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Marek's Disease (MD), which can result in neurological damage and tumour formation, has large effects on the economy and animal welfare of the poultry industry worldwide. Previously, we mapped autosomal MD QTL regions (QTLRs) by individual genotyping of an F 6 population from a full-sib advanced intercross line. We further mapped MD QTLRs on the chicken Z chromosome (GGZ) using the same F 6 population, and by selective DNA pooling (SDP) of 8 elite egg production lines. Here we used SDP of the same pools used on GGZ to map autosomal MD QTLRs. Thirty-seven QTLRs were found. Seven of the QTLRs were tested by all sires from the same 8 lines, individually genotyped for QTLR markers. Five of the tested QTLRs were confirmed. Linkage disequilibrium (LD) was calculated for all QTLR markers on the same chromosome, and complex LD blocks were found. Distribution of P and LD values were used to assess the QTLR causative elements. Allele substitution effects were calculated based on both pooled SNP microarray genotypes, and individual genotypes of QTLRs markers. Substantial allele effect and contribution to the phenotypic and genotypic variation were obtained. The results explain part of the MD response, and provide targets for mitigating MD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: Institutional Review Board Statement: The animal study protocol was approved by Hy-Line International Institutional Animal Care and Use Committee guidelines. Hy-Line do not have specific project identification codes. All of these samples had been collected in the past and stored frozen until use. At the termination of the study animals were humanely euthanized under the approval of the Hy-Line IACUC and supervision of licensed veterinarians., (© 2024. The Author(s).)

Intentional weight loss has been shown to increase bone loss short term but the long-term effects are not known. Data from the Look AHEAD clinical trial shows that a long term intentional weight loss intervention was associated with greater bone loss at the hip in men., Purpose: Intentional weight loss has been shown to increase bone loss short term and increase frailty fracture risk, but the long-term effects on bone mineral density (BMD) are not known., Methods: Data from a subgroup from the Look AHEAD (LA) multicenter, randomized clinical trial was used to evaluate whether a long term intentional weight loss intervention would increase bone loss. In a preplanned substudy, BMD was assessed at 5 of the 16 LA clinical centers using dual-energy X-ray absorptiometry at baseline, year 8, and the observational visit 12.6-16.3 years after randomization (year 12-16)., Results: At year 8, bone density loss (%) was greater in the Intensive Lifestyle Intervention (ILI) group compared with the control group (DSE) for the femoral neck (p = 0.0122) but this finding was not observed at the year 12-16 visit. In analyses stratified by gender, bone density loss (%) was greater at the total hip for men in the ILI group than the DSE group at both the year 8 and year 12-16 visits (year 8 p = 0.0263 and year 12-16 p = 0.0062). This finding was not observed among women., Conclusion: Long term intentional weight loss was associated with greater bone loss at the hip in men. These results taken with the previously published Look AHEAD data from the entire clinical trial showing increased frailty fracture risk with weight loss in the ILI group suggest that when intentional weight loss is planned, consideration of bone density preservation and fracture prevention strategies is warranted., Trial Registration: Clinicaltrials.gov Identifier: NCT00017953. June 21, 2001., (© 2023. The Author(s).)

Marek's Disease (MD) has a significant impact on both the global poultry economy and animal welfare. The disease pathology can include neurological damage and tumour formation. Sexual dimorphism in immunity and known higher susceptibility of females to MD makes the chicken Z chromosome (GGZ) a particularly attractive target to study the chicken MD response. Previously, we used a Hy-Line F 6 population from a full-sib advanced intercross line to map MD QTL regions (QTLRs) on all chicken autosomes. Here, we mapped MD QTLRs on GGZ in the previously utilized F 6 population with individual genotypes and phenotypes, and in eight elite commercial egg production lines with daughter-tested sires and selective DNA pooling (SDP). Four MD QTLRs were found from each analysis. Some of these QTLRs overlap regions from previous reports. All QTLRs were tested by individuals from the same eight lines used in the SDP and genotyped with markers located within and around the QTLRs. All QTLRs were confirmed. The results exemplify the complexity of MD resistance in chickens and the complex distribution of p -values and Linkage Disequilibrium (LD) pattern and their effect on localization of the causative elements. Considering the fragments and interdigitated LD blocks while using LD to aid localization of causative elements, one must look beyond the non-significant markers, for possible distant markers and blocks in high LD with the significant block. The QTLRs found here may explain at least part of the gender differences in MD tolerance, and provide targets for mitigating the effects of MD.

Background: Children with developmental disabilities are vulnerable to morbidity associated with COVID-19., Aims: To understand attitudes toward routine childhood vaccinations versus the COVID-19 vaccine in a population of families affected by mitochondrial disease (MtD), a form of developmental disability., Methods and Procedures: An online survey was administered via several advocacy groups for children with MtD., Outcomes and Result: Eighty-six percent of families reported being up to date with the childhood vaccine schedule and seventy percent reported that their affected child receives the annual flu shot. However, only fifty percent reported that the benefits of the COVID-19 vaccine outweighed the risk for their affected child. One quarter of families expressed concern that their child may become sick or deteriorate after the COVID-19 vaccine. In comparison to other routine childhood vaccines, families expressed less confidence in the COVID-19 vaccine., Conclusions and Implications: Families affected by this population of developmental disabilities are more comfortable with the vaccines included in the routine childhood immunization schedule than with the newly introduced COVID-19 vaccine, even despite this group's vulnerability., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to disclose., (Published by Elsevier Ltd.)

