33356 A multinational chart review to examine gastrointestinal symptoms and their management in patients treated with apremilast for plaque psoriasis

Background: Diarrhea and nausea are the most common adverse events observed in phase 3 clinical trials and real-world studies of apremilast, an oral phosphodiesterase-4 inhibitor indicated for moderate-to-severe plaque psoriasis. Methods: A retrospective chart review was conducted between June and November 2020 in the United States (US) and France among patients with moderate psoriasis experiencing gastrointestinal (GI) symptoms within 3 months of initiating apremilast. Results: Dermatologists in US (200) and in France (52) abstracted patient charts (US: 494, France: 128). The following GI symptoms were reported: ‒diarrhea (US: 67% [331/494]; France: 76% [97/128]) with median time from onset to resolution/improvement of 26 days (US) and 21 days (France) ‒nausea (US: 52% [255/494]; France: 34% [44/128]) with median time from onset to resolution/improvement of 21 days (US) and 24 days (France). Management strategies for diarrhea included pharmacologic (loperamide/bismuth subsalicylate/racecadotril) with or without nonpharmacologic (dietary modifications, taking with food)/fiber (US: 30% [99/331], France: 41% [40/97]) and nonpharmacologic only (US: 32% [105/331], France: 27% [26/97]). Management strategies for nausea included pharmacologic (diphenhydramine/metoclopramide/metopimazine) with or without nonpharmacologic (dietary modifications, taking with food, avoidance of vigorous activity) (US: 5% [14/255], France: 30% [13/44]) and nonpharmacologic only (US: 58% [147/255], France: 36% [16/44]). Resolution/improvement of GI symptoms was observed in patients who used pharmacologic strategies and nonpharmacologic strategies. Conclusions: Recommendations to manage diarrhea and nausea after apremilast initiation with pharmacologic or non-pharmacologic strategies were effective and symptoms usually resolved within 3-4 weeks of onset

Gene editing and Rett syndrome: does it make the cut?

Rett syndrome (RTT) is a rare neurogenetic disorder caused by pathogenic variants of the Methyl CpG binding protein 2 (MECP2) gene. The RTT is characterized by apparent normal early development followed by regression of communicative and fine motor skills. Comorbidities include epilepsy, severe cognitive impairment, and autonomic and motor dysfunction. Despite almost 60 clinical trials and the promise of a gene therapy, no cure has yet emerged with treatment remaining symptomatic. Advances in understanding RTT has provided insight into the complexity and exquisite control of MECP2 expression, where loss of expression leads to RTT and overexpression leads to MECP2 duplication syndrome. Therapy development requires regulated expression that matches the spatiotemporal endogenous expression of MECP2 in the brain. Gene editing has revolutionized gene therapy and promises an exciting strategy for many incurable monogenic disorders, including RTT, by editing the native locus and retaining endogenous gene expression. Here, we review the literature on the currently available editing technologies and discuss their limitations and applicability to the treatment of RTT

The Inq13 POOC::A Participatory Experiment in Open, Collaborative Teaching and Learning.

This article offers a broad analysis of a POOC (“Participatory Open Online Course”) offered through the Graduate Center, CUNY in 2013. The large collaborative team of instructors, librarians, educational technologists, videographers, students, and project leaders reflects on the goals, aims, successes, and challenges of the experimental learning project. The graduate course, which sought to explore issues of participatory research, inequality and engaged uses of digital technology with and through the New York City neighborhood of East Harlem, set forth a unique model of connected learning that stands in contrast to the popular MOOC (Massive Open Online Course) model

Associations between sitting time and a range of symptoms in mid-age women

Objective. The aim of this study was to explore longitudinal associations between sitting and physical and psychological symptoms in mid-age women

Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders

Response to Beretich and Beretich

no abstract availabl

The cultural politics of human rights and neoliberalism

Do human rights offer the potential to challenge neo-liberalism? I argue that rather than understanding human rights as ideology, as obscuring or legitimating neo-liberalism, it is more productive to see both human rights and neo-liberalism as hegemonic projects. In this article I explore convergences and divergences between dominant discourses and practices of human rights and neo-liberalism around key ideas ‘the state’, ‘the individual’ and ‘the nation’, to clear a space for appreciation of the cultural politics of human rights: divergences in constructions of responsibility and hierarchies of value of concrete individuals offer openings for challenging ideas and practices of neo-liberalism through campaigns for human rights

Pediatric Acupuncture: A Review of Clinical Research

Practiced in China for more than 2000 years, acupuncture has recently gained increased attention in the United States as an alternative treatment approach for a variety of medical conditions. Despite its growing prevalence and anecdotal reports of success among pediatric populations, few empirically based studies have assessed the efficacy of acupuncture for children and adolescents. This article presents a review of the current literature, including a systematic appraisal of the methodological value of each study and a discussion of potential benefits and adverse effects of acupuncture. While acupuncture holds great promise as a treatment modality for diverse pediatric conditions, a significant amount of additional research is necessary to establish an empirical basis for the incorporation of acupuncture into standard care

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2.

Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms