RESUMO
BACKGROUND: Food-grade titanium dioxide (E171), a white colourant widely used in ultra-processed food products, has been banned in the European Union. However, its usage is still permitted in medicines, and in several other countries. The estimated intake of E171 in children is higher than in adults, which led us to hypothesise that E171 induces differential effects depending on age, with adult mice being the most susceptible due to age, despite the lower dose. AIM: To evaluate the effects of oral administration of E171 on intestinal permeability, ileum, and colon histology, and how these effects impact anxious and depressive behaviour in young and adult mice of both sexes. METHODS: Young and adult mice of both sexes C57BL/6 mice received 10 mg/kgbw E171/3 times per week for 3 months. E171 was administered orally in water by pipetting, while control groups only received drinking water, then intestinal permeability, histology and animal behaviour were analysed. RESULTS: E171 showed an amorphous shape, primary particles sized below 1 µm and anatase crystalline structure. Oral administration of E171 disrupted the intestinal permeability in adult male and female mice, but no effects were observed in young mice of both sexes. E171 promoted ileal adenoma formation in half of the adult female population, moreover hyperplastic crypts, and hyperplastic goblet cells at histological level in adult mice of both sexes. The colon presented hyperplastic goblet cells, hyperchromatic nuclei, increased proliferation and DNA damage in adult mice of both sexes. The anxiety and depressive behaviour were only altered in adult mice treated with E171, but no changes were detected in young animals of both sexes. CONCLUSIONS: Adult mice displayed higher susceptibility in all parameters analysed in this study compared to young mice of both sexes.
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Aditivos Alimentares , Nanopartículas , Humanos , Criança , Masculino , Feminino , Animais , Camundongos , Aditivos Alimentares/química , Aditivos Alimentares/farmacologia , Camundongos Endogâmicos C57BL , Alimentos , Intestinos , Titânio/química , Nanopartículas/químicaRESUMO
Vasopressin regulates water homeostasis via the V2 receptor in the kidney at least in part through protein kinase A (PKA) activation. Vasopressin, through an unknown pathway, upregulates the activity and phosphorylation of Na+-Cl- cotransporter (NCC) and Na+-K+-2Cl- cotransporter 2 (NKCC2) by Ste20-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase 1 (OSR1), which are regulated by the with-no-lysine kinase (WNK) family. Phosphorylation of WNK4 at PKA consensus motifs may be involved. Inhibitor 1 (I1), a protein phosphatase 1 (PP1) inhibitor, may also play a role. In human embryonic kidney (HEK)-293 cells, we assessed the phosphorylation of WNK4, SPAK, NCC, or NKCC2 in response to forskolin or desmopressin. WNK4 and cotransporter phosphorylation were studied in desmopressin-infused WNK4-/- mice and in tubule suspensions. In HEK-293 cells, only wild-type WNK4 but not WNK1, WNK3, or a WNK4 mutant lacking PKA phosphorylation motifs could upregulate SPAK or cotransporter phosphorylation in response to forskolin or desmopressin. I1 transfection maximized SPAK phosphorylation in response to forskolin in the presence of WNK4 but not of mutant WNK4 lacking PP1 regulation. We observed direct PP1 regulation of NKCC2 dephosphorylation but not of NCC or SPAK in the absence of WNK4. WNK4-/- mice with desmopressin treatment did not increase SPAK/OSR1, NCC, or NKCC2 phosphorylation. In stimulated tubule suspensions from WNK4-/- mice, upregulation of pNKCC2 was reduced, whereas upregulation of SPAK phosphorylation was absent. These findings suggest that WNK4 is a central node in which kinase and phosphatase signaling converge to connect cAMP signaling to the SPAK/OSR1-NCC/NKCC2 pathway.NEW & NOTEWORTHY With-no-lysine kinases regulate the phosphorylation and activity of the Na+-Cl- and Na+-K+-2Cl- cotransporters. This pathway is modulated by arginine vasopressin (AVP). However, the link between AVP and WNK signaling remains unknown. Here, we show that AVP activates WNK4 through increased phosphorylation at putative protein kinase A-regulated sites and decreases its dephosphorylation by protein phosphatase 1. This work increases our understanding of the signaling pathways mediating AVP actions in the kidney.
