Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production.

Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α. We also identified a requirement for cystathionine-γ-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H2S) production. H2S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production.

Endogenous hydrogen sulfide production is essential for dietary restriction benefits.

Dietary restriction (DR) without malnutrition encompasses numerous regimens with overlapping benefits including longevity and stress resistance, but unifying nutritional and molecular mechanisms remain elusive. In a mouse model of DR-mediated stress resistance, we found that sulfur amino acid (SAA) restriction increased expression of the transsulfuration pathway (TSP) enzyme cystathionine γ-lyase (CGL), resulting in increased hydrogen sulfide (H2S) production and protection from hepatic ischemia reperfusion injury. SAA supplementation, mTORC1 activation, or chemical/genetic CGL inhibition reduced H2S production and blocked DR-mediated stress resistance. In vitro, the mitochondrial protein SQR was required for H2S-mediated protection during nutrient/oxygen deprivation. Finally, TSP-dependent H2S production was observed in yeast, worm, fruit fly, and rodent models of DR-mediated longevity. Together, these data are consistent with evolutionary conservation of TSP-mediated H2S as a mediator of DR benefits with broad implications for clinical translation. PAPERFLICK:

A comparative study on chromium-induced micronuclei assessment in the peripheral blood of Hsd:ICR mice.

This study investigated the genotoxic effects of chromium (Cr) in Hsd:ICR mice, considering factors such as oxidative state, apoptosis, exposure pathway, duration, pregnancy, and transplacental exposure. Genotoxicity was assessed using the erythrocytes' micronucleus (MN) assay, while apoptosis was evaluated in nucleated blood cells. The results showed that Cr(III) (CrK(SO4 )2 and CrCl3 ) did not induce any marked genotoxic damage. However, Cr(VI) (CrO3 , K2 Cr2 O7 , Na2 Cr2 O7 , and K2 CrO4 ) produced varying degrees of genotoxicity, with CrO3 being the most potent. MN frequencies increased following 24-h exposure, with a greater effect in male mice. Administering 20 mg/kg of CrO3 via gavage did not lead to significant effects compared to intraperitoneal administration. Short-term oral treatment with a daily dose of 8.5 mg/kg for 49 days elevated MN levels only on day 14 after treatment. Pregnant female mice exposed to CrO3 on day 15 of pregnancy exhibited reduced genotoxic effects compared to nonpregnant animals. However, significant increases in MN levels were found in their fetuses starting 48 h after exposure. In summary, data indicate the potential genotoxic effects of Cr, with Cr(VI) forms inducing higher genotoxicity than Cr(III). These findings indicate that gender, exposure route, and pregnancy status might influence genotoxic responses to Cr.

A single rapamycin dose protects against late-stage experimental cerebral malaria via modulation of host immunity, endothelial activation and parasite sequestration.

BACKGROUND: Maladaptive immune responses during cerebral malaria (CM) result in high mortality despite opportune anti-malarial chemotherapy. Rapamycin, an FDA-approved immunomodulator, protects against experimental cerebral malaria (ECM) in mice through effects on the host. However, the potential for reduced adaptive immunity with chronic use, combined with an incomplete understanding of mechanisms underlying protection, limit translational potential as an adjunctive therapy in CM. RESULTS: The results presented herein demonstrate that a single dose of rapamycin, provided as late as day 4 or 5 post-infection, protected mice from ECM neuropathology and death through modulation of distinct host responses to infection. Rapamycin prevented parasite cytoadherence in peripheral organs, including white adipose tissue, via reduction of CD36 expression. Rapamycin also altered the splenic immune response by reducing the number of activated T cells with migratory phenotype, while increasing local cytotoxic T cell activation. Finally, rapamycin reduced brain endothelial ICAM-1 expression concomitant with reduced brain pathology. Together, these changes potentially contributed to increased parasite elimination while reducing CD8 T cell migration to the brain. CONCLUSIONS: Rapamycin exerts pleotropic effects on host immunity, vascular activation and parasite sequestration that rescue mice from ECM, and thus support the potential clinical use of rapamycin as an adjunctive therapy in CM.

Human C1-Inhibitor Suppresses Malaria Parasite Invasion and Cytoadhesion via Binding to Parasite Glycosylphosphatidylinositol and Host Cell Receptors.

