Licorice extract inhibits porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and even death in piglets, resulting in significant economic losses to the pig industry. Because of the ongoing mutation of PEDV, there might be variations between the vaccine strain and the prevailing strain, causing the vaccine to not offer full protection against different PEDV variant strains. Therefore, it is necessary to develop anti-PEDV drugs to compensate for vaccines. This study confirmed the anti-PEDV effect of licorice extract (Le) in vitro and in vivo. Le inhibited PEDV replication in a dose-dependent manner in vitro. By exploring the effect of Le on the life cycle of PEDV, we found that Le inhibited the attachment, internalization, and replication stages of the virus. In vivo, all five piglets in the PEDV-infected group died within 72 h. In comparison, the Le-treated group had a survival rate of 80 % at the same time, with significant relief of clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Our results suggested that Le can exert anti-PEDV effects in vitro and in vivo. Le is effective and inexpensive; therefore it has the potential to be developed as a new anti-PEDV drug.

Development of Glycyrrhizinic Acid-Based Lipid Nanoparticle (LNP-GA) as An Adjuvant That Improves the Immune Response to Porcine Epidemic Diarrhea Virus Spike Recombinant Protein.

Porcine epidemic diarrhea virus (PEDV) has affected the pork industry worldwide and during outbreaks the mortality of piglets has reached 100%. Lipid nanocarriers are commonly used in the development of immunostimulatory particles due to their biocompatibility and slow-release delivery properties. In this study, we developed a lipid nanoparticle (LNP) complex based on glycyrrhizinic acid (GA) and tested its efficacy as an adjuvant in mice immunized with the recombinant N-terminal domain (NTD) of porcine epidemic diarrhea virus (PEDV) spike (S) protein (rNTD-S). The dispersion stability analysis (Z-potential -27.6 mV) confirmed the size and charge stability of the LNP-GA, demonstrating that the particles were homogeneously dispersed and strongly anionic, which favors nanoparticles binding with the rNTD-S protein, which showed a slightly positive charge (2.11 mV) by in silico analysis. TEM image of LNP-GA revealed nanostructures with a spherical-bilayer lipid vesicle (~100 nm). The immunogenicity of the LNP-GA-rNTD-S complex induced an efficient humoral response 14 days after the first immunization (p < 0.05) as well as an influence on the cellular immune response by decreasing serum TNF-α and IL-1ß concentrations, which was associated with an anti-inflammatory effect.

Evaluación de la eficacia de la N-acetilcisteína y la bromhexina en comparación con la atención estándar en la prevención de la hospitalización de pacientes ambulatorios con COVID-19: un ensayo clínico aleatorizado doble ciego / Evaluation of the efficacy of N-acetylcysteine and bromhexine compared with standard care in preventing hospitalization of outpatients with COVID-19: a double blind randomized clinical trial

Introducción y objetivo Desde su aparición en diciembre de 2019, la enfermedad por coronavirus causada por el síndrome respiratorio agudo severo coronavirus2 se ha convertido en una emergencia mundial, propagándose rápidamente por todo el mundo. En respuesta a la derivación temprana de estos pacientes a centros de salud ambulatorios, decidimos buscar tratamientos más eficaces en las primeras etapas de su derivación. Este estudio tiene como objetivo prevenir tanto la progresión como el deterioro de las condiciones físicas de los pacientes con COVID-19, reducir la tasa de derivaciones y mitigar los riesgos de hospitalización y de muerte. Material y métodos Realizado en el Centro Terapéutico Dibaj, ciudad de Hamadan, Irán, un ensayo controlado aleatorizado doble ciego abarcó 225 pacientes con COVID-19 de abril a septiembre de 2022. Se obtuvo la aprobación ética de la Universidad de Ciencias Médicas de Hamadan (Aprobación n.° IR.UMSHA .REC.1400.957), con el protocolo registrado en el Registro Iraní de Ensayos Clínicos (Registro n.° IRCT20220302054167N1). Los pacientes cumplieron con el diagnóstico de COVID-19 a través de la presentación de síntomas y la confirmación por PCR, excluyendo aquellos con antecedentes de vacunas y afectación de órganos. Los pacientes con una saturación de oxígeno superior al 92% se asignaron a tres grupos: el grupoA recibió N-acetilcisteína, el grupoB recibió bromhexina y el grupoC recibió atención estándar. Los seguimientos de los niveles de oxígeno, los síntomas y las necesidades de hospitalización se realizaron los días7 y 14, con pacientes hospitalizados monitorizados durante un mes después de la hospitalización. Resultados El estudio encontró que tanto la N-acetilcisteína como la bromhexina pueden reducir efectivamente las tasas de hospitalización y la mortalidad y acortar la duración de la hospitalización... (AU)

