Retrospective Analysis of Severe Dengue by Dengue Virus Serotypes in a Population with Social Security, Mexico 2023.

BACKGROUND: Risk factors for severe dengue manifestations have been attributed to various factors, including specific serotypes, sex, and age. Mexico has seen the re-emergence of DENV-3, which has not circulated in a decade. OBJECTIVE: To describe dengue serotypes by age, sex, and their association with disease severity in dengue-positive serum samples from epidemiological surveillance system units. MATERIALS AND METHODS: A descriptive analysis was conducted to evaluate the frequency of dengue severity by sex, age, disease quarter, geographical location, and dengue virus serotypes. The study was conducted using laboratory samples from confirmed dengue cases through RT-qPCR from the epidemiological surveillance laboratory network of the Mexican Social Security Institute, Mexico. Simple frequencies and proportions were calculated using the z-test for proportional differences between groups. Bivariate analysis with adjusted Chi2 was performed, and binary logistic regression models were constructed using the forward Wald method considering the model's predictive capacity. The measure of association was the odds ratio, with 95% confidence intervals. Statistical significance was set to an alpha level of <0.05. RESULTS: In 2023, 10,441 samples were processed for dengue RT-qPCR at the IMSS, with a predominance of serotype DENV-3 (64.4%). The samples were mostly from women (52.0%) and outpatient cases (63.3%). The distribution of dengue severity showed significant variations by age, with a lower proportion of severe cases in young children and a higher proportion in the 5- to 14-year-old group. Hospitalizations increased significantly with severity. Warm regions had more cases overall and severity. Cases were most frequent from July to September. While DENV-2 was associated with severity, DENV-4 was not. Binary regression identified higher risk in women, age extremes, and DENV-2, with an overall predictive model of 58.5%. CONCLUSIONS: Women, age groups at the extremes of life, and the DENV-2 serotype presented severe risk of dengue in a population with social security in Mexico during 2023.

Impact of vaccination on infection or death from COVID-19 in individuals with laboratory-confirmed cases: Case-control study.

OBJECTIVES: The objective of this study is to estimate the effectiveness of COVID-19 vaccines in people treated within the social security system whose vaccination status was reported to the epidemiological surveillance system. STUDY DESIGN: Case-control study. METHODS: This was a case-control study conducted. The records of individuals with suspected cases of COVID-19 registered in the epidemiological surveillance system between February 1 and June 30, 2021, were studied. RT-qPCR was performed to determine SARS-CoV-2 infection; those with a positive result were considered cases, and those with a negative result were considered controls. The ratio between cases and controls was 1:1.3. The crude and adjusted vaccine effectiveness was considered the prevention of symptomatic infection and death and calculated as the difference between the dose and the risk, with a survival analysis among vaccinated people. RESULTS: A total of 94,416 individuals were included, of whom 40,192 were considered cases and 54,224 controls; 3,781 (4.00%) had been vaccinated against COVID-19. Vaccination also proved to be a protective factor against COVID-19, especially in the population who received a second dose (OR = 0.31; 95% CI 0.28-0.35). With the application of the vaccine, there was a protective effect against mortality (OR = 0.76; 95% CI 0.66-0.87). Disease prevention was higher for the BNT162-2 mRNA vaccine (82%) followed by the ChAdOx1 vaccine (33%). In the survival analysis, vaccination provided a protective effect. CONCLUSIONS: There was a positive impact of vaccines for the prevention of symptomatic COVID-19, with a second dose generating greater efficacy and a reduction in deaths.

Diversity, composition, and networking of saliva microbiota distinguish the severity of COVID-19 episodes as revealed by an analysis of 16S rRNA variable V1-V3 region sequences.

Studies on the role of the oral microbiome in SARS-CoV-2 infection and severity of the disease are limited. We aimed to characterize the bacterial communities present in the saliva of patients with varied COVID-19 severity to learn if there are differences in the characteristics of the microbiome among the clinical groups. We included 31 asymptomatic subjects with no previous COVID-19 infection or vaccination; 176 patients with mild respiratory symptoms, positive or negative for SARS-CoV-2 infection; 57 patients that required hospitalization because of severe COVID-19 with oxygen saturation below 92%, and 18 fatal cases of COVID-19. Saliva samples collected before any treatment were tested for SARS-CoV-2 by PCR. Oral microbiota in saliva was studied by amplification and sequencing of the V1-V3 variable regions of 16S gene using an Illumina MiSeq platform. We found significant changes in diversity, composition, and networking in saliva microbiota of patients with COVID-19, as well as patterns associated with severity of disease. The presence or abundance of several commensal species and opportunistic pathogens were associated with each clinical stage. Patterns of networking were also found associated with severity of disease: a highly regulated bacterial community (normonetting) was found in healthy people whereas poorly regulated populations (disnetting) were characteristic of severe cases. Characterization of microbiota in saliva may offer important clues in the pathogenesis of COVID-19 and may also identify potential markers for prognosis in the severity of the disease. IMPORTANCE SARS-CoV-2 infection is the most severe pandemic of humankind in the last hundred years. The outcome of the infection ranges from asymptomatic or mild to severe and even fatal cases, but reasons for this remain unknown. Microbes normally colonizing the respiratory tract form communities that may mitigate the transmission, symptoms, and severity of viral infections, but very little is known on the role of these microbial communities in the severity of COVID-19. We aimed to characterize the bacterial communities in saliva of patients with different severity of COVID-19 disease, from mild to fatal cases. Our results revealed clear differences in the composition and in the nature of interactions (networking) of the bacterial species present in the different clinical groups and show community-patterns associated with disease severity. Characterization of the microbial communities in saliva may offer important clues to learn ways COVID-19 patients may suffer from different disease severities.

