Incidence of zygomycosis in transplant recipients

AbstractRecently, a remarkable increase in the incidence of zygomycosis has been reported from institutions in the USA and Europe. The use of voriconazole for the treatment of aspergillosis and, less frequently, the use of echinocandins as empirical treatment for invasive fungal infections are thought to be responsible for the increase. In addition, an increased incidence of this infection has been observed in transplant recipients, including both haematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) patients. There are no global surveys on the prevalence or incidence of zygomycosis, but data from individual institutions and countries show that zygomycosis is an emerging infection. The increased incidence of zygomycosis most probably reflects a greater frequency of predisposing factors, such as higher numbers of patients undergoing HSCT and immunosuppressive chemotherapy. In addition, the emergence of rare pathogens as a result of the rise in the use of antifungal therapy against common species can be postulated. Further, the availability of antifungal agents with activity profiles that are more specific for selected fungi increases the necessity of identifying pathogenic fungi; the frequency of Zygomycetes infections may have been underestimated until now because therapeutic decisions did not depend on the precise identification of pathogenic fungi

Randomized Clinical Trials of obesity treatments in Mexican population. Systematic Review and Meta-Analysis

Background: Mexicans and Mexican Americans share similar culture, genetic background, and predisposition for obesity and diabetes. Randomized clinical trials (RCT) assessing obesity treatments (ObT) are reliable to assess efficacy. To date, there is no systematic review to investigate ObT tested by RCT in Mexican adults. Methods: We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve ObT RCT from 1990 to 2019. The ObT included alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions. The analyzed RCT were at least three months of duration, and reported: BMI, weight, waist circumference, triglycerides, glucose and blood pressure. Results: We found 634 entries; after removal of duplicates and exclusions based on eligibility criteria, we analyzed 43 and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and did not have replications from other studies. The nutrition/behavioral interventions were difficult to blind, and most studies had medium to high risk of bias. Random effects meta-analysis of nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like plain water instead of sweet beverages decreased triglycerides and systolic blood pressure. Participants with obesity and hypertension had beneficial effects with antioxidants, and the treatment with insulin increased weight in those with T2D. Conclusions: The RCT’s in Mexico reported effects on metabolic components despite small sample sizes and lack of replication. In the future we should analyze ObT in population living on the U.S.-Mexico border; therefore, bi-national collaboration is desirable to disentangle cultural effects on ObT response

Project: Center for Diabetes and Metabolism [Centro de Diabetes y Metabolismo: CeDiMet], a collaborative dream comes true

Reynosa urban area has 690,000 inhabitants (384,000 adults \u3e20 years old), 35% moved from other states. The use of cell phones is in 81%, personal computer or laptop with 29%. The prevalence of overweight is 39%, obesity 36%, and T2D 13%. The expected adult population with T2D is 49,900 individuals. The are 5 clinics prepared to attend T2D, and few with specialized personnel. The CeDiMet is a collaborative clinic involving health personnel and researchers from the Universidad Mexico Americana del Norte, Universidad Autonoma de Tamaulipas, Hospital General de Mexico “Dr. Eduardo Liceaga”, University of Texas Rio Grande Valley, and the Texas Diabetes Institute in San Antonio. The funding source comes from private companies in Reynosa. The clinical structure includes physicians, nurses, nutritionists, psychologists, and a section for telemedicine for consulting specialists from USA and Mexico City. Besides clinical attendance, the CeDiMet will conduct educational activities in offices, factories, churches, and schools for prevention of obesity complications (T2D and hypertension), early detection of diabetic foot, fatty liver, and endothelial damage. “Tree of Health in the Family” is a program to encourage youth to know and understand the metabolic problems in their families to focus on prevention. Recently, we obtained a grant from COTACyT to explore the effect of COVID-19 in a cohort of 200 students and their families. The analysis of post-traumatic stress due to confinement and antibodies concentration to detect contacts and its association with metabolic problems is an example of the research we can perform

Fat Distribution and Differential Effects on Metabolic Liver Fat Infiltration in Young Mexicans in Reynosa, Mexico: A Collaborative Study across the U.S.-Mexico Border