Introduction and aim Since its emergence in December 2019, the coronavirus disease caused by the severe acute respiratory syndrome coronavirus2 has become a global emergency, spreading rapidly worldwide. In response to the early referral of these patients to outpatient health centers, we decided to seek more effective treatments in the early stages of their referral. This study aims to prevent both the progression and deterioration of the physical conditions of COVID-19 patients, reduce the rate of referrals, and mitigate the risks of hospitalization and death. Material and methods Conducted at Dibaj Therapeutic Center, Hamadan City, Iran, a double-blind randomized controlled trial encompassed 225 COVID-19 patients from April to September 2022. Ethical approval was obtained from Hamadan University of Medical Sciences (Approval No.: IR.UMSHA.REC.1400.957), with the protocol registered in the Iranian Registry of Clinical Trials (Registration No.: IRCT20220302054167N1). In this study, we included patients who tested positive for COVID-19 PCR and were symptomatic, excluding those who were pregnant or had received a COVID-19 vaccine. Patients with oxygen saturation above 92% were allocated to three groups: GroupA received N-acetylcysteine, GroupB received Bromhexine, and GroupC received standard care. Follow-ups on oxygen levels, symptoms, and hospitalization needs were conducted on days 7 and 14, with hospitalized patients monitored for one month post-hospitalization. Results The study found that both N-acetylcysteine and Bromhexine can effectively reduce hospitalization rates and mortality and shorten the duration of hospitalization. The third visit of patients who received N-acetylcysteine showed an increase of 1.33% in oxygen saturation compared to their first visit, and in patients who received Bromhexine, this increase was 1.19%. The mortality rate was 9.33% in the control group and zero in both groups of patients who received medication... (AU)

Ayush [Indian System of Medicines] Prophylaxis Against COVID-19: A Living Systematic Review and Meta-Analysis (Second Update).

Background: Ayush (Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy) system of medicine has been extensively used in India for the prevention and management of coronavirus disease 2019 (COVID-19). The present report is the second update of a living systematic review and meta-analysis and has been intended to assess the preventive potential and safety of Ayush drugs against COVID-19. Methods: A search of databases such as PubMed, the Cochrane central register of controlled trials, the World Health Organization (WHO) COVID-19 database, the clinical trial registry-India, the AYUSH research portal, and preprint repositories was performed till March 1, 2023. Randomized controlled trials or analytical observational studies were included. Incidences of COVID-19 infections and mortality were taken as primary outcome measures; and symptomatic severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection, incidences of hospital admissions, and adverse events were taken as secondary outcomes. The risk of bias was evaluated by version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB-2) and the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool. Data were synthesized through the RevMan 5.4 tool, and the certainty of the evidence was ranked through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Out of 2350 articles, 15 studies were included in the review. The pooled estimate of Guduchi [Tinospora cordifolia (Thunb.) Miers], Chyawanprasha, and Ayuraksha kit was obtained. Meta-analysis of the data suggested that Guduchi may reduce the incidences of COVID-19 infections (risk ratio [RR]: 0.67 [95% confidence interval, CI: 0.48-0.95]) and the symptom development among the infected (RR: 0.88 [95% CI: 0.73-1.08]), however, no change was observed in hospital admissions (RR: 0.96 [95% CI: 0.20-4.53]). It is uncertain that Chyawanprasha reduces the incidence of COVID-19 infection (RR: 0.28; [95% CI: 0.07-1.08]). Ayuraksha kit as chemoprophylaxis may reduce the incidences of COVID-19 infections (RR: 0.49; [95% CI: 0.32-0.77]). The certainty of the evidence was low to moderate mainly due to the serious risk of bias. Conclusion: Prophylactic use of Ayush medicines for populations at risk may help to prevent COVID-19 infection by reducing incidence and severity. However, considering the certainty and fewer studies, high-quality studies are still desired to confirm the efficacy and safety of Ayush chemoprophylaxis for COVID-19. Nevertheless, this update will serve as a torchbearer for policymakers, physicians, and other stakeholders for their decision-making through evidence-based medicine.

