Objectives
To analyse whether dynapenic abdominal obesity is a risk factor for Metabolic syndrome (MetS) and its components in individuals 50 years of age or older.
Design
A longitudinal study was ...conducted with an eight-year follow-up.
Setting
Representative sample of community-dwelling participants of the English Longitudinal Study of Ageing (ELSA).
Participants
3,952 individuals free of MetS at baseline.
Measurements
Dynapenic abdominal obesity was defined based on waist circumference (> 102 cm for men and > 88 cm for women) and grip strength (< 26 kg for men and < 16 kg for women). The participants were classified as non-abdominally obese/non-dynapenic (NAO/ND - reference group), abdominally obese/non-dynapenic (AO/ ND), non-abdominally obese/dynapenic (NAO/D) and abdominally obese/dynapenic (AO/D). The outcome was the incidence of MetS based on the presence of three or more of the following criteria: hypertriglyceridemia, hyperglycaemia, low HDL cholesterol, arterial hypertension or body mass index ≥ 30 kg/m2 throughout eight-year follow-up. Additionally, the incidence of each component of MetS was also analyzed. Poisson regression models were run and controlled for sociodemographic, behavioural and clinical variables.
Results
The mean age of the participants was 65 years and 55% were women. The prevalence of AO/ND, NAO/D and AO/D were 35.3, 4.3 and 2.2%, respectively. At the end of follow-up 558 incident cases of MetS were recorded. The adjusted model demonstrated that although abdominal obesity was a risk factor for MetS (IRR: 2.26; 95% CI: 1.87–2.73), the IRR was greater in AO/D individuals (IRR: 3.34; 95% CI: 2.03–5.50) compared with ND/NAO group. Furthermore, ND/AO was a risk factor for incidence of hypertriglyceridemia (IRR: 1.27; 95% CI: 1.06–1.52), hyperglycaemia (IRR: 1.41; 95% CI: 1.18–1.69), low HDL cholesterol (IRR: 1.70; 95% CI: 1.32–2.19) and BMI ≥ 30 kg/ m
2
(IRR: 2.58; 95% CI: 2.04–3.26) while D/AO was a risk factor for hyperglycaemia (IRR: 1.78; 95% CI: 1.02–3.10), low HDL cholesterol (IRR: 2.36; 95% CI: 1.10–5.08), and BMI ≥ 30 kg/m
2
(IRR: 2.79; 95% CI: 1.38–5.62).
Conclusions
Dynapenic abdominal obesity increases the risk of MetS, with a higher IRR compared to obesity alone. The understanding of this synergic action could guide specific clinical strategies, enabling the prevention of metabolic changes that can lead to cardiovascular disease, disability and death.
The activation of T cells is typically accompanied by inhibitory mechanisms within which the programmed cell death (PD1) receptor stands out. Upon binding the ligands PDL1 and PDL2, PD1 drives T ...cells to an unresponsive state called exhaustion, characterized by a markedly decreased capacity to exert effector functions. For this reason, PD1 has become one of the most important targets in cancer immunotherapy. Despite the numerous studies about PD1 signaling modulation, how the PD1 signaling is activated upon the ligands’ binding remains an open question. Several experimental facts suggest that the activation of the PD1-PLD1 pathway depends on the interaction with an unknown partner at the cellular membrane. In this work, we investigate the possibility that the target of PD1-PDL1 is the same PD1-PDL1 complex. We combined molecular docking with molecular dynamics and umbrella sampling simulations to explore different binding modes and assess the complexes’ stability. We predicted a stable dimeric form of the extracellular domains of the PD1-PDL1 complex. This dimeric complex has an affinity comparable to the PD1-PDL1 interaction and resembles the form of a linear lattice. We proposed a new model for PD1 activation where the PD1-PDL1 dimeric form could facilitate the interaction of the intracellular domains of PD1 and the further binding and activation of the SHP2 phosphatase. This model might explain the inhibitory effect of anti-PD1/PDL1 antibodies through the prevention of the formation of the PD1-PDL1 dimers and, subsequently, the abrogation of the SHP2 phosphatase activation.
•We determined the non-linear dynamic viscoelasticity of xanthan gum solutions as a function of NaCl.•SAOS tests are not sensitive to detect the influence of NaCl for “advanced performance” xanthan ...gum solutions.•LAOS were analysed by means of both full-cycle and local methods.•LAOS is more sensitive than SAOS to detect microstructure changes.
Large amplitude oscillatory shear (LAOS) results are shown to be useful to describe the mechanical behaviour of materials at large deformations, well beyond the linear viscoelastic region, which are closer to real processing conditions. We illustrate the applications of LAOS with xanthan gum aqueous dispersions at different NaCl concentrations, on account of the great technological interest in this bacterial polysaccharide. LAOS is shown to be much more sensitive than small amplitude oscillatory shear (SAOS) to the influence of NaCl concentration. This is illustrated by a complete rheological characterisation of the system by means of both full-cycle (average elastic modulus and dynamic viscosity) and local methods (strain-hardening and shear-thickening ratios). The different rheological behaviours observed were related to the microstructures of the xanthan gum molecules as a function of the NaCl content.
