Association between mortality and cardiovascular diseases in the vulnerable Mexican population: A cross-sectional retrospective study of the COVID-19 pandemic.

Cardiovascular diseases (CVDs) continue to be the leading cause of death worldwide. Over the past couple of years and with the surge of the COVID-19 pandemic, mortality from CVDs has been slightly overshadowed by those due to COVID-19, although it was during the peak of the pandemic. In the present study, patients with CVDs (CVDs; n = 41,883) were analyzed to determine which comorbidities had the largest impact on overall patient mortality due to their association with both diseases (n = 3,637). Obesity, hypertension, and diabetes worsen health in patients diagnosed positive for COVID-19. Hence, they were included in the overview of all patients with CVD. Our findings showed that 1,697 deaths were attributable to diabetes (p < 0.001) and 987 deaths to obesity (p < 0.001). Lastly, 2,499 deaths were attributable to hypertension (p < 0.001). Using logistic regression modeling, we found that diabetes (OR: 1.744, p < 0.001) and hypertension (OR: 2.179, p < 0.001) significantly affected the mortality rate of patients. Hence, having a CVD diagnosis, with hypertension and/or diabetes, seems to increase the likelihood of complications, leading to death in patients diagnosed positive for COVID-19.

Determinants of COVID-19 Vaccine Hesitancy: A Cross-Sectional Study on a Mexican Population Using an Online Questionnaire (COV-AHQ).

Mexico has become one of the most highly affected countries by coronavirus disease 2019 (COVID-19) pandemic in Latin America. Therefore, efficient vaccination programs are needed to address COVID-19 pandemic. Although recent advances around the world have made it possible to develop vaccines in record time, there has been increasing fear and misinformation around the vaccines. Hence, understanding vaccine hesitancy is imperative for modeling successful vaccination strategies. In this study, we analyzed the attitude and perceptions toward COVID-19 vaccination, in a Mexican population (n = 1,512), using the proposed COVID-19 Vaccine Acceptance and Hesitancy Questionnaire (COV-AHQ) (Cronbach's alpha > 0.8), which evaluates a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, fear of adverse effects of COVID-19 vaccination, and hesitancy of parent toward vaccination of children; furthermore, a section including sociodemographic variables was included. According to the results of this study, the statistical correlation analysis of the general vaccination posture seems to correlate significantly (p < 0.05) with a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, hesitancy of parent toward vaccination of children, willingness to get COVID-19 vaccine, previous influenza vaccination, perception of the vaccine that could help the economy of country, occupation, gender, age, and participants actively researching COVID-19 vaccine information. An in-depth analysis assisted by binary logistic regression concluded that the young adult population around ages 18-34 years are the most likely to get vaccinated. This posture seems to be highly influenced by a mild perception of danger and contamination with respect to COVID-19, a moderate perception of xenophobia generated throughout COVID-19 quarantine, fear of adverse effects of COVID-19 vaccination, and hesitancy of parents toward vaccination of children. While their own personal religious beliefs and economic status, the level of education does not seem to have an effect on the willingness to get vaccinated neither did having a previous COVID-19 diagnosis or even knowing someone with a positive COVID-19 diagnosis. Health authorities and policymakers could use the results of this study to aid in modeling vaccination programs and strategies and identify population groups with high vaccine hesitancy prevalence and assess significant public health issues.

Risk Factors for SARS-CoV-2 Infection, Pneumonia, Intubation, and Death in Northeast Mexico.

