Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

mtDNA Single-Nucleotide Variants Associated with Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.

Anaphylaxis to SARS-CoV-2 Vaccines in the Setting of a Nationwide Passive Epidemiological Surveillance Program.

BACKGROUND: Information on anaphylaxis among recipients of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains scarce. OBJECTIVE: To identify the observed incidence of anaphylaxis in recipients of different anti-SARS-CoV-2 vaccines. METHODS: A nationwide observational study among recipients of 61,414,803 doses of seven different anti-SARS-CoV-2 vaccines, describing the incidence and characteristics of adult patients (age ≥ 18 years) who developed anaphylaxis as an adverse event following immunization (AEFI) against SARS-CoV-2 vaccines between December 24, 2020, and October 15, 2021, in Mexico. RESULTS: Sixty-six patients developed anaphylaxis as an AEFI, for an overall observed incidence of 1.07 cases per 1,000,000 (95% CI 0.84-1.37) administered doses. Eighty-six percent of the patients were female, consistent with previous reports of AEFI to COVID-19 vaccines. mRNA-based vaccine recipients had the highest frequency of anaphylaxis, followed by adenovirus-vectored vaccines and inactivated virus recipients, with an observed incidence of 2.5, 0.7, and 0.2 cases per 1,000,000 doses administered, respectively. Only 46% of the patients received correct treatment with epinephrine as the first-line treatment through the appropriate route and dose. We detected one case of anaphylactic reaction-related death occurring 5 min following immunization with ChAdOx1 nCov-19 for a mortality rate of 1.5% among those who developed this AEFI. CONCLUSIONS: In our population, anaphylactic reactions were infrequent. Our study provides further evidence supporting the security of these newly developed vaccines.

Seizures following COVID-19 vaccination in Mexico: A nationwide observational study.

The COVID-19 pandemic led to the development and emergency approval of an array of effective vaccines against SARS-CoV-2. Given the relatively small number of patients included in vaccine trials, postapproval epidemiological surveillance is crucial to detect infrequent vaccine-related adverse events. We conducted a nationwide retrospective descriptive study evaluating the incidence of seizures among recipients of SARS-CoV-2 vaccines in Mexico from December 24, 2020 (date of administration of first doses nationwide) to October 29, 2021. Among 81 916 351 doses of any vaccine that were administered, we documented seizures in 53 patients, of which 31 (60%) were new onset seizures. The incidence rate of seizures per million doses was highest for mRNA-1273 (Moderna) with 2.73 per million, followed by BNT162b2 (Pfizer-BioNTech) with 1.02 per million, and Ad5-nCoV (CanSino) with 1.01 per million. Thus, we found that seizures following SARS-CoV-2 vaccination are exceedingly rare events.

Comparison of prevalence of diabetes complications in Brazilian and Mexican adults: a cross-sectional study.

BACKGROUND: Type 2 diabetes is more frequent in Latin American people than in non-Hispanic whites due to a combination of genetic and lifestyle risk factors. Brazil and Mexico are the most populous countries in Latin America. The present study aimed to compare the results of the National Health Survey "PNS" in Brazil and the National Survey Health and Nutrition "ENSANUT" in Mexico regarding the prevalence, complications and healthcare issues of diabetes in both countries. METHODS: A cross-sectional study was conducted with data from the National Health Survey (PNS) of 2013 in Brazil and the National Survey of Health and Nutrition (ENSANUT) of 2018 in Mexico. The prevalence of diabetes, complications and risk factors related to developing diabetes were considered. RESULTS: The respondents included 3636 individuals in Brazil and 4555 individuals in Mexico. There were significant differences in age and time living with diabetes between the two countries. Mexican people had twice as likely as Brazilian people to have a complication (p < 0.0001). The principal risk factor (OR 2.47; p ≤ 0.0001) for developing any diabetic complication was living with diabetes for more than 15 years. Visual impairment was the most frequent complication in both countries, but it was more prevalent in Mexico (p ≤ 0.001). CONCLUSIONS: Diabetes complications are important health problems in Brazil and Mexico. Visual impairment was the principal complication in both countries. Several factors, such as access to and type of health system, living in a rural area, treatment, BMI and performing preventive actions, affected the risk of developing a complication. However, living with diabetes for more than 15 years was the principal risk factor. National health surveys have added significant information on the impact of diabetes in these Latin American populations. This comparison of data could provide valuable information to guide national policies and program decisions in both countries.

