Focal-to-bilateral tonic-clonic seizures and High-grade CMV-infection are poor survival predictors in Tumor-related Epilepsy Adult-type diffuse gliomas-A single-center study and literature review.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications. Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant. Results: Sixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors. Conclusions: CMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results.

Neurococcidiomycosis in children with hydrocephalus: assessment of functional outcome, quality of life and survival in relation to neuroimaging findings.

PURPOSE: Coccidioidal meningitis (CM) is an uncommon disease frequently misdiagnosed. Neuroimaging and mortality are not considered in detail in previous pediatric CM series. Our objective is to evaluate outcome of pediatric neurococcidiomycosis in relation to neuroimaging findings. METHODS: We performed a prospective, observational, cross-sectional study in children with hydrocephalus and CM treated at Specialties Hospital in Torreon, Mexico (between 2015 and 2020). The outcome was evaluated by Hydrocephalus Outcome Questionnaire (HOQ) and the modified Rankin Scale (mRS). Follow-up was established at the first shunt surgery and survival since CM diagnosis confirmation. Neuroimaging was analyzed in relation to clinical data, outcome and survival. Kaplan-Meier analysis was performed with IBM-SPSS-25. RESULTS: Ten pediatric cases with CM and hydrocephalus were reported. Aged 6-228 months, 60% were female. Mean number of surgeries was 4.3 SD ± 3 (range 1-15). Asymmetric hydrocephalus was the most common neuroimaging finding (70%), followed by cerebral vasculitis (20%) and isolated fourth ventricle (IFV) (20%). The mean HOQ overall score was 0.338 SD ± 0.35. A minimum follow-up of 18 months was reported. Mean survival was 13.9 SD ± 6.15 months (range 3-24). Poor survival was correlated with asymmetric hydrocephalus (p = 0.335), cerebral vasculitis (p = 0.176), IFV (p < 0.001), bacterial superinfection (p = 0.017), lower mRS scores at hospital discharge (p = 0.017) and during follow-up (p = 0.004). The mortality rate was 20%. CONCLUSIONS: We report the largest series in Latin America of pediatric CM and hydrocephalus. Asymmetric hydrocephalus, IFV and cerebral vasculitis are complications that increase mortality and must be early diagnosed for a timely surgical and medical treatment. HOQ and mRS could be alternative scales to evaluate outcome in these patients. After a long follow-up (18 months), survival remained poor after diagnosis confirmation in our series.

Risk Factors and Clinical Phenotypes Associated with Severity in Patients with COVID-19 in Northeast Mexico.

Objective: The aim of this study is to describe the main clinical phenotypes, laboratory findings, and severity of coronavirus disease 2019 (COVID-19) in patients hospitalized at the High Specialty Medical Unit # 71 of the Mexican Social Security Institute. Methods: Prospective observational cohort study with a total of 105 patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the High Specialty Medical Unit # 71 (Torreón, Coahuila, Mexico), from May 15th to August 15th, 2020. The cases were confirmed to be COVID-19 positive through an RT-qPCR test. Clinical phenotypes and laboratory tests were evaluated to determine the degree of severity of the disease and the most frequent comorbidities. Results: The clinical characteristics of a total of 105 hospitalized patients (47 females and 58 males; median age being 52 years) with confirmed COVID-19 diagnoses were studied. The severity of the disease was classified as moderate grade (62.7%), severe grade (21.5%), and critical grade (15.6%). Among the most frequent underlying pathologies coexisted overweight (n = 75, 78.12%), obesity (n = 21, 21.87%), diabetes (n = 10, 9.52%), and hypertension (n = 6, 5.71%), some of these patients present more than one pathology. This association was found with diabetes (odds ratio [OR]: 1.42; 95% confidence interval [CI]: 1.23-1.97; p = 0.021) and high levels of D-dimer (OR: 1.01; 95% CI: 1.00-1.08; p = 0.001). Conclusion: In this retrospective cohort study of patients with COVID-19 from a specialty hospital in the northeast region of Mexico, it was observed that clinical phenotypes and D-dimer elevation were compatible with an inflammatory state by degree of severity; it was found that the hospitalized patients with underlying chronic medical conditions such as diabetes and elevated D-dimer levels were significantly associated with increased mortality from COVID-19. Age and sex (males) were two factors highly associated with mortality.

Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure.

An emerging concern is the influences of early life exposure to environmental toxicants on offspring characteristics in later life. Since recent evidence suggests a transgenerational transference of aberrant phenotypes from exposed-parents to non-exposed offspring related to adult-onset diseases including reproductive phenotype. The transgenerational potential of arsenic a well know genotoxic and epigenetic modifier agent has not been assessed in mammals until now. In this experimental study, we evaluated the transgenerational effects of arsenic in a rat model with chronic exposure to arsenic. Rats chronically exposed to arsenic in drinking water (1 mg As2O3/mL) (F0) were mated to produce the arsenic lineage (F1, F2, and F3). The arsenic toxic effects on were evaluated over the four generations by analyzing the DNA methylation percentage, genotoxicity in WBC and physical and reproductive parameters, including sperm quality parameters and histopathological evaluation of the gonads. Chronic exposure to arsenic caused genotoxic damage (F0-F3) different methylation patterns, alterations in physical and reproductive parameters, aberrant morphology in the ovaries (F0 and F1) and testicles (F1-F3), and a decrease in the quality of sperm (F0-F3, except F2). Parental chronic arsenic exposure causes transgenerational genotoxicity and changes in global DNA methylation which might be associated with reproductive defects in rats. Combined with recent studies reveal that disturbances in the early life of an individual can affect the health of later generations.

The immunogenetic diversity of the HLA system in Mexico correlates with underlying population genetic structure.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) allele groups and alleles by PCR-SSP based typing in a total of 15,318 mixed ancestry Mexicans from all the states of the country divided into 78 sample sets, providing information regarding allelic and haplotypic frequencies and their linkage disequilibrium, as well as admixture estimates and genetic substructure. We identified the presence of 4268 unique HLA extended haplotypes across Mexico and find that the ten most frequent (HF > 1%) HLA haplotypes with significant linkage disequilibrium (Δ'≥0.1) in Mexico (accounting for 20% of the haplotypic diversity of the country) are of primarily Native American ancestry (A*02~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*08~DQB1*04, A*68~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*14~DQB1*03:01, A*24~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*04~DQB1*03:02, A*02~B*40:02~DRB1*04~DQB1*03:02, A*68~B*35~DRB1*04~DQB1*03:02, A*02~B*15:01~DRB1*04~DQB1*03:02). Admixture estimates obtained by a maximum likelihood method using HLA-A/-B/-DRB1 as genetic estimators revealed that the main genetic components in Mexico as a whole are Native American (ranging from 37.8% in the northern part of the country to 81.5% in the southeastern region) and European (ranging from 11.5% in the southeast to 62.6% in northern Mexico). African admixture ranged from 0.0 to 12.7% not following any specific pattern. We were able to detect three major immunogenetic clusters correlating with genetic diversity and differential admixture within Mexico: North, Central and Southeast, which is in accordance with previous reports using genome-wide data. Our findings provide insights into the population immunogenetic substructure of the whole country and add to the knowledge of mixed ancestry Latin American population genetics, important for disease association studies, detection of demographic signatures on population variation and improved allocation of public health resources.

Increased Urinary Concentration of C-Terminal Telopeptide of Type II Collagen and Pain by Radiographic Grade in Women with Knee Osteoarthritis in Northeastern Mexico: A Cross-Sectional Study.

