Subtyping intractable functional constipation in children using clinical and laboratory data in a classification model.

Background: Children with intractable functional constipation (IFC) who are refractory to traditional pharmacological intervention develop severe symptoms that can persist even in adulthood, resulting in a substantial deterioration in their quality of life. In order to better manage IFC patients, efficient subtyping of IFC into its three subtypes, normal transit constipation (NTC), outlet obstruction constipation (OOC), and slow transit constipation (STC), at early stages is crucial. With advancements in technology, machine learning can classify IFC early through the use of validated questionnaires and the different serum concentrations of gastrointestinal motility-related hormones. Method: A hundred and one children with IFC and 50 controls were enrolled in this study. Three supervised machine-learning methods, support vector machine, random forest, and light gradient boosting machine (LGBM), were used to classify children with IFC into the three subtypes based on their symptom severity, self-efficacy, and quality of life which were quantified using certified questionnaires and their serum concentrations of the gastrointestinal hormones evaluated with enzyme-linked immunosorbent assay. The accuracy of machine learning subtyping was evaluated with respect to radiopaque markers. Results: Of 101 IFC patients, 37 had NTC, 49 had OOC, and 15 had STC. The variables significant for IFC subtype classification, according to SelectKBest, were stool frequency, the satisfaction domain of the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL), the emotional self-efficacy for Functional Constipation questionnaire (SEFCQ), motilin serum concentration, and vasoactive intestinal peptide serum concentration. Among the three models, the LGBM model demonstrated an accuracy of 83.8%, a precision of 84.5%, a recall of 83.6%, a f1-score of 83.4%, and an area under the receiver operating characteristic curve (AUROC) of 0.89 in discriminating IFC subtypes. Conclusion: Using clinical characteristics measured by certified questionnaires and serum concentrations of the gastrointestinal hormones, machine learning can efficiently classify pediatric IFC into its three subtypes. Of the three models tested, the LGBM model is the most accurate model for the classification of IFC, with an accuracy of 83.8%, demonstrating that machine learning is an efficient tool for the management of IFC in children.

LTBP4 Protects Against Renal Fibrosis via Mitochondrial and Vascular Impacts.

BACKGROUND: As a part of natural disease progression, acute kidney injury (AKI) can develop into chronic kidney disease via renal fibrosis and inflammation. LTBP4 (latent transforming growth factor beta binding protein 4) regulates transforming growth factor beta, which plays a role in renal fibrosis pathogenesis. We previously investigated the role of LTBP4 in chronic kidney disease. Here, we examined the role of LTBP4 in AKI. METHODS: LTBP4 expression was evaluated in human renal tissues, obtained from healthy individuals and patients with AKI, using immunohistochemistry. LTBP4 was knocked down in both C57BL/6 mice and human renal proximal tubular cell line HK-2. AKI was induced in mice and HK-2 cells using ischemia-reperfusion injury and hypoxia, respectively. Mitochondrial division inhibitor 1, an inhibitor of DRP1 (dynamin-related protein 1), was used to reduce mitochondrial fragmentation. Gene and protein expression were then examined to assess inflammation and fibrosis. The results of bioenergetic studies for mitochondrial function, oxidative stress, and angiogenesis were assessed. RESULTS: LTBP4 expression was upregulated in the renal tissues of patients with AKI. Ltbp4-knockdown mice showed increased renal tissue injury and mitochondrial fragmentation after ischemia-reperfusion injury, as well as increased inflammation, oxidative stress, and fibrosis, and decreased angiogenesis. in vitro studies using HK-2 cells revealed similar results. The energy profiles of Ltbp4-deficient mice and LTBP4-deficient HK-2 cells indicated decreased ATP production. LTBP4-deficient HK-2 cells exhibited decreased mitochondrial respiration and glycolysis. Human aortic endothelial cells and human umbilical vein endothelial cells exhibited decreased angiogenesis when treated with LTBP4-knockdown conditioned media. Mitochondrial division inhibitor 1 treatment ameliorated inflammation, oxidative stress, and fibrosis in mice and decreased inflammation and oxidative stress in HK-2 cells. CONCLUSIONS: Our study is the first to demonstrate that LTBP4 deficiency increases AKI severity, consequently leading to chronic kidney disease. Potential therapies focusing on LTBP4-associated angiogenesis and LTBP4-regulated DRP1-dependent mitochondrial division are relevant to renal injury.

Emerging therapies and recent advances for Tourette syndrome.

Tourette syndrome is the most prevalent hyperkinetic movement disorder in children and can be highly disabling. While the pathomechanism of Tourette syndrome remains largely obscure, recent studies have greatly improved our knowledge about this disease, providing a new perspective in our understanding of this condition. Advances in electrophysiology and neuroimaging have elucidated that there is a reduction in frontal cortical volume and reduction of long rage connectivity to the frontal lobe from other parts of the brain. Several genes have also been identified to be associated with Tourette syndrome. Treatment of Tourette syndrome requires a multidisciplinary approach which includes behavioral and pharmacological therapy. In severe cases surgical therapy with deep brain stimulation may be warranted, though the optimal location for stimulation is still being investigated. Studies on alternative therapies including traditional Chinese medicine and neuromodulation, such as transcranial magnetic stimulation have shown promising results, but still are being used in an experimental basis. Several new therapies have also recently been tested in clinical trials. This review provides an overview of the latest findings with regards to genetics and neuroimaging for Tourette syndrome as well as an update on advanced therapeutics.

Pilates-based core exercise improves health-related quality of life in people living with chronic low back pain: A pilot study.

PURPOSE: To investigate the effects of Pilates exercise on improving health-related quality of life in people living with chronic low back pain. METHODS: This was a single-blind, randomised clinical trial. Thirty-nine physically active subjects aged between 30 and 70 years with nonspecific chronic low back pain for more than three months were recruited. The study employed a pretest-posttest design, with a 4 -, 8 -, and 26-week follow-up. For eight weeks, the intervention group participated in a group-supervised, mat-based Pilates program, while the control group received the usual pharmacologic and rehabilitation standard of care, including patient education on chronic low back pain. The primary outcome was self-perceived health status measured using the EQ-5D questionnaire in a structured form and a visual analogue scale. Secondary outcomes included intensity of pain and degree of disability. RESULTS: By the end of the 8-week Pilates program, the intervention group achieved a better health-related quality of life on the EQ-5D visual analogue score than the control group. In assessing the trends in each individual group regarding pain, the intervention group demonstrated an earlier pain reduction than the control group that lasted until the end of the trial. CONCLUSIONS: An 8-week supervised Pilates-based core exercise program is an effective therapeutic modality for improving self-perceived health status in patients with chronic low back pain. This finding could inform clinicians of better alternatives when they suggest exercise interventions for chronic low back pain.