Ivermectin as a possible treatment for COVID-19: a review of the 2022 protocols.

Ivermectin is a safe and effective drug in humans and has been approved for use in numerous parasitic infections for over 50 years. In addition, many studies have already shown its antiviral activity. Ivermectin is generally well tolerated, with no indication of central nervous system-associated toxicity at doses up to 10 times the highest FDA-approved dose of 200 µg/kg. The in vitro results of ivermectin for reducing SARS-CoV-2 viral load are promising and show that Ivermectin kills SARS-CoV-2 within 48 hours. A hypothesized mechanism of action for this drug is a likely inhibition of IMPα/ß1-mediated nuclear import of viral proteins as demonstrated for other RNA viruses. However, controlled and randomized studies are needed to prove its effectiveness in COVID-19 in humans. In a single in vivo study with published results, patients confirmed to be infected with SARS-CoV-2 received at least one dose of ivermectin at any time during hospitalization. The use of ivermectin was associated with lower mortality during treatment with COVID-19, especially in patients who required increased inspired oxygen or ventilatory support. Additionally, 81 studies with the clinical use of ivermectin in humans are being carried out worldwide according to ClinicalTrials.gov. However, none of these data has been published so far. However, private and public entities in Brazil have been adopting this drug in their protocols as prophylaxis and in the initial phase of the disease. In addition, ivermectin has been used in mass treatment to prevent onchocerciasis and lymphatic filariasis in sub-Saharan Africa for many years. Surprisingly, this region has the lowest proportional mortality rate among the continents, despite the increasing numbers of infected people released by the World Health Organization.

A conserved Toll-like receptor-to-NF-κB signaling pathway in the endangered coral Orbicella faveolata.

Herein, we characterize the Toll-like receptor (TLR)-to-NF-κB innate immune pathway of Orbicella faveolata (Of), which is an ecologically important, disease-susceptible, reef-building coral. As compared to human TLRs, the intracellular TIR domain of Of-TLR is most similar to TLR4, and it can interact in vitro with the human TLR4 adapter MYD88. Treatment of O. faveolata tissue with lipopolysaccharide, a ligand for mammalian TLR4, resulted in gene expression changes consistent with NF-κB pathway mobilization. Biochemical and cell-based assays revealed that Of-NF-κB resembles the mammalian non-canonical NF-κB protein p100 in that C-terminal truncation results in translocation of Of-NF-κB to the nucleus and increases its DNA-binding and transcriptional activation activities. Moreover, human IκB kinase (IKK) and Of-IKK can both phosphorylate conserved residues in Of-NF-κB in vitro and induce C-terminal processing of Of-NF-κB in vivo. These results are the first characterization of TLR-to-NF-κB signaling proteins in an endangered coral, and suggest that these corals have conserved innate immune pathways.

Population structure and connectivity of the mountainous star coral, Orbicella faveolata, throughout the wider Caribbean region.

As coral reefs continue to decline worldwide, it becomes ever more necessary to understand the connectivity between coral populations to develop efficient management strategies facilitating survival and adaptation of coral reefs in the future. Orbicella faveolata is one of the most important reef-building corals in the Caribbean and has recently experienced severe population reductions. Here, we utilize a panel of nine microsatellite loci to evaluate the genetic structure of O. faveolata and to infer connectivity across ten sites spanning the wider Caribbean region. Populations are generally well-mixed throughout the basin (FST = 0.038), although notable patterns of substructure arise at local and regional scales. Eastern and western populations appear segregated with a genetic break around the Mona Passage in the north, as has been shown previously in other species; however, we find evidence for significant connectivity between Curaçao and Mexico, suggesting that the southern margin of this barrier is permeable to dispersal. Our results also identify a strong genetic break within the Mesoamerican Barrier Reef System associated with complex oceanographic patterns that promote larval retention in southern Belize. Additionally, the diverse genetic signature at Flower Garden Banks suggests its possible function as a downstream genetic sink. The findings reported here are relevant to the ongoing conservation efforts for this important and threatened species, and contribute to the growing understanding of large-scale coral reef connectivity throughout the wider Caribbean.

