Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated in time. To face the pandemic, preventive measures have been taken against contagions and the application of vaccines to prevent severe disease and death cases. For the COVID-19 treatment, antiviral, antiparasitic, anticoagulant and other drugs have been reused due to limited specific medicaments for the disease. Drug repurposing is an emerging strategy with therapies that have already tested safe in humans. One promising alternative for systematic experimental screening of a vast pool of compounds is computational drug repurposing (in silico assay). Using these tools, new uses for approved drugs such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir and tenofovir/emtricitabine have been conducted, showing effectiveness in vitro and in silico against SARS-CoV-2 and some of these, also in clinical trials. Additionally, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins and phenolics) with promising in vitro and in silico results for use in COVID-19 disease. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin and betulinic acid, which were proposed as SARS-CoV-2 inhibitors. Among the drugs reused to control the SARS-CoV2, better results have been observed for remdesivir in hospitalized patients and outpatients. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2 and in vivo, a nebulized formulation has demonstrated to alleviate the respiratory symptoms of COVID-19. This review shows the evidence of drug repurposing efficacy and the potential use of natural products as a treatment for COVID-19. For this, a search was carried out in PubMed, SciELO and ScienceDirect databases for articles about drugs approved or under study and natural compounds recognized for their antiviral activity against SARS-CoV-2.

Placenta accreta spectrum: intraoperatory analysis for immediate tele-help.

INTRODUCTION: Placenta accreta spectrum (PAS) is a potentially fatal disease. A quarter of PAS cases are not detected during prenatal evaluations, so obstetricians without experience with this disease may encounter complex cases without having the necessary resources. We report a series of PAS intraoperative finding (IOF) cases and analyze useful strategies to improve patient outcomes. CASE SERIES: Four cases of PAS IOF are reported. These patients were women with previous pregnancies terminated by cesarean section, with placenta previa/anterior, and whose prenatal ultrasound did not detect PAS. Three patients were candidates for the postponement of cesarean section and/or hysterectomy. One case had active vaginal bleeding, so it was not feasible to delay surgery. Patients who benefited from delaying surgery or seeking additional help through telesupport had better clinical outcomes. CONCLUSION: Decisions about which interventions to conduct and which to delay in cases of PAS intraoperative finding can determine the clinical outcome.

Hypoxia during embryonic development increases energy metabolism in normoxic juvenile chicks.

Environmental changes during perinatal development can affect the postnatal life. In this sense, chicken embryos that experience low levels of O2 over a specific phase of incubation can have their tissue growth reduced and the ventilatory response to hypoxia blunted, at least until hatching. Additionally, exposure to low level of O2 after birth reduces the thermogenesis as well. In the present study, we tested the hypothesis that hypoxia over the third week of incubation affects the thermoregulation of juvenile chicks at an age when thermogenesis is already expected to be well-developed. To this end, we measured body temperature (Tb) and oxygen consumption (V̇02) under acute hypoxia or different ambient temperatures (Ta) of 1 and 10day-old chicks that have been exposed to 21% O2 for entire incubation (Nx) or to 15% O2 in the last week of incubation (Hx). We also assessed the thermal preference under normoxia or acute hypoxia of the older chicks from both incubation groups in a thermocline. Hypoxia over incubation reduced growth but did not affect the cold-induced thermogenesis in hatchlings. Regarding the juvenile Hx, present data indicate a catch up growth with higher resting V̇02, a thermal preference for warmer Tas and a possible higher thermal conductance. In conclusion, our results show that hypoxia over the third week of incubation can affect the thermoregulation at least until 10days after hatch in chickens.