Genetic analysis of the endemic fungal pathogens Coccidioides posadasii and Coccidioides immitis in Mexico.

Coccidioidomycosis (CM) is a mycotic disease that affects mammals, including humans. Official data relative to CM in Mexico has not been collected since 1995, thus its prevalence remains unknown. The objectives of this study were to identify the predominant Coccidioides species in Mexico, infer their current geographical distribution and explore the correlation between species and clinical presentation. We collected 154 strains, which were cultured, inactivated, and processed for DNA extraction. Nine microsatellite loci, the Ag2/PRA gene and Umeyama Region were amplified from each isolate. To infer the current geographical distribution of Coccidioides spp. and to establish a correlation between genotype and clinical presentation, we evaluated genetic population structure under the following grouping criteria: putative origin and clinical presentation records. Microsatellite analysis showed that 82% of the isolates corresponded to C. posadasii and 18% were C. immitis. The species identification results obtained using Umeyama region, Ag2/PRA, and microsatellites of five of the isolates were inconsistent with the data collected for the remaining isolates. C. posadasii strains were found primarily in the northeastern region and C. immitis in the northwestern region. However, there was no relationship between clinical presentation and Coccidioides species. The molecular markers used in this study proved to have a high power of resolution to identify the Coccidioides species recovered in culture. While we found C. posadasii to be the most abundant species in Mexico, more detailed clinical records are needed in order to obtain more accurate information about the infections in specific geographical locations.

Amelioration of Cytogenotoxic Damage in Drug Abusers Supplemented with Folic Acid.

BACKGROUND: Cytogenotoxic damage caused by the consumption of legal and illegal drugs in drug abusers has been demonstrated, primarily due to alterations in their antioxidant capacity, cellular repair mechanisms, and increased production of free radicals. Folic acid shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and reducing genomic damage. METHODS: The intervention involved administering 15 mg of folic acid, divided into three doses per day, to a group of 44 drug abusers. The frequency of nuclear abnormalities (NAs) was determined; micronuclei (MNs), nuclear buds (NBUDs), binucleated cells (BNs), abnormally condensed chromatin (CC), karyorrhexis (KX), pyknotic nuclei (PNs), and karyolysis (KL) were determined at different pre-treatment (baseline) and post-treatment time points at 15 and 30 days. Additionally, a group of 44 healthy individuals was used as the control group. RESULTS: We observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before supplementation vs. 11.18 ± 7.42 at 15 days and 9.11 ± 10.9 at 30 days of supplementation). Specifically, it decreased the frequency of NBUDs, BNs, CC, KX, and PNs (p < 0.05). CONCLUSION: Our study demonstrates a clear improvement in cytogenotoxic damage in drug abusers supplemented with folic acid.

Cytogenotoxicity effects in addicts with multidrug consumption.

Drug abuse is considered a global health problem with serious social impact. In recent decades, changes in drug consumption patterns have shown a clear rising trend in the use of multiple drugs. Although the buccal micronucleus cytome (BMCyt) assay has evaluated cytotoxicity in drug abuse, there has not been an approach that takes into account this pattern of multiple drug use. Therefore, in this study, we evaluate for the first time the cytogenotoxic effects in multidrug users, and its correlation with the amount consumed and years of abuse. This study was conducted on 166 individuals by the BMCyt assay. A total of 83 individuals with a history of multiple licit (alcohol and tobacco) and at least one illicit drug abuse (marijuana, methamphetamines, cocaine, and/or inhalants), and 83 healthy individuals, non-drug abusers were analyzed. The results showed that drug abusers had higher frequencies of nuclear abnormalities nuclear buds, binucleated cells, pyknotic nuclei (PNs), karyorrhexis (KX), and abnormally condensed chromatin when compared with healthy controls. Moreover, results suggests that the use of licit and illicit drugs is related to cytogenotoxic damage, as was shown by an upward trend in the frequency of nuclear abnormalities identified in groups 1 (alcohol + tobacco + at least one illicit drug) and 2 (tobacco + at least one illicit drug). Furthermore, a positive correlation was found in the different groups, between the years and the amount of consumption of some drugs (alcohol, methamphetamine, and tobacco) with cytotoxicity markers such as KL, KX, and PNs.

Novel risk loci for COVID-19 hospitalization among admixed American populations.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Mitochondrial Control Region Variants Related to Breast Cancer.