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a descriptive term for NAFLD (Non-alcoholic) physiopathology associated with obesity. The age of onset linked to body fat distribution is poorly studied. Therefore, we aimed to assess the body fat effect on liver fat infiltration and stiffness (LSt) mediated by insulin resistance (IR). Methods: After obtaining informed consent, five hundred freshmen from two universities in Reynosa, Mexico (UMAN & UAT) were enrolled in the study. They completed a questionnaire focused on familial cardiometabolic risk and provided anthropometric measurements. In a subset of N=200, we obtained blood samples for biochemical measurements, body fat percentage (BF%) by bioimpedance, LSt (kPa), and fat infiltration (Continued Attenuation Parameter, CAP) by elastography. We used mediation analysis with structural equation models (Stata v16.1) to determine the relationship between BMI, BF%, and abdominal obesity with IR and liver stiffness and fat infiltration. The term “-\u3e” means ‘explain’ or ‘cause’. Results: We found that AO-\u3eIR (standardized values b=0.53, p=0.005), AO-\u3eCAP (b=0.69, pIR (b=0.23, p=0.007). BMI did not have an effect on CAP or IR. Also, BMI-\u3eLS (b=0.47, p=0.05) but AO-\u3eLS was absent. Finally, there was a bidirectional relationship between LS and IR [LS-\u3eIR (b=0.18, p=0.001), and IR-\u3eLS (b=0.27, p=0.001)]. Conclusion: Our findings suggest the adipose tissue measured as AO or BMI showed different phenotypic effects on liver fat infiltration or stiffness. Visceral fat had a direct effect on IR, meanwhile, subcutaneous adipose tissue was associated with liver stiffness. Our findings suggest that early age interventions should be focused on reducing visceral fat deposition

Neutralizing anti-RBD fraction for SARS-CoV-2 is associated with the interaction waist circumference and sex. An ESFUERSO preliminary report on university students

In a previous study we reported that 25% of college students had a family history of type 2 diabetes (T2D), and 39% of hypertension. Interestingly, between 17 to 47% reported not knowing about T2D or hypertension, neither the existing obesity-metabolic problems (ESFUERSO study). The COVID-19 pandemic forced confinement and modifications in food intake, physical activity, and psychological stress. This study aimed to analyze if the immune Ig-G anti-RBD (protective epitope in S protein) response associated with type of vaccination, metabolic risk, perceived stress, and history of COVID-19 contacts. We included 116 students at the 3th year of follow up in the ESFUERSO cohort at Reynosa. Mean age 21.4 (SD 1.04) years old, BMI 28 (6.6), females 70% (81/116). The serum concentration of Ig-G anti-RGB measured by ELISA adjusted by sex, age, body fat percentage, and BMI was analyzed. Researchers performed a multiple regression analysis with Stata V17.0. We found that 70% of the students had a family history of diabetes, hypertension, and/or obesity at baseline. Only 5 (4%) students did not have any vaccine at the time of the study, 102 (88%) were vaccinated with Moderna or Pfizer and 9 (8%) with other vaccines (Cansino, Sinovac). The prevalence of positive anti-RBD was 91%. The body fat percentage interacted with sex (p=0.034) explaining the serum concentration of anti-RBD decreased as adiposity increases in men, but increased in women. The interaction remained is spite of type of vaccination. We found no differences among metabolic risks for food consumption, distress, uncertainty, lack of sleep, sadness, and anxiety were associated with metabolic problems. Our model predicts neutralizing anti-RBD had multiplicative interaction by sex and body fat percentage (increases in females and decreases in males), with no effects on stress score or food consumption

Differences in Expression of IQSEC2 Transcript Isoforms in Male and Female Cases with Loss of Function Variants and Neurodevelopmental Disorder

Pathogenic hemizygous or heterozygous mutations in the IQSEC2 gene cause X-linked intellectual developmental disorder-1 (XLID1), characterized by a variable phenotype including developmental delay, intellectual disability, epilepsy, hypotonia, autism, microcephaly and stereotypies. It affects both males and females typically through loss of function in males and haploinsufficiency in heterozygous females. Females are generally less affected than males. Two novel unrelated cases, one male and one female, with de novo IQSEC2 variants were detected by trio-based whole exome sequencing. The female case had a previously undescribed frameshift mutation (NM_001111125:c.3300dup; p.Met1101Tyrfs*5), and the male showed an intronic variant in intron 6, with a previously unknown effect (NM_001111125:c.2459+21C>T). IQSEC2 gene expression study revealed that this intronic variant created an alternative donor splicing site and an aberrant product, with the inclusion of 19bp, confirming the pathogenic effect of the intron variant. Moreover, a strong reduction in the expression of the long, but also the short IQSEC2 isoforms, was detected in the male correlating with a more severe phenotype, while the female case showed no decreased expression of the short isoform, and milder effects of the disease. This suggests that the abnormal expression levels of the different IQSEC2 transcripts could be implicated in the severity of disease manifestations.This research was funded by INSTITUTO DE SALUD CARLOS III, institutional project Spain UDP and grant PT20CIII/00009.S

Cocoa coproducts-based and walnut oil gelled emulsion as animal fat replacer and healthy bioactive source in beef burgers

