Blast-related mild traumatic brain injury: a Bayesian random-effects meta-analysis on the cognitive outcomes of concussion among military personnel.

Throughout their careers, many soldiers experience repeated blasts exposures from improvised explosive devices, which often involve head injury. Consequentially, blast-related mild Traumatic Brain Injury (mTBI) has become prevalent in modern conflicts, often occuring co-morbidly with psychiatric illness (e.g., post-traumatic stress disorder [PTSD]). In turn, a growing body of research has begun to explore the cognitive and psychiatric sequelae of blast-related mTBI. The current meta-analysis aimed to evaluate the chronic effects of blast-related mTBI on cognitive performance. A systematic review identified 9 studies reporting 12 samples meeting eligibility criteria. A Bayesian random-effects meta-analysis was conducted with cognitive construct and PTSD symptoms explored as moderators. The overall posterior mean effect size and Highest Density Interval (HDI) came to d = -0.12 [-0.21, -0.04], with executive function (-0.16 [-0.31, 0.00]), verbal delayed memory (-0.19 [-0.44, 0.06]) and processing speed (-0.11 [-0.26, 0.01]) presenting as the most sensitive cognitive domains to blast-related mTBI. When dividing executive function into diverse sub-constructs (i.e., working memory, inhibition, set-shifting), set-shifting presented the largest effect size (-0.33 [-0.55, -0.05]). PTSD symptoms did not predict cognitive effects sizes, ß PTSD = -0.02 [-0.23, 0.20]. The results indicate a subtle, but chronic cognitive impairment following mTBI, especially in set-shifting, a relevant aspect of executive attention. These findings are consistent with past meta-analyses on multiple mTBI and correspond with past neuroimaging research on the cognitive correlates of white matter damage common in mTBI. However, all studies had cross-sectional designs, which resulted in universally low quality ratings and limited the conclusions inferable from this meta-analysis.

Delivering the CRISPR/Cas9 system for engineering gene therapies: Recent cargo and delivery approaches for clinical translation.

Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9 (CRISPR/Cas9) has transformed our ability to edit the human genome selectively. This technology has quickly become the most standardized and reproducible gene editing tool available. Catalyzing rapid advances in biomedical research and genetic engineering, the CRISPR/Cas9 system offers great potential to provide diagnostic and therapeutic options for the prevention and treatment of currently incurable single-gene and more complex human diseases. However, significant barriers to the clinical application of CRISPR/Cas9 remain. While in vitro, ex vivo, and in vivo gene editing has been demonstrated extensively in a laboratory setting, the translation to clinical studies is currently limited by shortfalls in the precision, scalability, and efficiency of delivering CRISPR/Cas9-associated reagents to their intended therapeutic targets. To overcome these challenges, recent advancements manipulate both the delivery cargo and vehicles used to transport CRISPR/Cas9 reagents. With the choice of cargo informing the delivery vehicle, both must be optimized for precision and efficiency. This review aims to summarize current bioengineering approaches to applying CRISPR/Cas9 gene editing tools towards the development of emerging cellular therapeutics, focusing on its two main engineerable components: the delivery vehicle and the gene editing cargo it carries. The contemporary barriers to biomedical applications are discussed within the context of key considerations to be made in the optimization of CRISPR/Cas9 for widespread clinical translation.

A Coordinated Multi-study Analysis of the Longitudinal Association Between Handgrip Strength and Cognitive Function in Older Adults.

OBJECTIVE: Handgrip strength, an indicator of overall muscle strength, has been found to be associated with slower rate of cognitive decline and decreased risk for cognitive impairment and dementia. However, evaluating the replicability of associations between aging-related changes in physical and cognitive functioning is challenging due to differences in study designs and analytical models. A multiple-study coordinated analysis approach was used to generate new longitudinal results based on comparable construct-level measurements and identical statistical models and to facilitate replication and research synthesis. METHODS: We performed coordinated analysis on 9 cohort studies affiliated with the Integrative Analysis of Longitudinal Studies of Aging and Dementia (IALSA) research network. Bivariate linear mixed models were used to examine associations among individual differences in baseline level, rate of change, and occasion-specific variation across grip strength and indicators of cognitive function, including mental status, processing speed, attention and working memory, perceptual reasoning, verbal ability, and learning and memory. Results were summarized using meta-analysis. RESULTS: After adjustment for covariates, we found an overall moderate association between change in grip strength and change in each cognitive domain for both males and females: Average correlation coefficient was 0.55 (95% CI = 0.44-0.56). We also found a high level of heterogeneity in this association across studies. DISCUSSION: Meta-analytic results from nine longitudinal studies showed consistently positive associations between linear rates of change in grip strength and changes in cognitive functioning. Future work will benefit from the examination of individual patterns of change to understand the heterogeneity in rates of aging and health-related changes across physical and cognitive biomarkers.

