Postklein4593

Pioglitazone is a thiazolidinedione oral antidiabetic agent. This study aimed to investigate the effects of pioglitazone as insulin sensitizer on β-arrestin2 signaling in classical insulin target tissues.

Experiments involved three groups of mice; the first one involved mice fed standard chow diet for 16 weeks; the second one involved mice fed high-fructose, high-fat diet (HFrHFD) for 16 weeks; and the third one involved mice fed HFrHFD for 16 weeks and received pioglitazone (30 mg/kg/day, orally) in the last four weeks of feeding HFrHFD.

The results showed significant improvement in the insulin sensitivity of pioglitazone-treated mice as manifested by significant reduction in the insulin resistance index. This improvement in insulin sensitivity was associated with significant increases in the β-arrestin2 levels in the adipose tissue, liver, and skeletal muscle. Moreover, pioglitazone significantly increased β-arrestin2 signaling in all the examined tissues as estimated from significant increases in phosphatidylinositol 4,5 bisphosphate and phosphorylation of Akt at serine 473 and significant decrease in diacylglycerol level.

To the best of our knowledge, our work reports a new mechanism of action for pioglitazone through which it can enhance the insulin sensitivity. Pioglitazone increases β-arrestin2 signaling in the adipose tissue, liver, and skeletal muscle of HFrHFD-fed mice.

To the best of our knowledge, our work reports a new mechanism of action for pioglitazone through which it can enhance the insulin sensitivity. Pioglitazone increases β-arrestin2 signaling in the adipose tissue, liver, and skeletal muscle of HFrHFD-fed mice.

Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated.

In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57-75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry.

Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated with plasma ln-XOR activity after adjusting for several confounders. see more Plasma XOR activity was significantly higher in CKD patients with (n = 26) than in those without (n = 92) DM (62.7 [32.3-122] vs. 25.7 [13.4-45.8] pmol/h/mL, p < 0.001). A total of 38 patients were taking uric acid-lowering drugs. Multiple regression analysis of CKD patients not administered uric acid-lowering drugs (n = 80) showed no significant association between eGFR and plasma ln-XOR activity. In contrast, association between glycemic control and plasma ln-XOR activity was significant even in CKD patients without uric acid-lowering drug treatment.

These results indicate the importance of glycemic control in CKD patients in regard to decreased XOR, possibly leading to a decrease in CVD events.

These results indicate the importance of glycemic control in CKD patients in regard to decreased XOR, possibly leading to a decrease in CVD events.

Further understanding of adverse clinical events in patients with chronic kidney disease (CKD) is needed. This study aimed to describe characteristics of patients with nondialysis-dependent (NDD) and dialysis-dependent (DD) CKD and to assess incidence rates of uncommon adverse clinical events of interest in these patients.

This retrospective study used electronic medical record data from USA CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 between January 1, 2010, and December 31, 2018, obtained from the USA-based TriNetX database. NDD-CKD and DD-CKD were diagnosed and staged from ≥2 consecutive eGFR readings, recorded ≥90 days apart. Dialysis was identified using procedure codes for renal replacement therapy. Outcomes assessed were select uncommon adverse clinical events, defined by International Classification of Disease, 9th and 10th Revision codes.

Incidence rates of adverse clinical events per 100 person-years (95% confidence interval) were generally higher in patients with DD-CKD versus NDD-CKD. Differences were particularly pronounced for hyperkalemia (26.9 [26.2-27.6] vs. 4.5 [4.5-4.6]), acidosis (15.1 [14.7-15.6] vs. 3.4 [3.4-3.4]), and sepsis (14.6 [14.2-15.1] vs. 3.3 [3.3-3.4]). Among DD-CKD patients, incidence rates of adverse events were particularly high during the first 3 months following dialysis initiation. Incidence of adverse clinical events generally increased with decreasing eGFR among patients with NDD-CKD and with hemoglobin <10 g/dL in both NDD- and DD-CKD patients.