Breast cancer has an important incidence in the worldwide female population. Although alterations in the mitochondrial genome probably play an important role in carcinogenesis, the actual evidence is ambiguous and inconclusive. Our purpose was to explore differences in mitochondrial sequences of cases with breast cancer compared with control samples from different origins. We identified 124 mtDNA sequences associated with breast cancer cases, of which 86 were complete and 38 were partial sequences. Of these 86 complete sequences, 52 belonged to patients with a confirmed diagnosis of breast cancer, and 34 sequences were obtained from healthy mammary tissue of the same patients used as controls. From the mtDNA analysis, two polymorphisms with significant statistical differences were found: m.310del (rs869289246) in 34.6% (27/78) of breast cancer cases and 61.7% (21/34) in the controls; and m.315dup (rs369786048) in 60.2% (47/78) of breast cancer cases and 38.2% (13/34) in the controls. In addition, the variant m.16519T>C (rs3937033) was found in 59% of the control sequences and 52% of the breast cancer sequences with a significant statistical difference. Polymorphic changes are evolutionarily related to the haplogroup H of Indo-European and Euro-Asiatic origins; however, they were found in all non-European breast cancers.

Class I MHC Polymorphisms Associated with Type 2 Diabetes in the Mexican Population.

Type 2 diabetes (T2D) has been linked to the expression of Human Leukocyte Antigens, principally to the Major Histocompatibility Complex Class II, with only scarce reports of Major Histocompatibility Complex Class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC Class I related to T2D in the Mexican population using the Genome-Wide Association Studies Slim Initiative in Genomic Medicine of the Americas (GWAS SIGMA) database. This database contains information on 3848 Mexican individuals with T2D and 4366 control individuals from the same population without a clinical or hereditary history of the disease. The searching criteria considered a p-value of <0.005 and an odds ratio (OR) of >1.0. Ten novel, statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01) and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related to the development of T2D complications.

The utility of genomic public databases to mitochondrial haplotyping in contemporary Mestizo population of Mexican origin.

There are different public databases and open access information that can be exploited to be reused in different research projects. With this concept in mind, we carried out a study to answer the question about the prevalence of haplogroups in human populations of modern Mexico. Since the publication of genomic and mitochondrial data in Latin American populations are very scarce and with very small samples, our work proposes to consider the availability of genomic and genetic data collections that can be reused for other purposes, different from those initially proposed in the investigations where the sequences were obtained. The objective of the present study was to explore the population structure of Mexico using available information in the public database. Through the search of information in the nucleotide database of National Center of Biotechnology Information (NCBI) of complete sequences of mitochondrial genome (16 Kb) of indigenous people, Mexican Mestizo population and Mexican-Americans living in the United States, they were classified according to the polymorphisms associated with haplogroups A, B, C and D reported in the literature as the most frequent. We obtained 283 sequences, of which 255 were selected with the criteria mentioned. The haplotyping results showed 113 different clades and subclades distributed in a general way in eight haplogroups. The most frequent groups that dominate the population were the haplogroup A with 90 individuals representing 36%, followed by haplogroup B in 65 individuals representing 26% of the sample.

Ecological niche modeling of Coccidioides spp. in western North American deserts.

Coccidioidomycosis is an endemic infectious disease in western North American deserts caused by the dimorphic ascomycete Coccidioides spp. Even though there has been an increase in the number of reported cases in the last years, few positive isolations have been obtained from soil samples in endemic areas for the disease. This low correlation between epidemiological and environmental data prompted us to better characterize the fundamental ecological niche of this important fungal pathogen. By using a combination of environmental variables and geospatially referenced points, where positive isolations had been obtained in southern California and Arizona (USA) and Sonora (Mexico), we have applied Genetic Algorithm for Rule Set Production (GARP) and Geographical Information Systems (GIS) to characterize the most likely ecological conditions favorable for the presence of the fungus. This model, based on environmental variables, allowed us to identify hotspots for the presence of the fungus in areas of southern California, Arizona, Texas, Baja California, and northern Mexico, whereas an alternative model based on bioclimatic variables gave us much broader probable distribution areas. We have overlapped the hotspots obtained with the environmental model with the available epidemiological information and have found a high match. Our model suggests that the most probable fundamental ecological niche for Coccidioides spp. is found in the arid lands of the North American deserts and provides the methodological basis to further characterize the realized ecological niche of Coccidioides spp., which would ultimately contribute to design smart field-sampling strategies.

[The epidemiology of coccidioidomycosis in Mexico]. / Epidemiología de la coccidioidomicosis en México.