Significado que construye el personal de enfermería sobre los cuidadores familiares de personas hospitalizadas / The Meaning of Family Caregivers of Inpatients Constructed by Nursing Personnel / Significado construído pelo pessoal de enfermagem sobre os cuidadores familiares de pessoas hospitalizadas

Objetivo: Conocer el significado que construye el personal de enfermería sobre los cuidadores familiares de personas hospitalizadas. Método: Cualitativo con enfoque etnográfico. Se realizaron 13 entrevistas y 50 horas de observación participante. Los participantes fueron el personal de enfermería que labora en salas de medicina interna en dos instituciones de la ciudad de Medellín, Colombia. El análisis se hizo a partir de la lectura de relatos, observaciones y notas de campo; se extractaron códigos que se agruparon en categorías y se procedió a la interpretación de los hallazgos. Resultados: Para el personal de enfermería el cuidador es importante en el ámbito hospitalario en la medida que está pendiente, colabora, facilita el cuidado y se interesa en aprender. En contraposición, es un obstáculo, porque no participa en las actividades de cuidado al paciente en el hospital, ya sea por miedo o falta de conocimientos. El contexto hospitalario no condiciona el significado que construye el personal de enfermería acerca del cuidador familiar, pues si bien el modelo de cuidado en ambas instituciones está centrado en el paciente y la familia, el cuidador familiar se utiliza como recurso alternativo de cuidado, sin considerar sus necesidades y vulnerabilidad en el ambiente hospitalario. Conclusiones: El personal de enfermería construye el significado acerca del cuidador familiar en el hospital de acuerdo con su utilidad o no en el apoyo que este realiza para las actividades de cuidado.

Objective: Learning about the meaning of family caregivers of inpatients constructed by nursing personnel. Method: Qualitative with an ethnographic focus. Thirteen (13) interviews and fifty (50) hours of participant observation were carried out. The participants were members of the nursing personnel working in the internal medicine rooms in two institutions of Medellin, Colombia. The analysis was performed based on the reading of stories, observations, and field notes. A series of codes were extracted and grouped in categories, followed by the interpretation of the findings. Results: For the nursing personnel, the caregiver is important in the hospital environment to the extent he is alert, cooperates, facilitates care, and shows willingness to learn. On the other hand, he is regarded as an obstacle as he does not take part in the hospital care activities, either because of fear or a lack of knowledge. The hospital context does not condition the meaning constructed by the nursing personnel regarding the family caregiver since, although the care model in both institutions is centered around the patient and the family, the family caregiver is used as an alternative mean for care, with no consideration for his needs and vulnerabilities in the hospital environment. Conclusions: The nursing personnel constructs a meaning around family caregivers according to their contributions, or lack thereof, to care activities.

Objetivo: Conhecer o significado construído pelo pessoal de enfermagem sobre os cuidadores familiares de pessoas hospitalizadas. Método: Qualitativa com enfoque etnográfico. Realizaram-se 13 entrevistas e 50 horas de observação participante. Os participantes foram o pessoal de enfermagem que trabalha em salas de medicina interna em duas instituições da cidade de Medellín, Colômbia. A análise foi feita a partir da leitura de relatos, observações e notas de campo; extrataram-se códigos que foram agrupados em categorias e procedeu-se à interpretação dos achados. Resultados: Para o pessoal de enfermagem o cuidador é importante no âmbito hospitalar na medida em que está atento, colabora, facilita o cuidado e se interessa por aprender. Na contraposição, é obstáculo porque não participa nas atividades de cuidado do paciente no hospital, bem por medo ou falta de conhecimento. O contexto hospitalar não condiciona o significado que constrói a equipe de enfermagem acerca do cuidador familiar, embora que o modelo de cuidado em ambas as instituições esteja focado no paciente e a família, o cuidador familiar é utilizado como recurso alternativo de cuidado, sem considerar suas necessidades e vulnerabilidade no ambiente hospitalar. Conclusões: O pessoal de enfermagem constrói o significado acerca do cuidador familiar no hospital segundo sua utilidade ou não no suporte que aquele realiza nas atividades de cuidado.

Interacción del personal de enfermería con el cuidador familiar en el ámbito hospitalario / Interaction of nursing staff with family caregivers in a hospital environment

Objetivo: describir cómo interactúa el personal de enfermería con el cuidador familiar del paciente hospitalizado con enfermedad crónica. Metodología: estudio cualitativo con enfoque etnográfico. Resultados: la comunicación entre el personal de enfermería y el cuidador familiar fue unidireccional, encaminada a promover acciones que permitieran aliviar la carga laboral, es decir, una interacción cuyo fin era meramente instrumental. La relación con el cuidador era positiva si este aprendía lo enseñado, colaboraba y participaba en las actividades de cuidado de su paciente. Conclusiones: la interacción personal de enfermería – cuidador familiar del paciente crónico hospitalizado, se construye a partir de una comunicación limitada a la entrega de información por parte del personal para instruirlo o entrenarlo en el cuidado tanto en el hospital como en la casa, desconociendo sus necesidades, saberes y sentimientos.