Plasmodium falciparum-induced severe malaria remains a continuing problem in areas of endemicity, with elevated morbidity and mortality. Drugs targeting mechanisms involved in severe malaria pathology, including cytoadhesion of infected red blood cells (RBCs) to host receptors and production of proinflammatory cytokines, are still necessary. Human C1-inhibitor (C1INH) is a multifunctional protease inhibitor that regulates coagulation, vascular permeability, and inflammation, with beneficial effects in inflammatory disease models, including septic shock. We found that human C1INH, at therapeutically relevant doses, blocks severe malaria pathogenic processes by 2 distinct mechanisms. First, C1INH bound to glycan moieties within P. falciparum glycosylphosphatidylinositol (PfGPI) molecules on the parasite surface, inhibiting parasite RBC invasion and proinflammatory cytokine production by parasite-stimulated monocytes in vitro and reducing parasitemia in a rodent model of experimental cerebral malaria (ECM) in vivo. Second, C1INH bound to host CD36 and chondroitin sulfate A molecules, interfering with cytoadhesion of infected RBCs by competitive binding to these receptors in vitro and reducing sequestration in specific tissues and protecting against ECM in vivo. This study reveals that C1INH is a potential therapeutic antimalarial molecule able to interfere with severe-disease etiology at multiple levels through specific interactions with both parasite PfGPIs and host cell receptors.

The Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity.

Senicapoc, a Gardos channel inhibitor, prevented erythrocyte dehydration in clinical trials of patients with sickle cell disease. We tested the hypothesis that senicapoc-induced blockade of the Gardos channel inhibits Plasmodium growth. Senicapoc inhibited in vitro growth of human and primate plasmodia during the clinical blood stage. Senicapoc treatment suppressed P. yoelii parasitemia in vivo in C57BL/6 mice. The reassuring safety and biochemical profile of senicapoc encourage its use in antimalarial development.

Protein and Calorie Restriction Contribute Additively to Protection from Renal Ischemia Reperfusion Injury Partly via Leptin Reduction in Male Mice.

BACKGROUND: Short-term dietary restriction (DR) without malnutrition preconditions against surgical stress in rodents; however, the nutritional basis and underlying nutrient/energy-sensing pathways remain poorly understood. OBJECTIVES: We investigated the relative contribution of protein restriction (PR) vs. calorie restriction (CR) to protection from renal ischemia reperfusion injury (IRI) and changes in organ-autonomous nutrient/energy-sensing pathways and hormones underlying beneficial effects. METHODS: Mice were preconditioned on experimental diets lacking total calories (0-50% CR) or protein/essential amino acids (EAAs) vs. complete diets consumed ad libitum (AL) for 1 wk before IRI. Renal outcome was assessed by serum markers and histology and integrated over a 2-dimensional protein/energy landscape by geometric framework analysis. Changes in renal nutrient/energy-sensing signal transduction and systemic hormones leptin and adiponectin were also measured. The genetic requirement for amino acid sensing via general control non-derepressible 2 (GCN2) was tested with knockout vs. control mice. The involvement of the hormone leptin was tested by injection of recombinant protein vs. vehicle during the preconditioning period. RESULTS: CR-mediated protection was dose dependent up to 50% with maximal 2-fold effect sizes. PR benefits were abrogated by EAA re-addition and additive with CR, with maximal benefits at any given amount of CR occurring with a protein-free diet. GCN2 was not required for functional benefits of PR. Activation and repression of nutrient/energy-sensing kinases, AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1), respectively, on PR reflected a state of negative energy balance, paralleled by 13% weight loss and an 87% decrease in leptin, independent of calorie intake. Recombinant leptin administration partially abrogated benefits of dietary preconditioning against renal IRI. CONCLUSIONS: In male mice, PR and CR both contributed to the benefits of short-term DR against renal IRI independent of GCN2 but partially dependent on reduced circulating leptin and coincident with AMPK activation and mTORC1 repression.

[Design of an electronic leech]. / Diseno de una sanguijuela electronica.

This research presents the development of a continual suction electromechanical device (CSED) which emulates the feeding characteristics of a medicinal leech to drain body fluids. After the research, design and building of the device, its performance in normal conditions with fluids of different viscosity was evaluated. Finally, the device was submitted to a test of blood draining in three adult male rabbits NZW with a weight of three kilograms, obtaining drain.

