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Background The application of artificial intelligence (AI) in medical education and patient interaction is rapidly growing. Large language models (LLMs) such as GPT-3.5, GPT-4, Google Gemini, and Claude 3 Opus have shown potential in providing relevant medical information. This study aims to evaluate and compare the performance of these LLMs in answering frequently asked questions (FAQs) about Total Knee Arthroplasty (TKA), with a specific focus on the impact of role-playing prompts. Methods Four leading LLMs—GPT-3.5, GPT-4, Google Gemini, and Claude 3 Opus—were evaluated using ten standardized patient inquiries related to TKA. Each model produced two distinct responses per question: one generated under zero-shot prompting (question-only), and one under role-playing prompting (instructed to simulate an experienced orthopaedic surgeon). Four orthopaedic surgeons evaluated responses for accuracy and comprehensiveness on a 5-point Likert scale, along with a binary measure for acceptability. Statistical analyses (Wilcoxon rank sum and Chi-squared tests; P  < 0.05) were conducted to compare model performance. Results ChatGPT-4 with role-playing prompts achieved the highest scores for accuracy (3.73), comprehensiveness (4.05), and acceptability (77.5%), followed closely by ChatGPT-3.5 with role-playing prompts (3.70, 3.85, 72.5%, respectively). Google Gemini and Claude 3 Opus demonstrated lower performance across all metrics. In between-model comparisons based on zero-shot prompting, ChatGPT-4 achieved significantly higher scores of both accuracy and comprehensiveness relative to Google Gemini ( P  = 0.031 and P  = 0.009, respectively) and Claude 3 Opus ( P  = 0.019 and P  = 0.002), and demonstrated higher acceptability than Claude 3 Opus ( P  = 0.006). Within-model comparisons showed role-playing significantly improved all metrics for ChatGPT-3.5 ( P  < 0.05) and acceptability for ChatGPT-4 ( P  = 0.033). No significant prompting effects were observed for Gemini or Claude. Conclusions This study demonstrates that role-playing prompts significantly enhance the performance of LLMs, particularly for ChatGPT-3.5 and ChatGPT-4, in answering FAQs related to TKA. ChatGPT-4, with role-playing prompts, showed superior performance in terms of accuracy, comprehensiveness, and acceptability. Despite occasional inaccuracies, LLMs hold promise for improving patient education and clinical decision-making in orthopaedic practice. Clinical trial number Not applicable.

Sonodynamic cancer therapy is based on the preferential uptake and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and the subsequent activation of the drug by ultrasound irradiation. In the present study, we investigated the sonodynamically-induced antitumoral effect with functionalized carbon nanotubes, such as poly-ethylene glycol-modified carbon nanotubes (PEG-modified CNTs). Antitumor effects were evaluated using histological observation and assessing tumor growth following sonodynamic exposure to PEG-modified CNTs. The combined treatment of 100 μM PEG-modified CNT and ultrasound induced a 2-fold cytotoxicity. Sodium azide, which quenches singlet oxygen, significantly inhibited ultrasonication induced cell damage in the presence of PEG-modified CNTs. This suggests that singlet oxygen produced by the combined use of PEG-modified CNTs and ultrasound is involved in the induction of antitumoral effects. The destruction of tumor tissue was observed with the ultrasonic treatment in combination with PEG-modified CNTs, while neither the treatment with PEG-modified CNTs alone nor ultrasound alone caused any necrosis. These results indicate that PEG-modified CNT functions as a sonosensitizer and is effective for sonochemical treatment of solid tumors.

Impulse control disorders (ICDs) are a debilitating non-motor symptom of Parkinson’s disease (PD), often associated with dopaminergic therapy. However, their occurrence in some patients but not others suggests additional biological mechanisms, including the gut microbiome. In this study, we analyzed 191 PD patients (14 with ICDs, 177 without) using 16S rRNA gene sequencing to explore the association between gut microbiota and ICDs. No significant differences were observed in alpha or beta diversity between groups, but several bacterial taxa showed differential abundances. Notably, Methanobrevibacter and Intestinimonas butyriciproducens were enriched in ICD patients. Functional pathway analysis revealed differences in metabolic pathways, including enrichment of xenobiotic degradation and nicotinate metabolism in the ICD group. These findings suggest that specific gut microbial taxa and their associated metabolic functions may contribute to ICDs in PD, highlighting a potential non-dopaminergic mechanism and opening new avenues for microbiome-targeted intervention.