Despite the social distancing and mobility restriction measures implemented for susceptible people around the world, infections and deaths due to COVID-19 continued to increase, even more so in the first months of 2021 in Mexico. Thus, it is necessary to find risk groups that can benefit from more aggressive preventive measures in a high-density population. This is a case-control study of suspected COVID-19 patients from Nuevo León, Mexico. Cases were: (1) COVID-19-positive patients and COVID-19-positive patients who (2) developed pneumonia, (3) were intubated and (4) died. Controls were: (1) COVID-19-negative patients, (2) COVID-19-positive patients without pneumonia, (3) non-intubated COVID-19-positive patients and (4) surviving COVID-19-positive patients. ≥ 18 years of age, not pregnant, were included. The pre-existing conditions analysed as risk factors were age (years), sex (male), diabetes mellitus, hypertension, chronic obstructive pulmonary disease, asthma, immunosuppression, obesity, cardiovascular disease, chronic kidney disease and smoking. The Mann-Whitney U tests, Chi square and binary logistic regression were used. A total of 56,715 suspected patients were analysed in Nuevo León, México, with 62.6% being positive for COVID-19 and, of those infected, 14% developed pneumonia, 2.9% were intubated and 8.1% died. The mean age of those infected was 44.7 years, while of those complicated it was around 60 years. Older age, male sex, diabetes, hypertension, and obesity were risk factors for infection, complications, and death from COVID-19. This study highlights the importance of timely recognition of the population exposed to pre-existing conditions to prioritise preventive measures against the virus.

Parent's Perspective towards Child COVID-19 Vaccination: An Online Cross-Sectional Study in Mexico.

COVID-19 vaccination programs continue in child populations. Thus, parents' attitude towards COVID-19 vaccination of their children is crucial for these strategies to succeed. The present study derives from the application of an online COVID-19 Vaccine Acceptance & Hesitancy Questionnaire (COV-AHQ) in which we measure parent's hesitancy towards children's vaccination (section 4 of the COV-AHQ) and other significant factors. A logistic regression analysis with backward stepwise method was used to quantify the associations between factors and parent's hesitancy. According to the correlation analysis, the most representative factors predicting vaccine hesitancy/acceptance were positive attitude towards vaccination, parents believing that the COVID-19 vaccine will enhance the economic situation of the country, parents actively researching information, having the willingness to obtain the COVID-19 vaccine themselves, and the possibility of their children developing adverse effects. Our findings also showed that parents are highly interested in having their children vaccinated. Nonetheless, parents expressed high levels of concern involving their children in developing adverse effects from the vaccine. In addition, obtaining influenza immunization prompted interest in obtaining the COVID-19 vaccine, and younger-aged parents are much more concerned with having their children vaccinated. Therefore, in order to ensure successful vaccination programs, policymakers and health authorities should design strategies to gain confidence and provide security amongst the population, including giving continuous information about the benefits of vaccination and presenting the frequency of side effects to bring parents on board with vaccinating their children.

Latent tuberculosis in migrants travelling through the northeast regions of Mexico.

BACKGROUND: Latent tuberculosis infection (LTBI) affects nearly a quarter of the global population. Public health interventions aimed at interrupting tuberculosis transmission do not routinely include systematic screening of migrant populations for LTBI in Mexico, nor other high-income countries. However, early detection and treatment of LTBI in immigrant populations from high-burden countries are recommended by the World Health Organization. OBJECTIVE: The objective of this study was to determine the proportion of migrants with LTBI in shelters in northeastern Mexico. METHODS: In this cross-sectional study, blood samples were obtained from 455 migrants living in shelters in northeastern Mexico during January 2017 to October 2019. LTBI was diagnosed using the QuantiFERON®-TB Gold Plus test. RESULTS: Most of the migrants evaluated in this study were from Honduras; ∼86% were male; the average age was 29 ±â€¯10 years. LTBI was identified in 18.4% of those from Central America. Migrants from El Salvador and Nicaragua were more likely to have LTBI than those from Honduras or Guatemala. Overweight or obese persons and older persons had a higher prevalence of LTBI. We detected no significant differences with respect to LTBI when the results were compared based on gender, education, or marital status. CONCLUSION: The LTBI rates amongst migrants from Central America recently screened in shelters in northeastern Mexico appears to be relatively low given recent estimates of LTBI prevalence in Mexico.

Spontaneous Bone Regeneration After Large Craniectomy in Pediatric Patient.

