Dissecting the association between gut microbiota, body mass index and specific depressive symptoms: a mediation Mendelian randomisation study.

Background: Observational studies highlight the association between gut microbiota (GM) composition and depression; however, evidence for the causal relationship between GM and specific depressive symptoms remains lacking. Aims: We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index (BMI). Methods: We performed a two-sample Mendelian randomisation (MR) analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies. The mediating role of BMI was subsequently explored using mediation analysis via two-step MR. Results: MR evidence suggested the Bifidobacterium genus (ß=-0.03; 95% CI -0.05 to -0.02; p<0.001 and ß=-0.03; 95% CI -0.05 to -0.02; p<0.001) and Actinobacteria phylum (ß=-0.04; 95% CI -0.06 to -0.02; p<0.001 and ß=-0.03; 95% CI -0.05 to -0.03; p=0.001) had protective effects on both anhedonia and depressed mood. The Actinobacteria phylum also had protective effects on appetite changes (ß=-0.04; 95% CI -0.06 to -0.01; p=0.005), while the Family XI had an antiprotective effect (ß=0.03; 95% CI 0.01 to 0.04; p<0.001). The Bifidobacteriaceae family (ß=-0.01; 95% CI -0.02 to -0.01; p=0.001) and Actinobacteria phylum (ß=-0.02; 95% CI -0.03 to -0.01; p=0.001) showed protective effects against suicidality. The two-step MR analysis revealed that BMI also acted as a mediating moderator between the Actinobacteria phylum and appetite changes (mediated proportion, 34.42%) and that BMI partially mediated the effect of the Bifidobacterium genus (14.14% and 8.05%) and Actinobacteria phylum (13.10% and 8.31%) on both anhedonia and depressed mood. Conclusions: These findings suggest a potential therapeutic effect of Actinobacteria and Bifidobacterium on both depression and obesity. Further studies are required to translate these findings into clinical practice.

Effects of selective serotonin reuptake inhibitors (SSRIs) on suicide: A network meta-analysis of double-blind randomized trials.

The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We conducted a network meta-analysis to examine the effects of SSRIs on suicide risk in patients with mental disorders. A comprehensive search was conducted across PubMed, Web of Science, PsycINFO, CENTRAL, Wanfang Database, and China National Knowledge Infrastructure for articles published until December 19, 2023. The main outcomes were suicidal ideation and instances of suicidal behavior. We included 29 double-blind randomized trials in our analysis. The findings suggest that SSRIs primarily offer short-term protection against suicidal ideation. By week 2, paroxetine, fluoxetine, escitalopram, and non-SSRI treatments were linked to a decreased suicide risk compared with a placebo, with the exception of sertraline. This protective effect was diminished by week 8. In contrast, studies on instances of suicidal behavior from weeks 1 to 10 found no significant difference in efficacy between SSRIs, non-SSRIs, and placebo. These results indicate that SSRIs may offer short-term protection against suicidal ideation. However, their long-term effectiveness in mitigating suicidal ideation and preventing suicidal behaviors is limited.

Electronic Skin Based on Polydopamine-Modified Superelastic Fibers with Superior Conductivity and Durability.

Owing to their excellent elasticities and adaptability as sensing materials, ionic hydrogels exhibit significant promise in the field of intelligent wearable devices. Nonetheless, molecular chains within the polymer network of hydrogels are susceptible to damage, leading to crack extension. Hence, we drew inspiration from the composite structure of the human dermis to engineer a composite hydrogel, incorporating dopamine-modified elastic fibers as a reinforcement. This approach mitigates crack expansion and augments sensor sensitivity by fostering intermolecular forces between the dopamine on the fibers, the hydrogel backbone, and water molecules. The design of this composite hydrogel elevates its breaking tensile capacity from 35 KJ to 203 KJ, significantly enhancing the fatigue resistance of the hydrogel. Remarkably, its electrical properties endure stability even after 2000 cycles of testing, and it manifests heightened sensitivity compared to conventional hydrogel configurations. This investigation unveils a novel method for crafting composite-structured hydrogels.

Network Meta-Analysis Indicates Superior Effects of Omega-3 Polyunsaturated Fatty Acids in Preventing the Transition to Psychosis in Individuals at Clinical High-Risk.

