Search

Background: Associations between body mass index (BMI) and psychological distress (PD) have been reported; however, few longitudinal studies have accounted for likely life-course differences in BMI and PD stability, consistency, and their interplay across time. Methods: Via random intercepts cross-lagged panel models, we assessed the predictive effects (from BMI to PD or vice-versa) across the last two centuries in the Coronary Artery Risk Development in Young Adults [CARDIA, beginning in 1985-6] study using the Center for Epidemiological Studies-Depression Scale [CES-D], and in the National Child Development Study [NCDS, beginning in 1958] and British Cohort Study [BCS, beginning in 1970] using the Malaise Inventory [MI]), assessed at least 4 times in adult life. Findings: In CARDIA (n = 4724), NCDS58 (n = 7149) and BCS70 (n = 5967), autoregressive effects were stronger for BMI than for PD, meaning that carry-over effects from one occasion to the next were larger for BMI than for PD. Small interindividual correlations between traits of higher BMI and higher PD were identified among females (rfemale

Background: The detailed extent of neuroinvasion or deleterious brain changes resulting from COVID-19 and their time courses remain to be determined in relation to “long-haul” COVID-19 symptoms. Our objective is to determine whether there are alterations in functional brain imaging measures among people with COVID-19 after hospital discharge or self-isolation. Methods: This paper describes a protocol for NeuroCOVID-19, a longitudinal observational study of adults aged 20–75 years at Sunnybrook Health Sciences Centre in Toronto, Ontario, that began in April 2020. We aim to recruit 240 adults, 60 per group: people who contracted COVID-19 and were admitted to hospital (group 1), people who contracted COVID-19 and self-isolated (group 2), people who experienced influenza-like symptoms at acute presentation but tested negative for COVID-19 and self-isolated (group 3, control) and healthy people (group 4, control). Participants are excluded based on premorbid neurologic or severe psychiatric illness, unstable cardiovascular disease, and magnetic resonance imaging (MRI) contraindications. Initial and 3-month follow-up assessments include multiparametric brain MRI and electroencephalography. Sensation and cognition are assessed alongside neuropsychiatric assessments and symptom self-reports. We will test the data from the initial and follow-up assessments for group differences based on 3 outcome measures: MRI cerebral blood flow, MRI resting state fractional amplitude of low-frequency fluctuation and electroencephalography spectral power. Interpretation: If neurophysiologic alterations are detected in the COVID-19 groups in our NeuroCOVID-19 study, this information could inform future research regarding interventions for long-haul COVID-19. The study results will be disseminated to scientists, clinicians and COVID-19 survivors, as well as the public and private sectors to provide context on how brain measures relate to lingering symptoms.

BackgroundBidirectional longitudinal relationships between depression and diabetes have been observed, but the dominant direction of their temporal relationships remains controversial.MethodsThe random-intercept cross-lagged panel model decomposes observed variables into a latent intercept representing the traits, and occasion-specific latent ‘state’ variables. This permits correlations to be assessed between the traits, while longitudinal ‘cross-lagged’ associations and cross-sectional correlations can be assessed between occasion-specific latent variables. We examined dynamic relationships between depressive symptoms and insulin resistance across five visits over 20 years of adulthood in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Possible differences based on population group (Black v. White participants), sex and years of education were tested. Depressive symptoms and insulin resistance were quantified using the Center for Epidemiologic Studies Depression (CES-D) scale and the homeostatic model assessment for insulin resistance (HOMA-IR), respectively.ResultsAmong 4044 participants (baseline mean age 34.9 ± 3.7 years, 53% women, 51% Black participants), HOMA-IR and CES-D traits were weakly correlated (r = 0.081, p = 0.002). Some occasion-specific correlations, but no cross-lagged associations were observed overall. Longitudinal dynamics of these relationships differed by population groups such that HOMA-IR at age 50 was associated with CES-D score at age 55 (β = 0.076, p = 0.038) in White participants only. Longitudinal dynamics were consistent between sexes and based on education.ConclusionsThe relationship between depressive symptoms and insulin resistance was best characterized by weak correlations between occasion-specific states and enduring traits, with weak evidence that insulin resistance might be temporally associated with subsequent depressive symptoms among White participants later in adulthood.

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P, Liew et al. report the first large-scale examination using high-resolution neuroimaging of subcortical nuclei and sensorimotor behaviour in 828 stroke patients from 28 cohorts worldwide. They discovered novel associations between post-stroke sensorimotor behaviour and specific subcortical nuclei, providing new insight for stroke rehabilitation., Graphical Abstract Graphical Abstract

This manuscript provides an introduction to the special issue: Where are we now? A consolidation of the research on long-term impact of child sexual abuse. Over the past thirty years, there has been an explosion of research about the long-term impacts of childhood sexual abuse (CSA) on adult functioning and wellbeing. However, the consolidation of this vast literature has not kept up with the creation of new research despite the complexity and sophistication of these newer investigations. We have compiled a special issue of the Journal of Child Sexual Abuse to summarize and analyze this vast literature into a cohesive, consolidated whole. The goal of this issue was to consolidate recent research about the effects of CSA on alcohol and substance use in survivors, revictimization, sexual risk and sexual well-being and couple and parenting functioning.

Objective:Peripheral artery disease (PAD) is an atherothrombotic disease of the lower limbs with substantial morbidity and mortality. We used next-generation sequencing to identify genome-wide expression signatures associated with prevalent PAD and its outcomes.Approach and Results:We performed whole blood RNA sequencing among patients with severe symptomatic PAD undergoing lower extremity revascularization and controls. Dysregulated pathways and blood transcriptional modules were identified by comparing patients with PAD (n=42) to age- and sex-matched controls (N=29). The identified signature was compared in patients with PAD before LER with or without incident major adverse cardiac or limb events (MACLE). A novel microRNA associated with prevalent PAD and incident MACLE was then evaluated in a mouse hindlimb ischemia model. One hundred twenty-seven transcripts were differentially expressed (77 upregulated and 50 downregulated; adjustedP0.5) and analyzed using weighted gene co-expression network analysis. Weighted gene co-expression network analysis revealed blood modules enriched for immune activation, secretory granules, and coagulation in patients with PAD. Of these 127 differentially expressed transcripts, 40 were significantly associated with MACLE (log-rank false discovery rate Conclusions:A whole blood transcript signature identified patients with symptomatic PAD and PAD patients at increased risk of MACLE. A previously uncharacterized transcript microRNA-4477b was overexpressed in prevalent PAD, incident MACLE, and in a mouse hindlimb ischemia model. Our novel transcriptomic signature provides insight into potential mechanisms of patients with severe symptomatic PAD.

