COVID-19: A complex disease with a unique metabolic signature.

Plasma of COVID-19 patients contains a strong metabolomic/lipoproteomic signature, revealed by the NMR analysis of a cohort of >500 patients sampled during various waves of COVID-19 infection, corresponding to the spread of different variants, and having different vaccination status. This composite signature highlights common traits of the SARS-CoV-2 infection. The most dysregulated molecules display concentration trends that scale with disease severity and might serve as prognostic markers for fatal events. Metabolomics evidence is then used as input data for a sex-specific multi-organ metabolic model. This reconstruction provides a comprehensive view of the impact of COVID-19 on the entire human metabolism. The human (male and female) metabolic network is strongly impacted by the disease to an extent dictated by its severity. A marked metabolic reprogramming at the level of many organs indicates an increase in the generic energetic demand of the organism following infection. Sex-specific modulation of immune response is also suggested.

Understanding Antimicrobial Resistance Using Genome-Scale Metabolic Modeling.

The urgent necessity to fight antimicrobial resistance is universally recognized. In the search of new targets and strategies to face this global challenge, a promising approach resides in the study of the cellular response to antimicrobial exposure and on the impact of global cellular reprogramming on antimicrobial drugs' efficacy. The metabolic state of microbial cells has been shown to undergo several antimicrobial-induced modifications and, at the same time, to be a good predictor of the outcome of an antimicrobial treatment. Metabolism is a promising reservoir of potential drug targets/adjuvants that has not been fully exploited to date. One of the main problems in unraveling the metabolic response of cells to the environment resides in the complexity of such metabolic networks. To solve this problem, modeling approaches have been developed, and they are progressively gaining in popularity due to the huge availability of genomic information and the ease at which a genome sequence can be converted into models to run basic phenotype predictions. Here, we review the use of computational modeling to study the relationship between microbial metabolism and antimicrobials and the recent advances in the application of genome-scale metabolic modeling to the study of microbial responses to antimicrobial exposure.

Metabolic Robustness to Growth Temperature of a Cold- Adapted Marine Bacterium.

Microbial communities experience continuous environmental changes, with temperature fluctuations being the most impacting. This is particularly important considering the ongoing global warming but also in the "simpler" context of seasonal variability of sea-surface temperature. Understanding how microorganisms react at the cellular level can improve our understanding of their possible adaptations to a changing environment. In this work, we investigated the mechanisms through which metabolic homeostasis is maintained in a cold-adapted marine bacterium during growth at temperatures that differ widely (15 and 0°C). We have quantified its intracellular and extracellular central metabolomes together with changes occurring at the transcriptomic level in the same growth conditions. This information was then used to contextualize a genome-scale metabolic reconstruction, and to provide a systemic understanding of cellular adaptation to growth at 2 different temperatures. Our findings indicate a strong metabolic robustness at the level of the main central metabolites, counteracted by a relatively deep transcriptomic reprogramming that includes changes in gene expression of hundreds of metabolic genes. We interpret this as a transcriptomic buffering of cellular metabolism, able to produce overlapping metabolic phenotypes, despite the wide temperature gap. Moreover, we show that metabolic adaptation seems to be mostly played at the level of few key intermediates (e.g., phosphoenolpyruvate) and in the cross talk between the main central metabolic pathways. Overall, our findings reveal a complex interplay at gene expression level that contributes to the robustness/resilience of core metabolism, also promoting the leveraging of state-of-the-art multi-disciplinary approaches to fully comprehend molecular adaptations to environmental fluctuations. IMPORTANCE This manuscript addresses a central and broad interest topic in environmental microbiology, i.e. the effect of growth temperature on microbial cell physiology. We investigated if and how metabolic homeostasis is maintained in a cold-adapted bacterium during growth at temperatures that differ widely and that match measured changes on the field. Our integrative approach revealed an extraordinary robustness of the central metabolome to growth temperature. However, this was counteracted by deep changes at the transcriptional level, and especially in the metabolic part of the transcriptome. This conflictual scenario was interpreted as a transcriptomic buffering of cellular metabolism, and was investigated using genome-scale metabolic modeling. Overall, our findings reveal a complex interplay at gene expression level that contributes to the robustness/resilience of core metabolism, also promoting the use of state-of-the-art multi-disciplinary approaches to fully comprehend molecular adaptations to environmental fluctuations.

Genomic Analysis of Endophytic Bacillus-Related Strains Isolated from the Medicinal Plant Origanum vulgare L. Revealed the Presence of Metabolic Pathways Involved in the Biosynthesis of Bioactive Compounds.