Sulfur Amino Acid Supplementation Abrogates Protective Effects of Caloric Restriction for Enhancing Bone Marrow Regrowth Following Ionizing Radiation.

Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance. Here, we report that 50% calorie restriction (CR) for 7-days or fasting for 3-days prior to irradiation improved mouse BM regrowth in the days and weeks post irradiation. Specifically, one week of 50% CR ameliorated loss of total BM cellularity post irradiation compared to ad libitum-fed controls. CR-mediated BM protection was abrogated by dietary sulfur amino acid (i.e., cysteine, methionine) supplementation or pharmacological inhibition of sulfur amino acid metabolizing and hydrogen sulfide (H2S) producing enzymes. Up to 2-fold increased proliferative capacity of ex vivo-irradiated BM isolated from food restricted mice relative to control mice indicates cell autonomy of the protective effect. Pretreatment with H2S in vitro was sufficient to preserve proliferative capacity by over 50% compared to non-treated cells in ex vivo-irradiated BM and BM HSPCs. The exogenous addition of H2S inhibited Ten eleven translocation 2 (TET2) activity in vitro, thus providing a potential mechanism of action. Short-term CR or fasting therefore offers BM radioprotection and promotes regrowth in part via altered sulfur amino acid metabolism and H2S generation, with translational implications for radiation treatment and aging.

Overweight and obesity significantly reduce pregnancy, implantation, and live birth rates in women undergoing In Vitro Fertilization procedures.

OBJECTIVE: The objective of this study was to evaluate the effects of overweight and obesity on fertility outcomes in IVF procedures. METHODS: This was a retrospective and nonrandomized study that included 191 IVF/ICSI cycles using non-donor oocytes performed between July 2016 and December 2018 that were allocated according to Body Mass Index (BMI) in three groups: Normal group: 18.5-24.9 (n=67 women), Overweight group: 25.0-29.9 (n=86 women) and Obesity group: ≥30.0 (n=38 women). We compared fertilization rates, embryo quality at day 3, development and quality of blastocyst, pregnancy rates, implantation rates, and live birth rates. RESULTS: Patients from all groups had similar stimulation days, but those women with overweight and obesity used more hormones compared to women with normal weight (p<0.05). Fertilization rates, zygotes that underwent cleavage and good-quality embryos at Day 3 were similar between the three evaluated groups. The groups of overweight and obesity had embryos at Day 3 with significantly less cells, compared to those from the normal group (p<0.05). The blastocyst development rate was significantly lower in women with overweight and obesity compared to women with normal BMI (p<0.05); but, the percentages of good blastocysts were similar in all studied patients. Pregnancy, implantation and live birth rates were significantly lower in the group of women with overweight and obesity, compared to those women with normal weight (p<0.05). Obese women had significantly more miscarriages compared to those in the other groups (p<0.05). CONCLUSIONS: Our data shows that an increased BMI affects embryo development and significantly reduces the pregnancy, implantation and live birth rates.

Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria.

Circulating levels of the adipokine leptin are linked to neuropathology in experimental cerebral malaria (ECM), but its source and regulation mechanism remain unknown. Here, we show that sequestration of infected red blood cells (iRBCs) in white adipose tissue (WAT) microvasculature increased local vascular permeability and leptin production. Mice infected with parasite strains that fail to sequester in WAT displayed reduced leptin production and protection from ECM. WAT sequestration and leptin induction were lost in CD36KO mice; however, ECM susceptibility revealed sexual dimorphism. Adipocyte leptin was regulated by the mechanistic target of rapamycin complex 1 (mTORC1) and blocked by rapamycin. In humans, although Plasmodium falciparum infection did not increase circulating leptin levels, iRBC sequestration, tissue leptin production, and mTORC1 activity were positively correlated with CM in pediatric postmortem WAT. These data identify WAT sequestration as a trigger for leptin production with potential implications for pathogenesis of malaria infection, prognosis, and treatment.

Analysis of innate defences against Plasmodium falciparum in immunodeficient mice.

