Search Results (880)

The LRRK2+ SAA− cohort of Parkinson’s disease (PD), characterized by the absence of hallmark α-synuclein pathology, remains under-explored. This limits opportunities for early detection and targeted intervention. This study analyzes data from this under-characterized subgroup and compares it with the LRRK2+ SAA+ cohort using longitudinal data from the Parkinson’s Progression Markers Initiative (PPMI). The PPMI dataset includes 115 LRRK2+ patients (70 SAA+, 45 SAA−) across 52 features encompassing clinical assessments, cognitive scores, DaTScan SPECT imaging, and motor severity. DaTScan binding ratios were selected as imaging-based indicators of early dopaminergic loss, while NP3TOT (MDS-UPDRS Part III total score) was used as a gold-standard clinical measure of motor symptom severity. Linear mixed-effects models were then applied to evaluate longitudinal predictors of DaTScan decline and NP3TOT progression, and statistical analyses of group comparisons revealed distinct drivers of symptoms differentiating SAA− from SAA+ patients. In SAA− patients, a decline in DaTScan was significantly associated with thermoregulatory impairment (p-value = 0.019), while NP3TOT progression was predicted by constipation (p-value = 0.030), sleep disturbances (p-value = 0.046), and longitudinal time effects (p-value = 0.043). In contrast, SAA+ patients showed significantly lower DaTScan values compared to SAA− (p-value = 0.0004) and stronger coupling with classical motor impairments, including freezing of gait (p-value = 0.016), rising from a chair (p-value = 0.007), and turning in bed (p-value = 0.016), along with cognitive decline (MoCA clock-hands test, p-value = 0.037). These findings support the hypothesis that LRRK2+ SAA− patients follow a distinct pathophysiological course, where progression is influenced more by autonomic and non-motor symptoms than by typical motor dysfunction. This study establishes a robust, multimodal modeling framework for examining heterogeneity in genetic PD and highlights the utility of combining DaTScan, NP3TOT, and symptom-specific features for early subtype differentiation. These findings have direct clinical implications, as stratifying LRRK2 carriers by SAA status may enhance patient monitoring, improve prognostic accuracy, and guide the design of targeted clinical trials for disease-modifying therapies. Full article

Background/Aims: Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the degeneration of dopaminergic neurons, leading to motor and non-motor symptoms that significantly impair quality of life (QoL). Oxidative stress (OS) and neuroinflammation play a key role in its progression. The ketogenic diet (KD) may have neuroprotective effects by reducing these factors through ketosis. The primary aim of this narrative review is to examine the impact of the ketogenic diet on the quality of life and symptomatology of patients with PD, evaluating its effects on motor and non-motor symptoms, as well as on certain metabolic parameters. Secondary aims included assessing the feasibility of and adherence to the diet, as well as its tolerability and safety. Methods: A search of PubMed, Scopus, Embase, CINAHL and Cochrane databases up to June 2025 was performed. Eligible studies included adults with PD following a KD regimen. Data were extracted regarding QoL outcomes, adverse events, and risk of bias included for synthesis. Results: A total of 152 patients were included across 6 studies. KD showed a small to moderate effect size on QoL improvements, particularly in non-motor domains such as fatigue and sleep quality. However, findings were inconsistent across studies. Risk of bias was rated moderate to high due to small sample sizes, heterogeneous methodologies, and lack of blinding. The most frequently reported adverse events were gastrointestinal disturbances (nausea, constipation), weight loss, and transient fatigue. Conclusions: Although preliminary evidence suggests a potential benefit of KD on QoL in PD patients, the small number of participants, short follow-up, and high heterogeneity significantly limit generalizability. Further large, controlled trials with rigorous methodology are warranted before relevant conclusion benefits can be drawn. Full article

