Risk of bias in exercise science: A systematic review of 340 studies.

Risk of bias can contribute to irreproducible science and mislead decision making. Analyses of smaller subsections of the exercise science literature suggest many exercise science studies have unclear or high risk of bias. The current review (osf.io/jznv8) assesses whether this unclear or high risk of bias is more widespread in the exercise science literature and whether this bias has decreased since the publication of the 1996 Consolidated Standards of Reporting Trials (CONSORT) guidelines. We report significant reductions in selection, performance, detection, and reporting biases in 2020 compared with 1995 in the 340 of 5,451 studies assessed using the Cochrane Risk of Bias tool. Despite these improvements, most 2020 studies still had unclear or high risks of bias. These results underscore the need for methodological vigilance, adherence to reporting standards, and education on experimental bias. Factors contributing to these improvements, such advancements in education and journal requirements, remain uncertain.

Utility of pharmacogenetic testing to optimise antidepressant pharmacotherapy in youth: a narrative literature review.

Pharmacogenetics (PGx) is the study and application of how interindividual differences in our genomes can influence drug responses. By evaluating individuals' genetic variability in genes related to drug metabolism, PGx testing has the capabilities to individualise primary care and build a safer drug prescription model than the current "one-size-fits-all" approach. In particular, the use of PGx testing in psychiatry has shown promising evidence in improving drug efficacy as well as reducing toxicity and adverse drug reactions. Despite randomised controlled trials demonstrating an evidence base for its use, there are still numerous barriers impeding its implementation. This review paper will discuss the management of mental health conditions with PGx-guided treatment with a strong focus on youth mental illness. PGx testing in clinical practice, the concerns for its implementation in youth psychiatry, and some of the barriers inhibiting its integration in clinical healthcare will also be discussed. Overall, this paper provides a comprehensive review of the current state of knowledge and application for PGx in psychiatry and summarises the capabilities of genetic information to personalising medicine for the treatment of mental ill-health in youth.

A "Patient Preference" Model of Recruitment for Research from Primary-Care-Based Memory Clinics: A Promising New Approach.

Recruiting persons with dementia for clinical trials can be challenging. Building on a guide initially developed to assist primary-care-based memory clinics in their efforts to support research, a key stakeholder working group meeting was held to develop a standardized research recruitment process, with input from patients, care partners, researchers, and clinicians. Discussions in this half-day facilitated meeting focused on the wishes and needs of patients and care partners, policy and procedures for researchers, information provided to patients, and considerations for memory clinics. Patients and care partners valued the opportunity to contribute to science and provided important insights on how to best facilitate recruitment. Discussions regarding proposed processes and procedures for research recruitment highlighted the need for a new, patient-driven approach. Accordingly, a key stakeholder co-designed "Memory Clinic Research Match" program was developed that has the potential to overcome existing barriers and to increase recruitment for dementia-related research.

Blenderized watermelon consumption decreases body mass index, body mass index percentile, body fat and HbA1c in children with overweight or obesity.

OBJECTIVES: Childhood obesity increases risk factors related to metabolic diseases. Watermelon's bioactive components can help reduce these risk factors. However, no study has investigated the effects of whole watermelon including both the flesh and rind or have assessed the impacts of any form of watermelon on children with overweight or obesity. The goal of this study was to examine the effects of whole-blenderized watermelon (BWM) consumption on cardiometabolic risk factors. METHODS: A randomized, cross-over clinical design was implemented. Boys and girls ages 10-17 years with overweight or obesity (BMI ≥ 85th percentile) consumed one cup of BWM or an isocaloric sugar-sweetened beverage (control) every day for 8 weeks with a 4-week washout between trials. Anthropometrics, dietary, biochemical and clinical measures were obtained before and at the end of each trial. RESULTS: A total of 17 participants completed the study. Eight weeks of BWM intake significantly decreased BMI (p = 0.032), BMI percentile (BMIP) (p = 0.038), body fat percentage (p = 0.036), and haemoglobin A1c (HbA1c) (p = 0.012) compared to the sugar-sweetened beverage. Sugar-sweetened beverage consumption increased BMIP (p = 0.014) compared to baseline. No significant differences were observed for inflammation, blood glucose, insulin, lipids, liver function enzymes, and satiety hormones. CONCLUSIONS: The results support that BWM consumption improved some cardiometabolic risk factors including BMI, BMIP, body fat, and HbA1c. Watermelon is a potential alternative to unhealthful snacks for improving anthropometry and some risk factors related to obesity in children.