Objective: to describe how nursing staff interact with the family caregivers of hospitalized patients with chronic disease.Methodology: qualitative study with ethnographic approach.Results: communication between nursing staff and family caregivers was unidirectional, aimed at promoting actions that allow the reduce the workload, ie, an interaction whose purpose was purely instrumental. The relationship with the caregiver was positive if this was learning what is taught, collaborated and participated in the activities of patient care. Conclusions: the interaction of the nursing staff - family caregivers of chronic hospitalized patient, is constructed from a limited communication to the release of information by the staff to instruct or training them in the care, both in hospital as same as in home, ignoring their needs, knowledge and feelings.

Objetivo: descrever a interação do pessoal de enfermagem com o cuidador familiar do paciente hospitalizado com doença crônica. Metodologia: estudo qualitativo com enfoque etnográfico. Resultados: a comunicação entre o pessoal de enfermagem e o cuidador familiar foi de mão única, encaminhada a promover ações que permitissem aliviar a carga de trabalho, ou seja, uma interação cujo fim era meramente instrumental. A relação com o cuidador era positiva se este aprendia o ensinado, colaborava e participava nas atividades do cuidado do seu paciente. Conclusões: a interação pessoal de enfermagem – cuidador familiar de paciente crónico hospitalizado constrói-se a partir de uma comunicação limitada à entrega de informação por parte do pessoal para instruí-lo ou treiná-lo no cuidado tanto no hospital como em casa, desconhecendo as suas necessidades, saberes e sentimentos.

Transcriptome analysis of the entomopathogenic oomycete Lagenidium giganteum reveals putative virulence factors.

A combination of 454 pyrosequencing and Sanger sequencing was used to sample and characterize the transcriptome of the entomopathogenic oomycete Lagenidium giganteum. More than 50,000 high-throughput reads were annotated through homology searches. Several selected reads served as seeds for the amplification and sequencing of full-length transcripts. Phylogenetic analyses inferred from full-length cellulose synthase alignments revealed that L giganteum is nested within the peronosporalean galaxy and as such appears to have evolved from a phytopathogenic ancestor. In agreement with the phylogeny reconstructions, full-length L. giganteum oomycete effector orthologs, corresponding to the cellulose-binding elicitor lectin (CBEL), crinkler (CRN), and elicitin proteins, were characterized by domain organizations similar to those of pathogenicity factors of plant-pathogenic oomycetes. Importantly, the L. giganteum effectors provide a basis for detailing the roles of canonical CRN, CBEL, and elicitin proteins in the infectious process of an oomycete known principally as an animal pathogen. Finally, phylogenetic analyses and genome mining identified members of glycoside hydrolase family 5 subfamily 27 (GH5_27) as putative virulence factors active on the host insect cuticle, based in part on the fact that GH5_27 genes are shared by entomopathogenic oomycetes and fungi but are underrepresented in nonentomopathogenic genomes. The genomic resources gathered from the L. giganteum transcriptome analysis strongly suggest that filamentous entomopathogens (oomycetes and fungi) exhibit convergent evolution: they have evolved independently from plant-associated microbes, have retained genes indicative of plant associations, and may share similar cores of virulence factors, such as GH5_27 enzymes, that are absent from the genomes of their plant-pathogenic relatives.

Chicken hatchlings prefer ambient temperatures lower than their thermoneutral zone.