BACKGROUND: In children, decompressive craniectomy is commonly performed in cases of increased intracranial pressure that is not medically managed. Currently, it is standard practice to perform cranioplasty after decompressive craniectomy, although optimal timing for the procedure remains controversial. To date, few studies have reported spontaneous cranial bone regeneration in children without intervention. CASE DESCRIPTION: A 7-year-old female presented with frontotemporal bone fractures accompanied by dura mater lacerations and brain edema after a motor vehicle accident. She underwent a large decompressive craniectomy and repair of the lacerated dura with a collagen dural substitute. The patient was discharged from the hospital and did not present for follow-up until 10 months after surgery. At that time, computed tomography imaging revealed remarkable spontaneous bone regeneration. With conservative management, she developed enough bone regeneration in the calvarial defect area that cranioplasty surgery was deemed unnecessary. To this date, the patient has no aesthetic deformation of the skull bone and does not exhibit any residual cognitive impairment or motor deficits. CONCLUSIONS: This case report shows that cranial bone regeneration is possible in children older than 6 years old, bypassing the need for cranioplasty after decompressive craniectomy. On the basis of this observation, we recommend that more studies should be performed to identify the factors involved in spontaneous skull bone regeneration in the pediatric population.

Adipsin, MIP-1b, and IL-8 as CSF Biomarker Panels for ALS Diagnosis.

Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder that selectively attacks motor neurons in the brain and spinal cord. Despite important advances in the knowledge of the etiology and progression of the disease, there are still no solid grounds in which a clinician could make an early objective and reliable diagnosis from which patients could benefit. Diagnosis is difficult and basically made by clinical rating scales (ALSRs and El Escorial). The possible finding of biomarkers to aid in the early diagnosis and rate of disease progression could serve for future innovative therapeutic approaches. Recently, it has been suggested that ALS has an important immune component that could represent either the cause or the consequence of the disease. In this report, we analyzed 19 different cytokines and growth factors in the cerebrospinal fluid of 77 ALS patients and 13 controls by decision tree and PanelomiX program. Results showed an increase of Adipsin, MIP-1b, and IL-6, associated with a decrease of IL-8 thresholds, related with ALS patients. This biomarker panel analysis could represent an important aid for diagnosis of ALS alongside the clinical and neurophysiological criteria.

A MicroRNA Perspective on Cardiovascular Development and Diseases: An Update.

In this review, we summarize the latest research pertaining to MicroRNAs (miRs) related to cardiovascular diseases. In today's molecular age, the key clinical aspects of diagnosing and treating these type of diseases are crucial, and miRs play an important role. Therefore, we have made a thorough analysis discussing the most important candidate protagonists of many pathways relating to such conditions as atherosclerosis, heart failure, myocardial infarction, and congenital heart disorders. We approach miRs initially from the fundamental molecular aspects and look at their role in developmental pathways, as well as regulatory mechanisms dysregulated under specific cardiovascular conditions. By doing so, we can better understand their functional roles. Next, we look at therapeutic aspects, including delivery and inhibition techniques. We conclude that a personal approach for treatment is paramount, and so understanding miRs is strategic for cardiovascular health.

Comparing stemness gene expression between stem cell subpopulations from peripheral blood and adipose tissue.

Cell therapy presents a promising alternative for the treatment of degenerative diseases. The main sources of adult stem cells are bone marrow, adipose tissue and peripheral blood. Within those tissues, there are cell subpopulations that share pluripotential characteristics. Nevertheless, there is insufficient data to determine which of these stem cell subtypes would have a better possibility to differentiate to a specific tissue. The objective of this research was to analyze and compare the stemness genes expression from peripheral blood and adipose tissue of plastic adherent cells, and those immune-selected by the CD133+ and CD271+ membrane markers. On all cell subpopulation groups, self-renew capacity, the membranes markers CD73, CD90 and CD105, as well as the stemness genes NANOG, OCT4, SOX2, REX1, NOTCH1 and, NESTIN expression were analyzed. Results showed that all samples presented the minimal criteria to define them as human stem cells. All cell subpopulation were capable of self-renewal. Nevertheless, the subpopulation cell types showed differences on the time needed to reach confluence. The slowest doubling times were for those cells bearing the CD133 marker from both sources. Surface markers determined by flow cytometry were positive for CD73, CD90 and, CD105, and negative for CD45. The stemness gene expression was positive in all subpopulation. However, there were significant differences in the amount and pattern of expression among them. Those differences could be advantageous in finding the best option for their application on cell therapy. Cells with high expression of OCT4 gene could be a better opportunity for neuron differentiation like CD133+ blood cells. On the other hand, lowest expression of NOTCH1 on CD271+ cells from the same source could be a better possibility for myoblast differentiation. The observed differences could be used as an advantage to find which cell type and from the different source; this represents the best option for its application on cell therapy. Experiments focused on the best response to specific differentiation, are conducted in order to confirm those possibilities.