An innovative approach to recruiting participants for dementia research: primary care and researcher perspectives.

Aim: To describe clinician and researcher perceptions of a new, patient preference focused approach to recruiting patients for research from primary care-based memory clinics. Methods: Memory clinic clinicians completed a survey and key informants completed an individual interview to gather their perceptions of this new program. Results: The majority of clinicians were 'satisfied' or 'very satisfied' with this recruitment approach and indicated that this approach would have minimal negative impact on patient care or create conflict of interest. Key informants valued the program for its patient-centred approach, the integration of research into care and potential for increased recruitment. Discussion: These findings are suggestive of support for this recruitment approach. Pilot testing will inform feasibility, effectiveness and process improvements.

Barriers and Facilitators to the Implementation of an Integrated Youth Services Network in Ontario.

Introduction: In response to the challenges of the traditional mental health system for youth both in Canada and abroad, models of integrated youth services (IYS) that span the integration of mental health, health, substance use, eucation, employment, peer support, and navigation into 'one-stop shops' are being established nationally and internationally. IYS models, however, need to be better described and evaluated to inform the replicability of this approach in other jurisdictions. Description: This paper describes the implementation of an IYS in a small urban city and rural county in Ontario, Canada, including insights from key informants into barriers, facilitators, and lessons learned. Discussion: This evaluation identified a number of barriers and facilitators to the implementation of the IYS model in this specific context. Implementation facilitators included youth and family engagement, network partner collaboration, leadership, governance structure, community enthusiasm and support, and collaborative funding models. Barriers to implementation included the COVID-19 pandemic and related public health restrictions, the diverse needs of youth, change management, sustainable funding, and transportation. Lessons learned: By establishing a shared vision of delivering youth services across the integrated network, and engaging youth early in the process of model development, IYS have the potential to transform the service system for youth and their families. Meeting the diverse needs and challenges of youth who live in rural or small urban communities will enhance service delivery and experience for young people.

Impacts of Bacteriostatic and Bactericidal Antibiotics on the Mitochondria of the Age-Related Macular Degeneration Cybrid Cell Lines.

We assessed the potential negative effects of bacteriostatic and bactericidal antibiotics on the AMD cybrid cell lines (K, U and J haplogroups). AMD cybrid cells were created and cultured in 96-well plates and treated with tetracycline (TETRA) and ciprofloxacin (CPFX) for 24 h. Reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔψM), cellular metabolism and ratio of apoptotic cells were measured using H2DCFDA, JC1, MTT and flow cytometry assays, respectively. Expression of genes of antioxidant enzymes, and pro-inflammatory and pro-apoptotic pathways were evaluated by quantitative real-time PCR (qRT-PCR). Higher ROS levels were found in U haplogroup cybrids when treated with CPFX 60 µg/mL concentrations, lower ΔψM of all haplogroups by CPFX 120 µg/mL, diminished cellular metabolism in all cybrids with CPFX 120 µg/mL, and higher ratio of dead cells in K and J cybrids. CPFX 120 µg/mL induced overexpression of IL-33, CASP-3 and CASP-9 in all cybrids, upregulation of TGF-ß1 and SOD2 in U and J cybrids, respectively, along with decreased expression of IL-6 in J cybrids. TETRA 120 µg/mL induced decreased ROS levels in U and J cybrids, increased cellular metabolism of treated U cybrids, higher ratio of dead cells in K and J cybrids and declined ΔψM via all TETRA concentrations in all haplogroups. TETRA 120 µg/mL caused upregulation of IL-6 and CASP-3 genes in all cybrids, higher CASP-7 gene expression in K and U cybrids and downregulation of the SOD3 gene in K and U cybrids. Clinically relevant dosages of ciprofloxacin and tetracycline have potential adverse impacts on AMD cybrids possessing K, J and U mtDNA haplogroups in vitro.

Recruitment of participants for dementia research: interprofessional perspectives from primary care-based memory clinics.