BACKGROUND: The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate the efficacy of pharmacological and nutritional interventions in CHR-P and whether these interventions can enhance the efficacy of psychological treatments. METHODS: We systematically reviewed data from 5 databases until July 24, 2021: PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, and WanFang Data. The primary outcome was the transition to psychosis. Network meta-analyses were conducted at 3 time points (6, 12, and ≥24 months) considering both pharmacological/nutritional interventions alone and its combination with psychotherapy. RESULTS: Out of 11 417 identified references, 21 studies were included, comprising 1983 participants. CHR-P participants receiving omega-3 polyunsaturated fatty acids treatment were associated with a lower probability of transition compared with placebo/control at 6 months (odds ratio [OR] = 0.07, 95% confidence interval [CI] = .01 to .054), 12 months (OR = 0.14, 95% CI = .03 to .66), and ≥24 months (OR = 0.16, 95% CI = .05 to .54). Moreover, risperidone plus psychotherapy was associated with a lower likelihood of transition at 6 months compared with placebo/control plus psychotherapy, but this result was not sustained over longer durations. CONCLUSION: Omega-3 polyunsaturated fatty acids helped in preventing transitions to psychosis compared with controls. PROSPERO REGISTRATION NUMBER: CRD42021256209.

Differential impacts of initial treatment status on long-term survival in patients with sarcomas treated in a referral center according to histologic type and anatomic site.

OBJECTIVE: The aim of this work was to estimate the magnitude of the differential impacts of initial treatment status relative to the impact of classic clinicopathologic factors on the long-term overall survival (OS) of sarcoma patients in a referral cancer center. METHODS: From the institutional database, we identified 2185 patients who presented to the institutional multidisciplinary team (MDT) prior to (N = 717, 32.8%) or after (N = 1468, 67.2%) initial treatment, with a first diagnosis of sarcoma from January 1999 to December 2018. Descriptive, univariate and multivariate analyses were applied to identify the factors related to OS. By performing propensity score matching of each completely MDT-treated patient to a referral patient with similar characteristics, the differential impacts of the identified risk and prognostic factors on OS in the 2 groups were estimated by the Kaplan‒Meier survival curves, log-rank test and Cox proportional hazard regression; the results were compared using calibrated nomograph models and forest plots. RESULTS: Adjusted for the clinicopathologic factors of patient age, sex, primary site, tumor grade, tumor size, resection margin and histology, hazard ratio-based modeling analysis indicated that the initial treatment status was an independent but intermediate prognostic factor associated with long-term OS. The major impacts of the initial and comprehensive MDT-based management on significant improvement of the 20-year OS of sarcomas were reflected in the subgroup of patients with stromal, undifferentiated pleomorphic, fibromatous, fibroepithelial, or synovial neoplasms and tumors in the breast, gastrointestinal tract, or soft tissues of limb and trunk. CONCLUSIONS: This retrospective study supports early referral of patients with soft tissue masses of unknown identity to a specialized MDT before biopsy and initial resection to reduce the risk of death but highlights an unmet need for a greater understanding of some of the most difficult sarcoma subtypes and subsites and their management.

Evaluating Teaching Effectiveness of Medical Humanities in an Integrated Clerkship Program by a Novel Prospective Propensity Score Matching Framework.

BACKGROUND: This study aims to rigorously compare the effectiveness of the educational programs of a new integrated clinical clerkship in medicine (3 months) and surgery (3 months) at a cancer center with the conventional subspecialty-based rotations at a tertiary teaching hospital, by this prospective, pre-post comparative method. METHODS: Between 2013-2016, we compared 69 students who had selected the integrated clerkship that emphasized clinical competency and medical humanities training with 138 matched peers who had completed conventional clerkships during the same period. Outcome measures for medical humanities included empathy, patient-centeredness, and other values and skills related to holistic health care professionalism by introducing prospective propensity score matching (PSM). RESULTS: At baseline, no significant between-group differences existed. At the completion of the core clerkships, students receiving the integrative clerkship had significantly higher scores on the Patient-Practitioner Orientation Scale (PPOS) and the Professionalism Climate in Clinical Teaching Environment (PCI), and similar Jefferson Scale of Physician Empathy Student Version (JSPE) scores, as compared with the comparison group. We also found that the students in this program did not perform worse than those in the traditional internship group in the comprehensive and formative OSCE medical clinical skills test. CONCLUSIONS: Our study develops an empirical basis for rigorous evaluation to design medical education to improve the medical humanities values and skills of interns. Features of the new integrated clerkship program that we developed include substantial participation by the students in patient-centered in-hospital culture, as well as reflection, discussion, and feedback on actual clinical cases.

