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To identify risk factors for the development of new-onset, postoperative diplopia following orbital decompression surgery based on patient demographics, clinical exam characteristics, radiographic parameters, and surgical techniques.We conducted a multi-center retrospective chart review of patients who underwent orbital decompression for thyroid eye disease (TED). Patient demographics, including age, gender, smoking history, preoperative exophthalmometry, clinical activity score (CAS), use of peribulbar and/or systemic steroids, and type of orbital decompression were reviewed. Postoperative diplopia was determined at a minimum of 3 months postoperatively and before any further surgeries. Cross-sectional area ratios of each extraocular muscle to orbit and total fat to orbit were calculated from coronal imaging in a standard fashion. All measurements were carried out using PACS imaging software. Multivariable logistic regression modeling was performed using Stata 14.2 (StataCorp, College Station, TX).A total of 331 patients without preoperative diplopia were identified. At 3 months postoperatively, 249 patients had no diplopia whereas 82 patients developed diplopia. The average postoperative follow-up was 22 months (range 3-156) months. Significant preoperative clinical risk factors for postoperative diplopia included older age at surgery, proptosis, use of peribulbar or systemic steroids, elevated clinical activity score, and presence of preoperative compressive optic neuropathy. Imaging findings of enlarged cross-sectional areas of each rectus muscle to the overall orbital area also conferred a significant risk of postoperative diplopia. Regarding surgical factors, postoperative diplopia was more common among those undergoing medial wall decompression, bilateral orbital surgery, and balanced decompression, whereas endoscopic medial wall decompression was found to be relatively protective.This study identifies risk factors associated with the development of diplopia following orbital decompression using multivariable data. This study demonstrates that several characteristics including age, clinical activity score, the cross-sectional muscle to orbit ratios, in addition to the type of orbital decompression surgery, are predictive factors for the development of new-onset postoperative diplopia.

Objectives Adolescent Medicine (AM) in Canada has undergone significant growth since being accredited by the Royal College of Physicians and Surgeons of Canada (RCPSC) in May 2007. A deeper understanding of the workforce is needed in order to identify current gaps, to improve clinical care and scholarly endeavors, and to inform future developments. Methods This is the first AM workforce survey administered in Canada and included 39 multiple-choice and 3 open-ended questions. Descriptive statistics were calculated, and thematic analysis was used for open-ended questions. Results We identified 62 AM specialists from across Canada. The overall response was 97% (60/62). Most AM specialists were women (39/53, 74%), Caucasian (38/53, 72%), between 30 and 39 years old (22/53, 42%), and completed their subspecialty training in either Toronto (24/48, 50%) or Montreal (12/48, 25%). Nearly half of participants worked in either the Toronto, Ontario (13/49, 27%) or Montreal, Quebec (10/49, 20%). Nearly all participants (46/49, 94%) practiced in large urban population centres and were based in academic health science centres. The primary clinical areas of focus included eating disorders (25/51, 49%) and mental health (9/51, 18%). Almost all participants were satisfied with their career choice (41/50, 82%). Two-thirds of the participants (31/48, 65%) believed that there was an insufficient number of AM specialists in Canada. Conclusions Highlighting current characteristics of the AM subspecialty will help government and academic policymakers in understanding the workforce available to care for Canadian adolescents and the need to develop training programs and policies to address gaps and shortages.

While blood antibodies mediate protective immunity in most organs, whether they protect nasal surfaces in the upper airway is unclear. Using multiple viral infection models in mice, we found that blood-borne antibodies could not defend the olfactory epithelium. Despite high serum antibody titers, pathogens infected nasal turbinates, and neurotropic microbes invaded the brain. Using passive antibody transfers and parabiosis, we identified a restrictive blood-endothelial barrier that excluded circulating antibodies from the olfactory mucosa. Plasma cell depletions demonstrated that plasma cells must reside within olfactory tissue to achieve sterilizing immunity. Antibody blockade and genetically deficient models revealed that this local immunity required CD4

