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• Using novel GWAS tools, we studied the genetic link between epilepsy and cognition. • General cognitive ability was estimated to be more polygenic than epilepsies. • We identified 66 epilepsy risk loci shared with general cognitive ability. • Of the 66 shared loci, 38 loci are novel epilepsy associations. • The study informs the shared genetic mechanisms between epilepsy and cognition. Cognitive impairment is prevalent among individuals with epilepsy, and increasing evidence indicates that genetic factors can underlie this relationship. However, the extent to which epilepsy subtypes differ in their genetic relationship with cognitive function, and information about the specific genetic variants involved remain largely unknown. We investigated the genetic relationship between epilepsies and general cognitive ability (COG) using complementary statistical tools, including linkage disequilibrium score (LDSC) regression, MiXeR and conjunctional false discovery rate (conjFDR). We analyzed genome-wide association study data on COG (n = 269,867) and common epilepsies (n = 27,559 cases, 42,436 controls), including the broad phenotypes 'all epilepsy', focal epilepsies and genetic generalized epilepsies (GGE), as well as specific subtypes. We functionally annotated the identified loci using several biological resources and validated the results in independent samples. Using MiXeR, COG (11.2k variants) was estimated to be almost four times more polygenic than 'all epilepsy', GGE, juvenile myoclonic epilepsy (JME), and childhood absence epilepsy (CAE) (2.5k – 2.9k variants). The other epilepsy phenotypes were insufficiently powered for MiXeR analysis. We quantified extensive genetic overlap between COG and epilepsy types, but with varying negative genetic correlations (-0.23 to -0.04). COG was estimated to share 2.9k variants with both GGE and 'all epilepsy', and 2.3k variants with both JME and CAE. Using conjFDR, we identified 66 distinct loci shared between COG and epilepsies, including novel associations for GGE (27), 'all epilepsy' (5), JME (5) and CAE (5). The implicated genes were significantly expressed in multiple brain regions. The results were validated in independent samples (COG: p = 3.62 × 10–7; 'all epilepsy': p = 2.58 × 10–3). Our study further dissects the substantial genetic basis shared between epilepsies and COG and identifies novel shared loci. An improved understanding of the genetic relationship between epilepsies and COG may lead to the development of novel comorbidity-targeted epilepsy treatments. [ABSTRACT FROM AUTHOR]

Genetic risk scores (GRSs) have been associated with CHD events and coronary artery calcium (CAC). We sought to evaluate the ability of a GRS to improve CAC as a screening test. Using the results of the most recent genome-wide association studies, we calculated a GRS in 6660 individuals from the Multi-Ethnic Study of Atherosclerosis and used it to determine the optimal age for an individual to undergo CAC screening. This 157-SNP GRS was predictive of non-zero CAC in individuals aged 44–54 and improved the positive yield of CAC as a screening test in this age group. The GRS was predictive of CAC in the entire multi-ethnic cohort and in each self-identified ethnic group (European American, Chinese American, African American, and Hispanic American) assessed individually. Given a specified target yield rate of non-zero CAC, an equation was derived to calculate an individual's optimal age to undergo CAC screening. In addition, a "direct-to-consumer" GRS consisting of only risk SNPs or their proxies that are directly genotyped on the 23andMe v5 chip (102-SNP GRS) was assessed in the European American population and was predictive of non-zero CAC in younger individuals. A GRS is associated with non-zero CAC in a multi-ethnic cohort and can be used to calculate the age of a person's first calcium scan, given a target threshold for CAC discovery. Furthermore, an inexpensive and widely available "direct-to-consumer" GRS was found to be a viable option to calculate the optimal age for CAC screening. [ABSTRACT FROM AUTHOR]

