Publications by authors named "Maria Molina"

396 Publications

Routine Biomarkers for the Severity of COVID-19 Pneumonia May Present Differently in Kidney Transplant Recipients.

Transplant Proc 2021 Aug 14. Epub 2021 Aug 14.

Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.

Background: The treatment of coronavirus disease 2019 (COVID-19) is based on the patient's clinical status and levels of inflammatory biomarkers. The comparative activity of these biomarkers in kidney transplant (KT) patients with COVID-19 pneumonia from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and non-SARS-CoV-2 etiologies is unknown. The aim of this study was to compare the clinical presentation and inflammatory parameters at admission of KT patients with COVID-19 pneumonia and those with non-COVID-19 pneumonia over the same period.

Methods: Biomarkers were measured and compared between KT patients with COVID-19 pneumonia (n = 57) and non-COVID-19 pneumonia (n = 20) from March 2020 to March 2021.

Results: Both groups showed comparable demographics. The KT patients with COVID-19 had fewer neutrophils (6824 ± 5000 vs 8969 ± 4206; P = .09) than the non-COVID group, although there was no significant difference in the lymphocyte count. Non-COVID-19 pneumonia was associated with higher d-dimer (median, 921 [interquartile range (IQR), 495-1680] vs median, 2215 [IQR, 879-3934]; P = 0.09) and interleukin-6 (median, 35 [IQR, 20-128] vs median, 222 [IQR, 38-500]; P = 0.006) levels. The ferritin level was higher in the COVID-19 group (median, 809 [IQR, 442-1,330] vs median, 377 [IQR, 276-885]; P = 0.008). In multivariable analysis, only d-dimer (hazard ratio [HR], 1; 95% confidence interval [CI],1-1.002; P = .02) and ferritin (HR, 1; 95% CI, 0.9-0.9; P = .02) increase the statistic signification.

Conclusion: COVID-19 pneumonia in KT patients shows a different presentation of inflammatory biomarkers than other non-COVID pneumonias. It could be useful to identify KT patients with COVID-19. More detailed studies are necessary to understand the presentation of biomarkers in KT with COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2021.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363433PMC
August 2021

ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part III: Pharmacology, medical and surgical management of post-transplant extrapulmonary conditions statements.

J Heart Lung Transplant 2021 Jul 31. Epub 2021 Jul 31.

The Lung Transplant Unit, St. Vincent's Hospital, Sydney, New South Wales, Australia.

Patients with connective tissues disease (CTD) are often on immunomodulatory agents before lung transplantation (LTx). Till now, there's no consensus on the safety of using these agents perioperative and post-transplant. The International Society for Heart and Lung Transplantation-supported consensus document on LTx in patients with CTD addresses the risk and contraindications of perioperative and post-transplant management of the biologic disease-modifying antirheumatic drugs (bDMARD), kinase inhibitor DMARD, and biologic agents used for LTx candidates with underlying CTD, and the recommendations and management of non-gastrointestinal extrapulmonary manifestations, and esophageal disorders by medical and surgical approaches for CTD transplant recipients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2021.07.013DOI Listing
July 2021

Consumption of alcoholic and non-alcoholic beverages: ELSA-Brasil results.

Cien Saude Colet 2021 30;26(suppl 2):3825-3837. Epub 2021 Aug 30.

Programa de Pós-Graduação em Saúde Coletiva. Universidade Federal do Espírito Santo. Av. Marechal Campos 1468, Bonfim. 29047-105 Vitória ES Brasil.

The study aims to describe the consumption of alcoholic and non-alcoholic beverages according to sociodemographic, health and location variables. Cross-sectional study with ELSA-Brasil data (2008-2010). A questionnaire was used to collect sociodemographic, food, health data and anthropometry. Descriptive analysis and association with variables of interest were carried out. In the sample, 8% of the total caloric value comes from non-alcoholic beverages (5.6%: sugary drinks), and 4% from alcoholic beverages (2.7%: beer). Consumers of unsweetened and artificially sweetened beverages reported moderate/strong physical activity, former smokers and higher education. The opposite was true for sugary drinks. Eutrophic people reported higher consumption of sugary drinks and those obese, artificially sweetened and beer. Alcohol consumption varied with age (young: beer; elderly: wine/spirits) and education (low education: beer/spirits; higher education: wine). Coffee, natural juice and soda were the most consumed non-alcoholic beverages and beer was the most prevalent alcoholic beverage. Consumption variation was observed according to geographic location. The consumption of sugary and alcoholic beverages is high in Brazil and public health strategies are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/1413-81232021269.2.30682019DOI Listing
September 2021

Clotrimazole-Induced Oxidative Stress Triggers Novel Yeast Pkc1-Independent Cell Wall Integrity MAPK Pathway Circuitry.

J Fungi (Basel) 2021 Aug 9;7(8). Epub 2021 Aug 9.

Departamento de Microbiología y Parasitología, Facultad de Farmacia, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Universidad Complutense de Madrid, 28040 Madrid, Spain.

Azoles are one of the most widely used drugs to treat fungal infections. To further understand the fungal response to azoles, we analyzed the MAPK circuitry of the model yeast that operates under treatment with these antifungals. Imidazoles, and particularly clotrimazole, trigger deeper changes in MAPK phosphorylation than triazoles, involving a reduction in signaling through the mating pathway and the activation of the MAPKs Hog1 and Slt2 from the High-Osmolarity Glycerol (HOG) and the Cell Wall Integrity (CWI) pathways, respectively. Clotrimazole treatment leads to actin aggregation, mitochondrial alteration, and oxidative stress, which is essential not only for the activation of both MAPKs, but also for the appearance of a low-mobility form of Slt2 caused by additional phosphorylation to that occurring at the conserved TEY activation motif. Clotrimazole-induced ROS production and Slt2 phosphorylation are linked to Tpk3-mediated PKA activity. Resistance to clotrimazole depends on HOG and CWI-pathway-mediated stress responses. However, Pkc1 and other proteins acting upstream in the pathway are not critical for the activation of the Slt2 MAPK module, suggesting a novel rewiring of signaling through the CWI pathway. We further show that the strong impact of azole treatment on MAPK signaling is conserved in other yeast species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jof7080647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399625PMC
August 2021

Microgenetic Analysis of Thought Trajectories: A Mixed Design.

Integr Psychol Behav Sci 2021 Aug 19. Epub 2021 Aug 19.