Assuntos
Arginina Vasopressina , Proteínas Serina-Treonina Quinases , Camundongos , Humanos , Animais , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Células HEK293 , Arginina Vasopressina/metabolismo , Cotransportadores de K e Cl- , Desamino Arginina Vasopressina , Colforsina , Proteína Fosfatase 1/metabolismo , Rim/metabolismo , Membro 3 da Família 12 de Carreador de Soluto/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismoRESUMO
Aging is believed to occur across multiple domains, one of which is body composition; however, attempts to integrate it into biological age (BA) have been limited. Here, we consider the sex-dependent role of anthropometry for the prediction of 10-year all-cause mortality using data from 18,794 NHANES participants to generate and validate a new BA metric. Our data-driven approach pointed to sex-specific contributors for BA estimation: WHtR, arm and thigh circumferences for men; weight, WHtR, thigh circumference, subscapular and triceps skinfolds for women. We used these measurements to generate AnthropoAge, which predicted all-cause mortality (AUROC 0.876, 95%CI 0.864-0.887) and cause-specific mortality independently of ethnicity, sex, and comorbidities; AnthropoAge was a better predictor than PhenoAge for cerebrovascular, Alzheimer, and COPD mortality. A metric of age acceleration was also derived and used to assess sexual dimorphisms linked to accelerated aging, where women had an increase in overall body mass plus an important subcutaneous to visceral fat redistribution, and men displayed a marked decrease in fat and muscle mass. Finally, we showed that consideration of multiple BA metrics may identify unique aging trajectories with increased mortality (HR for multidomain acceleration 2.43, 95%CI 2.25-2.62) and comorbidity profiles. A simplified version of AnthropoAge (S-AnthropoAge) was generated using only BMI and WHtR, all results were preserved using this metric. In conclusion, AnthropoAge is a useful proxy of BA that captures cause-specific mortality and sex dimorphisms in body composition, and it could be used for future multidomain assessments of aging to better characterize the heterogeneity of this phenomenon.
Assuntos
Envelhecimento , Composição Corporal , Masculino , Humanos , Feminino , Inquéritos Nutricionais , Composição Corporal/fisiologia , Antropometria , Comorbidade , Índice de Massa Corporal , Tecido Adiposo/metabolismoRESUMO
The use of mixed microbial cultures (MMCs) is seen as an attractive strategy for polyhydroxyalkanoate (PHA) production. In order to optimize the MMC-PHA production process, tools are required to improve our understanding of the physiological state of the PHA-storing microorganisms within the MMC. In the present study, we explored the use of flow cytometry to analyse the metabolic state and polyhydroxybutyrate (PHB) content of the microorganisms from an MMC-PHA production process. A sequencing batch reactor under a feast and famine regime was used to enrich an MMC with PHB-storing microorganisms. Interestingly, once the PHB-storing microorganisms are selected, the level of PHB accumulation depends largely on the metabolic state of these microorganisms and not exclusively on the consortium composition. These results demonstrate that flow cytometry is a powerful tool to help to understand the PHA storage response of an MMC-PHA production process. KEY POINTS: ⢠Flow cytometry allows to measure PHB content and metabolic activity over time. ⢠Microorganisms showing high PHB content also have high metabolic activity. ⢠PHB producers with low metabolic activity show low PHB content.
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Reatores Biológicos , Poli-Hidroxialcanoatos , Poli-Hidroxialcanoatos/metabolismo , Citometria de Fluxo , FermentaçãoRESUMO
OBJECTIVE: Serum uric acid (SUA) has been associated with cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify a unifying mechanism linking elevated SUA to IR and VAT. METHODS: We conducted analyses in 226 subjects from the UIEM cohort with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation and explored the role of SUA and adiponectin by developing a network of causal mediation analyses to assess their impact on IR and VAT. These models were then translated to two population-based cohorts comprising 6337 subjects from NHANES 2003-2004 and 2011-2012 cycles in the US and ENSANUT Medio Camino 2016 in Mexico, using HOMA2IR and adipoIR as indicators of peripheral and adipose tissue IR, and METS-VF as a surrogate for VAT accumulation. RESULTS: SUA has a mediating role inside a bidirectional relationship between IR and visceral obesity, which was similar using either gold standard measurements or surrogate measures for IR and VAT. Furthermore, adiponectin acts as a linking mediator between elevated SUA and both peripheral IR and VAT accumulation. The proportion of the mechanism for IR-mediated (in either peripheral or adipose tissue) VAT accumulation was greater, compared to VAT-mediated IR accumulation (10.53% [9.23%-12.00%] to 5.44% [3.78%-7.00%]). Normal-range SUA levels can be used to rule-out underlying cardio-metabolic abnormalities in both men and women. CONCLUSIONS: Elevated SUA acts as a mediator inside the bidirectional relationship between IR and VAT accumulation and these observations could be applicable at a phenotype scale.
Assuntos
Resistência à Insulina , Ácido Úrico , Tecido Adiposo , Feminino , Técnica Clamp de Glucose , Humanos , Gordura Intra-Abdominal , Inquéritos NutricionaisRESUMO
BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic in Mexico City has been sharp, as several social inequalities at all levels coexist. Here we conducted an in-depth evaluation of the impact of individual and municipal-level social inequalities on the COVID-19 pandemic in Mexico City. METHODS: We analyzed suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases, from the Mexico City Epidemiological Surveillance System from 24 February 2020 to 31 March 2021. COVID-19 outcomes included rates of hospitalization, severe COVID-19, invasive mechanical ventilation, and mortality. We evaluated socioeconomic occupation as an individual risk, and social lag, which captures municipal-level social vulnerability, and urban population density as proxies of structural risk factors. Impact of reductions in vehicular mobility on COVID-19 rates and the influence of risk factors were also assessed. Finally, we assessed discrepancies in COVID-19 and non-COVID-19 excess mortality using death certificates from the general civil registry. RESULTS: We detected vulnerable groups who belonged to economically unfavored sectors and experienced increased risk of COVID-19 outcomes. Cases living in marginalized municipalities with high population density experienced greater risk for COVID-19 outcomes. Additionally, policies to reduce vehicular mobility had differential impacts modified by social lag and urban population density. Finally, we report an under-registry of COVID-19 deaths along with an excess mortality closely related to marginalized and densely populated communities in an ambulatory setting. This could be attributable to a negative impact of modified hospital admission criteria during the pandemic. CONCLUSIONS: Socioeconomic occupation and municipality-wide factors played a significant role in shaping the course of the COVID-19 pandemic in Mexico City.