The aim of this work was to evaluate the effects on the chemical, physic-chemical, tech-nological, and sensory properties of beef burger when replacing different quantities of fat (50 and 100%) with different levels of oil-in-water-gelled emulsion elaborated with walnut oil and cocoa bean shell flour (GECW). The chemical composition of the samples was affected by the fat replace-ment. The reformulation increased the moisture and ash content while the fat and protein content decreased with respect to the control sample. The linolenic and linolenic acid content of the beef burgers increased as the GECW replacement was augmented. The polyunsaturated fatty/saturated fatty acid ratio increased in both raw and cooked burgers, whereas the atherogenicity index and thrombogenicity index were reduced in both raw and cooked burgers with respect to the control sample. The use of GECW as a fat replacer was found to be effective in improving the cooking loss. Similarly, there were positive effects on reductions in the diameter and the increases in the thickness of the beef burgers. Regarding lipid stability, in both the raw and cooked burgers, the reformulation increased the 2-thiobarbituric acid reactive substance (TBARs) values with respect to the control sample. In both types of reformulated burgers, three bound polyphenols (mainly catechin and epicatechin) and two free polyphenols were identified, as were methylxanthines theobromine and caffeine. The sensory properties for the control and partial pork backfat replacement treatments were similar, while the sample with the total pork backfat replacement treatment showed the lowest scores. The blend of cocoa bean shell flour and walnut oil could be used as new ingredients for the development of beef burgers with a healthier nutritional profile without demeriting their sensory or cooking characteristics and physic-chemical properties.This research was funded by Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo CYTED: 119RT0568.info:eu-repo/semantics/publishedVersio

Defining a Novel Role for the Coxsackievirus and Adenovirus Receptor in Human Adenovirus Serotype 5 Transduction In Vitro in the Presence of Mouse Serum

Human adenoviral serotype 5 (HAdV-5) vectors have predominantly hepatic tropism when delivered intravascularly, resulting in immune activation and toxicity. Coagulation FX binding to HAdV-5 mediates liver transduction and provides protection from virion neutralisation in mice. FX is dispensable for liver transduction in mice lacking IgM antibodies or complement, suggesting alternative transduction pathways exist. To identify novel factor(s) mediating HAdV-5 FX-independent entry, we investigated HAdV-5 transduction in vitro in the presence of serum from immunocompetent C57BL/6 or immunocompromised mice lacking IgM antibodies (Rag 2-/- and NSG). Sera from all three mouse strains enhanced HAdV-5 transduction of A549 cells. While inhibition of HAdV-5:FX interaction with X-bp inhibited transduction in the presence of C57BL/6 serum, it had negligible effect on the enhanced transduction observed in the presence of Rag 2-/- or NSG serum. Rag 2-/- serum also enhanced transduction of the FX-binding deficient AdT*. Interestingly, Rag 2-/- serum enhanced HAdV-5 transduction in a FX-independent manner in CHO-CAR and SKOV3-CAR cells. Additionally, blockade of CAR with soluble HAdV-5 fiber knob inhibited mouse serum-enhanced transduction in A549 cells, suggesting a potential role for CAR. Transduction of HAdV-5 KO1 and HAdV-5/F35 (CAR-binding deficient) in the presence of Rag 2-/- serum was equivalent to that of HAdV-5, indicating that direct interaction between HAdV-5 and CAR is not required. These data suggest that FX may protect HAdV-5 from neutralization but has minimal contribution to HAdV-5 transduction in the presence of immunocompromised mouse serum. Alternatively, transduction occurs via an unidentified mouse serum protein capable of bridging HAdV-5 to CAR

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

International audienceno abstrac

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R01NS109858, to VAG); the Paul A. Marks Scholar Program at the Columbia University Vagelos College of Physicians and Surgeons (to VAG); a TIGER grant from the TAUB Institute at the Columbia Vagelos College of Physicians and Scientists (to VAG); the Swiss National Science Foundation (SNF 31003A-179371, to TH); the European Joint Program on Rare Diseases (EJP RD+SNF 32ER30-187505, to TH); the Swiss Cancer League (KFS-4999-02-2020, to GD); the EPFL institutional fund (to GD); the Kristian Gerhard Jebsen Foundation (to GD); the Swiss National Science Foundation (SNSF) (310030_184926, to GD); the Swiss Foundation for Research on Muscle Disease (FSRMM, to MAL); the Natural Science and Engineering Research Council of Canada (Discovery Grant 2020-04241, to JEB); the Italian Ministry of Health Young Investigator Grant (GR-2011-02347754, to EL); the Fondazione Istituto di Ricerca Pediatrica – Città della Speranza (18-04, to EL); the Wroclaw Medical University (SUB.E160.21.004, to RS); the National Science Centre, Poland (2017/27/B/NZ5/0222, to RS); Telethon Undiagnosed Diseases Program (TUDP) (GSP15001); the Temple Street Foundation/Children’s Health Foundation Ireland (RPAC 19-02, to IK); the Deutsche Forschungsgemeinschaft (DFG) (PO2366/2–1, to BP); the Instituto de Salud Carlos III, Spain (to ELM, EBS, and BMD); the National Natural Science Foundation of China (81871079 and 81730036, to HG and KX); and the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH (R01 DK115574, to SSC).The DEFIDIAG study is funded by grants from the French Ministry of Health in the framewok of the national French initiative for genomic medicine. The funders were not involved in the study design, data acquisition, analysis, or writing of the manuscript. Funding for the DECIPHER project was provided by Wellcome. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12, granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.S