There are many case studies in the literature of cats, dogs and horses with subcutaneous emphysema. There is little written information on the treatment of subcutaneous emphysema in hedgehogs. This...

Objective Abnormal blood lipid levels are common in bipolar disorder (BD) and correlate with mood symptoms and neurocognition. However, studies have not examined the lipid-brain structure association in BD or youth. Methods This study examined low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglycerides, and total cholesterol (TC) levels in relation to brain structure utilizing T1-weighted images, among participants ages 13-20 with BD (n = 55) and healthy controls (HC; n = 47). General linear models investigated group differences in the association of lipids with anterior cingulate cortex (ACC), hippocampus, and inferior parietal lobe structure, controlling for age, sex, body mass index, and intracranial volume. For significant associations, post hoc within-group analyses were undertaken. Exploratory vertex-wise analyses further investigated group differences in the lipid-brain structure association. Results There were significant group differences in the association of LDL-C (β = -0.29 p = 0.001), and TC (β = -0.21 p = 0.016), with hippocampal volume, and triglycerides with ACC volume (β = -0.25 p = 0.01) and area (β = -0.26 p = 0.004). Elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC. Post hoc analyses revealed that elevated LDL-C (β = -0.27 p = 0.007) and reduced HDL-C (β = 0.24 p = 0.01) were associated with smaller hippocampal volume in the BD group. Exclusion of BD second-generation antipsychotic users did not alter these results. Vertex-wise analyses further showed that elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC, across the cortex. Conclusion Elevated lipids are associated with smaller brain structure in BD. Research evaluating lipid-brain structure associations prospectively and whether lipid optimization has salutary effects on brain structure is necessary.

Following effective treatment with systemic antifungal therapy, eyelid lesions from blastomycosis infection may be replaced by disfiguring fibrosis and scarring, which may be surgically challenging to correct. A 68-year-old man with biopsy-proven eyelid blastomycosis was treated with 6 months of oral voriconazole, but resolution of the lesion was complicated by cicatricial changes causing complete lower eyelid defect, epicanthal web, cicatricial mechanical ptosis, and skin plaques. Although repair adhered to the fundamentals of eyelid reconstruction, cicatricial changes associated with blastomycosis infection necessitated a modified approach and attachment sites. A tarsoconjunctival flap (Hughes flap) with modified flap connections utilizing cicatrix and remaining viable tissue was employed to reconstruct the lower eyelid defect and combined with tissue advancement using a Mustardé four-flap epicanthoplasty and post-auricular full-thickness skin graft. Satisfactory cosmetic outcome was achieved at last follow-up of 3.5 months postoperatively. This case demonstrates a feasible technique for reconstruction of significant eyelid defects following robust cicatricial changes such as those after blastomycosis. This report also presents the first description of reconstruction of lower eyelid defect and of posterior lamellar loss after blastomycosis infection.

Consistent cerebral blood flow (CBF) is fundamental to brain function. Cerebral autoregulation ensures CBF stability. Chronic hypertension can lead to disrupted cerebral autoregulation in older people, potentially leading to blood pressure levels interfering with CBF. This study tested whether low BP and AHD use are associated with contemporaneous low CBF, and whether longitudinal change in BP is associated with change in CBF, using arterial spin labelling (ASL) MRI, in a prospective longitudinal cohort of 186 community-dwelling older individuals with hypertension (77 ± 3 years, 53% female), 125 (67%) of whom with 3-year follow-up. Diastolic blood pressure, systolic blood pressure, mean arterial pressure, and pulse pressure were assessed as blood pressure parameters. As additional cerebrovascular marker, we evaluated the ASL signal spatial coefficient of variation (ASL SCoV), a measure of ASL signal heterogeneity that may reflect cerebrovascular health. We found no associations between any of the blood pressure measures and concurrent CBF nor between changes in blood pressure measures and CBF over three-year follow-up. Antihypertensive use was associated with lower grey matter CBF (−5.49 ml/100 g/min, 95%CI = −10.7|−0.27, p = 0.04) and higher ASL SCoV (0.32 SD, 95%CI = 0.12|0.52, p = 0.002). These results warrant future research on the potential relations between antihypertensive use and cerebral perfusion.

To investigate the patterns of care and outcomes of treatment of early stage tonsil cancers, controlling for human papillomavirus (HPV) status.Historical cohort study.National Cancer Database (NCDB).Review of the NCDB between 2010 and 2017 for all T1-2N0M0 tonsillar squamous cell carcinoma (SCC). Demographics, clinical characteristics, HPV status, treatment regimens, and survival were analyzed.A total of 4720 patients were identified with early stage SCC of the tonsil. Most were tested for HPV (2759 [58.5%]). Among tested patients, 1758 (63.7%) were positive for HPV and 1001 (36.3%) were negative for HPV. HPV-positive patients had higher 3-year survival compared to HPV-negative patients (93.2% vs 77.8%,Surgical- or radiation-based treatment resulted in similar survival in early stage HPV-positive tonsil cancer. Surgical-based treatments were associated with longer survival in HPV-negative cancers. These findings should be further investigated in a randomized prospective trial.

Background and Purpose: Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression. Methods: Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003–2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke. Results: Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X 2 =5.4; P =0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHR Depression =1.57 [1.24–1.98]) and incident dementia (aHR Depression =1.85 [1.40–2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHR Diabetes =1.20 [1.12–1.29]; aHR Depression =1.19 [1.04–1.37]), incident dementia (aHR Diabetes =1.14 [1.06–1.23]; aHR Depression =1.27 [1.08–1.49]), stroke/transient ischemic attack readmission (aHR Diabetes =1.18 [1.10–1.26]; aHR Depression =1.24 [1.07–1.42]), and all-cause mortality (aHR Diabetes =1.29 [1.23–1.36]; aHR Depression =1.16 [1.05–1.29]). Conclusions: The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.