Assuntos
COVID-19 , COVID-19/epidemiologia , Cidades/epidemiologia , Humanos , México/epidemiologia , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: SARS-CoV-2 testing capacity is important to monitor epidemic dynamics and as a mitigation strategy. Given difficulties of large-scale quantitative reverse transcription polymerase chain reaction (qRT-PCR) implementation, rapid antigen tests (Rapid Ag-T) have been proposed as alternatives in settings like Mexico. Here, we evaluated diagnostic performance of Rapid Ag-T for SARS-CoV-2 infection and its associated clinical implications compared to qRT-PCR testing in Mexico. METHODS: We analyzed data from the COVID-19 registry of the Mexican General Directorate of Epidemiology up to April 30th, 2021 (n = 6,632,938) and cases with both qRT-PCR and Rapid Ag-T (n = 216,388). We evaluated diagnostic performance using accuracy measures and assessed time-dependent changes in the Area Under the Receiver Operating Characteristic curve (AUROC). We also explored test discordances as predictors of hospitalization, intubation, severe COVID-19 and mortality. RESULTS: Rapid Ag-T is primarily used in Mexico City. Rapid Ag-T have low sensitivity 37.6% (95%CI 36.6-38.7), high specificity 95.5% (95%CI 95.1-95.8) and acceptable positive 86.1% (95%CI 85.0-86.6) and negative predictive values 67.2% (95%CI 66.2-69.2). Rapid Ag-T has optimal diagnostic performance up to days 3 after symptom onset, and its performance is modified by testing location, comorbidity, and age. qRT-PCR (-) / Rapid Ag-T (+) cases had higher risk of adverse COVID-19 outcomes (HR 1.54 95% CI 1.41-1.68) and were older, qRT-PCR (+)/ Rapid Ag-T(-) cases had slightly higher risk or adverse outcomes and ≥7 days from symptom onset (HR 1.53 95% CI 1.48-1.59). Cases detected with rapid Ag-T were younger, without comorbidities, and milder COVID-19 course. CONCLUSIONS: Rapid Ag-T could be used as an alternative to qRT-PCR for large scale SARS-CoV-2 testing in Mexico. Interpretation of Rapid Ag-T results should be done with caution to minimize the risk associated with false negative results.
Assuntos
Antígenos Virais/análise , Teste Sorológico para COVID-19 , COVID-19/diagnóstico , SARS-CoV-2/metabolismo , Adulto , Área Sob a Curva , COVID-19/epidemiologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , RNA Viral/análise , RNA Viral/metabolismo , Curva ROC , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Chronological age (CA) is a predictor of adverse coronavirus disease 2019 (COVID-19) outcomes; however, CA alone does not capture individual responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. METHOD: In this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (intensive care unit admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components. RESULTS: We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel >0 had higher risk of death and critical illness compared to those with lower values (log-rank p < .001). Using unsupervised clustering, we identified 4 adaptive responses to SARS-CoV-2 infection: (i) inflammaging associated with CA, (ii) metabolic dysfunction associated with cardiometabolic comorbidities, (iii) unfavorable hematological response, and (iv) response associated with favorable outcomes. CONCLUSIONS: Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.
Assuntos
Envelhecimento/imunologia , COVID-19/mortalidade , Inflamação/fisiopatologia , Metabolismo/fisiologia , Modelos Estatísticos , Comorbidade , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2RESUMO
We profiled cases with nonrespiratory symptoms (NRS) and asymptomatic severe acute respiratory syndrome coronavirus 2 infections assessed within Mexico City's Epidemiological Surveillance System. Initially asymptomatic or NRS cases have decreased risk of adverse outcomes compared with cases with respiratory symptoms. Comorbidity and age influence symptom development in initially asymptomatic cases.