Faculty of Psychology, Universidad del Desarrollo, Avenida La Plaza 680, Las Condes, Santiago de Chile, Chile.

This article reports the results of an investigation that used a mixed methodology with microgenetic orientation, to observe the genetic development of small acts of thought and their bodily manifestations. A qualitative design was carried out through a videographic record with 10 participants to explore thought trajectories and their genetic unfolding in gestures. In a second moment, a quantitative sequential analysis was conducted with 50 participants, who were invited to the laboratory to participate in a tachistoscopic presentation. The procedure was videotaped and coded, identifying categories of thought and their respective gestural expressions. An analysis of different trajectories was carried out to observe the transitions that thought takes and its gestural movements. The results show trajectories in the forms of thought that are investigated through a qualitative microgenetic analysis, which shows the anticipation of verbal meaning through gestures and the transitions backwards to then advance into more integrated forms of thought. On the other hand, trajectories between voluntary and involuntary forms of thought, as well as transitions in verbal and imaginative forms of thought are detected in a quantitative sequence analysis. Finally, the results are integrated and the utility of mixed designs to study the microgenesis of the consciousness phenomenon is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12124-021-09633-9DOI Listing
August 2021

Physical inactivity and headache disorders: Cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Cephalalgia 2021 Aug 18:3331024211029217. Epub 2021 Aug 18.

Universidade de São Paulo, Hospital Universitário, Centro de Pesquisa Clínica e Epidemiológica, São Paulo-SP, Brazil.

Background: Physical inactivity has been linked to headache disorders but estimates based on the current World Health Organization physical activity guidelines are unknown.

Objective: To test the associations between headache disorders and physical inactivity in the ELSA-Brasil cohort.

Methods: In a cross-sectional analysis, linear (continuous variables) and logistic regression models (categorical variables) tested the associations of physical activity levels in the leisure time, commuting time, and combined leisure time physical activity + commuting time physical activity domains with headache disorders, adjusted for the effects of sociodemographic data, cardiovascular risk variables, psychiatric disorders, and migraine prophylaxis medication.

Results: Of 15,105 participants, 14,847 (54.4% women) provided data on physical activity levels and headache. Higher physical activity levels (continuous values) in the leisure time physical activity domain associated with lower migraine and tension-type headache occurrence and lower headache attack frequency, while in the commuting time physical activity domain it associated with more frequent headache attacks. Compared to people who met World Health Organization physical activity levels in the leisure time physical activity or combining leisure time physical activity + commuting time physical activity domains (i.e. ≥150 min.wk of moderate and/or ≥75 min.wk of vigorous physical activity), physical inactivity associated with higher migraine occurrence, while somewhat active (i.e. not meeting World Health Organization recommendations) associated with higher migraine and tension-type headache occurrence. Physical inactivity in the commuting time physical activity domain associated with higher tension-type headache in men and lower migraine in women. Physical inactivity within vigorous leisure time physical activity intensity, but not moderate leisure time physical activity, associated with higher migraine, mostly in women. Finally, physical inactivity associated with higher headache attack frequency regardless headache subtype.

Conclusion: Physical inactivity and unmet World Health Organization physical activity levels associate with primary headaches, with heterogeneous associations regarding headache subtype, sex, physical activity domain/intensity, and headache frequency in the ELSA-Brasil study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/03331024211029217DOI Listing
August 2021

Pelvic Venous Congestion Secondary to a Circumaortic Renal Collar in an Adolescent Female: Report of a Case.

European J Pediatr Surg Rep 2021 Jan 10;9(1):e56-e60. Epub 2021 Aug 10.

Department of Pediatric Surgery, Hospital Clinico Universitario de Valladolid, Valladolid, Castilla y León, Spain.

We report a 13-year-old girl who presented with a recurrent abdominal pain that started after her menarche. The abdominal palpation revealed tenderness over the left ovarian point. The laboratory study, ultrasonography, and abdominal X-ray were normal. The computed tomography and magnetic resonance imaging showed a double left renal vein with a retroaortic component, an increased left parauterine circulation, and ipsilateral ovarian vein engorgement. A diagnostic and therapeutic phlebography allowed a selective catheterization of a group of pelvic varicose veins draining to the left ovarian and to the internal iliac veins. There were no complications during the procedure and the symptoms disappeared 2 days later. Circumaortic left renal vein may cause hematuria, proteinuria, pelvic congestion syndrome, and massive hemorrhage during surgery. A conservative treatment is recommended for patients without gynecourological/renal symptoms or with mild hematuria. The endovascular treatment by gonadal venous embolization is safe and effective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1730998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354767PMC
January 2021

Reference values for the triglyceride to high-density lipoprotein ratio and its association with cardiometabolic diseases in a mixed adult population: The ELSA-Brasil study.

J Clin Lipidol 2021 Jul 29. Epub 2021 Jul 29.

Department of Pathophysiology, Montes Claros State University (UNIMONTES), Montes Claros, MG, Brazil. Electronic address:

Background: Among several lipid ratios available, the triglyceride/HDL-cholesterol (TG/HDL-C) may detect individuals at risk of cardiometabolic diseases. However, its reference values for different ethnicities are not well established.

Objective: To define sex- and ethnicity-specific reference values for TG/HDL-C ratio in a large sample of healthy multiethnic adults and test its association with cardiometabolic conditions.

Methods: An apparently healthy sample (n = 2,472), aged 35-74, free of major cardiovascular risk factors, was used to generate the reference values for the TG/HDL-C. Exclusion criteria were diabetes, elevated blood pressure, obesity, hypercholesterolemia, severe hypertriglyceridemia, and smoking history. Cut-offs based on the reference values were tested in the whole ELSA Brasil study (n = 13,245), stratified by sex and ethnicity, to identify cardiometabolic conditions.

Results: TG/HDL-C ratio was higher in men than women, and did not change significantly with age, regardless of sex and ethnicity. Also, black individuals showed lower levels of TG/HDL-C as compared to other ethnic groups. ROC curve showed that the cut-off based on the 75th percentile displayed better sensitivities and specificities for men and women, regardless of ethnicity. Also, the sex- and ethnicity-specific cut-offs based on the 75th percentile were significantly associated with all tested cardiometabolic conditions (hypertension, diabetes, obesity, metabolic syndrome, and insulin resistance). Also, we observed that the use of a single sex-specific cut-off (men: 2.6; women: 1.7) could be used for the different ethnicities with good reliability.

