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The methylenetetrahydrofolate reductase ( MTHFR ) gene 677C➔T polymorphism is capable of altering folate metabolism and can modify certain neoplasia risk. Reports have suggested that folate can have an influence on bone development and so it is of interest to know if the MTHFR 677C➔T polymorphism is associated with the malignant transformation process of this tissue. The polymorphism was determined in 55 patients with osteosarcoma and in 180 healthy individuals. Compared with C/T+C/C genotypes, a 3.7-fold reduction in osteosarcoma probability is possible with the T/T genotype (OR 0.27, CI 95% 0.07-0.82). Undoubtedly, further studies, utilizing large samples and carried out on different populations, are necessary to confirm these results.

Salvia officinalis (SO) is one of the most widely used plants in traditional medicine worldwide. In the present study, the effect of an ethanolic extract of S. officinalis leaves on hallmarks of cancer of HPV-16-positive cancer tumorigenic cells, TC-1, was analyzed in vitro. Phytochemical and spectroscopic analysis were performed. Additionally, the extract's flavonoid content, reducing iron, and antioxidant capacity were determined. In regard to the in vitro tests, the cytotoxic activity and its effect on the replicative capacity and on the cell migration of TC-1 cells were analyzed by viability and clonogenic, survival, and wound healing assays. The effect of a pre-treatment or treatment on 3D culture formation, growth, and reversion capacity was also examined. The results of the phytochemical analysis allowed the detection of tannins, saponins, steroids, and flavonoids. The flavonoids content was found to be 153.40 ± 10.68 µg/mg of extract. Additionally, the extract exhibited an antioxidant capacity and a ferric-reducing capacity of around 40% compared to the ascorbic acid. Thin layer chromatographic (TLC) analysis and spectroscopic tests showed the presence of compounds similar to quercetin and catechin flavonoids in the extract. In the in vitro assays, the SO extract induced in a concentration-dependent way changes in cell morphology, the decrease of cell viability, survival, and migration. At a concentration of 125 µg/mL, the extract inhibited spheroid formation, reduced their growth, and affected their reversion to 2D. Ethanolic extract of S. officinalis leaves had inhibitory effects on hallmarks of the cancer line HPV-16+. This suggests that the phytochemicals present in it may be a source of chemotherapeutics against cervical cancer.

The human papillomavirus (HPV) is a non-enveloped DNA virus transmitted through skin-to-skin contact that infects epithelial and mucosal tissue. It has over 200 known genotypes, classified by their pathogenicity as high-risk and low-risk categories. High-risk HPV genotypes are associated with the development of different types of cancers, including cervical cancer, which is a leading cause of mortality in women. In clinical practice and the market, the principal tests used to detect HPV are based on cytology, hybrid detection, and qPCR. However, these methodologies may not be ideal for the required timely diagnosis. Tests have been developed based on isothermal nucleic acid amplification tests (INAATs) as alternatives. These tests offer multiple advantages over the qPCR, such as not requiring specialized laboratories, highly trained personnel, or expensive equipment like thermocyclers. This review analyzes the different INAATs applied for the detection of HPV, considering the specific characteristics of each test, including the HPV genotypes, gene target, the limit of detection (LOD), detection methods, and detection time. Additionally, we discuss the tests available on the market that are approved by the Food and Drug Administration (FDA). Finally, we address the challenges and potential solutions for the large-scale implementation of INAATs, particularly in rural or underserved areas.

Background: COVID-19 is an infectious disease caused by SARS-CoV-2. It is unclear whether influenza vaccination reduces the severity of disease symptoms. Previous studies have suggested a beneficial effect of influenza vaccination on the severity of COVID-19. The aim of this study was to evaluate the possible protective effect of the influenza vaccine on the occurrence of SARS-CoV-2 infection symptoms and prognosis in patients hospitalized with COVID-19., Methods: This was a retrospective cohort study of patients who tested positive for SARS-CoV-2, identified by quantitative real-time polymerase chain reaction. Chi-square tests, Kaplan-Meier analysis, and multivariate analysis were performed to assess the association between influenza vaccination and the presence of symptoms in hospitalized patients with COVID-19 and their outcome., Results: In this study, 1712 patients received positive laboratory tests for SARS-CoV-2; influenza vaccination was a protective factor against the presence of characteristic COVID-19 symptoms such as polypnea, anosmia, dysgeusia, and fever ( p < 0.001). Influenza-vaccinated patients had fewer days of hospitalization ( p = 0.029)., Conclusions: The findings of this study support that influenza vaccination is associated with a decrease in the number of symptoms in patients hospitalized due to COVID-19, with fewer days of hospitalization, but not with the outcome of disease.

In the ongoing fight against Coronavirus Disease 2019 (COVID-19), researchers are exploring potential treatments to improve outcomes, especially in severe cases. This includes investigating the repurposing of existing medications, such as furosemide, which is widely available. This study aimed to evaluate the impact of furosemide on mortality rates among COVID-19 patients with severe or critical illness. We assessed a cohort of 515 hospitalized adults who experienced a high mortality rate of 43.9%. Using a multivariate analysis with adjusted risk ratios (AdRRs), factors like smoking (AdRR 2.48, 95% CI 1.53-4.01, p < 0.001), a high Pneumonia Severity Index (PSI) score (AdRR 7.89, 95% CI 5.82-10.70, p < 0.001), mechanical ventilation (AdRR 23.12, 95% CI 17.28-30.92, p < 0.001), neutrophilia (AdRR 2.12, 95% CI 1.52-2.95, p < 0.001), and an elevated neutrophil-to-lymphocyte ratio (NLR) (AdRR 2.39, 95% CI 1.72-3.32, p < 0.001) were found to increase mortality risk. In contrast, vaccination and furosemide use were associated with reduced mortality risk (AdRR 0.58, p = 0.001 and 0.60, p = 0.008; respectively). Furosemide showed a pronounced survival benefit in patients with less severe disease (PSI < 120) and those not on hemodialysis, with mortality rates significantly lower in furosemide users (3.7% vs. 25.7%). A Kaplan-Meier analysis confirmed longer survival and better oxygenation levels in patients treated with furosemide. Furthermore, a Structure-Activity Relationship analysis revealed that furosemide's sulfonamide groups may interact with cytokine sites such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), potentially explaining its beneficial effects in COVID-19 management. These findings suggest that furosemide could be a beneficial treatment option in certain COVID-19 patient groups, enhancing survival and improving oxygenation.