Multidrug-resistant pathogens represent a serious threat to human health. The inefficacy of traditional antibiotic drugs could be surmounted through the exploitation of natural bioactive compounds of which medicinal plants are a great reservoir. The finding that bacteria living inside plant tissues, (i.e., the endophytic bacterial microbiome) can influence the synthesis of the aforementioned compounds leads to the necessity of unraveling the mechanisms involved in the determination of this symbiotic relationship. Here, we report the genome sequence of four endophytic bacterial strains isolated from the medicinal plant Origanum vulgare L. and able to antagonize the growth of opportunistic pathogens of cystic fibrosis patients. The in silico analysis revealed the presence of gene clusters involved in the production of antimicrobial compounds, such as paeninodin, paenilarvins, polymyxin, and paenicidin A. Endophytes' adaptation to the plant microenvironment was evaluated through the analysis of the presence of antibiotic resistance genes in the four genomes. The diesel fuel degrading potential was also tested. Strains grew in minimum media supplemented with diesel fuel, but no n-alkanes degradation genes were found in their genomes, suggesting that diesel fuel degradation might occur through other steps involving enzymes catalyzing the oxidation of aromatic compounds.

Utilidad de la reacción en cadena de la polimerasa en el diagnóstico de infección congénita por citomegalovirus: a propósito de un caso de meningitis aséptica / Polymerase chain reaction in the diagnosis of congenital infection cytomegalovirus: A purpose of a case of aseptic meningitis

Se informa del caso de un recién nacido que presentó trombocitopenia, hematuria y proteinuria. En el líquido cefalorraquídeo tenía aumento de proteínas y leucocitos, VDRL no reactiva. La madre tenía historia de sífilis gestacional. Las determinaciones de IgM para citomegalovirus, rubéola, Toxoplasma , herpes i y ii fueron negativas por lo que se consideró caso de sífilis congénita con compromiso de sistema nervioso central. Por persistir la trombocitopenia después del tratamiento, se tomó muestra de sangre para PCR para citomegalovirus, encontrándose 181.171 copias/ml. Se dio tratamiento con ganciclovir intravenoso 12 mg/kg de peso durante 21 días y solución al 10% de inmunoglobulina humana hiperinmune para citomegalovirus administrada así: 4 ml/kg de peso los días 0, 4 y 8, seguido de 2 ml/kg de peso los días 12 y 16. La evolución fue satisfactoria. Se evidenció la utilidad de PCR en el diagnóstico de infección congénita por citomegalovirus.

We report a case of a newborn with persistent thrombocytopenia, hematuria, proteinuria, as well as increased proteins and leukocytes in cerebrospinal fluid, with a non-reactive VDRL. His mother had history of gestational syphilis. IgM levels against cytomegalovirus, rubella, toxoplasma, herpes i and ii were negative, which led to suspicion of congenital syphilis with central nervous system involvement. A polymerase chain reaction test for cytomegalovirus showed 181.171 copies/ml in serum. The newborn was treated with intravenous ganciclovir at 12 mg per kg body weight for 21 days and a 10% solution of human cytomegalovirus hyperimmune immunoglobulin, administered as follows: 4 ml per kg body weight on days 0, 4 and 8, followed by 2 ml per kg weight on days 12 and 16. The clinical outcome was satisfactory. This study highlights the usefulness of PCR for the diagnosis of congenital CMV infection.

Disseminated toxoplasmosis in an immunocompetent patient from Peruvian Amazon.

We report a case of severe toxoplasmosis in an immunocompetent patient, characterized by pneumonia, retinochoroiditis, hepatitis and myositis. Diagnosis was confirmed by serology, T. gondii in thick blood smear and presence of bradyzoites in muscle biopsy. Treatment with pyrimethamine plus sulfadoxine was successful but visual acuity and hip extension were partially recovered. This is the first case report of severe toxoplasmosis in an immunocompetent patient from Peru.

Notificação da violência intrafamiliar contra crianças e adolescentes por profissionais de saúde no Brasil / Notification of domestic violence against children and teens by health professionals in Brazil

O presente estudo tem por objetivo analisar as produções científicas acerca da violência intrafamiliar contra crianças e adolescentes notificadas por profissionais de saúde. Trata-se de uma revisão da literatura realizada a partir de artigos, legislações, manuais do Ministério da Saúde, teses, dissertações e livros. Apoiando-se em Foucault, reconhece-se a notificação como uma manifestação de poder e resistência dos profissionais de saúde e, em especial, das enfermeiras, a um problema tão comum em nossa sociedade, causador de grande impacto social, político e econômico, e com alto potencial de comprometimento para a saúde e qualidade de vida das vítimas. As questões examinadas neste estudo podem subsidiar a reflexão dos profissionais sobre sua prática, buscando o enfrentamento da violência de forma a prevenir que o ciclo se reproduza na família.

El presente estudio tiene como objetivo analizar la producción científica sobre la violencia familiar contra los niños y adolescentes reportada por profesionales de la salud. Ésta es una revisión de la literatura realizada a partir de artículos, leyes, manuales del Ministerio de Salud, tesis, disertaciones y libros. Sobre la base de Foucault, se reconoce la notificación como una manifestación de la preocupación y la resistencia de los profesionales de la salud, especialmente las enfermeras, a un problema tan común en nuestra sociedad, causante de un enorme impacto social, político y económico, con alto potencial para el compromiso con la salud y la calidad de vida de las víctimas. Los temas examinados en este estudio pueden apoyar la reflexión de los profesionales sobre su práctica, tratando de hacer frente a la violencia con el fin de evitar que el evento se presente de manera cíclica en la familia.

