Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).

Early choroidal and retinal changes detected by swept-source oct in type 2 diabetes and their association with diabetic kidney disease: a longitudinal prospective study.

BACKGROUND: To evaluate structural changes in retina and choroid in patients with type 2 diabetes (T2D) and their association with diabetic kidney disease (DKD). METHODS: T2D patients with mild or no diabetic retinopathy (DR) were followed for 3 years using structural SS-OCT and OCT angiography (OCT-A) taken every 6 months. Parameters were compared longitudinally and according to the DKD status on baseline. RESULTS: One hundred and sixty eyes from 80 patients were followed for 3 years, 72 with no DKD (nDKD) at baseline and 88 with DKD. Trend analysis of T2D showed significant thinning in GCL + and circumpapillary retinal fiber neural layer (cRFNL), choroid, and decreased vascular density (VD) in superficial plexus and central choriocapillaris with foveal avascular zone (FAZ) enlargement. Patients with no DKD on baseline presented more significant declines in retinal center and choroidal thickness, increased FAZ and loss of nasal and temporal choriocapillaris volume. In addition, the nDKD group had worse glycemic control and renal parameters at the end of the study. CONCLUSION: Our data suggests the potential existence of early and progressive neurovascular damage in the retina and choroid of patients with Type 2 Diabetes (T2D) who have either no or mild Diabetic Retinopathy (DR). The progression of neurovascular damage appears to be correlated with parameters related to glycemic control and renal damage.

Genomics reveals the role of admixture in the evolution of structure among sperm whale populations within the Mediterranean Sea.

In oceanic ecosystems, the nature of barriers to gene flow and the processes by which populations may become isolated are different from the terrestrial environment, and less well understood. In this study we investigate a highly mobile species (the sperm whale, Physeter macrocephalus) that is genetically differentiated between an open North Atlantic population and the populations in the Mediterranean Sea. We apply high-resolution single nucleotide polymorphism (SNP) analysis to study the nature of barriers to gene flow in this system, assessing the putative boundary into the Mediterranean (Strait of Gibraltar and Alboran Sea region), and including novel analyses on structuring among sperm whale populations within the Mediterranean basin. Our data support a recent founding of the Mediterranean population, around the time of the last glacial maximum, and show concerted historical demographic profiles in both the Atlantic and the Mediterranean. In each region there is evidence for a population decline around the time of the founder event. The largest decline was seen within the Mediterranean Sea where effective population size is substantially lower (especially in the eastern basin). While differentiation is strongest at the Atlantic/Mediterranean boundary, there is also weaker but significant differentiation between the eastern and western basins of the Mediterranean Sea. We propose, however, that the mechanisms are different. While post-founding gene flow was reduced between the Mediterranean and Atlantic populations, within the Mediterranean an important factor differentiating the basins is probably a greater degree of admixture between the western basin and the North Atlantic and some level of isolation between the western and eastern Mediterranean basins. Subdivision within the Mediterranean Sea exacerbates conservation concerns and will require consideration of what distinct impacts may affect populations in the two basins.

Acute Chagas disease associated with ingestion of contaminated food in Brazilian western Amazon.

OBJECTIVE: To describe clinical, epidemiological and management information on cases of acute Chagas disease (ACD) by oral transmission in the state of Amazonas in western Amazon. METHODS: Manual and electronic medical records of patients diagnosed with ACD at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) were included. RESULTS: There were 147 cases of acute CD registered from 10 outbreaks that occurred in the state of Amazonas between 2004 and 2022. The transmission pathway was through oral route, with probable contaminated palm fruit juice (açaí and/or papatuá), and involved people from the same family, friends or neighbours. Of 147 identified cases, 87 (59%) were males; cases were aged 10 months to 82 years. The most common symptom was the febrile syndrome (123/147; 91.8%); cardiac alterations were present in 33/100 (33%), (2/147; 1.4%) had severe ACD with meningoencephalitis, and 12 (8.2%) were asymptomatic. Most cases were diagnosed through thick blood smear (132/147; 89.8%), a few (14/147; 9.5%) were diagnosed by serology and (1/147; 0.7%) by polymerase chain reaction (PCR) and blood culture. In all these outbreaks, 74.1% of the patients were analysed by PCR, and Trypanosoma cruzi TcIV was detected in all of them. No deaths were recorded. The incidence of these foci coincided with the fruit harvest period in the state of Amazonas. CONCLUSION: The occurrence of ACD outbreaks in the Amazon affected individuals of both sexes, young adults, living in rural and peri-urban areas and related to the consumption of regional foods. Early diagnosis is an important factor in surveillance. There was a low frequency of cardiac alterations. Continuous follow-up of most patients was not carried out due to difficulty in getting to specialised centres; therefore, little is known about post-treatment.