Background: Slow-transit constipation (STC) lacks durable and safe prokinetics. Deglycosylated-azithromycin (Deg-AZM), a novel small-molecule transgelin agonist that restores colonic motility in STC, has been approved for clinical trials in 2024. Objectives: This study aimed to assess the genetic toxicity and embryo–fetal development (EFD) toxicity of Deg-AZM through a series of standardized non-clinical safety studies. Methods: We conducted Ames, in vivo micronucleus, and chromosomal aberration tests to evaluate genotoxicity. Acute and 28-day repeated-dose oral toxicity studies were performed in Sprague-Dawley rats. EFD toxicity was assessed in pregnant rats administered Deg-AZM from gestation day (GD) 6 to 15. Toxicokinetic analyses were integrated into repeated-dose and EFD studies. Results: Deg-AZM demonstrated no mutagenic potential in the bacterial reverse-mutation assay at concentrations up to 2500 µg/plate (with metabolic activation) or 150 µg/plate (without metabolic activation). No clastogenic effects were observed in micronucleus or chromosomal aberration assays. The median lethal dose (LD₅₀) exceeded 1600 mg/kg in acute oral toxicity. In the 28-day study, no adverse effects were observed at doses up to 600 mg/kg, though mild hematological and hepatic changes were noted at high doses, all of which were reversible. In the EFD study, Deg-AZM did not induce maternal toxicity, teratogenicity, or adverse fetal outcomes at doses up to 600 mg/kg. Conclusions: Deg-AZM demonstrates a favorable safety profile with no evidence of genetic toxicity or developmental harm at pharmacologically relevant doses, supporting its further development as a therapeutic agent for STC. Full article

Background/Objectives: Disorders of gut–brain interaction (DGBI) include a spectrum of disorders with chronic/recurrent gastrointestinal symptoms, caused by dysregulation of microbiota–gut–brain interaction. Early-life events have been suggested as the main factors influencing the microbiota–gut–brain axis. We aimed to evaluate the prevalence of DGBI in 3-year-old children and its relationship with early-life events. Methods: The parents of children aged 3 years, who had been followed up in a well-baby clinic since they were 2 months old, were asked about any GI symptoms their child had experienced during the check-up visits between September 2023 and June 2024. The final diagnosis of DGBI was based on ROME IV criteria. Demographic data, including early-life factors, were collected. Results: Overall, 568 children (48.6% boys) were included, of whom 139 (24.5%) had symptoms consistent with at least one DGBI diagnosis. The most prevalent DGBI was functional constipation (20.4%), followed by colic (4.6%), infant regurgitation (2.8%), and dyschezia (1.6%). Approximately 48% of the children were breastfed for ≥6 months, and 21% were exposed to ≥1 antibiotic/antiviral drugs in the first year of life. DGBI prevalence was significantly higher in girls than in boys (28.1% vs. 20.7%; p = 0.041). Exclusive breastfeeding was the most significant protective factor against DGBI, particularly if performed for ≥3 months. Conclusions: Sex was the most significant factor affecting DGBI prevalence in children aged ≤3 years; breastfeeding offers the most effective protection against DGBI development. Full article

This study, for the first time, explored the preventive effects of a novel pectic polysaccharide from Premna microphylla Turcz leaves (PMTL) on experimental constipation. Diphenoxylate-induced constipation model (CM) rats were fed a standard rodent chow supplemented with or without PMTL (5%, 10%, and 20%) for 6 weeks. Supplementation of PMTL was shown to accelerate intestinal peristalsis, increase fecal water content, improve intestinal morphology, and suppress gut inflammation by facilitating the secretion of excitatory neurotransmitters (MTL, ACH, and SP) and decreasing the secretion of inhibitory neurotransexcitatory neurotransmittersmitters (SS and NO) in the CM rats. PMTL also reduced the expressions of the colonic aquaporins AQP3 and AQP4 in the CM rats to normalize the colonic water transport system. 16S rRNA gene sequencing revealed that PMTL relieved the gut microbiota disorder of the CM rats and promoted the proliferation of several beneficial bacteria, resulting in an increase in fecal short-chain fatty acids. These findings demonstrate that dietary PMTL consumption can ameliorate the development of constipation and PMTL can be considered as a great promising dietary supplement for alleviating constipation. Full article