Osteoarthritis (OA) of the knee causes disability, pain, and progressive destruction of cartilage in adult women. The objective of the study was to evaluate the concentrations of the urinary biomarker C-terminal telopeptide of type II collagen (CTX-II) and pain by radiographic grade in women with knee OA in northeastern Mexico: Cross-sectional study of 155 women with knee OA. Concentrations of biochemical parameters were evaluated and urine samples were collected to measure biomarker levels (uCTX-II) ng/mmol by competitive enzyme-linked immunoabsorbent assay (ELISA) technique and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale was used for pain classification; median age of 49 years and 29.1 kg/m2 of body mass index (BMI). uCTX-II biomarker levels were grade 2 (210.7 ng/mmol), grade 3 (314.8 ng/mmol), and grade 4 (478.8 ng/mmol) relative to Kellgren and Lawrence, uCTX-II levels were compared with WOMAC scale and presented significant statistical difference (p = 0.0001). An association of the biomarker CTX-II and an increase in BMI was found in female patients with knee OA (odds ratio = 1.01; 95% confidence interval 1.001-1.005; p = 0.047).This study demonstrates an increase in the levels of the biomarker uCTX-II, the degree of pain, and radiographic grade in women with knee OA in northeastern Mexico.

Analysis of Polymorphisms in the MATN3 and DOT1L Genes and CTX-II Urinary Levels in Patients with Knee Osteoarthritis in a Northeast Mexican-Mestizo Population.

Aims: To investigate the possible roles of the single nucleotide polymorphisms (SNPs) MATN3 (rs77245812) and DOT1L (rs12982744) with susceptibility to knee osteoarthritis (KOA) among mestizos from the northeast region of Mexico. In addition, we analyzed the relationship of their urinary levels of carboxy terminal telopeptide of collagen type II (CTX-II) and the radiological grade of disease. Materials and Methods: A total of 223 individuals from a Northeast Mexico Mestizo population were included in this study: 110 patients with primary KOA and 113 healthy controls. Genotyping of the MATN3 (rs77245812) and DOT1L (rs12982744) SNPs was performed by real-time polymerase chain reaction. Results: No association was found between the polymorphisms MATN3 (rs77245812), DOT1L (rs12982744), and the risk of developing KOA (odds ratio [OR] = 1.33, 95% confidence interval [CI] = 0.42-6.48, p = 0.621) (OR = 2.03, 95% CI = 0.35-11.5, p = 0.422). However, urinary CTX-II levels were considerably higher by radiographic grade. Conclusions: An increase in CTX-II per radiographic grade was observed in the case group, but no association was found between MATN3 and DOT1L genes and the risk of KOA in Mexican mestizos.

Genetic diversity of HLA system in two populations from Nuevo León, Mexico: Monterrey and rural Nuevo León.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 665 Mexicans from the state of Nuevo León living in the city of Monterrey (N = 226) and rural communities (N = 439), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Nuevo León include 12 Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Nuevo León are Native American (54.53 ±â€¯0.87% by ML; 48.88% of Native American haplotypes) and European (38.67 ±â€¯4.06% by ML; 32.59% of European haplotypes), and a less prominent African genetic component (6.80 ±â€¯4.30% by ML; 8.26% of African haplotypes).

Genetic diversity of HLA system in two populations from Durango, Mexico: Durango city and rural Durango.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 479 Mexicans from the state of Durango living in Durango city (N = 153) and rural communities (N = 326), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Durango include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in Durango are European (54.34 ±â€¯1.68%) and Native American (45.66 ±â€¯2.24%), while African genetic component was virtually absent (0.00 ±â€¯2.03%). However, African haplotypes could be estimated at a proportion of 9.13%.

Genetic diversity of HLA system in three populations from Chihuahua, Mexico: Chihuahua City, Ciudad Juárez and rural Chihuahua.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 461 Mexicans from the state of Chihuahua living in Chihuahua city (N = 119), Ciudad Juárez (N = 106) and rural communities (N = 236), to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes found in the state of Chihuahua include seven Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in Chihuahua are European (52.12 ±â€¯0.88% by ML; 41.53% of European haplotypes) and Native American (39.51 ±â€¯2.17% by ML; 37.45% of Native American haplotypes), while African genetic component was less apparent (8.36 ±â€¯1.47% by ML; 11.70% of African haplotypes).

Genetic diversity of HLA system in a population sample from Aguascalientes, Mexico.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 95 Mexicans from the state of Aguascalientes to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes in the state of Aguascalientes include four Native American, three European and one Asian haplotypes. Admixture estimates revealed that the main genetic components in the state of Aguascalientes are Native American (54.53 ±â€¯3.22% by ML; 44.21% of Native American haplotypes) and European (44.34 ±â€¯0.45% by ML; 40.53% of European haplotypes), and a relatively low African genetic component (1.13 ±â€¯2.33% by ML; 5.26% of African haplotypes).