INTRODUCTION Cardiovascular disease (CVD) is exceedingly prevalent, and occurs prematurely in individuals with bipolar disorder (BD). Cardiorespiratory fitness (CRF), arguably the most important modifiable CVD risk factor, is also associated with brain structure and function. There is a gap in knowledge regarding CRF in BD, particularly in relation to brain structure. METHODS Adolescents with BD (n = 54) and healthy controls (HC; n = 53) completed semi-structured diagnostic interviews, self-report questionnaires, and 20 minutes of cardiorespiratory exercise at 60-80% of estimated maximum heart rate (HR) on a bicycle ergometer. Average power (watts/kg) within this HR range served as a previously validated proxy for CRF. Brain magnetic resonance imaging (MRI) structural analysis was done using FreeSurfer. Analyses controlled for age and sex. RESULTS CRF was significantly lower in BD vs HC (0.91 ± 0.32 vs 1.01 ± 0.30, p = 0.03, F = 4.66, df=1, η2 =0.04). Within BD, greater depression symptoms were associated with lower CRF (P = .02), and greater physical activity (PA) was associated with greater CRF (P BD; P = .03) and sex (M > F; P

In the present study, we tested the hypothesis that higher amyloid-beta (Aβ) burden at baseline is associated with greater longitudinal decline in body mass index (BMI) in clinically normal adults. Participants from the Harvard Aging Brain Study (n = 312) and the Alzheimer's Disease Neuroimaging Initiative (n = 336) underwent Aβ positron emission tomography at baseline. BMI was assessed longitudinally over a median of >4 years. Linear mixed models showed that higher baseline Aβ burden was significantly associated with greater decline in BMI in both the Harvard Aging Brain Study (t = −1.93; p = 0.05) and Alzheimer's Disease Neuroimaging Initiative cohorts (t = −2.54; p = 0.01), after adjusting for covariates, including cognitive performance and depressive symptoms. In addition, the association of Aβ burden with longitudinal decline in BMI persisted in both cohorts after excluding participants with diabetes/endocrine disturbances and participants classified as underweight or obese (BMI 30). These findings suggest that decline in BMI in clinically normal adults may be an early manifestation related to cerebral amyloidosis that precedes objective cognitive impairment. Therefore, unintentional BMI decline in otherwise healthy individuals might alert clinicians to increased risk of Alzheimer's disease.

Introduction Few studies have examined memory decline among patients with type 2 diabetes using different oral hypoglycemic drugs. Methods Participants with normal cognition (NC) or Alzheimer's disease (AD) dementia using a hypoglycemic medication (2005 to 2019) were identified from the National Alzheimer's Coordinating Center database. Delayed memory was assessed using the Wechsler Memory Scale Revised–Logical Memory test. Associations between oral drug classes and memory over time were examined using mixed‐effects models with inverse probability treatment weights. Results In NC (n = 1192), metformin use was associated with better memory performance over time, whereas in AD (n = 807), dipeptidyl peptidase‐4 (DPP4) inhibitor use was associated with a slower rate of memory decline. Interaction effects suggested greater benefit associated with DPP4 inhibitor use among APOE ε4 carriers. Discussion Associations between different oral hypoglycemic drugs and memory change were not consistent between cognitively normal elderly and those with AD dementia. APOE ε4 genotype modified some relationships.

We asked whether pharmacological stimulation of endogenous neural precursor cells (NPCs) may promote cognitive recovery and brain repair, focusing on the drug metformin, in parallel rodent and human studies of radiation injury. In the rodent cranial radiation model, we found that metformin enhanced the recovery of NPCs in the dentate gyrus, with sex-dependent effects on neurogenesis and cognition. A pilot double-blind, placebo-controlled crossover trial was conducted (ClinicalTrials.gov, NCT02040376) in survivors of pediatric brain tumors who had been treated with cranial radiation. Safety, feasibility, cognitive tests and MRI measures of white matter and the hippocampus were evaluated as endpoints. Twenty-four participants consented and were randomly assigned to complete 12-week cycles of metformin (A) and placebo (B) in either an AB or BA sequence with a 10-week washout period at crossover. Blood draws were conducted to monitor safety. Feasibility was assessed as recruitment rate, medication adherence and procedural adherence. Linear mixed modeling was used to examine cognitive and MRI outcomes as a function of cycle, sequence and treatment. We found no clinically relevant safety concerns and no serious adverse events associated with metformin. Sequence effects were observed for all cognitive outcomes in our linear mixed models. For the subset of participants with complete data in cycle 1, metformin was associated with better performance than placebo on tests of declarative and working memory. We present evidence that a clinical trial examining the effects of metformin on cognition and brain structure is feasible in long-term survivors of pediatric brain tumors and that metformin is safe to use and tolerable in this population. This pilot trial was not intended to test the efficacy of metformin for cognitive recovery and brain growth, but the preliminary results are encouraging and warrant further investigation in a large multicenter phase 3 trial.

PURPOSE To describe the utilization of customized made-to-specification porous polyethylene implants and to evaluate clinical characteristics and outcomes of patients who received these implants for unilateral orbital defects. METHODS A retrospective review of 9 patients was performed. Three-dimensional surface models were generated from high-resolution computed tomography scans. Orbital constructs were modeled after the normal, contralateral orbits and mirrored across the vertical midline to generate the target orbital implant. Measured outcomes included globe position, extraocular motility, facial symmetry, and diplopia. RESULTS Patients ranged 25-56 years old (mean: 37) and included 6 males and 3 females. Cases consisted of 6 orbital floor fractures due to trauma, 1 lateral wall defect after neurofibroma resection, 1 floor/medial wall defect after myxoma resection, and 1 superior orbital rim defect after intraosseous hemangioma resection. Seven patients had ≥1 prior repair. All patients had previous hard and soft tissue defects and varying degrees of restrictive globe motility. Patients exhibited improved ductions after implant placement and improved facial appearance and symmetry. Post-operatively, 1 patient was found to have a small orbital hematoma between the implant and orbital floor, resolving within weeks. CONCLUSIONS Precision, personalized oculofacial surgery is the next wave in tailoring surgical care to the individual patient. Customizable implants are manufactured to specifically mold to an individual patient's unique bony architecture, which can lead to superior outcomes in reconstructing orbital and craniofacial bony defects. This technique is particularly useful in patients with prior unsuccessful repair.

