CNI therapy. Results. All patients tolerated belatacept therapy without any patient deaths or graft losses. No episodes of rejection, de novo donor-specific antibody formation, or major systemic infections were observed, and all patients demonstrated preserved liver and excellent renal allograft function. Patients received belatacept for a median duration of 13.2 mo, and at a median follow-up of 15.9 mo post–kidney transplant, 6 of 8 patients continued on belatacept with 3 completely off and 3 poised to transition off CNI. Conclusions. These findings are the first evidence that in liver transplant recipients requiring subsequent kidney transplantation, belatacept-based therapy can potentially facilitate CNI-free maintenance immunosuppression. This supports the possibility of belatacept conversion in stand-alone liver transplant recipients as a viable method of CNI avoidance.

Diphtheria is a re-emerging disease in resource-rich settings. We here report three cases of cutaneous diphtheria diagnosed and managed in our infectious disease department and discuss the determinants of its re-emergence. Migration, travel and vaccine scepticism are key factors not only for diphtheria re-emergence, but for the future of most preventable diseases.

We conducted a cohort study to determine sociodemographic risk factors for severe acute respiratory syndrome coronavirus 2 infection among obstetric patients in 2 urban hospitals in Atlanta, Georgia, USA. Prevalence of infection was highest among women who were Hispanic, were uninsured, or lived in high-density neighborhoods.

“Review of the book:” Dörfler, Thomas. Security Council Sanctions Governance: The Power and Limits of Rules. Routledge, 2019. 239 págs.