Background: Nipocalimab is a human IgG1 monoclonal antibody targeting FcRn that selectively reduces IgG levels without impacting antigen presentation, T- and B-cell functions. This study describes the effect of nipocalimab on vaccine response. Methods: Open-label, parallel, interventional study randomized participants 1:1 to receive intravenous 30mg/kg nipocalimab at Week0 and 15mg/kg at Week2 and Week4 (active) or no drug (control). On Day 3, participants received Tdap and PPSV®23 vaccinations and were followed through Wk16. Results: Twenty-nine participants completed the study and are included (active, n=15; control, n=14). Participants with a positive anti-tetanus IgG response was comparable between groups at Wk2 and Wk16, but lower at Wk4 (nipocalimab 3/15 [20%] vs control 7/14 [50%]; P=0.089). All maintained anti-tetanus IgG above the protective threshold (0.16IU/mL) through Wk16. While anti-pneumococcal-capsular-polysaccharide (PCP) IgG levels were lower during nipocalimab treatment, the percent increase from baseline at Wk2 and Wk16 was comparable between groups. Post-vaccination, anti-PCP IgG remained above 50mg/L and showed a 2-fold increase from baseline throughout the study in both groups. Nipocalimab co-administration with vaccines was safe and well-tolerated. Conclusions: These findings suggest that nipocalimab does not impact the development of an adequate IgG response to T-cell–dependent/independent vaccines and that nipocalimab-treated patients can follow recommended vaccination schedules.

Parkinson’s disease (PD) is a severe neurodegenerative disorder characterized by prominent motor and non-motor (e.g., cognitive) abnormalities. Notwithstanding Food and Drug Administration (FDA)-approved treatments (e.g., L-dopa), most persons with PD do not adequately benefit from the FDA-approved treatments and treatment emergent adverse events are often reasons for discontinuation. To date, no current therapy for PD is disease modifying or curative. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are central nervous system (CNS) penetrant and have shown to be neuroprotective against oxidative stress, neuroinflammation, and insulin resistance, as well as promoting neuroplasticity. Preclinical evidence suggests that GLP-1RAs also attenuate the accumulation of α-synuclein. The cellular and molecular effects of GLP-1RAs provide a basis to hypothesize putative therapeutic benefit in individuals with PD. Extant preclinical and clinical trial evidence in PD provide preliminary evidence of clinically meaningful benefit in the cardinal features of PD. Herein, we synthesize extant preclinical and early-phase clinical evidence, suggesting that GLP-1RAs may be beneficial as a treatment and/or illness progression modification therapeutic in PD.

This paper examined the interaction between narrative performance, language exposure, and standardized measures of morphosyntax and semantics, in bilingual children tested two times, 1 year apart. We aimed to 1) identify the factor structure of oral narrative measures, and 2) examine the direction and strength of the effects of (i) language exposure and (ii) the relationship between language domains and narrative production. A total of 143 Spanish (L1)-English (L2) bilingual children completed a battery of oral narrative and oral language proficiency assessments in Spanish and English at two time points (kindergarten and Grade 1). Factor analyses yielded an identical two-factor structure of bilingual oral narrative measurements, namely productivity (word production) and complexity (sentence structure), in both Spanish and English across the two time points. Cross-lagged analysis showed that narrative production predicted semantics and morphosyntax performance in Spanish and English one year later. Cross-language transfer from L1 to L2 on the complexity of narrative was noted. Language exposure predicted only Spanish narrative production, but not English. These results suggest within- and cross-language transfer, highlighting the importance of L1 language development. In addition, current findings highlight the importance of language exposure for L1 in early school-age children.