Highlights • Discriminating between glioblastoma (GBM) recurrence and treatment effects is challenging. • The utility of restriction spectrum imaging (RSI) in this setting was tested on 31 previously treated GBM patients. • The sensitivity, specificity, positive and negative predictive values of RSI were 84%, 86%, 95%, and 60%. • Histopathological review showed agreement between the RSI signal and cellularity of the tumor specimen. • These data support the use of RSI in the evaluation of treatment effects and tumor recurrence in GBM patients. Abstract Discriminating between tumor recurrence and treatment effects in glioblastoma patients undergoing radiation-temozolomide (RT/TMZ) therapy remains a major clinical challenge. Here, we report a pilot study to determine the utility of restriction spectrum imaging (RSI), an advanced diffusion-weighted MRI (DWI) technique that affords meso-scale resolution of cell density, in this assessment. A retrospective review of 31 patients with glioblastoma treated between 2011 and 2017 who underwent surgical resection or biopsy over radiographic concern for tumor recurrence following RT/TMZ was performed. All patients underwent RSI prior to surgical resection. Diagnostic utility of RSI for tumor recurrence was determined in comparison to histopathology. Analysis of surgical specimens revealed treatment effects in 6/31 patients (19%) and tumor recurrence in 25/31 patients (81%). There was general concordance between the measured RSI signal and histopathologic diagnosis. RSI was negative in 5/6 patients (83%) in patients with histological evidence of treatment effects. RSI was positive in 21/25 patients (84%) in patients with tumor recurrence. The sensitivity, specificity, positive and negative predictive values of RSI for glioblastoma recurrence were 84%, 86%, 95%, and 60%, respectively. Histopathologic review showed agreement between the RSI signal and cellularity of the tumor specimen. These data support the use of RSI in the evaluation of treatment effects versus tumor recurrence in glioblastoma patients after RT-TMZ therapy. [ABSTRACT FROM AUTHOR]

Highlights • Contrast enhancement can be correlated to gene expression of the underlying tumor. • Contrast enhancement intensity was associated with inflammatory response genes. • Tumor invasion genes were associated with heterogeneity of contrast enhancement. • Ratio of contrast enhancement volume was associated with metabolic stress genes. Abstract The physiologic processes underlying MRI contrast enhancement in glioblastoma patients remain poorly understood. MRIs of 148 glioblastoma subjects from The Cancer Imaging Archive were segmented using Iterative Probabilistic Voxel Labeling (IPVL). Three aspects of contrast enhancement (CE) were parametrized: the mean intensity of all CE voxels (CE i), the intensity heterogeneity in CE (CE h), and volumetric ratio of CE to necrosis (CE r). Associations between these parameters and patterns of gene expression were analyzed using DAVID functional enrichment analysis. Glioma CpG island methylator phenotype (G-CIMP) glioblastomas were poorly enhancing. Otherwise, no differences in CE parameters were found between proneural, neural, mesenchymal, and classical glioblastomas. High CE i was associated with expression of genes that mediate inflammatory responses. High CE h was associated with increased expression of genes that regulate remodeling of extracellular matrix (ECM) and endothelial permeability. High CE r was associated with increased expression of genes that mediate cellular response to stressful metabolic states, including hypoxia and starvation. Our results indicate that CE in glioblastoma is associated with distinct biological processes involved in inflammatory response and tissue hypoxia. Integrative analysis of these CE parameters may yield meaningful information pertaining to the biologic state of glioblastomas and guide future therapeutic paradigms. [ABSTRACT FROM AUTHOR]

Background Oral care of intubated patients is essential to the prevention of infection and patient discomfort. However, barriers to oral access and delivery of oral care have received little attention. Objective To determine prevalence and predictors of oral access difficulty. Design A prospective, observational, multi-center study. Settings Four intensive care units in Toronto, Canada. Participants Adult patients orally intubated for ≥48 h. Methods We screened consecutive admissions once a week to identify eligible participants. We observed each patient and asked the patient’s nurse about presence or absence of difficulty accessing the mouth to deliver oral care across three categories: (1) visualizing inside the mouth; (2) obtaining patient cooperation, or (3) inserting instruments for delivery of oral care. We asked nurses to identify presence of patient behaviors contributing to oral access difficulty and perceived level of difficulty on a Likert response scale. We examined patient and treatment characteristics associated with extreme difficulty (i.e., difficulty in all 3 categories) using a generalized estimating equation regression model. Results A total of 428 patients were observed, 58% admitted with a medical diagnosis. More than half (57%) had ≥2 oral devices up to maximum of 4. Oral care difficulty was identified in 83% of patients and rated as moderate to high for 217 (51%). Difficulty concerned visibility (74%), patient cooperation (55%), and space to insert instruments (53%). Patient behaviors contributing difficulty included coughing/gagging (60%), mouth closing (49%), biting (45%) and localizing (27%) during care. Variables associated with extreme difficulty included neurological (OR 1.92, 95% CI 1.42–2.60) or trauma admission (OR 1.83, 95% CI 1.16–2.89), lack of pain assessment or treatment in the 4 h prior to oral care (OR 1.43, 95% CI 1.14–1.80), more oral devices (OR 1.40, 95% CI 1.05–1.87), and duration of intubation (OR 1.05, 95% CI 1.01–1.10). Absence of documented agitation in the 4 h prior to oral care was associated with less difficulty (OR 0.68, 95% CI 0.54–0.86). Conclusions Oral care is complex and difficulties are experienced in a vast majority of intubated patients. Some difficulties are amenable to correction such as pain management. [ABSTRACT FROM AUTHOR]