The transient increase in torque of an electrically evoked twitch following a voluntary contraction is called postactivation potentiation (PAP). Phosphorylation of myosin regulatory light chains is the most accepted mechanism explaining the enhanced electrically evoked twitch torque. While many authors attribute voluntary postactivation performance enhancement (PAPE) to the positive effects of PAP, few actually confirmed that contraction was indeed potentiated using electrical stimulation (twitch response) at the time that PAPE was measured. Thus, this review aims to investigate if increases in voluntary performance after a conditioning contraction (CC) are related to the PAP phenomenon. For this, studies that confirmed the presence of PAP through an evoked response after a voluntary CC and concurrently evaluated PAPE were reviewed. Some studies reported increases in PAPE when PAP reaches extremely high values. However, PAPE has also been reported when PAP was not present, and unchanged/diminished performance has been identified when PAP was present. This range of observations demonstrates that mechanisms of PAPE are different from mechanisms of PAP. These mechanisms of PAPE still need to be understood and those studying PAPE should not assume that regulatory light chain phosphorylation is the mechanism for such enhanced voluntary performance.Novelty The occurrence of PAP does not necessarily mean that the voluntary performance will be improved. Improvement in voluntary performance is sometimes observed when the PAP level reaches extremely high values. Other mechanisms may be more relevant than that for PAP in the manifestation of acute increases in performance following a conditioning contraction.

Repository corticotropin injection (RCI) has recently gained attention in the field of ocular inflammatory disease. Data supporting the use of RCI therapy in ocular inflammation are limited to case reports or small series subject to publication bias toward positive results. How this therapy differs significantly from oral corticosteroids, which are significantly cheaper, is unknown. Clinical trials to investigate the efficacy of RCI are currently limited to open-labeled non-comparative studies. Side effects of RCI are not insignificant, have been reported in other fields of medicine, and require further scrutiny. Finally, the price of RCI has skyrocketed with average yearly cost of therapy estimated to be between $480,000-$850,000 with allegations of the RCI manufacturing drug company providing remuneration to induce healthcare providers to prescribe RCIs but without any repercussions from a regulatory standpoint. The significant cost of RCI combined with lack of evidence-based guidance on efficacy, safety, and indications for use in ocular inflammation warrant caution in utilizing this therapy.

International audience; This article details the design of a co-created, evidence-based biofeedback therapy game addressing the research question: is the biofeedback implementation efficient, effective, and engaging for promoting quality movement during a therapy game focused on hand gestures? First, we engaged nine young people with Cerebral Palsy (CP) as design partners to co-create the biofeedback implementation. A commercially available, tap-controlled game was converted into a gesture-controlled game with added biofeedback. The game is controlled by forearm electromyography and inertial sensors. Changes required to integrate biofeedback are described in detail and highlight the importance of closely linking movement quality to short- and long-term game rewards. After development, 19 participants (8–17 years old) with CP played the game at home for 4 weeks. Participants played 17 ± 9 min/day, 4 ± 1 day/week. The biofeedback implementation proved efficient (i.e. participants reduced compensatory arm movements by 10.2 ± 4.0%), effective (i.e. participants made higher quality gestures over time), and engaging (i.e. participants consistently chose to review biofeedback). Participants found the game usable and enjoyable. Biofeedback design in therapy games should consider principles of motor learning, best practices in video game design, and user perspectives. Design recommendations for integrating biofeedback into therapy games are compiled in an infographic to support interdisciplinary knowledge sharing.

Objectives To systematically characterize intra‐limb patterns of skeletal plasticity to loading among living women, in order to better understand regional complexity in structural adaptation within the lower limb and more accurately infer behavior in the past. Materials and methods We used peripheral quantitative computed tomography imaging of the femur, tibia, first and second metatarsals to quantify bone morphology among female controls and athletes representative of either terrestrial or marine mobility, grouped by loading category (odd‐impact, repetitive low‐impact, and high‐magnitude). Parameters included midshaft bone density, areas, rigidity, and shape, epiphyseal bone densities and areas. We assessed between‐group differences and the influence of training history on significant variation among the loading groups. Results Terrestrial mobility strategies were best distinguished by significant midshaft periosteal hypertrophy across the lower limb/foot relative to controls, and by particularly high midshaft femoral and tibial cortical bone areas relative to rowers. Enhanced midshaft bone area was typically paired with decreased bone density among athlete groups. Sport‐specific variation in training duration/timing was significantly correlated with multiple midshaft parameters. Discussion Results demonstrate characteristic patterns of intra‐limb adaptation to terrestrial and marine mobility strategies among active women relative to controls, and highlight components of these patterns that may be shaped in part by differences in loading duration/timing. Additionally, our findings support constraints on skeletal variation in the distal tibia and foot relative to more proximal locations about the knee among living women. For example, metatarsal variation was constrained, but where present reflected sport‐specific variation in force distribution in the foot.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

BACKGROUND Arterial stiffness in large arteries is a risk factor for cerebral small vessel disease and neurodegeneration. The challenge of accessing intracranial pulsatility noninvasively is one reason few studies provide empirical insight on the relationship between large artery and tissue pulsatility in the human brain. PURPOSE To investigate the association between the functional magnetic resonance imaging (fMRI)-derived cardiac-related pulsatility in the insular cortex and the ultrasound-derived pulsatility index in the middle cerebral artery (MCA-PI). STUDY TYPE Cross-sectional. POPULATION Younger adults (11; 25 ± 4 years) and older adults with and without cardiovascular risk factors (44; 70 ± 6 years). FIELD STRENGTH/SEQUENCE T1 -weighted, fluid attenuated inversion recovery, and T2 *-weighted blood oxygenation level-dependent (BOLD) sequences at 3T. ASSESSMENT MCA-PI and cardiac-related pulsatility were assessed at rest by transcranial Doppler ultrasound and BOLD fMRI, respectively. STATISTICAL TESTS Multivariate analyses of covariance between MCA-PI and cardiac-related pulsatility. Analysis of variance was used to assess regional differences. RESULTS MCA-PI was associated with cardiac-related insular pulsatility (P = 0.037), but not whole-brain pulsatility (P = 0.81). Left insular pulsatility was higher than right insular pulsatility (P