BACKGROUND: Mice with genetic deficiencies in adaptive immunity are used for the grafting of human cells or pathogens, to study human diseases, however, the innate immune responses to xenografts in these mice has received little attention. Using the NOD/SCID Plasmodium falciparum mouse model an analysis of innate defences responsible for the substantial control of P. falciparum which remains in such mice, was performed. METHODS: NOD/SCID mice undergoing an immunomodulatory protocol that includes, clodronate-loaded liposomes to deplete macrophages and an anti-polymorphonuclear leukocytes antibody, were grafted with human red blood cells and P. falciparum. The systematic and kinetic analysis of the remaining innate immune responses included the number and phenotype of peripheral blood leukocytes as well as inflammatory cytokines/chemokines released in periphery. The innate responses towards the murine parasite Plasmodium yoelii were used as a control. RESULTS: Results show that 1) P. falciparum induces a strong inflammation characterized by an increase in circulating leukocytes and the release of inflammatory cytokines; 2) in contrast, the rodent parasite P. yoelii, induces a far more moderate inflammation; 3) human red blood cells and the anti-inflammatory agents employed induce low-grade inflammation; and 4) macrophages seem to bear the most critical function in controlling P. falciparum survival in those mice, whereas polymorphonuclear and NK cells have only a minor role. CONCLUSIONS: Despite the use of an immunomodulatory treatment, immunodeficient NOD/SCID mice are still able to mount substantial innate responses that seem to be correlated with parasite clearance. Those results bring new insights on the ability of innate immunity from immunodeficient mice to control xenografts of cells of human origin and human pathogens.

Biological activities of C1 inhibitor.

Broadly speaking, C1 inhibitor plays important roles in the regulation of vascular permeability and in the suppression of inflammation. Vascular permeability control is exerted largely through inhibition of two of the proteases involved in the generation of bradykinin, factor XIIa and plasma kallikrein (the plasma kallikrein-kinin system). Anti-inflammatory functions, however, are exerted via several activities including inhibition of complement system proteases (C1r, C1s, MASP2) and the plasma kallikrein-kinin system proteases, in addition to interactions with a number of different proteins, cells and infectious agents. These more recently described, as yet incompletely characterized, activities serve several potential functions, including concentration of C1 inhibitor at sites of inflammation, inhibition of alternative complement pathway activation, inhibition of the biologic activities of gram negative endotoxin, enhancement of bacterial phagocytosis and killing, and suppression of the influx of leukocytes into a site of inflammation. C1 inhibitor has been shown to be therapeutically useful in a variety of animal models of inflammatory diseases, including gram negative bacterial sepsis and endotoxin shock, suppression of hyperacute transplant rejection, and treatment of a variety of ischemia-reperfusion injuries (heart, intestine, skeletal muscle, liver, brain). In humans, early data appear particularly promising in myocardial reperfusion injury. The mechanism (or mechanisms) of the effect of C1 inhibitor in these conditions is (are) not completely clear, but involve inhibition of complement and contact system activation, in addition to variable contributions from other C1 inhibitor activities that do not involve protease inhibition.

En época de pandemia: eficacia de los desinfectantes de uso hospitalario en áreas críticas

Introducción: Las Infecciones Asociadas a la Atención en Salud (IAAS) son un serio problema para los establecimientos de salud, no solo como causal de morbimortalidad sino también por los altos costos que generan. La contaminación de ambientes son un peligro para cualquier establecimiento sanitario. Objetivo: Determinar la eficacia de los desinfectantes de uso hospitalario frente a microorganismos aislados de superficies (respirador, monitor y superficie de la cama clínica) de áreas críticas del Hospital "Santa Rosa", Lima, Perú. Material y Métodos: Estudio observacional, prospectivo y transversal, se evaluaron varios productos de desinfección de superficies. Se utilizó la prueba de reto en superficie utilizando cepas control. Las muestras fueron recolectadas de los servicios de Unidad de Cuidados Intensivos Adultos (UCI), Unidad de Cuidados Intensivos Neonatal (UCINEO), Unidad de Cuidados Especiales de Medicina (UCEM) del Hospital "San Rosa". El efecto de los desinfectantes evaluados se realizó a los 5, 10 y 15 minutos. Resultados: En las condiciones del ensayo y considerando los tiempos y velocidad de muerte bacteriana por efecto del desinfectante, los productos de mayor eficacia resultaron ser el amonio cuaternario (Supersafe D) e hipoclorito de sodio a 1 %. Conclusiones: Ninguno de los desinfectantes logró alcanzar las exigencias del test de Chambers. Los productos lograron efectos esperados a partir de los 10 ó15 minutos.

