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Proinsulin C-peptide has a protective effect against diabetic complications; however, its role in hyperglycemia-induced pulmonary fibrosis is unknown. In this study, we investigated the inhibitory effect of C-peptide on hyperglycemia-induced pulmonary fibrosis and the molecular mechanism of C-peptide action in the lungs of diabetic mice and in human pulmonary microvascular endothelial cells (HPMVECs). We found that, in the lungs of diabetic mice, C-peptide supplementation using osmotic pumps attenuated hyperglycemia-induced pulmonary fibrosis and expression of fibrosis-related proteins. In HPMVECs, C-peptide inhibited vascular endothelial growth factor-induced adherens junction disruption and endothelial cell permeability by inhibiting reactive oxygen species generation and transglutaminase (TGase) activation. In the lungs, C-peptide supplementation suppressed hyperglycemia-induced reactive oxygen species generation, TGase activation, and microvascular leakage. Fulvestrant research buy C-peptide inhibited hyperglycemia-induced inflammation and apoptosis, which are involved in the pathological process of pulmonary fibrosis. We also demonstrated the role of TGase2 in hyperglycemia-induced vascular leakage, inflammation, apoptosis, and pulmonary fibrosis in the lungs of diabetic TGase2-null (Tgm2-/-) mice. Furthermore, we demonstrated a long-term inhibitory effect of systemic delivery of C-peptide using K9-C-peptide hydrogels on hyperglycemia-induced fibrosis in diabetic lungs. Overall, our findings suggest that C-peptide alleviates hyperglycemia-induced pulmonary fibrosis by inhibiting TGase2-mediated microvascular leakage, inflammation, and apoptosis in diabetes.
It is largely unknown whether individuals with diabetic neuropathy face an increased risk of developing mental illness. Therefore, in a population-based cohort study, we aimed to examine whether individuals with diabetic neuropathy are at elevated risk of being diagnosed with a mental disorder compared to diabetes-duration-matched individuals without diabetic neuropathy.
We used the nationwide Danish registers to identify all individuals diagnosed with diabetic neuropathy between January 1, 1996, and January 1, 2019. For each of these individuals, we identified up to five individuals with diabetes, matched on the duration of illness, who were not diagnosed with diabetic neuropathy. We then compared incidence rates of mental disorders between individuals with diabetic neuropathy and the diabetes-duration-matched individuals using a Cox proportional-hazards model.
Individuals with diabetic neuropathy had a substantial and statistically significant increased risk of being diagnosed with any mental disorder (age- and sex-adjusted hazard rate ratio 1.40, 95% CI 1.31-1.48) as well as all specific mental disorders (psychotic disorder, bipolar disorder, unipolar depression, and/or anxiety disorder) compared with diabetes-duration-matched individuals without diabetic neuropathy.
Diabetic neuropathy appears to be associated with a substantially increased risk of developing a mental disorder. Knowledge of the potential mechanisms underlying this association could inform prevention and treatment and should therefore be pursued further.
Diabetic neuropathy appears to be associated with a substantially increased risk of developing a mental disorder. Knowledge of the potential mechanisms underlying this association could inform prevention and treatment and should therefore be pursued further.
Molecular classification is important for the diagnosis and prognosis of adrenocortical tumors (ACT). Transcriptome profiles separate adrenocortical adenomas 'C2' from carcinomas, and identify two groups of carcinomas 'C1A' and 'C1B', of poor and better prognosis respectively. However, many ACT cannot be profiled because of improper or absent freezing procedures, a mandatory requirement so far. The main aim was to determine transcriptome profiles on formalin-fixed paraffin-embedded (FFPE) samples, using the new 3'-end RNA-sequencing technology. A secondary aim was to demonstrate the ability of this technique to explore large FFPE archives, by focusing on the rare oncocytic ACT variants.
We included 131 ACT a training cohort from Cochin hospital and an independent validation cohort from Wuerzburg hospital. The 3' transcriptome was generated from FFPE samples using QuantSeq (Lexogen, Vienna, Austria) and NextSeq500 (Illumina, San Diego, CA, USA).
In the training cohort, unsupervised clustering identified three groups 'C1A' aggressive carcinomas (n = 28, 29%), 'C1B' more indolent carcinomas (n = 28, 29%), and 'C2' adenomas (n = 39, 41%). The prognostic value of FFPE transcriptome was confirmed in the validation cohort (5-year OS 26% in 'C1A' (n = 26) and 100% in 'C1B' (n = 10), P = 0.003). FFPE transcriptome was an independent prognostic factor in a multivariable model including tumor stage and Ki-67 (OS HR 7.5, P = 0.01). Oncocytic ACT (n = 19) did not form any specific cluster. Oncocytic carcinomas (n = 6) and oncocytic ACT of uncertain malignant potential (n = 4) were all in 'C1B'.
The 3' RNA-sequencing represents a convenient solution for determining ACT molecular class from FFPE samples. This technique should facilitate routine use and large retrospective studies.