Background: Chronic constipation lacks effective long-term treatments. Non-digestible oligosaccharides (NDOs) are short-chain carbohydrates that resist digestion and may improve bowel function. This systematic review and meta-analysis examines the effect of NDOs on constipation-related outcomes in humans. Methods: We searched Ovid MEDLINE, Embase, and Web of Science (2010–May 2025) for randomized controlled trials (RCTs) comparing NDOs with placebo, reporting stool frequency, stool consistency, fecal pH, or short-chain fatty acids (SCFAs). Data were pooled using random-effects meta-analysis. All effect estimates are reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Subgroups were analyzed based on baseline constipation status and treatment duration. Results: We included 20 RCTs (1786 participants) evaluating seven NDO types. NDO supplementation significantly increased stool frequency overall, with larger effects in constipated individuals (SMD 0.99, 95% CI 0.58–1.28) than in non-constipated population (SMD 0.30, 95% CI 0.10–0.51). By duration, shorter interventions (≤3 weeks) yielded greater frequency gains (SMD 0.89, 95% CI 0.40–1.38) than longer ones (SMD 0.24, 95% CI 0.09–0.38). While the overall effect on stool consistency was non-significant, constipated patients (SMD 0.46, 95% CI 0.19–0.74) and short-term trials (SMD 0.20, 95% CI 0.03–0.37) showed modest improvements. NDOs also lowered fecal pH (SMD −1.02, 95% CI −1.25–−0.79). Data on SCFAs were inconclusive and based on very limited studies. Conclusions: NDOs modestly increase stool frequency and lower fecal pH, with greater effects in constipated individuals and short-term interventions. However, evidence certainty remains low due to heterogeneity and study limitations. Further studies are needed to establish clinical utility. Full article

Postbiotics, as a novel class of functional components, have garnered considerable scholarly and industrial interest due to their distinctive advantages in food processing applications and their positive impact on human health. Although postbiotics have demonstrated potential in alleviating constipation, their specific mechanism of action and bioactive components remain unclear. This study aimed to investigate the ameliorative effects and potential mechanisms of postbiotics derived from Bifidobacterium animalis subsp. lactis BL-99 (BL-99) on FC using both in vivo and in vitro models. The findings revealed that both BL-99 and its postbiotics significantly mitigated FC symptoms, as evidenced by enhanced intestinal motility, and elevated fecal water content. Additionally, treatment with BL-99 postbiotics was associated with an increase in the thickness of the intestinal muscular layer and a reduction in apoptosis of intestinal smooth muscle cells (SMCs). Mechanistically, BL-99 postbiotics were found to enhance the contractile response and promote the proliferation of intestinal SMCs. Furthermore, untargeted metabolomics analysis identified two key bioactive peptides, Glu-Val and Glu-Leu, as the active components in BL-99 responsible for regulating SMC function. Collectively, these findings highlight the potential of BL-99 postbiotics as a promising functional food ingredient for alleviating FC, providing a novel and effective strategy for the developing dietary interventions targeting this condition. Full article