Entrainment of Breast Cell Lines Results in Rhythmic Fluctuations of MicroRNAs.

Circadian rhythms are essential for temporal (~24 h) regulation of molecular processes in diverse species. Dysregulation of circadian gene expression has been implicated in the pathogenesis of various disorders, including hypertension, diabetes, depression, and cancer. Recently, microRNAs (miRNAs) have been identified as critical modulators of gene expression post-transcriptionally, and perhaps involved in circadian clock architecture or their output functions. The aim of the present study is to explore the temporal expression of miRNAs among entrained breast cell lines. For this purpose, we evaluated the temporal (28 h) expression of 2006 miRNAs in MCF-10A, MCF-7, and MDA-MB-231 cells using microarrays after serum shock entrainment. We noted hundreds of miRNAs that exhibit rhythmic fluctuations in each breast cell line, and some of them across two or three cell lines. Afterwards, we validated the rhythmic profiles exhibited by miR-141-5p, miR-1225-5p, miR-17-5p, miR-222-5p, miR-769-3p, and miR-548ay-3p in the above cell lines, as well as in ZR-7530 and HCC-1954 using RT-qPCR. Our results show that serum shock entrainment in breast cells lines induces rhythmic fluctuations of distinct sets of miRNAs, which have the potential to be related to endogenous circadian clock, but extensive investigation is required to elucidate that connection.

Induction of Nestin Early Expression as a Hallmark for Mesenchymal Stem Cells Expression of PDX-1 as a Pre-disposing Factor for Their Conversion into Insulin Producing Cells.

Diabetes constitutes a worldwide epidemic that affects all ethnic groups. Cell therapy is one of the best alternatives of treatment, by providing an effective way to regenerate insulin-producing cells lost during the course of the disease, but many issues remain to be solved. Several groups have been working in the development of a protocol capable of differentiating Mesenchymal Stem Cells (MSCs) into physiologically sound Insulin Producing Cells (IPCs). In order to obtain a simple, fast and direct method, we propose in this manuscript the induction of MSCs to express NESTIN in a short time period (2 h), proceeded by incubation in a low glucose induced medium (24 h) and lastly by incubation in a high glucose medium. Samples from cell cultures incubated in high glucose medium from 12 to 168 h were obtained to detect the expression of INSULIN-1, INSULIN -2, PDX-1 and GLUT-2 genes. Induced cells were exposed to a glucose challenge, in order to assess the production of insulin. This method allowed us to obtain cells expressing PDX-1, which resembles a progenitor insulin-producing cell.

Detection of Autoantibodies to Vascular Endothelial Growth Factor Receptor-3 in Bile Duct Ligated Rats and Correlations with a Panel of Traditional Markers of Liver Diseases.