Integrated network pharmacology and experimental validation-based approach to reveal the underlying mechanisms and key material basis of Jinhua Qinggan granules against acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinhua Qinggan granules (JHQG), the traditional Chinese formula come into the market in 2016, has been proved clinically effective against coronavirus disease. Acute lung injury (ALI) is a major complication of respiratory infection such as coronavirus and influenza virus, with a high clinical fatality rate. Macrophage activation-induced inflammatory response plays a crucial role in the pathogenesis of ALI. However, the participation of inflammatory response in the efficacy of JHQG and its material basis against ALI is still unknown. AIM OF THE STUDY: The research aims to investigate the inflammatory response-involved efficacy of JHQG on ALI, explore the "ingredient-target-pathway" mechanisms, and searching for key material basis of JHQG by integrated network pharmacology and experimental validation-based approach. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-induced ALI mice was established to assess the protective impact of JHQG. Network pharmacology was utilized to identify potential targets of JHQG and investigate its action mechanisms related to inflammatory response in treating ALI. The therapeutic effect and mechanism of the primary active ingredient in JHQG was verified through high performance liquid chromatography (HPLC) and a combination of wet experiments. RESULTS: JHQG remarkably alleviated lung damage in mice model via suppressing macrophage activation, and inhibiting pro-inflammatory mediator level, p-ERK and p-STAT3 expression, TLR4/NF-κB activation. Network pharmacology combined with HPLC found luteolin is the main effective component of JHQG, and it could interact with TLR4/MD2 complex, further exerting the anti-inflammatory property and the protective role against ALI. CONCLUSIONS: In summary, our finding clarified the underlying mechanisms and material basis of JHQG therapy for ALI by integrated network pharmacology and experimental validation-based strategy.

Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).

BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov  id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.

Engineering a Holistic Response to the Global Crisis of Forced Displacement.

The global coronavirus pandemic has demonstrated the necessity of engineering approaches, from research and development to rapid prototyping and production, in saving lives all across the world [1]. From personal protective equipment design to vaccine production and distribution, engineering has been the bedrock of an effective global response. However, despite major gains made in the last several decades, there are still millions all across the world, including the vulnerable displaced, who rarely benefit from new developments at the interface of engineering, biology, and health.

Integrative transcriptomic and metabolomic analysis in mice reveals the mechanism by which ginseng stem-leaf saponins enhance mucosal immunity induced by a porcine epidemic diarrhea virus vaccination.

Porcine epidemic diarrhea virus (PEDV) is a main cause of severe enteric disease in piglets, leading to millions of dollars lost annually in the global pig industry. Parenteral vaccination is limited in generating sufficient mucosal immunity, which is crucial for early defense against PEDV. Here, we orally administered ginseng stem-leaf saponins (GSLS) to mice before parenteral vaccination and found that GSLS significantly enhanced the phagocytosis of dendritic cells, promoted the activities of CD4+ T cells and increased PEDV-specific IgA antibodies in the intestinal mucosa. Transcriptomic results showed that the altered genes following GSLS treatment were mostly related to the immune response and metabolism. In addition, integrated analysis of the transcriptome and metabolome revealed that the mechanism by which GSLS enhances mucosal immunity may be associated with progesterone-related pathways. Further studies are needed to explore the detailed molecular mechanisms.

Galdieria sulphuraria: An Extremophilic Alga as a Source of Antiviral Bioactive Compounds.

In the last decades, the interest in bioactive compounds derived from natural sources including bacteria, fungi, plants, and algae has significantly increased. It is well-known that aquatic or terrestrial organisms can produce, in special conditions, secondary metabolites with a wide range of biological properties, such as anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. In this study, we focused on the extremophilic microalga Galdieria sulphuraria as a possible producer of bioactive compounds with antiviral activity. The algal culture was subjected to organic extraction with acetone. The cytotoxicity effect of the extract was evaluated by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The antiviral activity was assessed through a plaque assay against herpesviruses and coronaviruses as enveloped viruses and poliovirus as a naked one. The monolayer was treated with different concentrations of extract, ranging from 1 µg/mL to 200 µg/mL, and infected with viruses. The algal extract displayed strong antiviral activity at non-toxic concentrations against all tested enveloped viruses, in particular in the virus pre-treatment against HSV-2 and HCoV-229E, with IC50 values of 1.7 µg/mL and IC90 of 1.8 µg/mL, respectively. However, no activity against the non-enveloped poliovirus has been detected. The inhibitory effect of the algal extract was confirmed by the quantitative RT-PCR of viral genes. Preliminary chemical profiling of the extract was performed using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS), revealing the enrichment in primary fatty acid amides (PFAA), such as oleamide, palmitamide, and pheophorbide A. These promising results pave the way for the further purification of the mixture to explore its potential role as an antiviral agent.

School-Based Telemedicine and Reduced Avoidable Emergency Care Among Rural Pediatric Patients.