Assuntos
COVID-19 , SARS-CoV-2 , Infecções Assintomáticas/epidemiologia , Comorbidade , Humanos , México/epidemiologiaRESUMO
BACKGROUND: Healthcare workers (HCWs) could be at increased occupational risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections due to increased exposure. Information regarding the burden of coronavirus disease 2019 (COVID-19) epidemic in HCWs living in Mexico is scarce. Here, we aimed to explore the epidemiology, symptoms, and risk factors associated with adverse outcomes in HCWs in Mexico City. METHODS: We explored data collected by the National Epidemiological Surveillance System in Mexico City, in HCWs who underwent real-time reverse transcription polymerase chain reaction (RT-PCR) test. We explored COVID-19 outcomes in HCWs and the performance of symptoms to detect SARS-CoV-2 infection. RESULTS: As of 20 September 2020, 57â 758 HCWs were tested for SARS-CoV-2 and 17â 531 were confirmed (30.35%); 6610 were nurses (37.70%), 4910 physicians (28.0%), 267 dentists (1.52%), and 5744 laboratory personnel and other HCWs (32.76%). Overall, 2378 HCWs required hospitalization (4.12%), 2648 developed severe COVID-19 (4.58%), and 336 required mechanical-ventilatory support (.58%). Lethality was recorded in 472 (.82%) cases. We identified 635 asymptomatic SARS-CoV-2 infections (3.62%). Compared with general population, HCWs had higher incidence, testing, asymptomatic cases, and mortality rates. No individual symptom offers adequate performance to detect SARS-CoV2. Older HCWs with chronic noncommunicable diseases and severe respiratory symptoms were associated with higher risk for adverse outcome; physicians were at higher risk compared with nurses and other HCWs. CONCLUSIONS: We report a high prevalence of SARS-CoV-2 infection in HCWs in Mexico City. Symptoms as a screening method are not efficient to discern those HCWs with a positive PCR-RT test. Particular attention should focus on HCWs with risk factors to prevent adverse outcomes.
Assuntos
COVID-19 , Pessoal de Saúde , Humanos , México , RNA Viral , SARS-CoV-2RESUMO
OBJECTIVES: To describe, evaluate, and identify the characteristics, prognostic factors, and visual outcomes in patients with intraocular foreign body (IOFB) in a Latin American population. METHODS: A retrospective, observational case-series of patients with a diagnosis of IOFB. Variables analyzed included age, gender, initial and final best correct visual acuity (BCVA), ocular trauma score, intraocular pressure, mechanism of injury, material and number of IOFB, zone of injury, timing of primary repair and IOFB removal, complications, and follow up. RESULTS: Sixty-one patients with IOFB were identified of which 97% were male with a mean age of 37.9 years (SD 2.16). The most common IOFB location was intravitreal (43%). IOFBs were metallic in 78%, vegetal in 3%, and other materials in 11%. Primary repair and secondary IOFB removal were performed at a mean timepoint of 3 days and 5 days, respectively. Systemic and topical antibiotics were administered to all patients. The initial BCVA was 1.62 logMAR and the final was 0.6 logMAR, which was statistically significant (Pearson's chi-squared test, p value 0.01). No cases of endophthalmitis were seen. CONCLUSION: IOFB removal can be delayed when there are no signs of infection or evidence of retinal detachment, without an increased risk of endophthalmitis and a negative impact on visual outcomes. Use of topical and systemic antibiotics appear sufficient to prevent endophthalmitis in these cases.
Assuntos
Corpos Estranhos no Olho , Ferimentos Oculares Penetrantes , Corpos Estranhos no Olho/diagnóstico , Corpos Estranhos no Olho/cirurgia , Ferimentos Oculares Penetrantes/diagnóstico , Ferimentos Oculares Penetrantes/cirurgia , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Centros de Traumatologia , Resultado do Tratamento , VitrectomiaRESUMO
BACKGROUND: COVID-19 has had a disproportionate impact on older adults. Mexico's population is younger, yet COVID-19's impact on older adults is comparable to countries with older population structures. Here, we aim to identify health and structural determinants that increase susceptibility to COVID-19 in older Mexican adults beyond chronological aging. METHODS: We analyzed confirmed COVID-19 cases in older adults using data from the General Directorate of Epidemiology of Mexican Ministry of Health. We modeled risk factors for increased COVID-19 severity and mortality, using mixed models to incorporate multilevel data concerning healthcare access and marginalization. We also evaluated structural factors and comorbidity profiles compared to chronological age for COVID-19 mortality risk prediction. RESULTS: We analyzed 20 804 confirmed SARS-CoV-2 cases in adults aged 60 and older. Male sex, smoking, diabetes, and obesity were associated with pneumonia, hospitalization, and intensive care unit (ICU) admission in older adults, CKD and COPD were associated with hospitalization. High social lag indexes and access to private care were predictors of COVID-19 severity and mortality. Age was not a predictor of COVID-19 severity in individuals without comorbidities and combination of structural factors and comorbidities were better predictors of COVID-19 lethality and severity compared to chronological age alone. COVID-19 baseline lethality hazards were heterogeneously distributed across Mexican municipalities, particularly when comparing urban and rural areas. CONCLUSIONS: Structural factors and comorbidity explain excess risk for COVID-19 severity and mortality over chronological age in older Mexican adults. Clinical decision-making related to COVID-19 should focus away from chronological aging onto more a comprehensive geriatric care approach.
