Archives of Medical Research最新文献

Maternal obesity predisposes offspring (F1) to cardiovascular disease. To evaluate basal heart function and ischemia-reperfusion (IR) responses in F1 males and females of obese mothers, female Wistar rats (F0) were fed chow or an obesogenic (MO) diet from weaning through pregnancy and lactation. Non-sibling F1 males and females were weaned to chow at postnatal day (PND) 21 and euthanized at PND 550. Offspring of MO mothers (MOF1) rarely survive beyond PND 650. Hearts were immediately isolated from euthanized F1s and subjected to 30 min ischemia with 20 min reperfusion. Retroperitoneal fat, serum triglycerides, glucose, insulin, and insulin resistance were measured. Baseline left ventricular developed pressure (LVDP) was lower in male and female MOF1 than in controls. After global ischemia, LVDP in control (C) male and female F1 recovered 78 and 83%, respectively, while recovery in MO male and female F1 was significantly lower at 28 and 52%, respectively. Following the IR challenge, MO hearts showed a higher functional susceptibility to reperfusion injury, resulting in lower cardiac reserve than controls in both sexes. Female hearts were more resistant to IR. Retroperitoneal fat was increased in male MOF1 vs. CF1. Circulating triglycerides and insulin resistance were increased in male and female MOF1 vs. CF1. These data show that MO programming reduces F1 cardiac reserve associated with age-related insulin resistance in a sex-specific manner.

Background

Cardiovascular disease (CVD) is one of the main causes of death and disability worldwide. The etiology of CVD is often associated with multiple risk factors, with environmental factors receiving considerable attention. Individuals with precarious jobs are among the groups most affected by chronic exposure to environmental pollutants.

Aim

This study aimed to evaluate occupational exposure to heavy metals among individuals in precarious job settings and investigate atherogenic indices as biomarkers of cardiovascular risk.

Methods

A total of 137 workers participated in this cross-sectional study conducted in three work environments in San Luis Potosi, Mexico. Urine and blood samples were collected to assess metal exposure and biochemical profiles, including atherogenic indices.

Results

The results showed that workers in the brick sector exhibited the highest levels of metal exposure, particularly arsenic (44.06 µg/L), followed by stonecutters and garbage collectors (24.7 and 16.9 µg/L, respectively). Similarly, Castelli risk index (CRI) and the atherogenic index of plasma (AIP) were higher in brickmakers (3.883 and 0.499) compared to stonecutters (3.285 and 0.386) and garbage collectors (3.329 and 0.367).

Conclusions

Evidence of exposure to heavy metals was observed in the three populations, in addition to the fact that individuals with greater exposure to arsenic also exhibited higher CRI and AIP.

Introduction

Uremic toxicity changes the gut structure and permeability, allowing bacterial toxins to translocate from the lumen to the blood during chronic kidney failure (CKD). Clinical fluid overload and tissue edema without uremia have similar effects but have not been adequately demonstrated and analyzed in CKD.

Aims

To investigate the effect of sodium intake on the plasma concentration of gut-derived uremic toxins, indoxyl sulfate (IS), and p-cresyl sulfate (pCS) and the expression of genes and proteins of epithelial gut tight junctions in a rat model of CKD.

Methods

Sham-operated (control group, CG) and five-sixths nephrectomized (5/6Nx) Sprague-Dawley rats were randomly assigned to low (LNa), normal (NNa), or high sodium (HNa) diets., Animals were then sacrificed at 8 and 12 weeks and analyzed for IS and pCS plasma concentrations, as well as for gene and protein expression of thigh junction proteins, and transmission electron microscopy (TEM) in colon fragments.

Results

The HNa 5/6Nx groups had higher concentrations of IS and pCS than CG, NNa, and LNa at eight and twelve weeks. Furthermore, HNa 5/6Nx groups had reduced expression of the claudin-4 gene and protein than CG, NNa, and LNa. HNa had reduced occludin gene expression compared to CG. Occludin protein expression was more reduced in HNa than in CG, NNa, and LNa. The gut epithelial tight junctions appear dilated in HNa compared to NNa and LNa in TEM.

Conclusion

Dietary sodium intake and fluid overload have a significant role in gut epithelial permeability in the CKD model.

Background

The relationship between GEMIN4 genetic variants and cancer, especially bladder carcinoma (BLCA), has been explored without conclusive results. This study aims to elucidate the link between GEMIN4 polymorphisms and BLCA susceptibility through genetic analyses, bioinformatics, and molecular dynamics (MD) simulations.

Methods

A cohort of 249 participants (121 BLCA patients and 128 unrelated controls) was enrolled. PCR was employed for allelic discrimination of GEMIN4 variants, followed by subgroup stratification, haplotype analyses, structural prediction using the AlphaFold2 prediction tool, subsequent MD simulations, structural analysis, and residue interaction mapping using Desmond, UCSF ChimeraX, and Cytoscape softwares.

Results

The rs.2740348*G variant demonstrated a protective role against BLCA in allelic (OR = 0.55, p = 0.002) and recessive (OR = 0.54, p = 0.017) models, whereas the rs.7813*T variant increased BLCA risk under the recessive model (OR = 1.90, p = 0.019). Haplotype analysis revealed a significant association between GEMIN4 haplotype (rs.2740348*C/rs.7813*T) with increased BLCA risk (OR = 2.01, p = 0.004). Univariate analysis revealed associations of the variants with albumin levels and absolute neutrophil count in BLCA patients. Pathogenicity evaluation categorized p.Gln450Glu as neutral and p.Arg1033Cys as deleterious. MD simulations revealed structural alterations and conformational shifts in the GEMIN4 protein induced by the Glu450 and Cys1033 mutations.