Conclusion: The defined TG/HDL-C cut-offs (men: 2.6; women: 1.7) are reliable and showed good clinical applicability to detect cardiometabolic conditions in a multiethnic population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacl.2021.07.005DOI Listing
July 2021

Anti-RNA polymerase III antibodies in systemic sclerosis: Multicentric study from Argentina.

Reumatol Clin (Engl Ed) 2021 Aug 5. Epub 2021 Aug 5.

Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", UBA, Ciudad Autónoma de Buenos Aires, Argentina.

Objective: To describe the frequency of anti-RNA polymerase III antibody in patients with Systemic Sclerosis (SSc) of a group of healthcare centres from Argentina and to explore differences among patients with positive and negative anti-RNA polymerase III antibody.

Patients And Methods: Data from clinical records, anamnesis and physical examination were collected from 135 patients with SSc (ACR/EULAR 2013). A serum sample from each patient was obtained for the detection of anti-RNA polymerase III IgG antibodies by ELISA.

Results: In all, 97.8% were women and the median age at diagnosis was 53 years (range 12-87), 77.7% had limited cutaneous SSc (lcSSC), 19,3% patients had diffuse cutaneous SSc (dcSSC) and 2.9% had scleroderma sine scleroderma. The 67.5% of the patients were from a Mestizos or Amerindian ethnic group. Anti-RNA polymerase III was positive in 5.9% of the patients. In 36 patients, the anticentromere (ACA) and anti-Scl70 antibodies were negative; anti-RNA polymerase III was positive in 16.7% of these 36 patients. Pitting scars and pulmonary artery hypertension were more frequent in anti-RNA polymerase III positive patients who were also older at diagnosis. No association with gastric antral vascular ectasia was found. The only patient with scleroderma renal crisis was anti-RNA polymerase III positive.

Conclusions: Anti-RNA polymerase III frequency found in this study was one of the lowest reported, which could be related to the predominance of the Amerindian and Mestizo ethnic group. It is possible that the detection of anti RNA polymerase III allows better classification of SSc patients, to know their prognosis and to improve their follow-up, therefore more studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.reumae.2021.02.003DOI Listing
August 2021

Food insecurity and nutritional status among older adults: a systematic review.

Nutr Rev 2021 Aug 2. Epub 2021 Aug 2.

M.H.Q. Pereira and M.L.A.S. Pereira are with Center of Biological and Health, Science, Federal University of the Western of Bahia, Barreiras, Bahia, Brazil. M.H.Q. Pereira, M.L.A.S. Pereira, and M.C.B. Molina are with the Postgraduate Program in Collective Heath, Federal University of Espírito Santo, Vitória, Brazil. G.C. Campos is with the Federal University of Espírito Santo, Vitória, Brazil. M.C.B. Molina is with the Postgraduate Program in Health and Nutrition, Federal University of Ouro Preto, Ouro Preto, Brazil.

Context: Food insecurity (FI), characterized by difficulty or inability to access adequate food, has become a public health problem.

Objective: To analyze studies relating FI with nutritional status (NS) among older adults and the associated factors.

Data Search: Articles published up to June 2020 were investigated in 5 databases: PubMed, Embase, Scopus, LILACS, and Web of Science. The search, selection, extraction, and quality evaluation were carried out by 2 reviewers.

Data Extraction: The authors identified characteristics of the studies and the main data regarding the relationship of interest.

Results: Twenty-two studies were included in the review and their characteristics are summarized and presented using narrative synthesis. In 10 studies (45.4%), a relationship was observed between FI and malnutrition; in another 6 (27.3%), a relationship was observed between FI and being overweight.

Conclusion: A relationship was identified between FI, especially severe forms, and malnutrition, as well as between FI, especially mild forms, and people being overweight. Thus, FI among older adults relates to a 2-fold burden of nutritional outcomes, depending on the level.

Systematic Review Registration: PROSPERO registration no. CRD42020185086.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nutrit/nuab044DOI Listing
August 2021

Heterologous Expression and Auto-Activation of Human Pro-Inflammatory Caspase-1 in and Comparison to Caspase-8.

Front Immunol 2021 14;12:668602. Epub 2021 Jul 14.

Departamento de Microbiología y Parasitología, Facultad de Farmacia, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Universidad Complutense de Madrid, Madrid, Spain.

Caspases are a family of cysteine proteases that play an essential role in inflammation, apoptosis, cell death, and development. Here we delve into the effects caused by heterologous expression of human caspase-1 in the yeast and compare them to those of caspase-8. Overexpression of both caspases in the heterologous model led to their activation and caused mitochondrial hyperpolarization, damage to different organelles, and cell death. All these effects were dependent on their protease activity, and caspase-8 was more aggressive than caspase-1. Growth arrest could be at least partially explained by dysfunction of the actin cytoskeleton as a consequence of the processing of the yeast Bni1 formin, which we identify here as a likely direct substrate of both caspases. Through the modulation of the promoter by using different galactose:glucose ratios in the culture medium, we have established a scenario in which caspase-1 is sufficiently expressed to become activated while yeast growth is not impaired. Finally, we used the yeast model to explore the role of death-fold domains (DD) of both caspases in their activity. Peculiarly, the DDs of either caspase showed an opposite involvement in its intrinsic activity, as the deletion of the caspase activation and recruitment domain (CARD) of caspase-1 enhanced its activity, whereas the deletion of the death effector domain (DED) of caspase-8 diminished it. We show that caspase-1 is able to efficiently process its target gasdermin D (GSDMD) when co-expressed in yeast. In sum, we propose that provides a manageable tool to explore caspase-1 activity and structure-function relationships.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.668602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317575PMC
July 2021

[Remdesivir in kidney transplant patients with SARS-CoV-2 pneumonia].

Nefrologia 2021 Jul 12. Epub 2021 Jul 12.

Departamento de Nefrología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, España.

Background: Remdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in Kidney transplant (KT) patients are limited to some published cases.

Methods: We performed a retrospective observational study that included all KT patients admitted between August 01, 2020 and December 31, 2020 with SARS-CoV-2 pneumonia who received remdesivir.The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir.

Discussion: A total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30mL/min or they did not present clinical criteria. In addition to remdesivir, all pacients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53-71) years. Median time from transplantation was 43 (16-82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low oxygen flow therapy upon admission, requiring high flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9-27) days.

Conclusions: Our study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nefro.2021.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272977PMC
July 2021

Alcoholic beverage consumption, changes in blood pressure, and incidence of hypertension in the Longitudinal Adult Health Study (ELSA-Brasil).