Introduction: Infections Associated with Health Care (IAAS) are a serious problem for health care facilities, not only as a cause of morbidity and mortality but also because of the high costs they generate. Contaminated environments are a danger for any health care facilities. Objective: To determine the efficacy of hospital disinfectants against microorganisms isolated from surfaces (ventilator, monitor and surface of the hospital bed) in critical areas of the "Santa Rosa" Hospital, Lima-Peru. Material and Methods: An observational, prospective and cross-sectional study was conducted to evaluate disinfection products used to clean floors and surfaces. The surface challenge test was performed using control strains. Samples were collected from the adult intensive care unit (ICU), the neonatal intensive care unit (NICU) and the special care unit (SCU) of the Santa Rosa Hospital. The effect of the disinfectants was evaluated at the fifth, tenth and fifteen minutes. Results: Under the study conditions and considering the time and speed of bacterial death due to the disinfectant effect, the most effective products were quaternary ammonium (Supersafe-D) and 1% sodium hypochlorite. Conclusions: None of the disinfectants met the chamber test requirements. The products achieved the expected effects after 10 to 15 minutes.

Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection.

Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. vivax asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systematic study of P. vivax stage distributions in infected tissues of nonhuman primate (NHP) malaria models as well as in blood from human infections. In a comparative analysis of the transcriptomes of P. vivax and Plasmodium falciparum blood-stage parasites, we found a conserved cascade of stage-specific gene expression despite the greatly different gametocyte maturity times of these two species. Using this knowledge, we validated a set of conserved asexual- and gametocyte-stage markers both by quantitative real-time PCR and by antibody assays of peripheral blood samples from infected patients and NHP (Aotus sp.). Histological analyses of P. vivax parasites in organs of 13 infected NHP (Aotus and Saimiri species) demonstrated a major fraction of immature gametocytes in the parenchyma of the bone marrow, while asexual schizont forms were enriched to a somewhat lesser extent in this region of the bone marrow as well as in sinusoids of the liver. These findings suggest that the bone marrow is an important reservoir for gametocyte development and proliferation of malaria parasites.IMPORTANCEPlasmodium vivax malaria continues to cause major public health burdens worldwide. Yet, significant knowledge gaps in the basic biology and epidemiology of P. vivax malaria remain, largely due to limited available tools for research and diagnostics. Here, we present a systematic examination of tissue sequestration during P. vivax infection. Studies of nonhuman primates and malaria patients revealed enrichment of developing sexual stages (gametocytes) and mature replicative stages (schizonts) in the bone marrow and liver, relative to those present in peripheral blood. Identification of the bone marrow as a major P. vivax tissue reservoir has important implications for parasite diagnosis and treatment.

Plasmodium gametocytes display homing and vascular transmigration in the host bone marrow.

Transmission of Plasmodium parasites to the mosquito requires the formation and development of gametocytes. Studies in infected humans have shown that only the most mature forms of Plasmodium falciparum gametocytes are present in circulation, whereas immature forms accumulate in the hematopoietic environment of the bone marrow. We used the rodent model Plasmodium berghei to study gametocyte behavior through time under physiological conditions. Intravital microscopy demonstrated preferential homing of early gametocyte forms across the intact vascular barrier of the bone marrow and the spleen early during infection and subsequent development in the extravascular environment. During the acute phase of infection, we observed vascular leakage resulting in further parasite accumulation in this environment. Mature gametocytes showed high deformability and were found entering and exiting the intact vascular barrier. We suggest that extravascular gametocyte localization and mobility are essential for gametocytogenesis and transmission of Plasmodium to the mosquito.

Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5-dependent and -independent mechanisms.

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Dietary interventions based on protein restriction (PR) reduce circulating triglycerides (TGs), but underlying mechanisms and clinical relevance remain unclear. Here, we show that 1 week of a protein-free diet without enforced calorie restriction significantly lowered circulating TGs in both lean and diet-induced obese mice. Mechanistically, the TG-lowering effect of PR was due, in part, to changes in very low-density lipoprotein (VLDL) metabolism both in liver and peripheral tissues. In the periphery, PR stimulated VLDL-TG consumption by increasing VLDL-bound APOA5 expression and promoting VLDL-TG hydrolysis and clearance from circulation. The PR-mediated increase in Apoa5 expression was controlled by the transcription factor CREBH, which coordinately regulated hepatic expression of fatty acid oxidation-related genes, including Fgf21 and Ppara. The CREBH-APOA5 axis activation upon PR was intact in mice lacking the GCN2-dependent amino acid-sensing arm of the integrated stress response. However, constitutive hepatic activation of the amino acid-responsive kinase mTORC1 compromised CREBH activation, leading to blunted APOA5 expression and PR-recalcitrant hypertriglyceridemia. PR also contributed to hypotriglyceridemia by reducing the rate of VLDL-TG secretion, independently of activation of the CREBH-APOA5 axis. Finally, a randomized controlled clinical trial revealed that 4-6 weeks of reduced protein intake (7%-9% of calories) decreased VLDL particle number, increased VLDL-bound APOA5 expression, and lowered plasma TGs, consistent with mechanistic conservation of PR-mediated hypotriglyceridemia in humans with translational potential as a nutraceutical intervention for dyslipidemia.