Modification of HIF-1α, NF-aκB, IGFBP-3, VEGF and adiponectin in diabetic foot ulcers treated with hyperbaric oxygen.

Introduction: Diabetic foot ulcers are a frequent complication of diabetes and the first cause of non-traumatic lower limb amputation. They affect quality of life, restrict social productivity and generate a high economic burden for health care systems. Hyperbaric oxygen (HBO2) therapy is an adjunctive treatment option because it improves wound healing in the short term. However, its ability to modulate the pro- and anti-inflammatory balance and the hypoxic cell response in the clinical setting has not been fully described. Objective: To determine modifications in HIF-1α, NF-κB, IGFBP-3, and VEGF expression in wounds as well as circulating inflammatory cytokines in patients with diabetic foot ulcers subjected to HBO2. Materials and methods: We studied 17 ambulatory patients and one hospitalized patient with diabetic foot ulcers classified as Grade 3 or 4 according to the Wagner scale. All underwent HBO2 therapy. Tissue expression of HIF-1α, NF-κB, IGFBP-3, and VEGF was determined by immunohistochemistry. Plasma levels of adiponectin, IL-6, IFN-γ, IL-10 and IL-4 were measured by ELISA and chemiluminescence. Fibrosis and angiogenesis were determined by Masson's trichrome staining. Results: Ulcers in all patients healed after one month of HBO2, and none presented relapses at the one-year follow-up. At the beginning of treatment, HIF-1α and NF-κB expression was observed mainly in the nucleus, whereas these proteins were localized in the cytoplasm at the end of HBO2. There were significant modifications in VEGF expression after therapy, an increase in the plasma level of proinflammatory IL-6, and a decrease in that of IFN-γ. IGFBP-3 expression and plasma levels of adiponectin were increased at the end of HBO2. Increases in fibrosis and angiogenesis were also observed. Conclusion: These results suggest that adjuvant HBO2 modifies the proinflammatory balance related to the cellular response to hypoxia.

In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential.

The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.

Modification of gene products involved in resistance to apoptosis in metastatic colon cancer cells: roles of Fas, Apaf-1, NFkappaB, IAPs, Smac/DIABLO, and AIF.

BACKGROUND: Colon cancer becomes resistant to apoptosis as it acquires metastatic potential. SW480 and SW620 colon cancer cells were established from the same patient at different stages of tumor progression. The stage III colorectal cancer cell line (SW620) is more resistant to apoptosis. In the present report, we investigated the apoptotic gene products that might account for colon cancer evasion of immune attack and chemoradioresistance-induced apoptosis. METHODS: SW480 and SW620 cells were used for this experiment. Type 1 apoptosis was induced by CH-11. Type 2 apoptosis was induced by cisplatin and ionizing radiation. Apoptosis was determined by caspase-3 activity and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling. Gene products Fas, TRAIL, c-FLIP, Bid, BAX, Bcl-2, Bcl-xL, Apaf-1, nuclear factor-kappa B, Smac/DIABLO, apoptosis inducing factor, and the inhibitors of apoptosis were investigated by immunocytochemistry and Western blot analyses. RESULTS: SW620 cell lines were more resistant to both Type 1 and Type 2 apoptosis induced by CH-11, cisplatin, and ionizing radiation, respectively. Examination of the extrinsic pathway demonstrated Fas receptor to be down-regulated in SW620. Apaf-1 was decreased in SW620 cells; while other members of the mitochondrial pathway including Bax, Bid, Bcl-xL, and Bcl-2 demonstrated minimal alterations of protein levels in both cell lines. Survivin and XIAP protein levels were increased in SW620 cells, which correlated with nuclear expression of nuclear factor-kappa B in SW620 cells but not SW480. Mitochondrial-released factors including Smac/DIABLO and apoptosis inducing factor were increased in SW480 cells. CONCLUSIONS: SW620 cells have acquired genetic defects both in the intrinsic and extrinsic pathways of apoptosis, which may explain in part the ability of colon cancer cells to escape the immune system and to become chemoradioresistant. These genes may be potential targets for chemoradiosensitization in advanced colorectal cancer.