Aim: To understand clinician attitudes and the barriers that impede research recruitment from specialized primary care-based memory clinics. Materials & methods: Clinicians completed a survey on attitudes and barriers to research recruitment from memory clinics. Results: Comfort and willingness to recruit for research were low to moderate and were lower for drug trials than for observational and non-drug trials. Respondents believed that it is important to have a standardized recruitment process. Identified barriers provide some insights into the factors that contribute to discomfort and lack of willingness to recruit research participants. Discussion: Findings can inform future efforts to develop a recruitment process that addresses identified barriers, while also providing an opportunity to increase participant recruitment in dementia research.

Recruitment of persons living with dementia from primary care for research is challenging and can be a barrier to study completion. Multispecialty Interprofessional Team (MINT) Memory Clinics may provide a unique opportunity for recruiting patients for research studies. In this study, clinicians completed a survey on attitudes and barriers to research recruitment from memory clinics in primary care. Clinician comfort and willingness to recruit for research were low to moderate. A number of barriers to recruiting patients for research from MINT Clinics were identified and included limited time, workload issues, limited information to share with patients, and their lack of knowledge about and experience with research. These study findings can help to develop a recruitment process that addresses identified barriers and helps to increase participant recruitment in dementia research.

Meiotic cDNA libraries reveal gene truncations and mitochondrial proteins important for competitive fitness in Saccharomyces cerevisiae.

Gametogenesis is an evolutionarily conserved developmental program whereby a diploid progenitor cell undergoes meiosis and cellular remodeling to differentiate into haploid gametes, the precursors for sexual reproduction. Even in the simple eukaryotic organism Saccharomyces cerevisiae, the meiotic transcriptome is very rich and complex, thereby necessitating new tools for functional studies. Here, we report the construction of 5 stage-specific, inducible complementary DNA libraries from meiotic cells that represent over 84% of the genes found in the budding yeast genome. We employed computational strategies to detect endogenous meiotic transcript isoforms as well as library-specific gene truncations. Furthermore, we developed a robust screening pipeline to test the effect of each complementary DNA on competitive fitness. Our multiday proof-of-principle time course revealed 877 complementary DNAs that were detrimental for competitive fitness when overexpressed. The list included mitochondrial proteins that cause dose-dependent disruption of cellular respiration as well as library-specific gene truncations that expose a dominant negative effect on competitive growth. Together, these high-quality complementary DNA libraries provide an important tool for systematically identifying meiotic genes, transcript isoforms, and protein domains that are important for a specific biological function.

Enabling Advance Care Planning in Dementia Care: A Primary Care Approach.

BACKGROUND: Lack of tools to support advance care planning (ACP) has been identified as a significant barrier to implementing these discussions. AIM: We pilot tested an ACP framework tool for use with persons living with dementia (PLWD) in primary care-based memory clinics and an Adult Day Program; this study describes user and recipient experiences with this framework. METHODS: We used a mixed methods approach. Health professionals completed an online survey following pilot testing and PLWD and substitute decision makers (SDM) completed survey immediately following the ACP discussion assessing their satisfaction (5-point scale) with the framework and exploring potential outcomes. Interviews with health professionals, PLWD, and SDM were conducted to gather more in-depth information on their perceptions of the ACP framework/ discussion. RESULTS: Surveys were completed by 12 health professionals, 13 PLWD, and 16 SDM. While PLWD and SDM were satisfied with the ACP discussion (M = 4.0/5), health professionals were minimally satisfied with the ease of use of the framework (M = 2.0/5), acceptability for patients (M = 2.4/5) and feasibility in practice (M = 1.9/5). Sixteen interviews were completed with 8 health professionals, 1 PLWD, and 7 SDM. While health professionals valued ACP, lack of time and training were identified barriers to framework use. SDM felt better prepared for future decisions and PLWD were put at ease, knowing that their wishes for care were understood. CONCLUSION: PLWD and SDM value the opportunity for ACP, and although health professionals identified some concerns with framework administration, they acknowledge the value and importance of ACP. Continuing efforts to refine ACP processes are justified.

European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects.