Conocimiento sobre viruela del mono en profesionales de la salud, Lima-Perú / Knowledge about monkeypox among health professionals, Lima-Peru

Introducción: la pandemia por SARS-CoV 2 nos demostró que no estábamos preparados, que no se repita. Objetivo: conocer el nivel de conocimiento sobre etiología, síntomas, tratamiento y prevención de la enfermedad viruela del mono en profesionales de la salud. El estudio: observacional-descriptivo, incluyó 251 profesionales de la salud, ambos sexos participación voluntaria. Se elaboró un cuestionario incluyéndose las variables edad, sexo y preguntas sobre la enfermedad viruela del mono; análisis descriptivos de los datos. Hallazgos: bajo conocimiento sobre etiología, síntomas, tratamiento y prevención de la enfermedad. Menor conocimiento sobre formas de contagio (21,9%), tiempo de incubación (21,9%), características del virus (24,3%) y diagnóstico laboratorial (25,1%); mayor conocimiento sobre contagiosidad en periodo de incubación (61,0%), presencia de erupciones como característica de la enfermedad (53,8%) y no existencia de tratamiento específico (52,2%). Conclusión: conocimiento bajo; urge la formulación de estrategias para poder enfrentar, de ser necesario, los posibles casos.

Background:the SARS-CoV 2 pandemic showed us that we were not prepared, that it will not happen again. to know the level of knowledge about Objective:the etiology, symptoms, treatment and prevention of monkeypox disease in health professionals. observational-descriptive, included 251 The study:health professionals, both sexes, voluntary participation. Aquestionnaire was developed including the variables age, sex and questions about the monkeypox disease, descriptive analysis of the data. Finding: low knowledge about the etiology, symptoms, treatment and prevention of the disease. Less knowledge about forms of contagion (21.9%), incubation time (21.9%), characteristics of the virus (24.3%) and laboratory diagnosis (25.1%); greater knowledge about contagiousness in the incubation period (61.0%), presence of rashes as a characteristic of the disease (53.8%) and lack of specific treatment (52.2%). Conclusion: low knowledge; The formulation of strategies is urgently needed to be able to face possible cases, if necessary.

Respuesta inmune humoral a cuatro vacunas contra el SARS-CoV-2 en profesionales de la salud

Objetivo: Describir la concentración de los anticuerpos neutralizantes detectados en el suero de profesionales de la salud que recibieron alguna de las vacunas contra el SARS-CoV-2, desarrollada por las empresas Sinopharm, Pfizer, Johnson & Johnson o el candidato vacunal de CureVac. Materiales y métodos: Investigación observacional, descriptiva, retrospectiva, de corte transversal. Se incluyeron en el estudio un total de 217 profesionales de la salud que recibieron el esquema completo de las vacunas de Sinopharm, Pfizer, Johnson & Johnson o del candidato de CureVac. A estos individuos se les había determinado la presencia de anticuerpos neutralizantes contra el SARS-CoV-2 en el suero mediante la técnica de inmunoensayo por electroquimioluminiscencia (eCLIA). Se consideraron las variables edad, sexo, antecedentes de infección con el SARS-CoV-2, concentración de anticuerpos neutralizantes y tipo de vacuna administrada. Resultados: El 16,60 % de los profesionales de la salud manifestó haber tenido COVID-19 antes de haber recibido la vacunación. Ellos se inmunizaron con las vacunas de Sinopharm (74,65 %), Pfizer (12,90 %), Johnson & Johnson (5,07 %) y el candidato de CureVac (7,37 %). Independientemente de la vacuna recibida, el 42,50 % de las personas sin infección previa que recibieron la vacuna no desarrollaron anticuerpos neutralizantes, mientras que el 16,70 % de los que sí tuvieron enfermedad previa no desarrolló estos anticuerpos. La vacuna de Pfizer indujo mayor concentración de anticuerpos neutralizantes (196,27 UA/mL) en pacientes con o sin infección previa. Conclusiones: El estudio confirma que la vacunación refuerza la inmunidad contra el nuevo coronavirus en individuos con diagnóstico previo de COVID-19, y sugiere que la vacuna desarrollada por Pfizer estimula de manera más eficaz la producción de anticuerpos neutralizantes.

