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The etiologies of Parkinson's disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these causes or risk factors do not account for the majority of cases. Other, less visible factors must be at play. Among these is a widely used industrial solvent and common environmental contaminant little recognized for its likely role in PD: trichloroethylene (TCE). TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. The colorless chemical was first linked to parkinsonism in 1969. Since then, four case studies involving eight individuals have linked occupational exposure to TCE to PD. In addition, a small epidemiological study found that occupational or hobby exposure to the solvent was associated with a 500% increased risk of developing PD. In multiple animal studies, the chemical reproduces the pathological features of PD.Exposure is not confined to those who work with the chemical. TCE pollutes outdoor air, taints groundwater, and contaminates indoor air. The molecule, like radon, evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected. Despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited. Here, through a literature review and seven illustrative cases, we postulate that this ubiquitous chemical is contributing to the global rise of PD and that TCE is one of its invisible and highly preventable causes. Further research is now necessary to examine this hypothesis.

Introduction: Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting. Methods: Random-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach. Results: Meta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefitwith liso-cel (HR: 0.37; 95%CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel. Discussion: CAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL. [ABSTRACT FROM AUTHOR]

Immune check-point inhibitors (ICPi) are immunomodulating agents, which have revolutionized the management of advanced metastatic cancers. Being immunomodulating agents, they are predisposed to causing colitis. This descriptive review article emphasized on the management of ICPi-associated colitis in advanced metastatic cancers. We used PubMed, Google Scholar, Scopus, and Embase databases for literature review, and terminologies commonly searched were "management," "immune check-point inhibitors," "colitis," "metastatic," "cancers," "literature," and "review." We reviewed a total of 11 articles done in the last 15 years relevant to ICPi colitis and its management; all the articles showed that diarrhea and colitis are the most common adverse effects observed in patients on ICPi, but prior to establishing the diagnosis of ICPi-causing colitis, possibility of Clostridium difficle or cytomegalovirus infections should be ruled out. Once the diagnosis of ICPi colitis is established, treatment should be started depending upon the severity of colitis. In mild severity, discontinuation of ICPi can resolve the symptoms but, in most of the patients with moderate to high severity of colitis, corticosteroids are considered a cornerstone treatment. Patients unresponsive to steroid treatment should be re-evaluated for infections after which anti-TNF therapy--infliximab or vedolizumab, cyclosporine, mycophenolate mofetil--can be considered. [ABSTRACT FROM AUTHOR]

Background: Environmental exposure to trichloroethylene (TCE), a carcinogenic dry‐cleaning chemical, may be linked to Parkinson's disease (PD). Objective: The objective of this study was to determine whether PD and cancer were elevated among attorneys who worked near a contaminated site. Methods: We surveyed and evaluated attorneys with possible exposure and assessed a comparison group. Results: Seventy‐nine of 82 attorneys (96.3%; mean [SD] age: 69.5 [11.4] years; 89.9% men) completed at least one phase of the study. For comparison, 75 lawyers (64.9 [10.2] years; 65.3% men) underwent clinical evaluations. Four (5.1%) of them who worked near the polluted site reported PD, more than expected based on age and sex (1.7%; P = 0.01) but not significantly higher than the comparison group (n = 1 [1.3%]; P = 0.37). Fifteen (19.0%), compared to four in the comparison group (5.3%; P = 0.049), had a TCE‐related cancer. Conclusions: In a retrospective study, diagnoses of PD and TCE‐related cancers appeared to be elevated among attorneys who worked next to a contaminated dry‐cleaning site. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The city of Jeddah experienced a severe flood in 2020, resulting in loss of life and damage to property. In such scenarios, a flood forecasting model can play a crucial role in predicting flood events and minimizing their impact on communities. The proposed study aims to evaluate the performance of machine learning algorithms in predicting floods and non-flood regions, including Gradient Boosting, Extreme Gradient Boosting, AdaBoosting Gradient, Random Forest, and the Light Gradient Boosting Machine, using the dataset from Jeddah City, Saudi Arabia. This study identified fourteen continuous parameters and various classification variables to assess the correlation between these variables and flooding incidents in the analyzed region. The performance of the proposed algorithms was measured using classification matrices and regression matrices. The highest accuracy (86%) was achieved by the Random Forest classifier, and the lowest error rate (0.06) was found with the Gradient Boosting regressor machine. The performance of other algorithms was also exceptional compared to existing literature. The results of the study suggest that the application of these machine learning algorithms can significantly enhance flood prediction accuracy, enabling various industries and sectors to make more informed decisions. [ABSTRACT FROM AUTHOR]

Plant extracts antiproliferative effects were determined by using mammalian cells along the expression profile of Caspases 3, 8, and the BID gene of the death receptor-induced pathway. Two medicinal plants viz., Turmeric (Curcuma longa) and Amla (Emblica officinalis) extracts were examined for antiproliferative effect through Neutral Red-Dye uptake assay on Vero and MDA-MB 231 cell lines. A reverse transcriptase polymerase chain reaction was used to determine the expression of genes while GAPDH expression was used as an internal control. Expression of BID was up-regulated in methanolic turmeric extract-induced MDA-MB 231 cells while Caspases 3,8 expressions were the same in induced and uninduced MDA-MB 231 cells. Activated BID cleaved into tBID and activated the intrinsic pathway which caused death in methanolic turmeric extract-induced cancerous cells. Ethanolic extracts of turmeric exerted the strongest antiproliferative effects on Vero and methanolic extracts on MDA-MB 231 cells. The morphological studies of cell lines and gene expression analysis of turmeric methanolic extract-treated cells showed activation of apoptosis via converting BID into t-BID (intrinsic pathway) and activating Caspase-3 and Caspase-8 (extrinsic pathway). With the differential cytotoxicity and induction of apoptosis in induced cancer cells in comparison to uninduced cancerous cells, hence turmeric is a natural source of new anti-cancerous compounds. [ABSTRACT FROM AUTHOR]

In Pakistan, female have been facing numerous challenges during search of best marriage proposal. Over the globe ideal beauty standards have been implicated for female which might be negatively influence their mental and physical health. Findings of the current study analyzed the differences in perception, thoughts, exposure and feelings of individuals regarding their personal or physical appearance and society's positive or negative influences over their perception while looking for marriage proposal. The present study identified the in-depth experience or perception of individual through interviews of 12 females who have been rejected in different marriage proposals and who have been perceived the social norms and cultural barriers that female have been facing all around them while searching for life partner. When females' perception were analyzed through content analyses technique, 8 major themes identified followed by initial coding and sub-themes i.e. self-perception, societal pressure, self-care/beauty charmer, rejection factors, media networking, psychological issues, gender Differences, and self V/S society. About 15 major themes emerged from the analysis of responses of the participants who had gone through with typical rejection process during marriage proposal were as following; selfperception, societal pressure, selection criteria, religious perspective, beauty standards, rejection factor, social comparison/responsibilities, psychological issues, socialization, socio-economic comparison, social networking, self v/s society, marriage proposal, gender difference, and culture. The study came into limelight the religious aspects of beauty that is universal and standardized, that was created by the almighty Creator of each and everything which is beautiful and complete in its all aspects. Also, the issues that have been created for females due to socio-cultural expectation believes regarding ideal beauty standards which imparted psychological and physical consequences that were usually negative or detrimental for female health and well-being. The rejection has been basically announced on the basis of typical selection criteria formulated by specific class and followed within that social circle. [ABSTRACT FROM AUTHOR]