Our results help establish baseline rates of uncommon adverse clinical events and provide additional evidence of increased morbidity for patients with DD-CKD versus NDD-CKD.

Our results help establish baseline rates of uncommon adverse clinical events and provide additional evidence of increased morbidity for patients with DD-CKD versus NDD-CKD.Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors' objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.Lupus erythematosus (LE) is an autoimmune disease with a wide range of clinical and cutaneous manifestations. Along with the well-known typical cutaneous manifestations of LE, some cutaneous manifestations are rarer, but still characteristic, enabling the dermatologist and the general practitioner who know them to suspect cutaneous LE (CLE) and investigate a possible underlying systemic involvement. Indeed, not infrequently a skin manifestation is the first presentation of systemic LE (SLE), and >75% of SLE patients show signs of skin disease during the course of the illness. Especially, SLE involvement occurs in cases of acute CLE, while it is uncommon in subacute CLE and rare in chronic CLE. This review aims to concentrate especially on atypical cutaneous manifestations of LE to enable the clinician to diagnose even the rarest forms of CLE.

The aim of this case was to investigate the association of the Zika virus infection in utero with the autism spectrum disorder (ASD) as clinical outcome that presented no congenital anomalies.

ASD was diagnosed in the second year of life by different child neurologists and confirmed by DSM-5 and ASQ. After that, an extensive clinical, epidemiological, and genetic evaluations were performed, with main known ASD causes ruled out.

An extensive laboratorial search was done, with normal findings. SNP array identified no pathogenic variants. Normal neuroimaging and EEG findings were also obtained. ZIKV (Zika virus) IgG was positive, while IgM was negative. Other congenital infections were negative. The exome sequencing did not reveal any pathogenic variant in genes related to ASD.

Accordingly, this report firstly associates ZIKV exposure to ASD.

Accordingly, this report firstly associates ZIKV exposure to ASD.Implantable telemetric transponders for contactless measurement of physiological parameters are often used in animal-based research. After explantation, single-use devices cannot be re-implanted because of non-validated functionality and necessary re-sterilisation. This is disadvantageous because the battery life would enable a second implantation cycle in another animal. To save costs and time taken for the manufacturer's refurbishing process, we validated and implemented a re-sterilisation protocol for single-use transponders using hydrogen peroxide gas. The described protocol was established with models, i.e., for large (n = 7) and small (n = 3) animals, of telemetric device from 2 different manufacturers (Data Science International and EMKA). All transponders, prepared according to the protocol, were previously implanted subcutaneously in the flank of pigs or rats for a duration of 21 days. Our investigations demonstrate that disinfection only is not sufficient against bacterial contamination and that sterility can only be achieved by additional gas sterilisation with hydrogen peroxide. Furthermore, re-implantation of the re-sterilised transponders into pigs caused neither undesired tissue reactions along the transponder nor impairment of the measured values when compared to the first implantation and after necropsy in 4 cases. We were able to demonstrate that, using our protocol, re-implantation of reprocessed single-use telemetric devices can be performed without compromising transponder quality.

Childhood atopic dermatitis (AD) is an inflammatory skin disease which sometimes predisposes to allergies. Environmental factors (low humidity, irritants, etc.) are prominent causative triggers of AD.

This study aims to explore the effects of both meteorological factors and air pollutants on childhood AD, and the modification effects by season in Shanghai, China.

Quasi-Poisson generalized linear regression model, combined with a distributed lag nonlinear model was used to examine the nonlinear and lagged effects of environmental factors on childhood AD from 2009 to 2017 in Shanghai. We also performed a season-stratified analysis to determine the modification effects of environmental exposure by season on childhood AD.

There were 1,043,240 outpatient visits for childhood AD in total, at 3 major pediatric hospitals. Low temperature and relative humidity (RH), and high daily temperature difference (DTD) and air pollutants (i.e., NO2) increased the relative risks (RRs) of outpatient visits for childhood AD in the whole year.