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.

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.

Symptomatic SARS-COV-2 reinfection: healthcare workers and immunosuppressed individuals at high risk.

BACKGROUND: Knowledge regarding factors predicting the SARS-COV-2 reinfection risk is scarce and it has major implications in public health policies. We aimed to identify factors associated with the risk of symptomatic SARS-COV-2 reinfection. METHODS: We conducted a nationwide retrospective cohort study and 99,993 confirmed cases of COVID-19 were analyzed. RESULTS: The overall risk of reinfection (28 or more elapsed days between both episodes onset) was 0.21% (incidence density, 2.5 reinfections per 100,000 person-days) and older subjects and those with the mild primary disease were at reduced risk of the event. Healthcare workers and immunosuppressed or renal patients had at greater risk of SARS-COV-2 reinfection. CONCLUSIONS: If replicated in other populations, these results may be useful to prioritize efforts focusing on the reduction of SARS-COV-2 spread and the related burden.

Effectiveness of BNT162b2 COVID-19 Vaccine in Preventing Severe Symptomatic Infection among Healthcare Workers.

Background and Objectives: This study aims to evaluate the effectiveness of the BNT162b2 COVID-19 (coronavirus disease 2019) in preventing severe symptomatic laboratory-confirmed infection among healthcare workers in a real-world scenario. Materials and Methods: A cross-sectional analysis of a prospective cohort study was conducted. Subjects with onset illness from January to February 2021 were eligible and classified according to the number of vaccine doses received (single-shot, n = 8; two-shot, n = 12; unvaccinated, n = 290). Results: The vaccine effectiveness against severe illness was 100% in the single and two-shot group. The presented results suggest that vaccination reduces the frequency of severe symptomatic COVID-19 in working-age adults. Conclusions: Efforts focusing on maximizing the number of immunized subjects in the study population may reduce associated economic and social burdens.

Performance of Antigen-Based Testing as Frontline Diagnosis of Symptomatic COVID-19.

Background and Objectives: To evaluate the performance of antigen-based detection tests as the frontline diagnosis of coronavirus disease 2019 (COVID-19). Materials and Methods: We conducted a nationwide retrospective cohort study in Mexico. A cross-sectional analysis of a cohort study was conducted in Mexico and data from 15,408 suspected (all of them symptomatic) cases of COVID-19 were analyzed. The results of antigen-based tests were compared with those obtained by molecular (polymerase chain reaction-based) assays. Results: The antigen-based tests showed sensitivity below 50% and high specificity in all the analyzed age groups. The highest Youden index (J) was observed among adults aged 25-44 years old (45.5, 95% CI 43.7-47.3). Conclusions: We documented the poor performance of serologic techniques as frontline diagnosis of symptomatic COVID-19 and inaccurate results may impact negatively on pandemic progression.

Male gender and kidney illness are associated with an increased risk of severe laboratory-confirmed coronavirus disease.

BACKGROUND: To identify factors predicting severe coronavirus disease 2019 (COVID-19) in adolescent and adult patients with laboratory-positive (quantitative reverse-transcription polymerase chain reaction) infection. METHOD: A retrospective cohort study took place, and data from 740 subjects, from all 32 states of Mexico, were analyzed. The association between the studied factors and severe (dyspnea requiring hospital admission) COVID-19 was evaluated through risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Severe illness was documented in 28% of participants. In multiple analysis, male gender (RR = 1.13, 95% CI 1.06-1.20), advanced age ([reference: 15-29 years old] 30-44, RR = 1.02, 95% CI 0.94-1.11; 45-59, RR = 1.26, 95% CI 1.15-1.38; 60 years or older, RR = 1.44, 95% CI 1.29-1.60), chronic kidney disease (RR = 1.31, 95% CI 1.04-1.64) and thoracic pain (RR = 1.16, 95% CI 1.10-1.24) were associated with an increased risk of severe disease. CONCLUSIONS: To the best of our knowledge, this is the first study evaluating predictors of COVID-19 severity in a large subset of the Latin-American population. Male gender and kidney illness were independently associated with the risk of severe COVID-19. These results may be useful for health care protocols for the early detection and management of patients that may benefit from opportune and specialized supportive medical treatment.

Type 2 Diabetes Alters Vascular Cannabinoid Receptor 1 Expression, Phosphorylation Status, and Vasorelaxation in Rat Aorta.