Autologous stem cell transplantation (auto-HSCT) is an effective treatment strategy for hematological malignancies. The standard mode of handling hematopoietic progenitors for the autologous ...procedure (CRYO) consists on its collection and freezing with dimethyl sulfoxide (DMSO) and its subsequent thawing and re-infusion. This process is toxic and expensive. Non-cryopreserved (non-CRYO) is a less expensive mode of auto-HSCT. We designed a comparative study between both strategies performed in two different centers to analyze the short-term complications. In total 111 auto-HSCT were performed from January/2015 to October/2016 (42 non-CRYO and 74 CRYO). There were 74 males and 69 (62%) patients had the underlying diagnosis of multiple myeloma. No differences were seen on the characteristics of the apheresis products and their viability. Engraftment was significantly faster in the non-CRYO group (p = 0.001). Febrile neutropenia and severe mucositis were lower in the non-CRYO group (40% vs 92% p = 0.0001 and 11% vs 64%, p = 0.001, respectively). In addition, length of hospitalization was 5 days shorter in the non-CRYO group (p = 0.0001). Overall responses and transplantation outcomes were similar. Our data demonstrate a clear advantage of the non-CRYO over CRYO auto-HSCT with faster engraftment, lower incidence of febrile neutropenia and shorter hospital stay after the transplantation procedure. These data are especially relevant for centers with high transplant activity or with limited resources.
The complex nature of cyber-physical energy systems (CPES) makes systematic testing of new technologies for these setups challenging. Co-simulation has been identified as an efficient and flexible ...test approach that allows consideration of interdisciplinary dynamic interactions. However, basic coupling of simulation models alone fails to account for many of the challenges of simulation-based multi-domain testing such as expert collaboration in test planning. This paper illustrates an extended CPES test environment based on the co-simulation framework mosaik. The environment contains capabilities for simulation planning, uncertainty quantification and the development of multi-agent systems. An application case involving virtual power plant control is used to demonstrate the platform’s features. Future extensibility of the highly modular test environment is outlined.
Introduction: Medical students represent a new generation of medical thought, and if they have a favourable attitude towards organ donation this will greatly encourage its promotion.
Objective: To ...analyse the attitude of medical students in Spanish universities towards the donation of their own organs and to determine the factors affecting this attitude.
Material and Methods: Type of study: A sociological, interdisciplinary, multicentre, and observational study in Spain. Study population: Students studying a degree in medicine enrolled in Spain (n = 34,000). Sample size: A sample of 9598 students (confidence of 99% and precision of ±1%), stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ donation and transplantation (PCID-DTO RIOS) was self-administered and completed anonymously.
Results: The questionnaire completion rate was 95.7% (n = 9.275). 80% were in favour of donation, 2% against and 18% were undecided. The following main variables were related to a favourable attitude: being of the female sex (Odds Ratio = 1.739); being in the sixth year of the degree (OR = 2.506); knowing a donor (OR = 1.346); having spoken about the subject with one's family (OR = 2.132) and friends (OR = 1.333); having a family circle that is in favour, more specifically, having a father (OR = 1.841), mother (OR = 2.538) or partner in favour (OR = 2.192); being a blood donor (OR = 2.824); acceptance of the mutilation of the body if it were necessary (OR = 2.958); and being an atheist or an agnostic (OR = 1.766).
Conclusions: Spanish medical students generally have a favourable attitude towards organ donation, although 20% are not in favour.
The objective of this study was to determine the risk factors of postoperative acute renal failure (ARF) in orthotopic liver transplantation (OLT). We reviewed 184 consecutive OLT. Postoperative ARF ...was defined as a persistent rise of 50% increase or more of the S-creatinine (S-Cr). The patients were classified as early postoperative ARF (E-ARF) (first week) and late postoperative ARF (L-ARF) (second to fourth week). Preoperative variables were age, sex, comorbidity, indication for OLT, Child–Pugh stage, united network for organ sharing status, analysis of the blood and urine, and donor's data. Intraoperative variables were systolic arterial pressure, mean arterial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance index. Surgical technique, number of blood products transfused, need for adrenergic agonist drugs, and intraoperative complications were also important. Postoperative variables were duration of stay in the intensive care unit, time on mechanic ventilation, liver graft dysfunction, need for adrenergic agonist drugs, units of blood products infused, episodes of acute rejection, re-operations, and bacterial infections. Firstly we carried out a univariate statistical analysis, and secondly a logistic regression analysis. The risk factors for E-ARF were: pretransplant ARF (odds ratio (OR)=10.2, P=0.025), S-albumin (OR=0.3, P=0.001), duration of treatment with dopamine (OR=1.6, P=0.001), and grade II–IV dysfunction of the liver graft (OR=5.6, P=0.002). The risk factors for L-ARF were: re-operation (OR=3.1, P=0.013) and bacterial infection (OR=2.9, P=0.017). The development of E-ARF is influenced by preoperative factors such as ARF and hypoalbuminemia, as well as postoperative factors such as liver dysfunction and prolonged treatment with dopamine. The predicting factors of L-ARF differ from E-ARF and correspond to postoperative causes such as bacterial infection and surgical re-operation.
