An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.

The Retinoid-related orphan receptor beta (RORß) gene encodes a developmental transcription factor and has 2 predominant isoforms created through alternative first exon usage; one specific to the retina and another present more broadly in the central nervous system, particularly regions involved in sensory processing. RORß belongs to the nuclear receptor family and plays important roles in cell fate specification in the retina and cortical layer formation. In mice, loss of RORß causes disorganized retina layers, postnatal degeneration, and production of immature cone photoreceptors. Hyperflexion or "high-stepping" of rear limbs caused by reduced presynaptic inhibition by Rorb-expressing inhibitory interneurons of the spinal cord is evident in RORß-deficient mice. RORß variants in patients are associated with susceptibility to various neurodevelopmental conditions, primarily generalized epilepsies, but including intellectual disability, bipolar, and autism spectrum disorders. The mechanisms by which RORß variants confer susceptibility to these neurodevelopmental disorders are unknown but may involve aberrant neural circuit formation and hyperexcitability during development. Here we report an allelic series in 5 strains of spontaneous Rorb mutant mice with a high-stepping gait phenotype. We show retinal abnormalities in a subset of these mutants and demonstrate significant differences in various behavioral phenotypes related to cognition. Gene expression analyses in all 5 mutants reveal a shared over-representation of the unfolded protein response and pathways related to endoplasmic reticulum stress, suggesting a possible mechanism of susceptibility relevant to patients.

Community coalition and key stakeholder perceptions of the community opioid epidemic before an intensive community-level intervention.

INTRODUCTION: Opioid overdoses are a major public health emergency in the United States. Despite effective treatments that can save lives, access to and utilization of such treatments are limited. Community context plays an important role in addressing treatment barriers and increasing access. The HEALing Communities Study (HCS) is a multisite community-level cluster-randomized trial that will study implementation and outcomes of a community coalition-based intervention (Communities that HEAL [CTH]) that implements evidence-based practices (EBPs) to reduce opioid overdose deaths in four states. To examine contextual factors critical to understanding implementation, we assessed the perspectives of community members about their communities, current substance use-related services, and other important issues that could impact intervention implementation. METHODS: Researchers conducted 382 semi-structured qualitative interviews in the HCS communities. Interviews were audio-recorded and transcribed; researchers subsequently analyzed data using directed content analysis based on the constructs of the RE-AIM/PRISM implementation science framework to identify key themes within the external community context. RESULTS: Despite the diversity in states and communities, four similar themes related to the external community context emerged across communities: These themes included the importance of understanding: 1) community risk perceptions, 2) levels of stigma, 3) the health services environment and the availability of substance use services, and 4) funding for substance use services. CONCLUSION: Understanding and addressing the external community context in which the CTH intervention and EBPs are implemented are crucial for successful health services-related and community engaged interventions. While implementing EBPs is a challenging undertaking, doing so will help us to understand if and how a community-based intervention can successfully reduce opioid overdose deaths and influence both community beliefs and the community treatment landscape.

Exploring perspectives on changing opioid prescribing practices: A qualitative study of community stakeholders in the HEALing Communities Study.

BACKGROUND: Community-based perspectives are needed to more broadly inform policy-makers, public health practitioners, prescribers, and pharmacists about community-led and broader efforts to reduce opioid overprescribing, and ultimately reduce prescription opioid use disorder, overdoses and fatalities. The aim of this study is to explore community-based perspectives on efforts to change opioid prescribing practices in their communities. METHODS: Semi-structured interviews were conducted with 388 community stakeholders across four states (Kentucky, Massachusetts, New York, Ohio) from November 2019 to January 2020 about community approaches and goals of community-led responses to the opioid crisis. Data analysis combined deductive and inductive approaches to identify themes and sub-themes related to improving opioid prescribing practices. RESULTS: Three major themes and different subthemes were characterized: (1) acknowledging progress (i.e., healthcare providers being part of the solution, provider education, and prescription drug monitoring programs); (2) emergent challenges (i.e., physician nonadherence with safer opioid prescribing guidelines, difficulty identifying appropriate use of opioids, and concerns about accelerating the progression from opioid misuse to drug abuse); and (3) opportunities for change (i.e., educating patients about safer use and proper disposal of opioids, expanding prescriber and pharmacist education, changing unrealistic expectations around eliminating pain, expanding and increasing insurance coverage for alternative treatment options). CONCLUSIONS: Community stakeholders appeared to support specific opportunities to reduce prescription opioid misuse and improve safer prescribing. The opportunities included culture change around pain expectations, awareness of safe disposal, additional provider education, and increased coverage and acceptability of non-opioid treatments.

Papilledema Secondary to Neurologic Lyme Borreliosis: A Meta-Case Series.

BACKGROUND: Papilledema can be a manifestation of neurologic Lyme borreliosis (LB). The clinical manifestations and progression of these cases have not been comprehensively documented to date. We aimed to describe clinical and diagnostic features and to assess patient outcomes in cases of papilledema secondary to neurologic LB. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Database from inception to August 2019. We did not restrict our search by study design or by publication date, status, or language. RESULTS: Twenty-eight studies describing 46 cases of papilledema secondary to neurologic LB were included. Common clinical features included cranial neuropathy (68%) and diplopia (61%). Most patients did not recall tick bite (71%) and were afebrile (74%). Brain imaging was normal in 64% cases. Cerebrospinal fluid analysis showed lymphocytic pleocytosis (77%). Initial treatment with intravenous ceftriaxone was given in 52% of cases and resulted in a 100% resolution rate. Concomitant treatment with acetazolamide resulted in favorable outcomes. CONCLUSIONS: For patients in endemic regions who describe symptoms suggestive of intracranial hypertension and papilledema, especially accompanied by facial nerve palsy and other cranial nerve palsies, underlying neurologic LB should be considered.