Functional alterations of the suicidal brain: a coordinate-based meta-analysis of functional imaging studies.

Altered brain activities in suicidal subjects have been reported in a number of neuroimaging studies. However, the activity aberrances were inconsistent in previous investigations. Thus, we aimed to address activity abnormalities in suicidal individuals. Databases were searched to perform a meta-analysis of whole-brain functional MRI studies of suicidal individuals through January 14, 2020. Meta-analyses were conducted using Seed-based d Mapping software. Based on a meta-analysis of 17 studies comprising 381 suicidal individuals and 642 controls, we mainly found that increased activity in the bilateral superior temporal gyrus, left middle temporal gyrus, and bilateral middle occipital gyrus, along with decreased activity in the right putamen and left insula, were detected in suicidal individuals compared with nonsuicidal subjects. To reduce methodological heterogeneity between the included studies, subanalyses of behavioral domains were conducted, and the right superior temporal gyrus was found to increase in all subanalyses of domains. In subanalyses of suicidal attempters and ideators, suicide attempters displayed hyperactivation in the bilateral superior temporal gyrus and left middle temporal gyrus and blunted responses in the left insula relative to controls. Suicidal ideators demonstrated elevated activation in the right middle occipital gyrus and reduced activity in the right putamen relative to controls. The bilateral superior temporal gyrus was the most robust finding, replicable in all data sets in the jackknife sensitive analysis. Moreover, increased activity in the right superior temporal gyrus, left middle temporal gyrus, and right middle occipital gyrus was found to be involved with higher suicide ideation scores. This study revealed several brain regions associated with suicidality. These findings may contribute to our understanding of the pathophysiology of suicide and have important implications for suicide prevention and interventions.

A numerical study on the effect of CO2 addition for methane explosion reaction kinetics in confined space.

To explore the influence of the CO2 volume fraction on methane explosion in confined space over wide equivalent ratios, the explosion temperature, the explosion pressure, the concentration of the important free radicals, and the concentration of the catastrophic gas generated after the explosion in confined space were studied. Meanwhile, the elementary reaction steps dominating the gas explosion were identified through the sensitivity analysis. With the increase of the CO2 volume fraction, the explosion time prolongs, and the explosion pressure and temperature decrease monotonously. Moreover, the concentrations of the investigated free radicals also decrease as the increase of the CO2 volume fraction. For the catastrophic gas, the concentration of the gas product CO increases and the concentrations of CO2, NO, and NO2 decrease as the volume fraction of CO2 increases. When 7% methane is added with 10% CO2, the increase rate of CO is 76%, and the decrease rates of CO2, NO, and NO2 are 27%, 37%, and 39%, respectively. If the volume fraction of CO2 is constant, the larger the volume fraction of methane in the blend gas, the greater the mole fraction of radical H and the lower the mole fraction of radical O. For radical OH, its mole fraction first increases, and then decreases with the location of peak value of 9.5%, while the CO concentration increases with the increase of the methane concentration. For all the investigated volume fraction of methane, the addition of CO2 reduces the sensitivity coefficients of each key elementary reaction step, and the sensitivity coefficient of reaction promoting methane consumption decreases faster than that of the reaction inhibit methane consumption, which indicates that the addition of CO2 effectively suppresses the methane explosion.

Does Prosthesis-Based Breast Reconstruction Affect the Clinical Outcome of Postmastectomy Radiotherapy?

BACKGROUND: In the last 5 decades, there has been significant advancement of breast reconstruction and postmastectomy radiotherapy for breast cancer care. There has been concern that breast reconstruction may adversely affect the efficacy of postmastectomy radiotherapy. This, however, has not been proven by clear clinical evidence. METHODS: By comparing the locoregional recurrence rates and overall survival after postmastectomy radiotherapy between those with and without prosthesis-based breast reconstruction, a retrospective cohort study of the breast cancer patients was done. Multivariable Cox proportional hazards analysis was used to control the confounding factors. RESULTS: From January 1, 1998 to December 31, 2011, 1015 patients receiving postmastectomy radiotherapy were identified. Among them, 111 patients had prosthesis-based breast reconstruction, and the other 904 did not have breast reconstruction. Thirty-four of 904 (3.8%) patients in the nonreconstructed group and 4 of 111 (3.6%) patients in the reconstructed group developed locoregional recurrence. Multivariable survival analysis found no significant difference both in locoregional recurrence-free survival (hazard ratio, 0.852; P = 0.771) and in overall survival (hazard ratio = 1.317; P = 0.246) between the nonreconstructed group and reconstructed group. CONCLUSIONS: Although postmastectomy radiotherapy has been shown to affect the surgical and cosmetic outcomes of breast reconstruction, prosthesis-based breast reconstruction does not seem to have significant adverse impacts on the locoregional recurrence-free survival and overall survival of postmastectomy radiotherapy.

Investigation of Prognostic Features in Primary Cutaneous and Soft Tissue Angiosarcoma After Surgical Resection: A Retrospective Study.

Primary cutaneous and soft tissue angiosarcoma is a rare but highly aggressive malignancy. To date, surgical resection is the mainstay of treatment, but poor prognosis is expected. To investigate whether there are factors associated with poor prognosis after surgical resection and to develop a treatment guideline for current therapy, we retrospectively collected data on 28 patients who underwent surgery as initial treatment and reviewed patient demographics, tumor characteristics, disease courses, and prognoses from September 1996 to May 2013. Of these 28 patients, 17 (60.7%) were men and the mean age at first diagnosis was 66.57 ± 18.57 years. Anatomically, 17 (60.7%) tumors were in the scalp and 11 (39.3%) were in other sites of the body. Of the 28 patients, 23 (82.1%) had achieved negative surgical margins, 24 (85.7%) received adjuvant radiation therapy, and 17 (60.7%) received adjuvant chemotherapy. Twenty-one patients (75%) died during a mean follow-up time of 35.86 ± 28.91 months, and all deaths were caused by angiosarcoma. The 5-year overall survival rate was 17.86%. Sixteen (57.1%) patients had locoregional tumor recurrence, and 20 (71.4%) had distant metastases, with a median of 9.17 (range, 1.9-98.07) months to recurrence or metastasis. Possible predictors of poor prognosis (P < 0.05) in terms of disease-free survival after surgical resection were male sex, cardiovascular disease, smoking, and scalp angiosarcomas, those in terms of overall survival were older than 70 years, male sex, cardiovascular disease, smoking, scalp angiosarcomas, distant metastases, and not receiving adjuvant chemotherapy. In conclusion, although multimodal treatments are used, the overall prognosis after surgical resection is still poor, especially for patients with the above predictive factors. An early diagnosis and complete resection of the primary tumor with or without adjuvant radiotherapy and chemotherapy are suggested for a potential better outcome. For those who have a diffuse lesion pattern with the involvement of vital structures, recurrence, or metastasis, palliative resection could be an alternative treatment choice.

Risk of infection is associated more with drain duration than daily drainage volume in prosthesis-based breast reconstruction: A cohort study.

In prosthesis-based breast reconstruction, drains are used to prevent seroma formation and to reduce the risk of infection. However, prolonged drainage increases the risk of ascending infection. Although the volume often accepted for drain removal is ≤30 mL per day, the optimal timing to remove the drain for best clinical outcome remains controversial.We did a retrospective cohort study of 569 patients of prosthesis-based breast reconstruction with infection rate as the outcome variable; drain duration and last daily drainage volume as the main independent variables. Data on age, smoking history, diabetes mellitus history, body mass index, breast weight, tissue expander size, drain size, number of retrieved lymph nodes, tumor size, number of metastatic lymph nodes, tumor stage, mastectomy type, reconstruction type, submuscular implantation, skin defect, operative time, duration of antibiotics use, chemotherapy, and radiotherapy were collected as covariates. Multivariable logistic regression analysis was used to control for confounding.The total infection rate was 5.1% (29/569). The daily drainage volume ≥30 mL/d at the time of drain removal was not found associated with increased infection rate (P = 0.32). Of the various cutoff values of last daily drainage volume, none was found to be a determinant for drain removal where the risk of infection was concerned. By contrast, drain duration over 21 days significantly increased infection rate (P = 0.001). The multivariable logistic regression analysis showed an increase of 76.2% in the infection rate with each additional week of drain retention (P = 0.001). Breast weight also had a significant influence on risk of infection. Chemotherapy and drain size showed borderline effect on risk of infection whereas the last daily drainage volume was not associated with risk of infectionIn summary, our study revealed that drain duration, rather than the last daily drainage volume, significantly affects the infection rate in prosthesis-based breast reconstruction. We recommend that the drain is better removed no longer than 3 weeks postoperatively and can be removed as early as postoperative day 7, even when the drainage is over 30 mL in a 24-hour period.

