Depressive symptoms in high-performance athletes and non-athletes: a comparative meta-analysis.

OBJECTIVE: To assess whether a difference exists in the prevalence of mild or more severe depressive symptoms between high-performance athletes and non-athletes. DESIGN: Comparative OR meta-analysis. DATA SOURCES: We searched PsycINFO, PubMed, MEDLINE, CINAHL, SPORTDiscus and Google Scholar, as well as the reference lists of reviews of mental health issues in high-performance athletes. ELIGIBILITY: We included studies that compared high-performance athletes and non-athletes, included a validated measure of depressive symptoms and included the prevalence of individuals who indicated at least mild depressive symptoms. RESULTS: Five articles reporting data from 1545 high-performance athletes and 1811 non-athletes were examined. A comparative OR meta-analysis found high-performance athletes were no more likely than non-athletes to report mild or more severe depressive symptoms (OR=1.15, 95% CI=0.954 to 1.383, p=0.145). Male high-performance athletes (n=940) were no more likely than male non-athletes (n=605) to report mild or more severe depressive symptoms (OR=1.17, 95% CI=0.839 to 1.616, p=0.362). For females, high-performance athletes (n=948) were no more likely than non-athletes (n=605) to report mild or more severe depressive symptoms (OR=1.11, 95% CI=0.846 to 1.442, p=0.464). Overall, male high-performance athletes (n=874) were 52% less likely to report mild or more severe depressive symptoms than female high-performance athletes (n=705) (OR=0.48, 95% CI=0.369 to 0.621, p<0.001). SUMMARY/CONCLUSIONS: High-performance athletes were just as likely as non-athletes to report depressive symptoms. Researchers need to move beyond self-report measures of depressive symptoms and examine the prevalence of clinically diagnosed depressive disorders in athletes.

Future Strategic Priorities of the Swiss Decentralized Healthcare System: A COVID-19 Case Study.

The COVID-19 pandemic exposed a multitude of vulnerabilities in Switzerland's decentralized healthcare system and highlighted the urgent need to strengthen Switzerland's capacity to respond to health crises and disease outbreaks. In this article, we draw on three distinct areas of analysis of the current functioning of the Swiss healthcare system to examine its strengths and weaknesses, which can serve as a basis for future considerations and strategic priorities. First, we analyze the different levels of nine non-pharmaceutical interventions (NPIs), as defined by the ETH KOF Stringency Index and implemented in the Swiss cantons of Zurich, Vaud, and Ticino, compared with the rate of positive COVID-19 cases, hospitalizations, and deaths. We find that there was no strong correlation between the severity of the nine non-pharmaceutical interventions implemented and lower rates of positive COVID-19 cases, hospitalizations, and deaths. Second, we examine the challenges of Switzerland's decentralized healthcare system through a literature review and with empirical data obtained from semi-structured interviews with health professionals in Switzerland. We conclude our analysis with the role of central authorities during the COVID-19 pandemic. The results demonstrate that during a national emergency in Switzerland, taking into account other factors that influence the success of a pandemic strategy, there is an opportunity for a more unified, centralized response to reduce the social and economic toll of the pandemic without necessarily risking greater health damage. We recommend that the Swiss federal government use a combination of decentralized and centralized public health and policy approaches and promote greater private-public collaboration with direct communication channels among policymakers, public health stakeholders, and the public to improve pandemic preparedness and response.

Rhabdomyolysis in the Setting of Concomitant Use of Tafamidis, Atorvastatin, and Amiodarone.

An 85-year-old women with transthyretin cardiac amyloidosis presented with generalized weakness, elevated liver function test levels, and creatinine kinase consistent with rhabdomyolysis 1 week after starting tafamidis. She was already taking atorvastatin and amiodarone, raising the possibility of a drug-drug interaction inhibiting the breakdown and excretion of atorvastatin, causing drug-induced rhabdomyolysis. (Level of Difficulty: Intermediate.).

A systematic comparison of lipopolymers for siRNA delivery to multiple breast cancer cell lines: In vitro studies.

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were effective in all cell types used in this study, indicating the possibility of universal carriers for siRNA therapy. The delivery efficiency for effective lipopolymers was not correlated with dextran uptake in the cells tested, which indicated a receptor-mediated internalization for siRNA complexes with lipopolymers, unlike fluid-phase transfer associated with dextran uptake. Consistent with this, specific inhibitors involved in clathrin- and caveolin-mediated endocytosis significantly (>50%) reduced the internalization of siRNA complexes in all cell types. Using JAK2 and STAT3 silencing in MDA-MB-231 and MDA-MB-468 cells, a general correlation between the uptake and silencing efficiency at the mRNA level was evident, but it appeared that the choice of the target rather than the cell type was more critical for consistent silencing. We conclude that siRNA therapy with lipopolymers can be undertaken in multiple breast cancer cell phenotypes with similar efficiency, indicating the general applicability of non-viral RNAi in clinical management of molecularly heterogeneous breast cancers. STATEMENT OF SIGNIFICANCE: The manuscript investigated the efficacy of siRNA carriers across multiple breast cancer cell lines. The lipopolymeric carriers were capable of delivering effective dose of siRNA to a range of breast cancer cells. Despite some differences in uptake efficiency among cell types, the mechanism of delivery was similar, with CME and CvME significantly involved in the internalization of polyplexes, while fluid-phase endocytosis was not significant. Specific target silencing was correlated to delivery efficiency, but we did notice the presence of lipopolymers that achieved high silencing with minimal siRNA delivery. Silencing specific targets in different cell types were more uniformly achieved as compared to targeting different targets in the same cells. Our studies enhance the feasibility of delivering siRNA to different types of breast cancer cells.

Amphiphilic Peptides for Efficient siRNA Delivery.

A number of amphiphilic cyclic peptides-[FR]4, [WR]5, and [WK]5-containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]5 with lipid DOPE significantly enhanced the efficiency of siRNA delivery by up to ~2-fold compared to peptide alone. Based on the data indicating the efficiency of [WR]5 in siRNA delivery, peptides containing arginine residues on the ring and tryptophan residues on the side chain, [R6K]W6 and [R5K]W5, were also evaluated, and demonstrated improved delivery of siRNA. The presence of DOPE again enhanced the siRNA delivery in most cases. [WR]5, [R5K]W5, and [R6K]W6 did not show any significant toxicity in MDA-MB-231, MDA-MB-468, and AU565 WT cells at N/P ratios of 20:1 or less, in the presence and absence of DOPE. Silencing of kinesin spindle protein (KSP) and Janus kinase 2 (JAK2) was evaluated in MDA-MB-231 cells in the presence of the peptides. The addition of DOPE significantly enhanced the silencing efficiency for all selected peptides. In conclusion, peptides containing tryptophan and arginine residues were found to enhance siRNA delivery and to generate silencing of targeted proteins in the presence of DOPE.