The present study aims to analyze the scientific production about family violence against children and adolescents reported by health professionals. This is a literature review performed from articles, laws, manuals Ministry of Health, theses, dissertations and books drawing on Foucault, recognizes the notification as a manifestation of power and strength and health professionals, especially nurses, to such a common problem in our society, causing enormous social, political and economic impact, and with high potential for commitment to the health and quality of life of the victims. The issues examined in this study can support the professionals' reflection on their practice, seeking to deal with violence in order to prevent the cycle play in the family.

Disseminated toxoplasmosis in an immunocompetent patient from Peruvian Amazon / Toxoplasmosis diseminada en un paciente inmunocompetente procedente de la Amazonía peruana

We report a case of severe toxoplasmosis in an immunocompetent patient, characterized by pneumonia, retinochoroiditis, hepatitis and myositis. Diagnosis was confirmed by serology, T. gondii in thick blood smear and presence of bradyzoites in muscle biopsy. Treatment with pyrimethamine plus sulfadoxine was successful but visual acuity and hip extension were partially recovered. This is the first case report of severe toxoplasmosis in an immunocompetent patient from Peru.

Reportamos un caso de toxoplasmosis severa en un paciente inmunocompetente caracterizado por neumonía, retinocoroiditis, hepatitis y miositis. El diagnóstico fue confirmado por serología, el hallazgo de T. gondii en gota gruesa y la presencia de bradizoitos en biopsia muscular. El tratamiento con pirimetamina mas sulfadoxina fue exitoso pero solo hubo una parcial recuperación de la agudeza visual y de la capacidad de extensión de la cadera. Este es el primer reporte de un caso de toxoplasmosis severa en el Perú.

Características del personal del Hospital de Emergencias José Casimiro Ulloa y nivel de conocimiento de medidas de acción durante sismo / Features staff at Hospital de Emergencias Jose Casimiro Ulloa and knowledge level action measures during earthquake

Objetivo: Determinar si existe asociación entre las características del personal que labora en el HEJCU y el nivel de conocimiento de las medidas de acción a tomar durante un sismo según el Plan de Respuesta Hospitalario del HEJCU. Materiales y Métodos: Se realizó un estudio de tipo Analítico Observacional de corte Transversal en el HEJCU. Para la recolección de datos se utilizó un cuestionario autodesarrollado de 13 preguntas dirigido a todo el personal que labora en el HEJCU. Se utilizó la prueba estadística de Chi-cuadrado para determinar las asociaciones. Resultados: Se analizaron 246 encuestas. El 50.81% de la población encuestada fueron varones, y 49.19% fueron mujeres. El 61.4% de la población tiene un nivel de conocimiento medio de las medidas de acción a tomar durante sismo. El 92.28% no pertenece a Brigadas operativas. El 13.01% de los entrevistados está totalmente capacitado (recibió el Plan de Respuesta Hospitalario del HEJCU y participó en talleres de capacitación para desastres). Se encontró asociación entre nivel de conocimientos y actividad laboral (p=0.02), OR= 5.56 [IC:1.74-17.80]. No se encontró asociación entre el nivel de conocimientos y las otras características del personal del HEJCU. Conclusión: El personal asistencial tiene mayor nivel de conocimientos que el personal administrativo en las medidas de acción a tomar durante un sismo. El haber recibido capacitación, el mayor tiempo de servicio y la participación en simulacros no muestra un mayor nivel de conocimientos en las medidas de acción a tomar durante sismo.

Objective: To determine whether there is an association between the characteristics of the workers from Hospital de Emergencias José Casimiro Ulloa (HEJCU) and their level of knowledge of how to perform during an earthquake according to the Hospital Response Plan from HEJCU. Material and Methods: This is a crosssectional study. It was performed at HEJCU, Lima-Peru. A 13 question self-administered survey was used to collect the data and all the employees were considered for the interview. In order to determine the association between variables, we used Chi-square statistic tests. Results: Two hundred forty-six questionnaires out of 259 were eligible to make the analysis. 50.81% of the population were male. 61.4% had a medium level of knowledge of how to perform during an seisms. 92.28% do not belong to earthquake brigades, 75.2% have participated in simulations, 13.01% have been well trained, in other words, have received the Hospital Disaster and Emergency Response Plan from HEJCU and have attended to the workshops on disaster management. An association between level of knowledge and labor activities was found (p=0.02), OR= 5.56 [IC:1.74-17.80]. There were not found an association between level of knowledge and other characteristics of the employees from HEJCU. Conclusion: Employees with medical activities had higher level of knowledge than employees with administrative activities. Time of service at the hospital, participation in simulations and having received training do not influence on the level of knowledge of the ways to perform during an earthquake.