Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

INTRODUCTION: Several studies on the effectiveness of exercise in improving sleep quality in the elderly have been done but have conficting results. This meta-analysis aimed to determine the effect of low- to moderate-intensity aerobic exercise in improving sleep quality among the elderly. METHODS: EBSCO, ClinicalKey, PubMed, Wiley Online Library, and Cochrane Library were searched for articles using the terms “exercise AND sleep quality AND elderly”. The risk of bias assessment was done using the Cochrane Collaboration tool and encoded using RevMan 5.4. Data on outcome measures were subjected to meta-analysis using inverse variance methods. RESULTS: Seven articles with a total of 225 participants were included. There was a statistically signifcant improvement in sleep quality with low to moderate intensity aerobic exercise (MD = -3.87 points; 95% CI -5.56, -2.19 points; p < 0.001). There was a statistically signifcant decrease in total sleep time after intervention (MD = -8.86; 95% CI -16.31, -1.41 points; p = 0.02). There was no improvement in sleep effciency. CONCLUSION Low and moderate intensity exercise improves sleep quality in the elderly and may be used as a non-pharmacologic intervention to enhance sleep quality.

Coccidiosis in chickens is an intestinal parasitic disease caused by protozoan parasites named Eimeria spp. In some Eimeria infections, intestinal lymphocytes are known to highly express chicken NK-lysin (cNK-lysin), an antimicrobial peptide with anticoccidial activity. Therefore, this study aims to investigate the expression of cNK-lysin in E. necatrix-infected chickens and its role in E. necatrix infection. The expression of cNK-lysin transcript was significantly increased in E. necatrix sporozoites-treated lymphocytes. In E. necatrix infection, cNK-lysin transcript was induced in intestinal lymphocytes but not in the spleen. The recombinant cNK-lysin exhibited anticoccidial activity against E. necatrix sporozoites as well as immunomodulatory activity on macrophages by inducing proinflammatory cytokines. These results indicated that E. necatrix infection induces high local expression of cNK-lysin and the secreted cNK-lysin helps protect coccidiosis.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the “2019 Seoul Consensus on Esophageal Achalasia Guidelines”) were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.

Background/Aims: To determine whether the expression of tight junction proteins (TJPs) differs depending on the subtype of functional dyspepsia (FD) and sex. Methods: Control (n = 95) and FD (n = 165) groups based on Rome III criteria were prospectively enrolled. Gastric mucosal mRNA expression levels of various TJPs (claudins [CLDN] 1, 2, and 4; zonula occludens-1; occludin [OCLN]) were assessed by reverse transcription polymerase chain reaction. Western blot was performed to determine the levels of various TJPs. Helicobacter pylori infection status was evaluated by histology, rapid urease test, and culture. Questionnaires were analyzed. Results: In all groups irrespective of H. pylori , FD group showed significantly higher CLDN2 mRNA levels than control group (P = 0.048). The level of CLDN4 mRNA expression was significantly lower in female FD group than in male FD group (P = 0.018). In H. pylori uninfected subjects, the level of CLDN1 mRNA expression in female FD group was significantly lower than that of male FD group (P = 0.014). The level of CLDN2 mRNA expression was significantly higher in the male postprandial distress syndrome (P = 0.001) and male epigastric pain syndrome (P = 0.023) groups than in the male control group. In Western blot analysis, the expression of OCLN was significantly elevated 48 hour after the culture with H. pylori strain 43504. Conclusions H. pylori can affect a variety of TJPs, particularly claudin-4 and occludin. Claudin-2 is thought to be involved in FD irrespective of H. pylori status, especially in the pathophysiology of male FD.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.
Antioxidants ; Classification ; Clinical Protocols ; Diagnosis ; DNA ; Embryonic Structures ; Female ; Fertility ; Health Expenditures ; Humans ; Infertility ; Infertility, Male ; Male ; Membranes ; Ovum ; Oxidants ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species ; Reducing Agents ; Reproductive Health ; Semen ; Spermatozoa ; Subject Headings

In vitro prediction of hepatotoxicity can enhance the performance of non-clinical animal testing for identifying chemical hazards. In this study, we assessed high-content analysis (HCA) using multi-parameter cell-based assays as an in vitro hepatotoxicity testing model using various hepatotoxicants and human hepatocytes such as HepG2 cells and human primary hepatocytes (hPHs). Both hepatocyte types were exposed separately to multiple doses of ten hepatotoxicants associated with liver injury whose mechanisms of action have been described. HCA data were obtained using fluorescence probes for nuclear size (Hoechst), mitochondrial membrane potential (TMRM), cytosolic free calcium (Fluo-4AM), and lipid peroxidation (BODIPY). Cellular alterations were observed in response to all hepatotoxicants tested. The most sensitive parameter was TMRM, with high sensitivity at a low dose, next was BODIPY, followed by Fluo-4AM. HCA data from HepG2 cells and hPHs were generally concordant, although some inconsistencies were noted. Both hepatocyte types showed mild or severe mitochondrial impairment and lipid peroxidation in response to several hepatotoxicants. The results demonstrate that the application of HCA to in vitro hepatotoxicity testing enables more efficient hazard identification, and further, they suggest that certain parameters could serve as sensitive endpoints for predicting the hepatotoxic potential of chemical compounds.
Animals ; Calcium ; Cytosol ; Fluorescence ; Hep G2 Cells ; Hepatocytes ; Humans ; In Vitro Techniques ; Lipid Peroxidation ; Liver ; Membrane Potential, Mitochondrial

The gut microbiota has an important role in the gut barrier, inflammation and metabolic functions. Studies have identified a close association between the intestinal barrier and metabolic diseases, including obesity and type 2 diabetes (T2D). Recently, Akkermansia muciniphila has been reported as a beneficial bacterium that reduces gut barrier disruption and insulin resistance. Here we evaluated the role of A. muciniphila-derived extracellular vesicles (AmEVs) in the regulation of gut permeability. We found that there are more AmEVs in the fecal samples of healthy controls compared with those of patients with T2D. In addition, AmEV administration enhanced tight junction function, reduced body weight gain and improved glucose tolerance in high-fat diet (HFD)-induced diabetic mice. To test the direct effect of AmEVs on human epithelial cells, cultured Caco-2 cells were treated with these vesicles. AmEVs decreased the gut permeability of lipopolysaccharide-treated Caco-2 cells, whereas Escherichia coli-derived EVs had no significant effect. Interestingly, the expression of occludin was increased by AmEV treatment. Overall, these results imply that AmEVs may act as a functional moiety for controlling gut permeability and that the regulation of intestinal barrier integrity can improve metabolic functions in HFD-fed mice.