Assuntos
COVID-19/mortalidade , COVID-19/fisiopatologia , Disparidades nos Níveis de Saúde , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , COVID-19/epidemiologia , Comorbidade , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Previous reports in European populations demonstrated the existence of five data-driven adult-onset diabetes subgroups. Here, we use self-normalizing neural networks (SNNN) to improve reproducibility of these data-driven diabetes subgroups in Mexican cohorts to extend its application to more diverse settings. RESEARCH DESIGN AND METHODS: We trained SNNN and compared it with k-means clustering to classify diabetes subgroups in a multiethnic and representative population-based National Health and Nutrition Examination Survey (NHANES) datasets with all available measures (training sample: NHANES-III, n=1132; validation sample: NHANES 1999-2006, n=626). SNNN models were then applied to four Mexican cohorts (SIGMA-UIEM, n=1521; Metabolic Syndrome cohort, n=6144; ENSANUT 2016, n=614 and CAIPaDi, n=1608) to characterize diabetes subgroups in Mexicans according to treatment response, risk for chronic complications and risk factors for the incidence of each subgroup. RESULTS: SNNN yielded four reproducible clinical profiles (obesity related, insulin deficient, insulin resistant, age related) in NHANES and Mexican cohorts even without C-peptide measurements. We observed in a population-based survey a high prevalence of the insulin-deficient form (41.25%, 95% CI 41.02% to 41.48%), followed by obesity-related (33.60%, 95% CI 33.40% to 33.79%), age-related (14.72%, 95% CI 14.63% to 14.82%) and severe insulin-resistant groups. A significant association was found between the SLC16A11 diabetes risk variant and the obesity-related subgroup (OR 1.42, 95% CI 1.10 to 1.83, p=0.008). Among incident cases, we observed a greater incidence of mild obesity-related diabetes (n=149, 45.0%). In a diabetes outpatient clinic cohort, we observed increased 1-year risk (HR 1.59, 95% CI 1.01 to 2.51) and 2-year risk (HR 1.94, 95% CI 1.13 to 3.31) for incident retinopathy in the insulin-deficient group and decreased 2-year diabetic retinopathy risk for the obesity-related subgroup (HR 0.49, 95% CI 0.27 to 0.89). CONCLUSIONS: Diabetes subgroup phenotypes are reproducible using SNNN; our algorithm is available as web-based tool. Application of these models allowed for better characterization of diabetes subgroups and risk factors in Mexicans that could have clinical applications.
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Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Aprendizado de Máquina , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Inquéritos Nutricionais , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The SARS-CoV-2 outbreak poses a challenge to health care systems due to its high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity, and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of the Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19-related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among the 177â 133 subjects at the time of writing this report (May 18, 2020), we observed 51â 633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, chronic obstructive pulmonary disease, advanced age, hypertension, immunosuppression, and chronic kidney disease (CKD); we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for intensive care unit admission and intubation. Our predictive score for COVID-19 lethality included ageâ ≥â 65 years, diabetes, early-onset diabetes, obesity, ageâ <â 40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (C-statisticâ =â 0.823). CONCLUSIONS: Here, we propose a mechanistic approach to evaluate the risk for complications and lethality attributable to COVID-19, considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first-contact scenario.
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Betacoronavirus , Infecções por Coronavirus/mortalidade , Diabetes Mellitus/mortalidade , Obesidade/mortalidade , Pneumonia Viral/mortalidade , Adulto , Fatores Etários , Idoso , COVID-19 , Comorbidade , Infecções por Coronavirus/imunologia , Bases de Dados Factuais , Suscetibilidade a Doenças , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hospedeiro Imunocomprometido , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Prognóstico , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/mortalidade , Insuficiência Renal Crônica/mortalidade , Medição de Risco/métodos , Fatores de Risco , SARS-CoV-2 , Fatores SexuaisRESUMO
RATIONALE & OBJECTIVE: Mesoamerican nephropathy (MeN), a form of chronic kidney disease (CKD) of unknown cause in Central America, affects young individuals working in physically strenuous occupations. Repeated episodes of work-related kidney injury may lead to CKD in this setting. We aimed to better understand the burden and natural history of acute kidney injury (AKI) in workers at risk for MeN. STUDY DESIGN: Cross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI. SETTING & PARTICIPANTS: 326 sugarcane workers with normal preharvest serum creatinine (Scr) values and no history of CKD in an MeN hotspot in Nicaragua near the end of the harvest, and prospective follow-up of workers with AKI. PREDICTOR: AKI during the harvest, as defined by Scr level increase ≥ 0.3mg/dL over baseline to a level ≥ 1.3mg/dL. OUTCOMES: Kidney function trajectory and development of CKD over 12 months. ANALYTICAL APPROACH: Linear regression models were used to analyze the association between job category and kidney function. For workers with AKI, the effect of time on Scr level was evaluated using linear mixed effects. RESULTS: 34 of 326 participants were found to have AKI, with a median late-harvest Scr level of 1.64mg/dL in the AKI group. Workers without AKI had a median Scr level of 0.88mg/dL. AKI was more common among cane cutters compared with other field workers. Participants with AKI had variable degrees of kidney function recovery, with median 6- and 12-month Scr values of 1.25 and 1.27mg/dL, respectively (P < 0.001 for each follow-up value compared to late-harvest Scr). When we compared workers' kidney function before the AKI episode to their kidney function at last follow-up, 10 participants with AKI developed de novo estimated glomerular filtration rate < 60mL/min/1.73m2 and 11 had a >30% decrease in estimated glomerular filtration rate. LIMITATIONS: Follow-up limited to 1 year and some loss to follow-up in the prospective component of the study. Broad definition of AKI that includes both acute and subacute kidney injury. CONCLUSIONS: In a group of sugarcane workers with normal preharvest kidney function, newly decreased kidney function developing during the harvest season was common. Of those with kidney injury, nearly half had established CKD 12 months later.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Doenças Profissionais/etiologia , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/epidemiologia , Saccharum/efeitos adversos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Adulto , América Central/epidemiologia , Creatinina/sangue , Estudos Transversais , Bases de Dados Factuais , Progressão da Doença , Fazendeiros/estatística & dados numéricos , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/fisiopatologia , Saúde Ocupacional , Prevalência , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Medição de RiscoRESUMO