Objectives: To analyze the gene variants of the renin-angiotensin-aldosterone system and determine their association with the severity and outcome of COVID-19., Methods: A total of 104 patients were included in the study: 34 asymptomatic patients with COVID-19 as controls and 70 symptomatic patients as cases. The genetic variants ACE rs4343, ACE2 rs2074192, AGTR1 rs5182, and AGT rs4762 were identified using TaqMan genotyping tests., Results: Patients with the T/T genotype of AGTR1 rs5182 have a higher probability of developing symptomatic COVID-19 (odds ratio [OR] 12.25, 95% confidence interval [CI] 1.34-111.9, P ≤0.001) and a higher risk of hospitalization because of disease (OR 14.00, 95% CI 1.53-128.49, P = 0.012). The haplotype CTG (AGTR1 rs5182, ACE2 rs2074192, ACE rs4343) decreased the odds of death related to COVID-19 in the study population (OR 0.03, 95% CI 0.0-0.06, P = 0.026)., Conclusions: The T/T genotype of the AGTR1 rs5182 variant increased the probability of symptomatic COVID-19 and hospitalization, whereas the haplotype CTG (consisting of AGTR1 rs5182, ACE2 rs2074192, and ACE rs4343) decreased the odds of death related to COVID-19 by 97% in the hospitalized patients with COVID-19. These results support the participation of renin-angiotensin-aldosterone system gene variants as modifiers of the severity of symptoms associated with SARS-CoV-2 infection and the outcome of COVID-19., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Endometrial cancer (EC) is a significant cause of cancer-related deaths in women. MicroRNAs (miRs) play a role in cancer development, acting as oncogenes or tumor suppressors. This study evaluated the diagnostic potential of hsa-miR-185-5p and hsa-miR-191-5p in EC and their correlation with clinical and histopathological features. A cross-sectional study analyzed formalin-fixed, paraffin-embedded tissue samples from 59 patients: 18 with EC, 21 with endometrial hyperplasia (EH), 17 with normal endometrium (NE), and 3 with endometrial polyps (EPs). Quantitative reverse transcription-polymerase chain reaction and TaqMan probes were used for miR expression analysis. The Shapiro-Wilk test was used to analyze the normal distribution of the data. Subsequently, parametric or non-parametric tests were used to evaluate the associations between the expression levels of each miR and clinical parameters. Both miRs were underexpressed in some precursor and malignant lesions compared to certain NE subtypes and benign lesions. Specifically, hsa-miR-185-5p showed underexpression in grade 3 EC compared to some NE and EH subtypes (FC: -57.9 to -8.5, p < 0.05), and hsa-miR-191-5p was underexpressed in EH and EC compared to secretory endometrium and EPs (FC: -4.2 to -32.8, p < 0.05). SETD1B , TJP1 , and MSI1 were common predicted target genes. In conclusion, hsa-miR-185-5p and hsa-miR-191-5p are underexpressed in EC tissues, correlating with histopathological grades, highlighting their potential as diagnostic biomarkers and their role as tumor suppressors in EC.

Introduction: Cardiovascular risk factors such as obesity, type 2 diabetes, hypertension, smoking, and dyslipidemia enfold heart disease morbimortality. Diagonal earlobe crease has been proposed as a prognostic marker of extension and severity of illness in patients with acute coronary syndrome. But its usefulness remains unclear in patients with or without coronary disease., Methods: A case-control study was carried out on a total of 805 patients with and without cardiovascular risk factors or acute coronary syndrome. Univariate and multivariate binary logistic regression analyses were used to determine the probability of having diagonal earlobe crease with the presence of cardiovascular risk factors and acute coronary syndrome. Data were summarized as odds ratio with 95% confidence intervals and P values., Results: An unadjusted (univariate) analysis showed that being male, being older than 55 years, obesity, type 2 diabetes mellitus, arterial hypertension, smoking, and dyslipidemia, as well as having acute coronary syndrome, were associated with the presence of diagonal earlobe crease. The multivariate analysis showed that men (OR 1.6, 95% IC 1.1-2.4, P =0.007), being over 55 years old (OR 4.8, 95% IC 3.2-7.2, P < 0.001), being obese (OR 2.1, 95% IC 1.4-3.1, P < 0.001), having arterial hypertension (1.5, 95% IC 1.1-2.3, P =0.025), or suffering from acute coronary syndrome (OR 5.3, 95% IC 2.5-11.1, P < 0.001), were independent factors associated with diagonal earlobe crease. The rest of cardiovascular risk factors were not relevant in the multivariate model., Conclusions: In Mexican adults, having an acute coronary syndrome is not the only factor associated with diagonal earlobe crease but also being a man, older than 55 years, having high blood pressure and obesity. Diagonal earlobe crease may simply be caused by changes in the skin and connective tissues of the ears because of the aging process, obesity, and/or being male. These factors, by themselves, enfold cardiovascular risk due to well-known pathophysiological causes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Rogelio Molina-Gallardo et al.)

Vitamin D3 or calcitriol (VitD3) has been shown to have anticancer and anti-inflammatory activity in in vitro models and clinical studies. However, its effect on HPV-16-related cancer has been sparsely explored. In this study, we aimed to determine whether monotherapy or combination therapy with cisplatin (CP) reduces tumor growth and affects survival and systemic inflammation. Treatments were administered to C57BL/6 mice with HPV-16-related tumors (TC-1 cells) as follows: (1) placebo (100 µL vehicle, olive oil, orally administered daily); (2) VitD3 (3.75 µg/kg calcitriol orally administered daily); (3) CP (5 mg/kg intraperitoneally, every 7 days); and (4) VitD3+CP. Tumor growth was monitored for 25 days, survival for 60 days, and the neutrophil-to-lymphocyte ratio (NLR) was evaluated on days 1 (baseline), 7, and 14. VitD3+CP showed greater success in reducing tumor volume compared to CP monotherapy ( p = 0.041), while no differences were observed between CP and VitD3 monotherapy ( p = 0.671). Furthermore, VitD3+CP prolonged survival compared to CP ( p = 0.036) and VitD3 ( p = 0.007). Additionally, at day 14 the VitD3 and VitD3+CP groups showed significantly lower NLR values than the CP group ( p < 0.05, for both comparisons). Vitamin D3 could be a promising adjuvant in the treatment of cervical cancer or solid tumors and deserves further investigation.

Clinical data from hospital admissions are typically utilized to determine the prognostic capacity of Coronavirus disease 2019 (COVID-19) indices. However, as disease status and severity markers evolve over time, time-dependent receiver operating characteristic (ROC) curve analysis becomes more appropriate. The present analysis assessed predictive power for death at various time points throughout patient hospitalization. In a cohort study involving 515 hospitalized patients (General Hospital Number 1 of Mexican Social Security Institute, Colima, Mexico from February 2021 to December 2022) with COVID-19, seven severity indices [Pneumonia Severity Index (PSI) PaO 2 /FiO 2 arterial oxygen pressure/fraction of inspired oxygen (Kirby index), the Critical Illness Risk Score (COVID-GRAM), the National Early Warning Score 2 (NEWS-2), the quick Sequential Organ Failure Assessment score (qSOFA), the Fibrosis-4 index (FIB-4) and the Viral Pneumonia Mortality Score (MuLBSTA were evaluated using time-dependent ROC curves. Clinical data were collected at admission and at 2, 4, 6 and 8 days into hospitalization. The study calculated the area under the curve (AUC), sensitivity, specificity, and predictive values for each index at these time points. Mortality was 43.9%. Throughout all time points, NEWS-2 demonstrated the highest predictive power for mortality, as indicated by its AUC values. PSI and COVID-GRAM followed, with predictive power increasing as hospitalization duration progressed. Additionally, NEWS-2 exhibited the highest sensitivity (>96% in all periods) but showed low specificity, which increased from 22.9% at admission to 58.1% by day 8. PSI displayed good predictive capacity from admission to day 6 and excellent predictive power at day 8 and its sensitivity remained >80% throughout all periods, with moderate specificity (70.6-77.3%). COVID-GRAM demonstrated good predictive capacity across all periods, with high sensitivity (84.2-87.3%) but low-to-moderate specificity (61.5-67.6%). The qSOFA index initially had poor predictive power upon admission but improved after 4 days. FIB-4 had a statistically significant predictive capacity in all periods (P=0.001), but with limited clinical value (AUC, 0.639-0.698), and with low sensitivity and specificity. MuLBSTA and IKIRBY exhibited low predictive power at admission and no power after 6 days. In conclusion, in COVID-19 patients with high mortality rates, NEWS-2 and PSI consistently exhibited predictive power for death during hospital stay, with PSI demonstrating the best balance between sensitivity and specificity., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Mendoza-Hernandez et al.)