Nutrition 2021 Jun 7;91-92:111387. Epub 2021 Jun 7.

Post Graduate Program in Public Health, Federal University of Espírito Santo, Espírito Santo, Brazil. Electronic address:

Objectives: Alcohol consumption is generally associated with increased risk of hypertension. We aimed to investigate, prospectively, the effect of alcoholic-beverage consumption on blood pressure (BP) and incidence of hypertension, after a 4-y follow-up, in participants of the Longitudinal Adult Health Study (ELSA-Brasil).

Methods: We analyzed information from 3,990 participants (ages 35-74 y), men and women, from educational and research institutions, at baseline (2008-2010) and follow-up (2012-2014). Socioeconomic, hemodynamic, anthropometric, and health data were collected. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg and/or use of antihypertensive medication. Change in alcohol consumption (g/d) was estimated by subtracting total consumed at follow-up from total consumed at baseline, and was categorized in tertiles.

Results: The consumption of alcoholic beverages was associated with changes in BP and hypertension only in men. Individuals who reduced total consumption of alcohol showed a smaller increase in systolic BP (1.1 versus 2.3 mm Hg; P = 0.03) and diastolic BP (1.3 versus 2.2 mm Hg; P = 0.008) compared to individuals who increased consumption. In addition, individuals in the highest tertiles of total consumption of alcohol (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.14-2.29) and consumption of beer (OR, 1.51; 95% CI, 1.07-12.13), wine (OR, 1.71; 95% CI, 1.01-2.86), and spirits (OR, 2.01; 95% CI, 1.21-3.32) showed higher odds ratios for hypertension compared to the lowest tertile.

Conclusions: Increased consumption of alcoholic beverages was positively associated with increased BP levels and higher chances of developing hypertension in men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nut.2021.111387DOI Listing
June 2021

Overweight and obesity prevalence trend in Espírito Santo, Brazil: an ecological study, 2009-2018.

Epidemiol Serv Saude 2021 9;30(3):e2020961. Epub 2021 Jul 9.

Universidade Federal do Espírito Santo, Programa de Pós-Graduação em Saúde Coletiva, Vitória, ES, Brasil.

Objective: To analyze trends in the prevalence of overweight and obesity in the state of Espírito Santo, Brazil, between 2009 and 2018.

Methods: This was an ecological study, with data from the Food and Nutritional Surveillance System (SISVAN). Overweight and obesity were classified as recommended by the World Health Organization. Prais-Winsten regression was used to estimate the trend of the prevalence.

Results: There was an increasing trend of overweight (5.5 to 8.6%) and obesity (4.4 to 8.3%), in both sexes and in different regions of the state. In the stratified analysis, there was an increase in overweight and obesity in children, adolescents and adult women (4.2 to 8.6%; p<0.05). Obesity increased among male adolescents, in the south, central and north regions of the state, while in the south region, in all age groups (5.1% growth; p=0.01).

Conclusion: There was an increase in overweight and obesity in Espírito Santo, from 2009 to 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/S1679-49742021000300017DOI Listing
July 2021

COVID-19 in Solid Organ Transplant Recipients in Spain Throughout 2020: Catching the Wave?

Transplantation 2021 Jun 25. Epub 2021 Jun 25.

1 Organización Nacional de Trasplantes, Madrid, Spain. 2 Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). 3 Kidney Transplant Unit. Nephrology Department. Hospital Universitario Vall d´Hebrón, Barcelona, Spain. 4 Nephrology Service. Hospital Universitario 12 de Octubre, Madrid, Spain 5 Nephrology Service. Hospital Universitario de Cruces, Barakaldo, Spain. 6 Nephrology Service. Hospital Germans Trias i Pujol, Badalona, Spain. 7 Nephrology Service. Hospital Regional Universitario de Málaga, Málaga, Spain. 8 Nephrology Service. Hospital del Mar, Barcelona, Spain. Transplant Working Group of the Spanish Society of Nephrology. REDinREN (RD16/0009/0013). 9 Kidney Transplant Unit. Fundación Puigvert, Barcelona, Spain 10 Nephrology Service. Hospital General Universitario Gregorio Marañón, Madrid, Spain. 11 Nephrology Service. Hospital Virgen de las Nieves, Granada, Spain. 12 Hepato-Biliary Surgery and Transplant Unit. General Surgery Service. Hospital Universitario 12 de Octubre, Madrid, Spain. 13 Kidney Transplant Unit, Clinical Management Unit Nephrology-Urology. Hospital Universitario Virgen del Rocío, Sevilla, Spain. 14 Kidney Transplant Unit, Nephrology Service. Hospital Universitario de Bellvitge, Barcelona, Spain. 15 Department of Pulmonology, Lung transplant Unit, Hospital Universitario Vall d´Hebrón, Barcelona, Spain. 16 Kidney Transplant Unit. Nephrology Service. Hospital Clinic, Barcelona, Spain. 17 Liver Transplant Unit. Hospital Universitario de Bellvitge, IDIBELL, Barcelona, Spain. 18 Kidney Transplant Unit, Nephrology Service. Hospital Universitario Puerta del Mar, Cádiz, Spain. 19 Hepatology and Liver Transplantation Unit, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 20 Kidney Transplant Unit, Nephrology Service. Hospital Universitario La Fe, Valencia, Spain. 21 Liver Unit. Hospital Universitario Vall d´Hebron, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR). CIBERehd, Instituto de Salud Carlos III. 22 Lung Transplant Unit. Neumology Service. Hospital Universitario 12 de Octubre, Madrid, Spain. Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12). 23 Kidney Transplant Unit, Nephrology Service. Hospital Universitario Reina Sofía, Instituto para la Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain. 24 Kidney Transplant Unit, Nephrology Service. Hospital Universitario Central de Asturias, Oviedo, Spain. 25 Gastroenterology Service. Hospital Universitario Ramón y Cajal, Madrid, Spain. 26 Heart Failure and Transplant Unit. Cardiology Service. Hospital Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV). 27 Cardiology Service, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV).

Background: Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with COVID-19 across different pandemic waves.

Methods: In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020.

Results: Out of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second period, respectively. Compared with the first wave, recipients in the second were younger (median: 63 [IQR: 53-71] versus 59 [IQR: 49-68] years; p<0.001) and less likely to receive anti-SARS-CoV-2 drugs (81.8% versus 8.1%; p<0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; p=0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; p<0.001). Hospital admission (86.7% versus 58.1%; p<0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; p<0.001), and case-fatality rate (25.8% versus 16.7%; p<0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% CI: 1.12-1.93; p=0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI: 0.73-1.29; p=0.873) or intensive care unit (ICU) admission (OR: 0.65; 95% CI: 0.35-1.18; p=0.157).