Coccidioidomycosis, also known as San Joaquin Valley Fever, is an endemic mycosis restricted to the American deserts, caused by the ascomycete Coccidioides spp. In 2000 it was estimated that more than 100,000 cases of the disease took place in the United States, and that these numbers have been rising over time. The current impact of this disease in Mexico is unknown, but the available data suggest that an increase of the incidence of this mycosis in California and Arizona might have the same impact in Mexican nearby States. These two USA States both have a bioclimatic pattern similar to the nearby Mexican States endemic for coccidioidomycosis. The main objective of this study was to collect the available information on the historical and epidemiological research done in Mexico to assess the impact of the disease and to evaluate whether the disease have a tendency to increase in the endemic areas and if this grow could represent a problem of public health in Mexico. We have conducted an extensive search on this topic in Health institutions and Academic facilities of California, Arizona and Mexico. After analyzing the scarce Mexican records we found that: 1) the main studies conducted in Mexico are limited to the northern desert areas of the country, mainly in the states of Sonora, Coahuila, Nuevo Leon and the Baja California peninsula; 2) until 1994 an increase of coccidioidomycosis in Mexico was noted; and 3) we found that Mexico shares a similar epidemiological data as that reported in the United States. For instance, the most affected groups in Mexico were children under 5 years-old and adults over 45 years-old. The collective information suggests the need to implement joined organized efforts and multi-institutional collaboration to clarify the current situation of this important endemic disease of North America to administer a viable early detection plan of this mycosis in Mexico.

Detection of coccidioidal antibodies in serum of a small rodent community in Baja California, Mexico.

Coccidioidomycosis (Valley Fever) represents a serious threat to inhabitants of endemic areas of North America. Despite successful clinical isolations of the fungal etiological agent, Coccidioides spp., the screening of environmental samples has had low effectiveness, mainly because of the poor characterization of Coccidioides ecological niche. We explored Valle de las Palmas, Baja California, Mexico, a highly endemic area near the U.S.-Mexico border, where we previously detected Coccidioides via culture-independent molecular methods. By testing the serum from 40-trapped rodents with ELISA, we detected antibodies against Coccidioides in two species: Peromyscus maniculatus and Neotoma lepida. This study comprises the first report of wild rodent serum tested for coccidioidal antibodies, and sets the basis to analyze this pathogen in its natural environment and explore its potential ecological niche.

Los cianoacrilatos en cirugía / Cyano-acrylates in surgery

Desde su introducción en la cirugía hace más de 35 años, los cianoacrilatos se han usado en diversos campos de las especialidades quirúrgicas. A pesar de sus múltiples ventajas sobre la sutura convencional, muchos cirujanos dejaron de usarlos por su gran histotoxicidad y las dificultades de su aplicación. En los últimos años, nuevamente se han comenzado a utilizar los olvidadod adhesivos con excelentes resultados. En esta revisión se comentan aspectos históricos, características físicas, químicas y biológicas de estos adhesivos; Métodos de síntesis, metabolismo, respuesta inmunitaria y carcinogénesis después de aplicarse en el organismo y usos actuales y potenciales de los cianoacrilatos en la cirugía

Infección urinaria recurrente: recaida o reinfección / Recurrent urinary infection: re-infection or relapsing

La infección recurrente del tracto urinario es un síndrome que en la consulta diaria se encuantra con bastante frecuencia. Estas recurrencias de la enfermedad representan lo que se conoce como reinfeccion o recaída. Se comentan algunos mecanismos fisiopatológicos que se han asociado con este padecimiento y algunas de las posibles conductas a seguir de primera intención para su adecuado tratamiento

Traumatismo abdominal cerrado: revisión de 53 casos atendidos en el Hospital Central Militar / Closed abdominal trauma: a 53 case review seen at the Central Military Hospital

Se revisa el caso de 53 individuos con traumatismo abdominal cerrado atendidos en el Hospital Central Militar. Las principales causas de traumatismo abdominal cerrado fueron: accidentes automovilísticos (28 por ciento), agresiones (15 por ciento) y los accidentes por atropellamiento de un vehículo automotor (15 por ciento). La mayor parte de las contusiones del abdomen implican el abordaje amplio para descartar lesiones en órganos blandos, por lo que la laparotomía exploratoria está indicada en su manejo y posterior tratamiento. De esta revisión se concluye que el manejo de este tipo de lesiones en la sala de urgencias del Hospital Central Militar y su posterior evolución en las salas de cirugía es satisfactoria