Purpose: Exercise after breast cancer diagnosis is associated with lower cancer-specific mortality, but the biological mechanisms through which exercise impacts breast cancer are not fully understood. The Pre-Operative Health and Body (PreHAB) Study was a randomized window-of-opportunity trial designed to test the impact of exercise on Ki-67, gene expression, and other biomarkers in women with breast cancer. Experimental Design: Inactive women with newly diagnosed breast cancer were randomized to an exercise intervention or mind–body control group, and participated in the study between enrollment and surgery (mean 29.3 days). Tumor and serum were collected at baseline and surgery. Results: Forty-nine women were randomized (27 exercise, 22 control). At baseline, mean age was 52.6, body mass index was 30.2 kg/m2, and exercise was 49 minutes/week. Exercise participants significantly increased exercise versus controls (203 vs. 23 minutes/week, P < 0.0001). There were no differences in changes of expression of Ki-67, insulin receptor, and cleaved caspase-3 in exercise participants versus controls. KEGG pathway analysis demonstrated significant upregulation of 18 unique pathways between the baseline biopsy and surgical excision in exercise participants and none in control participants (q < 0.1). Top-ranked pathways included several implicated in immunity and inflammation. Exploratory analysis of tumor immune infiltrates demonstrated a trend toward a decrease in FOXP3+ cells in exercise versus control participants over the intervention period (P = 0.08). Conclusions: A window-of-opportunity exercise intervention did not impact proliferation but led to alterations in gene expression in breast tumors, suggesting that exercise may have a direct effect on breast cancer. See related commentary by Koelwyn and Jones, p. 5179

Background Cardiovascular conditions contribute to brain volume loss, reduced cerebrovascular health, and increased dementia risk in aging adults. Altered hippocampal connectivity has also been observed in individuals with cardiovascular conditions, yet the functional consequences of these changes remain unclear. In the present study, we collected functional magnetic resonance imaging data during memory encoding and used a psychophysiological interaction analysis to examine whether cardiovascular burden, indexed using the Framingham risk score, was associated with encoding-related hippocampal connectivity and task performance in cognitively-intact older adults between 65 and 85 years of age. Our goal was to better understand the early functional consequences of vascular and metabolic dysfunction in those at risk for cognitive decline. Results High Framingham risk scores were associated with lower total brain volumes. In addition, those with high Framingham risk scores showed an altered relationship between left hippocampal-medial prefrontal coupling and task performance compared to those with low Framingham risk scores. Specifically, we found a significant interaction of Framingham risk and learning on connectivity between the left hippocampus and primarily left midline prefrontal regions comprising the left ventral anterior cingulate cortex and medial prefrontal cortex. Those with lower Framingham risk scores showed a pattern of weaker connectivity between left hippocampal and medial prefrontal regions associated with better task performance. Those with higher Framingham risk scores showed the opposite pattern; stronger connectivity was associated with better performance. Conclusions Findings from the current study show that amongst older adults with cardiovascular conditions, higher Framingham risk is associated with lower brain volume and altered left hippocampal-medial prefrontal coupling during task performance compared to those with lower Framingham risk scores. This may reflect a compensatory mechanism in support of memory function and suggests that older adults with elevated cardiovascular risk are vulnerable to early Alzheimer disease-like dysfunction within the episodic memory system.

Background The Global Rating Scale (GRS) is a web-based self-assessment quality improvement tool used to identify gaps in health care, change the focus to patient-centred care and standardize care. There are four levels of achievement ranging from basic-(D) to excellent-(A) service delivery. The goal was to develop a GRS for inflammatory bowel disease (IBD) to improve the quality of care for patients on a system level. Methods The IBD GRS was developed through an iterative process and modeled upon the successful endoscopy GRS programs in the United Kingdom and Canada. Dimensions, items and statements were drafted based on expert opinions, patient-informed quality indicators and best available evidence, then reviewed and modified by a core committee. A working group of IBD and GRS experts voted in-person to establish consensus on the inclusion and quality of statements. Results Two dimensions (Clinical Quality and Quality of Patient Experience), 10 items and 89 statements made up the IBD GRS. There was a 100% response rate for each of the 40 votes for statements in the IBD GRS. All statements within each level received a mean rating score between four (agree) and five (strongly agree). Revisions agreed upon during the voting process were incorporated into the IBD GRS. Group consensus was achieved on the inclusion of statements, and 10 items were selected as standards within the two dimensions. Conclusions We have developed the first IBD GRS with the aim of improving quality of care through ongoing evaluations and improvements by health care teams, focusing on patient-centred care.

Objectives Vascular‐brain associations are well established in adults but neglected in youth and psychiatric populations, who are at greater cardiovascular risk. We therefore examined the association of retinal vascular caliber with regional brain structure in adolescents with and without bipolar disorder (BD). Methods One hundred and three adolescents (n = 51 BD, n = 52 healthy control [HC]) completed retinal fundus imaging, yielding arteriolar and venular diameters, followed by T1‐weighted 3‐Tesla MRI. Region of interest (ROI) analyses examined ventrolateral prefrontal cortex (vlPFC) and ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, and hippocampus, complemented by vertex‐wise analyses. Linear regression assessed the association between retinal measures and brain structure, adjusting for covariates including age, sex, BMI, and intracranial volume (ICV). Results In the overall sample, arteriolar caliber was negatively associated with ACC volume (β = −0.20, puncorrected = .046) and surface area (β = −0.19, puncorrected = .049). There were no other significant ROI findings. Vertex‐wise analyses detected several significant positive bilateral associations of arteriovenous ratio (AVR) with volume and surface area in regions including rostral middle frontal gyrus (left p = .001; right p = .006), isthmus cingulate cortex (left and right p

OBJECTIVE: To investigate the preliminary efficacy of a high n-3 plus low n-6 (H3-L6) dietary intervention in improving mood stability in Bipolar Disorder (BD) when compared to dietary intervention with usual U.S. levels of n-6 and n-3 polyunsaturated fatty acid (PUFA) intakes (control diet, CD). METHODS: This 2-arm, parallel-group, randomized, modified double-blind, controlled 48-week study of 12-week intensive diet intervention in subjects with BD was conducted at a single suburban-rural site in the mid-Atlantic region. Participants with DSM-IV TR BD I or II with hypomanic or depressive symptoms were randomized, stratified on gender (N = 82). The intervention included the provision of group-specific study foods and dietary counseling. Variability of mood symptoms was measured by a twice-daily, 12-week ecological momentary analysis (EMA) paradigm, and group differences were analyzed using multilevel models. Circulating n-3 and n-6 fatty acids were measured at baseline and after 4, 8, and 12 weeks of diet exposure. RESULTS: All 82 randomized participants were included in biochemical analyses. Seventy participants completed at least 2 EMA surveys and were included in primary EMA analyses. Variability in mood, energy, irritability, and pain as measured using EMA was reduced in the H3-L6 group compared to the CD group. No significant differences in mean ratings of mood symptoms, or any other symptom measures, were detected. The dietary intervention effect on target PUFAs significantly differed by the group over time. CONCLUSIONS: A dietary intervention adjunctive to usual care showed preliminary efficacy in improving variability in mood symptoms in participants with BD. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02272010.

