Defined neuronal populations drive fatal phenotype in a mouse model of leigh syndrome

Altres ajuts: Seattle Children's Research Institute: Seed Funds;NINDS: R01 NIH/NS 102796; University of Washington Neurological Surgery Department: Ellenbogen Neurological Surgery Research Funds; University of Washington: The Ryan J. Murphy SUDEP Research Funds; Mitochondrial Research Guild: Seed FundsMitochondrial deficits in energy production cause untreatable and fatal pathologies known as mitochondrial disease (MD). Central nervous system affectation is critical in Leigh Syndrome (LS), a common MD presentation, leading to motor and respiratory deficits, seizures and premature death. However, only specific neuronal populations are affected. Furthermore, their molecular identity and their contribution to the disease remains unknown. Here, using a mouse model of LS lacking the mitochondrial complex I subunit Ndufs4, we dissect the critical role of genetically-defined neuronal populations in LS progression. Ndufs4 inactivation in Vglut2expressing glutamatergic neurons leads to decreased neuronal firing, brainstem inflammation, motor and respiratory deficits, and early death. In contrast, Ndufs4 deletion in GABAergic neurons causes basal ganglia inflammation without motor or respiratory involvement, but accompanied by hypothermia and severe epileptic seizures preceding death. These results provide novel insight in the cell type-specific contribution to the pathology, dissecting the underlying cellular mechanisms of MD

Assessment of formats and completeness of paper-based referral letters among urban hospitals in Rwanda: a retrospective baseline study

Abstract Background Patient referral is a process in which a healthcare provider decides to seek assistance due to the limitations of available skills, resources and services offered locally. Paper-based referrals predominantly used in low-income countries hardly follow any procedure. This causes a major gap in communication, coordination, and continuity of care between primary and specialized levels, leading to poor access, delay, duplication and unnecessary costs. The goal of this study is to assess the formats and completeness of existing paper-based referral letters in order to improve health information exchange, coordination, and continuity of care. Methods A retrospective exploratory research was conducted in eight public and three private healthcare facilities in the city of Kigali from May to October 2021. A purposive sampling method was used to select hospitals and referral letters from patients’ files. A data capture sheet was designed according to the contents of the referral letters and the resulting responses were analyzed descriptively. Results In public hospitals, five types of updated referral letters were available, in total agreement with World Health Organization (WHO) standards of which two (neonatal transfer form and patient monitoring transfer form) were not used. There was also one old format that was used by most hospitals and another format designed and used by a district hospital (DH) separately. Three formats were designed and used by private hospitals (PH) individually. A total of 2,304 referral letters were perused and the results show that “external transfer” forms were completed at 58.8%; “antenatal, delivery, and postnatal external transfer” forms at 47.5%; “internal transfer” forms at 46.6%; “Referral/counter referral” forms at 46.0%; district hospital referrals (DH2) at 73.4%. Referrals by private hospitals (PH1, PH2 and PH3) were completed at 97.7%, 70.7%, and 0.0% respectively. The major completeness deficit was observed in counter referral information for all hospitals. Conclusion We observed inconsistencies in the format of the available referral letters used by public hospitals, moreover some of them were incompatible with WHO standards. Additionally, there were deficits in the completeness of all types of paper-based referral letters in use. There is a need for standardization and to disseminate the national patient referral guideline in public hospitals with emphasis on referral feedback, referral registry, triage, archiving and a need for regular training in all organizations

Proceedings of the Sleep and Epilepsy Workshop: Section 1 Decreasing Seizures-Improving Sleep and Seizures, Themes for Future Research.

Epileptic seizures, sleep, and circadian timing share bilateral interactions, but concerted work to characterize these interactions and to leverage them to the advantage of patients with epilepsy remains in beginning stages. To further the field, a multidisciplinary group of sleep physicians, epileptologists, circadian timing experts, and others met to outline the state of the art, gaps of knowledge, and suggest ways forward in clinical, translational, and basic research. A multidisciplinary panel of experts discussed these interactions, centered on whether improvements in sleep or circadian rhythms improve decrease seizure frequency. In addition, education about sleep was lacking in among patients, their families, and physicians, and that focus on education was an extremely important low hanging fruit to harvest. Improvements in monitoring technology, experimental designs sensitive to the rigor required to dissect sleep versus circadian influences, and clinical trials in seizure reduction with sleep improvements were appropriate