Montoyaasmussen6352

Data on the presence of subclinical fibrosis across multiple organs in patients with idiopathic lung fibrosis (IPF) are lacking. Our study aimed at investigating through hepatic transient elastography (HTE) the prevalence and clinical impact of subclinical liver fibrosis in a cohort of patients with IPF. Patients referred to the Centre for Rare Lung Disease of the University Hospital of Modena (Italy) from March 2012 to February 2013 with established diagnosis of IPF and without a documented history of liver diseases were consecutively enrolled and underwent HTE. Based on hepatic stiffness status as assessed through METAVIR score patients were categorized as "with liver fibrosis" (corresponding to a METAVIR score of F1-F4) and "without liver fibrosis" (METAVIR F0). Potential predictors of liver fibrosis were investigated through logistic regression model among clinical and serological variables. The overall survival (OS) was assessed according to liver fibrosis and multivariate Cox regression analysis was used to identify independent predictors. In 13 out of 37 patients (35%) with IPF, a certain degree of liver fibrosis was documented. No correlation was found between liver stiffness and clinical-functional parameters. OS was lower in patients 'with liver fibrosis' than in patients 'without liver fibrosis' (median months 33 [23-55] vs. 63 [26-94], p = 0.038). Patients 'with liver fibrosis' presented a higher risk of death at seven years as compared to patients 'without liver fibrosis' (HR = 2.6, 95% CI [1.003-6.7], p = 0.049). Higher level of AST to platelet ratio index (APRI) was an independent predictor of survival (HR = 4.52 95% CI [1.3-15.6], p = 0.02). In our cohort, more than one-third of IPF patients had concomitant subclinical liver fibrosis that negatively affected OS. These preliminary claims further investigation aimed at clarifying the mechanisms beyond multiorgan fibrosis and its clinical implication in patients with IPF.Myristica fragrans (Myristicaceae) is a tropical evergreen tree that yields the two famous spices nutmeg and mace. Despite its socio-economic importance, the spatial distribution of its genetic diversity is barely documented. In this aim, 48 nuclear microsatellite markers were isolated of which 14 were polymorphic in M. fragrans. Number of alleles per locus ranged from 2 to 6. The level of observed heterozygosity ranged from 0.038 to 0.929 across loci. Transferability of these microsatellites in other Myristica species (M. fatua, M. argentea, and M. crassipes) and Myristicaceae species (Horsfieldia palauensis) was tested and successful. These new microsatellites will be useful for future investigation on genetic diversity and population structure of M. fragrans and phylogenetically-related species.Despite advances in classification, treatment, and imaging, neuroendocrine tumours remain a clinically complex subject. In this work, we studied the genetic profile of well-differentiated pancreatic neuroendocrine tumours (PanNETs) in a cohort of Caucasian patients and analysed the signalling pathways and candidate genes potentially associated with the development of this oncological disease. Twenty-four formalin-fixed paraffin-embedded (FFPE) samples of well-differentiated PanNETs were subjected to massive parallel sequencing using the targeted gene panel (409 genes) of the Illumina NextSeq 550 platform (San Diego, USA). In 24 patients, 119 variants were identified in 54 genes. The median mutation rate per patient was 5 (2.8-7). The detected genetic changes were dominated by missense mutations (67%) and nonsense mutations (29%). 18% of the mutations were activating, 35% of the variants led to a loss of function of the encoded protein, and 52% were not classified. Twenty-six variants were described as new. Functionally significant changes in the tertiary structure and activity of the protein molecules in an in silico assay were predicted for 5 new genetic variants. The 5 highest priority candidate genes were selected CREB1, TCF12, PRKAR1A, BCL11A, and BUB1B. Genes carrying the identified mutations participate in signalling pathways known to be involved in PanNETs; in addition, 38% of the cases showed genetic changes in the regulation of the SMAD2/3 signalling pathway. Well-differentiated PanNETs in a Russian cohort demonstrate various molecular genetic features, including new genetic variations and potential driver genes. The highlighted molecular genetic changes in the SMAD2/3 signalling pathway suggest new prospects for targeted therapy.Diabetic nephropathy (DN) is one of the notorious diabetes associated complications. Despite many therapeutic strategies available, metabolic control of DN continues to poses a challenge. In this study, the interactions of mangiferin with selected oral hypoglycemic drugs, metformin and gliclazide to effectively alleviate the symptoms of renal injury in DN are evaluated. Male Sprague Dawley rats were used as experimental model and type II diabetes was induced by administration of high fat diet and low dose streptozotocin. Oral intervention of mangiferin with metformin and gliclazide for a period of 28 days was given to diabetic rats. At the end of the treatment period, biochemical parameters, kidney function markers, anti-oxidant enzymes levels, oxidative stress mediated gene expression and histology were analysed. Significant reduction in the serum biochemical markers (glucose, urea and creatinine) were observed in the groups treated with combination drugs. Marked improvement in the combination treated groups in terms of inflammation and oxidative damage in the gene (TNFα, NFκB, TGFβ, VEGF, PKC) and protein expression (NFκB, VEGF) were noted in the kidney tissue alleviating the symptoms of DN. These results were further corroborated with histopathological results. Scientific data in the present study reveals that the combinations of mangiferin with the oral hypoglycemic drugs have been favorable in alleviating renal injury. Hence, a combination therapy to alleviate