Bradicardia extrema por infarto talámico paramediano bilateral / Extreme bradycardia due to bilateral paramedian thalamic infarction

RESUMEN Alteraciones autonómicas agudas por infartos cerebrales se han descrito con frecuencia comprometiendo la región insular, dentro de las anormalidades se han documentado alteraciones de severidad variable del ritmo cardíaco, incluyendo la bradicardia extrema sintomática; en la literatura solo hay un reporte de caso de bradi-cardia extrema asociado a un infarto talámico paramediano bilateral, a continuación, describimos un segundo caso de un infarto talámico con la misma presentación.

SUMMARY Acute autonomic disturbances due to cerebral in farcts has been describe frequently with association of the insular cortex, within the describe abnormalities had been document a variety of cardiac disturbances including extreme symptomatic bradycardia; In the literature just exist a case report of extreme bradycardia associate with a bilateral paramedian thalamic infarct, in the following article, we describe a second case of this infarct with the same presentation.

The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review.

OBJECTIVES: To evaluate the efficacy and safety of estriol for the treatment of vulvovaginal atrophy in postmenopausal women. METHODS: A systematic literature review was performed. We searched the following electronic databases: Medline, Cochrane, Embase, Lilacs, CINHAL and Google Scholar. The studies selected included controlled clinical trials and quasi-experimental studies. Selections were made in pairs and independently, first by title and abstract and then complete texts. RESULTS: We identified 188 studies, 22 of which met the inclusion criteria; 13 were controlled clinical trials and nine were quasi-experimental, and 1217 women were included. These studies confirmed the efficacy of local estrogens to treat symptoms of vulvovaginal atrophy with few adverse effects reported. Following treatment, serum estriol levels rose, peaking at 1 h. At the 6-month follow-up, there was no increase in serum estriol in treated women. CONCLUSIONS: The available evidence (of low and moderate quality) shows that, when administered vaginally, estriol preparations appear to be safe for women who have risk factors related to systemic estrogen therapy.

Life or death: disease-tolerant coral species activate autophagy following immune challenge.

Global climate change has increased the number and severity of stressors affecting species, yet not all species respond equally to these stressors. Organisms may employ cellular mechanisms such as apoptosis and autophagy in responding to stressful events. These two pathways are often mutually exclusive, dictating whether a cell adapts or dies. In order to examine differences in cellular response to stress, we compared the immune response of four coral species with a range of disease susceptibility. Using RNA-seq and novel pathway analysis, we were able to identify differences in response to immune stimulation between these species. Disease-susceptible species Orbicella faveolata activated pathways associated with apoptosis. By contrast, disease-tolerant species Porites porites and Porites astreoides activated autophagic pathways. Moderately susceptible species Pseudodiploria strigosa activated a mixture of these pathways. These findings were corroborated by apoptotic caspase protein assays, which indicated increased caspase activity following immune stimulation in susceptible species. Our results indicate that in response to immune stress, disease-tolerant species activate cellular adaptive mechanisms such as autophagy, while susceptible species turn on cell death pathways. Differences in these cellular maintenance pathways may therefore influence the organismal stress response. Further study of these pathways will increase understanding of differential stress response and species survival in the face of changing environments.

Actividad física en residentes de medicina familiar de Bogotá y su recomendación a los pacientes / Physical Activity in Bogotá Family Practice Residents and their recommendation to Patients

Objetivo: Identificar los hábitos de actividad física (AF) en residentes de medicina familiar de Bogotá y las recomendaciones que dan sobre esta a los pacientes. Metodología: Estudio de corte transversal con aplicación de parte de la encuesta de Healthy Doctor = Healthy Patient y preguntas sobre las "Características del médico y de la práctica clínica" de la iniciativa Exercise is Medicine® en los profesionales en formación en medicina familiar de 5 universidades de Bogotá. Resultados: El total de participantes fue de 9? residentes, quienes reportaron AF vigorosa, moderada y leve. Conclusiones: Los resultados evidenciados y comparados con la literatura internacional disponible (Reino Unido, Estados Unidos, Nueva Zelanda y Canadá) muestran que hay convergencia en la necesidad de capacitar médicos de atención primaria en la forma correcta de interrogar y recomendar la AF, de forma escrita, teniendo el formato incluido en la historia clínica esto respaldado por iniciativas internacionales.