Background The incidence of ischemic stroke has increased among adults aged 18 to 64 years, yet little is known about relationships between specific risk factors and outcomes. This study investigates in‐hospital and long‐term outcomes in patients with stroke aged Methods and Results Consecutive patients aged Conclusions Focused secondary prevention and risk factor management may be needed to address poor long‐term outcomes for patients with stroke aged

Background Early in the pandemic, inadequate SARS-CoV-2 testing limited understanding of transmission. Chief among barriers to large-scale testing was unknown feasibility, particularly in non-urban areas. Our objective was to report methods of high-volume, comprehensive SARS-CoV-2 testing, offering one model to augment disease surveillance in a rural community. Methods A community-university partnership created an operational site used to test most residents of Bolinas, California regardless of symptoms in 4 days (April 20th – April 23rd, 2020). Prior to testing, key preparatory elements included community mobilization, pre-registration, volunteer recruitment, and data management. On day of testing, participants were directed to a testing lane after site entry. An administrator viewed the lane-specific queue and pre-prepared test kits, linked to participants’ records. Medical personnel performed sample collection, which included finger prick with blood collection to run laboratory-based antibody testing and respiratory specimen collection for polymerase chain reaction (PCR). Results Using this 4-lane model, 1,840 participants were tested in 4 days. A median of 57 participants (IQR 47–67) were tested hourly. The fewest participants were tested on day 1 (n = 338 participants), an intentionally lower volume day, increasing to n = 571 participants on day 4. The number of testing teams was also increased to two per lane to allow simultaneous testing of multiple participants on days 2–4. Consistent staffing on all days helped optimize proficiency, and strong community partnership was essential from planning through execution. Conclusions High-volume ascertainment of SARS-CoV-2 prevalence by PCR and antibody testing was feasible when conducted in a community-led, drive-through model in a non-urban area.

The Trail Making Test (TMT) is widely used to probe brain function and is performed with pen and paper, involving Parts A (linking numbers) and B (alternating between linking numbers and letters). The relationship between TMT performance and the underlying brain activity remains to be characterized in detail. Accordingly, sixteen healthy young adults performed the TMT using a touch-sensitive tablet to capture enhanced performance metrics, such as the speed of linking movements, during simultaneous electroencephalography (EEG). Linking and non-linking periods were derived as estimates of the time spent executing and preparing movements, respectively. The seconds per link (SPL) was also used to quantify TMT performance. A strong effect of TMT Part A and B was observed on the SPL value as expected (Part B showing increased SPL value); whereas the EEG results indicated robust effects of linking and non-linking periods in multiple frequency bands, and effects consistent with the underlying cognitive demands of the test.

Background: Healthy diet and exercise are associated with reduced risk of dementia in older adults. Evidence for the impact of clinical trials on brain health is less consistent, especially with dietary interventions which often rely on varying intervention approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counselling approach among older adults with vascular risk factors (VRFs) and early dementia risk. Methods: Participants with VRF’s and SCD or early MCI were cluster randomized into the intervention (exercise + Baycrest Brain-healthy Eating Approach (EX+DIET)) or control group (exercise + brain health education (EX+ED)). Both groups participated in 1-hour of supervised exercise per week and were prescribed additional exercise at home. EX+DIET involved 1-hour per week of group-based dietary counselling comprising didactic education focused on brain healthy eating recommendations, goal setting and strategy training. Whereas, EX+ED involved 1-hour per week of group-based brain health education. The primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included fitness, diet, cognition, and blood biomarkers. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy. Results: Of 190 older adults contacted, 14 (7%) were eligible and randomized, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and diet/education sessions on average. All 6-month follow-up assessments pre-COVID-19 were completed but disruptions to testing during the pandemic resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the intervention. Mean improvements in peak oxygen consumption were observed in both EX+DIET (d = .98) and EX+ED (d =1.15) groups. Substantial improvements in diet and HbA1c were observed in the EX+DIET group compared to EX+ED (d = 1.75 and 1.07, respectively). Conclusions: High adherence and retention rates were observed among LEAD participants and preliminary findings illustrate improvements in cardiorespiratory fitness and diet quality. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. Trial Registration: ClinicalTrials.gov identifier: NCT03056508

Objective Brain-derived neurotrophic factor (BDNF) rs6265 single-nucleotide polymorphism has been associated with bipolar disorder (BD), and with brain structure among adults with BD. We set out to investigate the association of the BDNF rs6265 Met allele with neurostructural phenotypes in youth BD. Methods Caucasian youth (N = 99; 13-20 years; n = 56 BD, n = 43 age and sex-matched healthy controls) underwent 3-Tesla Magnetic Resonance Imaging and genotyping for BDNF rs6265. Region of interest (ROI) analyses of the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and hippocampus were complemented by vertex-wise analyses examining cortical thickness, surface area (SA) and volume. Multivariable models included the main effects of diagnosis and gene, and a diagnosis-by-genotype interaction term, controlling for age, sex, and intracranial volume. Results There were no significant gene main effects or diagnosis-by-gene interaction effects in ROI analyses. The vertex-wise analysis yielded a significant gene main effect whereby Met allele carriers had greater middle temporal gyrus SA (p = 0.001) and supramarginal gyrus volume (p = 0.03) than Val/Val individuals. Significant interaction effects were found on lateral occipital lobe SA (p = 0.03), whereby the Met allele was associated with increased SA in BD only. Interaction effects were also found on postcentral gyrus SA (p = 0.049) and supramarginal gyrus SA (p = 0.04), with smaller SA in BD Met carriers versus healthy control Met carriers. Conclusion These findings suggest that BDNF rs6265 is differentially associated with regional SA in youth BD. Further investigation is warranted to evaluate whether BDNF protein levels mediate the observed effects, and to evaluate rs6265-related developmental changes.