Between 2 and 8.5% of patients who recover from COVID-19 do not develop antibodies, and the durability of IgG antibodies is under scrutiny. Therefore, the presence and persistence of IgM and IgG antibodies were evaluated in a group of patients diagnosed with SARS-CoV-2 from May to August 2020. Out of 2199 suspected COVID-19 cases, 1264 were confirmed for SARS-CoV-2 by rRT-PCR; 328 consented to participate in the study, with 220 participants followed for 9 months, including 124 men (56%) and 96 women (44%). The primary symptoms were headache, dry cough, and fever. IgG antibodies developed in 95% of patients within 4 weeks post-diagnosis, and a second evaluation at 9 months showed that 72.7% still had detectable IgG antibodies. The presence of IgM in one individual (0.45%) suggested the possibility of reinfection.

Introduction: The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome., Methods: This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 ( RNASEL ), rs10774671 ( OAS1 ), rs1293767 ( OAS2 ), and rs2285932 ( OAS3 ) were screened and discriminated using a predesigned 5'-nuclease assay with TaqMan probes., Results: Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15-0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2-0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease ( p < 0.05)., Conclusions: Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes.

Moringa oleifera (MO) is a native tree of Asia and is cultivated in some areas of Mexico as part of traditional horticulture. The aim of the present study was to compare the efficacy of MO infusion vs. MO ethanolic extract for the simultaneous treatment of nonalcoholic fatty liver (NAFLD), hyperlipidemia, and hyperglycemia in a murine model fed with a high-fat diet (HFD). BALB/c mice were fed a balanced diet (healthy control) or an HFD for 6 months. With this, the NAFLD model was established before starting a therapeutic intervention with MO for two months. The phytochemical analysis by nuclear magnetic resonance in 1 H and 13 C experiments showed signals for pyrrole alkaloids and triterpenes as the main constituents of the extract and infusion preparation. A significant reduction of SGPT, SGOT, lipids, urea, and glucose in blood among NAFLD groups treated with MO (infusion or extract) was found, when compared to the NAFLD-placebo group. Steatosis and liver inflammation were found to be decreased in the MO groups, as infusion or ethanolic extract. Infusion produced a better therapeutic effect than the extract in all parameters, except glycemic control, where the extract was better. As an additional finding, it is noteworthy that treatment with MO, particularly through infusion, resulted in improved motor activity. Moreover, a reduction in anxiety-like behavior was observed exclusively with the administration of infusion. These observations provide valuable insights into the potential broader effects of Moringa oleifera beyond the primary aim of the study., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Salma I. Cortes-Alvarez et al.)

The COVID-19 pandemic has had a significant impact on the health and economy of the global population. Even after recovery from the disease, post-COVID-19 symptoms, such as pulmonary fibrosis, continue to be a concern. This narrative review aims to address pulmonary fibrosis (PF) from various perspectives, including the fibrotic mechanisms involved in idiopathic and COVID-19-induced pulmonary fibrosis. On the other hand, we also discuss the current therapeutic drugs in use, as well as those undergoing clinical or preclinical evaluation. Additionally, this article will address various biomarkers with usefulness for PF prediction, diagnosis, treatment, prognosis, and severity assessment in order to provide better treatment strategies for patients with this disease.

COVID-19 vaccines primarily prevent severe illnesses or hospitalization, but there is limited data on their impact during hospitalization for seriously ill patients. In a Mexican cohort with high COVID-19 mortality, a study assessed vaccination's effects. From 2021 to 2022, 462 patients with 4455 hospital days were analyzed. The generalized multivariate linear mixed model (GENLINMIXED) with binary logistic regression link, survival analysis and ROC curves were used to identify risk factors for death. The results showed that the vaccinated individuals were almost half as likely to die (adRR = 0.54, 95% CI = 0.30-0.97, p = 0.041). When stratifying by vaccine, the Pfizer group (BNT162b2) had a 2.4-times lower risk of death (adRR = 0.41, 95% CI = 0.2-0.8, p = 0.008), while the AstraZeneca group (ChAdOx1-S) group did not significantly differ from the non-vaccinated (adRR = 1.04, 95% CI = 0.5-2.3, p = 0.915). The Pfizer group exhibited a higher survival, the unvaccinated showed increasing mortality, and the AstraZeneca group remained intermediate ( p = 0.003, multigroup log-rank test). Additionally, BNT162b2-vaccinated individuals had lower values for markers, such as ferritin and D-dimer. Biochemical and hematological indicators suggested a protective effect of both types of vaccines, possibly linked to higher lymphocyte counts and lower platelet-to-lymphocyte ratio (PLR). It is imperative to highlight that these results reinforce the efficacy of COVID-19 vaccines. However, further studies are warranted for a comprehensive understanding of these findings.

The present study highlighted the repositioning of the drug dapsone (DDS) for cancer therapy. Due to its mechanism of action, DDS has a dual effect as an antibiotic and as an anti-inflammatory/immunomodulator; however, at high doses, it has important adverse effects. The derivative DDS-13 [N,N'-(sulfonyl bis (4,1-phenylene)) dioctanamide] was synthesized through an N-acylation reaction to compare it with DDS. Its cytotoxic effects in cancer cells (DU145 and HeLa) and non-cancer cells (HDFa) were observed at concentrations ranging 0.01-100 µM and its physicochemical/pharmacokinetic properties were analyzed using the SwissADME tool. The objectives of the present study were to evaluate the anticancer activity of both DDS and DDS-13 and to identify the physicochemical and pharmacokinetic properties of DDS-13. The results showed that DDS-13 presented a cytotoxic effect in the DU145 cell line (IC 50 =19.06 µM), while DDS showed a cytotoxic effect on both the DU145 (IC 50 =11.11 µM) and HeLa (IC 50 =13.07 µM) cell lines. DDS-13 appears to be a good cytotoxic candidate for the treatment of prostate cancer, while DDS appears to be a good candidate for both cervical and prostate cancer. Neither candidate showed a cytotoxic effect in non-cancerous cells. The different pharmacokinetic properties of DDS-13 make it a new candidate for evaluation in preclinical models for the treatment of cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Cabral-Pacheco et al.)

Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different ( p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22-0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17-0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population.