We investigated whether or not the preferred ambient temperature (Tapref) of the 1-day old chicken hatchling, a precocial neonate with excellent locomotory capacity, clearly identifiable thermogenesis and independence from maternal care, coincides with the lower critical temperature (LCT) of thermoneutrality and minimal oxygen consumption (V̇(O(2))). Tapref of single chicks measured in a thermocline (N=16) averaged 33.5±0.3 °C (mode, 33.3±0.4 °C). The same value was obtained in hatchlings studied in pairs. LCT was computed from the ambient temperature (Ta)-V̇(O(2)) relationship, constructed by slowly decreasing the Ta of a respirometer from 38 to 29 °C over 2.5h, while continuously measuring V̇(O(2)) by an open-flow methodology; LCT averaged 36.4 °C±0.3 or 36.8 °C±0.4, depending on the method of computation. In all hatchlings Tapref was lower than LCT (P<0.001), by a magnitude that depended on the method of computation of the two variables, 2.8 °C±0.3 (P<0.001) or 3.9 °C±0.5. The Tapref-LCT difference implied that, at Tapref, V̇(O(2)) was higher than at thermoneutrality. We conclude that in the chicken hatchling thermal preference does not coincide with thermoneutrality, probably because during development what seems optimal from a thermoregulatory viewpoint may not necessarily be so for other regulatory functions.

Thermogenesis, vocalization, and temperature preference of 1-day-old chicken hatchlings after cold-exposure in late embryogenesis.

In a thermal gradient the preferred ambient temperature (T(a) pref) of chicken hatchlings is a few degrees lower than thermoneutrality. To investigate whether a correlation may exist between T(a) pref and the autonomic thermogenic capacity or not we studied a group of hatchlings (N = 15) exposed to cold at end-incubation, a procedure known to increase their postnatal thermogenesis. Chicken embryos were exposed to cold (34.5 °C instead of 38 °C) at days 18-20 of incubation. By comparison to Controls (N = 15), they hatched a few hours later, with similar body weight, body temperature, vocalization (number of sounds produced per unit time), and oxygen consumption (VO2, measured in a respirometer by an open-flow methodology). When exposed to slow cooling these hatchlings had a higher lower critical temperature (LCT) of thermoneutrality and higher VO2, and slightly higher vocalization than Controls. In a thermal gradient, T(a) pref averaged 34.3 ± 0.3 °C, or 1 °C higher than in Controls (33.4 ± 0.3 °C; P < 0.05), in proportion with their higher LCT (38 ± 0.1 °C instead of 36.7 ± 0.3 °C; P < 0.001), so that the T(a) pref - LCT difference (-3.6 ± 0.3 °C) was similar to Controls (-3.3 ± 0.3 °C). In conclusion, in chicken hatchlings T(a) pref was lower than LCT irrespective of the magnitude of their thermogenic response. It was estimated that, at T(a) pref, VO2 was ~20 % higher than at thermoneutrality. Such metabolic increase could carry some physiological advantage and the choice of T a pref may reflect the hatchling's needs to maintain VO2 slightly elevated.

Breathing pattern and ventilatory chemosensitivity of the 1-day old Muscovy duck (Cairina moschata) in relation to its metabolic demands.

Adult birds have a ventilatory equivalent (pulmonary ventilation-oxygen consumption ratio, V˙ E/ [Formula: see text] ) lower than mammals because of the superior gas exchange efficiency of their respiratory apparatus. In particular, adult Muscovy ducks (Cairina moschata) have been reported to have an extraordinary low ventilatory equivalent (~14mL STPD·mL BTPS(-1)). We asked if similar high efficiency was already apparent in duck hatchlings. Breathing pattern and V˙E were measured by the barometric technique and [Formula: see text] by an open-flow methodology in 1-day old Muscovy duck hatchlings (N=21); same measurements were performed on chicken hatchlings (N=21) for purpose of comparison. During air breathing V˙E/ [Formula: see text] was slightly, yet significantly, lower in ducklings (20.8) than in chicks (25.3), mostly because of a lower breathing frequency (f). The hatchlings of both species (N=14 per group) responded to inspired hypoxia (15 or 10% O2) or hypercapnia (2 or 4% CO2) with a clear hyperventilation; however, in ducklings the hypercapnic hyperventilation was smaller than in chicks because of a smaller increase in tidal volume and lower f. We conclude that duck and chicken hatchlings just a few hours old have the high ventilatory efficiency typical of birds, although possibly not as high as their adults. The low f and blunted V˙E response to hypercapnia of the newborn duck could be related to the aquatic habitat of the species. In such a case, it would mean that these characteristics are genetic traits, the phenotypic expression of which does not require diving experience.