Depression is the largest global contributor to non-fatal disease burden(1). A growing body of evidence suggests that dietary behaviours, such as higher fruit and vegetable intake, may be protective against the risk of depression(2). However, this evidence is primarily from high-income countries, despite over 80% of the burden of depression being experienced in low- and middle-income countries(1). There are also limited studies to date focusing on older adults. The aim of this study was to prospectively examine the associations between baseline fruit and vegetable intake and incidence of depression in adults aged 45-years and older from 10 cohorts across six continents, including four cohorts from low and middle-income countries. The association between baseline fruit and vegetable intake and incident depression over a 3–6-year follow-up period was examined using Cox proportional hazard regression after controlling for a range of potential confounders. Participants were 7771 community-based adults aged 45+ years from 10 diverse cohorts. All cohorts were members of the Cohort Studies of Memory in an International Consortium collaboration(3). Fruit intake (excluding juice) and vegetable intake was collected using either a comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated depression measures, and depression was defined as a score greater than or equal to a validated cut-off. Prior to analysis all data were harmonised. Analysis was performed by cohort and then cohort results were combined using meta-analysis. Subgroup analysis was performed by sex, age (45 – 64 versus 65+ years) and income level of country (high income countries versus low- and middle-income countries). There were 1537 incident cases of depression over 32,420 person-years of follow-up. Mean daily intakes of fruit were 1.7 ± 1.5 serves and vegetables 1.9 ± 1.4. serves. We found no association between fruit and vegetable intakes and risk of incident depression in any of the analyses, and this was consistent across the subgroup analyses. The low intake of fruit and vegetables of participants, diverse measures used across the different cohorts, and modest sample size of our study compared with prior studies in the literature, may have prevented an association being detected. Further investigation using standardised measures in larger cohorts of older adults from low- to middle-income countries is needed. Future research should consider the potential relationship between different types of fruits and vegetables and depression.

Background: Poorly-defined cases (PDCs) of focal epilepsy are cases with no/subtle MRI abnormalities or have abnormalities extending beyond the lesion visible on MRI. Here, we evaluated the utility of Arterial Spin Labeling (ASL) MRI perfusion in PDCs of pediatric focal epilepsy. Methods: ASL MRI was obtained in 25 consecutive children presenting with poorly-defined focal epilepsy (20 MRI- positive, 5 MRI-negative). Qualitative visual inspection and quantitative analysis with asymmetry and Z-score maps were used to detect perfusion abnormalities. ASL results were compared to the hypothesized epileptogenic zone (EZ) derived from other clinical/imaging data and the resection zone in patients with Engel I/II outcome and >18 month follow-up. Results: Qualitative analysis revealed perfusion abnormalities in 17/25 total cases (68%), 17/20 MRI-positive cases (85%) and none of the MRI-negative cases. Quantitative analysis confirmed all cases with abnormalities on qualitative analysis, but found 1 additional true-positive and 4 false-positives. Concordance with the surgically-proven EZ was found in 10/11 cases qualitatively (sensitivity=91%, specificity=50%), and 11/11 cases quantitatively (sensitivity=100%, specificity=23%). Conclusions: ASL perfusion may support the hypothesized EZ, but has limited localization benefit in MRI-negative cases. Nevertheless, owing to its non-invasiveness and ease of acquisition, ASL could be a useful addition to the pre-surgical MRI evaluation of pediatric focal epilepsy.

The aim of this study was to assess which machine, Radixact or CyberKnife, can deliver better treatment for lung and prostate stereotactic body radiation therapy (SBRT) with the use of Synchrony® real-time motion tracking system. Ten and eight patients treated with lung and prostate SBRT, respectively, using the CyberKnife system were selected for the assessment. For each patient, a retrospective Radixact plan was created and compared with the original CyberKnife plan. There was no statistically significant difference in the new conformity index of the Radixact plans and that of the Cyberknife plans in both lung and prostate SBRT. The average homogeneity index in the Radixact plans was better in both lung and prostate SBRT with statistical significance (p = 0·04 for lung and p = 0·02 for prostate). In lung SBRT, the dose to lungs was lower in Cyberknife plans (p = 0·002). In prostate SBRT, there was no statistically significant difference in organs at risk sparing between Cyberknife plans and Radixact plans. In conclusion, CyberKnife was better in lung SBRT while Radixact was better in prostate SBRT.

Background: Poorly-defined cases (PDCs) of focal epilepsy are cases with no/subtle MRI abnormalities or have abnormalities extending beyond the lesion visible on MRI. Here, we evaluated the utility of Arterial Spin Labeling (ASL) MRI perfusion in PDCs of pediatric focal epilepsy. Methods: ASL MRI was obtained in 25 consecutive children presenting with poorly-defined focal epilepsy (20 MRI- positive, 5 MRI-negative). Qualitative visual inspection and quantitative analysis with asymmetry and Z-score maps were used to detect perfusion abnormalities. ASL results were compared to the hypothesized epileptogenic zone (EZ) derived from other clinical/imaging data and the resection zone in patients with Engel I/II outcome and >18 month follow-up. Results: Qualitative analysis revealed perfusion abnormalities in 17/25 total cases (68%), 17/20 MRI-positive cases (85%) and none of the MRI-negative cases. Quantitative analysis confirmed all cases with abnormalities on qualitative analysis, but found 1 additional true-positive and 4 false-positives. Concordance with the surgically-proven EZ was found in 10/11 cases qualitatively (sensitivity=91%, specificity=50%), and 11/11 cases quantitatively (sensitivity=100%, specificity=23%). Conclusions: ASL perfusion may support the hypothesized EZ, but has limited localization benefit in MRI-negative cases. Nevertheless, owing to its non-invasiveness and ease of acquisition, ASL could be a useful addition to the pre-surgical MRI evaluation of pediatric focal epilepsy.