Background Habitual practices are challenged by chronic illness. Cardiac rehabilitation (CR) involves changes to habits of diet, activity and tobacco use, and although it is effective for people with diabetes and cardiovascular disease (CVD), some participants are reportedly less likely to complete programs and adopt new health related practices. Within the first three months of enrolling in CR, attrition rates are highest for women and for people with diabetes. Previous studies and reviews indicate that altering habits is very difficult, and the social significance of such change requires further study. Purpose The purpose of the study was to use Bourdieu's concepts of habitus, capital and field to analyse the complexities of adopting new health practices within the first three months after enrolling in a CR program. We were particularly interested in gender issues. Methods Thirty-two men and women with diabetes and CVD were each interviewed twice within the first three months of their enrolment in one of three CR programs in Toronto, Canada. Results Attention to CR goals was not always the primary consideration for study participants. Instead, a central concern was to restore social dignity within other fields of activity, including family, friendships, and employment. Thus, study participants evolved improvised tactical approaches that combined both physical and social rehabilitation. These improvised tactics were socially embedded and blended new cultural capital with existing (often gendered) cultural capital and included: concealment , mobilizing cooperation , re-positioning , and push-back . Conclusions Our findings suggest that success in CR requires certain baseline levels of capital – including embodied, often gendered, cultural capital – and that efforts to follow CR recommendations may alter social positioning. [ABSTRACT FROM AUTHOR]

The article talks about the Medial Collateral Ligament (MCL) injury and its reconstruction, wherein topics include increased risk of Anterior Cruciate Ligament (ACL) injuries due to grade III MCL injury, how to physically examine MCL and ACL injuries, and surgical techniques for the same.

Summary A post hoc analysis was conducted using data from participants ( N = 631) with a DSM-IV-TR defined diagnosis of major depressive disorder (MDD) or bipolar disorder (BD) who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. It was determined that 20.6% of adults with mood disorders as part of the IMDCP fulfilled criteria for binge eating behaviour (BE). A higher percentage of individuals with BD met criteria for BE when compared to MDD (25.4% vs. 16%; p = 0.004) Univariate analyses indicated that individuals with a mood disorder (i.e., MDD or BD) and BE had greater scores on measures of anxiety severity ( p = 0.013) and higher rates of lifetime and current substance dependence, lifetime alcohol abuse ( p = 0.007, p = 0.006, and p = 0.015, respectively), Attention Deficit Hyperactivity Disorder (ADHD) ( p = 0.018) and measures of neuroticism ( p = 0.019). Individuals with a mood disorder and concurrent BE had lower scores on measures of conscientiousness ( p = 0.019). Individuals meeting criteria for BE were also significantly more likely to be obese (i.e., BMI ≥ 30 kg/m 2 ) (50% vs. 25.5%; p < 0.001). Binge eating is common amongst adults utilising tertiary care services principally for a mood disorder. The presence of BE identifies a subset of adults with mood disorders who have greater illness complexity as evidenced by course of illness variables and comorbidity. Screening for BE amongst individuals with mood disorders is warranted; parsing neurobiological substrates subserving non-homeostatic eating behaviour amongst individuals with mood disorders is a future research vista. [ABSTRACT FROM AUTHOR]

Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING). [ABSTRACT FROM AUTHOR]

Hemophilia is an X-linked recessive deficiency of clotting factor VIII (hemophilia A) or IX (hemophilia B) that can result in hemarthrosis of various joints, including the elbow. Left unchecked, this can lead to progressive joint destruction and significant morbidity. Appropriate management of the elbow joint through prophylactic measures, accurate imaging, and timely intervention is essential. Replacing or supplementing deficient factor with a plasma-derived or recombinant factor concentrate can minimize bleeding episodes. Joints should be routinely monitored for damage. Plain films offer an inexpensive window into bone disease and joint space changes but lack soft tissue detail and may not detect early changes. Magnetic resonance imaging provides a high level of detail but may be limited by its cost and need for sedation in younger patients. Ultrasound may not achieve the same level of resolution as magnetic resonance imaging, but it is increasingly used as a convenient, effective, and relatively inexpensive alternative. Patients who experience hemarthrosis of the elbow with joint damage often require more invasive treatment. Radiosynovectomy and arthroscopic synovectomy are effective at minimizing pain and preventing future bleeding episodes, whereas extensive joint damage may necessitate total elbow replacement. [ABSTRACT FROM AUTHOR]