There is a need for new noninvasive biomarkers (NIBMs) able to assess cholestasis and fibrosis in chronic cholestatic liver diseases (CCLDs). Tumorigenesis can arise from CCLDs. Therefore, autoantibodies to tumor-associated antigens (TAA) may be early produced in response to abnormal self-antigen expression caused by cholestatic injury. Vascular endothelial growth factor receptor-3 (VEGFR-3) has TAA potential since it is involved in cholangiocytes and lymphatic vessels proliferations during CCLDs. This study aims to detect autoantibodies directed at VEGFR-3 during bile duct ligation- (BDL-) induced cholestatic injury in rat sera and investigate whether they could be associated with traditional markers of liver damage, cholestasis, and fibrosis. An ELISA was performed to detect anti-VEGFR-3 autoantibodies in sera of rats with different degree of liver injury and results were correlated with aminotransferases, total bilirubin, and the relative fibrotic area. Mean absorbances of anti-VEGFR-3 autoantibodies were significantly increased from week one to week five after BDL. The highest correlation was observed with total bilirubin (R (2) = 0.8450, P = 3.04e - 12). In conclusion, anti-VEGFR-3 autoantibodies are early produced during BDL-induced cholestatic injury, and they are closely related to cholestasis, suggesting the potential of anti-VEGFR-3 autoantibodies as NIBMs of cholestasis in CCLDs and justifying the need for further investigations in patients with CCLD.

Identification of circadian-related gene expression profiles in entrained breast cancer cell lines.

Cancer cells have broken circadian clocks when compared to their normal tissue counterparts. Moreover, it has been shown in breast cancer that disruption of common circadian oscillations is associated with a more negative prognosis. Numerous studies, focused on canonical circadian genes in breast cancer cell lines, have suggested that there are no mRNA circadian-like oscillations. Nevertheless, cancer cell lines have not been extensively characterized and it is unknown to what extent the circadian oscillations are disrupted. We have chosen representative non-cancerous and cancerous breast cell lines (MCF-10A, MCF-7, ZR-75-30, MDA-MB-231 and HCC-1954) in order to determine the degree to which the circadian clock is damaged. We used serum shock to synchronize the circadian clocks in culture. Our aim was to initially observe the time course of gene expression using cDNA microarrays in the non-cancerous MCF-10A and the cancerous MCF-7 cells for screening and then to characterize specific genes in other cell lines. We used a cosine function to select highly correlated profiles. Some of the identified genes were validated by quantitative polymerase chain reaction (qPCR) and further evaluated in the other breast cancer cell lines. Interestingly, we observed that breast cancer and non-cancerous cultured cells are able to generate specific circadian expression profiles in response to the serum shock. The rhythmic genes, suggested via microarray and measured in each particular subtype, suggest that each breast cancer cell type responds differently to the circadian synchronization. Future results could identify circadian-like genes that are altered in breast cancer and non-cancerous cells, which can be used to propose novel treatments. Breast cell lines are potential models for in vitro studies of circadian clocks and clock-controlled pathways.

Internal ribosome entry site (IRES) from Encephalomyocarditis virus (EMCV) as a tool for shuttle expression plasmids.

In eukaryotes, IRES sequences aid the recruitment of factors needed for translation to occur, enabling protein production independent of 5' capped mRNA. Many patents and commercially available plasmids exploit their properties for polycistronic expression of recombinant proteins. However, these applications have been restricted to eukaryotic organisms, since it was thought that elements of this origin were essential for their activity. Here, using two tricistronic vectors designed for expression in mammalian hosts, we present evidence of EMCV IRES activity in prokaryotes. This finding enables the development of new and more versatile plasmid vectors for the production of recombinant proteins in multiple hosts from a single construct. Additionally, it provides new hints for the elaboration of alternative models describing the molecular mechanism of EMCV IRES mediated translation, in the absence of eukaryotic elements that were considered indispensable for its function.

Liver fibrosis and mechanisms of the protective action of medicinal plants targeting inflammation and the immune response.

Inflammation is a central feature of liver fibrosis as suggested by its role in the activation of hepatic stellate cells leading to extracellular matrix deposition. During liver injury, inflammatory cells are recruited in the injurious site through chemokines attraction. Thus, inflammation could be a target to reduce liver fibrosis. The pandemic trend of obesity, combined with the high incidence of alcohol intake and viral hepatitis infections, highlights the urgent need to find accessible antifibrotic therapies. Medicinal plants are achieving popularity as antifibrotic agents, supported by their safety, cost-effectiveness, and versatility. The aim of this review is to describe the role of inflammation and the immune response in the pathogenesis of liver fibrosis and detail the mechanisms of inhibition of both events by medicinal plants in order to reduce liver fibrosis.