Conclusions

The study highlights the dual role of GEMIN4 variants in BLCA susceptibility, with rs.2740348 conferring protection and rs.7813 increasing risk. The Glu450 residue positively impacted protein stability, while Cys1033 had a detrimental effect on protein function. These findings underscore the significance of GEMIN4 variants in BLCA susceptibility and pave the way for future diagnostic and therapeutic initiatives.

Background and Aims

Vitamin D deficiency is a global health problem. The determinants of this deficiency have not been evaluated in developing countries such as Mexico. Thus, this study aimed to determine vitamin D intake and sun exposure and its relationship with plasma concentrations of 25-hydroxyvitamin D -25(OH)D- in young adults from Mexico City.

Methods

One hundred fifty five urban adult subjects were enrolled during 2017 and 2018. Sociodemographic, anthropometric, and clinical data, vitamin D intake, and sun exposure habits were collected. Plasma concentrations of 25(OH)D were also determined.

Results

The proportion of vitamin D deficiency was significantly higher in women than in men (65.7 vs. 43.4%, p = 0.012). The overall median dietary vitamin D intake was 112 IU/d (less than 20% of the recommended daily intake; RDI). 25-hydroxyvitamin D correlated directly with vitamin D intake, sun exposure score, waist-to-hip ratio, and age; an inverse significant association was found with body fat percentage. A multiple regression analysis was performed; simultaneous and significant (p <0.01) effects of sun exposure score, dietary vitamin D, the season of the year (spring-summer vs. fall-winter), and age were observed on 25(OH)D levels.

Conclusion

High rates of vitamin D deficiency and insufficiency were observed in young adults from Mexico City. According to the RDI of this vitamin, its consumption, assessed by a 24 h multi-step nutritional questionnaire, was significantly low. A linear multiple regression model identified several predictors of plasma 25(OH)D concentrations. This multiple regression model was statistically validated.

Background

Chagas disease and cutaneous leishmaniasis, two parasitic diseases caused by Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana), respectively, have a major global impact. Current pharmacological treatments for these diseases are limited and can cause severe side effects; thus, there is a need for new antiprotozoal drugs.

Methods

Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved drug library against Trypanosoma cruzi and Leishmania mexicana glycolytic enzyme triosephosphate isomerase (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested in vitro to confirm their biological activity.

Results

The study showed that five compounds: nilotinib, chlorhexidine, protriptyline, cyproheptadine, and montelukast, were more active against T. cruzi, than the reference drugs, nifurtimox and benznidazole while chlorhexidine and protriptyline were the most active against L. mexicana.

Conclusions

The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.

Background

SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability.

Aims

To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19.

Methods

A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded.

Results

Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died.

Conclusions

IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

Background

Retinopathy of prematurity (ROP) is a vasoproliferative disease of the retina that occurs in premature infants. The prevalence of ROP reported so far is inconsistent.

Aim

To conduct a systematic review to describe the trend of ROP prevalence between 1985 and 2021, and to determine the influence of countries’ economic conditions on ROP prevalence.

Methods

We searched PubMed, Embase, and Google Scholar for studies published between January 1985 and December 2021 using the following MeSH terms: “retinopathy of prematurity”, “ROP”, “incidence”, and “prevalence”. Two independent reviewers examined the articles to select studies that met the selection criteria and performed data extraction and study quality assessment. For the meta-analysis, the pooled prevalence was calculated using a random-effects model and R software.

Results

Of 5,250 titles and abstracts, 139 original studies met the inclusion criteria; a total of 121,618 premature infants were included in these studies. The pooled prevalence of ROP was 31.9% (95% confidence interval [CI] 29.0–34.8) and that of severe ROP was 7.5% (6.5–8.7). In general, no significant differences in prevalence were found over the four decades; however, we found a higher prevalence in premature infants ≤28 weeks of gestational age. In addition, the highest ROP prevalence was found in lower-middle-income countries with high mortality rates. In contrast, the highest severe ROP prevalence was found in high-income countries.

Conclusion

ROP remains a common cause of morbidity in premature infants worldwide. Therefore, it seems necessary to maintain early identification strategies for patients at higher risk, particularly in low- and middle-income countries.

Purpose

Analysis of four newborn screening modes using newborn genomic sequencing (nGS) and traditional biochemical screening (TBS).

Methods

Prospective clinical study with a total of 1,012 newborn samples from retrospective TBS. Three independent groups performed the study under strict double-blind conditions according to the screening modes: independent biochemical (IBS), independent NeoSeq (INS), sequential (SS), and combined (CS) screening. Using targeted sequencing, the NeoSeq panel included 154 pathogenic genes covering 86 diseases.

Results

Of the 1,012 newborns, 120 were diagnosed were diagnosed with genetic diseases Among them, 52 cases were within the scope of TBS and 68 additional cases were identified through nGS. The number of cases detected per screening mode was 50, 113, 56, and 119 for IBS, INS, SS, and CS, respectively. CS was the most satisfactory screening mode, with the detection rate of 99.17%, the specificity and positive predictive value of 100%, and the negative predictive value of 99.89%. In addition, of the 68 cases identified by nGS (96 variants in 31 pathogenic genes), only four participants (5.9%) had clinical manifestations consistent with the disease. The experimental reporting cycles of CS and INS were the shortest.

Conclusions

CS was the most satisfactory method for newborn screening, which combined nGS with TBS to improve early diagnosis.