The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the ...factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.
This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.
A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.
The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.
Antimicrobial stewardship programs (ASPs) have been shown to be effective and safe, contributing to reducing and adjusting antimicrobial use in clinical practice. Such programs not only reduce ...antibiotic selection pressure and therefore the selection of multidrug-resistant strains, but also reduce the potential deleterious effects for individual patients and even improve the prognosis by adjusting the choice of drug and dosage, and lessening the risk of adverse effects and interactions. Gram-negative bacilli (GNB), particularly multidrug-resistant strains (MDR-GNB), represent the main infectious problem in the Intensive Care Unit (ICU), and are therefore a target for ASPs. The present review provides an update on the relationship between ASPs and MDR-GNB.
Los programas de optimización del uso de antimicrobianos (PROAs) han demostrado ser una herramienta eficaz y segura que disminuye y ajusta el uso de antimicrobianos en la práctica clínica. El beneficio mostrado es doble, por un parte reduce la presión antibiótica y por tanto la selección de cepas multi-resistentes, y por otro disminuye los potenciales efectos deletéreos en el paciente concreto e incluso mejora el pronóstico al ajustar la elección del fármaco, la posología y los posible efectos adversos e interacciones. Los bacilos Gram-negativos (BGN), especialmente aquellas cepas con mecanismos de resistencia (BGN-MDR), representan el principal problema infeccioso en las unidades de cuidados intensivos y por tanto son el objetivo de los PROAs. En la siguiente revisión actualizaremos aquellos aspectos que combinan y justifican la relación entre los PROAs y los BGN-MDR.
Display omitted
•Two new Diplomystidae catfish species are supported by model-based species delimitation analyses and a species tree.•.The new species are described based on a DNA-based taxonomy ...approach with diagnosis based solely on DNA data.•The southernmost new species is found to have survived the Last Glacial Maximum in situ based on the dated species tree.•Phylogenetic diversity analyses put the highest conservation priority on the basins where the two new species are from.
Diplomystidae is an early-diverged family of freshwater catfish endemic to southern South America. We have recently collected five juvenile specimens belonging to this family from the Bueno River Basin, a basin which the only previous record was a single juvenile specimen collected in 1996. This finding confirms the distribution of the family further South in northern Patagonia, but poses new questions about the origin of this population in an area with a strong glacial history. We used phylogenetic analyses to evaluate three different hypotheses that could explain the origin of this population in the basin. First, the population could have originated in Atlantic basins (East of the Andes) and dispersed to the Bueno Basin after the Last Glacial Maximum (LGM) via river reversals, as it has been proposed for other population of Diplomystes as well as for other freshwater species from Patagonia. Second, the population could have originated in the geographically close Valdivia Basin (West of the Andes) and dispersed south to its current location in the Bueno Basin. Third, regardless of its geographic origin (West or East of the Andes), the Bueno Basin population could have a longer history in the basin, surviving in situ through the LGM. In addition, we conducted species delimitation analyses using a recently developed method that uses a protracted model of speciation. Our goal was to test the species status of the Bueno Basin population along with another controversial population in Central Chile (Biobío Basin), which appeared highly divergent in previous studies with mtDNA. The phylogenetic analyses showed that the population from the Bueno Basin is more related to Atlantic than to Pacific lineages, although with a deep divergence that predated the LGM, supporting in situ survival rather than postglacial dispersal. In addition, these analyses also showed that the species D. nahuelbutaensis is polyphyletic, supporting the need for a taxonomic reevaluation. The species delimitation analyses supported two new species which are described using molecular diagnostic characters: Diplomystes arratiae sp. nov. from the Biobío, Carampangue, and Laraquete basins, maintaining D. nahuelbutaensis valid only for the Imperial Basin, and Diplomystes habitae sp. nov. from the Bueno Basin. This study greatly increases the number of species within both the family Diplomystidae and Patagonia, and contributes substantially to the knowledge of the evolution of southern South American freshwater biodiversity during its glacial history. Given the important contribution to the phylogenetic diversity of the family, we recommend a high conservation priority for both new species. Finally, this study highlights an exemplary scenario where species descriptions based only on DNA data are particularly valuable, bringing additional elements to the ongoing debate on DNA-based taxonomy.
PDF