Animal models of kidney iron overload and ferroptosis: a review of the literature.

In recent years, it has been identified that excess iron contributes to the development of various pathologies and their complications. Kidney diseases do not escape the toxic effects of iron, and ferroptosis is identified as a pathophysiological mechanism that could be a therapeutic target to avoid damage or progression of kidney disease. Ferroptosis is cell death associated with iron-dependent oxidative stress. To study the effects of iron overload (IOL) in the kidney, numerous animal models have been developed. The methodological differences between these models should reflect the IOL-generating mechanisms associated with human IOL diseases. A careful choice of animal model should be considered for translational purposes.

Pan-American Guidelines for the treatment of SARS-CoV-2/COVID-19: a joint evidence-based guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API).

BACKGROUND: Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population. METHODS: Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system. RESULTS: Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged. CONCLUSION: This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.

No evidence of inbreeding depression despite a historical severe bottleneck in the endangered Bermuda petrel (Pterodroma cahow).

The Bermuda petrel Pterodroma cahow is an island endemic seabird that belongs to the Procellariiformes, one of the most endangered orders of birds. Historical records suggest a significant population size decline following human settlement in Bermuda, bringing the species to near extinction. Since the 1950s, the population has been recovering aided by the implementation of an ongoing conservation plan. However, it still faces several threats, and negative genetic effects resulting from that drastic decline are to be expected, including inbreeding and genetic drift. We studied genetic diversity and levels of inbreeding, and their effects on individual fitness and mating choice. We also tested for a genetic signature of the recent demographic bottleneck. For this, we analyzed variation in thousands of nuclear single-nucleotide polymorphisms derived from double digest restriction site-associated DNA sequencing and 1 mitochondrial gene (cytochrome oxidase I). The results revealed that the Bermuda petrel suffered a recent genetic bottleneck and shows low mitochondrial diversity compared with other petrel species. Conversely, nuclear diversity was similar to that of other endangered petrels. Inbreeding levels were not high overall, although some individuals were highly inbred. However, we found no evidence that individual inbreeding or relatedness between mates affected hatching success, or that mate choice is influenced by kinship in this very small population.

Evaluation of the ratio of different major and trace elements in the lens of dogs with cataract.

BACKGROUND: Understanding the elements that support cataract development and searching for available therapeutic methods is essential for scientific and social interest. For that purpose, the role of trace elements has been investigated in this study to better understand the development of cataracts in dogs. OBJECTIVE: The aim of this study was to evaluate the ratio of the major and trace elements by X-ray fluorescence spectrometry in dog cataract lenses to contribute to diagnostic, non-surgical, and ophthalmological preventive data. METHODS: A single lens with a cataract from each of a total of 88 dogs (cataract group) and a healthy lens from each of 6 dogs (control group) were evaluated. The elements calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), magnesium (Mg), manganese (Mn), and potassium (K) were analyzed by energy dispersive X-ray fluorescence and X-ray microfluorescence. RESULTS: The results indicated an increase of Ca, Fe, Cu, and Zn, in association with the reabsorption mechanism of hypermature cataracts. CONCLUSIONS: The ratio of elements Ca, Fe, Cu, and Zn was different in cataract lenses than in healthy lenses, and our results may support the development of therapeutic strategies for cataracts in dogs. The Ca concentrations were distinct in the cataract development stages, and the Fe concentration was relatively higher in males when compared to females. Finally, this research stands out with a particular contribution to the understanding of both cataract formation and prevention.

Assessment of Genetic Damage Induced via Glyphosate and Three Commercial Formulations with Adjuvants in Human Blood Cells.