Since the beginning of 2020, the coronavirus disease (COVID-19) pandemic has dramatically influenced almost every aspect of human life. Activities requiring human gatherings have either been postponed, canceled, or held completely virtually. To supplement lack of in-person contact, people have increasingly turned to virtual settings online, advantages of which include increased inclusivity and accessibility and a reduced carbon footprint. However, emerging online technologies cannot fully replace in-person scientific events. In-person meetings are not susceptible to poor Internet connectivity problems, and they provide novel opportunities for socialization, creating new collaborations and sharing ideas. To continue such activities, a hybrid model for scientific events could be a solution offering both in-person and virtual components. While participants can freely choose the mode of their participation, virtual meetings would most benefit those who cannot attend in-person due to the limitations. In-person portions of meetings should be organized with full consideration of prevention and safety strategies, including risk assessment and mitigation, venue and environmental sanitation, participant protection and disease prevention, and promoting the hybrid model. This new way of interaction between scholars can be considered as a part of a resilience system, which was neglected previously and should become a part of routine practice in the scientific community.

Grape marc (GPM) is a viticulture by-product that is rich in secondary compounds, including condensed tannins (CT), and is used as a supplement in livestock feeding practices. The aim of this study was to determine whether feeding GPM to lactating dairy cows would alter the milk proteome through changes in nitrogen (N) partitioning. Ten lactating Holstein cows were fed a total mixed ration (TMR) top-dressed with either 1.5 kg dry matter (DM)/cow/day GPM (GPM group; n = 5) or 2.0 kg DM/cow/day of a 50:50 beet pulp: soy hulls mix (control group; n = 5). Characterization of N partitioning and calculation of N partitioning was completed through analysis of plasma urea-N, urine, feces, and milk urea-N. Milk samples were collected for general composition analysis, HPLC quantification of the high abundance milk proteins (including casein isoforms, α-lactalbumin, and β-lactoglobulin) and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the low abundance protein enriched milk fraction. No differences in DMI, N parameters, or calculated N partitioning were observed across treatments. Dietary treatment did not affect milk yield, milk protein or fat content or yield, or the concentrations of high abundance milk proteins quantified by HPLC analysis. Of the 127 milk proteins that were identified by LC-MS/MS analysis, 16 were affected by treatment, including plasma proteins and proteins associated with the blood-milk barrier, suggesting changes in mammary passage. Immunomodulatory proteins, including butyrophilin subfamily 1 member 1A and serum amyloid A protein, were higher in milk from GPM-fed cows. Heightened abundance of bioactive proteins in milk caused by dietary-induced shifts in mammary passage could be a feasible method to enhance the healthfulness of milk for both the milk-fed calf and human consumer. Additionally, the proteome shifts observed in this trial could provide a starting point for the identification of biomarkers suitable for use as indicators of mammary function.