Background: Many factors associated with constipation have not been sufficiently investigated. The aim of this study was to assess the factors associated with constipation, defined as low stool frequency, in a community-dwelling adult population. Methods: A cross-sectional study was carried out between 2010 and 2012 among adults who live in the Kielce District of Poland. The participants comprised 11,488 persons aged 37–66 years. Data on depressive symptoms, eating frequency, physical activity and smoking, as well as sociodemographic data, were collected using face-to-face interviews. Constipation was defined as < 3 defecations per week. Dietary patterns (DPs) were identified using a factor analysis. Associations between DPs and the likelihood of constipation were assessed using a logistic regression analysis. Results: The factors associated with constipation were moderate and severe depressive symptoms, regular use of antidepressants, a sedentary lifestyle and past smoking (in women) (all p < 0.05). The likelihood of constipation was significantly decreased by male sex and obesity, as well as by a diet belonging to the highest terciles of the ‘Carbohydrates’, ‘Vegetables and Meat’ and ‘Healthy’ DPs (all p < 0.05). For the ‘Unhealthy’ DP, a high level of physical activity (Q4 vs. Q1 of MVPA) decreased the likelihood of constipation (OR = 0.75; 95%CI: 0.57–0.99). Conclusions: Preventing the onset or reoccurrence of depression by improving one’s mental resistance, reducing the risk factors for depression and promoting a healthy lifestyle, primarily a diet high in vegetables and a limited sitting time, reduces the risk of constipation. Further longitudinal studies are needed to better understand which factors are associated with the occurrence of constipation. Full article

Dietary fiber (DF) is essential for digestive health, and wheat bran is a potential source because of its high fiber content. Extrusion processing enhances wheat bran’s functional properties by modifying its structure. This study aimed to examine the effects of extrusion-modified wheat bran dietary fiber (E-WBDF) on biscuits, focusing on textural, color, and digestive characteristics, and evaluate its ability to alleviate constipation using a mouse model. E-WBDF-enriched biscuits exhibited lower brightness, deeper color, reduced hardness, and a significant decline in digestion rate compared with conventional biscuits. In the mouse model, E-WBDF biscuits increased fecal volume and moisture, shortened defecation time, and accelerated small intestine transit. The results indicate that E-WBDF can enhance the physical properties of biscuits while reducing their digestion rate, thereby exhibiting a potential therapeutic effect in alleviating constipation in the mouse model. This study provides novel insights into using E-WBDF in biscuit formulations, offering a promising strategy for developing functional foods that promote digestive health. Full article

Background/Objectives: A variant of autism spectrum disorder (ASD) known as Asperger syndrome (AS) shows increasing incidence worldwide, affecting between 0.02% and 0.03% of children. Patients display abnormal conduct, are limited in social interaction and communication, and are more often affected by micturition disorders, incontinence, and voiding symptoms than typically developing children. Methods: The present study aimed to review the literature related to the current management of lower urinary tract conditions in children with Asperger syndrome and to present a case of a 14-year-old girl with ASD, with characteristic impairments, including communication challenges, stereotyped, repetitive behaviors, and chronic constipation with concomitant bladder dysfunction, presenting recurrent urinary tract infections (UTIs) and lower urinary tract symptoms (LUTS), including voiding and filling storage symptoms. For the AS, she was treated with a selective serotonin reuptake inhibitor (Sertraline). An abdominal ultrasound, PLUTTS—pediatric lower urinary symptoms scoring (21); QL-quality of life (3); voiding diary; and uroflowmetry were performed, revealing an incomplete urinary retention (incomplete bladder emptying of 120 mL), a prolonged and interrupted curve, a maximum urinary flow rate (Qmax) 7 mL/s, and a UTI with Enterococcus. Results: Besides psychiatric reevaluation and antibiotic therapy, functional magnetic stimulation (FMS) sessions were performed. After eight sessions (20 min, 35 MHz, every second day), the ultrasound control and the uroflowmetry showed no residual urine, and the Qmax was 17 mL/s. The curve continued to be interrupted: PLUTSS-11, QL-1. FMS was continued at two sessions per week. At the 3-month follow-up, no residual urine was detected, and Qmax reached 24 mL/s. Conclusions: ASD is an incapacitating/debilitating condition that significantly impairs social functioning. In many cases, in addition to psychological symptoms, other conditions such as LUTS and constipation may coexist. Antipsychotics and antidepressants are frequently prescribed for these patients, often leading to various side effects, including micturition disorders. Therefore, screening for LUTS is recommended, and, if indicated, treatment—especially non-pharmacological and non-invasive approaches, such as FMS—should be considered. Full article