Objective: To identiíy habits and physical activity recommendations in family medicine residente of Bogotá. Methodologyt Cross

Características de pacientes ingresados a la unidad de cuidado intensivo neonatal en la Clínica Universidad de La Sabana / Features of patients hospitalized to the newborn intensive care at Clínica Universidad de La Sabana

Introducción: Es pertinente conocer las características de los pacientes que ingresan a las unidades de cuidado intensivo neonatal para que las acciones en salud respondan a sus necesidades particulares. Objetivo: Caracterizar los pacientes que ingresaron a la Unidad de Cuidado Intensivo Neonatal (UCIN) de la Clínica de la Universidad de La Sabana de enero a diciembre del 2012. Materiales y Métodos: estudio retrospectivo con n=206 neonatos que ingresaron a la UCIN de la Clínica Universidad de La Sabana en el 2012, se revisaron las historias clínicas de los pacientes ingresados para identificar sus características, se calcularon frecuencias relativas y absolutas; y para las variables cuantitativas se describieron medidas de tendencia central y dispersión. Resultados: el 56,3% eran hombres, el promedio de edad gestacional de 36,5 semanas (SD 3,3 semanas), el peso promedio fue de 2625,9 g (SD 757,5 g). La mediana de los días de estancia fue de 4 (IQR: 2 a 9). El principal diagnóstico fue ictericia neonatal en (21,8%), el 22% de los pacientes requirieron ventilación mecánica (VM). La media de la edad gestacional y del peso en pacientes con requerimientos de VM fue de 32.7 semanas (SD: 3,7 semanas) y 1883 g (SD: 779 g) respectivamente, comparado con 37,6 semanas (SD: 2,2 semanas) y 2840 g (SD: 601 g) en los que no requirieron VM. Conclusiones: características como bajo peso al nacer, edad gestacional temprana y el uso de surfactante, se asociaron con el requerimiento de VM, adicionalmente la mortalidad calculada fue del 2,8%.

Introduction: It is relevant to know the characteristics of patients who enter to neonatal intensive care units in order to learn how to respond to their specific conditions and which health actions can be applied for their particular needs. Objective: The aim of this study is describe patients admitted at Clinica Universidad de La Sabana (Neonatal Intensive Care -NIC) from January to December 2012. Materials and Methods: Retrospective study with n=206 neonates admitted to the NIC at Clinica Universidad de La Sabana in 2012, medical records of patients admitted were reviewed to identify its characteristics, as well absolute and relative frequencies were calculated. In terms of quantitative variables, they were measured with central tendency and dispersion. Results: 56.3% of patients were men, the average gestational age was 36.5 weeks (SD 3.3 weeks), the average weight was 2625 gr (SD 757.5 gr). The median days of stay was 4 (IQR:2-9). The main diagnosis was neonatal icterus (21.8%); 22% of patient's required mechanical ventilation (MV). The mean gestational age and weight in patients with VM requirements was 32.7 weeks (SD: 3.7 weeks) and 1883 gr (SD: 779 gr) respectively. Contrasted with the gestational age and weight of newborns that not requiring VM was 37.6 weeks (SD 2.2 weeks) and 2840 gr (SD: 601 gr). Conclusions: Low birth weight, early gestational age and the use of surfactant, were associated with the requirement of VM, and the mortality found was 2.8% for the whole cohort.

The link between immunity and life history traits in scleractinian corals.

