Vitamin D receptor gene polymorphisms role in COVID-19 severity: Results of a Mexican patients' cohort.

Vitamin D status has been involved with coronavirus disease 19 (COVID-19) severity. This may be mediated by vitamin D metabolism regulatory genes. Of interest is the vitamin D receptor (VDR) gene, which has been previously associated with other inflammatory and respiratory diseases. In order to investigate the role of VDR gene polymorphisms in COVID-19 severity and outcome, a total of 292 COVID-19 patients were classified according to severity in moderate (n = 56), severe (n = 89) and critical (n = 147) and, according to outcome in survivor (n = 163) and deceased (n = 129), and analysed for FokI and TaqI VDR gene polymorphisms by polymerase chain reaction-based restriction enzyme digestion. The FokI and TaqI single nucleotide polymorphisms (SNPs) were not associated with COVID-19 severity or mortality individually but when analysed by haplotype, TC was associated with an increased risk of presenting critical COVID-19. Additionally, FokI CT genotype was more frequent in COVID-19 patients with hypertension, and T allele carriers presented higher aspartate aminotransferase levels. Our results suggest a relationship between VDR FokI and TaqI SNPs and COVID-19 severity in Mexican population. Although there are some previous reports of VDR polymorphisms in COVID-19, this represents the first report in Latin American population. Further studies on other populations are encouraged.

Association of the HLA-G rs66554220 variant with non-segmental vitiligo and its clinical features in Northwestern Mexico population.

Introduction: The HLA-G molecule functions as a critical immunomodulatory checkpoint, its expression is significantly associated with pathological processes that may be responsible in part for autoimmune conditions such as non-segmental vitiligo (NS-V), characterized by chronic skin depigmentation. In this sense, the rs66554220 (14 bp ID) variant located in the 3'UTR, implicated in the regulation of HLA-G production, is associated with autoimmune diseases. Aim: To evaluate the role of the HLA-G rs66554220 variant in NS-V and its clinical features in Northwestern Mexicans. Material and methods: We genotyped the rs66554220 variant by SSP-PCR in 197 NS-V patients and 198 age-sex matched non-related healthy individuals (HI). Results: Del allele and genotype Del/Ins were the most prevalent in both study groups (NS-V/HI = 56%/55% and 46.70%/46.46%, respectively). Despite lacking association between the variant and NS-V, we found an association of the Ins allele in different inheritance models with familial clustering, onset of the illness, universal clinical subtype and Koebner's phenomenon. Conclusions: The rs66554220 (14 bp ID) variant is not a risk factor for NS-V in the Mexican population studied. To our knowledge, this is the first report about the topic in the Mexican population and worldwide that includes clinical features related with this HLA-G genetic variant.

Analysis of the heat shock protein 70 (HSP70) genetic variants in nonsegmental vitiligo patients.

BACKGROUND: Vitiligo is an autoimmune disease that courses with skin depigmentation because of the destruction of melanocytes. Vitiliginous melanocyte is prone to damage because of oxidative stress which activates cellular stress response and the release of heat shock proteins such as HSP70 promoting immune activation against the melanocyte. Variants in HSP70 genes (HSPA) might alter their expression and thus modulate vitiligo susceptibility. Therefore, we sought to evaluate the role of the 5' untranslated region HSPA1A G/C (rs1043618) and the exonic HSPA1B A/G (rs1061581) and HSPA1L T/C (rs2227956) gene variants in nonsegmental vitiligo. METHODS: A total of 200 nonsegmental vitiligo patients and 208 age/gender-matched healthy subjects were genotyped for rs1043618, rs1061581, and rs2227956 variants by PCR-RFLP. RESULTS: Variants rs1043618 and rs1061581 were not associated with vitiligo susceptibility. On the other hand, the rs2227956 C allele and TC genotype were associated with protection against vitiligo. A similar effect was observed for the GAC haplotype. Any of the aforementioned HSP70 gene variants were associated with the clinical characteristics of vitiligo. CONCLUSION: Our findings suggest that the HSPA1L rs2227956 gene variant might influence the susceptibility to vitiligo. Being the first study of HSP70 gene variants in vitiligo, further research is encouraged to corroborate these results.