Purpose: This study aims to develop and evaluate a cost-effective, user-friendly multiplex quantitative real-time polymerase chain reaction (qPCR) method for detecting multiple tick-borne pathogens associated with human and veterinary diseases., Methods: In silico PCR was performed to design and evaluate primer sequences reported for amplifying Rickettsia spp., Borrelia spp., and Ehrlichia spp. Single and multiplex qPCR assays were then standardized to detect individual pathogens and multiple pathogens in a single reaction. Positive controls were generated to determine the dynamic range of the methods. In the validation phase, a total of 800 samples were screened for the presence of tick-borne pathogens., Results: Identification in a single qPCR reaction (multiplex) of Ehrlichia spp., and Borrelia spp. with a limit of detection of 10 copies and Rickettsia spp. with 100 copies, a PCR efficiency (E) of 90-100% and a coefficient of correlation (R 2 ) of 0.998-0.996 for all pathogens., Conclusion: The ability to detect three significant pathogens (Ehrlichia spp., Rickettsia spp., and Borrelia spp.) in a single qPCR reaction offers a significant advantage in the field of molecular diagnostics for tick-borne diseases. This advancement has a profound impact on public health as it facilitates the selection of appropriate treatment protocols, thereby reducing complications associated with disease progression. The streamlined approach provided by this method simplifies the diagnostic process and enables timely intervention, ultimately improving patient outcomes and mitigating the potential risks associated with untreated or misdiagnosed tick-borne infections., (© 2023. The Author(s).)

Acute lymphoblastic leukemia (ALL) is a hematological disease characterized by the dysfunction of the hematopoietic system that leads to arrest at a specific stage of stem cells development, suppressing the average production of cellular hematologic components. BCP-ALL is a neoplasm of the B-cell lineage progenitor. BCP-ALL is caused and perpetuated by several mechanisms that provide the disease with its tumor potential and genetic and cytological characteristics. These pathological features are used for diagnosis and the prognostication of BCP-ALL. However, most of these paraclinical tools can only be obtained by bone marrow aspiration, which, as it is an invasive study, can delay the diagnosis and follow-up of the disease, in addition to the anesthetic risk it entails for pediatric patients. For this reason, it is crucial to find noninvasive and accessible ways to supply information concerning diagnosis, prognosis, and the monitoring of the disease, such as circulating biomarkers. In oncology, a biomarker is any measurable indicator that demonstrates the presence of malignancy, tumoral behavior, prognosis, or responses to treatments. This review summarizes circulating molecules associated with BCP-ALL with potential diagnostic value, classificatory capacity during monitoring specific clinic features of the disease, and/or capacity to identify each BCP-ALL stage regarding its evolution and outcome of the patients with BCP-ALL. In the same way, we provide and classify biomarkers that may be used in further studies focused on clinical approaches or therapeutic target identification for BCP-ALL.

In developed countries, endometrial cancer (EC) is one of the most common neoplasms of the female reproductive system. MicroRNAs (miRs) are a class of single-stranded noncoding RNA molecules with lengths of 19-25 nucleotides that bind to target messenger RNA (mRNA) to regulate post-transcriptional gene expression. Although there is a large amount of research focused on identifying miRs with a diagnostic, prognostic, or response to treatment capacity in EC, these studies differ in terms of experimental methodology, types of samples used, selection criteria, and results obtained. Hence, there is a large amount of heterogeneous information that makes it difficult to identify potential miR biomarkers. We aimed to summarize the current knowledge on miRs that have been shown to be the most suitable potential markers for EC. We searched PubMed and Google Scholar without date restrictions or filters. We described 138 miRs with potential diagnostic, prognostic, or treatment response potential in EC. Seven diagnostic panels showed higher sensitivity and specificity for the diagnosis of EC than individual miRs. We further identified miRs up- or downregulated depending on the FIGO stage, precursor lesions, and staging after surgery, which provides insight into which miRs are expressed chronologically depending on the disease stage and/or that are modulated depending on the tumor grade based on histopathological evaluation.

The use of derivatives of natural and synthetic origin has gained attention because of their therapeutic effects against human diseases. Coumarins are one of the most common organic molecules and are used in medicine for their pharmacological and biological effects, such as anti-inflammatory, anticoagulant, antihypertensive, anticonvulsant, antioxidant, antimicrobial, and neuroprotective, among others. In addition, coumarin derivates can modulate signaling pathways that impact several cell processes. The objective of this review is to provide a narrative overview of the use of coumarin-derived compounds as potential therapeutic agents, as it has been shown that substituents on the basic core of coumarin have therapeutic effects against several human diseases and types of cancer, including breast, lung, colorectal, liver, and kidney cancer. In published studies, molecular docking has represented a powerful tool to evaluate and explain how these compounds selectively bind to proteins involved in various cellular processes, leading to specific interactions with a beneficial impact on human health. We also included studies that evaluated molecular interactions to identify potential biological targets with beneficial effects against human diseases.

Doxycycline (Doxy) is an antibiotic, which has exhibited anti-inflammatory activity and glucose metabolism improvement. The present study was proposed to evaluate its effects on glucose metabolism and other associated processes, such as lipemia and adipogenesis, as well as, to evaluate its effects on the liver, pancreas, and aorta in subjects fed with an occidental high-fat diet (HFD). The trial followed three groups of BALB/c mice for 6 months: (1) Standard diet (SD); (2) HFD-placebo (saline solution); and (3) HFD-Doxy (10 mg/kg/day). Intrahepatic fat accumulation (steatohepatosis) and the epididymal fat pad, as well as the hepatic inflammatory infiltrate and ALT serum levels were higher in both groups with the HFD (with/without doxycycline) in comparison with the SD group. The thickness of the aorta (preclinic atherosclerosis) was significantly elevated in the HFD group with respect to the HFD + Doxy and SD group, these two being similar groups to each other. The HFD-Doxy group had pancreatic morphological parameters very similar to those of the SD group; on the contrary, the HFD group reduced the number of pancreatic islets and the number of β cells per mm 2 , in addition to losing large islets. The index of β cell function (∆Insulin0-30/∆Glucose0-30 ratio) was significantly higher in the HFD + Doxy group, compared to the rest of the groups.

Background and Objectives : Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods : The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results : The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions : Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later.

Diabetes mellitus is a disease with no cure that can cause complications and even death. Moreover, over time, it will lead to chronic complications. Predictive models have been used to identify people with a tendency to develop diabetes mellitus. At the same time, there is limited information regarding the chronic complications of patients with diabetes. Our study is aimed at creating a machine-learning model that will be able to identify the risk factors of a diabetic patient developing chronic complications such as amputations, myocardial infarction, stroke, nephropathy, and retinopathy. The design is a national nested case-control study with 63,776 patients and 215 predictors with four years of data. Using an XGBoost model, the prediction of chronic complications has an AUC of 84%, and the model has identified the risk factors for chronic complications in patients with diabetes. According to the analysis, the most crucial risk factors based on SHAP values (Shapley additive explanations) are continued management, metformin treatment, age between 68 and 104 years, nutrition consultation, and treatment adherence. But we highlight two exciting findings. The first is a reaffirmation that high blood pressure figures across patients with diabetes without hypertension become a significant risk factor at diastolic > 70 mmHg (OR: 1.095, 95% CI: 1.078-1.113) or systolic > 120 mmHg (OR: 1.147, 95% CI: 1.124-1.171). Furthermore, people with diabetes with a BMI > 32 (overall obesity) (OR: 0.816, 95% CI: 0.8-0.833) have a statistically significant protective factor, which the paradox of obesity may explain. In conclusion, the results we have obtained show that artificial intelligence is a powerful and feasible tool to use for this type of study. However, we suggest that more studies be conducted to verify and elaborate upon our findings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Sergio A. Zaizar-Fregoso et al.)