Previous studies have suggested a role of the endocannabinoid system in metabolic diseases, such as diabetes. We investigated the effect of diabetes on cannabinoid receptor type 1 (CB1) expression and cannabinoid-induced vasorelaxation in rat aorta rings. Aortas from healthy rats and from rats with experimentally induced diabetes were used to compare the vasorelaxant effect of the cannabinoid agonist arachidonylcyclopropylamide (ACPA) and CB1 expression and localization. After 4-8 weeks of diabetes induction, CB1 receptor expression and CB1 phosphorylation were higher in aortic rings, in association with greater vasorelaxation induced by the CB1 agonist ACPA compared to healthy rats. The vasorelaxant effect observed in healthy rats is similar throughout the study. Further studies are needed to elucidate the implications of CB1 receptor overexpression in diabetes and its influence on the progression of the cardiovascular complications of this metabolic disease.

Effects of Chronic Administration of Capsaicin on Biomarkers of Kidney Injury in Male Wistar Rats with Experimental Diabetes.

Capsaicin is an agonist of the transient receptor potential vanilloid type 1 (TRPV1) channel, which has been related to the pathophysiology of kidney disease secondary to diabetes. This study aimed to evaluate the chronic effect of capsaicin administration on biomarkers of kidney injury in an experimental rat model of diabetes. Male Wistar rats were assigned to four groups: (1) healthy controls without diabetes (CON), (2) healthy controls plus capsaicin at 1 mg/kg/day (CON + CAPS), (3) experimental diabetes without capsaicin (DM), and (4) experimental diabetes plus capsaicin at 1 mg/kg/day (DM + CAPS). For each group, 24-h urine samples were collected to determine diuresis, albumin, cystatin C, ß2 microglobulin, epidermal growth factor (EGF), alpha (1)-acid glycoprotein, and neutrophil gelatinase-associated lipocalin (NAG-L). Blood samples were drawn to measure fasting glucose. After 8 weeks, the CON + CAPS and DM + CAPS groups showed increased diuresis compared to the CON and DM groups, but the difference was significant only in the DM + CAPS group. The two-way ANOVA only showed a statistically significant effect of CAPS on the urinary EGF levels, as well as a tendency to have a significant effect in the urinary NAG-L levels. The EGF levels decreased in both CAPS-treated groups, but the change was only significant in the CON + CAPS group vs. CON group; and the NAG-L levels were lower in both CAPS-treated groups. These results show that capsaicin had a diuretic effect in healthy and diabetic rats; additionally, it increased the urinary EGF levels and tended to decrease the urinary NAG-L levels.

Effect of chronic administration of forskolin on glycemia and oxidative stress in rats with and without experimental diabetes.

Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8­OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant.

Metal concentrations and KIM-1 levels in school-aged children: a cross-sectional study.

Environmental exposure to heavy metals and metalloids, originating from sources such as mining and manufacturing activities, has been linked to adverse renal effects. This cross-sectional study assessed children's exposure to these elements and its association with urinary kidney injury molecule-1 (KIM-1). We analyzed data from 99 school-aged children residing in nine localities within the state of Colima, Mexico, during the latter half of 2023. Levels of 23 metals/metalloids and urinary KIM-1 were measured using inductively coupled plasma mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay, respectively. Detectable levels of these contaminants were found in over 91% of participants, with varied exposure profiles observed across locations ( p = 0.019). After adjusting for confounding factors like gender, age, and locality, higher levels of six metals/metalloids (boron, cadmium, cesium, lithium, selenium, zinc) were significantly associated with increased KIM-1 levels. Tailored mitigation efforts are crucial to protect children from regional pollutant burdens. However, limitations exist, as our study did not capture all potential factors influencing heavy metal/metalloid and KIM-1 levels.

Exploring Heavy Metal and Metalloid Exposure in Children: A Pilot Biomonitoring Study near a Sugarcane Mill.

Sugarcane production has been linked to the release of heavy metals and metalloids (HM/MTs) into the environment, raising concerns about potential health risks. This study aimed to assess the levels of 19 HM/MTs in children living near a sugarcane mill through a pilot biomonitoring investigation. We investigated sex-related differences in these element levels and their correlations. A cross-sectional study was conducted, analyzing data from 20 children in the latter part of 2023. Spearman correlation coefficients with 95% confidence intervals (CIs) were used to assess the relationships between urinary HM/MT levels. Detectable levels of 17 out of the 19 HM/MTs were found across the entire study sample, with arsenic and copper detectable in 95% of the children. Titanium exhibited higher levels in boys compared to girls (p = 0.017). We identified 56 statistically significant correlations, with 51 of them being positive, while the remaining coefficients indicated negative relationships. This study characterized HM/MT levels in school-aged children residing near a sugarcane mill through a pilot biomonitoring investigation. Further research employing larger sample sizes and longitudinal assessments would enhance our understanding of the dynamics and health impacts of HM/MT exposure in this vulnerable population.