The Chemokine MIG is Associated with an Increased Risk of COVID-19 Mortality in Mexican Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emergent viral disease in which the host inflammatory response modulates the clinical outcome. Severe outcomes are associated with an exacerbation of inflammation in which chemokines play an important role as the attractants of immune cells to the tissues. OBJECTIVE: To evaluate the relationship of the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10 with COVID-19 severity and outcomes in Mexican patients. METHODS: We analyzed the serum levels of IL-8, RANTES, MIG, MCP-1 and IP-10 in 148 COVID-19 hospitalized patients classified as mild (n=20), severe (n=61), and critical (n=67), as well as in healthy individuals (n=10), by flow cytometry bead array assay. RESULTS: Chemokine levels were higher in patients than in the healthy individuals, but only MIG, MCP-1, and IP-10 increased according to the disease severity, showing the highest levels in the critical group. MIG, MCP-1, and IP-10 levels were also higher in COVID-19 patients with comorbidities such as renal disease, type 2 diabetes, and hypertension. Moreover, elevated MIG levels seem to be related to organic failure/shock, and an increased risk of death. CONCLUSIONS: Our results suggest that the increased levels of MCP-1, IP-10, and especially MIG might be useful in predicting severe COVID-19 outcomes and could be promising therapeutic targets.

The Usefulness of Peripheral Blood Cell Counts to Distinguish COVID-19 from Dengue during Acute Infection.

COVID-19 and dengue disease are challenging to tell apart because they have similarities in clinical and laboratory features during the acute phase of infection, leading to misdiagnosis and delayed treatment. The present study evaluated peripheral blood cell count accuracy to distinguish COVID-19 non-critical patients from non-severe dengue cases between the second and eleventh day after symptom onset. A total of 288 patients infected with SARS-CoV-2 (n = 105) or dengue virus (n = 183) were included in this study. Neutrophil, platelet, and lymphocyte counts were used to calculate the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the neutrophil-lymphocyte*platelet ratio (NLPR). The logistic regression and ROC curves analysis revealed that neutrophil and platelet counts, NLR, LPR, and NLPR were higher in COVID-19 than dengue. The multivariate predictive model showed that the neutrophils, platelets, and NLPR were independently associated with COVID-19 with a good fit predictive value (p = 0.1041). The neutrophil (AUC = 0.95, 95% CI = 0.84-0.91), platelet (AUC = 0.89, 95% CI = 0.85-0.93) counts, and NLR (AUC = 0.88, 95% CI = 0.84-0.91) were able to discriminate COVID-19 from dengue with high sensitivity and specificity values (above 80%). Finally, based on predicted probabilities on combining neutrophils and platelets with NLR or NLPR, the adjusted AUC was 0.97 (95% CI = 0.94-0.98) to differentiate COVID-19 from dengue during the acute phase of infection with outstanding accuracy. These findings might suggest that the neutrophil, platelet counts, and NLR or NLPR provide a quick and cost-effective way to distinguish between dengue and COVID-19 in the context of co-epidemics in low-income tropical regions.

ß-defensin 1 Gene Polymorphisms are Associated with Kidney Disease in Northwestern Mexicans with Type 2 Diabetes.