Background: Cisplatin, a powerful antitumor agent, causes formation of DNA adducts, and activation of apoptotic pathways. Presently, cisplatin resistance develops in up to 70% of patients but the underlying molecular mechanism(s) are unclear and there are no markers to determine which patients will become resistant. Mitochondria play a significant role not only in energy metabolism but also retrograde signaling (mitochondria to nucleus) that modulates inflammation, complement, and apoptosis pathways. Maternally inherited mitochondrial (mt) DNA can be classified into haplogroups representing different ethnic populations that have diverse susceptibilities to diseases and medications. Methods: Transmitochondrial cybrids, where all cell lines possess identical nuclear genomes but either the H (Southern European) or J (Northern European) mtDNA haplogroups, were treated with cisplatin and analyzed for differential responses related to viability, oxidative stress, and expression levels of genes associated with cancer, cisplatin-induced nephrotoxicity and resistance, apoptosis and signaling pathways. Results: The cisplatin-treated-J cybrids showed greater loss of cell viability along with lower levels of reactive oxygen species and mitochondrial membrane potential compared to cisplatin-treated-H cybrids. After cisplatin treatment, J cybrids showed increased gene expression of BAX, CASP3, and CYP51A, but lower levels of SFRP1 compared to untreated-J cybrids. The cisplatin-treated-H cybrids had elevated expression of CDKN1A/P21, which has a role in cisplatin toxicity, compared to untreated-H cybrids. The cisplatin-treated H had higher transcription levels of ABCC1, DHRS2/HEP27, and EFEMP1 compared to cisplatin-treated-J cybrids. Conclusions: Cybrid cell lines that contain identical nuclei but either H mtDNA mitochondria or J mtDNA mitochondria respond differently to cisplatin treatments suggesting involvement of the retrograde signaling (from mitochondria to nucleus) in the drug-induced cell death. Varying toxicities and transcription levels of the H vs. J cybrids after cisplatin treatment support the hypothesis that mtDNA variants play a role in the expression of genes affecting resistance and side effects of cisplatin.

Person-centered risk assessment framework: assessing and managing risk in older adults living with dementia.

AIM: This study pilot-tested the person-centered risk assessment framework (PCRAF), a framework for managing risk among persons living with dementia (PLWD) in primary care. METHODS: Healthcare providers (N = 7) piloting the PCRAF completed a survey, rating their satisfaction with the tool, and an interview to gather their perceptions of the PCRAF. PLWD and care partners (N = 12) completed a survey, rating their satisfaction with safety planning. RESULTS: Care providers were very satisfied with the tool; however, patient or care partner inability to perceive or understand safety risks was a challenge. Use of the PCRAF was perceived as an opportunity to empower self-management, gather PLWD and care partner perspectives, reduce burden for care partners and increase understanding of potential risks. Patients and care partners were very satisfied with the way in which they were included in the risk discussion. CONCLUSION: The PCRAF is a promising new tool to reduce risks associated with dementia.

Persons with dementia and care partners' perspectives on memory clinics in primary care.

AIMS: To understand persons with dementia (PWD) and care partners' experiences with the Primary Care Collaborative Memory Clinic (PCCMC) care model. METHODS: Interviews were conducted with a purposeful sample of PWD (n = 12) and care partners (N = 16) to identify their perspectives of care received in the clinic and suggestions for improvement. RESULTS: PWD and care partners were satisfied with care received within the PCCMC, had positive interactions with and perceived a strong sense of support from team members and felt listened to; the necessity of cognitive testing was recognized but disliked. CONCLUSIONS: The PCCMC care model can address many existing gaps in dementia care as experienced by PWD and care partners.

Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-ß-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-ß-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD.

A Content Analysis of Newspaper Coverage of the Seasonal Flu Vaccine in Ontario, Canada, October 2001 to March 2011.

Seasonal flu vaccine uptake has fallen dramatically over the past decade in Ontario, Canada, despite promotional efforts by public health officials. Media can be particularly influential in shaping the public response to seasonal flu vaccine campaigns. We therefore sought to identify the nature of the relationship between risk messages about getting the seasonal flu vaccine in newspaper coverage and the uptake of the vaccine by Ontarians between 2001 and 2010. A content analysis was conducted to quantify risk messages in newspaper content for each year of analysis. The quantification allowed us to test the correlation between the frequency of risk messages and vaccination rates. During the time period 2001-2010, vaccination rates were positively and significantly related to the frequency of risk messages in newspaper coverage (r = .691, p < .05). The most commonly identified risk messages related to the flu vaccine being ineffective, the flu vaccine being poorly understood by science, and the flu vaccine causing harm. Newspaper coverage plays an important role in shaping public response to seasonal flu vaccine campaigns. Public health officials should work alongside media to ensure that the public are exposed to information necessary for making informed decisions regarding vaccination.