Conclusions: We observed meaningful changes in demographics, therapeutic approaches, level of care and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003873DOI Listing
June 2021

Critical Care Education and Skills Validation Course for Internal Medicine Physicians in the Military.

Mil Med 2021 Jun 23. Epub 2021 Jun 23.

Pulmonary & Critical Care Medicine Service, Department of Medicine, Brooke Army Medical Center, San Antonio, TX 78234, USA.

Introduction: Military internist and internal medicine (IM) subspecialist physicians must be prepared to function in both traditional inpatient and outpatient settings, as well as manage critically ill patients within a deployed austere environment. As many critical care procedures are not performed on a routine basis in general IM practice, many active duty IM physicians experience skills degradation and lack confidence in performing these procedures. In order to address this perceived deficiency, the U.S. Army and Air Force Internal Medicine Education and Skills Validation Course was developed to provide essential training in critical care procedures for active duty military IM physicians and subspecialists.

Materials And Methods: Staff internist and subspecialist physicians at multiple military treatment facilities participated in a 2-day simulation-based training course in critical care procedures included in the Army Individual Critical Task Lists and the Air Force Comprehensive Medical Readiness Program. Educational content included high-yield didactic lectures, multi-disciplinary Advanced Cardiac Life Support/Advanced Trauma Life Support high-fidelity simulation scenarios, and competency training/validation in various bedside procedures, including central venous and arterial line placement, trauma-focused ultrasound exam, airway management and endotracheal intubation, chest tube thoracotomy, and mechanical ventilation, among others.

Results: A total of 87 staff IM physicians participated in the course with an average of 2-4 years of experience following completion of graduate medical education. Upon course completion, all participants successfully achieved rigorous, checklist-based, standardized validation in all the required procedures. Survey data indicated a significant improvement in overall skills confidence, with 100% of participants indicating improvement in their ability to function independently as deployed medical officers.

Conclusions: Broad implementation of this program at military hospitals would improve pre-deployment critical care procedural readiness in military IM physicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/milmed/usab210DOI Listing
June 2021

An unusual extranodal natural killer/T-cell lymphoma presenting as chronic laryngitis: A case report.

Medicine (Baltimore) 2021 Jun;100(25):e26314

Service of Rheumatology, Hospital Clínico de la Universidad de Chile, Santiago de Chile.

Rationale: Nasal-type, extranodal natural killer (NK)/T-cell lymphoma is a rare lymphoma. The tumor usually shows ulcerative and necrotic lesions in the nasal cavities and sinuses. Tissue involvement outside the nasal cavity is uncommon.

Patient Concern: We describe a 30-year-old man with a 2-month history of hoarseness, weight loss, and dyspnea.

Diagnosis: Magnetic resonance image (MRI) showed edema of the larynx with obliteration of the airway. Laryngoscopic examination described necrotic tissue in the glottis and larynx. The biopsy showed chronic, necrotizing laryngitis, with no granulomas, vasculitis, or atypical cells. The immunologic and microbiologic study was negative. Later, after immunosuppressive therapy, the patient presented erythema and diffuse enlargement of the right arm. MRI showed myositis of the biceps and brachial muscles. Infection was rule out, and direct microscopy showed an extensive muscle infiltration by mononuclear cells and abundant mitosis. Immunohistochemistry was positive for CD3, CD8, Ki 67 (90%), and CD56 compatible with extranodal NK/T cell lymphoma.

Interventions: The patient initially received immunosuppression treatments (corticoids, cyclofosfamide, and Rituximab) with relapsing episodes. When lymphoma was diagnosed, chemotherapy was started.

Outcomes: The patient died during chemotherapy.

Lessons: Nasal-type, extranodal NK/T-cell lymphoma should be suspected even when there are no classical findings of neoplasms on histology. Immunohistochemistry is mandatory to rule it out.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000026314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238288PMC
June 2021

Diet and Lifestyle Changes During the COVID-19 Pandemic in Ibero-American Countries: Argentina, Brazil, Mexico, Peru, and Spain.

Front Nutr 2021 2;8:671004. Epub 2021 Jun 2.

Public Health Program, Health Sciences Center, Federal University of Espírito Santo, Vitória, Brazil.

This study aimed to evaluate changes in dietary and lifestyle habits during the period of confinement due to the first wave of the COVID-19 pandemic in Ibero-American countries. A cross-sectional investigation was conducted with 6,325 participants of both genders (68% women), over 18 years of age and from five countries: Brazil ( = 2,171), Argentina ( = 1,111), Peru ( = 1,174), Mexico ( = 686), and Spain ( = 1,183). Data were collected during the year 2020, between April 01 and June 30 in Spain and between July 13 and September 26, in the other countries studied using a self-administered online survey designed for the assessment of sociodemographic, employment, physical activity, health status, and dietary habits changes. Most participants (61.6%), mainly those from Spain, remained constant, without improving or worsening their pattern of food consumption. Among those who changed, a pattern of better eating choices prevailed (22.7%) in comparison with those who changed toward less healthy choices (15.7%). Argentina and Brazil showed the highest proportion of changes toward a healthier pattern of food consumption. Peruvians and Mexicans were less likely to make healthy changes in food consumption (OR: 0.51; 95% CI: 0.4-0.6 and OR: 0.69; 95% CI: 0.4-0.8, respectively), when compared to Argentinians. Most respondents did not change their pattern of meal consumption, but those who did reduced their consumption of main meals and increased intake of small meals and snacks. Although most participants affirmed to be doing physical activity at home, about one-half reported perception of weight gain. Individuals with alterations in sleep pattern (either by increasing or decreasing sleep time) were more likely to change their diets to a healthier pattern. In contrast, individuals with confirmed diagnosis of COVID-19 and those who reported feeling anxious were more likely to perform changes to a less healthy eating pattern (OR: 1.72; 95% CI: 1.2-2.3 and OR: 1.21; 95% CI: 1.1-1.4, respectively). In conclusion, although most participants remained constant in their eating habits, lifestyle changes and anxiety feelings were reported. Among those who changed patterns of food consumption, healthier choices prevailed, with differences between countries. However, there were alterations in the distribution of meals, with higher consumption of snacks and small meals. These results can be used to guide policies to prevent deleterious consequences that may affect the incidence of chronic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2021.671004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206276PMC
June 2021

Coronavirus disease 2019 in heart transplant recipients: Risk factors, immunosuppression, and outcomes.

