An updated meta-analysis of effectiveness and safety of mTOR inhibitors in the management of tuberous sclerosis complex patients.

PURPOSE: Tuberculous sclerosis complex (TSC) is an autosomal dominant multi-system disease. In TSC patients, the inhibition of mTOR pathway is weakened, which leads to the uncontrolled proliferation of normal resting cells. Therefore, mTOR inhibitors have many therapeutic potentials in the treatment of TSC. However, there is no consensus on the safety and efficacy of mTOR inhibitors so far. This article aimed to present new evidence for the efficacy and safety of mTOR inhibitors in the treatment of TSC by evaluating published clinical trials. METHODS: A systemic search of online databases, such as Cochrane Library, Embase, PubMed, and the US National Institutes of Health Clinical Trials Registry, was conducted. The researchers selected studies that met the following entry criteria: randomized, double-blinded or single-blinded, placebo-controlled, parallel-group studies with active and control arms receiving rapamycin or everolimus and matched placebo, respectively. The meta-analysis included seven studies. Tumor response or epilepsy seizure frequency response rates were considered efficacy outcomes. RESULTS: In seven studies involving 877 patients, using of mTOR inhibitors therapy showed an improvement in both tumor response and seizure frequency outcomes in TSC. In combination of AML (angiomyolipomas), SEGA (subependymal giant cell astrocytoma), epilepsy, and facial angiofibroma subjects, the RR is 3.01 (95% CI 2.03 to 4.45, p = 0.000) with observed heterogeneity (I-squared = 55.4%). The main side effect of mTOR inhibitors was stomatitis. CONCLUSION: The updated meta-analysis suggests that the use of mTOR inhibitors is an effective therapy for patients with TSC.

[Craving in Substance Addiction: A Concept Analysis].

Craving in the context of substance addiction is considered an important predictor of substance addictive disorders and relapse risk. Behavior therapy, mindfulness, and exercise may be employed clinically to alleviate cravings. However, many scholars have offered various interpretations of craving in substance addiction. Despite these definitions sharing some overlapping elements, a consensus has yet to be reached. Although many studies have presented the effects of and interventions for craving to alleviate substance addiction, this issue has rarely been explored in the clinical nursing context, resulting in a lack of understanding of the concept of craving in substance addiction among nursing professionals. Therefore, based on the conceptual analysis approach proposed by Walker and Avant (2019), a conceptual analysis of craving in substance addiction was conducted in this study by interpreting and defining the characteristics, pre-factors, consequences, and effects of craving in substance addiction using examples of typical, borderline, related, and contrary cases. The findings are intended to help nurses gain a more comprehensive understanding of craving in substance addiction and become more familiar with cases requiring clinical care.

Psychometric evaluation of Suicide Management Competency Scale for nursing students: A cross-sectional study.

Suicide management skills are essential for nursing students, as they are often the initial healthcare contact for individuals at risk of suicide. Recognising signs of suicidal ideation and behaviour is critical for initiating timely interventions. This study aimed to develop and access the psychometric evaluation of the Suicide Management Competency Scale (SMCS) for nursing students. A first draft of the SMCS was initially developed following literature and focus group, and a scale containing 28 items was constructed. We recruited 216 participants from two nursing schools. Construct validity was evaluated with exploratory factor analysis (EFA). Internal consistency reliability was determined with Cronbach's alpha, and test-retest reliability was examined with intra-class correlation. After four rounds of EFA and item analysis, we reduced the number of items to 16. We deleted 12 items, including 4 items for communalities less than 0.40, 3 items for cross-loading, 3 items for factor loading less than 0.40, and 2 items for low corrected item-total correlation. The final 16-item SMCS resulted in three subscales, which explained 55.813% of the total variance: emotional challenges in suicide risk assessment, delivering suicide interventions, and suicide risk nursing competence and confidence. Cronbach's alpha was 0.854 for the total score and 0.748 to 0.847 for the subscales. The newly developed SMCS was found to have good reliability and validity, suggesting that this scale could be used to evaluate nursing students' perceived competency in managing suicide, which might help cultivate competence in nurses' ability to effectively manage and prevent suicide, thus contributing to saving lives.

Dual-task training in older adults with cognitive impairment: A meta-analysis and trial sequential analysis of randomized controlled trials.

OBJECTIVE: To determine the effects of simultaneous dual-task training on cognitive function, physical function, and depression in older adults with mild cognitive impairment or dementia. METHODS: Comprehensive database searches were conducted in PubMed, Embase, the Cochrane Library, CINAHL, Ovid-Medline, Web of Science, and Scopus up to December 2022. Randomized controlled trials were included to assess the efficacy of simultaneous dual-task training for older adults with mild cognitive impairment or dementia. The analysis utilized Comprehensive Meta-Analysis version 3.0, presenting Hedges' g and the corresponding 95 % confidence interval (CI) for the pooled effect size and, applying a random-effects model. The I2 and Cochran's Q tests were employed to evaluate heterogeneity. The Cochrane Risk of Bias 2.0 tool was employed to assess study quality. The Copenhagen Trial Unit (version 0.9.5.10 Beta) was employed for trial sequential analysis, providing a rigorous methodology for evaluating cumulative evidence from multiple studies. RESULTS: Of the 1676 studies identified, 20 studies involving 1477 older adults with cognitive impairment were included. Dual-task training significantly enhanced global cognition (0.477, 95 % CI: 0.282 to 0.671), executive function (-0.310, 95 % CI: -0.586 to -0.035), working memory (0.714, 95 % CI: 0.072 to 1.355), gait (0.418, 95 % CI: 0.252 to 0.583), physical activity (0.586, 95 % CI: 0.012 to 1.16), and depression (-0.703, 95 % CI: -1.253 to -0.153). Trial sequential analyses revealed the robustness of this meta-analysis, which was based on a sufficient sample size from the included studies. Moreover, dual-task training demonstrated beneficial effects on global cognition, executive function, working memory, and gait. CONCLUSIONS: Dual-task training improved cognition, physical function, and depression among older adults with cognitive impairment. Accordingly, dual-task training should be considered a clinical nonpharmacological intervention for older adults with mild cognitive impairment or dementia. Nevertheless, the trial sequential analysis results were consistent with those of the pairwise meta-analysis but only global cognition reached significance by crossing the trial sequential analysis boundary. Future studies with higher-quality designs and larger sample sizes are required to obtain more conclusive results regarding other outcomes. REGISTRATION: PROSPERO CRD42023418598.

Smac is another pathway in the anti-tumour activity of Trichosanthin and reverses Trichosanthin resistance in CaSki cervical cancer cells.

Trichosanthin (TCS), or Tin Hua Fen, is a renowned traditional Chinese medicine and is still used in Chinese clinics for midterm abortion and the treatment of choriocarcinoma. Many studies have demonstrated that TCS has anti-tumour action as a type I ribosome-inactivating protein. We hypothesized that there is another pathway of the anti-tumour activity of TCS. cDNA array analysis was applied to profile changes in gene expression of human CaSki in response to TCS stimulation. Smac, a mitochondrial protein, was identified as the highly upregulated protein in response to TCS treatment. The mRNA and protein levels of Smac were determined by real-time RT-PCR and Western blotting respectively. We analysed the methylation status of Smac using methylation-specific PCR (MSP) and indicates that TCS promotes Smac demethylation and increases its expression in cervical CaSki cells. Tumour cells develop resistance to TCS during prolonged treatment, as with other classic chemotherapeutic agents. Smac expression was downregulated and Twist was upregulated in TCS-resistant cells. These results indicate that TCS has demethylating activity and that Smac is involved in both TCS response and TCS resistance.