Objetivo: identificar los factores relacionados al cumplimiento y abandono del tratamiento antituberculoso en pacientes del Hospital Rosario Lacayo de la ciudad de León, Nicaragua. Método: estudio de casos y controles no pareados en pacientes con tuberculosis durante octubre 2015- agosto 2016. Se definieron como casos los pacientes que abandonaron el tratamiento por 30 días consecutivos o más; como controles los que completaron el tratamiento y fueron dados de alta por curación. Los factores se identificaron mediante el cálculo de odds ratios y los intervalos de confianza al 95%. Resultados: se estudiaron 28 casos y 98 controles. El abandono del tratamiento se asoció al sexo masculino, a no recibir explicación acerca de la enfermedad, a que no se brindaran consejos sobre estilo de vida, a no conocer el esquema de tratamiento empleado y a la mala relación con el personal de salud. Conclusión: el abandono del tratamiento antituberculoso se relacionó a factores no modificables (sexo masculino) y a otros cuyo control optimizaría el cumplimiento (no recibir explicación sobre la enfermedad y mala relación con el personal de salud). Además, es prioritario brindar atención de forma integral a los pacientes y mejorar la información recibida sobre tuberculosis.
Objective: to identify factors related to compliance and abandonment of antituberculosis treatment in patients of the Rosario Lacayo Hospital in the city of León, Nicaragua. Method: study of unpaired cases and controls in patients with tuberculosis during October 2015 to August 2016. Patients who abandoned treatment for 30 consecutive days or longer were defined as cases; As controls those who completed the treatment and were discharged by cure. Factors were identified by calculating odds ratios and 95% confidence intervals. Results: we studied 28 cases and 98 controls. The abandonment of the treatment was associated with the male sex, not receiving an explanation about the disease, no advice on lifestyle, not knowing the treatment scheme used and poor relationship with health personnel. Conclusion: the abandonment of tuberculosis treatment was related to non-modifiable factors (male sex) and to others whose control would optimize compliance (not receiving explanation about the disease and poor relation with health personnel). In addition, it is a priority to provide comprehensive care to patients and to improve the information received about tuberculosis.
Objetivo: identificar os fatores relacionados ao atendimento e ao abandono do tratamento da tuberculose em pacientes do Hospital Rosario Lacayo da cidade de Leon, na Nicarágua. Métodos: estudo de caso-controle não pareado em pacientes com tuberculose durante outubro de 2015 e agosto de 2016. Os pacientes que interromperam o tratamento por 30 dias consecutivos ou mais foram definidos como casos; como controles aqueles que completaram o tratamento e receberam alta por cura. Os fatores foram identificados calculando odds ratio e intervalos de confiança de 95%. Resultados: a idade média dos participantes foi de 19,1 anos, o sexo feminino predominou com 82,0%. 25,4% mencionado estudo e trabalho. 65,3% do total da amostra relataram níveis de estresse moderado a elevado. A prevalência do consumo de álcool no último ano e no último mês foi de 59,0 e 32,2%, respectivamente. 27,5% do total da amostra relataram consumo dependente, seguido por 16,6% do consumo prejudicial. Conclusão: o abandono do tratamento da tuberculose foi relacionada a fatores não modificáveis (masculinos) e a outros cujo o controle otimizaria o cumprimento (não receber uma explicação sobre a doença e má relação com o pessoal de saúde). Além disso, é prioridade ofertar atenção integral aos pacientes e melhorar as informações recebidas sobre a tuberculose.
Assuntos
Tuberculose , Cooperação do Paciente , Saúde PúblicaRESUMO
La radionecrosis del tallo cerebral es una de las complicaciones de la radioterapia en pacientes que han recibido tratamiento para un tumor intracraneal, y aunque afortunadamente no es lo más frecuente, sus consecuencias pueden ser devastadoras, pues la importancia del tejido comprometido hace que se generen lesiones que pueden producir secuelas altamente incapacitantes y hasta la muerte del paciente como en efecto sucedió en el presente caso. Según la FDA (Food and Drug Administration) el Oxígeno Hiperbárico (OHB) se encuentra indicado en la radionecrosis ósea y radionecrosis de tejidos blandos (1); el Comité Europeo para Medicina Hiperbárica incluyó la radionecrosis del tejido nervioso central en las indicaciones del oxígeno hiperbárico (2). El caso reportado es el de una paciente de 28 años de edad, con un meduloblastoma de fosa posterior que fue tratado con cirugía y químio-radioterapia, quedando la paciente muy bien clínicamente. 21 meses después del tratamiento inicial presenta síntomas que sugieren una lesión en el tallo cerebral, por lo que nuevamente consulta y posterior a estudios imagenológicos se logra determinar que se trata de una lesión del tallo cerebral por radionecrosis. En julio de 2011 la paciente ya presentaba disartria, bradilalia, lateropulsión izquierda, diplopía, cefalea, marcha atáxica y espasticidad de las cuatro extremidades con predominio del hemicuerpo izquierdo. Al momento de iniciar el tratamiento con OHB (septiembre de 2011), se encontró cuadriparesia no funcional. Se realizaron 6 sesiones con OHB, tratamiento con bevacizumab y corticoides, a pesar de lo cual, la evolución de la paciente fue tórpida y rápidamente fulminante llevándola a la muerte en menos de seis meses. La discusión que surge con este caso clínico, es si el tratamiento con OHB debería ser más enfocado a la prevención y profilaxis que al tratamiento de lesiones que por su ubicación anatómica revisten una alta gravedad y pueden ser irreversibles, una vez que se encuentran instauradas.
