Notes

Assessment regarding muscle pathology utilizing visual polarimetry.
Maternal use of antibiotics during pregnancy was associated with an increased risk of tonsillitis reported at four years of age. Antibiotics could favour the potential transmission of an unfavourable microbiome from mother to child.Preclinical studies have demonstrated that activation of the NOTCH pathway plays a key role in the pathogenesis of kidney damage. There is currently no information on the role of the Delta-like homologue 1 (DLK1), a NOTCH inhibitor, in the regulation of renal damage. Here, we investigated the contribution of DLK1 to experimental renal damage and the underlying molecular mechanisms. Using a Dlk1-null mouse model in the experimental renal damage of unilateral ureteral obstruction, we found activation of NOTCH, as shown by increased nuclear translocation of the NOTCH1 intracellular domain, and upregulation of Dlk2/hey-1 expression compared to wild-type (WT) littermates. NOTCH1 over-activation in Dlk1-null injured kidneys was associated with a higher inflammatory response, characterized by infiltration of inflammatory cells, mainly CD4/IL17A + lymphocytes, and activation of the Th17 immune response. selleck compound Furthermore, pharmacological NOTCH blockade inhibited the transcription factors controlling Th17 differentiation and gene expression of the Th17 effector cytokine IL-17A and other related-inflammatory factors, linked to a diminution of inflammation in the injured kidneys. We propose that the non-canonical NOTCH ligand DLK1 acts as a NOTCH antagonist in renal injury regulating the Th17-mediated inflammatory response.Acute kidney injury (AKI) is a common clinical problem, and patients who survive AKI have a high risk of chronic kidney disease (CKD). The mechanism of CKD post-AKI, characterized by progressive renal fibrosis, is still unclear. Maladaptive tubular epithelial cells (TECs) after AKI are considered a leading cause of renal fibrosis post-AKI. TECs under maladaptive repair manifest characteristics of senescence. Removing senescent TECs by genetic ablation has been proven effective in reducing renal fibrosis. Senolytics, which eliminate senescent cells by pharmacological intervention, have been studied in a series of degenerative diseases. To our knowledge, the effects of senolytics on renal fibrosis post-AKI have not been verified before. Here, we confirmed renal senescence in the unilateral ischemia/reperfusion injury murine model. Senescent TECs could activate fibroblasts and senolytics specifically induced apoptosis of senescent TECs. Next, we demonstrated that senolytics could reduce renal senescence and ameliorate renal fibrosis in both unilateral renal ischemia/reperfusion injury and multiple-cisplatin-treatment murine models. Our results indicate senescent TECs as a vital factor in renal fibrosis progression, and senolytic therapy might be promising for treating CKD post-AKI.
To assess the efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sodium-glucose co-transporter 2 (SGLT2) inhibitors, administered without metformin on cardiovascular outcomes in type 2 diabetes patients.

A systematic review was performed according to Cochrane's methodological standards. We included randomized clinical trials (RCTs) on adult type 2 diabetes patients, assessing the efficacy of SGLT2 inhibitors and GLP1-RAs compared to other glucose-lowering drugs and/or RCTs that presented data of a subgroup of type 2 diabetes patients without metformin use at baseline. The main outcome was the reduction of the risk of any major adverse cardiovascular events (MACE) reported individually or as a composite outcome.

Five RCTs including 50,725 type 2 diabetes patients, of whom 10,013 had not received metformin, were included in this meta-analysis. Three of these studies assessed the efficacy of GLP1-RAs and two of SGLT2 inhibitors. In patients without metformin at baseline, GLP1-RAs in comparison with placebo reduced the risk of MACE significantly by 20% (HR 0.80; 95% CI 0.71-0.89). SGLT2 inhibitors also significantly reduced the risk of MACE by 32% (HR 0.68; 95% CI 0.57-0.81).

SGLT2 inhibitors and GLP1-RAs provided without metformin at baseline may reduce the risk of MACE in comparison with placebo in type 2 diabetes patients at increased risk of cardiovascular events.
SGLT2 inhibitors and GLP1-RAs provided without metformin at baseline may reduce the risk of MACE in comparison with placebo in type 2 diabetes patients at increased risk of cardiovascular events.
The role of donor-derived cell-free DNA (dd-cfDNA) in screening for cardiac allograft vasculopathy (CAV) is unknown. We hypothesized that dd-cfDNA correlates with CAV, markers of inflammation, and angiogenesis in stable heart transplant (HT) recipients.

Sixty-five HT recipients ≥2years post-transplant, without recent rejection, were stratified by high (≥0.12%) versus low levels (<0.12%) of dd-cfDNA. A targeted amplification, next-generation sequencing assay (AlloSure
; CareDx, Inc.) was used to detect dd-cfDNA. Peripheral blood inflammatory and angiogenesis markers were assessed using a multiplex immunoassay system (Bioplex
).

Of 65 patients, 58 patients had a known CAV status and were included. Thirty had high levels of dd-cfDNA (≥0.12%), and 28 had low levels (<0.12%). CAV was present in 63% of patients with high dd-cfDNA vs. 35% with low dd-cfDNA (p=.047). Donor-specific antibodies were present in 25% of patients with high dd-cfDNA vs. 3.8% in those with low dd-cfDNA (p=.03). There were no differences in rejection episodes, inflammatory, or angiogenesis markers. Importantly, dd-cfDNA levels were not different when stratified by time post-transplant.

Higher dd-cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd-cfDNA levels and CAV severity and whether dd-cfDNA can predict CAV progression.
Higher dd-cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd-cfDNA levels and CAV severity and whether dd-cfDNA can predict CAV progression.
To demonstrate the efficacy and safety of mini-percutaneous nephrolithotomy, micro-percutaneous nephrolithotomy, and flexible ureteroscopy for pediatric upper urinary tract calculi and to develop nomograms predicting surgical outcomes.

A prospectively managed database containing children who were diagnosed with upper urinary tract calculi and treated with mini-percutaneous nephrolithotomy, micro-percutaneous nephrolithotomy, and flexible ureteroscopy between June 2014 and April 2019 was analysed. Patient demographics, intraoperative data, stone characteristics, stone-free rate, and complication rate were analysed and compared. Nomograms predicting the postoperative stone-free rate and complication rate were established based on predictors, and internal validation was performed. Calibration curves and decision curves were generated to assess the predictive efficacy and clinical benefit.

Forty-three children underwent mini-percutaneous nephrolithotomy on 56 sides in 47 operations, 30 children underwent micro-percutaneous nephrolithotomy on 30 sides in 30 operations, and 275 children underwent flexible ureteroscopy on 320 sides in 288 operations.
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