Background: Pediatric patients undergoing intestinal rehabilitation (IR) using parenteral nutrition (PN) are at higher risk for intestinal failure-associated liver disease (IFALD). Nutrition support, growth, and liver enzymes must be closely monitored while incorporating hepatoprotective lipid injectable emulsions for optimal patient outcomes., Objective: Describe trends of liver profile and nutrition outcomes for pediatric patients undergoing IR using SMOFlipid[SO,MCT,OO,FO-ILE])., Methods: After IRB approval, patients undergoing IR using SO,MCT,OO,FO-ILE were observed prospectively from January 1, 2017, through December 1, 2019. The following values were documented monthly: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), triene/tetraene ratio (TTR), micronutrient and trace element levels, z-scores for growth, and nutrition support regimen. Values were compared., Results: The group involved 16 pediatric patients for an average of 16.4 months on SO,MCT,OO,FO-ILE. By the end of the study, mean PN hours per day decreased by 34.7%, P < 0.0001. Mean PN calories per kilogram decreased from 60.4 to 48.3, P = 0.004. SO,MCT,OO,FO-ILE calories met the recommended dietary intake goal of 30% at the average 1.6 g/kg. Growth z-scores increased in those <2 YOA , although the body mass index decreased in our >2 YOA cohort. Total nutrition received from PN decreased to 62%: a 32% change, P = 0.001. There were no statistically significant changes in AST or ALT. TB decreased by 67.08%, P <0.05. No essential fatty acid deficiency was reported (TTR < 0.02). There were no changes in micronutrient and trace element deficiencies. There was zero new incidences of IFALD., Conclusions: SO,MCT,OO,FO-ILE may be used long term in pediatric patients while promoting growth and development., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background and Objectives: Anti-NMDA receptor encephalitis (anti-NMDARE) is one of the most common causes of encephalitis. It typically presents in adolescence and young adulthood, but little is known about its potential long-term consequences across the lifespan. Adaptive behavior describes an individual's ability to respond and adapt to environmental demands and unanticipated changes in daily routines. In this study, we evaluate the relationship between features from clinical presentation, including age, and long-term adaptive behavior in participants with anti-NMDARE., Methods: Cross-sectional informant-reported data were collected between 2017 and 2019 from 41 individuals/caregivers of individuals with anti-NMDARE treated at 3 major academic hospitals. Neurologic disability was assessed by record review using the modified Rankin Scale (mRS). Functional outcomes were assessed using the validated Adaptive Behavior Assessment System, Third Edition (ABAS-3)., Results: The mean age at the time of study enrollment was 23.4 years (SD 17.0 years), and the mean time from symptom onset to study enrollment was 4.0 years. Seventeen participants were aged <12 years at symptom onset, 19 participants were aged 12-30 years, and 5 participants were aged >30 years. Mean ABAS-3 scores at study enrollment for all participants were in the average range (mean general adaptive composite standard score 92.5, SD 18.7). Individuals aged <12 years at symptom onset had lower mean ABAS-3 scores and were in the below average range compared with those aged 12-30 years at symptom onset, whose mean scores were in the average range (87 vs 99, p < 0.05). Similar differences were seen in 3 of the individual subscales (functional academics, health and safety, and self-care). There were no significant differences in mRS scores between age groups ( p > 0.05)., Discussion: Although anti-NMDARE is associated with an overall favorable outcome, younger age at onset associates with worse long-term adaptive behavior despite no differences in neurologic disability. These findings suggest that the disease may have distinct consequences on the early developing brain. Future studies should evaluate behavioral recovery and quality of life after anti-NMDARE and identify additional factors associated with differential recovery., (© 2022 American Academy of Neurology.)

Background: A challenge during the COVID-19 pandemic has been widespread adherence to risk-reducing behaviors. Individuals with mitochondrial disease (MtD) are special population with an increased risk of morbidity associated with infection., Purpose: To measure risk mitigation behaviors (RMBs) in families affected by MtD and identify factors that may influence these behaviors., Methods: An online questionnaire was distributed in April and June 2020. Individuals with MtD or their caregivers completed the survey., Results: We received 529 eligible responses with n = 312 completing all questions for our multivariate regression model. The most common RMBs were increased hand washing (96%), social distancing (94%), and avoiding public gatherings (93%). Higher numbers of recent healthcare visits (b = 0.62, p < 0.05) and expressed fear of the MtD patient contracting COVID-19 (b = 0.92, p < 0.05) were associated with more RMBs. Living in a rural community (b = -0.99,p < 0.05) and a history of COVID-19 testing (b = -2.14,p < 0.01) were associated with fewer RMBs., Conclusions: Our results suggest that during the COVID-19 pandemic, families affected by MtD have near universal adherence to basic RMBs. This may be motivated by fear of the severe morbidity associated with infection in MtD. Patients with frequent healthcare visits may be sicker and therefore take more precautions. Living in a rural community may also impact these behaviors. People who practice fewer RMBs may be more likely to seek testing. Our findings may generalize to other chronic diseases., (© 2021 Published by Elsevier Inc.)