Genetic diversity of HLA system in two populations from Tamaulipas, Mexico: Ciudad Victoria and rural Tamaulipas.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 148 Mexicans from the state of Tamaulipas living in Ciudad Victoria (N = 23) and rural communities (N = 125), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in the state of Tamaulipas include ten Native American, three European and one African haplotypes. Admixture estimates revealed that the main genetic components in the state of Tamaulipas are Native American (54.69 ±â€¯0.93% by ML; 47.65% of Native American haplotypes) and European (34.66 ±â€¯5.62% by ML; 33.56% of European haplotypes), and a relatively high African genetic component (10.65 ±â€¯5.05% by ML; 12.42% of African haplotypes).

Genetic diversity of HLA system in two populations from San Luis Potosí, Mexico: San Luis Potosí City and rural San Luis Potosí.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 117 Mexicans from the state of San Luis Potosí living in the city of San Luis Potosí (N = 30) and rural communities (N = 87), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state include 13 Native American, six European, two African and two Asian haplotypes. Admixture estimates revealed that the main genetic components are Native American (52.72 ±â€¯0.66% by ML; 48.29% of Native American haplotypes) and European (34.62 ±â€¯4.28% by ML; 32.48% of European haplotypes), and a relatively high African genetic component (12.66 ±â€¯4.61% by ML; 10.26% of African haplotypes).

Genetic diversity of HLA system in three populations from Coahuila, Mexico: Torreón, Saltillo and rural Coahuila.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 684 Mexicans from the state of Coahuila living in Saltillo (N = 72), Torreón (N = 396) and rural communities (N = 216), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Coahuila include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Coahuila are European (49.72 ±â€¯4.18% by ML; 37.49% of European haplotypes) and Native American (45.01 ±â€¯2.69% by ML; 42.98% of Native American haplotypes), while African genetic component is less apparent (5.27 ±â€¯1.88% by ML; 9.92% of African haplotypes).

Genetic diversity of HLA system in three populations from Zacatecas, Mexico: Zacatecas city, Fresnillo and rural Zacatecas.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 453 Mexicans from the state of Zacatecas living in Zacatecas city (N = 84), Fresnillo (N = 103) and rural communities (N = 266) to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes for the state of Zacatecas include seven Native American most probable ancestry (A*02 ∼ B*39 ∼ DRB1*04 ∼ DQB1*03:02; A*02 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04; A*24 ∼ B*39 ∼ DRB1*14 ∼ DQB1*03:01; A*02 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*24 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*68 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02 and A*24 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04) and two European MPA haplotypes (HLA ∼ A*01 ∼ B*08 ∼ DRB1*03:01 ∼ DQB1*02 and A*29 ∼ B*44 ∼ DRB1*07 ∼ DQB1*02). Admixture estimates revealed that the main genetic components in the state of Zacatecas are European (47.61 ±â€¯1.85%) and Native American (44.74 ±â€¯1.12%), while the African genetic component was less apparent (7.65 ±â€¯1.12%). Our findings provide a starting point for the study of population immunogenetics of urban and rural populations from the state of Zacatecas and add to the growing knowledge on the population genetics of Northern Mexico.

Telomere length analysis in residents of a community exposed to arsenic.

Differentiated cells telomere length is an indicator of senescence or lifespan; however, in peripheral blood leukocytes the relative shortening of the telomere has been considered as a biological marker of aging, and lengthening telomere as an associated risk to cancer. Individual's age, type of tissue, lifestyle, and environmental factors make telomere length variable. The presence of environmental carcinogens such as arsenic (As) influence as causal agents of these alterations, the main modes of action for As described are oxidative stress, reduction in DNA repair capacity, overexpression of genes, alteration of telomerase activity, and damage to telomeres. The telomeres of leukocytes resulting a finite capacity of replication due to the low or no activity of the telomerase enzyme, therefore, elongation telomere in this kind of cells is a potential biological marker associated with the development of chronic diseases and carcinogenesis.