Objective: Children living in rural communities have disparate access to preventive health care, shifting the burden of care delivery to emergency services. This study examined the association of school-based telemedicine (SBT) and avoidable emergency department (ED) utilization in rural historically underserved pediatric patients served through an SBT program. Methods: A retrospective analysis was conducted using electronic medical records and claims data from a large integrated health care system serving as the majority health care provider in the area. Participants included all pediatric patients served through an SBT program between 2017 and 2020 across three rural North Carolina counties. The study was a quasi-experimental before/after design comparing 12-month time periods before and after a patient's index virtual care visit. A subset of patients served 12 months before the start of the coronavirus 2019 (COVID-19) pandemic in 2020 was extracted and analyzed separately for a sensitivity analysis. Results: The complete sample included 1,236 patients. The odds of having an avoidable ED visit were reduced by 33% between time periods, and the estimated count of visits was reduced by 26%. (Models were adjusted for race/ethnicity, gender, age, and insurance payer.) No significant differences in unavoidable ED utilization were observed. The sensitivity analysis showed similar trends. Conclusions: Results demonstrate that telemedicine can improve access to health care and may offset the burden of avoidable care through emergency health services. Policy changes and increased use during the COVID-19 pandemic have created an optimal environment for telemedicine expansion to reduce health care access disparities.

Effect of oral vitamin A supplementation on host immune response to infectious bronchitis virus infection in specific pathogen-free chicken.

Vitamin A is a fat-soluble vitamin that is a crucial mediator of the immune system. In this study, we evaluated the effect of oral vitamin A supplementation on host immune responses to infectious bronchitis virus (IBV) infection in chickens. Forty 1-day-old specific pathogen-free (SPF) chickens were fed a basal diet and randomly divided into 2 groups (n = 20 birds per group). Chickens in the experimental group were treated orally with vitamin A (dissolved in 0.1 mL soybean oil, at a dose of 8,000 IU per kg diet) daily. Birds in the control group were orally administered 0.1 mL soybean oil without vitamin A until 21 d of age. On d 21 after birth, all chickens were infected with 0.1 mL of 106.5 50% median embryo infectious dose of a pathogenic IBV strain (CK/CH/LDL/091022) by intraocular and intranasal routes. The results demonstrated that oral vitamin A supplementation did not affect the clinical course of disease and growth performance of SPF chickens. However, vitamin A supplementation increased the IBV-specific IgG serum levels and decreased the viral load in some tissues of IBV-infected chickens. In addition, the results demonstrated that vitamin A supplementation decreased the expression levels of most immune-related molecules in some tissues of IBV-infected chickens. Vitamin A supplementation decreased the mRNA expression levels of some avian ß-defensins (AvBD2, 3, 6, 7, 11, and 13) and increased the expression levels of AvBD9 and AvBD12 in some tissues of IBV-infected chickens. Similarly, vitamin A supplementation decreased the mRNA expression levels of some cytokines (interferon-γ, interleukin-1ß [IL-1ß], and IL-6) and increased the mRNA expression levels of IL-2 in some tissues of IBV-infected chickens. Furthermore, vitamin A supplementation decreased the mRNA expression levels of myeloid differentiation primary response protein 88, nuclear factor-κB p65, toll-like receptor 3, toll-like receptor 7, and CD4. In summary, the present study suggests that vitamin A supplementation enhances the immune function of SPF chickens against IBV infection by inhibiting viral replication, increasing the IBV-specific antibody titer, and suppressing the excessive inflammatory responses to IBV infection.

ICU Nursing Team Mental Health in The Face of the COVID-19 Pandemic: An Integrative Review / Saúde mental da equipe de enfermagem intensivista ante a pandemia da covid-19: revisão integrativa / Salud mental de los profesionales de enfermería intensivistas ante la pandemia de la COVID-19: revisión integradora

Introduction: During the COVID-19 pandemic, health professionals were at an increased risk of developing psychological conditions, especially in Intensive Care Units. A gap is verified in the knowledge about ICU Nursing teams' mental health in the care provided to patients affected by COVID-19. Objective: To review the literature to identify the mental health conditions of ICU Nursing professionals during the COVID-19 pandemic. Materials and method: This is an integrative literature review with data collection from January to April 2022 in the Embase, Cumulative Index to Nursing and Allied Health Literature, PubMed, Scopus Content Overview and Web of Science databases. The following descriptors were listed: "Intensive Care Units," "COVID-19," "Mental Health," and "Nurse." The materials included were studies produced since 2020, available in full in the Spanish, English and Portuguese languages, and which answered the research question. Search and selection of the articles were the duty of two duly trained researchers, who worked independently through peer discussion. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations were followed. Results: From a sample of 16 articles, it was observed that the critical care of COVID-19 patients affected Nursing professionals' mental health with an emphasis on depression, anxiety, stress and fear. This was associated with a lack of evidence-based training, scarcity of human and physical resources, work overload and insufficient work experience. Conclusions: ICU Nursing professionals are mentally shaken; therefore, it is imperative to implement policies, strategies and methods to improve the psychological conditions of these professionals, to ensure the quality of services.