Introduction: Ursus americanus Pallas 1780 is the largest carnivore and the only ursid in Mexico. It is considered an endangered species in the country because its distribution and population have been reduced by up to 80% because of habitat loss or furtive hunting. These problems can lead to a diet change, which could result in metabolic disorders, such as fatty acid β-oxidation defects or organic acid metabolism disorders. In our study, a free amino acid and acylcarnitine profile was characterized., Methods: Peripheral blood samples were drawn from nine free-ranging black bears in a period of five months, from June to October of 2019 in Northeastern Mexico, and 12 amino acids and 30 acylcarnitines were determined and quantified. Age differences were observed in the samples through ANOVA and post-hoc Tukey test., Results: Only three metabolites showed a significant difference with age: alanine (Ala) [cubs vs juvenile], free-carnitine (C0) [juvenile vs cubs] and acetylcarnitine (C2) [cubs vs adults and juvenile vs cubs]., Conclusion: Metabolites with variability due to age were identified, making them potential biomarkers to monitor metabolic status as early diagnosis in endangered species. This is the first study of black bear amino acid and acylcarnitine profiles, and the values found could be used as reference for free amino acid and acylcarnitine concentrations in further studies of the species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Abellan-Borja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The social distancing policies implemented by the health authorities during the COVID-19 pandemic in Mexico and elsewhere led to major changes in teaching strategies for college undergraduates. So far, there is limited data regarding the impact of the lockdown on the academic stress and mental health of these students., Objective: To assess the occurrence of academic difficulties, anxiety, depression, and academic stressors resulting in somatization with subsequent coping strategies linked to the pandemic., Materials and Methods: A cross-sectional study was conducted with 728 medical students (years 1-5). A purposely designed questionnaire to assess academic difficulties associated with the pandemic was administered electronically. The validated Goldberg anxiety and depression scale was also used, as well as the SISCO-II inventory on academic stress., Results: Screening for anxiety and depression led to a prevalence of 67.9 and 81.3%, respectively. Most relevant stressors, reported always or nearly always, included professors' evaluations (63.9%), and reading overload of academic papers (50.6%). Factorial analyses showed that women were more prone to stress than men ( p  < 0.001). Somatization symptomatology included drowsiness or increased need of sleep, anxiety, anguish, desperation, chronic fatigue, and sleep disorders. Common coping strategies included practicing a hobby, done always or nearly always by 65% of students with high stress, and 34% of those with low stress ( p  < 0.001)., Conclusion: There was a relevant impact of the mandatory lockdown during COVID-19 pandemic on the mental health of medical students reflected in the high prevalence rates of anxiety, depression, and stressors in the studied population pointing to the need for designing and implementing preventive strategies to deal with the effects of lockdowns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Avila-Carrasco, Díaz-Avila, Reyes-López, Monarrez-Espino, Garza-Veloz, Velasco-Elizondo, Vázquez-Reyes, Mauricio-González, Solís-Galván and Martinez-Fierro.)

Background: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID., Methods: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale., Results: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1-3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0-4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08-3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2-47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1-3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4-0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2-0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%)., Conclusions: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID.

The amniotic membrane (AM) is the inner part of the placenta. It has been used therapeutically for the last century. The biological proprieties of AM include immunomodulatory, anti-scarring, anti-microbial, pro or anti-angiogenic (surface dependent), and tissue growth promotion. Because of these, AM is a functional tissue for the treatment of different pathologies. The AM is today part of the treatment for various conditions such as wounds, ulcers, burns, adhesions, and skin injury, among others, with surgical resolution. This review focuses on the current surgical areas, including gynecology, plastic surgery, gastrointestinal, traumatology, neurosurgery, and ophthalmology, among others, that use AM as a therapeutic option to increase the success rate of surgical procedures. Currently there are articles describing the mechanisms of action of AM, some therapeutic implications and the use in surgeries of specific surgical areas, this prevents knowing the therapeutic response of AM when used in surgeries of different organs or tissues. Therefore, we described the use of AM in various surgical specialties along with the mechanisms of action, helping to improve the understanding of the therapeutic targets and achieving an adequate perspective of the surgical utility of AM with a particular emphasis on regenerative medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Munoz-Torres, Martínez-González, Lozano-Luján, Martínez-Vázquez, Velasco-Elizondo, Garza-Veloz and Martinez-Fierro.)

Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by periods of activity and remission. IBD includes Crohn's disease (CD) and ulcerative colitis (UC), and even though IBD has not been considered as a heritable disease, there are genetic variants associated with increased risk for the disease. 5-Hydroxytriptamine (5-HT), or serotonin, exerts a wide range of gastrointestinal effects under both normal and pathological conditions. Furthermore, Serotonin Transporter (SERT) coded by Solute Carrier Family 6 Member 4 ( SLC6A4 ) gene (located in the 17q11.1-q12 chromosome), possesses genetic variants, such as Serotonin Transporter Gene Variable Number Tandem Repeat in Intron 2 (STin2-VNTR) and Serotonin-Transporter-linked promoter region (5-HTTLPR), which have an influence over the functionality of SERT in the re-uptake and bioavailability of serotonin. The intestinal microbiota is a crucial actor in normal human gut physiology, exerting effects on serotonin, SERT function, and inflammatory processes. As a consequence of abnormal serotonin signaling and SERT function under these inflammatory processes, the use of selective serotonin re-uptake inhibitors (SSRIs) has been seen to improve disease activity and extraintestinal manifestations, such as depression and anxiety. The aim of this study is to integrate scientific data linking the intestinal microbiota as a regulator of gut serotonin signaling and re-uptake, as well as its role in the pathogenesis of IBD. We performed a narrative review, including a literature search in the PubMed database of both review and original articles (no date restriction), as well as information about the SLC6A4 gene and its genetic variants obtained from the Ensembl website. Scientific evidence from in vitro, in vivo, and clinical trials regarding the use of selective serotonin reuptake inhibitors as an adjuvant therapy in patients with IBD is also discussed. A total of 194 articles were used between reviews, in vivo, in vitro studies, and clinical trials.

The impact of the COVID-19 health crisis on the mental health of the population requires the implementation of new primary screening strategies of mental health disorders to intervene in a timelier manner, and technology may provide solutions. We aimed to evaluate the usefulness of the mobile app Mentali (version 1.1.2; creators: Jorge Alfonso Solís Galván Sodel Vázquez Reyes, Margarita de la Luz Martínez Fierro, Perla Velasco Elizondo, Idalia Garza Veloz, Alejandro Mauricio González and Claudia Caldera Villalobos, Zacatecas, México) as a primary screening tool for anxiety and depression disorders in medical students and to assess the triggering risk factors. This was a descriptive and longitudinal study and included 155 Mexican medical students. Participants interacted with Mentali for 6 months. The mobile app integrated the Beck anxiety and depression inventories together with a mood module. At the end of the interaction, the students received psychological and psychiatric interventions to confirm their primary diagnoses. Symptoms of moderate/severe anxiety and depression were present in 62.6% and 54.6% of the studied population. When corroborating the diagnoses, Mentali obtained a sensitivity of 100%, 95%, and 43% to classify a mental health disorder, anxiety, and depression, respectively. The most important triggers found were as follows: belonging to a dysfunctional family, being introverted, and having suffered from bullying. The proportion of users with excellent/good mood decreased from 78.7% to 34.4% at the end of the semester, and the proportion of users who claimed to have bad/very bad mood increased from 7.4% to 34.4% at the end of the semester (p < 0.05). Mentali was useful for identifying users with anxiety and/or depression, and as an auxiliary tool to coordinate the provision of specialized interventions, allowing us to increase the proportion of patients who needed psychological care and received it by 30%. The efficacy of Mentali in identifying activities through time with an impact on the mood and mental health of the users was confirmed. Our results support the use of Mentali for the primary screening of mental health disorders in young adults, including medical students.