Diabetic kidney disease (DKD) is one of the more limiting complications to the quality of life of diabetes mellitus patients. Studies including cultured cells, animal models, and case-control studies highlight the role of human ß-defensin-1 (hBD-1) in diabetes.This study assessed the association of hBD-1 gene (DEFB1) functional variations -52 G/A (rs1799946), -44 C/G (rs1800972) and -20 G/A (rs11362) with type 2 diabetes mellitus (T2DM) in order to investigate its effects on genetic susceptibility and progression to DKD in a Mexican population. A total of 214 T2DM patients with and without DKD (n = 102 and n = 112, respectively) and 117 healthy subjects participated in this case-control study. Genotyping was made by PCR-RFLPs. Clinical and biochemical parameters of all patients were measured. There was no statistically significant difference in genotype or allele frequencies between patients and healthy individuals. Nevertheless, compared with patients without DKD, DKD patients have a reduced prevalence of AA genotype of -52 G/A (OR = 0.307, 95% CI = 0.104-0.905, p =.026), as well as a higher frequency of GA genotype of -20 G/A variant (OR = 1.875, 95%CI = 1.031-3.409, p = .038). Our results suggest that rs1799946 and rs11362 could be useful variants to stratify T2DM Mexican patients in order to prescribe closer follow-up to prevent or retard DKD. Further tests in different ethnic groups are encouraged.

More Evidence of the Link of Interleukin-6 and Interleukin-10 with Critical COVID-19: A Report in Mexican Patients.

BACKGROUND: According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19. OBJECTIVE: To determine the association of serum cytokine levels with COVID-19 severity. METHODS: We studied the cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and the IFN-γ serum levels through flow cytometry in 56 COVID-19 patients (24 critical and 32 non-critical) from Northwest Mexico. RESULTS: We observed a significant increase in the IL-6 and the IL-10 levels in the sera of critical patients. These cytokines were also associated with mechanical ventilation necessity and death, IL-6 showing AUC values above 0.7 for both variables; and correlated with Na+, creatinine, and platelet levels. On the other hand, no association was found between IL-2, IL-4, TNF-α, and IFN-γ with tested variables. CONCLUSION: Our results corroborate previous observations regarding IL-6 and IL-10 involvement in the severity of COVID-19.

Lack of Effects of the Genetic Polymorphisms of Interleukin-10 in Clinical Outcomes of COVID-19.

Interleukin-10 (IL-10) gene polymorphisms have been associated with severity and outcomes in patients with respiratory and nonrespiratory viral infections. The aim of this study was to assess whether rs1800871 and rs1800872 polymorphisms of IL-10 gene are associated with the clinical outcomes of COVID-19 in a Mexican population. Study subjects were 193 COVID-19 patients. The genotyping was carried out with real-time PCR and serum IL-10 levels were measured with enzyme-linked immunosorbent assay. Logistic regression analysis was used for analysis association with clinical outcomes. There was no evidence of an association between alleles, genotypes, or haplotypes frequencies between patient groups according to severity and outcomes. The rs1800871 and rs1800872 polymorphisms might not be genetic risk factors for severity and mortality for COVID-19 in Mexican mestizos patients from northwest Mexico.

Case Report: Severe Craniofacial Coccidioidomycosis in a Pregnant Woman.

Coccidioidomycosis is a systemic fungal disease caused by Coccidioides immitis and Coccidioides posadasii. The lungs are the most common and often the initial site of involvement, and the non-pulmonary presentation is infrequent. We describe an unusual case of primary craniocutaneous coccidioidomycosis in a pregnant woman with infected bilateral periorbital nodules, intense pain at paranasal sinuses, and several osteolytic skull lesions. The analysis of 54 cases available in the literature makes us suggest that the area between the United States and Mexico is a risk zone for primary cutaneous coccidioidomycosis.

Intramedullary clear cell ependymoma of the lower thoracic spinal cord: report of a new case.