There is considerable controversy regarding the genotoxicity of glyphosate (N-(phosphonomethyl) glycine). It has been suggested that the genotoxicity of this herbicide is increased by the adjuvants added to commercial formulations based on glyphosate. The effect of various concentrations of glyphosate and three commercial glyphosate-based herbicides (GBH) on human lymphocytes was evaluated. Human blood cells were exposed to glyphosates of 0.1, 1, 10 and 50 mM as well as to equivalent concentrations of glyphosate on commercial formulations. Genetic damage (p < 0.05) was observed in all concentrations with glyphosate and with FAENA and TACKLE formulations. These two commercial formulations showed genotoxicity that was concentration-dependent but in a higher proportion compared to pure glyphosate only. Higher glyphosate concentrations increased the frequency and range of tail lengths of some migration groups, and the same was observed for FAENA and TACKLE, while in CENTELLA the migration range decreased but the frequency of migration groups increased. We show that pure glyphosate and commercial GBH (FAENA, TACKLE and CENTELLA) gave signals of genotoxicity in human blood samples in the comet assay. The genotoxicity increased in the formulations, indicating genotoxic activity also in the added adjuvants present in these products. The use of the MG parameter allowed us to detect a certain type of genetic damage associated with different formulations.

Impact of Sea Warming and 17-α-Ethinylestradiol Exposure on the Lipid Metabolism of Ruditapes philippinarum Clams.

This paper reports on an NMR metabolomics study of lipophilic extracts of Ruditapes philippinarum clams exposed to the hormonal contaminant 17-α-ethinylestradiol (EE2), at 17 °C and 21 °C. The results reveal that exposure at 17 °C triggers a weak response at low EE2 concentrations, suggestive of a slight increase in membrane rigidity, followed by lipid metabolic stability at higher EE2 concentrations. On the other hand, at 21 °C, lipid metabolism begins to respond at 125 ng/L EE2, with antioxidant docosahexaenoic acid (DHA) helping to tackle high-oxidative-stress conditions, in tandem with enhanced storage of triglycerides. Exposure to 625 ng/L EE2 (highest concentration) enhances phosphatidylcholine (PtdCho) and polyunsaturated fatty acid (PUFA) levels, their direct intercorrelation suggesting PUFA incorporation in new membrane phospholipids. This should lead to increased membrane fluidity, probably aided by a decrease in cholesterol. PUFA levels, considered a measure of membrane fluidity, were strongly (and positively) correlated to intracellular glycine levels, thus identifying glycine as the main osmolyte entering the cells under high stress. Membrane fluidity also seems to elicit the loss of taurine. This work contributes to the understanding of the mechanisms of response of R. philippinarum clams to EE2 in tandem with warming while unveiling novel potential markers of stress mitigation, namely high levels of PtdCho, PUFAs (or PtdCho/glycerophosphocholine and PtdCho/acetylcholine ratios) and linoleic acid and low PUFA/glycine ratios.

Exercise Induces an Augmented Skeletal Muscle Mitochondrial Unfolded Protein Response in a Mouse Model of Obesity Produced by a High-Fat Diet.

Increase in body fat contributes to loss of function and changes in skeletal muscle, accelerating sarcopenia, a phenomenon known as sarco-obesity or sarcopenic obesity. Studies suggest that obesity decreases the skeletal muscle (SM)'s ability to oxidize glucose, increases fatty acid oxidation and reactive oxygen species production, due to mitochondrial dysfunction. Exercise improves mitochondrial dysfunction in obesity; however, it is not known if exercise regulates the mitochondrial unfolded protein response (UPRmt) in the SM. Our study aimed to determine the mito-nuclear UPRmt in response to exercise in a model of obesity, and how this response is associated with the improvement in SM functioning after exercise training. C57BL/6 mice were fed a normal diet and high-fat diet (HFD) for 12 weeks. After 8 weeks, animals were subdivided into sedentary and exercised for the remaining 4 weeks. Grip strength and maximal velocity of mice submitted to HFD improved after training. Our results show an increase in the activation of UPRmt after exercise while in obese mice, proteostasis is basally decreased but shows a more pronounced increase with exercise. These results correlate with improvement in the circulating triglycerides, suggesting mitochondrial proteostasis could be protective and could be related to mitochondrial fuel utilization in SM.

Chemical Composition, Antioxidant Properties, and Antibacterial Activity of Essential Oils of Satureja macrostema (Moc. and Sessé ex Benth.) Briq.