Introdução: durante a pandemia da covid-19, os profissionais de saúde apresentaram risco aumentado para o desenvolvimento de afecções psíquicas, especialmente na unidade de terapia intensiva. Verifica-se lacuna de conhecimento sobre a saúde mental da equipe de enfermagem intensivista no atendimento aos pacientes acometidos pela covid-19. Objetivo: identificar, na literatura científica, as condições da saúde mental do profissional de enfermagem intensivista durante a pandemia da covid-19. Materiais e método: esta é uma revisão integrativa da literatura; a coleta de dados ocorreu de janeiro a abril de 2022 nas fontes de dados Embase, Cumulative Index to Nursing and Allied Health Literature, PubMed, Scopus Content Overview e Web of Science. Elencaram-se os seguintes descritores: "Intensive Care Units", "Covid 19", "Mental Health", "Nurse". Incluíram-se estudos produzidos desde 2020, disponíveis na íntegra, em espanhol, inglês e português, e que respondessem à questão de pesquisa. A busca e seleção dos artigos foram executadas por dois pesquisadores treinados, de modo independente, mediante discussão por pares. As recomendações do Preferred Reporting Items for Systematic Reviews and Meta-Analyses foram seguidas. Resultados: a partir de uma amostra de 16 artigos, observou-se que o cuidado crítico de pacientes com covid-19 afetou a saúde mental dos profissionais de enfermagem com destaque para depressão, ansiedade, estresse e medo. Isso se associou à falta de tratamento baseado em evidências, à carência de recursos humanos e físicos, à sobrecarga de trabalho e às experiências de trabalho insuficientes. Conclusões: os profissionais de enfermagem intensivistas estão mentalmente abalados; portanto, é imperativa a implantação de políticas, estratégias e métodos para melhorar as condições psicológicas desses profissionais, para, assim, garantir a qualidade nos serviços.

Introducción: durante la pandemia de la covid-19, los profesionales de la salud han presentado riesgo aumentado para el desarrollo de afecciones psíquicas, especialmente en la unidad de terapia intensiva. Se encuentra vacío de conocimiento acerca de la salud mental de los profesionales de enfermería intensivistas en la atención a los pacientes acometidos por la covid-19. Objetivo: identificar, en la literatura científica, las condiciones de la salud mental del profesional de enfermería intensivista durante la pandemia de la covid-19. Materiales y método: se trata de una revisión integradora de la literatura; la recolección de datos ocurrió de enero a abril de 2022 en las fuentes de dados Embase, Cumulative Index to Nursing and Allied Health Literature, PubMed, Scopus Content Overview y Web of Science. Se han relacionado los siguientes descriptores: "Intensive Care Units", "Covid 19", "Mental Health", "Nurse". Se han incluido estudios producidos desde el 2020, disponibles de forma integral, en español, inglés y portugués, y que atendieran a la pregunta de investigación. La búsqueda y selección de los artículos se ejecutaron por dos investigadores capacitados, de modo independiente, mediante discusión por pares. Se siguieron las recomendaciones del Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Resultados: desde una amuestra de 16 artículos, se ha observado que la atención crítica a pacientes con covid-19 ha afectado la salud mental de los profesionales de enfermería con énfasis para depresión, ansiedad, estrés y miedo. Lo anterior se asocia a la falta de tratamiento basado en evidencia, la carencia de recursos humanos y físico, la sobrecarga de trabajo y las experiencias de trabajo insuficientes. Conclusiones: los profesionales de enfermería intensivistas están mentalmente debilitados; por lo tanto, urge la implantación de políticas, estrategias y métodos para mejorar las condiciones psicológicas de estos profesionales para, así, asegurar la calidad en los servicios.

Pinostrobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism.

Coronaviruses, as enveloped positive-strand RNA viruses, manipulate host lipid compositions to enable robust viral replication. Temporal modulation of the host lipid metabolism is a potential novel strategy against coronaviruses. Here, the dihydroxyflavone pinostrobin (PSB) was identified through bioassay that inhibited the increment of human coronavirus OC43 (HCoV-OC43) in human ileocecal colorectal adenocarcinoma cells. Lipid metabolomic studies showed that PSB interfered with linoleic acid and arachidonic acid metabolism pathways. PSB significantly decreased the level of 12, 13- epoxyoctadecenoic (12, 13-EpOME) and increased the level of prostaglandin E2. Interestingly, exogenous supplement of 12, 13-EpOME in HCoV-OC43-infected cells significantly stimulated HCoV-OC43 virus replication. Transcriptomic analyses showed that PSB is a negative modulator of aryl hydrocarbon receptor (AHR)/cytochrome P450 (CYP) 1A1signaling pathway and its antiviral effects can be counteracted by supplement of FICZ, a well-known AHR agonist. Integrative analyses of metabolomic and transcriptomic indicated that PSB could affect linoleic acid and arachidonic acid metabolism axis through AHR/CYP1A1 pathway. These results highlight the importance of the AHR/CYP1A1 pathway and lipid metabolism in the anti-coronavirus activity of the bioflavonoid PSB.