Assessing the Relationship between Annual Surface Temperature Changes and the Burden of Dengue: Implications for Climate Change and Global Health Outcomes.

Dengue fever remains a significant global health concern, imposing a substantial burden on public health systems worldwide. Recent studies have suggested that climate change, specifically the increase in surface temperatures associated with global warming, may impact the transmission dynamics of dengue. This study aimed to assess the relationship between annual surface temperature changes from 1961 to 2019 and the burden of dengue in 185 countries. The dengue burden was evaluated for 2019 using disability-adjusted life years (DALYs) and the annual rate of change (ARC) in DALY rates assessed from 1990 to 2019. A cross-sectional and ecological analysis was conducted using two publicly available datasets. Regression coefficients (ß) and 95% confidence intervals (CI) were used to examine the relationship between annual surface temperature changes and the burden of dengue. The results revealed a significant negative relationship between mean surface temperatures and DALY rates in 2019 (ß = -16.9, 95% CI -26.9 to -6.8). Similarly, a significant negative relationship was observed between the temperature variable and the ARC (ß = -0.99, 95% CI -1.66 to -0.32). These findings suggest that as temperatures continue to rise, the burden of dengue may globally decrease. The ecology of the vector and variations in seasons, precipitation patterns, and humidity levels may partially contribute to this phenomenon. Our study contributes to the expanding body of evidence regarding the potential implications of climate change for dengue dynamics. It emphasizes the critical importance of addressing climate change as a determinant of global health outcomes.

Assessing the Burden of Dengue during the COVID-19 Pandemic in Mexico.

The transmission of the dengue virus in Mexico has historically been high, and its burden during the COVID-19 pandemic is currently not well understood. Our objective was to assess the burden of dengue-related disability-adjusted life years (DALYs) between 2020 and 2022. We conducted a cross-sectional analysis of databases resulting from an epidemiological surveillance of vector-borne diseases and computed DALYs using the protocol of the Global Burden of Disease (GBD) study 2019. Our results showed that there were 218,807 incident cases of dengue during the study period, resulting in 951 deaths. The calculated DALYs (and their 95% confidence intervals) were 8121 (7897-8396), 4733 (4661-4820), and 8461 (8344-8605) in 2020, 2021, and 2022, respectively. The DALY rates (per 100,000) were 6.5 (6.3-6.6), 3.8 (3.7-3.9), and 6.7 (6.6-6.8), respectively. The rates for 2020 and 2022 were similar to the historical mean (6.4, p = 0.884), whereas the rate for 2021 was lower than the mean. Premature mortality (years of life lost, YLL) contributed to 91% of the total burden. Our findings suggest that dengue fever remained a significant cause of disease burden during the COVID-19 pandemic, especially in terms of premature mortality.

Association between Vaccination Status for COVID-19 and the Risk of Severe Symptoms during the Endemic Phase of the Disease.

The global health emergency caused by COVID-19 concluded in May 2023, marking the beginning of an endemic phase. This study aimed to evaluate the association between vaccination status and other patient characteristics and the risk of severe disease during this new endemic period. A nationwide cohort study was conducted in Mexico, where we analyzed data from 646 adults who had received positive confirmation of COVID-19 through PCR testing from May to August 2023. The overall risk of severe symptoms in the study sample was 5.3%. The average time elapsed from the last vaccine shot to symptom onset was over six months in all the immunized groups (1, 2 or 3 vaccine doses). Compared to unvaccinated patients, those with three vaccine doses showed an elevated risk of severe symptoms. Advancing age and various chronic comorbidities (specifically cardiovascular, kidney, and obstructive pulmonary conditions) were associated with a heightened risk of severe COVID-19 manifestations. These findings underscore the ongoing seriousness of COVID-19, even in an endemic phase, underscoring the urgent need for tailored interventions aimed at high-risk patients.

Increased Frequency of Giant Miniature End-Plate Potentials at the Neuromuscular Junction in Diabetic Rats.