BACKGROUND: Clear cell ependymomas (CCEs) are a rare variant of tumors of the nervous system, the main location is the intracranial compartment. Special differential diagnosis should be done with oligodendrogliomas, neurocytoma, glioneurocytoma, astrocytoma, or metastatic renal cell carcinoma, lesions that somehow share cells with clear cytoplasm. Most of these lesions are benign but differential diagnosis is essential to decide further treatment. Few case reports of intramedullary CCEs have being published and there is no strict consensus on the diagnostic criteria. CASE DESCRIPTION: We hereby describe a new case of an intramedullary clear CCE with very few neurological symptoms, surgical treatment is satisfactory, histological and immunohistochemical analysis was confirmatory. After gross total resection and 3-year follow-up no recurrence of the lesion is evident. CONCLUSION: After this case presentation and review of the limited literature, it is evident that methodical clinical suspicion, radiological imaging combined with histological, and modern immunohistochemical techniques are essential for the diagnosis. Surgical options with gross total resection remain the cornerstone of its treatment. Neurophysiological monitoring is extremely useful to avoid postoperative morbidity.

Regulatory SNP rs5743417 impairs constitutive expression of human ß-defensin 1 and has high frequency in Africans and Afro-Americans.

The prediction of regulatory single nucleotide polymorphisms (rSNPs) in proximal promoters of disease-related genes could be a useful tool for personalized medicine in both patient stratification and customized therapy. Using our previously reported method of rSNPs prediction (currently a software called SNPClinic v.1.0) as well as with PredictSNP tool, we performed in silico prediction of regulatory SNPs in the antimicrobial peptide human ß-defensin 1 gene in three human cell lines from 1,000 Genomes Project (1kGP), namely A549 (epithelial cell line), HL-60 (neutrophils) and TH 1 (lymphocytes). These predictions were run in a proximal pseudo-promoter comprising all common alleles on each polymorphic site according to the 1,000 Genomes Project data (1kGP: ALL). Plasmid vectors containing either the major or the minor allele of a putative rSNP rs5743417 (categorized as regulatory by SNPClinic and confirmed by PredictSNP) and a non-rSNP negative control were transfected to lung A549 human epithelial cell line. We assessed functionality of rSNPs by qPCR using the Pfaffl method. In A549 cells, minor allele of the SNP rs5743417 G→A showed a significant reduction in gene expression, diminishing DEFB1 transcription by 33% when compared with the G major allele (p-value = .03). SNP rs5743417 minor allele has high frequency in Gambians (8%, 1kGP population: GWD) and Afro-Americans (3.3%, 1kGP population: ASW). This SNP alters three transcription factors binding sites (TFBSs) comprising SREBP2 (sterols and haematopoietic pathways), CREB1 (cAMP, insulin and TNF pathways) and JUND (apoptosis, senescence and stress pathways) in the proximal promoter of DEFB1. Further in silico analysis reveals that this SNP also overlaps with GS1-24F4.2, a lincRNA gene complementary to the X Kell blood group related 5 (XKR5) mRNA. The potential clinical impact of the altered constitutive expression of DEFB1 caused by rSNP rs5743417 in DEFB1-associated diseases as tuberculosis, COPD, asthma, cystic fibrosis and cancer in African and Afro-American populations deserves further research.

[Fatal invasive pulmonary aspergillosis in a patient with multiple non-classic risk factors]. / Aspergilosis pulmonar invasiva fatal en un paciente con factores de riesgo no clásicos.

BACKGROUND: Pulmonary aspergillosis is a severe invasive infection that mainly affects immunocompromised patients, causing a great mortality. CLINICAL CASE: We present a male patient with chronic ethilism, diabetes mellitus, and work exposure of inhalated harmful chemicals, who had a fatal outcome, that even when not presenting typical risk factors, developed a clinical presentation compatible, and mycological evaluation that support the diagnosis of a probably invasive pulmonary aspergillosis. CONCLUSION: The effect of the combination of the described non-typical situations as predisposing factors for pulmonary aspergillosis requires further research, given that they are non-typical factors.