Liver fibrosis and protection mechanisms action of medicinal plants targeting apoptosis of hepatocytes and hepatic stellate cells.

Following chronic liver injury, hepatocytes undergo apoptosis leading to activation of hepatic stellate cells (HSC). Consequently, activated HSC proliferate and produce excessive extracellular matrix, responsible for the scar formation. The pandemic trend of obesity, combined with the high incidence of alcohol intake and viral hepatitis infections, highlights the urgent need to find accessible antifibrotic therapies. Treatment strategies should take into account the versatility of its pathogenesis and act on all the cell lines involved to reduce liver fibrosis. Medicinal plants are achieving popularity as antifibrotic agents, supported by their safety, cost-effectiveness, and versatility. This review will describe the role of hepatocytes and HSC in the pathogenesis of liver fibrosis and detail the mechanisms of modulation of apoptosis of both cell lines by twelve known hepatoprotective plants in order to reduce liver fibrosis.

A role for 1α,25-dihydroxyvitamin d3 in the expression of circadian genes.

The active form of vitamin D, 1α,25-(OH)2D3, has been associated with metabolism control, cell growth, differentiation, antiproliferation, apoptosis, and adaptive/innate immune responses, besides its functions in the integrity of bone and calcium homeostasis. The circadian rhythm regulates a variety of biological processes, many of them related to the functions associated with 1α,25-(OH)2D3. In the present study, we determine whether 1α,25-(OH)2D3 alters the expression of circadian genes in adipose-derived stem cells (ADSCs). The effect of 1α,25-(OH)2D3 on the expression of circadian genes BMAL1 and PER2 was measured by qPCR, over a 60-h period every 4 h, in serum shocked ADSCs, serum shocked ADSCs supplemented with 1α,25-(OH)2D3, and ADSCs under the presence of only 1α,25-(OH)2D3. The results showed that 1α,25-(OH)2D3 was able to synchronize circadian clock gene expression in ADSCs. The expression of circadian genes BMAL1 and PER2 in ADSCs that contained only 1α,25-(OH)2D3 has a profile similar to that found in the ADSCs synchronized by a serum shock. The results suggest an important role of 1α,25-(OH)2D3 in the regulation of the molecular clock.

Amyotrophic lateral sclerosis in pregnancy: clinical outcome during the post-partum period after stem cell transplantation into the frontal motor cortex.

BACKGROUND AIMS: Amyotrophic lateral sclerosis (ALS) is rare in pregnant patients. Stem cell therapy has been proposed as a potential therapeutic strategy for ALS. METHODS: We describe a young woman with sporadic ALS that started during the second trimester of pregnancy with a rapid progression after delivery and severe motor impairment. Several drugs and stem cell injection by lumbar puncture were performed without changes before the patient was referred to our institution. RESULTS: After bilateral autologous stem cell transplantation into the frontal motor cortices, we observed stabilization in ALS functional rating scale, significant delay of ALS progression and an extension in her life expectancy. CONCLUSIONS: Stem cell transplantation may alter the clinical course of ALS and improve quality of life in pre-menopausal women.

Protective mechanisms of medicinal plants targeting hepatic stellate cell activation and extracellular matrix deposition in liver fibrosis.

During chronic liver injury, hepatic stellate cells (HSC) are activated and proliferate, which causes excessive extracellular matrix (ECM) deposition, leading to scar formation and fibrosis. Medicinal plants are gaining popularity as antifibrotic agents, and are often safe, cost-effective, and versatile. This review aims to describe the protective role and mechanisms of medicinal plants in the inhibition of HSC activation and ECM deposition during the pathogenesis of liver fibrosis. A systematic literature review on the anti-fibrotic mechanisms of hepatoprotective plants was performed in PubMed, which yielded articles about twelve relevant plants. Many of these plants act via disruption of the transforming growth factor beta 1 signaling pathway, possibly through reduction in oxidative stress. This reduction could explain the inhibition of HSC activation and reduction in ECM deposition. Medicinal plants could be a source of anti-liver fibrosis compounds.