The 3' RNA-sequencing represents a convenient solution for determining ACT molecular class from FFPE samples. This technique should facilitate routine use and large retrospective studies.During the last decades, the knowledge on follicular cell-derived thyroid cancer molecular biology has led to the evolution of a number of novel therapies for these tumors, mainly tyrosine kinase inhibitors. Lenvantinib, sorafenib and recently cabozantinib have been approved for differentiated thyroid cancer (DTC), while larotrectinib and entrectinib for neurotrophic-tropomyosin receptor kinase-fusion thyroid cancer. For radioiodine (RAI) refractory DTCs ongoing research aims to identify agents that may restore RAI-avidity via redifferentiation protocols (vemurafenib or dabrafenib and trametinib) or combination treatments. These treatments are based on the tumor molecular signature. The treatment with targeted therapies has changed the therapeutic strategies and the disease prognosis, however drug resistance remains the main reason for treatment failure. Thus, the understanding of both molecular pathways implicated in tumorigenesis, and tumoral escape mechanisms, are of paramount significance for the development of new therapies for DTC. The present review focuses on the molecular landscape of DTC, the approved targeted therapies as well as the mechanisms of drug resistance. Furthermore, it points to the ongoing research and the future perspectives for the development of more efficient drugs for DTC.
Cognitive impairment is a mental disorder that commonly affects elderly people. Serious games, which are games that have a purpose other than entertainment, have been used as a nonpharmacological intervention for improving cognitive abilities. The effectiveness and safety of serious games for improving cognitive abilities have been investigated by several systematic reviews; however, they are limited by design and methodological weaknesses.
This study aims to assess the effectiveness and safety of serious games for improving cognitive abilities among elderly people with cognitive impairment.
A systematic review of randomized controlled trials (RCTs) was conducted. The following 8 electronic databases were searched MEDLINE, Embase, CINAHL, PsycINFO, ACM Digital Library, IEEE Xplore, Scopus, and Google Scholar. We also screened reference lists of the included studies and relevant reviews, as well as checked studies citing our included studies. Two reviewers independently carried out the study selection, dgnitive training games have the potential to improve global cognition among elderly people with cognitive impairment. However, our findings remain inconclusive because the quality of evidence in all meta-analyses was very low, mainly due to the risk of bias raised in the majority of the included studies, high heterogeneity of the evidence, and imprecision of total effect sizes. Therefore, psychologists, psychiatrists, and patients should consider offering serious games as a complement and not a substitute to existing interventions until further more robust evidence is available. Further studies are needed to assess the effect of exergames, the safety of serious games, and their long-term effects.
Cardiorespiratory decompensation (CRD) visits have a profound effect on adult emergency departments (EDs). Respiratory pathogens like respiratory syncytial virus (RSV) and influenza virus are common reasons for increased activity in pediatric EDs and are associated with CRD in the adult population. Given the seasonal aspects of such challenging pathology, it would be advantageous to predict their variations.
The goal of this study was to evaluate the increased burden of CRD in adult EDs during flu and bronchiolitis outbreaks in the pediatric population.
An ecological study was conducted, based on admissions to the adult ED of the Centre Hospitalier Universitaire (CHU) of Grenoble and Saint Etienne from June 29, 2015 to March 22, 2020. The outbreak periods for bronchiolitis and flu in the pediatric population were defined with a decision-making support tool, PREDAFLU, used in the pediatric ED. A Kruskal-Wallis variance analysis and a Spearman monotone dependency were performed in order to study the relatbreaks such as PREDAFLU can be used to provide early warnings of increased activity in adult EDs for CRD visits.
This study established that CRD visits and bed occupancy for adult EDs were significantly increased during bronchiolitis and pediatric influenza outbreaks. Therefore, a prediction tool for these outbreaks such as PREDAFLU can be used to provide early warnings of increased activity in adult EDs for CRD visits.
To address the matter of limited resources for treating individuals with mental disorders, e-mental health has gained interest in recent years. More specifically, mobile health (mHealth) apps have been suggested as electronic mental health interventions accompanied by cognitive behavioral therapy (CBT).
This study aims to identify the therapeutic aspects of CBT that have been implemented in existing mHealth apps and the technologies used. From these, we aim to derive research gaps that should be addressed in the future.
Three databases were screened for studies on mHealth apps in the context of mental disorders that implement techniques of CBT PubMed, IEEE Xplore, and ACM Digital Library. The studies were independently selected by 2 reviewers, who then extracted data from the included studies. Data on CBT techniques and their technical implementation in mHealth apps were synthesized narratively.
Of the 530 retrieved citations, 34 (6.4%) studies were included in this review. mHealth apps for CBT exploi health interventions.
There are CBT techniques that can be implemented in mHealth apps. Additional research is needed on the efficacy of the mHealth interventions and their side effects, including inequalities because of the digital divide, addictive internet behavior, lack of trust in mHealth, anonymity issues, risks and biases for user groups and social contexts, and ethical implications. Further research is also required to integrate and test psychological theories to improve the impact of mHealth and adherence to the e-mental health interventions.
Read More: https://www.selleckchem.com/products/Fulvestrant.html
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