Notes

Text message feedback system being a top quality assurance system: knowledge coming from a home questionnaire in non-urban Asia.
Previous research suggests that aggression is associated with ADHD symptoms and this may partly reflect problems with emotional regulation. Using data from the D2M study (n=260) we found that ADHD symptoms were associated with both emotional lability and aggression, but emotional lability did not mediate the ADHD-aggression association. Results suggest that other factors may be more important for explaining elevated levels of aggression in ADHD.
Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are linked to several mitochondrial alterations. Cigarette smoke (CS) alters the structure and function of mitochondria. OPA1 is the main inner mitochondrial GTPase responsible for the fusion events. OPA1 undergoes proteolytic cleavage from long to short forms during acute stress and mitophagy. However, the exact role of OPA1 isoforms and related proteins during CS-induced mitophagy and COPD is not clear.

Lung tissues from non-smokers, smokers, COPD and IPF were used to determine the relative expression of OPA1 and related proteins. Additionally, we used mouse lungs from chronic (6 months) CS exposure to evaluate the status of OPA1. Primary lung fibroblasts from normal and COPD patients and naked mole rat (NMR) lung fibroblasts, human fetal lung fibroblast (HFL1), mouse embryonic fibroblast from wild type (WT), OPA1
, MFN1 and MFN2
were used to determine the effect of CS on OPA1 isoforms.tophagy/mitochondrial dysfunction in COPD, which may be used as a novel therapeutic target in COPD.
The long OPA1 isoform along with SLP2 and prohibitins play a crucial role in CS-induced lung damage, causing mitophagy/mitochondrial dysfunction in COPD, which may be used as a novel therapeutic target in COPD.
Dual amylin and calcitonin receptor agonists (DACRAs) are novel therapeutic agents that not only improve insulin sensitivity but also work as an adjunct to established T2DM therapies. DACRAs are currently administered once daily, though it is unknown whether DACRAs with increased plasma half-life can be developed as a once-weekly therapy.

The invitro potencies of the KBP-066A and KBP-066 (non-acylated) were assessed using reporter assays. Transmembrane Transporters inhibitor Acylation functionality was investigated by a combination of pharmacokinetics and acute food intake in rats. invivo efficacies were investigated head-to-head in obese (HFD) and T2D (ZDF) models.

In invitro, KBP-066A activated the CTR and AMY-R potently, with no off-target activity. Acylation functionality was confirmed by acute tests, as KBP-066A demonstrated a prolonged PK and PD response compared to KBP-066. Both compounds induced potent and dose-dependent weight loss in the HFD rat model. In ZDF rats, fasting blood glucose/fasting insulin levels (tAUC) were reduced by 39%/50% and 36%/47% for KBP-066 and KBP-066A, respectively. This effect resulted in a 31% and 46% vehicle-corrected reduction in HbA1c at the end of the study for KBP-066 and KBP-066A, respectively.

Here, we present pre-clinical data on an acylated DACRA, KBP-066A. The invivo efficacy of KBP-066A is significantly improved compared to its non-acylated variant regarding weight loss and glycemic control in obese (HFD) and obese diabetic rats (ZDF). This compendium of pre-clinical studies highlights KBP-066A as a promising, once-weekly therapeutic agent for treating T2DM and obesity.
Here, we present pre-clinical data on an acylated DACRA, KBP-066A. The in vivo efficacy of KBP-066A is significantly improved compared to its non-acylated variant regarding weight loss and glycemic control in obese (HFD) and obese diabetic rats (ZDF). This compendium of pre-clinical studies highlights KBP-066A as a promising, once-weekly therapeutic agent for treating T2DM and obesity.
Exclusive enteral nutrition (EEN) is used to treat pediatric Crohn's disease (CD), but therapeutic benefits are variable, and EEN can lead to microbial dysbiosis. Because of reported lower efficacy EEN is not routinely used to treat pediatric ulcerative colitis (UC). Inulin-type fructans (IN) beneficially modulate the gut microbiome and promote expansion of anti-inflammatory immune cells. We hypothesized that enriching EEN with IN (EEN IN) would enhance treatment efficacy. To test this, we examined the effects of EEN IN on colitis development, the gut microbiome, and CD4
T cells using an adoptive T-cell transfer model of colitis.

TCR-β deficient (
) mice were randomized to 1 of 4 groups (1) Control, (2) Chow, (3) EEN, and (4) EEN IN, and naive CD4
T cells were adoptively transferred into groups 2-4, after which mice were monitored for 5 weeks before experimental endpoint.

Mice fed EEN IN showed greater colitis protection, with colonic shortening, goblet cell, and crypt density loss reduced compared with EEN fed mice and reduced disease activity and immune cell infiltration compared with chow fed mice, and less crypt hyperplasia and higher survival compared with both groups. EEN IN mice had less deterioration in the colonic mucus layer and had increased levels of Foxp3
IL-10
and Rorγt
IL-22
and reduced levels of Tbet
IFNγ
and Tbet
TNF
CD4
T cells. EEN IN also led to higher butyrate concentrations, Bifidobacterium spp. and Anaerostipes caccae relative abundance, and lower [Clostridium] innocuum group spp. and Escherichia-Shigella spp relative abundance.

The EEN IN group showed reduced colitis development as compared with the chow and EEN groups. This highlights the potential benefits of EEN IN as a novel induction therapy for pediatric CD and UC patients.
The EEN IN group showed reduced colitis development as compared with the chow and EEN groups. This highlights the potential benefits of EEN IN as a novel induction therapy for pediatric CD and UC patients.
Reduced forced expiratory flow between 25% and 75% of vital capacity percent predicted (FEF
%) representing small airway dysfunction (SAD) was associated with asthma development and progression.

To investigate whether FEF
% was superior to forced expiratory volume in 1 second in predicted (FEV
%) in reflecting asthma features in adult patients.

A retrospective spirometry dataset comprising 1801 adult patients with confirmed asthma and a subgroup of 332 patients having detailed clinical data were used to explore the association of FEF
% and/or FEV
% with clinical features of asthma.

Of the 1801 subjects, FEV
% and FEF
% ranged from 136.8% to 10.2% and 127.3% to 3.1%, respectively. FEF
% < 65% was present in 1,478 (82.07%) of patients. FEF
% was strongly correlated with matched FEV
% (r=0.900, P < .001). FEF
% and FEV
% were both correlated with airway hyperresponsiveness (r= 0.436, P<.001; r= 0.367, P < .001), asthma control test score (r=0.329, P < .001; r= 0.335, P < .001), and sputum eosinophil count (r=-0.
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