Differential Expression of Complement Markers in Normal and AMD Transmitochondrial Cybrids.

PURPOSE: Variations in mitochondrial DNA (mtDNA) and abnormalities in the complement pathways have been implicated in the pathogenesis of age-related macular degeneration (AMD). This study was designed to determine the effects of mtDNA from AMD subjects on the complement pathway. METHODS: Transmitochondrial cybrids were prepared by fusing platelets from AMD and age-matched Normal subjects with Rho0 (lacking mtDNA) human ARPE-19 cells. Quantitative PCR and Western blotting were performed to examine gene and protein expression profiles, respectively, of complement markers in these cybrids. Bioenergetic profiles of Normal and AMD cybrids were examined using the Seahorse XF24 flux analyzer. RESULTS: Significant decreases in the gene and protein expression of complement inhibitors, along with significantly higher levels of complement activators, were found in AMD cybrids compared to Older-Normal cybrids. Seahorse flux data demonstrated that the bioenergetic profiles for Older-Normal and Older-AMD cybrid samples were similar to each other but were lower compared to Young-Normal cybrid samples. CONCLUSION: In summary, since all cybrids had identical nuclei and differed only in mtDNA content, the observed changes in components of complement pathways can be attributed to mtDNA variations in the AMD subjects, suggesting that mitochondrial genome and retrograde signaling play critical roles in this disease. Furthermore, the similar bioenergetic profiles of AMD and Older-Normal cybrids indicate that the signaling between mitochondria and nuclei are probably not via a respiratory pathway.

Central Retinal Vein Occlusion: A Review of Current Evidence-based Treatment Options.

A central retinal vein occlusion (CRVO) can induce an ischemic and hypoxic state with resulting sequelae of macular edema and neovascularization. Many treatment options have been studied. Our review aims to investigate the safety and efficacy of the multiple treatment options of CRVO. A PubMed and Cochrane literature search was performed. Well-controlled randomized clinical trials that demonstrated strong level 1 evidence-based on the rating scale developed by the British Centre for Evidence-Based Medicine were included. Seven clinical trials met inclusion criteria to be included in this review. These included studies that investigated the safety and efficacy of retinal photocoagulation (1 study), intravitreal steroid treatment (2 studies), and antivascular endothelial growth factor treatment (4 studies) for the treatment of CRVO. In addition, studies evaluating surgical treatment options for CRVO were also included. Many treatment modalities have been demonstrated to be safe and efficacious in the treatment of CRVO. These treatment options offer therapeutic benefits for patients and clinically superior visual acuity and perhaps the quality of life after suffering from a CRVO.

Image-Guided Endoscopic Combined With Deep Lateral Orbitotomy Removal of a Small Foreign Body at the Deep Lateral Orbital Apex.

To remove a small foreign body located at the deep orbit apex presents an extremely challenging problem. Small foreign bodies located in shallow lateral orbital and nasal orbital apex have been reported successfully removing in endoscopic surgery with the help of surgical navigation system. Here, the authors first describe successfully removal of a small foreign body at the deep lateral orbital apex with the help of image-guided endoscopic. A 56-year-old man presented with blurred vision and eye movement pain of the left eye while grinding metal 4 days prior to admission. A computed tomography scan showed a small metallic foreign body lodged in the deep lateral orbital apex. The foreign body was smoothly removed without any complications by endoscopic surgery under the help of surgical navigation system combined with deep lateral orbitotomy. Eye movement pain was disappeared and visual acuity was improved after surgery.

Cystoid macular edema and macular pigmentation associated with nab-Paclitaxel therapy.

PURPOSE: To report the first known case of retinal pigment epithelium hyperpigmentation changes and cystoid macular edema in a patient on nab-paclitaxel therapy. METHODS: Observational case report. RESULTS: A 72-year-old man on nab-paclitaxel therapy for non-small cell lung carcinoma developed cystoid macular edema with minimal capillary leakage with subsequent retinal pigment epithelium hyperpigmentation after resolution of cystoid macular edema. CONCLUSION: Nab-paclitaxel therapy may be associated with the development of retinal pigment epithelium hyperpigmentation in the setting of resolved minimal capillary leakage cystoid macular edema.