Enhanced expression of microrna-1273g-3p contributes to alzheimer’s disease pathogenesis by regulating the expression of mitochondrial genes

Alzheimer’s disease (AD) is the most common form of dementia in the elderly population, but its underlying cause has not been fully elucidated. Recent studies have shown that microRNAs (miRNAs) play important roles in regulating the expression levels of genes associated with AD development. In this study, we analyzed miRNAs in plasma and cerebrospinal fluid (CSF) from AD patients and cognitively normal (including amyloid positive) individuals. miR-1273g-3p was identified as an AD-associated miRNA and found to be elevated in the CSF of early-stage AD patients. The overexpression of miR-1273g-3p enhanced amyloid beta (Aβ) production by inducing oxidative stress and mitochondrial impairments in AD model cell lines. A biotin-streptavidin pull-down assay demonstrated that miR-1273g-3p primarily interacts with mitochondrial genes, and that their expression is downregulated by miR-1273g-3p. In particular, the miR-1273g-3p-target gene TIMM13 showed reduced expression in brain tissues from human AD patients. These results suggest that miR1273g-3p expression in an early stage of AD notably contributes to Aβ production and mitochondrial impairments. Thus, miR-1273g-3p might be a biomarker for early diagnosis of AD and a potential therapeutic target to prevent AD progression

Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the posttreatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0→4.2, p=0.000); lactulose group (11.3→5.0, p=0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

A Comparative Analysis of Robot-Assisted Laparoscopic Pyeloplasty in Pediatric and Adult Patients: Does Age Matter?

We investigated factors that affect the surgical outcomes of robotic pyeloplasty by comparing the surgical results of pediatric and adult patients with ureteropelvic junction stricture (UPJO). We retrospectively reviewed patients who underwent robotic pyeloplasty for UPJO between January 2013 and February 2022. The patients were categorized into two groups: the pediatric (≤18 years) and adult (>18 years) groups. The perioperative and postoperative outcomes and surgical complications were comparatively analyzed. Prognostic factors for predicting surgical failure were analyzed with multivariable logistic regression analysis. The pediatric group showed longer total operation and console times. The mean pain score was lower in the pediatric group than in the adult group on days 1 and 2 after surgery. The average amount of morphine used in the pediatric group was lower during postoperative days 0–2. No differences in the length of hospital stay, incidence of surgical failure, and incidence of urolithiasis requiring treatment after robotic pyeloplasty were observed between the groups. The only factor that predicted surgical failure was a history of urolithiasis before surgery. The results showed that age did not affect the surgical outcome

Surgical Outcomes of Clitoroplasty in Children with Congenital Adrenal Hyperplasia and Clitoral Hypertrophy: A 19-Year Experience of a Single Surgeon

This study aimed to describe the experience with clitoroplasty for clitoral hypertrophy in patients with congenital adrenal hyperplasia of a single surgeon. The medical records of female pediatric patients with congenital adrenal hyperplasia who underwent clitoroplasty at a tertiary referral hospital between 2002 and 2020 were retrospectively analyzed. Three different surgical techniques were applied for clitoroplasty: recession without reduction, reduction and recession, and girth reduction and recession. A total of 104 patients underwent clitoroplasty for clitoral hypertrophy. The median patient age at the time of surgery was 10 months (range, 4 months to 10 years). The operation time was longer in reduction clitoroplasty than in recession clitoroplasty without reduction (median, 153 vs. 111 min, p = 0.003). The mean postoperative pain score of the patients did not differ among the different clitoroplasty techniques. During the mean follow-up of 37.7 months, nine (8.6%) patients underwent reperformed clitoroplasty. The rate of reperformed operation was significantly higher in patients who underwent reduction clitoroplasty (17.3%) than in those who underwent recession without reduction (2%) or girth reduction and recession (0%) (p = 0.031). Early clitoroplasty in patients with congenital adrenal hyperplasia yielded good mid-term surgical outcomes in terms of cosmesis and recurrence rate, with minimal perioperative complications