INTRODUCCIÓN: la aspergilosis pulmonar es una infección invasiva severa que afecta principalmente a pacientes inmunocomprometidos y representa una causa importante de mortalidad. CASO CLÍNICO: presentamos un paciente con antecedentes de etilismo crónico, diabetes mellitus y exposición laboral recurrente a sustancias químicas nocivas inhaladas, quien tuvo un desenlace fatal, y que, incluso al no presentar factores de riesgo típicos, desarrolló una presentación clínica compatible y tuvo estudios micológicos que apoyan el diagnóstico de una probable aspergilosis invasiva. CONCLUSIÓN: el efecto de la combinación de tales situaciones no típicas como factores predisponentes de aspergilosis pulmonar amerita mayor investigación, dado que se trata de factores de riesgo no típicos.

First Evidence of Vertical Infection of Dengue Virus 2 in Aedes aegypti Mosquitoes from Sinaloa, Mexico.

Fourteen pools of Aedes aegypti larvae collected within the urban area of Culiacán, Sinaloa, were analyzed by RT-PCR. The results demonstrate, for the first time, the vertical infection of serotype-2 dengue virus (DENV-2) in Sinaloa, Mexico, suggesting that Ae. aegypti acts as a natural reservoir of DENV-2 in this region.

Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Susceptibility to Dengue Virus Infection in a Mexican Population.

To evaluate the association of the -308 and -238 tumor necrosis factor alpha (TNF-α) gene polymorphisms with clinical manifestations of dengue and TNF-α serum levels in a northwestern Mexican population. The study populations included dengue fever (DF) and dengue hemorrhagic fever (DHF) patients, and a group of healthy controls (HCs) without history of dengue. Polymerase chain reaction-restriction fragment length polymorphism and Enzyme-Linked Immunosorbent Assay were performed to determine genotypes and serum concentration of TNF-α, respectively. There were no significant differences in alleles, genotypes, and haplotype frequencies between patients and HCs. However, when patients were separated into DF and DHF, there was an increased prevalence of the -308 GA genotype in HCs compared to DHF (odds ratio [OR] = 0.129, 95% confidence interval [CI] = 0.018-0.945, p = 0.025), as well as the GG haplotype (OR = 0.49, 95% CI = 0.273-0.880, p = 0.01757) in DF. The genotypes of both polymorphisms were not associated with hematologic manifestations. Serum TNF-α levels were significantly higher in patients than in HCs (p = 0.004). Our results suggest a minimal effect of the -308 and -238 TNF-α gene polymorphisms in dengue patients and that their increased serum levels of TNF-α are independent of genotypes.

[Coexistence of acute appendicitis and dengue fever: A case report]. / Coexistencia de apendicitis aguda y fiebre por dengue: informe de un caso.

BACKGROUND: Dengue is the most important human viral disease transmitted by mosquitoes. It can be asymptomatic or it can present in any of its 3clinical forms: Dengue fever, dengue haemorrhagic fever and dengue shock syndrome. However, some atypical manifestations have been reported in surgical emergencies caused by acute appendicitis in patients with dengue fever. CLINICAL CASE: We report the case of an 18-year-old Mexican male who presented to the emergency department of the General Hospital of Culiacan, Sinaloa, with symptoms of dengue fever, accompanied by crampy abdominal pain with positive Rovsing and Dunphy signs. Dengue infection was confirmed by a positive NS1 antigen test performed by enzyme-linked immunosorbent assay. An abdominal ultrasound revealed an appendicular process; as the abdominal pain in the right side kept increasing, an open appendectomy was performed. Abundant inflammatory liquid was observed during the surgery, and the pathology laboratory reported an oedematous appendix with fibrinopurulent plaques, which agreed with acute ulcerative appendicitis. The patient was discharged fully recovered without complications during the follow-up period. CONCLUSIONS: Acute abdominal pain can be caused in some cases by dengue infection. This can be confusing, which can lead to unnecessary surgical interventions, creating additional morbidities and costs for the patient. This unusual and coincident acute appendicitis with dengue highlights the importance of performing careful clinical studies for appropriate decision making, especially in dengue endemic regions during an outbreak of this disease.