The article discusses research examining the volume of the brain's hippocampus and atrophy in men aged 51-60 years participating in the Vietnam Era Twin Study of Aging (VETSA). Research methodology, which included magnetic resonance imaging (MRI)-derived hippocampus occupancy (HOC), differences in HOC between normal cognitive functioning, amnestic, and non-amnestic mild cognitive impairment (MCI), and neuroanatomical support for different neuropsychological definitions of MCI are discussed.

Background: Cognitive dysfunction and depression severity are key mediators of workplace adjustment in adults with major depressive disorder (MDD). Herein, we sought to determine the extent to which measures of depression severity and cognitive dysfunction were associated with perceived global disability, workplace performance and quality of life. Method: Apost hoc analysis was conducted using data from 260 participants with a diagnosis of DSM-IV-TR-defined MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. Measures of workplace function, global disability, depression severity, cognitive function, and quality of lifewere employed. These datawere analyzed using amultiple variable linear regression equations. Results: Perceived global disability was significantly predicted by clinical ratings of depression severity (β = 0.54), and perceived inattention (β = 0.24), accounting for 37% of the variance. In addition, perceived inattention (β = 0.58) and clinical ratings of depression severity (β = 0.18), were also significant predictors of perceived workplace productivity/performance, accounting for 38% of the variance. Finally, both clinical ratings of depression severity (β = -0.54), and perceived inattention (β = -0.18) were significant inverse predictors of perceived quality of life, accounting for 34% of the variance. Conclusion: The overarching finding in the analysis herein is that workplace performance variability is explained by subjective measures of cognitive dysfunction to a greater extent than total depression symptom severity. Conversely, total depression symptom severity accounts for a greater degree of variability in global measures of disability relative to cognitive measures. Treatment strategies for adults with major depressive disorder should address issues of cognitive dysfunction to improve workforce participation and performance. [ABSTRACT FROM AUTHOR]

Highlights: [•] Pre-existing frontal brain volume differences were found in future drinkers. [•] Adolescent drinkers showed greater brain volume reduction post-alcohol initiation. [•] Volume reduction occurred in subcortical and temporal regions. [•] QUARC is a useful tool for quantifying longitudinal brain volume changes. [Copyright &y& Elsevier]

• Patients with hematologic malignancies represent an increasing population in ICUs. • Symptoms of ICU patients with hematologic malignancies are minimally understood. • Poor symptom knowledge may negatively impact ICU care delivery and outcomes. Critically-ill patients with hematologic malignancies are increasingly admitted to intensive care units globally. Unrelieved symptoms during intensive care treatment may contribute to poor outcomes. To better understand the symptom experience(s) for critically-ill patients with hematologic malignancies. A scoping review was conducted searching Medline, CINAHL, PychInfo, Embase, and ProQuest databases, the Cochrane Library, and the grey literature between January 1st, 1990 and July 15th, 2020. Two authors independently reviewed articles for inclusion and verified abstracted data. Seventeen articles met inclusion criteria, including 11 cohort studies, 1 case-control study, and five review articles. No qualitative or mixed-method studies were retrieved. Symptoms were reported as the primary outcome across two studies (17%). Reported hematologic malignancy subtypes included leukemia and/or myelodysplastic syndrome (9, 53%), lymphoma (8, 47%), multiple myeloma (7, 41%), and aplastic anemia (2, 12%). The principal indication for ICU admission was respiratory failure, followed by cardiogenic shock/cardiac failure, endocrine disturbances, sepsis, and neurological failure. Only one study used validated tools for evaluating symptoms. Thirty-four symptoms were reported: altered level of consciousness/coma (35%); diarrhea (35%); nausea (35%); dyspnea (35%); vomiting (29%); and pain (29%). Two articles (13%) identified symptom clusters. There is minimal research that measures and explores the symptom experiences of critically-ill patients with hematologic malignancies. New research in this domain is needed to inform targeted symptom care for this vulnerable patient population. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The purpose of this study was to calculate the gain in signal-to-noise ratio (SNR) of four human abdominal tissues at 3.0 Tesla (T) compared with standard 1.5 T and to validate this calculation in vivo. Materials and Methods: The expected gain in SNR at 3.0 T in the liver, pancreas, spleen, and kidney compared with standard 1.5 T was approximated theoretically for a T2-weighted HASTE (half-Fourier acquisition single-shot turbo spin-echo) and a T1-weighted gradient-echo in- and opposed-phase sequence. Fifteen healthy male subjects underwent abdominal MR imaging using a 1.5 T and 3.0 T scanner. Coronal T2-weighted HASTE images and axial T1-weighted gradient-echo in- and opposed-phase images were acquired using the sequence parameters optimized by the vendor. Results: Except for opposed-phased imaging of pancreatic tissue, in vivo adjusted SNR values of all abdominal tissues were significantly higher at 3.0 T for all sequences (P < .05). The highest overall gain in SNR was achieved with the HASTE sequence ranging from 3.8-fold for renal imaging to 7.4-fold for hepatic imaging. The theoretical calculation of SNR gain was in good agreement with the experimentally measured gain in SNR for the HASTE and the in-phase sequence. Conclusion: High-field abdominal MR imaging at 3.0 T offers significantly higher SNR compared with standard 1.5 T MR imaging. [Copyright &y& Elsevier]