Satureja macrostema is a plant that is located in various regions of Mexico and is used in a traditional way against illness. Essential oils (EOs) were obtained from leaves Satureja macrostema and the chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). The antioxidant effect of the oil was assayed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and by Trolox Equivalent Antioxidant Capacity (TEAC). In vitro antibacterial activity against Escherichia coli and Staphylococcus aureus was determined using a broth microdilution assay and thin layer chromatography-direct bioautography (TLC-DB) to identify active antibacterial compounds. The EOs analysis showed 21 compounds, 99% terpenes, and 96% oxygenated monoterpenes, with trans-piperitone epoxide (46%), cis-piperitone epoxide (22%), and piperitenone oxide (11%) as more abundant compounds. Likewise, S. macrostema EOs showed an antioxidant activity of DPPH = 82%, with 50% free radical scavenging (IC50) = 7 mg/mL and TEAC = 0.005, an antibacterial effect against E. coli of 73% inhibition, and 81% over S. aureus at dose of 100 µL of undiluted crude oil. The TLC-DB assay showed that the most active compounds were derived from piperitone. The comparison with other studies on S. macrostema shows variability in the compounds and their abundances, which can be attributed to climatic factors and the maturity of plants with similar antioxidant and antibacterial activities.

Antigenotoxic Effect of Ascorbic Acid and Resveratrol in Erythrocytes of Ambystoma mexicanum, Oreochromis niloticus and Human Lymphocytes Exposed to Glyphosate.

Glyphosate is a controversial herbicide. Its genotoxicity and presence in various ecosystems have been reported. The use of ascorbic acid and resveratrol could protect different organisms from glyphosate-induced genetic damage. In the present study, specific genetic damage induced by glyphosate was evaluated in erythrocytes of Oreochromis niloticus, Ambystoma mexicanum and human lymphocytes. Simultaneously, the antigenotoxic capacity of various concentrations of ascorbic acid and resveratrol was evaluated by means of pretreatment and simultaneous treatment protocols. The 0.03, 0.05 and 0.07 mM concentrations of glyphosate induced significant genotoxic activity (p < 0.05) in human lymphocytes and in erythrocytes of the species studied, and could cause genomic instability in these populations. The reduction in genetic damage observed in human lymphocytes exposed to high concentrations of glyphosate is only apparent: excessive genetic damage was associated with undetectable excessive tail migration length. A significant (p < 0.05) antigenotoxic effect of ascorbic acid and resveratrol was observed in all concentrations, organisms and protocols used. Both ascorbic acid and resveratrol play an important role in maintaining the integrity of DNA. Ascorbic acid in Oreochromis niloticus, Ambystoma mexicanum reduced glyphosate-induced genetic damage to a basal level. Therefore, our data indicate that these antioxidants could help preserve the integrity of the DNA of organisms exposed to glyphosate. The consumption of antioxidants is a useful tool against the genotoxicity of glyphosate.

Strong and lasting impacts of past global warming on baleen whales and their prey.

Global warming is affecting the population dynamics and trophic interactions across a wide range of ecosystems and habitats. Translating these real-time effects into their long-term consequences remains a challenge. The rapid and extreme warming period that occurred after the Last Glacial Maximum (LGM) during the Pleistocene-Holocene transition (7-12 thousand years ago) provides an opportunity to gain insights into the long-term responses of natural populations to periods with global warming. The effects of this post-LGM warming period have been assessed in many terrestrial taxa, whereas insights into the impacts of rapid global warming on marine taxa remain limited, especially for megafauna. In order to understand how large-scale climate fluctuations during the post-LGM affected baleen whales and their prey, we conducted an extensive, large-scale analysis of the long-term effects of the post-LGM warming on abundance and inter-ocean connectivity in eight baleen whale and seven prey (fish and invertebrates) species across the Southern and the North Atlantic Ocean; two ocean basins that differ in key oceanographic features. The analysis was based upon 7032 mitochondrial DNA sequences as well as genome-wide DNA sequence variation in 100 individuals. The estimated temporal changes in genetic diversity during the last 30,000 years indicated that most baleen whale populations underwent post-LGM expansions in both ocean basins. The increase in baleen whale abundance during the Holocene was associated with simultaneous changes in their prey and climate. Highly correlated, synchronized and exponential increases in abundance in both baleen whales and their prey in the Southern Ocean were indicative of a dramatic increase in ocean productivity. In contrast, the demographic fluctuations observed in baleen whales and their prey in the North Atlantic Ocean were subtle, varying across taxa and time. Perhaps most important was the observation that the ocean-wide expansions and decreases in abundance that were initiated by the post-LGM global warming, continued for millennia after global temperatures stabilized, reflecting persistent, long-lasting impacts of global warming on marine fauna.