Abstract Background Recurrent and severe Clostridium difficile infections (CDI) are treated with fecal microbiota transplant (FMT). Uncertainty exists regarding FMT effectiveness for CDI with underlying inflammatory bowel disease (IBD) and regarding its effects on disease activity and effectiveness in transferring the donor microbiota to patients with and without IBD. Methods Subjects with and without IBD who underwent FMT for recurrent or severe CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) frequency of IBD flare after FMT; (3) microbiota engraftment after FMT; (and 4) predictors of CDI recurrence. Results One hundred thirty-four patients, 46 with IBD, were treated with FMT. Follow-up was available in 83 and 118 patients at 6 and 2 months, respectively. There was no difference in recurrence in patients with and without IBD at 6 months (38.7% vs 36.5%; P > 0.99) and 2 months (22.5% vs 17.9%; P = 0.63). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. Pre-FMT microbiota was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment, with no difference in engraftment based on CDI recurrence or IBD endoscopic severity at FMT. Conclusions Inflammatory bowel disease did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiota was not predictive of recurrence, and microbial engraftment was impacted in those requiring IBD treatment escalation, though not by CDI recurrence or IBD disease severity.

Background Increasing evidence suggests that glucagon-like peptide 1 (GLP-1) receptor agonists (RA) can stabilize glycemic variability (GV) and interfere with eating behavior. This study compared the impact of insulin, GLP-1 RA, and dietary components on GV using professional continuous glucose monitoring (CGM). Methods Patients with type 2 diabetes underwent CGM before and after switching from a twice-daily pre-mixed insulin treatment regimen to a GLP-1 RA (liraglutide) plus basal insulin regimen. The dietary components were recorded and analyzed by a certified dietitian. The interactions between the medical regimen, GV indices, and nutrient components were analyzed. Results Sixteen patients with type 2 diabetes were enrolled in this study. No significant differences in the diet components and total calorie intake between the two regimens were found. Under the pre-mixed insulin regimen, for increase in carbohydrate intake ratio, mean amplitude of glucose excursion (MAGE) and standard deviation (SD) increased; in contrast, under the new regimen, for increase in fat intake ratio, MAGE and SD decreased, while when the protein intake ratio increased, the coefficient of variation (CV) decreased. The impact of the food intake ratio on GV indices disappeared under the GLP-1 RA regimen. After switching to the GLP-1 RA regimen, the median MAGE, SD, and CV values decreased significantly. However, the significant difference in GV between the two regimens decreased during the daytime. Conclusion A GLP-1 RA plus basal insulin regimen can stabilize GV better than a regimen of twice-daily pre-mixed insulin, especially in the daytime, and can diminish the effect of food components on GV.

Approximately half of patients with Parkinson’s disease (PD) suffer from unintentional weight loss and are underweight, complicating the clinical course of PD patients. Gut microbiota alteration has been proven to be associated with PD, and recent studies have shown that gut microbiota could lead to muscle wasting, implying a possible role of gut microbiota in underweight PD. In this study, we aimed to (1) investigate the mechanism underlying underweight in PD patients with respect to gut microbiota and (2) estimate the extent to which gut microbiota may mediate PD-related underweight through mediation analysis. The data were adapted from Hill‐Burns et al., in which 330 participants (199 PD, 131 controls) were enrolled in the study. Fecal samples were collected from participants for microbiome analysis. 16S rRNA gene sequence data were processed using DADA2. Mediation analysis was performed to quantify the effect of intestinal microbial alteration on the causal effect of PD on underweight and to identify the key bacteria that significantly mediated PD-related underweight. The results showed that the PD group had significantly more underweight patients (body mass index (BMI) < 18.5) after controlling for age and sex. Ten genera and four species were significantly different in relative abundance between the underweight and non-underweight individuals in the PD group. Mediation analysis showed that 42.29% and 37.91% of the effect of PD on underweight was mediated through intestinal microbial alterations at the genus and species levels, respectively. Five genera (Agathobacter, Eisenbergiella, Fusicatenibacter, Roseburia, Ruminococcaceae_UCG_013) showed significant mediation effects. In conclusion, we found that up to 42.29% of underweight PD cases are mediated by gut microbiota, with increased pro-inflammatory bacteria and decreased SCFA-producing bacteria, which indicates that the pro-inflammatory state, disturbance of metabolism, and interference of appetite regulation may be involved in the mechanism of underweight PD.