Contributing Towards a Cultural Neuropsychology Assessment Decision-Making Framework: Comparison of WAIS-IV Norms from Colombia, Chile, Mexico, Spain, United States, and Canada.

OBJECTIVE: Test and normative data selection in cross-cultural neuropsychology remain a complex issue. Despite growing awareness, more studies and instruments are needed to adequately address the impact of cultural factors, such as quantity and quality of education. In this study, we examine the interpretive effects of applying six relevant WAIS-IV norms to a Colombian sample. METHOD: A sample of 305 highly educated Colombian corporate executives completed the WAIS-IV. Data were scored using norms from Colombia, Chile, Mexico, Spain, United States, and Canada and scores were compared using ANOVA. Additionally, a comparative sociodemographic framework was established to contextualize our sample to the standardization samples and populations of the six countries. RESULTS: Colombian and Chilean norms yielded systematically similar FSIQ/Index scores (mean range = 117-121), while incrementally lower scores were found with norms from Mexico (-3-9 points), Spain (-3-11 points), USA (-8-13 points), and Canada (-11-18 points). Verbal scores differed, with highest scores obtained with Mexican and Spanish norms. Working memory and processing speed scores had the lowest score agreement across norms. CONCLUSIONS: Although the Chilean norms are more frequently used in Colombia, the recently developed Colombian norms appear optimal for our sample; the scores do not have meaningful differences with those obtained with Chilean norms and offer local population representation fidelity. Mexican, Spanish, US, and Canadian norms underestimated WAIS-IV scores and distorted the sample's score distribution. Finally, verbal scores highlight potential education representation within Spanish and Mexican norms, while working memory and processing speed scores suggest cultural nuances likely captured within different norms.

A Multi-study Coordinated Meta-analysis of Pulmonary Function and Cognition in Aging.

BACKGROUND: Substantial research is dedicated to understanding the aging-related dynamics among individual differences in level, change, and variation across physical and cognitive abilities. Evaluating replicability and synthesizing these findings has been limited by differences in measurements and samples, and by study design and statistical analyses confounding between-person differences with within-person changes. In this article, we conducted a coordinated analysis and summary meta-analysis of new results on the aging-related dynamics linking pulmonary function and cognitive performance. METHODS: We performed coordinated analysis of bivariate growth models in data from 20,586 participants across eight longitudinal studies to examine individual differences in baseline level, rate of change, and occasion-specific variability in pulmonary and cognitive functioning. Results were summarized using meta-analysis. RESULTS: We found consistent but weak baseline and longitudinal associations in levels of pulmonary and cognitive functioning, but no associations in occasion-specific variability. CONCLUSIONS: Results provide limited evidence for a consistent link between simultaneous changes in pulmonary and cognitive function in a normal aging population. Further research is required to understand patterns of onset of decline and differences in rates of change within and across physical and cognitive functioning domains, both within-individuals and across countries and birth cohorts. Coordinated analysis provides an efficient and rigorous approach for replicating and comparing results across independent longitudinal studies.

Derivation, Replication, and Validity Analyses of a Screener for the Behavioral Assessment of Executive Functions in Young Adults.

Ecologically valid indicators of executive functions are designed to capture dysfunction not easily measured in a lab setting. Here, we present two studies on the development and validity analyses of a behavioral screener for executive functions among young adults. In Study 1, we derived a four-factor (problem solving, attentional control, behavioral control, and emotional control) behavioral screener using a sample of 765 individuals. We used invariance analyses to evaluate the screener's measurement reliability across sex. In Study 2, we replicated the screener derivation analyses using an independent sample of 197 undergraduates. To further examine the screener's validity, we evaluated it against a well-known executive functions rating scale. The four-factor model was supported in both samples and analyses provided support for this screener as a valid and reliable measure for everyday executive functions among young adults.