Analysis of class 2 integrons as a marker for multidrug resistance among gram negative bacilli

Class 1 and 2 integrons are considered the paradigm of multidrug resistant (MDR) integrons. Although class 1 integrons have been found statistically associated to Enterobacteriaceae MDR isolates, this type of study has not been conducted for class 2 integrons. Escherichia coli and 3 species that were found that harbored more than 20% of class 2 integrons in clinical isolates, were selected to determine the role of intI2 as MDR marker. A total of 234 MDR/191 susceptible non-epidemiologically related isolates were analyzed. Seventy-four intI2 genes were found by PCR and sequencing. An intI2 relationship with MDR phenotypes in Acinetobacter baumannii and Enterobacter cloacae was found. No statistical association was identified with MDR E. coli and Helicobacter pylori isolates. In other words, the likelihood of finding intI2 is the same in susceptible and in MDR E. coli and H. pylori strains, suggesting a particular affinity between the mobile element Tn7 and some species. The use of intI2 as MDR marker was species-dependent, with fluctuating epidemiology at geographical and temporal gradients. The use of intI2 as MDR marker is advisable in A. baumannii, a species that can reach high frequencies of this genetic element.Fil: Rodriguez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cassini, Marcelo Hernan. Universidad Nacional de Luján; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Delgado, Gabriela del Valle. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hospital del Ni?o Jesus; ArgentinaFil: Argentinian Integron Study Group. No especifica;Fil: Ramirez, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. California State University; Estados UnidosFil: Centron, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Reward-related gustatory and psychometric predictors of weight loss following bariatric surgery: a multicenter cohort study

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]: Reward sensitivity has been proposed as a potential mediator of outcomes for bariatric surgery. Objectives: We aimed to determine whether gustatory and psychometric measures of reward-related feeding are predictors of bariatric-induced weight loss. Methods: A multicenter longitudinal cohort study was conducted in patients scheduled for bariatric surgery (surgical group), assessed at baseline and 2 follow-up assessments. Predictions of % weight loss from baseline (%WL) according to baseline gustatory measures, including intensity and pleasantness ratings of sweet and other tastants, and psychometric measures of reward-related feeding behavior, including hedonic hunger scores, were assessed with multivariable linear regression. Exploratory analyses were conducted to test for associations between %WL and changes in gustatory and psychophysical measures, as well as for comparisons with data from patients on the surgery waiting list (control group). Results: We included 212 patients, of whom 96 in the surgical group and 50 in the control group were prospectively assessed. The groups were similar at baseline and, as expected, bariatric surgery resulted in higher %WL (BTreatment-Time = 2.4; 95% CI: 2.1-2.8; P < 0.0001). While variation in gustatory measures did not differ between groups, in the surgery group baseline sweet intensity predicted %WL at the primary endpoint (11 to 18 months postoperatively; β = 0.2; B = 0.2, 95% CI: 0.02 to 0.3; P = 0.02), as did hedonic hunger scores (β = -0.2; B = -2.0, 95% CI: -3.8 to -0.3; P = 0.02). Furthermore, at this endpoint, postsurgical reduction of sweet taste intensity and acceptance of sweet foods were associated with %WL (β = -0.3; B = -3.5, 95% CI: -5.8 to -1.3; P = 0.003, and β = -0.2; B = -4.7, 95% CI: -8.5 to -0.8; P = 0.02, respectively). The use of sweet intensity as a predictor of weight change was confirmed in another bariatric cohort. Conclusions: Sweet intensity ratings and hedonic hunger scores predict %WL after surgery. The variability of sweet intensity ratings is also associated with %WL, further suggesting they may reflect physiological processes that are variably modulated by bariatric surgery, influencing clinical outcomes.AJO-M is a recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests; is national coordinator for Portugal of a non-interventional study (EDMS-ERI-143085581, 4.0) to characterize a treatment-resistant depression cohort in Europe, sponsored by Janssen-Cilag Ltd; and is national coordinator of a trial of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT NUMBER: 2017–003288–36).info:eu-repo/semantics/publishedVersio

Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia : a multicentre, double-blind, randomised, placebo-controlled trial

CITATION: Hofmeyr, G. J., et al. 2019. Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia : a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet, 393(10169):P330-339, doi:10.1016/S0140-6736(18)31818-X.The original publication is available at https://www.thelancet.comBackground: Reducing deaths from hypertensive disorders of pregnancy is a global priority. Low dietary calcium might account for the high prevalence of pre-eclampsia and eclampsia in low-income countries. Calcium supplementation in the second half of pregnancy is known to reduce the serious consequences of pre-eclampsia; however, the effect of calcium supplementation during placentation is not known. We aimed to test the hypothesis that calcium supplementation before and in early pregnancy (up to 20 weeks’ gestation) prevents the development of pre-eclampsia Methods: We did a multicountry, parallel arm, double-blind, randomised, placebo-controlled trial in South Africa, Zimbabwe, and Argentina. Participants with previous pre-eclampsia and eclampsia received 500 mg calcium or placebo daily from enrolment prepregnancy until 20 weeks’ gestation. Participants were parous women whose most recent pregnancy had been complicated by pre-eclampsia or eclampsia and who were intending to become pregnant. All participants received unblinded calcium 1·5 g daily after 20 weeks’ gestation. The allocation sequence (1:1 ratio) used computer-generated random numbers in balanced blocks of variable size. The primary outcome was pre-eclampsia, defined as gestational hypertension and proteinuria. The trial is registered with the Pan-African Clinical Trials Registry, number PACTR201105000267371. The trial closed on Oct 31, 2017. Findings: Between July 12, 2011, and Sept 8, 2016, we randomly allocated 1355 women to receive calcium or placebo; 331 of 678 participants in the calcium group versus 320 of 677 in the placebo group became pregnant, and 298 of 678 versus 283 of 677 had pregnancies beyond 20 weeks’ gestation. Pre-eclampsia occurred in 69 (23%) of 296 participants in the calcium group versus 82 (29%) of 283 participants in the placebo group with pregnancies beyond 20 weeks’ gestation (risk ratio [RR] 0·80, 95% CI 0·61–1·06; p=0·121). For participants with compliance of more than 80% from the last visit before pregnancy to 20 weeks’ gestation, the pre-eclampsia risk was 30 (21%) of 144 versus 47 (32%) of 149 (RR 0·66, CI 0·44–0·98; p=0·037). There were no serious adverse effects of calcium reported. Interpretation: Calcium supplementation that commenced before pregnancy until 20 weeks’ gestation, compared with placebo, did not show a significant reduction in recurrent pre-eclampsia. As the trial was powered to detect a large effect size, we cannot rule out a small to moderate effect of this intervention. ernal and Child Health.https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31818-X/fulltextPublisher's versio

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for &gt;12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11%&nbsp;versus&nbsp;0%,&nbsp;p=0.030), lymphopenia (42%&nbsp;versus&nbsp;18%,&nbsp;p=0.020), C-reactive protein level of &gt;30 mg/L (35%&nbsp;versus&nbsp;0%,&nbsp;p=0.0001), and D-dimer level of &gt;1000 ng/mL (43%&nbsp;versus&nbsp;6%,&nbsp;p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11%&nbsp;versus&nbsp;2%,&nbsp;p=0.178) and cardiac alterations on echocardiogram (33%&nbsp;versus&nbsp;22%,&nbsp;p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100]&nbsp;versus&nbsp;81 [34-100],&nbsp;p=0.012), and school score (60 [15-100]&nbsp;versus&nbsp;70 [15-95],&nbsp;p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome

: The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc

Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis

Introduction: The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). Methods: In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes. Results: No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis. Conclusions: Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old