Anxiety affects 25-49% of Parkinson's disease (PD) patients, exacerbating non-motor symptoms and significantly reducing quality of life. Growing evidence suggests that gut microbiota plays a role in anxiety, but whether its impact differs between PD and non-PD populations remains unclear. This study explores the heterogeneity of gut microbiota-associated anxiety in PD and non-PD individuals. Participants from the NeuroGenetics Research Consortium provided clinical data, including PD status, anxiety status, and stool samples analyzed via 16S rRNA sequencing. After excluding nine participants with missing anxiety data, 322 individuals were included (193 PD, 129 non-PD). We assessed α-diversity, β-diversity, taxonomic composition, and functional pathways to compare microbial differences between anxious and non-anxious individuals within and across PD and non-PD groups. Beta diversity analysis revealed significant microbial differences between anxious and non-anxious PD patients (p = 0.043 in Bray-Curtis index) but not in the non-PD group. was significantly enriched in non-anxious PD patients (p = 0.011). Functional pathway analysis identified distinct metabolic alterations associated with anxiety in PD and non-PD individuals. In non-PD participants, anxiety was linked to increased activity in glycosphingolipid biosynthesis, sphingolipid metabolism, other glycan degradation, glycosphingolipid biosynthesis, and glycosaminoglycan degradation. In contrast, PD patients with anxiety exhibited enrichment in indole alkaloid biosynthesis, linoleic acid metabolism, and polyketide sugar unit biosynthesis. Gut microbiota-associated anxiety differs between PD and non-PD populations, suggesting distinct pathophysiological mechanisms. These findings underscore the potential of microbiome-targeted interventions as novel therapeutic strategies for anxiety in PD patients.

Parkinson's disease (PD) is a worldwide neurodegenerative disease with an increasing global burden, while constipation is an important risk factor for PD. The gastrointestinal tract had been proposed as the origin of PD in Braak's gut-brain axis hypothesis, and there is increasing evidence indicating that intestinal microbial alteration has a role in the pathogenesis of PD. In this study, we aim to investigate the role of intestinal microbial alteration in the mechanism of constipation-related PD. We adapted our data from Hill-Burns et al., in which 324 participants were enrolled in the study. The 16S rRNA gene sequence data were processed, aligned, and categorized using DADA2. Mediation analysis was used to test and quantify the extent by which the intestinal microbial alteration explains the causal effect of constipation on PD incidence. We found 18 bacterial genera and 7 species significantly different between groups of constipated and non-constipated subjects. Among these bacteria, nine genera and four species had a significant mediation effect between constipation and PD. All of them were short-chain fatty acid (SCFA)-producing bacteria that were substantially related to PD. Results from the mediation analysis showed that up to 76.56% of the effect of constipation on PD was mediated through intestinal microbial alteration. Our findings support that gut dysbiosis plays a critical role in the pathogenesis of constipation-related PD, mostly through the decreasing of SCFA-producing bacteria, indicating that probiotics with SCFA-producing bacteria may be promising in the prevention and treatment of constipation-related PD. 1) Several potential confounders that should be adjusted were not provided in the original dataset. 2) Our study was conducted based on the assumption of constipation being the etiology of PD; however, constipation and PD may mutually affect each other. 3) Further studies are necessary to explain the remaining 23.44% effect leading to PD by constipation.

Entacapone, one of the most common drugs distributed among patients with Parkinson's disease, is a peripherally acting catechol-O-methyltransferase (COMT) inhibitor that is used in addition to levodopa to control symptoms. However, there have been negative effects reported against entacapone, namely, gastrointestinal (GI) problems and drowsiness. In this pilot study, we aim to examine the hypothesis that the discomfort induced by entacapone might be originated from the shift of microbial composition by adjusting the effect of levodopa. The population in this pilot study consisted of 13 PD patients treated with levodopa only and 11 with both levodopa and entacapone. The 16S rRNA gene sequence data were processed, aligned, and categorized using the DADA2. Alpha diversity indices for Observed, Chao1, Shannon, and Simpson metrics were calculated with Phyloseq 1.32.0. Dissimilarities were calculated using unweighted unique fraction metrics (Unifrac), weighted Unifrac, and Canberra distance. Functional differences were calculated by PICRUSt2 based on the KEGG database. Results of 16S rRNA sequencing analysis showed that while entacapone did not influence the species richness, the composition of the microbial community shifted considerably. Relative abundances of bacteria related to constipation and other GI disorders also altered significantly. Functional enrichment analysis revealed changes in the metabolic activity of alanine, aspartate, and glutamate. These amino acids are related to common side effects of entacapone such as auditory hallucinations, fatigue, and nightmare. Our findings provide testable hypothesis on the cause of unpleasant side effects of entacapone, which in the long run could possibly be reduced through gut microbiota manipulation.