To evaluate the utility and side effect profile of subcutaneous repository corticotropin gel (RCI) in ocular sarcoidosis.Retrospective chart review.Among six identified patients on RCI therapy, 4 had uveitis, one had optic neuritis and one had uveitis and optic neuritis secondary to sarcoidosis. The average follow-up was 43.5 months. RCI therapy was continuous in 4 patients (average 7.7 months) and intermittent in 2 patients (24 and 12 months). Five of the 6 patients continued with local and/or systemic corticosteroids for ocular inflammation control while on RCI therapy. Two-thirds of patients experienced adverse effects including hyperpigmentation, alopecia, and severe hypertension. RCI therapy was discontinued in 5 of the 6 patients due to continued inflammation and side/adverse effects (4 patients) and loss of follow-up (1 patient).In this small cohort, the majority of patients failed to achieve adequate steroid-sparing ocular inflammation control and experienced side effects while on RCI therapy. Additional studies are needed to elucidate the role of RCI in ocular inflammation.

A variety of health benefits associated with physical activity depends upon the frequency, intensity, duration, and type of exercise. Intensity of exercise is the most elusive of these elements and yet has important implications for the health benefits and particularly cardiovascular outcomes elicited by regular physical activity. Authorities recommend that we obtain 150min of moderate to vigorous intensity physical activity (MVPA) each week. The current descriptions of moderate to vigorous intensity are not sufficient, and we wish to enhance understanding of MVPA by recognition of important boundaries that define these intensities. There are two key thresholds identified in incremental tests: ventilatory and lactate thresholds 1 and 2, which reflect boundaries related to individualized disturbance to homeostasis that are appropriate for prescribing exercise. VT2 and LT2 correspond with critical power/speed and respiratory compensation point. Moderate intensity physical activity approaches VT1 and LT1 and vigorous intensity physical activity is between the two thresholds (1 and 2). The common practice of prescribing exercise at a fixed metabolic rate (# of METs) or percentage of maximal heart rate or of maximal oxygen uptake (V̇O2max) does not acknowledge the individual variability of these metabolic boundaries. As training adaptations occur, these boundaries will change in absolute and relative terms. Reassessment is necessary to maintain regular exercise in the moderate to vigorous intensity domains. Future research should consider using these metabolic boundaries for exercise prescription, so we will gain a better understanding of the specific physical activity induced health benefits.

Implantation of a palpebral spring in the upper eyelid can reduce corneal exposure in patients with paralytic lagophthalmos while also providing moderate blink dynamics. However, the spring may dis...

BACKGROUND Gaps in hospital-based nutrition care practices and opportunities to improve care of patients at risk of malnutrition or malnourished have been demonstrated by several US hospitals implementing quality improvement (QI) projects. This study examined the impact of nutrition care process improvements focused on better documentation of identification and diagnosis of malnutrition in 5 hospital services and differences between nutritionally targeted vs nontargeted services. METHODS Data on malnutrition risk screening, nutrition assessment, malnutrition diagnosis, and nutrition care plan delivery were collected from 32,723 hospital encounters for patients admitted to the intensive care unit, pulmonology, oncology, urology, and general medicine services (targeted) as well as the rest of the nontargeted hospital services between 2017 and 2019. RESULTS Higher rates of morbidity in targeted service patients compared with those in the patient population admitted in the nontargeted services were observed, including higher rates of malnutrition risk (37.43% vs 19.16%, P < .001), higher rates of moderate and severe malnutrition first identified by a registered dietitian nutritionist (20.27% vs 9.67%, P < .001), and malnutrition diagnosis confirmed by an admitting physician (16.72% vs 6.74%, P < .001). CONCLUSIONS The findings suggest sustained improvements in confirmed rates of malnutrition identification and diagnosis are achievable. Targeting malnutrition QI efforts to hospital services with higher patient morbidity is an effective method for improving malnutrition diagnosis, in particular in hospitals with limited resources, which in turn can result in improved nutrition care delivery.

Adolescence is a period of rapid development of the brain’s inherent functional and structural networks; however, little is known about the region-to-region organization of adolescent cerebral blood flow (CBF) or its relationship to neuroanatomy. Here, we investigate both the regional covariation of CBF MRI and the covariation of structural MRI, in adolescents with and without bipolar disorder. Bipolar disorder is a disease with increased onset during adolescence, putative vascular underpinnings, and evidence of anomalous CBF and brain structure. In both groups, through hierarchical clustering, we found CBF covariance was principally described by clusters of regions circumscribed to the left hemisphere, right hemisphere, and the inferior brain; these clusters were spatially reminiscent of cerebral vascular territories. CBF covariance was associated with structural covariance in both the healthy group (n = 56; r = 0.20, p

Evidence suggests exercise is “good medicine” after stroke, yet consensus is lacking on the time to initiate, type, exertion level, and duration per session. It remains a challenge to identify outcome measures for stroke−exercise trials that are sufficiently sensitive to intervention parameters. Cerebrovascular assessments, namely cerebral blood flow and intracranial pulsatility, are herein discussed as examples of quantitative brain-specific measures that may be useful to monitor exercise-related brain changes and help to guide stroke rehabilitation interventions. Novelty: Cerebral blood flow and arterial stiffness are potential vascular targets for stroke exercise trials.

There is currently no effective treatment for spinal cord injury leaving around 90% of patients with permanent disabilities. Stem cell therapies are showing promise in preclinical studies of central nervous system injury and there is increasing evidence suggesting the improvements in functional recovery are mediated by paracrine actions. In this systematic review and meta-analysis, we aimed to determine the overall efficacy of stem cell secretome therapies in promoting recovery in preclinical models of spinal cord injury. We searched PubMed and Embase to identify relevant studies. A random effects meta-analysis was conducted using the restricted maximum likelihood estimator. We assessed risk of bias using a modified CAMARADES checklist. Publication bias was then assessed using funnel plots and trim-and-fill analysis. We identified 26 studies that met our inclusion criteria. Overall, stem cell secretome therapies conferred improvement in locomotor score (SMD: 2.30, 95% CI: 1.68-2.91), reduction in lesion size (SMD: 3.27, 95% CI: 2.06-4.48) and increased axonal profiles in the lesion (SMD: 2.36, 95% CI: 1.02-3.71). We found there was significant asymmetry in the funnel plots for all three outcome measures, suggesting publication bias. Trim-and-fill analysis estimated 19 and 3 unpublished studies in the locomotor score and axonal profiles datasets respectively. The median score on the modified CAMARADES checklist was 4 (IQR 4-5). Reporting of power calculations and allocation concealment was absent. The stem cell secretome is showing great potential as a therapy for spinal cord injury. As the vast majority of studies began treatment acutely and favoured reduction in lesion size, we argue neuroprotection is likely the key mechanism of action. Future studies should focus on exploring the contribution of other mechanisms, the mediators involved and effect of treatment at a chronic stage of injury.