Immunity is an important biological trait that influences the survival of individuals and the fitness of a species. Immune defenses are costly and likely compete for energy with other life-history traits, such as reproduction and growth, affecting the overall fitness of a species. Competition among these traits in scleractinian corals could influence the dynamics and structural integrity of coral reef communities. Due to variability in biological traits within populations and across species, it is likely that coral colonies within population/species adjust their immune system to the available resources. In corals, the innate immune system is composed of various pathways. The immune system components can be assessed in the absence (constitutive levels) and/or presence of stressors/pathogens (immune response). Comparisons of the constitutive levels of three immune pathways (melanin synthesis, antioxidant and antimicrobial) of closely related species of Scleractinian corals allowed to determine the link between immunity and reproduction and colony growth. First, we explored differences in constitutive immunity among closely related coral species of the genus Meandrina with different reproductive patterns (gonochoric vs. hermaphrodite). We then compared fast-growing branching vs. slow-growing massive Porites to test co-variation between constitutive immunity and growth rates and morphology in corals. Results indicate that there seems to be a relationship between constitutive immunity and sexual pattern with gonochoric species showing significantly higher levels of immunity than hermaphrodites. Therefore, gonochoric species maybe better suited to resist infections and overcome stressors. Constitutive immunity varied in relation with growth rates and colony morphology, but each species showed contrasting trends within the studied immune pathways. Fast-growing branching species appear to invest more in relatively low cost pathways of the immune system than slow-growing massive species. In corals, energetic investments in life-history traits such as reproduction and growth rate (higher energy investment) seem to have a significant impact on their capacity to respond to stressors, including infectious diseases and coral bleaching. These differences in energy investment are critical in the light of the recent environmental challenges linked to global climate change affecting these organisms. Understanding physiological trade-offs, especially those involving the immune system, will improve our understanding as to how corals could/will respond and survive in future adverse environmental conditions associated with climate change.

Relationship between phylogeny and immunity suggests older Caribbean coral lineages are more resistant to disease.

Diseases affect coral species fitness and contribute significantly to the deterioration of coral reefs. The increase in frequency and severity of disease outbreaks has made evaluating and determining coral resistance a priority. Phylogenetic patterns in immunity and disease can provide important insight to how corals may respond to current and future environmental and/or biologically induced diseases. The purpose of this study was to determine if immunity, number of diseases and disease prevalence show a phylogenetic signal among Caribbean corals. We characterized the constitutive levels of six distinct innate immune traits in 14 Caribbean coral species and tested for the presence of a phylogenetic signal on each trait. Results indicate that constitutive levels of some individual immune related processes (i.e. melanin concentration, peroxidase and inhibition of bacterial growth), as well as their combination show a phylogenetic signal. Additionally, both the number of diseases affecting each species and disease prevalence (as measures of disease burden) show a significant phylogenetic signal. The phylogenetic signal of immune related processes, combined with estimates of species divergence times, indicates that among the studied species, those belonging to older lineages tend to resist/fight infections better than more recently diverged coral lineages. This result, combined with the increasing stressful conditions on corals in the Caribbean, suggest that future reefs in the region will likely be dominated by older lineages while modern species may face local population declines and/or geographic extinction.

Thermal characterization of magnetically aligned carbonyl iron/agar composites.

Composites of magnetic particles into polymeric matrices have received increasing research interest due to their capacity to respond to external magnetic or electromagnetic fields. In this study, agar from Gelidium robustum has been chosen as natural biocompatible polymer to build the matrix of the magnetic carbonyl iron particles (CIP) for their uses in biomedical fields. Heat transfer behavior of the CIP-agar composites containing different concentrations (5, 10, 15, 20, 25 and 30% w/w) of magnetically aligned and non-aligned CIP in the agar matrix was studied using photothermal radiometry (PTR) in the back-propagation emission configuration. The morphology of the CIP-agar composites with aligned and non-aligned CIP under magnetic field was also evaluated by scanning electron microscopy (SEM). The results revealed a dominant effect of CIP concentration over the alignment patterns induced by the magnetic field, which agrees with the behavior of the thermal diffusivity and thermal conductivity. Agar served as a perfect matrix to be used with CIP, and CIP-agar composites magnetically aligned at 20% CIP concentration can be considered as promising 'smart' material for hyperthermia treatments in the biomedical field.

Identification of soluble forms of vascular endothelial growth factor receptors, sVEGFR-1 and sVEGFR-2, in bovine dominant follicles.