A 2-year long, multisite research study that evaluated cardiopulmonary resuscitation skill decay among nursing students was conducted at 10 schools of nursing across the United States. The study was conducted in two phases and required carefully timed sessions for skill performance. Multisite studies in nursing education need to be carefully planned. Time delays should be anticipated with processes and Institutional Review Board protocols across sites. All team members were trained and consistently supported during the entire study. While challenges and obstacles were identified, innovative solutions were implemented that assisted the research team to successfully complete the study. The use of new and existing technology allowed the team to surmount many of the challenges encountered in this study. The purpose of this article is to describe the logistics, processes, challenges, and lessons learned related to conducting a complex multisite study.

Cellular differentiation requires both activation of target cell transcriptional programs and repression of non-target cell programs. The Myt1 family of zinc finger transcription factors contributes to fibroblast to neuron reprogramming in vitro. Here, we show that ztf-11 (Zinc-finger Transcription Factor-11), the sole Caenorhabditis elegans Myt1 homolog, is required for neurogenesis in multiple neuronal lineages from previously differentiated epithelial cells, including a neuron generated by a developmental epithelial-to-neuronal transdifferentiation event. ztf-11 is exclusively expressed in all neuronal precursors with remarkable specificity at single-cell resolution. Loss of ztf-11 leads to upregulation of non-neuronal genes and reduced neurogenesis. Ectopic expression of ztf-11 in epidermal lineages is sufficient to produce additional neurons. ZTF-11 functions together with the MuvB corepressor complex to suppress the activation of non-neuronal genes in neurons. These results dovetail with the ability of Myt1l (Myt1-like) to drive neuronal transdifferentiation in vitro in vertebrate systems. Together, we identified an evolutionarily conserved mechanism to specify neuronal cell fate by repressing non-neuronal genes., eLife digest The human body contains many cell types that each have different job and can look very different from each other. However, each of the cells in an individual’s body contains almost exactly the same genes, because all of them share the same DNA inherited from the individual’s parents. Cells therefore become different from one another by controlling the activity of sets of genes. They do this by using proteins called transcription factors, which find specific genes and turn them either on or off. Nerve cells or neurons form and develop in a process called neurogenesis. During neurogenesis, some genes including those specific to neurons need to be switched on while other non-neuronal genes need to be switched off. The “off-switch” is particularly important when neurons are generated by conversion from skin cells, which sometimes happens in animals. Before these cells can become mature nerve cells, they require transcription factors to ensure that skin-specific genes are off. The transcription factors turning on nerve cell-specific genes are well-understood, but far less is known about those that turn off other genes. Lee et al. therefore set out to search for transcription factors that might switch off non-neuronal genes during neurogenesis and focused on one transcription factor that is known to be important for the development of nerve cells in a variety of animal species. Experiments using the worm C. elegans revealed that this transcription factor – called ZTF-11 in worms – was present in all cells destined to be nerve cells, but not in cells that would assume other roles. These experiments are possible with C. elegans because the final role, or ‘fate’, of each cell in the body are already known, all the way from the fertilized egg to the adult. Further work, using genetically engineered worms revealed that ZTF-11 worked by turning off genes that are related to the development of non-nerve cells. Deleting the gene for ZTF-11 in immature nerve cells allowed these cells to turn on different sets of genes and resulted in adult worms with fewer mature nerve cells than normal worms. On the other hand, forcing other cell types (which would not normally become part of the nervous system) to produce ZTF-11 was sufficient to convert them into nerve cells. These results are an important step forward in understanding how nerve cells are built in the developing body, especially how nerve cells can be made from other cell types. In the future, this knowledge could be used to help people with diseases of the nervous system, such as Parkinson’s disease.