Background: Ophthalmology education is changing amidst the COVID-19 pandemic. The purpose of this study is to describe and evaluate the implementation of webinars combined with online resources for review for ophthalmology trainees. Methods: This is a single-center descriptive survey study. A validated survey tool was distributed 2 months after implementation of webinar education. The survey population comprised residents, fellows, and faculty in a Chicago ophthalmology training program.Results: Eighteen residents (100% response rate), 9 fellows (81.8% response rate) and 20 faculty members (44.4% response rate) responded to the survey. Barriers to webinar education and limitations to learning during webinars were rated as low in both groups (avg. 1.98 ± 2.04 and 2.16 ± 1.82, respectively). The educational value of the webinars was moderately well rated (avg. 7.35 ± 1.66). Interest in webinars replacing in-person lectures was neutral (avg. 5.45 ± 2.54). Faculty expressed fewer barriers (p = 0.005), and a higher preference to use webinar education frequently (p = 0.003) and instead of in-person lectures (p = 0.009), compared to trainees. Conclusions: The findings of this survey suggest that webinars in ophthalmology education are effective and feasible, with some perceived limitations.

Background Gait deficits are associated with brain atrophy and white matter hyperintensities (WMH) - both markers of underlying cerebral small vessel disease (SVD). Given reduced subcortical cerebral blood flow (CBF) is prevalent in SVD, we tested the hypothesis that regional CBF is positively associated with gait performance among older adults. Methods Thirty-two older adults (55-80 years) with at least one vascular risk factor were recruited. We assessed gait during 2 consecutive walking sequences using a GAITRite system: (1) at a self-selected pace, and (2) while performing a serial subtraction dual-task challenge. We quantified CBF using pseudo-continuous arterial spin labeling MRI within 4 regions of interest: putamen, pallidum, thalamus, and hippocampus. We investigated associations between gait characteristics and overall CBF adjusting for age, sex, and height in an omnibus approach using multivariate analysis of variance, followed by regression analysis with each individual region. We also conducted further regression analyses to investigate associations between gait characteristics and frontal lobe CBF. Sensitivity analyses examined how the observed associations were modified by WMH, executive function, and depressive symptoms. A change of 10% in the model's adjusted r2 and effect size was considered as a threshold for confounding. Results Overall subcortical CBF was not associated with self-paced gait. When examining individual ROI, gait velocity was directly related to thalamic CBF (p = 0.026), and across all gait variables the largest effect sizes were observed in relation to thalamic CBF. In the dual-task condition, gait variables were not related to CBF in either the omnibus approach or individual multiple regressions. Furthermore, no significant associations were observed between frontal CBF and gait variables in either the self-paced or dual-task condition. Sensitivity analyses which were restricted to examine the association of velocity and thalamic CBF identified a cofounding effect of depressive symptoms which increased the effect size of the CBF-gait association by 12%. Conclusion Subcortical hypoperfusion, particularly in regions that comprise central input/output tracts to the cortical tissue, may underlie the association between gait deficits and brain aging.

Background Headache diaries and recall questionnaires are frequently used to assess headache frequency and severity in clinical and research settings. Methods Using 20 weeks of data from an intervention trial with 182 participants, we evaluated concordance between an electronic headache diary administered on a daily basis and designed to capture the presence and severity of headaches on an hourly basis (the headache diary) and a recall questionnaire, with retrospective estimation of the number of headache days assessed on a monthly basis. We further examined whether the duration or severity of headaches assessed by the electronic diary impacted concordance between these two measures. Results Over the course of four 28-day periods, people with migraine participating in a dietary intervention reported an average of 13.7 and 11.1 headache days in the headache diary and recall questionnaire, respectively. Conclusion Over time, the concordance between headache days reported in these two measures tended to increase; however, the recall questionnaire headache estimates were lower than the diary measures in all four periods. When analysis was restricted to headaches lasting 8 hours or more, the number of headache days was more closely aligned with days reported in the recall questionnaire, indicating that the accuracy of recall estimates is likely to be influenced by headache duration. Restriction of analyses to moderate-to-severe headaches did not change results as much as headache duration. The findings indicate that recall questionnaires administered on a monthly basis may underestimate headache frequency and therefore should not be used interchangeably with headache diaries. Clinical Trials.gov Identifier: NCT02012790

Intubation of the lacrimal outflow apparatus can help maintain patency after surgical repair or in cases of partial nasolacrimal duct obstruction (NLDO). The tubing acts as a temporary stent in the canaliculi and duct, maintaining patency while the tissues around the stent heal, thereby preventing cicatricial closure. Stent placement may also be combined with dacryocystorhinostomy surgery to maintain patency of the newly created ostium.

Background: Malaria is a leading cause of morbidity and mortality among children under five in Malawi. Children from rural areas of central Malawi have a high burden of malaria morbidity compared to other regions. The goal of this study was to examine the prevalence and determinants of malaria infection among children in rural areas of the Dowa district in central Malawi.Methods: A multistage cross-sectional study design was used to systematically sample 523 child‑mother dyads from postnatal clinics. A survey was administered to mothers to collect quantitative data, and rapid diagnostic tests were used to test for malaria infection in children. The main outcome was positive malaria diagnostic tests in children. Logistic regressions were used to determine risk factors associated with malaria among children aged 2 to 59 months.Results: The prevalence of malaria among children under five years was 35.4%. The results of the multivariate analyses showed that children of mothers who experienced recent intimate partner violence (IPV) were more likely to be diagnosed with malaria (AOR: 1.88, 95% CI: 1.19–2.97; P = 0.007) than children of mothers who did not. Children of mothers who had no formal education were more likely to be diagnosed with malaria (AOR: 2.77, 95% CI: 1.24–6.19; P = 0.013) than children of mothers who had received secondary education. In addition, children in the age ranges of 2 to 5 months and 6 to 11 months were less likely to be diagnosed with malaria (AOR: 0.21, 95% CI: 0.10–0.46; P = 0.000 and AOR: 0.43; 95% CI: 0.22–0.85; P = 0.016, respectively) than children in the age range of 24 to 59 months. Conclusion: The study found that the prevalence of malaria infection among children in the study area was comparable to the national level. We propose that in addition to available malaria control programs, further attention should be paid to children whose mothers have no formal education, children aged 24 to 59 months and mothers that are exposed to IPV in the area.