Background: Post-colonoscopy syndrome is an emerging clinical entity characterised by the onset of gastrointestinal symptoms following a colonoscopy. The current management of this syndrome has not yet been established, although probiotics have been proposed. The therapeutic potential of a combination nutraceutical compound based on HBQ-Complex^®, butyrate, and probiotics (Lactobacillus acidophilus, Bifidobacterium animalis, and Lactiplantibacillus plantarum) in this setting remains unknown. Methods: A retrospective, multicentre, observational study was conducted in adult patients undergoing colonoscopy in the absence of known gastrointestinal diseases, assessing the onset of upper and lower gastrointestinal symptoms post-colonoscopy immediately after the procedure (T₀), at 2 weeks (T₁), and 4 weeks (T₂) thereafter, using a VAS (0–10). Two groups were analysed, one undergoing nutraceutical supplementation and a control group. Results: A total of 599 patients were included (64.9% receiving nutraceutical supplementation and 35% in the control group). Several variations were observed involving the treated group compared to the control for abdominal pain (59.9% vs. 33.3%), meteorism (64.9% vs. 35.1%), diarrhoea (46.9% vs. 19.5%), and bloating (59.3% vs. 26.7%) (p < 0.001 for all). Logistic regression analysis showed a reduction in constipation (OR: 3.344) and bloating (OR: 3.791) scores. Conclusions: Nutraceutical supplementation based on this combinational compound was associated with a reduction in gastrointestinal symptoms arising after colonoscopy, suggesting potential benefit in this setting. These findings pose a rationale for controlled prospective studies to confirm such evidence in broader clinical settings. Full article

Obstruction differential diagnosis involves tumors, “acute abdomen”, and chronic pseudo-obstruction (CIPO). Pediatric CIPO cases have different backgrounds than adults’ and impairs development. The cases are rare; diagnosis and treatment are still not well established. Diagnosis is complex; clinical, radiological, molecular, and manometric pathologic data are essential. The performance of broad radiological investigations and manometry is cumbersome in a small intestine. Herein, we present cases of a 14-year-old girl and 11-year-old boy with visceral myopathies (VMs). Presented cases show unique hardship in the analysis of standing and contrast bedside X-ray images—the colon distension alone speaks to Hirschsprung, and the clinicians could not confirm suspected short-segment disease for a long time. VMs are usually diagnosed up to 12 months of life and accompanied by other organ dysfunctions, which are herein absent. The key features here were also the involvement of the small intestine, lack of distant colon contraction, and for the long-lasting case in the boy, loss of haustration. The initial diagnosis relied on clinical data (vomiting, malabsorption, >6-month obstruction, and uncharacteristic biochemical tests), radiology (lack of tumor, enlargement of diameter, and fluid in small and large intestines), and manometry (presence of propagation wave and of anal inhibitory reflex in recto–anal manometry). Examination of intestinal muscle biopsies involved hematoxylin-eosin, trichrome-Masson staining, and immunohistochemistry. The characteristics were fibrosis, small vacuoles, muscle layer thinning, and decreased expression of smooth muscle actin and desmin. The localization of biopsies was chosen after X-ray examination, due to interruption and with various degree changes. The final diagnosis was put forward after the analysis of all accessible data. The diagnosis of VM underlines the importance of interdisciplinary co-work. An earlier intestine muscle biopsy and well-designed molecular panel might fasten the process of diagnosis. Deeper exploration of phenotype–genotype correlation of various VM presentations in the future is crucial for personalized treatment. Full article