J Heart Lung Transplant 2021 09 19;40(9):926-935. Epub 2021 May 19.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear.

Methods: We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant.

Results: The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy.

Conclusions: We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131557PMC
September 2021

The EP300/TP53 pathway, a suppressor of the Hippo and canonical WNT pathways, is activated in human hearts with arrhythmogenic cardiomyopathy in the absence of overt heart failure.

Cardiovasc Res 2021 Jun 16. Epub 2021 Jun 16.

Center for Cardiovascular Genetics, Institute of Molecular Medicine and Department of Medicine, University of Texas Health Sciences Center at Houston, Texas, 77030.

Aim: Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure.

Methods And Results: Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and 5 control samples were analyzed by RNA-Seq (discovery group). These cases presented with cardiac arrhythmias and had a normal right ventricular function. The RNA-Seq analysis identified ∼5,000 differentially expressed genes (DEGs), which predicted suppression of the Hippo and canonical WNT pathways, among others.Dysregulated genes and pathways, identified by RNA-Seq, were tested for validation in the right and left ventricular tissues from 5 independent autopsy-confirmed ACM cases with defined mutations (validation group), who were victims of SCD and had no history of heart failure. Protein levels and nuclear localization of the cWNT and Hippo pathway transcriptional regulators were reduced in the right and left ventricular validation samples. In contrast, levels of acetyltransferase EP300, known to suppress the Hippo and canonical WNT pathways, were increased and its bona fide target TP53 was acetylated. RNA-Seq data identified apical junction, reflective of cell-cell attachment, as the most disrupted biological pathway, which was corroborated by disrupted desmosomes and intermediate filament structures. Moreover, the DEGs also predicted dysregulation of over a dozen canonical signal transduction pathways, including the Tec kinase and integrin signaling pathways. The changes were associated with increased apoptosis and fibro-adipogenesis in the ACM hearts.

Conclusion: Altered apical junction structures is associated with activation of the EP300-TP53 and suppression of the Hippo/cWNT pathways in human ACM caused by defined mutations in the absence of an overt heart failure. The findings implicate altered mechanotransduction in the pathogenesis of ACM.

Translational Perspective: The findings suggest that altered mechanosensing at the cell-cell junction instigates a cascade of molecular events through the activation of acetyltransferase EP300/TP53 and suppression of gene expression through the Hippo/canonical WNT pathways in human arrhythmogenic cardiomyopathy (ACM) caused by defined mutations. These molecular changes occur early and in the absence of overt heart failure. Consequently, one may envision cell type-specific interventions to target the dysregulated transcriptional, mechanosensing, and mechanotransduction pathways to prevent the evolving phenotype in human ACM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvab197DOI Listing
June 2021

Sugar-sweetened soft drinks consumption and risk of hyperuricemia: Results of the ELSA-Brasil study.

Nutr Metab Cardiovasc Dis 2021 06 18;31(7):2004-2013. Epub 2021 Apr 18.

Postgraduate Program in Public Health, Federal University of Espírito Santo, ES, Brazil. Electronic address:

Background And Aims: The prospective association between sugar-sweetened beverages consumption and hyperuricemia is controversial. The aim was to investigate the association of the consumption of sugar-sweetened soft drinks and unsweetened fruit juices with the incidence of hyperuricemia and the levels of serum uric acid in the participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods And Results: Longitudinal analysis in ELSA-Brasil participants (baseline 2008-2010 and follow-up 2012-2014). The sample consisted of 10,072 civil servants (35-74 years, both sexes). The consumption of beverages estimated by a food frequency questionnaire (baseline) was divided into five categories: nonconsumption and quartiles (≥0.1 mL/day). Hyperuricemia was defined as uric acid ≥7.0 mg/dL (men) and ≥5.7 mg/dL (women). Poisson regression with robust variance and multiple linear regression were tested. The average consumption of soft drinks was 84 ± 191 mL/day in men and 42 ± 128 mL/day in women. After 4 years of follow-up, the higher consumption of soft drinks (men: 401 ± 303 mL/day; women: 390 ± 290 mL/day) increased the relative risk of hyperuricemia by 30% (men) and 40% (women), and was associated with increased mean uric acid (men: β = 0.14 mg/dL; 95% CI 0.41-0.24; women: β = 0.11 mg/dL; 95% CI 0.00-0.21). The consumption of unsweetened juice was not associated with hyperuricemia.

Conclusion: High consumption of sugar-sweetened soft drinks is associated with an increased relative risk of hyperuricemia and elevated serum uric acid levels in Brazilian adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2021.04.008DOI Listing
June 2021

Protein haploinsufficiency drivers identify MYBPC3 variants that cause hypertrophic cardiomyopathy.

J Biol Chem 2021 07 5;297(1):100854. Epub 2021 Jun 5.

Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Electronic address:

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Variants in MYBPC3, the gene encoding cardiac myosin-binding protein C (cMyBP-C), are the leading cause of HCM. However, the pathogenicity status of hundreds of MYBPC3 variants found in patients remains unknown, as a consequence of our incomplete understanding of the pathomechanisms triggered by HCM-causing variants. Here, we examined 44 nontruncating MYBPC3 variants that we classified as HCM-linked or nonpathogenic according to cosegregation and population genetics criteria. We found that around half of the HCM-linked variants showed alterations in RNA splicing or protein stability, both of which can lead to cMyBP-C haploinsufficiency. These protein haploinsufficiency drivers associated with HCM pathogenicity with 100% and 94% specificity, respectively. Furthermore, we uncovered that 11% of nontruncating MYBPC3 variants currently classified as of uncertain significance in ClinVar induced one of these molecular phenotypes. Our strategy, which can be applied to other conditions induced by protein loss of function, supports the idea that cMyBP-C haploinsufficiency is a fundamental pathomechanism in HCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbc.2021.100854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260873PMC
July 2021

Documenting and protecting traditional knowledge in the era of open science: Insights from two Spanish initiatives.

J Ethnopharmacol 2021 Oct 16;278:114295. Epub 2021 Jun 16.

