Allelic contribution of Nrxn1α to autism-relevant behavioral phenotypes in mice.

Copy number variations (CNVs) in the Neurexin 1 (NRXN1) gene, which encodes a presynaptic protein involved in neurotransmitter release, are some of the most frequently observed single-gene variants associated with autism spectrum disorder (ASD). To address the functional contribution of NRXN1 CNVs to behavioral phenotypes relevant to ASD, we carried out systematic behavioral phenotyping of an allelic series of Nrxn1 mouse models: one carrying promoter and exon 1 deletion abolishing Nrxn1α transcription, one carrying exon 9 deletion disrupting Nrxn1α protein translation, and one carrying an intronic deletion with no observable effect on Nrxn1α expression. We found that homozygous loss of Nrxn1α resulted in enhanced aggression in males, reduced affiliative social behaviors in females, and significantly altered circadian activities in both sexes. Heterozygous or homozygous loss of Nrxn1α affected the preference for social novelty in male mice, and notably, enhanced repetitive motor skills and motor coordination in both sexes. In contrast, mice bearing an intronic deletion of Nrxn1 did not display alterations in any of the behaviors assessed. These findings demonstrate the importance of Nrxn1α gene dosage in regulating social, circadian, and motor functions, and the variables of sex and genomic positioning of CNVs in the expression of autism-related phenotypes. Importantly, mice with heterozygous loss of Nrxn1, as found in numerous autistic individuals, show an elevated propensity to manifest autism-related phenotypes, supporting the use of models with this genomic architecture to study ASD etiology and assess additional genetic variants associated with autism.

How to Be Irish in an Epidemic: A Dossier Article on HIV and AIDS in Ireland, Then and Now.

This dossier article contains four short and varied contributions from activists and other service and healthcare providers who have been agitating and working on the frontlines of HIV/AIDS in Ireland since the early 1980s. The dossier contains: (1) a history, by Bill Foley, of the early collective efforts of a group of gay men to provoke government action and healthcare under the umbrella of Gay Health Action (GHA) (2) a speech delivered by Dr. Erin Nugent to government officials on the re-branding of HIV Ireland in 2015; (3) a brief history, recounted by Noel Donnellan, of ACT UP Dublin since it was revitalized in 2016 by a small cohort of dedicated activists from a dormant group into a vibrant collective that has achieved great legislative change with regards to pre-exposure prophylaxis (PrEP); and (4) a polemic, written by Thomas Strong, on living with HIV as a queer man in Ireland that demonstrates the ways in which HIV stigma not only thrives in but molds and shapes twenty-first-century gay men's communities, both in real life and online.

Mulligan Knee Taping Using Both Elastic and Rigid Tape Reduces Pain and Alters Lower Limb Biomechanics in Female Patients With Patellofemoral Pain.

BACKGROUND: Evidence supports the use of Mulligan knee taping in managing patellofemoral pain (PFP). However, no studies have compared the efficacy of rigid and elastic tape using this technique. HYPOTHESIS: Mulligan knee taping applied with both rigid and elastic tape will produce similar reductions in knee pain, hip internal rotation, and knee flexion moments compared with no tape. Elastic tape will also be more comfortable than rigid tape. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 19 female patients (mean age, 26.5 ± 4.5 years) with PFP performed a self-selected pain provocative task, single-leg squat (SLSq) task, and running task while wearing Mulligan knee taping applied with rigid tape, elastic tape at 100% tension, and no tape. Pain and taping comfort were recorded using 11-point numeric rating scales. An 18-camera motion capture system and in-ground force plates recorded 3-dimensional lower limb kinematics and kinetics for the SLSq and running tasks. Statistical analysis involved a series of repeated-measures analyses of variance. The Wilcoxon signed rank test was used for analyzing taping comfort. RESULTS: Compared with no tape, both rigid and elastic tape significantly reduced pain during the pain provocative task (mean difference [MD], -0.97 [95% CI, -1.57 to -0.38] and -1.42 [95% CI, -2.20 to -0.64], respectively), SLSq (MD, -1.26 [95% CI, -2.23 to -0.30] and -1.13 [95% CI, -2.09 to -0.17], respectively), and running tasks (MD, -1.24 [95% CI, -2.11 to -0.37] and -1.16 [95% CI, -1.86 to -0.46], respectively). Elastic tape was significantly more comfortable than rigid tape generally (P = .005) and during activity (P = .022). Compared with no tape, both rigid and elastic tape produced increased knee internal rotation at initial contact during the running task (MD, 5.5° [95% CI, 3.6° to 7.4°] and 5.9° [95% CI, 3.9° to 7.9°], respectively) and at the commencement of knee flexion during the SLSq task (MD, 5.8° [95% CI, 4.5° to 7.0°] and 5.8° [95% CI, 4.1° to 7.4°], respectively), greater peak knee internal rotation during the running (MD, 1.8° [95% CI, 0.4° to 3.3°] and 2.2° [95% CI, 0.9° to 3.6°], respectively) and SLSq tasks (MD, 3.2° [95% CI, 2.1° to 4.3°] and 3.8° [95% CI, 2.3° to 5.2°], respectively), and decreased knee internal rotation range of motion during the running (MD, -3.6° [95% CI, -6.1° to -1.1°] and -3.7° [95% CI, -6.2° to -1.2°], respectively) and SLSq tasks (MD, -2.5° [95% CI, -3.9° to -1.2°] and -2.0° [95% CI, -3.2° to -0.9°], respectively). CONCLUSION: Mulligan knee taping with both rigid and elastic tape reduced pain across all 3 tasks and altered tibiofemoral rotation during the SLSq and running tasks. CLINICAL RELEVANCE: Both taping methods reduced pain and altered lower limb biomechanics. Elastic tape may be chosen clinically for comfort reasons.