Background: Some oral lesions have been described in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); the possibility has been raised that the buccal lesions observed in patients with the coronavirus disease 2019 (COVID-19) are due to this virus and the patient's systemic condition. The aim of this review was to integrate the knowledge related to the oral lesions associated with COVID-19 and the participation of the buccal cavity in the establishment of immunity against SARS-CoV-2., Methods: A literature search on the manifestations of buccal lesions from the beginning of the pandemic until October 2021 was carried out by using the PubMed database. A total of 157 scientific articles were selected from the library, which included case reports and reports of lesions appearing in patients with COVID-19., Results: Oral lesions included erosions, ulcers, vesicles, pustules, plaques, depapillated tongue, and pigmentations, among others. The oral cavity is a conducive environment for the interaction of SARS-CoV-2 with the mucosal immune system and target cells; direct effects of the virus in this cavity worsen the antiviral inflammatory response of underlying oral disorders, immunodeficiencies, and autoimmunity primarily., Conclusions: The oral cavity is an accessible and privileged environment for the interaction of SARS-CoV-2 with the mucosal immune system and target cells; the direct effects of the virus in this cavity worsen the antiviral inflammatory response of underlying oral disorders, in particular those related to immunodeficiencies and autoimmunity.

The abnormal implantation of the trophoblast during the first trimester of pregnancy precedes the appearance of the clinical manifestations of preeclampsia (PE), which is a hypertensive disorder of pregnancy. In a previous study, which was carried out in a murine model of PE that was induced by NG-nitro-L-arginine methyl ester (L-NAME), we observed that the intravenous administration of fibroblast growth factor 2 (FGF2) had a hypotensive effect, improved the placental weight gain and attenuated the fetal growth restriction, and the morphological findings that were induced by L-NAME in the evaluated tissues were less severe. In this study, we aimed to determine the effect of FGF2 administration on the placental gene expression of the vascular endothelial growth factor (VEGFA), VEGF receptor 2 (VEGFR2), placental growth factor, endoglin (ENG), superoxide dismutase 1 (SOD1), catalase (CAT), thioredoxin (TXN), tumor protein P53 (P53), BCL2 apoptosis regulator, Fas cell surface death receptor (FAS), and caspase 3, in a Sprague Dawley rat PE model, which was induced by L-NAME. The gene expression was determined by a real-time polymerase chain reaction using SYBR green. Taking the vehicle or the L-NAME group as a reference, there was an under expression of placental VEGFA, VEGFR2, ENG, P53, FAS, SOD1, CAT, and TXN genes in the group of L-NAME + FGF2 (p < 0.05). The administration of FGF2 in the murine PE-like model that was induced by L-NAME reduced the effects that were generated by proteinuria and the increased BP, as well as the response of the expression of genes that participate in angiogenesis, apoptosis, and OS. These results have generated valuable information regarding the identification of molecular targets for PE and provide new insights for understanding PE pathogenesis.

Rheumatoid arthritis is globally present in about 1% of the population. This autoinflammatory disease modifies the connective tissue, causing pain and inflammation of the joints. Over time, it causes the loss of joint cartilage and bone mass, decreasing the patient's quality of life. Treatment options now available either give symptomatic alleviation or alter the disease process. Nonetheless, adherence to chronic treatment is typically limited due to adverse effects. As a result, new therapy approaches, such as systemic administration of neutral electrolyzed saline to improve patients' quality of life, are being investigated. The study is a randomized prospective preclinical trial with a single-blind and a 4-arm parallel group using a collagen-induced mice model to generate rheumatoid arthritis. It was carried out on 36 male BALB/c mice, with the primary outcome measure being a scoring system for histopathologic assessment. When all groups are compared, there are significant differences. In addition, the animal model was validated by the healthy group. The animals treated with neutral electrolyzed saline had much less cartilage degradation, bone erosion, pannus development, and inflammation than the placebo-treated mice. Serum IL-6 levels were evaluated in parallel with disease severity expressed as synovitis grading of the affected joints. Spearman's rank correlation coefficient (Rs) = 0.399 ( P =0.016) between serum IL-6 levels and the synovitis grading suggests a direct correlation between IL-6 production and disease severity. An additional trial of 20 male BALB/c mice (10 treated with placebo and 10 with neutral electrolyzed saline for 30 days) showed no clinical nor histopathological evidence of adverse effects. According to histopathological and blood test results, we conclude that neutral electrolyzed saline minimizes mechanical and inflammatory damage to the joint and may be helpful as an alternative to rheumatoid arthritis therapy., Competing Interests: BPM and ACL declare that they have a commercial affiliation with Esteripharma. All other authors declare that they have no conflicts of interest., (Copyright © 2022 Sergio A Zaizar-Fregoso et al.)

Chronic hyperglycemia increases the risk of developing severe COVID-19 symptoms, but the related mechanisms are unclear. A mean glucose level upon hospital admission >166 mg/dl correlates positively with acute respiratory distress syndrome in patients with hyperglycemia. The objective of this study was to evaluate the relationship between sustained hyperglycemia and the outcome of hospitalized patients with severe COVID-19. We also evaluated the effect of high glucose concentrations on the expression of angiotensin-converting enzyme 2 (ACE2). We carried out a case-control study with hospitalized patients with severe COVID-19 with and without sustained hyperglycemia. In a second stage, we performed in vitro assays evaluating the effects of high glucose concentrations on ACE2 gene expression. Fifty hospitalized patients with severe COVID-19 were included, of which 28 (56%) died and 22 (44%) recovered. Patients who died due to COVID-19 and COVID-19 survivors had a high prevalence of hyperglycemia (96.4% versus 90.9%), with elevated central glucose upon admission (197.7 mg/dl versus 155.9 mg/dl, p = 0.089) and at discharge (185.2 mg/dl versus 134 mg/dl, p = 0.038). The mean hypoxemia level upon hospital admission was 81% in patients who died due to COVID-19 complications and 88% in patients who survived (p = 0.026); at the time of discharge, hypoxemia levels were also different between the groups (68% versus 92%, p ≤ 0.001). In vitro assays showed that the viability of A549 cells decreased (76.41%) as the glucose concentration increased, and the ACE2 gene was overexpressed 9.91-fold after 72 h (p ≤ 0.001). The relationship between hyperglycemia and COVID-19 in hospitalized patients with COVID-19 plays an important role in COVID-19-related complications and the outcome for these patients. In patients with chronic and/or sustained hyperglycemia, the upregulation of ACE2, and its potential glycation and malfunction, could be related to complications observed in patients with COVID-19.