During late childhood behavioral changes, such as increased risk-taking and emotional reactivity, have been associated with the maturation of cortico-cortico and cortico-subcortical circuits. Understanding microstructural changes in both white matter and subcortical regions may aid our understanding of how individual differences in these behaviors emerge. Restriction spectrum imaging (RSI) is a framework for modelling diffusion-weighted imaging that decomposes the diffusion signal from a voxel into hindered, restricted, and free compartments. This yields greater specificity than conventional methods of characterizing diffusion. Using RSI, we quantified voxelwise restricted diffusion across the brain and measured age associations in a large sample (n = 8086) from the Adolescent Brain and Cognitive Development (ABCD) study aged 9–14 years. Older participants showed a higher restricted signal fraction across the brain, with the largest associations in subcortical regions, particularly the basal ganglia and ventral diencephalon. Importantly, age associations varied with respect to the cytoarchitecture within white matter fiber tracts and subcortical structures, for example age associations differed across thalamic nuclei. This suggests that age-related changes may map onto specific cell populations or circuits and highlights the utility of voxelwise compared to ROI-wise analyses. Future analyses will aim to understand the relevance of this microstructural developmental for behavioral outcomes. [ABSTRACT FROM AUTHOR]

Sustainable management of invasive arthropod pests requires insecticide-alternative, integrated strategies, such as protected culture. During 2016–2017, we studied the efficacy of exclusion netting at reducing infestation damage in fall-bearing raspberries caused by an invasive vinegar fly, Drosophila suzukii Matsumura. In an effort to manage outbreak infestation, we studied the efficacy of baited attracticidal spheres in netted and open plots. We also monitored the effects of netting on fruit marketability, abiotic conditions near the fruiting zone, and pollination effects due to exclusion. The results showed that while 80 g HDPE netting sufficiently deterred D. suzukii infestation early in the season, late-season infestation was often greater in netted zones compared to insecticide-treated open plots. The introduction of baited attracticidal spheres under the netting did not consistently reduce infestation, and in some cases even increased infestation late in the season, likely due to the presence of the olfactory bait. During both test years, fruit marketability was greater in netted plots compared with open plots, and in open plots, we observed more overripe fruit and additional feeding damage caused by other herbivores. However, the incidence of crumbly berry was higher in netted plots, indicating pollination deficits. Supplemental pollination appeared to reduce these effects. Although temperature did not differ significantly between netted and open plots, we also observed greater incidence of botrytis infection in netted plots containing attracticidal spheres, which was not present in netted plots alone. These data suggest that while exclusion netting may be a valuable tool for D. suzukii pest management, unless outbreak infestation under the netting and supplementation pollination are addressed, significant challenges may impede large scale implementation. • Spotted-wing drosophila is an invasive vinegar fly damaging berry crops worldwide. • We studied whether exclusion netting reduces SWD infestation in raspberries. • While netting reduced early season infestation, effective control required outbreak management. • Baited-attracticidal spheres may further increase infestation under netting. • Supplemental pollination may be required to reduce poor fruit set. [ABSTRACT FROM AUTHOR]