Time-dependent evolution of IgG antibody levels after first and second dose of mRNA-based SARS-CoV-2 vaccination in haemodialysis patients: a multicentre study.

BACKGROUND: Vaccination programs are essential for the containment of the coronavirus disease 2019 pandemic, which has hit haemodialysis populations especially hard. Early reports suggest a reduced immunologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in dialysis patients, in spite of a high degree of seroconversion. We aimed to identify risk factors for a reduced efficacy of an mRNA vaccine in a cohort of haemodialysis patients. METHOD: In a multicentre study, including 294 Portuguese haemodialysis patients who had received two doses of BNT162b2 with a 3-week interval, immunoglobulin G-class antibodies against the SARS-CoV-2 spike protein were determined 3 weeks after the first dose (M1) and 6 weeks after the second dose (M2). The threshold for seroconversion was 10 UR/mL. Demographic and clinical data were retrieved from a quality registry. Adverse events were registered using a questionnaire. RESULTS: At M2, seroconversion was 93.1% with a median antibody level of 197.5 U/mL (1.2-3237.0) and a median increase of 180.0 U/mL (-82.9 to 2244.6) from M1. Age [beta -8.9; 95% confidence interval (95% CI) -12.88 to -4.91; P < 0.0001], ferritin >600 ng/mL (beta 183.93; 95% CI 74.75-293.10; P = 0.001) and physical activity (beta 265.79; 95% CI 30.7-500.88; P = 0.03) were independent predictors of SARS-CoV-2 antibody levels after two vaccine doses. Plasma albumin >3.5 g/dL independently predicted the increase of antibody levels between both doses (odds ratio 14.72; 95% CI 1.38 to 157.45; P = 0.03). Only mild adverse reactions were observed in 10.9% of patients. CONCLUSIONS: The SARS-CoV-2 vaccine BNT162b2 is safe and effective in haemodialysis patients. Besides age, iron status and nutrition are possible modifiable modulators of the immunologic response to SARS-CoV-2 mRNA vaccines. These data suggest the need for an early identification of populations at higher risk for diminished antibody production and the potential advantage of the implementation of oriented strategies to maximize the immune response to vaccination in these patients.

A Preliminary Comparison on Faecal Microbiomes of Free-Ranging Large Baleen (Balaenoptera musculus, B. physalus, B. borealis) and Toothed (Physeter macrocephalus) Whales.

Large baleen and toothed whales play crucial ecological roles in oceans; nonetheless, very little is known about their intestinal microbiomes. Based on striking differences in natural history and thus in feeding behaviours, it can be expected that intestinal microbiomes of large baleen whales and toothed whales are different. To test this hypothesis, the phylogenetic composition of faecal microbiomes was investigated by a 16S rRNA gene amplicon sequence-based approach for Bacteria and Archaea. Faecal samples from free-ranging large whales collected off the Azores Archipelago (Portugal) were used, comprising 13 individual baleen whales (one sei, two blue and ten fin whales) and four sperm whales. The phylogenetic composition of the Bacteria faecal microbiomes of baleen and toothed whales showed no significant differences at the phylum level. However, significant differences were detected at the family and genus levels. Most abundant phyla were Firmicutes, Bacteroidetes, Proteobacteria, Tenericutes and Spirochaeta. Few highly abundant bacterial genera were identified as key taxa with a high contribution to differences among baleen and toothed whales microbiomes. Only few archaeal sequences were detected, primarily Methanomassiliicoccales representing potential methanogenic Archaea. This is the first study that directly compares the faecal bacterial and archaeal microbiomes of free-ranging baleen and toothed whales which represent the two parvorders of Cetacea which members are fully aquatic large mammals which were evolutionary split millions of years ago.