Departamento de Biología (Botánica), Universidad Autónoma de Madrid, C/Darwin 2, Campus de Cantoblanco, 28049, Madrid, Spain; Centro de Investigación en Biodiversidad y Cambio Global (CIBC-UAM), Universidad Autónoma de Madrid, 28049, Madrid, Spain. Electronic address:

Ethnopharmacological Relevance: The documentation and protection of traditional knowledge face new challenges in the era of open science. Focusing on medicinal and food uses, we discuss two innovative initiatives in Spain to document, protect and return to the society traditional knowledge.

Materials And Methods: The Spanish Inventory of Traditional Knowledge related to Biodiversity has compiled and published information on the traditional use and management of flora, fauna, fungi, geodiversity, and ecosystems. CONECT-e (www.conecte.es) is an online platform where citizens can document knowledge and uses of wild and domesticated species. We describe the extent of these initiatives in terms of participation and accomplishment, and discuss their complementarities and challenges.

Results: The initiatives described have fostered the establishment of a common standard for organizing traditional knowledge in databases that facilitate knowledge documentation: 131,066 uses and 152,246 local names have been documented so far. Using open data and copyleft licenses, these initiatives also contribute to the maintenance of traditional knowledge in the commons domain, guaranteeing the free exchange and reproduction of knowledge. However, the extensive focus of these initiatives on data sharing does not necessarily guarantee knowledge holders' data sovereignty.

Conclusion: To protect TEK in a context of open science more efforts should be done to operationalize traditional knowledge holders' rights to data sovereignty.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114295DOI Listing
October 2021

Electrocardiographic Screening of Arrhythmogenic Cardiomyopathy in Genotype-Positive and Phenotype-Negative Relatives.

Front Cardiovasc Med 2021 7;8:646391. Epub 2021 May 7.

Department of Cardiology, Virgen de la Arrixaca University Hospital, Murcia, Spain.

Arrhythmogenic cardiomyopathy is a hereditary cause of ventricular arrhythmias and sudden death. Identifying the healthy genetic carriers who will develop the disease remains a challenge. A novel approach to the analysis of the digital electrocardiograms of mutation carriers through signal processing may identify early electrocardiographic abnormalities. A retrospective case-control study included a population of healthy genetics carriers and their wild-type relatives. Genotype-positive/phenotype-negative individuals bore mutations associated with the development of arrhythmogenic cardiomyopathy. The relatives included had a non-pathological 12-lead electrocardiogram, echocardiogram, and a cardiac magnetic resonance. Automatic digital electrocardiographic analyses comprised QRS and terminal activation delay duration, the number of QRS fragmentations, ST slope, and T-wave voltage. Digital 12-lead electrocardiograms from 41 genotype-positive/ phenotype-negative (29 simple carriers and 12 double mutation carriers) and 73 wild-type relatives were analyzed. No differences in the QRS length, the number of QRS fragmentations, and the voltage of the T-wave were observed. After adjusting for potential confounders, double carriers showed an average ST-slope flatter than those of the simple carriers and wild type [5.18° (0.73-8.01), 7.15° (5.14-11.05), and 11.46° (3.94-17.49), respectively, = 0.005]. There was a significant negative correlation between the ST slope and the age in genotype-positive/phenotype-negative relatives ( = 0.376, = 0.021) not observed in their wild-type counterparts ( = 0.074, = 0.570). A flattened ST segment may be an early sign of electrical remodeling that precedes T-wave inversion in healthy genetic carriers. A thorough analysis of the digital electrocardiographic signal may help identify and measure early electrical abnormalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.646391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137826PMC
May 2021

A walk-through MAPK structure and functionality with the 30-year-old yeast MAPK Slt2.

Int Microbiol 2021 May 15. Epub 2021 May 15.

Departamento de Microbiología y Parasitología, Facultad de Farmacia, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad Complutense de Madrid, Pza. Ramón y Cajal s/n, 28040, Madrid, Spain.

Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved signaling proteins involved in the regulation of most eukaryotic cellular processes. They are downstream components of essential signal transduction pathways activated by the external stimuli, in which the signal is conveyed through phosphorylation cascades. The excellent genetic and biochemical tractability of simple eukaryotes such as Saccharomyces cerevisiae has significantly contributed to gain fundamental information into the physiology of these key proteins. The budding yeast MAPK Slt2 was identified 30 years ago and was later revealed as a fundamental element of the cell wall integrity (CWI) pathway, one of the five MAPK routes of S. cerevisiae. As occurs with other MAPKs, whereas Slt2 displays the core typical structural traits of eukaryotic protein kinases, it also features conserved domains among MAPKs that allow an exquisite spatio-temporal regulation of their activity and binding to activating kinases, downregulatory phosphatases, or nuclear transcription factors. Additionally, Slt2 bears a regulatory extra C-terminal tail unique among S. cerevisiae MAPKs. Here, we review the structural and functional basis for the signaling role of Slt2 in the context of the molecular architecture of this important family of protein kinases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10123-021-00183-zDOI Listing
May 2021

Anti-RNA Polymerase III Antibodies in Systemic Sclerosis: Multicentric Study from Argentina.

Reumatol Clin (Engl Ed) 2021 Apr 28. Epub 2021 Apr 28.

Servicio de Inmunología, Instituto de Investigaciones Médicas «Dr. Alfredo Lanari», UBA, Ciudad Autónoma de Buenos Aires, Argentina.

Objective: To describe the frequency of anti-RNA polymerase III antibody in patients with Systemic Sclerosis (SSc) of a group of healthcare centres from Argentina and to explore differences among patients with positive and negative anti-RNA polymerase III antibody.

Patients And Methods: Data from clinical records, anamnesis and physical examination were collected from 135 patients with SSc (ACR/EULAR 2013). A serum sample from each patient was obtained for the detection of anti-RNA polymerase III IgG antibodies by ELISA.

Results: In all, 97.8% were women and the median age at diagnosis was 53 years (range: 12-87), 77.7% had limited cutaneous SSc (lcSSC), 19,3% patients had diffuse cutaneous SSc (dcSSC) and 2.9% had scleroderma sine scleroderma. The 67.5% of the patients were from a Mestizos or Amerindian ethnic group. Anti-RNA polymerase III was positive in 5.9% of the patients. In 36 patients, the anticentromere (ACA) and anti-Scl70 antibodies were negative; anti-RNA polymerase III was positive in 16.7% of these 36 patients. Pitting scars and pulmonary artery hypertension were more frequent in anti-RNA polymerase III positive patients who were also older at diagnosis. No association with gastric antral vascular ectasia was found. The only patient with scleroderma renal crisis was anti-RNA polymerase III positive.