Introduction: Our team developed “The Ottawa Troponin Pathway” (OTP) for Non-ST Elevation Myocardial Infarction (NSTEMI) diagnosis using serial conventional troponin (cTnI) 3 hours apart to aid in safe and early disposition of ED patients. The primary objective of this study is to validate the diagnostic accuracy of the OTP in the cohort of patients with cTnI values above the 99th percentile ( > 45ng/L). Methods: This study is a health records review conducted at the Civic and General Campuses of The Ottawa Hospital from August 2017 to December 2017. Adults (≥18 years) who presented to the ED with symptoms of ACS, and who had serial cTnI (at least two values 3 hours ±15 minutes apart) performed for diagnosis of NSTEMI and at least one cTnI value > 45ng/L were included. Patients with cardiac arrest, STEMI, unstable angina or those with TnI values ≤45ng/L were excluded. The outcomes were death due to unknown cause or NSTEMI adjudicated by two blinded investigators within 30 days. Data collected include baseline characteristics, ED management, length of stay, cTnI values and times of measurement, disposition, and outcome. We used descriptive statistics and test diagnostic characteristics to analyze our data. Results: We screened 53,077 patients, of whom 635 patients were included in the study (mean age 71.6 years; 57.6% males; 59.7% hospitalized; median ED length of stay 4.7 hours.). 107 patients (16.9%; 95%CI 14.1%-20.0%) were diagnosed with NSTEMI within 30 days. Among patients with TNI values above the 99th percentile, the OTP did not miss any patients diagnosed with NSTEMI. The sensitivity and the specificity of the OTP were 100% (95%CI 96.6%-100%) and 32.2% (95%CI 28.2%-36.4%) respectively. Conclusion: Our results show that the OTP is diagnostically accurate in ruling out NSTEMI among patients with cTNI values above the 99th percentile with symptoms concerning for ACS. Using the OTP will allow for early referral to consulting services for management, safe and early discharge home, and improve ED crowding.

BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.

Introduction: Creatine kinase (CK) measurement, despite not being recommended for the diagnosis of a Non-ST Elevation Myocardial Infarction (NSTEMI) is still routinely performed in the emergency department (ED) for the workup of NSTEMI. The diagnostic utility of CK among ED patients with suspected NSTEMI is still not well understood. The objectives of this study were to assess: the additional value of CK in NSTEMI diagnosis and the correlation between the highest CK/TNI values and ejection fraction (EF) on follow-up echocardiography among patients with suspected NSTEMI. Methods: This was a prospective cohort study conducted at the Civic and General Campuses of The Ottawa Hospital from March 2014 to March 2016. We enrolled adults (18 years) for whom troponin (TNI) and CK were ordered for chest pain or non-chest pain symptoms within the past 24 hours concerning for NSTEMI and excluded those with suspected ST-Elevation Myocardial Infarction (STEMI). Primary outcome was a 30-day NSTEMI adjudicated by two blinded physicians. Demographics, medical history, and ED CK/TNI values were collected. We used descriptive statistics and report test diagnostic characteristics. Results: Of the 1,663 patients enrolled, 84 patients (5.1%) suffered NSTEMI. The sensitivity and specificity of CK was 30.9% (95%CI 21.1, 40.8) and 91.4% (95%CI 90.0, 92.8) respectively. The sensitivity and specificity of troponin was 96.4% (95%CI 92.4, 100) and 88.1% (95%CI 86.5, 89.7) respectively. Among 3 (0.2%) patients with missed NSTEMI diagnosis with TNI, CK measurements did not add value. The mean CK values were not significantly different between those with normal and abnormal EF on follow-up (132.4 U/L and 146.3 U/L respectively; p=0.44), whereas the mean TNI values were significantly different (0.5 µg/L and 1.3 µg/L respectively; p=0.046). Conclusion: CK measurements neither provide any additional value in the work-up of NSTEMI in the ED nor correlate with EF on follow-up. Discontinuing routine CK measurements would reduce overall costs and improve resource utilization in the ED, and streamline the management of patients in the ED with chest pain.

Hand, foot, and mouth disease (HFMD), usually a self-limiting illness for young children, could cause a significant burden for parents because it can take up to 1–2 weeks for a sick child to recover. We conducted a two-wave longitudinal study over one summer peak season (May–July 2014) of HFMD to examine parents’ HFMD-related risk perceptions and protective responses. In total, 618 parents with at least one child aged ⩽12 years, recruited using randomly-dialled household telephone calls completed the baseline survey interview, 452 of whom subsequently completed the follow-up survey. Around two-thirds of participants perceived the chance of their child being infected by HFMD was ‘zero/very small/small’ but the likelihood of being hospitalized once infected was ‘somewhat likely/likely/very likely’. At follow-up, 82% reported washing child's hands frequently (Hygiene), 16% would keep their child away from school if HFMD cases were identified in school (Distancing) and 23% were ‘very likely/certainly’ to take the child for HFMD vaccination if available (Vaccination). Anticipated regret was consistently the strongest predictor for Hygiene (OR 3.34), and intention of Distancing (OR 2.58) and Vaccination (OR 3.16). Interventions focusing on anticipated regret may be effective to promote protective behaviour against HFMD among parents for their children.