A Cell-Specific Analysis Of Gene Expression In The Neural Crest Of Zebrafish.

This thesis presents a new approach to the rapid and systematic identification of genes expressed differentially between specific cell types. The approach is based upon the hybridization of amplified tissue or cell-specific complex cDNA probes to robotically arrayed cDNA libraries and the computer-assisted analysis ('electronic subtraction') of the resulting hybridization patterns. This approach was applied to two populations of cultured zebrafish neural crest cells, as well as to tissue from ventral trunk neural tube. Sets of cDNA clones were assembled that putatively represent genes expressed in early-migrating trunk neural crest cells (390 clones), late-migrating trunk neural crest cells (422 clones), or both neural crest cell populations (292 clones), but not in ventral trunk neural tube. The procedures and techniques used were tested for reproducibilty and initial conclusions are made about the feasibility and validity of the approach. A critical assessment of the techniques apphed suggests aspects of the approach which might be improved in its future application

Treatment-resistant OCD: Pharmacotherapies in adults

Serotonin reuptake inhibitor (SRI) medications are well established as first-line pharmacotherapeutic treatment for Obsessive-Compulsive Disorder (OCD). However, despite the excellent safety profile and demonstrated ef-ficacy of these medications, a substantial proportion of individuals with OCD fail to attain sufficient benefit from SRIs. In this narrative review, we discuss clinical features of OCD that have been associated with poorer response to SRIs, and we present pharmacotherapeutic interventions that have been explored as augmenting or alternative treatments for treatment-resistant OCD. We additionally highlight non-SRI interventions for OCD that are currently under investigation. Pharmacotherapeutic interventions were identified via expert consensus. To assess the evidence base for in-dividual pharmacotherapies, targeted searches for relevant English-language publications were performed on standard biomedical research databases, including MEDLINE. Information relevant to ongoing registered clinical trials in OCD was obtained by search of ClinicalTrials.gov. Pharmacotherapies are grouped for review in accordance with the general principles of Neuroscience-based Nomenclature (NbN). Clinical features of OCD that may suggest poorer response to SRI treatment include early age of onset, severity of illness, duration of untreated illness, and the presence of symmetry/ordering or hoarding-related symptoms. Based on evolving pathophysiologic models of OCD, diverse agents engaging serotonin, dopamine, norepi-nephrine, glutamate, and anti-inflammatory pathways have been explored as alternative or adjunctive therapies for treatment-resistant OCD and have at least preliminary evidence of efficacy. Medications with dopamine antagonist activity remain the most robustly evidence-based of augmenting in-terventions, yet dopamine antagonists benefit only a minority of those who try them and carry elevated risks of adverse effects. Interventions targeting glutamatergic and anti-inflammatory pathways are less well evidenced, but may offer more favorable benefit to risk profiles. Ongoing research should explore whether specific in-terventions may benefit individuals with particular features of treatment-resistant OCD

Identity gripping or identity flight? Two distinct experiences correlated with self-reported depression in retired professional ice hockey players

This study presents qualitative data on the retirement experiences of retired professional ice hockey players and the relationship of these experiences to self-reported depressive symptoms and measures of athletic identity. Data were obtained from an online survey sent to retired professional hockey players within the Professional Hockey Players’ Association (PHPA) database. A total of 213 retired players completed the qualitative section of the survey and were included in the study. Former players expressed an array of responses to questions about the best and most difficult parts of their athletic retirement experiences, and what they believe would help future generations of retiring hockey players. Within these responses, there were two distinct patterns of identity-based challenges among depressed former players. One subset of depressed former players, captured by our proposed term athletic identity flight, scored lower in athletic identity, and emphasized positive aspects of retirement related to “building a new identity.” A second subset of depressed former players, who we described with the term athletic identity gripping, noted an identity crisis upon retiring and retained a strong athletic identity post-career. Non-depressed former players in our sample were more likely to emphasize the importance of career support to help future retiring hockey players, whereas depressed former players emphasized the importance of mental health support. Our findings may inform future preventative interventions to assist retiring hockey players in their end-of-athletic-career transition and suggest the value of tailoring interventions based on the strength of athletic identity and the presence of depressive symptoms