The motility of the chicken embryo: energetic cost and effects of hypoxia.

We estimated the energetic cost of embryonic motility by relating the changes in embryo's motion to the changes in oxygen consumption (VO2). Measurements were conducted on chicken embryos between day 10 and 18 of incubation. Embryonic gross body movement was quantified over ten continuous 3-min periods from the pressure oscillations inside the egg, measured through an implanted catheter, and was correlated to the synchronous changes in VO2, measured by an open-flow methodology. Over the 30 min recording, movements could vary around the mean by up to four folds. The corresponding changes in VO2 were minuscule (0.116 µl O2/mmHg) or, for all age groups combined, only 2.3% of the mean VO2, ranging from ≈ 8% (day 10) to ≈ 0.5% (day 16). At E18, hypercapnia and cold respectively increased and decreased motility. Differently, the effects of hypoxia on motility were variable among embryos. It is concluded that, in chicken embryos over the age period investigated, the cost of motility represents an almost negligible fraction of the total energy budget. Because of its low cost, motility can be maintained in hypoxia; conversely, reduction of motility in hypoxia does not provide an important energy saving.

Ventilatory response to hypoxia of the 1-day old chicken hatchling after prenatal cold-induced hypometabolism.

Sustained prenatal hypoxia decreases the growth and metabolic rate of the embryo and causes a blunted hypoxic ventilatory response (HVR) in the newborn. The most likely interpretation is that the sustained hypoxic stimulation may interfere with the normal prenatal development of the chemoreceptors. However, we wanted to consider the possibility that the prolonged hypoxic hypometabolism may be a contributing factor. Chicken embryos were incubated at 35°C (Cold group, N=14), which is known to lower the embryonic oxygen consumption (VO2) by ≈ 30% throughout incubation, or at 37.5°C (Controls, N=16). Cold incubation delayed hatching by ≈ 2 days. The 1-day old hatchlings had normal pulmonary ventilation (VE), measured by the barometric technique, and oxygen consumption (VO2), simultaneously measured by an open flow methodology. During acute hypoxia (≈ 15% or ≈ 11% O2) the hyperventilation (increase in VO2), the hyperpnea and the hypometabolism were almost identical between the two groups of hatchlings. We conclude that a sustained decrease in metabolic rate during the embryonic period by itself does not carry obvious consequences on the newborn's resting VE and HVR.

Palynological composition of a Lower Cretaceous South American tropical sequence: climatic implications and diversity comparisons with other latitudes.

PREMISE OF THE STUDY: Reconstruction of floristic patterns during the early diversification of angiosperms is impeded by the scarce fossil record, especially in tropical latitudes. Here we collected quantitative palynological data from a stratigraphic sequence in tropical South America to provide floristic and climatic insights into such tropical environments during the Early Cretaceous. METHODS: We reconstructed the floristic composition of an Aptian-Albian tropical sequence from central Colombia using quantitative palynology (rarefied species richness and abundance) and used it to infer its predominant climatic conditions. Additionally, we compared our results with available quantitative data from three other sequences encompassing 70 floristic assemblages to determine latitudinal diversity patterns. KEY RESULTS: Abundance of humidity indicators was higher than that of aridity indicators (61% vs. 10%). Additionally, we found an angiosperm latitudinal diversity gradient (LDG) for the Aptian, but not for the Albian, and an inverted LDG of the overall diversity for the Albian. Angiosperm species turnover during the Albian, however, was higher in humid tropics. CONCLUSIONS: There were humid climates in northwestern South America during the Aptian-Albian interval contrary to the widespread aridity expected for the tropical belt. The Albian inverted overall LDG is produced by a faster increase in per-sample angiosperm and pteridophyte diversity in temperate latitudes. However, humid tropical sequences had higher rates of floristic turnover suggesting a higher degree of morphological variation than in temperate regions.