the vascular complication, diabetic nephropathy may be considered as a possible therapeutic strategy by including natural phytocompounds as an add on therapy to conventional oral hypoglycemic drugs.The interest on applying mesenchymal stromal cells (MSCs) in orthopedic disorders has risen tremendously in the last years due to scientific successes in preclinical in vitro and animal model studies. In a wide range of diseases and injuries of the musculoskeletal system, MSCs are currently under evaluation, but so far have found access to clinical use only in few cases. The current assignment is to translate the acquired knowledge into clinical practice. Therefore, this review aims at presenting a synopsis of the up-to-date status of the use of MSCs and MSC related cell products in musculoskeletal indications. Clinical studies were included, whereas preclinical and animal study data not have been considered. Most studies published so far investigate the final outcome applying bone marrow derived MSCs. In fewer trials the use of adipose tissue derived MSCs and allogenic MSCs was investigated in different applications. Although the reported results are equivocal in the current literature, the vast majority of the studies shows a benefit of MSC based therapies depending on the cell sources and the indication in clinical use. In summary, the clinical use of MSCs in patients in orthopedic indications has been found to be safe. Standardized protocols and clear definitions of the mechanisms of action and the mode and timing of application as well as further coordinated research efforts will be necessary for finally adding MSC based therapies in standard operating procedures and guidelines for the clinicians treating orthopedic disorders.HIV prevalence is elevated among transgender populations with an estimated 13.7% of transgender adults living with HIV in the USA. In addition, transgender people experience significant disparities in biomedical HIV prevention and treatment. The efficacy of topical microbicides for prevention of HIV acquisition have not been tested among transgender people and may be impacted by hormonal therapies and/or surgeries undertaken by some transgender people to align their anatomy with their gender identity. Low pre-exposure prophylaxis (PrEP) uptake and adherence as well as potential drug-hormone interactions impact the efficacy of PrEP among transgender women. Few transgender men have been engaged in the PrEP continuum, and they have been largely excluded from PrEP research until very recently. Prioritisation of hormone therapy over HIV treatment as well as concerns about drug-hormone interactions may impact transgender women's adherence to antiretroviral therapy. More research is needed to clarify the clinical significance of identified drug-hormone interactions and better inform interventions to improve HIV prevention and care for transgender people.Chronic constipation is one of the five most common symptoms seen by gastroenterologist. In the absence of alarm symptoms, a confident symptom-based diagnosis can often be made using the Rome criteria. Avasimibe cost Three different subtypes have been identified to date normal transit constipation, defaecatory disorders and slow transit constipation. Differentiation between these subtypes can be made through functional testing using tests such as anorectal manometry with balloon expulsion and a radio-opaque marker test. In general, patients are initially advised to increase their fluid and fibre intake. When these general lifestyle recommendations do not improve patients' symptoms, a step-wise and add-on treatment approach should be applied. This review summarises the diagnostic criteria to differentiate functional constipation from other causes of chronic constipation. In addition, current drug treatment options, including discussion of new therapeutic targets are discussed. Further, practical treatment approaches (choice and dosing), include discussion of combination/augmentation, treatment failure (adherence/expectations), and relapse prevention are mentioned. Finally, treatment and management of pain and bloating aspects are included.G-Quadruplexes (G4s) are non-canonical secondary structures formed within guanine-rich regions of DNA or RNA. G4 sequences/structures have been detected in human and in viral genomes, including Coronaviruses Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and SARS-CoV-2. Here, we outline the existing evidence indicating that G4 ligands and inhibitors of SARS-CoV-2 helicase may exert some antiviral activity reducing viral replication and can represent a potential therapeutic approach to tackle the COVID-19 pandemic due to SARS-CoV-2 infection. We also discuss how repositioning of FDA-approved drugs against helicase activity of other viruses, could represent a rapid strategy to limit deaths associated with COVID-19 pandemic.Background Change-of-direction (CoD) speed is a physical fitness attribute in many field-based team and individual sports. To date, no systematic review with meta-analysis available has examined the effects of resistance training (RT) on CoD speed in youth and adults. Objective To aggregate the effects of RT on CoD speed in youth and young physically active and athletic adults, and to identify the key RT programme variables for training prescription. Data sources A systematic literature search was conducted with PubMed, Web of Science, and Google Scholar, with no date restrictions, up to October 2019, to identify studies related to the effects of RT on CoD speed. Study eligibility criteria Only controlled studies with baseline and follow-up measures were included if they examined the effects of RT (i.e., muscle actions against external resistances) on CoD speed in healthy youth (8-18 years) and young physically active/athletic male or female adults (19-28 years). Study appraisal and synthesis methods A random-effects model was used to calculate weighted standardised mean differences (SMD) between intervention and control groups.