Objective: To describe the concentration of neutralizing antibodies in serum from healthcare professionals who received any of the SARS-CoV-2 vaccines developed by Sinopharm, Pfizer or Johnson & Johnson, or CureVac's vaccine candidate. Materials and methods: An observational, descriptive, retrospective, cross-sectional research which included 217 healthcare professionals fully vaccinated with Sinopharm, Pfizer or Johnson & Johnson's vaccines, or CureVac's vaccine candidate. The presence of anti-SARS-CoV-2 neutralizing antibodies in serum was determined in these individuals using the electrochemiluminescence immunoassay (ECLIA). Variables such as age, sex, history of infection with SARS-CoV-2, concentration of neutralizing antibodies and brand of vaccine administered were considered. Results: Sixteen point six zero percent (16.60 %) of the healthcare professionals stated that they had already had COVID-19 before receiving the vaccine. They were immunized with the vaccines developed by Sinopharm (74.65 %), Pfizer (12.90 %) or Johnson & Johnson (5.07 %), or CureVac's vaccine candidate (7.37 %). Regardless of the vaccine received, 42.50 % of the individuals who had not been previously infected with SARS-CoV-2 and 16.70 % of those who had been previously infected did not develop neutralizing antibodies. Pfizer's vaccine produced the highest concentration of neutralizing antibodies (196.27 AU/mL) in patients with or without previous infection. Conclusions: The study demonstrates that vaccination boosts immunity in people previously infected with the novel coronavirus and suggests that Pfizer's vaccine produces the highest concentration of neutralizing antibodies.

Covid 19, mortalidad en adulto mayor y factores asociados / Covid 19, mortality in the elderly and associated factors

Objetivo: Determinar las variables asociadas a la mortalidad por COVID 19 en población adulta mayor. El estudio: estudio observacional, 521 pacientes de 60 a más años con diagnóstico clínico/laboratorial de COVID -19; incluyó variables edad, sexo, prioridad de atención, procedencia, comorbilidades, estancia, frecuencia respiratoria y cardiaca, SO2, temperatura y signos/síntomas. Hallazgos: fallecidos, mayor frecuencia en julio (50.7%), 91,9% prioridad I/II, edad 70.1 ± 7.5 años, masculinos (71,0%), FC 103,7 ± 18,1 lat./min, FR 29,4 ± 6,4 resp./min (p<0,001), SO2 75,1% ± 14,35 y estancia 6,9 días ± 5,7; tos (68,3%), fiebre (38,0%) y cefalea (23,3%) signos/síntomas más frecuentes. El asma se asoció a la mortalidad (p=0,049). Conclusiones: El adulto mayor es una prioridad para los sistemas de salud pública; a mayor edad, masculino, que presente fiebre, tos y asma tendría mal pronóstico frente a la COVID-19.

Objetive:to determine the variables associated with mortality from COVID 19 in the older adult population. : observational study, 521 patients The studyaged 60 years and over with a clinical/laboratory diagnosis of COVID -19; variables included age, sex, priority of care, origin, comorbidities, stay, respiratory and heart rate, SO2, temperature and signs/symptoms. Findings: deaths, higher frequency in July (50.7%), 91.9% priority I/II, age 70.1 ± 7.5 years, male (71.0%), HR 103.7 ± 18.1 beats/min, RF 29.4 ± 6.4 breaths/min (p<0.001), SO2 75.1% ± 14.35 and stay 6.9 days ± 5.7; cough (68.3%), fever (38.0%) and headache (23.3%) most frequent signs/symptoms. Asthma was associated with mortality (p=0.049). The elderly is a priority for Conclusions:public health systems; older, male, with fever, cough and asthma have a poor prognosis against COVID-19.