The development of dominant follicles requires the parallel growth of a vascular network, regulated by VEGF and its receptors VEGFR-1 and VEGFR-2. Here, we demonstrate the presence of mRNA for the soluble forms of VEGFR-1 and VEGFR-2 by RT-PCR and the respective proteins by Western blot, in bovine dominant follicles. The 3' end of the mRNA coding region and the deduced C-terminal amino acid sequence of the bovine VEGFR soluble forms were similar to those previously described in human and mice. The relative abundance of sVEGFR-1 was higher in dominant follicles of day 4, decreasing on day 6 and further on day 9 of the cycle. In contrast, sVEGFR-2 expression was low on day 4 follicles and increased as the cycle advanced, becoming greater on day 9. The changes of sVEGFR-1 and sVEGFR-2 with the age of the bovine dominant follicle indicate a physiological role in its growth and atresia.

Correlation of the genotoxic activation and kinetic properties of Salmonella enterica serovar Typhimurium nitroreductases SnrA and cnr with the redox potentials of nitroaromatic compounds and quinones.

Bacterial nitroreductases (NRs) catalyse the oxygen-insensitive reduction of several nitro-substituted compounds and quinones. SnrA and cnr NRs have been previously identified in Salmonella enterica serovar Typhimurium; they reduce several environmental nitro compounds that display mutagenic activity in the Ames test. Although some of their biochemical properties have been reported, the substrate specificity of each protein over mutagenic nitro compounds is unknown; even more, the possible relationship between their capacity to activate nitro compounds into mutagens and the redox properties of putative substrates has been poorly investigated. We have purified SnrA and cnr and investigated their capacity to activate several mutagens in the Ames test as well as their kinetic parameters K(m) and V(max). Our results show that SnrA and cnr are able to activate 2,7-dinitrofluorene with the same efficiency and a similar mutagenic potency in the YG7132 tester strain; 1-nitropyrene and 1,3-dinitropyrene were efficiently activated by cnr, whereas 1,8-dinitropyrene, 1,6-dinitropyrene and 2-nitrofluorene were scarcely activated by either NR. The mutagenic potency of nitro compounds obtained in the presence of either enzyme correlates with their redox potential reported in the literature. On the other hand, a good correlation was obtained between the catalytic efficiency (V(max)/K(m)) of the purified cnr with the redox potential of eight molecules including nitro-substituted compounds and quinones. No correlation between redox potential and catalytic efficiency by SnrA was observed, suggesting that factors other than redox potential such as the structure of the compounds are involved in the catalytic efficiency of SnrA.

Reduced amide pseudopeptide analogues of a malaria peptide possess secondary structural elements responsible for induction of functional antibodies which react with native proteins expressed in Plasmodium falciparum erythrocyte stages.

A psi[CH2NH] isoster bond was introduced by replacing one peptide bond at a time within the 1513 malaria peptide KEKMV motif to obtain a set of five pseudopeptides. The motif belongs to a Plasmodium falciparum malarial peptide coded 1513, derived from the MSP-1 protein. This high-binding motif included in the 1513 peptide is involved in the attachment of the malarial parasite to human erythrocytes. The novel malaria 1513 psi[CH2NH] surrogates were analyzed using RP-HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance experiments allowed definition of the five pseudopeptide analogues' secondary structural features. Such structures are present in only a very few molecules in the 1513 parent peptide. A molecular model demonstrating the solution of the three-dimensional structure of the 1 513 peptide Pse-437 analogue was constructed on the basis of 1H-NMR spectral parameters. Monoclonal antibodies were generated to the five 1513 malaria peptide pseudopeptide analogues. These antibodies not only recognize the native MSP-1 (195 kDa) and its 83 kDa and 42 kDa proteolytic processing proteins but also different SPf(66)n malaria vaccine batches containing the native sequence. In addition, the mAbs were able to modify the kinetics of Plasmodium falciparum parasites' intraerythrocytic development and their ability to invade new RBCs. The presented evidence suggests that peptide bond-modified peptides could reproduce a transient state in 1513's native sequence and represent useful candidates in the development of a second generation of effective malarial vaccines.