Identifying the Anti-MERS-CoV and Anti-HcoV-229E Potential Drugs from the Ginkgo biloba Leaves Extract and Its Eco-Friendly Synthesis of Silver Nanoparticles.

The present study aimed to estimate the antiviral activities of Ginkgo biloba (GB) leaves extract and eco-friendly free silver nanoparticles (Ag NPs) against the MERS-CoV (Middle East respiratory syndrome-coronavirus) and HCoV-229E (human coronavirus 229E), as well as isolation and identification of phytochemicals from GB. Different solvents and high-performance liquid chromatography (HPLC) were used to extract and identify flavonoids and phenolic compounds from GB leaves. The green, silver nanoparticle synthesis was synthesized from GB leaves aqueous extract and investigated for their possible effects as anti-coronaviruses MERS-CoV and HCoV-229E using MTT assay protocol. To verify the synthesis of Ag NPs, several techniques were employed, including X-ray diffraction (XRD), scan, transmission electron microscopy, FT-IR, and UV-visible spectroscopy. The highest contents of flavonoids and phenolic compounds were recorded for acetone, methanol, and ethanol as mixtures with water, in addition to pure water. HPLC flavonoids were detected as apegenin, luteolin, myricetin, and catechin, while HPLC phenolic compounds were pyrogallol, caffeic acid, gallic acid, and ellagic acid. In addition, our results revealed that Ag NPs were produced through the shift from yellow to dark brown. TEM examination of Ag NPs revealed spherical nanoparticles with mean sizes ranging from 5.46 to 19.40 nm and an average particle diameter of 11.81 nm. A UV-visible spectrophotometric investigation revealed an absorption peak at λ max of 441.56 nm. MTT protocol signified the use of GB leaves extract as an anti-coronavirus to be best from Ag NPs because GB extract had moderate anti-MERS-CoV with SI = 8.94, while had promising anti-HCov-229E, with an SI of 21.71. On the other hand, Ag NPs had a mild anti-MERS-CoV with SI = 4.23, and a moderate anti-HCoV-229E, with an SI of 7.51.

Mapa de evidências sobre sequelas e reablitação da covid-19 pós-aguda: uma versão atualizada em julho de 2022

[RESUMO]. Objetivo. Atualizar o mapa de evidências sobre os efeitos de intervenções para reabilitação de covid-19 pós-aguda. Métodos. O escopo da busca foi definido conforme a população (pacientes que tiveram covid-19 sintomática e sequelas da doença pós-aguda), o contexto (intervenções para recuperação das sequelas) e o tipo de estudo (revisão sistemática, revisão sistemática rápida, revisão de escopo ou revisão de revisões). Após a busca na PubMed e na Biblioteca Virtual em Saúde, dois autores independentes selecionaram estudos de revisão. A atualização do mapa feita em 27 de julho de 2022 seguiu os mesmos procedimentos descritos anteriormente. Resultados. O mapa inicial de evidências continha 22 estudos (quatro revisões sistemáticas, quatro revisões rápidas, quatro revisões de estudos de caso, uma revisão de escopo e nove protocolos de revisão sistemá- tica). Nesta atualização, outros 10 estudos foram incluídos. Foram identificados quatro grupos de intervenções (multimodal, terapêutica, terapias complementares e farmacológica) e sete grupos de desfechos (condições patológicas, doenças/transtornos respiratórios, dor, indicadores fisiológicos e metabólicos, saúde mental/ qualidade de vida, funções sensoriais, mortalidade), totalizando 166 associações entre intervenções e desfe- chos. As terapias complementares tiveram mais associações com os desfechos (n = 94). Entre os desfechos, destacaram-se os indicadores fisiológicos e metabólicos, as condições patológicas e a saúde mental/quali- dade de vida (44, 41 e 35 associações, respectivamente). Conclusões. Na atualização do mapa, analisaram-se 69 associações, com destaque para exercício (isolado, multicomponente ou intervenção multimodal, apresentando 23 efeitos positivos e quatro potencialmente posi- tivos) e intervenções farmacológicas e terapias complementares para funções sensoriais (15 associações). O alto número de protocolos indica que a literatura permanece incipiente.