The sensory nervous system of C. elegans comprises cells with varied molecular and functional characteristics, and is, therefore, a powerful model for understanding mechanisms that generate neuronal diversity. We report here that VAB-3, a C. elegans homolog of the homeodomain-containing protein Pax6, has opposing functions in regulating expression of a specific chemosensory fate. A homeodomain-only short isoform of VAB-3 is expressed in BAG chemosensory neurons, where it promotes gene expression and cell function. In other cells, a long isoform of VAB-3, comprising a Paired homology domain and a homeodomain, represses expression of ETS-5, a transcription factor required for expression of BAG fate. Repression of ets-5 requires the Eyes Absent homolog EYA-1 and the Six-class homeodomain protein CEH-32. We determined sequences that mediate high-affinity binding of ETS-5, VAB-3 and CEH-32. The ets-5 locus is enriched for ETS-5-binding sites but lacks sequences that bind VAB-3 and CEH-32, suggesting that these factors do not directly repress ets-5 expression. We propose that a promoter-selection system together with lineage-specific expression of accessory factors allows VAB-3/Pax6 to either promote or repress expression of specific cell fates in a context-dependent manner. This article has an associated 'The people behind the papers' interview.

Anorexia nervosa may arise from a wide range of influences, often involving an interplay of biological, psychological, and sociocultural factors. The present study examines the nature of triggers for children and adolescents with anorexia nervosa at the time of diagnosis.A qualitative retrospective chart review of 50 patients diagnosed with anorexia nervosa-restrictive subtype was conducted, revealing both specific and non-specific themes for triggers of anorexia nervosa.Specific themes revealed triggers pertaining to internalization of the thin ideal, healthy eating education, sports performance motivations, and weight-related teasing. Non-specific factors included general preoccupations about weight, shape, and healthiness.Examining adolescent perceptions of healthy messages from key players, including teachers, family, and peers, can better inform researchers and policy makers of the impact of health-focused messages on child and adolescent populations.L’anorexie mentale peut venir d’une vaste gamme d’influences, comportant souvent une interaction de facteurs biologiques, psychosociaux et socioculturels. La présente étude examine la nature des déclencheurs pour les enfants et les adolescents souffrant d’anorexie mentale au moment du diagnostic.Une revue rétrospective qualitative des dossiers de 50 patients ayant reçu un diagnostic d’anorexie mentale, du sous-type restrictif, a été menée, révélant des thèmes spécifiques et non spécifiques pour les déclencheurs de l’anorexie mentale.Des thèmes spécifiques ont révélé des déclencheurs relatifs à l’internalisation de l’idéal de minceur, de l’éducation en alimentation saine, de la motivation de performance sportive, et des taquineries liées au poids. Les facteurs non spécifiques incluaient des préoccupations générales sur le poids, la forme et la santé.L’examen des perceptions qu’ont les adolescents des messages de santé lancés par les principaux acteurs, notamment les enseignants, la famille et les pairs est plus apte à informer les chercheurs et les décideurs de l’impact des messages axés sur la santé sur les populations des enfants et des adolescents.

Lysophosphatidic acid (LPA) activates cognate G protein-coupled receptors (GPCRs) to initiate biological signaling cascades. Lysophospholipid (LP) receptor binding properties remain incompletely assessed because of difficulties with ligand lipophilicity and lipid “stickiness.” These inherent attributes produce high levels of nonspecific binding within cell-membrane preparations used to assess GPCRs, as has been shown in classical binding assays using radiolabeled ligands, making accurate measurements of lipid binding kinetics difficult to achieve. Backscattering interferometry (BSI) is an optical technology that measures molecular binding interactions by reporting changes in the refractive index of a solution after binding events. Here, we report the use of BSI to assess LPA(1) for its ability to bind to naturally occurring lipids and a synthetic LPA(1) antagonist (ONO-9780307), under both primary- and competition-binding conditions. Assessment of 12 different lipids demonstrated that the known LP ligand, 1-oleoyl-LPA, as well as an endocannabinoid metabolite, anandamide phosphate, are specific ligands for LPA(1), whereas other LPs tested were not. Newly determined dissociation constants (K(d) values) for orthosteric lipid ligands approximated 10(−9) M, substantially lower (i.e., with higher affinity) than measured K(d) values in classical binding or cell-based assays. These results demonstrate that BSI may have particular utility in assessing binding interactions between lipid receptors and their lipid ligands and could provide new screening approaches for lipid receptor identification and drug discovery.