SARS-CoV-2 is the etiological agent of COVID-19 and may evolve from asymptomatic disease to fatal outcomes. Real-time reverse-transcription polymerase chain reaction (RT-PCR) screening is the gold standard to diagnose severe accurate respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but this test is not 100% accurate, as false negatives can occur. We aimed to evaluate the potential false-negative results in hospitalized patients suspected of viral respiratory disease but with a negative previous SARS-CoV-2 RT-PCR and analyze variables that may increase the success of COVID-19 diagnosis in this group of patients. A total of 55 hospitalized patients suspected of viral respiratory disease but with a previous negative RT-PCR result for SARS-CoV-2 were included. All the participants had clinical findings related to COVID-19 and underwent a second SARS-CoV-2 RT-PCR. Chest-computed axial tomography (CT) was used as an auxiliary tool for COVID-19 diagnosis. After the second test, 36 patients (65.5%) were positive for SARS-CoV-2 (COVID-19 group), and 19 patients (34.5%) were negative (controls). There were differences between the groups in the platelet count and the levels of D-dimer, procalcitonin, and glucose (p < 0.05). Chest CT scans categorized as COVID-19 Reporting and Data System 5 (CO-RADS 5) were more frequent in the COVID-19 group than in the control group (91.7% vs. 52.6%; p = 0.003). CO-RADS 5 remained an independent predictor of COVID-19 diagnosis in a second SARS-CoV-2 screening (p = 0.013; odds ratio = 7.0, 95% confidence interval 1.5−32.7). In conclusion, chest CT classified as CO-RADS 5 was an independent predictor of a positive second SARS-CoV-2 RT-PCR, increasing the odds of COVID-19 diagnosis by seven times. Based on our results, in hospitalized patients with a chest CT classified as CO-RADS 5, a second SARS-CoV-2 RT-PCR test should be mandatory when the first one is negative. This approach could increase SARS-CoV-2 detection up to 65% and could allow for isolation and treatment, thus improving the patient outcome and avoiding further contagion.

Mefenamic acid is a non‑steroidal anti‑inflammatory drug exhibiting a wide range of anti‑inflammatory, antipyretic, analgesic and probable antiviral activities. The present study evaluated the efficacy of treatment with mefenamic acid combined with standard medical care vs. standard medical care plus a placebo in ambulatory patients with coronavirus disease 2019 (COVID‑19; nasal/oropharyngeal swabs reverse transcription‑PCR test results positive for severe acute respiratory syndrome coronavirus 2). The present study is a phase II prospective, two‑arm, parallel‑group, randomized, double‑blind placebo‑controlled clinical trial which analyzed 36 patients. Two aspects were evaluated during the 14‑day follow‑up period: i) The time for reaching a patient acceptable symptom state (PASS), and ii) the last day of each COVID‑19 symptom presentation. Adverse effects were evaluated. The clinical severity for all the patients in the study was mild (88.9%) and moderate (11.1%). The control (placebo) group achieved PASS on day 8.0±1.3, compared with day 4.4±0.8 in the mefenamic acid group (P=0.020, Kaplan‑Meier analyses using log‑rank tests). Patients that received mefenamic acid plus standard medical care had a ~16‑fold higher probability of achieving PASS on day 8 (adjusted RR, 15.57; 95% CI, 1.22‑198.71; P=0.035), compared with the placebo plus standard medical care group. All symptoms lasted for fewer days in the mefenamic acid group, compared with the placebo group; however, only the symptoms of headache (P=0.008), retro‑orbital eye pain (P=0.049), and sore throat (P=0.029) exhibited statistically significant differences. The experimental treatment produced no severe adverse effects. On the whole, the present study demonstrates that the administration of mefenamic acid markedly reduced the symptomatology and time to reach PASS in ambulatory patients with COVID‑19. Due to its probable antiviral effects and potent anti‑inflammatory mechanisms, mefenamic acid may prove to be useful in the treatment of COVID‑19, in combination with other drugs, including the new antivirals (remdesivir, molnupiravir, or favipiravir). However, future studies are also required to confirm these findings.

Background: The pandemic of COVID-19 has represented a major threat to global public health in the last century and therefore to identify predictors of mortality among COVID-19 hospitalized patients is widely justified. The aim of this study was to evaluate the possible usefulness of Charlson Comorbidity Index (CCI) as mortality predictor in patients hospitalized because COVID-19. Methods: This study was carried out in Zacatecas, Mexico, and it included 705 hospitalized patients with suspected of SARS-CoV-2 infection. Clinical data were collected, and the CCI score was calculated online using the calculator from the Sociedad Andaluza de Medicina Intensiva y Unidades Coronarias; the result was evaluated as mortality predictor among the patients with COVID-19. Results: 377 patients were positive for SARS-COV-2. Obesity increased the risk of intubation among the study population (odds ratio (OR) = 2.59; 95 CI: 1.36-4.92; p = 0.003). The CCI values were higher in patients who died because of COVID-19 complications than those observed in patients who survived ( p < 0.001). Considering a CCI cutoff > 31.69, the area under the ROC curve was 0.75, with a sensitivity and a specificity of 63.6% and 87.7%, respectively. Having a CCI value > 31.69 increased the odds of death by 12.5 times among the study population (95% CI: 7.3-21.4; p < 0.001). Conclusions: The CCI is a suitable tool for the prediction of mortality in patients hospitalized for COVID-19. The presence of comorbidities in hospitalized patients with COVID-19 reflected as CCI > 31.69 increased the risk of death among the study population, so it is important to take precautionary measures in patients due to their condition and their increased vulnerability to SARS-CoV-2 infection.

Introduction: Coronavirus disease 19 (COVID-19) has been a global public health emergency, with 209.89 million cases of infection with SARS-CoV-2 recorded, resulting in 4,401,675 deaths. After recuperation, it is probable that COVID-19 patients have sequelae of the disease. This study aimed to evaluate the respiratory anatomical-functional sequelae in Mexican patients who recovered from COVID-19., Methodology: This study included twenty-four patients who recovered from COVID-19 and eight non-infected patients (controls). Participants were screened for SARS-CoV-2 and the presence of IgM/IgG antibodies. Pulmonary function and lung anatomical abnormalities were evaluated by spirometry and computerized tomography., Results: A total of 45.8% of the patients had pulmonary function with obstructive patterns: 70.8% of recovered cases had COVID-19 Reporting and Data System (CO-RADS) 1, 20.8% CO-RADS 3 and 16.7% CO-RADS 4. A total of 35.3% of patients with CO-RADS 1 also showed bilateral nodal growth; 70.8% of patients tested positive for IgG and 8.4% for IgG/IgM, and 20.8% tested negative for both antibodies., Conclusions: There were respiratory anatomical and functional sequelae in Mexican patients who recovered from COVID-19, with a high occurrence of pulmonary obstructive patterns in the study population. These observations indicate the importance of the routine evaluation of sequelae in Mexican patients who recovered from COVID-19 and the need for strict follow-up to improve the quality of life of these patients., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Margarita de la Luz Martinez-Fierro, Jose Isaias Badillo-Almaraz, Jose Ramon Munoz-Torres, Griselda Aide Cabral Pacheco, Idalia Garza-Veloz, Edgar Fernando Gutierrez-Vela, Lucia Socorro Hernandez-Marquez, Lizbeth Areli Hernandez-Marquez, Alondra Daniela Torres-Gaytan, Juan Carlos Alvarez-Castro, Claudia Caldera-Villalobos, Ivan Delgado-Enciso, Iram Pablo Rodriguez-Sanchez, Oscar Gustavo Meza-Zavala, Yolanda Ortiz-Castro.)

Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vargas-Rodriguez, Garza-Veloz, Flores-Morales, Badillo-Almaraz, Rocha-Pizaña, Valdés-Aguayo and Martinez-Fierro.)

The increase of insecurity levels in Mexico, as well as the fact that violence is a frequent experience among health personnel, motivated this study whose purpose was to evaluate the perception of security and violence that social service medical interns (SSMI) had on the institutions and localities where they carried out their social work and make visible the main types of violence to which they were exposed. This was a cross-sectional study, based on a perception survey self-administered to 157 SSMI from Zacatecas, in Mexico. A high proportion of the participants (75.8%) stated that they were victims of violence, describing 134 incidents; however, only 33.6% of SSMI made an official report. The reported incidents were related to organized crime (31.9%), verbal violence (20.6%), violence by the authorities (14.7%) and sexual harassment (11.8%). One hundred percent of the victims of sexual harassment were women ( p = 0.039). According to the above, it is a priority to generate strategies to prevent and reduce the risk of exposure to the violence generated in the medical units and communities where SSMI carry out their activities as medical graduates, as well as, to efficiently process formal violence reports to promote a safe environment that favors the fulfillment of the practice of SSMIs in Mexico.

Introduction: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient's outcome., Methods: A total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene., Results: There were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/μl ± 0.30) and controls (3.3 ng/μl ± 0.16) ( p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild ( p = 0.005) and moderate ( p = 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/μl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/μl) were also observed ( p  = 0.037)., Conclusion: High levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Valdés-Aguayo, Garza-Veloz, Vargas-Rodríguez, Martinez-Vazquez, Avila-Carrasco, Bernal-Silva, González-Fuentes, Comas-García, Alvarado-Hernández, Centeno-Ramirez, Rodriguez-Sánchez, Delgado-Enciso and Martinez-Fierro.)

During phase 2 of the COVID-19 pandemic in a Mexican City, informal street vendors (cases) and formal employees (controls) were interviewed. A total of 82.6% of street vendors preferred to expose themselves to the coronavirus than to stop working, compared with 18.4% of formal employees (adjusted OR = 19.4, 95%CI: 4.6-81.7, p < 0.001). Street vendors had 7 times less fear of dying from coronavirus (adjusted OR = 0.14, 95% CI: 0.03-0.5, p = 0.005) and showed a 16-times greater lack of real concern for the increase in cases in their community than the formal employees (adjusted OR = 0.06, 95% CI: 0.01-0.3, p = 0.002). Street vendors were the group with the poorest adherence to household and work area containment measures that continued to be in contact with others. The corresponding authorities must plan specific strategies that allow street vendors to survive economically, while at the same time, protecting community health., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Josuel Delgado-Enciso, Marina Delgado-Machuca, Karen A Mokay-Ramirez, Carlos E Barajas-Saucedo, Jessica C Romero-Michel, Mercedes Fuentes-Murguia, Nomely S Aurelien-Cabezas, Daniel Tiburcio-Jimenez, Jose A Toscano-Velazquez, Carmen Meza-Robles, Alejandra E Hernandez-Rangel, Mireya Walle-Guillen, Osiris G Delgado-Enciso, Jose Guzman Esquivel, Fabian Rojas-Larios, Sergio A Zaizar-Fregoso, Margarita L Martinez-Fierro, Iram P Rodriguez Sanchez, Valery Melnikov, Francisco Espinoza-Gomez, Ivan Delgado-Enciso.)

The primary function of the skin is that of a physical barrier against the environment and diverse pathogens; therefore, its integrity is essential for survival. Skin regeneration depends on multiple stem cell compartments within the epidermis, which, despite their different transcriptional and proliferative capacity, as well as different anatomical location, fall under the general term of skin stem cells (SSCs). Skin wounds can normally heal without problem; however, some diseases or extensive damage may delay or prevent healing. Non-healing wounds represent a serious and life-threatening scenario that may require advanced therapeutic strategies. In this regard, increased focus has been directed at SSCs and their role in wound healing, although emerging therapeutical approaches are considering the use of other stem cells instead, such as mesenchymal stem cells (MSCs). Given its extensive and broad nature, this review supplies newcomers with an introduction to SSCs, wound healing, and therapeutic strategies for skin regeneration, thus familiarizing the reader with the subject in preparation for future in depth reading.

Background: The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies., Methods: This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans., Results: Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis., Conclusions: This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.

In the present study, the inhibitory effect of chlorogenic acid (CGA), a phenolic compound with potential antitumor effects, on circulating microRNA 31 (miR-31), was evaluated in RKO colon cancer cells. The capacity of gold nanoparticles (AuNPs) to enhance miR-31 quantification after treatment with CGA was assessed. RKO cells were treated with different concentrations of CGA for 24, 48 and 72 h, after which AuNPs coupled to CD81 were added to the supernatants. Total RNA was extracted, and miR-31 was quantified by reverse transcription-quantitative PCR. The results revealed an 85% decrease in miR-31 level following treatment with 1,000 µM CGA for 72 h, and the highest capacity to detect miR-31 (after treatment and isolation with AuNPs + CD81) was observed at 24 h. Furthermore, CGA decreased the expression of the miR-31 oncogene in an in vitro colon cancer model, and the use of AuNPs enhanced the levels of miRNA detection. The results suggest that miR-31 inhibition is one mechanism by which CGA decreases colon cancer cell proliferation. Moreover, AuNPs can increase the capacity of miR-31 quantification, representing a new strategy to develop non-invasive tools for the molecular diagnosis and monitoring of colon cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Luque-Badillo et al.)

Background and Objectives . The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion's membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions . While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.

Coronavirus disease 2019 (COVID-19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID-19. A prospective, 2-arm, parallel-group, randomized, open-label, multi-center, phase I-II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20-day follow-up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro-pharyngeal detection by reverse transcription-quantitative (RT-q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03-0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01-0.42, P=0.007) and also resulted in an 18-fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29-45.09, P<0.001), compared with usual medical care alone. Overall, neutral electrolyzed saline solution was better than usual medical care alone. Of the patients analyzed, >50% were negative for the virus as detected by RT-qPCR in naso/oro-pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C-reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone-cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID-19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX-COVID19: RPCEC00000309)., Competing Interests: BAPM and ACL declare that they work for the company Esteripharma, who provided the neutral electrolyzed saline administered in this trial. The company owns a patent for the synthesis of the electrolyzed saline, but had no role in the study design, data collection and analysis or decision to publish the manuscript. Those authors did not participate in the study design, data collection or data analyses. The other authors declare that they have no competing interests., (Copyright: © Delgado-Enciso et al.)