[ABSTRACT]. Objective. To update the evidence map on the effects of interventions for post-acute COVID-19 rehabilitation. Method. The search scope was defined according to the population (patients with symptomatic COVID-19 and post-acute COVID sequelae), the context (interventions for rehabilitation), and the type of study (systema- tic reviews, rapid reviews, scoping reviews or overviews of reviews). Following a search in PubMed and the Virtual Health Library, two independent authors selected the articles for review. The map was updated on July 27, 2022, using the same procedures employed in the initial review. Results. The initial evidence map included 22 studies (four systematic reviews, four rapid reviews, four reviews of case reports, one scoping review, and nine systematic review protocols). In the present update, an addi- tional 10 studies were included. The analysis revealed four groups of interventions (multimodal, therapeutic, complementary, and pharmacological) and seven groups of outcomes (pathological conditions, diseases/ respiratory disorders, pain, physiological and metabolic markers, mental health/quality of life, sensory func- tion, and mortality), totaling 166 associations between interventions and outcomes. The highest number of associations was observed for complementary therapies (n = 94). Among the outcomes, the highest number of associations was observed for physiological and metabolic markers, pathological conditions, and mental health/quality of life (44, 41, and 35 associations respectively). Conclusions. The map update involved the analysis of 69 associations, most notably exercise (isolated, multicomponent, or multimodal intervention), with 23 positive and four potentially positive effects) and pharma- cologic and complementary therapies for sensorial functions (15 associations). The high number of systematic review protocols indicates that the literature is still incipient.

[RESUMEN]. Objetivo. Actualizar el mapa de evidencia de los efectos de las intervenciones de rehabilitación tras la COVID- 19 aguda. Métodos. El alcance de la búsqueda se definió en función de la población (pacientes que habían tenido COVID-19 sintomática y secuelas tras un cuadro agudo de la enfermedad), el contexto (intervenciones de recuperación de las secuelas) y el tipo de estudio (revisión sistemática, revisión sistemática rápida, revisión del alcance o revisión de revisiones). Después de realizar búsquedas en PubMed y en la Biblioteca Virtual de Salud, dos autores independientes seleccionaron los estudios de revisión. En la actualización del mapa realizada el 27 de julio del 2022 se siguieron los mismos procedimientos descritos anteriormente. Resultados. El mapa de evidencia inicial contenía 22 estudios (cuatro revisiones sistemáticas, cuatro revi- siones rápidas, cuatro revisiones de estudios de casos, una revisión del alcance y nueve protocolos de revisión sistemática). En esta actualización se incluyeron otros 10 estudios. Se encontraron cuatro grupos de intervenciones (multimodales y terapéuticas, y tratamientos complementarios y farmacológicos) y siete grupos de resultados (afecciones patológicas, enfermedades y trastornos respiratorios, dolor, indicadores fisiológicos y metabólicos, salud mental/calidad de vida, funciones sensoriales y mortalidad), con un total de 166 asociaciones entre las intervenciones y los resultados. Los tratamientos complementarios presentaron más asociaciones con los resultados (n = 94). Entre los resultados, se destacaron los indicadores fisiológi- cos y metabólicos, las afecciones patológicas y la salud mental/calidad de vida (44, 41 y 35 asociaciones, respectivamente). Conclusiones. En la actualización del mapa, se analizaron 69 asociaciones entre las cuales se destacan el ejercicio (aislado o compuesto o una intervención multimodal, con 23 efectos positivos y cuatro potencial- mente positivos) y las intervenciones farmacológicas y los tratamientos complementarios para las funciones sensoriales (15 asociaciones). El elevado número de protocolos indica que la bibliografía sigue siendo incipiente.

Risk factors for the population's mental health amidst the COVID-19 pandemic / Factores de riesgo para la salud mental de la población en medio de la pandemia de COVID-19 / Fatores de risco para a saúde mental da população em meio a pandemia de COVID-19

ABSTRACT Objective: To identify risk factors for mental health in the population in times of COVID-19 through the analysis of levels of socio-cognitive mindfulness and perception of stress in individuals. Method: This is a cross-sectional observational study with a quantitative approach, carried out through online data collection using the Perceived Stress Scale and the Langer Mindfulness Scale in a sample of 955 individuals from different regions of Brazil. Results: Women, younger people and individuals with low socioeconomic conditions had higher levels of perceived stress; on the other hand, older men and individuals with high socioeconomic status had higher levels of mindfulness. Conclusion: Socio-cognitive mindfulness was not a protective factor for perceived stress in the context of the COVID-19 pandemic.