Decreased survival in children inpatients with COVID-19 and antibiotic prescription.

BACKGROUND: The empirical prescription of antibiotics to inpatients with Coronavirus Disease 2019 (COVID-19) is frequent despite uncommon bacterial coinfections. Current knowledge of the effect of antibiotics on the survival of hospitalized children with COVID-19 is limited. OBJECTIVE: To characterize the survival experience of children with laboratory-positive COVID-19 in whom antibiotics were prescribed at hospital admission. METHODS: A retrospective cohort study was conducted in Mexico, with children hospitalized due to COVID-19 from March 2020 to December 2021. Data from 1601 patients were analyzed using the Kaplan-Meier method and the log-rank test. We computed hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the effect of the analyzed exposures on disease outcomes. RESULTS: Antibiotics were prescribed to 13.2% ([Formula: see text] = 211) of enrolled children and a higher mortality rate [14.9 (95% CI 10.1-19.8) vs. 8.3 (95% CI 6.8-9.8)] per 1000 person-days, [Formula: see text] < 0.001) was found among them. At any given cut-off, survival functions were lower in antibiotic-positive inpatients ([Formula: see text] < 0.001). In the multiple model, antibiotic prescription was associated with a 50% increase in the risk of fatal outcome (HR = 1.50, 95% CI 1.01-2.22). A longer interval between illness onset and healthcare-seeking and pneumonia at hospital admission was associated with a poorer prognosis. CONCLUSIONS: Our results suggest that antibiotic prescription in children hospitalized due to COVID-19 is associated with decreased survival. If later replicated, these findings highlight the need for rational antibiotics in these patients.

Capsaicin Decreases Kidney Iron Deposits and Increases Hepcidin Levels in Diabetic Rats with Iron Overload: A Preliminary Study.

Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg-1·day-1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.

COVID-19 Pneumonia in Fully Vaccinated Adults during the Dominance of the Omicron Sublineages BA.1.1 and BA.2 in Mexico.

Background and Objectives: A nationwide retrospective cohort study was conducted to evaluate the factors associated with the risk of laboratory-confirmed coronavirus disease 2019 (COVID-19)-related pneumonia in fully vaccinated adults during the dominance of the Omicron sublineages in Mexico. Materials and Methods: Fully COVID-19-vaccinated adults with laboratory-positive illness and symptom onset from April to mid-June 2022 were eligible. We computed the eta-squared (η2) to evaluate the effect size of the study sample. The characteristics predicting pneumonia were evaluated through risk ratios (RRs), and the 95% confidence intervals (CIs) were computed through generalized linear models. Results: The data from 35,561 participants were evaluated, and the overall risk of pneumonia was 0.5%. In multiple analyses, patients aged ≥ 60 years old were at increased risk of developing pneumonia (vs. 20−39 years old: RR = 1.031, 95% CI = 1.027−1.034). Chronic pulmonary obstructive disease, type 2 diabetes mellitus, arterial hypertension, chronic kidney disease (any stage), and immunosuppression (any cause) were also associated with a higher pneumonia risk. The η2 of all the variables included in the multiple models was <0.06. Conclusions: Our study suggests that, even when fully COVID-19-vaccinated, older adults and those with chronic conditions were at increased risk of pneumonia during the dominance of the Omicron sublineages BA.1.1 and BA.2.

Exploring Conflict of Interest in University Accreditation in Chile.

The university accreditation system in Chile appears to be influenced by tensions between interest groups from well-established institutions and newer (private) institutions. These institutions depend to a certain extent on accreditation decisions to obtain indirect public funding. However, the system relies on faculty nominated by conglomerates formed by these same institutions to decide on accreditation. This arrangement creates a potential conflict of interest that can jeopardize the accreditation's legitimacy. We explore this potential bias through an empirical study examining voting behaviour by commissioners of the Chilean National Commission of Accreditation from March 2013 to October 2016. We assess whether commissioners appeared as favouring institutions within their appointing conglomerates. To our knowledge, this is the first study in the region designed to examine the presence of bias in higher education accreditation. Findings indicate commissioners, on average, tended to favour institutions in their appointing conglomerates. We discuss the findings in the broader context of a forthcoming reform of the accreditation system.