Brain stem radionecrosis is a complication of radiotherapy in patients who have been treated for a tumor, and although fortunately not very common, its consequences can be devastating since the importance of the involved tissue causes generation of lesions which can give as a result highly disabling lesions or even the patient's death, as indeed happened in this case. According to the FDA (Food and Drug Administration), Hyperbaric Oxygen (HBO) is indicated in bone and soft tissues radionecrosis (Regulations, 2012), including in the latter the central nervous system. The reported case is a 28-year female patient presenting with a posterior fossa medulloblastoma that was treated with surgery and chemo-radiotherapy. Twenty one months after the initial treatment, she presents with symptoms suggestive of a brain stem lesion for which reason she consults once again, and after imaging studies, a brain stem lesion due to radionecrosis is ascertained. In July 2011 the patient was already presenting with dysarthria, bradilalia, left lateropulsion, diplopy, cephalea, ataxic gait and symmetrical spasticity with predominance of left hemibody. Upon treatment initiation with OHB (September 2011) nonfunctional quadriparesis was found. Six sessions with OHB were performed, and treatment with bevacizumab and corticosteroid agents was given despite which the patient's evolution was poor and fulminating leading to death within less than six months. The discussion rising from this clinical case is whether treatment with OHB should be more focused on prevention and prophylaxis than on treatment of lesions which, because of their anatomical location, entail high seriousness and can be irreversible once they are set up.
O radionecrose tronco cerebral é uma das complicações da radioterapia em pacientes tratados por um tumor intracraniano, e embora felizmente não tão freqüentes, as conseqüências podem ser devastadoras, como a importância da comprometidas causas lesão tecidual gerados que pode produzir altamente seqüelas incapacitantes e até mesmo a morte do paciente como de fato aconteceu neste caso. De acordo com o FDA (Food and Drug Administration) Oxigenoterapia Hiperbárica (OHB) a terapia é indicada na radionecrose radionecrose ossos e tecidos moles (1), o Comité Europeu de Medicina Hiperbárica incluído necrose radiação do tecido nervoso central nas indicações da oxigenoterapia hiperbárica (2). O caso é relatado de um 28-year-old com um meduloblastoma fossa posterior que foi tratado com cirurgia e quimio-radioterapia, o paciente permanecer clinicamente bem. 21 meses após o tratamento inicial tem sintomas que sugerem uma lesão no tronco cerebral, por isso novamente depois de estudos de consulta e de imagem foram capazes de determinar que é um prejuízo para o radionecrose tronco cerebral. Em julho de 2011, o paciente já teve disartria, bradilalia, lateropulsão esquerda, diplopia, cefaléia, ataxia de marcha e espasticidade de todos os quatro membros com dominância do hemisfério esquerdo. Ao iniciar o tratamento com HBO (Setembro de 2011), não encontrou quadriplegia funcional. Foram realizadas 6 sessões com OHB, bevacizumab e terapia com esteróides, apesar de que, a evolução do paciente foi entorpecida e rapidez fulminante levando à sua morte, em menos de seis meses.
Assuntos
Humanos , Feminino , Adulto , Oxigenoterapia Hiperbárica , Radioterapia , Tronco Encefálico , MeduloblastomaRESUMO
La Enfermedad Arterial Oclusiva Crónica (EAOC), es una entidad de sensibles impactos, dado que en sus mecanismos fisiopatológicos se genera una isquemia e hipoxia, que desvitalizan elementos tisulares dando paso a alteraciones integumentarias con aparición de úlceras de difícil manejo que se pueden sobreinfectar e incluso generar la amputación de extremidades. No siendo frecuente que en los tratamientos clínicos se dé la aplicación de oxígenoterapia hiperbárica, que podría reversar los mecanismos de alteraciones fisiopatológicas. Este trabajo corresponde a un estudio transversal desarrollado en la Unidad de Medicina Hiperbárica del Hospital Militar Central. Que contó con cuarenta y cinco pacientes intervenidos entre los años de 2004 a 2008.que presentaron úlceras arteriales arteriales. Los pacientes tenían una edad media de 68 años, habiendo recibido el 50% de ellos, un número de 20 sesiones, con una presión de 1.5 atmosferas en el 50% de los casos, lográndose una satisfactoria evolución de sus compromisos en el 77.7% de los casos (n=35, error estándar=0.03).