Conclusions: Anti-RNA polymerase III frequency found in this study was one of the lowest reported, which could be related to the predominance of the Amerindian and Mestizo ethnic group. It is possible that the detection of anti-RNA polymerase III allows better classification of SSc patients, to know their prognosis and to improve their follow-up, therefore more studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.reuma.2021.02.005DOI Listing
April 2021

Heat-killed Helicobacter pylori upregulates NKG2D ligands expression on gastric adenocarcinoma cells via Toll-like receptor 4.

Helicobacter 2021 Aug 29;26(4):e12812. Epub 2021 Apr 29.

Faculty of Medicine, Immunology Program, Biomedical Sciences Institute (ICBM), University of Chile, Santiago de Chile, Chile.

Background: Natural killer (NK) cells are paramount for immunity against infectious agents and tumors. Their cytokine and cytolytic responses can be mediated by natural killer group 2, member D (NKG2D), an activating receptor whose ligands (NKG2DL) expression is induced in conditions of cell stress and malignant transformation. Since sustained expression of NKG2DL MICA is related to lower survival rates in gastric adenocarcinoma patients, and Helicobacter pylori infection contributes to tumorigenesis; we asked whether H. pylori stimulus could promote NKG2DL expression on human gastric adenocarcinoma cells.

Methods: Heat-killed H. pylori (HKHP) was used to stimulate MKN45 cells before analysis of NKG2DL and Toll-like receptor 4 (TLR4) protein levels by flow cytometry and transcripts by real-time PCR. LPS from Rhodobacter sphaeroides and inhibitory peptide Pepinh MYD were used to inhibit TLR4/MyD88 signaling pathway to assess its participation on NKG2DL expression. NK cell-mediated cytotoxicity was measured by lactate dehydrogenase (LDH) and CD107a mobilization assays.

Results: Stimulation of MKN45 cells with HKHP increased MICA, ULBP4 (another NKG2DL), and TLR4 at the protein and transcriptional levels. MICA, but not ULBP4 expression, was upregulated in a TLR4/MyD88-dependent manner. Furthermore, the presence of NKG2DL on the surface of HKHP-stimulated MKN45 cells enabled NK cell cytotoxic activation.

Conclusions: Our data indicate that induction of NKG2DL expression on gastric adenocarcinoma cells by H. pylori promotes an immune response that may ultimately contribute to either gastric tissue damage, as a consequence of persistent activation of immunity, or tumor immune evasion due to chronic NKG2DL expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hel.12812DOI Listing
August 2021

Incidence of excess body weight and annual weight gain in women and men: Results from the ELSA-Brasil cohort.

Am J Hum Biol 2021 Apr 28:e23606. Epub 2021 Apr 28.

Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Brazil.

Objective: To estimate annual weight gain and the incidence of overweight and obesity, stratified according to gender and socioeconomic factors.

Methods: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we included 13 625 women and men aged 35-74 (2008-2010) who attended a follow-up visit after a mean 3.8-years. Standardized questionnaires were used to record sociodemographic data, and height and weight were measured on all participants during in-person visits at research centers. The incidence rate to overweight was calculated among those not having excess weight at baseline, and incident obesity among those not having this condition at baseline. We evaluated the incidence of overweight and obesity in men and women, adjusted by age, through Poisson regression with robust variance. Large annual weight gain by gender was being defined as ≥90th percentile in the cohort.

Results: A global incidence of 7.7% for overweight and 10.6% for obesity was observed, with higher levels seen among black woman (28.5%), young men (21.1%) and woman with low educational level (35.0%). The proportions of overweight and obesity increased with age at both time points, more commonly among those with the lowest levels of per capita income and fewer years of schooling. Large annual weight gain was greater among participants with an intermediate level of education and those who self-identified as black.

Conclusions: A high overall risk of becoming overweight/obese was found, especially among women. The roles of race and education level are fundamental to understanding the effects produced by social inequalities in rates of excess weight.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajhb.23606DOI Listing
April 2021

Major Histocompatibility Complex Class I-Related Chain A (MICA) Allelic Variants Associate With Susceptibility and Prognosis of Gastric Cancer.

Front Immunol 2021 31;12:645528. Epub 2021 Mar 31.

Immunology Program, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), University of Chile, Santiago, Chile.

Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA002 (A9) as the most frequent allele in both, patients and controls, followed by MICA008 allele (A5.1). MICA009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39-18.74], = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICAA5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12-0.98], = 0.046). Survival analysis after gastrectomy showed that patients with MICA002/002 or MICA002/004 alleles had significantly higher survival rates than those patients bearing MICA002/008 ( = 0.014) or MICA002/009 (MICA002/049) alleles ( = 0.040). The presence of threonine in the position MICA-181 (MICA009/049 allele) was more frequent in GC patients than controls ( = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.645528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045969PMC
September 2021

Characteristics and Outcomes of COVID-19 in Patients on Left Ventricular Assist Device Support.

Circ Heart Fail 2021 Apr 5;14(4):e007957. Epub 2021 Apr 5.

Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (J.A.-G., D.M.M., N.M.).

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to afflict millions of people worldwide. Patients with end-stage heart failure and left ventricular assist devices (LVADs) may be at risk for severe COVID-19 given a high prevalence of complex comorbidities and functional impaired immunity. The objective of this study is to describe the clinical characteristics and outcomes of COVID-19 in patients with end-stage heart failure and durable LVADs.

Methods: The Trans-CoV-VAD registry is a multi-center registry of LVAD and cardiac transplant patients in the United States with confirmed COVID-19. Patient characteristics, exposure history, presentation, laboratory data, course, and clinical outcomes were collected by participating institutions and reviewed by a central data repository. This report represents the participation of the first 9 centers to report LVAD data into the registry.

Results: A total of 40 patients were included in this cohort. The median age was 56 years (interquartile range, 46-68), 14 (35%) were women, and 21 (52%) were Black. Among the most common presenting symptoms were cough (41%), fever, and fatigue (both 38%). A total of 18% were asymptomatic at diagnosis. Only 43% of the patients reported either subjective or measured fever during the entire course of illness. Over half (60%) required hospitalization, and 8 patients (20%) died, often after lengthy hospitalizations.

Conclusions: We present the largest case series of LVAD patients with COVID-19 to date. Understanding these characteristics is essential in an effort to improve the outcome of this complex patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059761PMC
April 2021
-->