There is a need for research addressing the functional characteristics of the motor end-plate in diabetes to identify mechanisms contributing to neuromuscular dysfunction. Here, we investigated the effect of diabetes on spontaneous acetylcholine release in the rat neuromuscular junction. We studied two randomized groups of male Wistar rats (n = 7 per group, 350 ± 50 g, 12-16 weeks of age): one with streptozotocin-induced experimental diabetes, and a healthy control group without diabetes. After 8 weeks of monitoring after diabetes induction, rats in both groups were anesthetized with pentobarbital. Then, the diaphragm muscle was dissected for electrophysiological recordings of miniature end-plate potentials (MEPPs) using a single electrode located at the region of the muscle end-plate. All experiments were conducted at environmental temperature (20-22 °C) in rat Ringer solution with constant bubbling carbogen (95% O2, 5% CO2). Compared to healthy controls, in the diaphragm neuromuscular end-plate derived from diabetic rats, the MEPPs were higher in amplitude and frequency, and the proportion of giant MEPPs was elevated (7.09% vs. 1.4% in controls). Our results showed that diabetes affected the acetylcholine MEPP pattern and increased the number of giant potentials compared to healthy controls.

Predictors of Recurrent Laboratory-Confirmed Symptomatic SARS-CoV-2 Infections in a Cohort of Healthcare Workers.

BACKGROUND: Repeated SARS-CoV-2 infections are plausible and related published data are scarce. We aimed to identify factors associated with the risk of recurrent (three episodes) laboratory-confirmed symptomatic SARS-CoV-2 infections. METHODS: A retrospective cohort study was conducted, and 1,700 healthcare workers were enrolled. We used risk ratios (RR) and 95% confidence intervals (CI) to evaluate the factors associated with symptomatic SARS-CoV-2 infections. RESULTS: We identified 14 participants with recurrent illness episodes. Therefore, the incidence rate was 8.5 per 10,000 person months. In a multiple-model study, vaccinated adults (vs. unvaccinated, RR = 1.05 [1.03-1.06]) and those with a severe first illness episode (vs. mild disease, RR = 1.05 [1.01-1.10]) were at increased risk for repeated symptomatic SARS-CoV-2 reinfections. Increasing age showed a protective effect (per each additional year of age: RR = 0.98 [0.97-0.99]). CONCLUSIONS: Our results suggest that recurrent SARS-CoV-2 infections are rare events in adults, and they seem to be determined, partially, by vaccination status and age.

Assessing the relationship between energy-related methane emissions and the burden of cardiovascular diseases: a cross-sectional study of 73 countries.

The energy industry significantly contributes to anthropogenic methane emissions, which add to global warming and have been linked to an increased risk of cardiovascular diseases (CVD). This study aims to evaluate the relationship between energy-related methane emissions and the burden of CVD, measured in disability-adjusted life years (DALYs), in 2019. We conducted a cross-sectional analysis of datasets from 73 countries across all continents. The analyzed datasets included information from 2019 on environmental energy-related methane emissions, burden of DALYs due to CVD. The age-standardized prevalence of obesity in adults and life expectancy at birth were retrieved. The relationship between the variables of interest was evaluated using multiple linear regression models. In the multiple model, we observed a positive linear association between methane emissions and the log-transformed count of DALYs related to CVD. Specifically, for each unit increase in energy-related methane emissions, the burden of CVD increased by 0.06% (95% CI 0.03-0.09%, p < 0.001). The study suggests that reducing methane emissions from the energy industry could improve public health for those at risk of CVD. Policymakers can use these findings to develop strategies to reduce methane emissions and protect public health.

Survival Analysis and Contributing Factors among PCR-Confirmed Adult Inpatients during the Endemic Phase of COVID-19.

In May 2023, the global health emergency status of COVID-19 concluded, marking the onset of an endemic era. This study assessed survival rates among PCR-confirmed adult inpatients during this phase and determined contributing factors. Employing a survival analysis approach, this investigation utilized a nationwide Mexican cohort encompassing 152 adult inpatients. Survival rates were computed using the Kaplan-Meier method, and a proportional Cox model identified mortality risk factors. Survival rates remained above 65% on day 14 after admission. Vaccination status, including the number of doses administered, was not significantly associated with fatal outcomes. Chronic kidney disease or a history of immunosuppression (due to any cause) increased mortality risk. Our findings underscore the persistent severity of COVID-19 beyond the global health emergency, emphasizing the necessity for tailored interventions for vulnerable patients.