D-β-Hydroxybutyrate Is Protective in Mouse Models of Huntington's Disease

Abnormalities in mitochondrial function and epigenetic regulation are thought to be instrumental in Huntington's disease (HD), a fatal genetic disorder caused by an expanded polyglutamine track in the protein huntingtin. Given the lack of effective therapies for HD, we sought to assess the neuroprotective properties of the mitochondrial energizing ketone body, D-β-hydroxybutyrate (DβHB), in the 3-nitropropionic acid (3-NP) toxic and the R6/2 genetic model of HD. In mice treated with 3-NP, a complex II inhibitor, infusion of DβHB attenuates motor deficits, striatal lesions, and microgliosis in this model of toxin induced-striatal neurodegeneration. In transgenic R6/2 mice, infusion of DβHB extends life span, attenuates motor deficits, and prevents striatal histone deacetylation. In PC12 cells with inducible expression of mutant huntingtin protein, we further demonstrate that DβHB prevents histone deacetylation via a mechanism independent of its mitochondrial effects and independent of histone deacetylase inhibition. These pre-clinical findings suggest that by simultaneously targeting the mitochondrial and the epigenetic abnormalities associated with mutant huntingtin, DβHB may be a valuable therapeutic agent for HD

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Centralization of services: standard setting and outcomes

OBJECTIVE: To test specific standards set in the newly established cleft lip and palate service in three regions of the U.K. The standards relate to record collection and outcomes. DESIGN: Retrospective analysis. PATIENTS: Records of 31 children, 5 years of age, who were born in 1997 with complete unilateral clefts of lip and palate and were treated by surgeons in three regions. MAIN OUTCOME MEASURES: Record collection standards were measured by collecting dental study models. Outcomes were measured with the 5-Year-Old Index. RESULTS: Of the 31 subjects, 52% had excellent and good outcomes. The 31 cases represented 62% of the total records collected. CONCLUSIONS: The three regions examined fell short of the standards set, but the outcomes were improved compared with previous national outcomes. The failings in record collection need to be rectified. This study provides baseline data for further development of cleft services within three regions

Centralization of services: standard setting and outcomes.

OBJECTIVE: To test specific standards set in the newly established cleft lip and palate service in three regions of the U.K. The standards relate to record collection and outcomes. DESIGN: Retrospective analysis. PATIENTS: Records of 31 children, 5 years of age, who were born in 1997 with complete unilateral clefts of lip and palate and were treated by surgeons in three regions. MAIN OUTCOME MEASURES: Record collection standards were measured by collecting dental study models. Outcomes were measured with the 5-Year-Old Index. RESULTS: Of the 31 subjects, 52% had excellent and good outcomes. The 31 cases represented 62% of the total records collected. CONCLUSIONS: The three regions examined fell short of the standards set, but the outcomes were improved compared with previous national outcomes. The failings in record collection need to be rectified. This study provides baseline data for further development of cleft services within three regions