Increased urinary markers of kidney damage in the institutionalized frail elderly due to recurrent urinary tract infections.

Objective: To characterize the impact on kidney injury of recurrent urinary tract infections (RUTI) in the frail elderly. Methods: Prospective observational study in 200 frail elderly subjects for 1 year. Groups: GA (n = 100): subjects without RUTI, GB (n = 100): subjects with RUTI. Variables: age, concomitant diseases, glomerular filtration rate (GFR), urine neutrophil gelatinase-associated lipocalin (NGAL) at the beginning (NGAL-1) and end (NGAL-2) of the study, urine N-acetyl glucosaminidase (NAG) at the beginning (NAG-1) and the end (NAG-2) of the study, urine transforming growth factor-beta 1 (TGFbeta-1). Descriptive statistics, Mann-Whitney test, Chi-squared test, Fisher's exact test, and multivariate analysis were used. Results: Mean age was 84.33 (65-99) years old, with no difference between GA and GB. Mean NGAL-1 was 1.29 ng/ml (0.04-8). There was lower in GA than in GB. Mean NGAL-2 was 1.41 ng/ml (0.02-9.22). NGAL-2 was lower in GA than in GB. Mean NAG-1 was 0.38 UU.II/ml (0.01-2.63. NAG-1 in GA was lower than in GB. Mean NAG-2 was 0.44 UU.II/ml (0-3.41). NAG-2 was lower in GA compared with GB. Mean TGFbeta-1 was 23.43 pg/ml (0.02-103.76). TGFbeta-1 was lower in GA than GB. There were no differences in the presence of secondary diagnoses between GA and GB. NAG-2 and NGAL-1 were the most determining factors of renal function; in GA it was NGAL-2, followed by NAG-1; in GB it was NGAL-1, followed by NAG-2. Conclusion: Frail elderly with RUTI have higher urinary levels of renal injury markers, specifically NGAL, NAG, and TGFbeta-1, chronically in periods between urinary tract infection (UTI). Urinary markers of renal injury, specifically NGAL, NAG, and TGFbeta-1, identify early deterioration of renal function, compared with serum creatinine, or albuminuria, in frail elderly with recurrent urinary infections

Mejora del m?todo de deducci?n de intereses en el financiamiento entre empresas y su efecto fiscal en el Per?

Con la promulgaci?n del Decreto Legislativo N? 1424 se prev?, a partir del a?o 2012, la aplicaci?n de una norma anti elusiva cuyo objeto es limitar la deducci?n de intereses generados por pr?stamos suscritos entre empresas. Dicha norma ha sido analizada, pudi?ndose apreciar como resultado de dicho an?lisis que la misma presenta debilidades en su estructura, lo cual generar?a un impacto considerable, ocasionando perjuicios econ?micos a las empresas. En estas circunstancias, se propone una mejora a la norma anti elusiva, la cual se sustenta en la legislaci?n comparada, los an?lisis de informaci?n financiera de las principales empresas nacionales, las entrevistas realizadas a especialistas y las diversas publicaciones especializadas de reconocidos juristas tributarios

Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-? are targets of the autoimmune response in type 1 diabetes

Type 1 diabetes (T1D) results from the destruction of pancreatic beta-cells by the immune system, and CD8(+) T lymphocytes are critical actors in this autoimmune response. Pancreatic islets are surrounded by a mesh of nervous cells, the peri-insular Schwann cells, which are also targeted by autoreactive T lymphocytes and express specific antigens, such as the neurotrophic factor S100-beta. Previous work has shown increased proliferative responses to whole S100-beta in both human T1D patients and the nonobese diabetic (NOD) mouse model. We describe for the first time naturally processed and presented epitopes (NPPEs) presented by class I human leukocyte antigen-A*02:01 (A2.1) molecules derived from S100-beta. These NPPEs triggered IFN-gamma responses more frequently in both newly diagnosed and long-term T1D patients compared with healthy donors. Furthermore, the same NPPEs are recognized during the autoimmune response leading to diabetes in A2.1-transgenic NOD mice as early as 4 wk of age. Interestingly, when these NPPEs are used to prevent diabetes in this animal model, an acceleration of the disease is observed together with an exacerbation in insulitis and an increase in S100-beta-specific cytotoxicity in vaccinated animals. Whether these can be used in diabetes prevention needs to be carefully evaluated in animal models before use in future clinical assays.-Calvino-Sampedro, C., Gomez-Tourino, I., Cordero, O. J., Reche, P. A., Gomez-Perosanz, M., Sanchez-Trincado, J. L., Rodriguez, M. A., Sueiro, A. M., Vinuela, J. E., Calvino, R. V. Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-beta are targets of the autoimmune response in type 1 diabetes

LipoDDx: a mobile application for identification of rare lipodystrophy syndromes

BACKGROUND: Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx(R). Our aim was to establish the effectiveness of LipoDDx(R). Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx(R). The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. RESULTS: LipoDDx(R) provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx(R) the success rate was 17 +/- 20%, while with LipoDDx(R) the success rate was 79 +/- 20% (p < 0.01). CONCLUSIONS: LipoDDx(R) is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value

Continuous?Flow Synthesis of Orange Emitting Sn(II)?Doped CsBr Materials

An ongoing demand toward lead-free all-inorganic cesium metal halide perovskites has presented Sn(II) as an ideal substitute of Pb(II) for applications in optoelectronic devices. The major concern regarding Sn(II) is the instability due to the ambient oxidation to Sn(IV). To expand the scope of traditional perovskite and analogues, herein the synthesis and optical performance of Sn(II)-doped CsBr, a new material formed by interstitial doping of Sn(II) into the CsBr matrix, are reported for the first time. This material is prepared following an antisolvent mediated recrystallization method using a continuous flow reactor, which is beneficial for scaling up the production compared to traditional batch reactors. Sn(II)-doped CsBr exhibits broadband orange emission with full-width-half-maximum of 180 nm and a photoluminescence quantum yield of 21.5%. The emission turned to be highly stable over 7 months despite containing Sn(II). It is suggested that this is due to interstitial location of Sn(II) atoms in bulk of microcrystals. A broadband emission and high aerobic stability are attractive properties of the material for white-light emitting applications

Health Outcome Predictive Evaluation for COVID 19 international registry (HOPE COVID-19), rationale and design

The disease produced by the new coronavirus known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), named COVID-19 (Coronavirus Disease-2019) has recently been classified as a pandemic by the World Health Organization (WHO). However, scarce clinical data is available and generally limited to the Chinese population due to the first cases were identified in Wuhan (Hubei, China).This article describes the rationale and design of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID 19) registry (ClinicalTrials.gov Identifier: NCT04334291). With an ambispective cohort design, eligible patients are those discharged, deceased or alive, from any hospital center with a confirmed diagnosis or a COVID-19 high suspicion. With a current recruitment of more than 7000 cases, in 46 hospitals in 8 countries, since it is not possible to estimate the sample size based on literature reports, the investigators will try to get the maximum numbers of patients possible. The study primary objective is all cause mortality and aims to characterize the clinical profile of patients infected in order to develop a prognostic clinical score allowing, rapid logistic decision making. As secondary objectives, the analysis of other clinical events, the risk-adjusted influence of treatments and previous comorbidities of patients infected with the disease will be performed.The results of HOPE COVID-19 will contribute to a better understanding of this condition. We aim to describe the management of this condition as well as the outcomes in relation to the therapy chosen, in order to gain insight into improving patient care in the coming months. Clinical Trial registration: ClinicalTrials.gov. Unique identifier: NCT04334291

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series