Chronic Occlusive Arterial Disease (COAD) is an entity that has a significant impact since over its pathophysiological mechanisms ischemia and hypoxia are generated thus devitalizing tissue elements and giving rise to disturbances with the appearance of integumentary ulcers that can be unmanageable and even lead to superinfection and subsequent amputation of limbs. However, it is not common in clinical treatment to administer hyperbaric oxygen therapy even though it might reverse the mechanisms of such pathophysiological disturbances. This work corresponds to a cross-sectional study carried out in the Hyperbaric Medicine Unit of the Central Military Hospital in 45 patients with mean age of 68 years who had arterial ulcers and underwent surgical procedures between 2004 and 2008. Fifty percent of patients received 20 sessions with a pressure of 1.5 atmospheres in 50% of cases, achieving a satisfactory evolution of the involved areas in 77.7% of cases (n = 35, standard error = 0.03).
A doença arterial obstrutiva crônica (DAOC) é uma entidade de sensíveis impactos, dado que em seus mecanismos fisiopatológicos se gera uma isquemia e hipoxia, que desvitalizam elementos tisulares levando a alterações tegumentárias com aparição de úlceras de difícil tratamento, que podem se infetar e inclusive gerar a amputação de membros. Não sendo frequente que nos tratamentos clínicos se dê a aplicação de oxigenoterapia hiperbárica, que poderia reverter os mecanismos de alterações fisiopatológicas. Este trabalho corresponde a um estudo transversal desenvolvido na Unidade de Medicina Hiperbárica do Hospital Militar Central, que contou com quarenta e cinco pacientes intervindos entre os anos de 2004 a 2008, que apresentaram úlceras arteriais. Os pacientes tinham uma idade média de 68 anos, havendo recebido 50% deles, um número de 20 sessões, com una pressão de 1.5 atmosferas em 50% dos casos e conseguindo-se uma satisfatória evolução de seus compromissos em 77.7% dos casos (n=35, erro padrão=0.03).
Assuntos
Humanos , Doença Arterial Periférica , Oxigenoterapia , Terapêutica , ColômbiaRESUMO
Total cDNA isolated from cellulolytic fungi cultured in cellulose was examined for the presence of sequences encoding for endoglucanases. Novel sequences encoding for glycoside hydrolases (GHs) were identified in Fusarium oxysporum, Ganoderma applanatum and Trametes versicolor. The cDNA encoding for partial sequences of GH family 61 cellulases from F. oxysporum and G. applanatum shares 58 and 68% identity with endoglucanases from Glomerella graminicola and Laccaria bicolor, respectively. A new GH family 5 endoglucanase from T. versicolor was also identified. The cDNA encoding for the mature protein was completely sequenced. This enzyme shares 96% identity with Trametes hirsuta endoglucanase and 22% with Trichoderma reesei endoglucanase II (EGII). The enzyme, named TvEG, has N-terminal family 1 carbohydrate binding module (CBM1). The full length cDNA was cloned into the pPICZαB vector and expressed as an active, extracellular enzyme in the methylotrophic yeast Pichia pastoris. Preliminary studies suggest that T. versicolor could be useful for lignocellulose degradation.
Assuntos
Celulases/genética , Proteínas Fúngicas/genética , Trametes/enzimologia , Trametes/genética , Sequência de Aminoácidos , Sequência de Bases , Celulases/química , Celulases/metabolismo , Clonagem Molecular , DNA Fúngico/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Expressão Gênica , Genes Fúngicos , Dados de Sequência Molecular , Filogenia , Pichia/enzimologia , Pichia/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de AminoácidosRESUMO
BACKGROUND: Pre-diabetic Latino subjects have shown higher incidence of type 2 diabetes mellitus (DM2) compared with other populations. The incidence is unknown in the Mexican population. Our aim was to identify the annual incidence of DM2 among a Mexican pre-diabetic population. METHODS: An inception cohort of healthy Mexican patients was followed from 2001 to 2006. Those who fulfilled diagnosis of DM2 (ADA criteria) were registered at one and 2 years of follow-up among pre-diabetic and normoglucemic individuals. We compared relevant variables between both groups, those who developed diabetes and those who did not. RESULTS: 656 subjects were included; at one year, 14 patients were diagnosed with DM2, 11 among pre-diabetics, incidence of 4.5 %; 3 among normoglucemic subjects, incidence of 0.72 %. The relative risk for the development of DM2 in the pre-diabetic group was 7.7 (IC95 % 2.1-27.9), and among the normoglucemic group of 1.04 (IC95 % 1.02-1.08). At the 2nd year, DM2 incidence was 7.6 % in pre-diabetics, and 0.6 % in normoglucemics. Risk factors associated were higher fast glucose and greater BMI. CONCLUSIONS: We found a constant annual incidence of DM2 among prediabetics of 6 cases per 100 patient/year in follow-up. Higher fast glucose determinations and greater BMI are the main determinants for DM2 development.