Nosocomial RSV-related In-hospital Mortality in Children:A Global Case Series

Background: According to the World Health Organization, the global burden of nosocomial infections is poorly characterized as surveillance systems are lacking. Nosocomial infections occur at higher rates in low- and lower-middle-income countries (LMICs) than in high-income countries (HICs). Current global RSV burden estimates are largely based on community-acquired infection. We aimed to characterize children with nosocomial RSV-related mortality and to understand the potential impact of RSV immunization strategies. Materials: RSV GOLD is a global registry of children younger than 5 years who died with laboratory-confirmed RSV infection. We compared clinical and demographic characteristics of children with nosocomial and community-acquired RSV in-hospital mortality. Results: We included 231 nosocomial and 931 community-acquired RSVrelated in-hospital from deaths from 65 countries. Age at death was similar for both groups (5.4 vs. 6 months). A higher proportion of nosocomial deaths had comorbidities (87% vs. 57%; P < 0.001) or was born preterm (46% vs. 24%; P < 0.001) than community-acquired deaths. The proportion of nosocomial deaths among all RSV deaths was lower in LMICs than in upper-middle-income countries (UMICs) and HICs (12% vs. 18% and 26%, respectively). Conclusions: This is the first global case series of children dying with nosocomial RSV infection. Future infant-targeted immunization strategies could prevent the majority of nosocomial RSV-related deaths. Although nosocomial RSV deaths are expected to occur at highest rates in LMICs, the number of reported nosocomial RSV deaths was low in these countries. Hospital-based surveillance is needed to capture the full burden of nosocomial RSV mortality in LMICs.Fil: Löwensteyn, Yvette N.. University Medical Center Utrecht; Países BajosFil: Willemsen, Joukje E.. University Medical Center Utrecht; Países BajosFil: Mazur, Natalie I.. University Medical Center Utrecht; Países BajosFil: Scheltema, Nienke M.. University Medical Center Utrecht; Países BajosFil: Van Haastregt, Nynke C. J.. University Medical Center Utrecht; Países BajosFil: Ten Buuren, Amber A. A.. University Medical Center Utrecht; Países BajosFil: Van Roessel, Ichelle. University Medical Center Utrecht; Países BajosFil: Scheepmaker, Dunja. University Medical Center Utrecht; Países BajosFil: Nair, Harish. Respiratory Syncytial Virus Network Foundation; Países Bajos. University of Edinburgh; Reino UnidoFil: Van De Ven, Peter M.. University Medical Center Utrecht; Países BajosFil: Bont, Louis J.. University Medical Center Utrecht; Países Bajos. Respiratory Syncytial Virus Network Foundation; Países BajosFil: Caballero, Mauricio Tomás. Fundación Infant; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Music, Medicine, and the Art of Listening

The use of the arts in medical education has become increasingly widespread. Narrative and visual media, in particular, have received great attention as tools for teaching skills of empathy, observation and reflection. Music, however, has been relatively less applied in this context, and may be perceived as lacking immediate relevance to medicine. In this article, we first review various areas of interface between music and medicine. We then describe a curricular innovation undertaken at our institution using musical performance to demonstrate the value of music as a metaphor for communication in the practice of medicine

A Role for Dystonia-Associated Genes in Spinal GABAergic Interneuron Circuitry

Spinal interneurons are critical modulators of motor circuit function. In the dorsal spinal cord, a set of interneurons called GABApre presynaptically inhibits proprioceptive sensory afferent terminals, thus negatively regulating sensory-motor signaling. Although deficits in presynaptic inhibition have been inferred in human motor diseases, including dystonia, it remains unclear whether GABApre circuit components are altered in these conditions. Here, we use developmental timing to show that GABApre neurons are a late Ptf1a-expressing subclass and localize to the intermediate spinal cord. Using a microarray screen to identify genes expressed in this intermediate population, we find the kelch-like family member Klhl14, implicated in dystonia through its direct binding with torsion-dystonia-related protein Tor1a. Furthermore, in Tor1a mutant mice in which Klhl14 and Tor1a binding is disrupted, formation of GABApre sensory afferent synapses is impaired. Our findings suggest a potential contribution of GABApre neurons to the deficits in presynaptic inhibition observed in dystonia