RESUMEN Objetivo: Identificar factores de riesgo para la salud mental en la población en tiempos de COVID-19 a través del análisis de los niveles de mindfulness sociocognitivo y percepción de estrés en los individuos. Método: Se trata de un estudio observacional transversal con enfoque cuantitativo, realizado a través de la recolección de datos en línea utilizando la Escala de Estrés Percibido y la Escala de Mindfulness de Langer en una muestra de 955 individuos de diferentes regiones de Brasil. Resultados: Las mujeres, los jóvenes y las personas con condiciones socioeconómicas bajas presentaron mayores niveles de estrés percibido. Por el contrario, los hombres mayores y las personas con un nivel socioeconómico alto tenían niveles más altos de atención plena. Conclusión: El mindfulness sociocognitivo no fue un factor protector para el estrés percibido en el contexto de la pandemia de COVID-19.

RESUMO Objetivo: Identificar fatores de risco para a saúde mental na população em tempos de COVID-19 por meio da análise dos níveis atenção plena sociocognitiva e de percepção ao estresse nos indivíduos. Método: Trata-se de um estudo observacional do tipo transversal com abordagem quantitativa, realizado por meio de coleta de dados online utilizando a Escala de Estresse Percebido e a Escala de Atenção Plena de Langer em uma amostra de 955 indivíduos de diversas regiões do Brasil. Resultados: Mulheres, pessoas mais jovens e indivíduos com baixas condições socioeconômicas apresentaram maiores níveis de estresse percebido. Em contrapartida, os homens mais velhos e indivíduos com altas condições socioeconômicas apresentaram maiores níveis de atenção plena. Conclusão: A atenção plena sociocognitiva não se constituiu fator de proteção ao estresse percebido no contexto pandêmico da COVID-19.

Multifaceted Effects and Mechanisms of N-Acetylcysteine on Intestinal Injury in a Porcine Epidemic Diarrhea Virus-Infected Porcine Model.

SCOPE: This study investigates the potential effects of N-acetylcysteine (NAC) on intestinal injury in a porcine epidemic diarrhea virus (PEDV)-infected porcine model. METHODS AND RESULTS: Thirty-two piglets are randomly assigned to one of four groups: the control, PEDV, NAC, and NAC+PEDV. Piglets in the NAC+PEDV group are orally administrated with NAC (100 mg (kg·BW)-1  day-1 ) for 4 consecutive days after 2 days of PEDV infection. The results show that NAC administration decreases the diarrhea rate and improves intestinal morphology. The concentration of diamine oxidase and intestinal fatty-acid binding protein, as well as IL-1ß, IL-8, and TNF-α in the plasma, is decreased by NAC. Intriguingly, NAC administration significantly increases the viral load in the jejunum and ileum and down-regulates the expression of interferon-related genes. Microarray and proteomic analyses show that the differentially expressed genes/proteins between NAC+PEDV and PEDV groups are highly enriched in substance transport. Furthermore, aquaporin 8/10 expression is significantly increased by NAC upon PEDV infection. CONCLUSION: NAC administration alleviates PEDV-induced intestinal injury by inhibiting inflammatory responses and improving substance transport, but promotes viral replication by inhibiting interferon signaling. These results suggest NAC exhibits multifaceted effects upon PEDV infection, and thus caution is required when using NAC as a dietary supplement to prevent viral infection.

Isolation and Genetic Characterization of a Bovine Coronavirus KBR-1 Strain from Calf Feces in South Korea.

Bovine coronavirus (BCoV) causes severe diarrhea in neonatal calves, winter dysentery in adult cattle, and respiratory disease in feedlot cattle, resulting in economic losses. A total of 16/140 calf diarrheic feces samples collected in South Korea between 2017 and 2018 were positive for BCoV. Phylogenetic analysis of the complete spike and hemagglutinin/esterase genes revealed that the 16 Korean BCoV strains belonged to group GIIa along with Korean strains isolated after 2000, whereas Korean BCoV strains isolated before 2000 belonged to group GI. Mice and goats inoculated with an inactivated KBR-1 strain (isolated from this study) generated higher antibody titers (96 ± 13.49 and 73 ± 13.49, respectively) when mixed with the Montanide01 adjuvant than when mixed with the Carbopol or IMS1313 adjuvants. Viral antigens were detected in the large intestine, jejunum, and ileum of calves inoculated with inactivated KBR-1 vaccine (104.0 TCID50/mL) at 14 days of post-challenge (DPC). However, no viral antigens were detected in calves vaccinated with a higher dose of inactivated KBR-1 strain (106.0 TCID50/mL) at 14 DPC, and they had high antibody titers and stable diarrhea scores. Currently, the group GIIa is prevalent in cows in South Korea, and although further research is needed in the future, the recently isolated KBR-1 strain has potential value as a new vaccine candidate.

Comparative efficacy and safety of pharmacological interventions for severe COVID-19 patients: An updated network meta-analysis of 48 randomized controlled trials.

BACKGROUND: To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19. METHODS: We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs). RESULTS: We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients. CONCLUSION: This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study.