Background: Several prognostic factors, including the early recovery pattern of acute low back pain (ALBP), are related to the chronicity of LBP. However, the association between systemic symptoms and ALBP remains underexplored from a holistic perspective. Hence, this study aimed to investigate this relationship and identify novel clinical prognostic predictors for LBP. Methods: This retrospective cross-sectional study included patients with ALBP admitted to the Department of Korean Medicine Rehabilitation at the Dongguk University Bundang Hospital between 1 January 2021 and 30 April 2025. Data extracted from medical records included demographics, treatment-related information, pain characteristics, past medical history, and systemic symptoms. Statistical analyses included independent t-tests, Mann–Whitney U tests, chi-squared tests, Fisher’s exact tests, correlation analysis, and multiple linear regression models. Results: A total of 194 patients with ALBP were included in the analysis. Among systemic symptoms, dyspepsia was significantly associated with higher pain at discharge and smaller absolute and relative pain changes. Although sleep disturbance and constipation showed associations with higher pain at discharge in univariate analyses, these associations were not statistically significant in regression models. Beyond systemic symptoms, alcohol consumption was significantly associated with lower pain at discharge and greater relative pain change, while hospitalization and symptom duration exhibited non-linear relationships. These findings remained robust in sensitivity and subgroup analyses. Conclusions: Systemic symptoms, especially dyspepsia, may serve as prognostic factors impeding ALBP recovery, representing potential early markers for identifying patients at risk of chronicity. The findings highlight the prospect of multidimensional strategies in reducing pain and enhancing patients’ quality of life in clinical practice. Full article

The medlar (Mespilus germanica) is a deciduous tree that belongs to the Rosaceae family. This plant has been valued throughout history for its culinary uses and medicinal applications. Medlar fruit contains a high amount of vitamin C, carbohydrates, and pectin, making it a valuable remedy for treating scurvy. In folk medicine, medlar is used to treat constipation and other digestive issues. This study investigates the quantitative composition and seasonal variation in phenolic compounds in flowers, leaves, and fruits of Mespilus germanica L. using high performance liquid chromatography, as well as total phenolic content and antioxidant activity. The predominant class of phenolics in flowers were flavonols, with 52.5% of the total phenolic content. On the other hand, dominant phenolics in fruits were flavan-3-ols, with procyanidin B2 and epicatechin being most abundant, whereas in leaves, hydroxycinnamic acids were the most prevalent phenolic compounds. Seasonal variations were noted for analyzed compounds in various plant parts. This study highlights significant changes in the phenolic profile of M. germanica during various harvesting periods and suggests that both fruits and leaves are rich sources of bioactive compounds. However, its nutraceutical potential might depend on harvesting time. Full article

Background/Objectives: This study investigates the pharmacological potential of 1,4-dihydropyridine derivatives, functionalized with an imidazo[2,1-b]thiazole scaffold, as selective modulators of intestinal motility. Given their structural similarity to both L-type calcium channel blockers and spasmolytics such as Otilonium Bromide (OB), we explored their repurposing for the treatment of gut motility disorders. Methods: A focused library of 83 1,4-dihydropyridine derivatives was screened for spasmolytic activity on potassium (80 mM)-induced depolarization in isolated guinea pig ileal and colonic tissues. Compounds showing pharmacodynamic profiles similar to OB and nifedipine were further evaluated for their effects on the spontaneous contractility of longitudinal and circular smooth muscle layers. Additional functional assays assessed intestinal transit, visceral nociception, and mixing/fragmentation efficiency. Microbiota safety was preliminarily tested on mixed cultures of Bifidobacterium and Lactobacillus species. Results: Compounds 62 and 65 selectively relaxed intestinal smooth muscle, primarily targeting the longitudinal layer without affecting vascular contractility. Ex vivo testing highlights that compounds 62 and 65 could both modulate gut transit and mixing without causing functional constipation or pain. Microbiota analyses showed no detrimental effects on “good” bacterial species Bifidobacterium and Lactobacillus spp. Conclusions: The favorable gastrointestinal and microbiological profiles of compounds 62 and 65, combined with their structural versatility, support their potential repurposing for functional bowel disorders. Their selective activity suggests a promising role in therapies targeting intestinal motility while preserving microbiota homeostasis, supporting the need for extended pharmacological characterization. Full article