A clinical clerkship collaborative program in Taiwan: Acquiring core clinical competencies through patient care responsibility.

BACKGROUND/PURPOSE: Traditionally, clinical clerkship training in Taiwan does not provide medical students with sufficient patient care responsibilities and often results in inadequate clinical skills. METHODS: We implemented a pilot clerkship program at a comprehensive cancer center that emphasizes core clinical competency through direct patient care and dedicated faculty and mentors. Students were an integral part of the patient care team held accountable for providing coordinated and holistic care. Students' self-assessment of clinical competencies, faculty evaluation, and objective structured clinical examination were compared against their peers trained by traditional clerkship at a main teaching hospital. RESULTS: Fifty medical students completed the clerkship program in the first 3 years. At the end of the clerkship, participants rated themselves significantly higher than their peers in almost all patient care and clinical skill domains. The most significant areas included physical examination, clinical reasoning, developing management plan, holistic approach, handling ethical issues, and time management skills. The students rated their clerkship teachers significantly higher in time spent with students, skills and enthusiasm in teaching, as well as giving students appropriate patient care responsibilities. There was no significant difference in the end-of-clerkship objective structured clinical examination performance, but participants of the program achieved better grades in their subsequent internship. CONCLUSION: This pilot collaborative program presented a successful model for clinical education in the teaching of core clinical competencies through direct patient care responsibilities at the clerkship stage. It is hoped that the project will become a catalyst for medical education reform in Taiwan and regions with similar traditions.

The prognosis of patients with primary osteosarcoma who have undergone unplanned therapy.

OBJECTIVE: For diagnosing osteosarcoma correctly, a combination of clinical, radiological and histological examinations is required. Erroneous treatment may cause local contamination and systemic seeding in patients. The purpose of this study was to compare outcomes of planned and unplanned treatment for osteosarcoma. METHODS: A retrospective review of patients with high-grade osteosarcoma who received appropriate surgical treatment and chemotherapy (n = 134) and those who were misdiagnosed and received unplanned surgery (n = 16) between July 1995 and February 2005. RESULTS: Patients who received unplanned treatment were older (mean age: 29.7 vs. 19.7 years; P = 0.003) and had a smaller mean tumor volume (119 vs. 280 ml; P = 0.015). The 5-year survival rate was not statistically different between the groups. Patients who had unplanned treatment had a higher local recurrence rate (43.8 vs. 17.9%; P = 0.024) and a shorter mean time for recurrence (11.9 vs. 20.8 months; P = 0.036). Furthermore, in patients who underwent unplanned treatment, lung metastases occurred earlier (6.1 vs. 16.2 months P = 0.021) and the final limb salvage rate was less (68.7 vs. 87.3%; P < 0.001). CONCLUSIONS: Unplanned treatment for high-grade osteosarcoma can result in failure of local control and earlier systemic metastases.

A novel human stem cell coculture system that maintains the survival and function of culture islet-like cell clusters.

Islet-like cell clusters (ICCs) have been suggested to be a source of insulin-producing tissue for xenotransplantation in type 1 diabetes. We designed an approach to maintain the cultured rat pancreatic ICC survival and function, when cocultured with human umbilical cord mesenchymal stem cells (HUMSCs). HUMSCs in coculture have the ability to maintain ICC survival and function, for which number and insulin secretion of ICCs are increasing and lasting for 3 months, while ICCs gradually crash, which results in cell death after a period of 12 days of culture without HUMSCs. Cytokine protein array showed it has more than a twofold increase in levels of several cytokines (interleukin-6, tissue inhibitor of metalloproteinases-1, tissue inhibitor of metalloproteinases-2, monocyte chemoattractant protein-1, growth related oncogene, hepatocyte growth factor, insulin-like growth factor binding proteins 4, and interleukin-8) on coculture medium, implying an important role of these cytokines in this coculture system. These findings suggest that coculture with HUMSCs may have a significant potential to protect ICCs from damage during culture, and may be employed in a novel culture approach to maintain islet cell survival and function before transplantation.