The sensory nervous system of C. elegans comprises cells with varied molecular and functional characteristics, and is, therefore, a powerful model for understanding mechanisms that generate neuronal diversity. We report here that VAB-3, a C. elegans homolog of the homeodomain-containing protein Pax6, has opposing functions in regulating expression of a specific chemosensory fate. A homeodomain-only short isoform of VAB-3 is expressed in BAG chemosensory neurons, where it promotes gene expression and cell function. In other cells, a long isoform of VAB-3, comprising a Paired homology domain and a homeodomain, represses expression of ETS-5, a transcription factor required for expression of BAG fate. Repression of ets-5 requires the Eyes Absent homolog EYA-1 and the Six-class homeodomain protein CEH-32. We determined sequences that mediate high-affinity binding of ETS-5, VAB-3 and CEH-32. The ets-5 locus is enriched for ETS-5-binding sites but lacks sequences that bind VAB-3 and CEH-32, suggesting that these factors do not directly repress ets-5 expression. We propose that a promoter-selection system together with lineage-specific expression of accessory factors allows VAB-3/Pax6 to either promote or repress expression of specific cell fates in a context-dependent manner. This article has an associated ‘The people behind the papers’ interview.

Lysophosphatidic acid (LPA) is a bioactive phospholipid that is present in all tissues examined to date. LPA signals extracellularly via cognate G protein-coupled receptors to mediate cellular processes such as survival, proliferation, differentiation, migration, adhesion and morphology. These LPA-influenced processes impact many aspects of organismal development. In particular, LPA signalling has been shown to affect fertility and reproduction, formation of the nervous system, and development of the vasculature. Here and in the accompanying poster, we review the developmentally related features of LPA signalling.

Posttraumatic stress symptoms (PTS) are associated with increased risk of obstetric complications among pregnant survivors of trauma, abuse and interpersonal violence, but little is known about how PTS affects women's actual experiences of obstetric care. This study investigated the rate at which abuse history was detected by obstetricians, whether abuse survivors experienced more invasive exams than is typically indicated for routine obstetric care, and whether psychological distress was associated with abuse survivors' sense of self-efficacy when communicating their obstetric care needs.Forty-one pregnant abuse survivors completed questionnaires about abuse history, current psychological distress and self-efficacy for communicating obstetric care needs and preferences. Electronic medical records (EMRs) were reviewed to examine frequency of invasive prenatal obstetric procedures (e.g. removal of clothing for external genital examination, pelvic exams and procedures) and to examine the detection rate of abuse histories during the initial obstetric visit.The majority of participants (83%) reported at least one past incident of violent physical or sexual assault. Obstetricians detected abuse histories in less than one quarter of cases. Nearly half of participants (46%) received invasive exams for non-routine reasons. PTS and depression symptoms were associated with lower self-efficacy in communicating obstetric care preferences.Women most at risk for experiencing distress during their obstetric visits and/or undergoing potentially distressing procedures may also be the least likely to communicate their distress to obstetricians. Results are discussed with implications for improving screening for abuse screening and distress symptoms as well as need for trauma-sensitive obstetric practices.

Single-nucleus gene expression Identifying the genes expressed at the level of a single cell nucleus can better help us understand the human brain. Blue et al. developed a single-nuclei sequencing technique, which they applied to cells in classically defined Brodmann areas from a postmortem brain. Clustering of gene expression showed concordance with the area of origin and defining 16 neuronal subtypes. Both excitatory and inhibitory neuronal subtypes show regional variations that define distinct cortical areas and exhibit how gene expression clusters may distinguish between distinct cortical areas. This method opens the door to widespread sampling of the genes expressed in a diseased brain and other tissues of interest. Science , this issue p. 1586

The quality of postoperative care received by patients undergoing resident-performed cataract surgery is not well described. In a retrospective chart review, this study investigated the prevalence and preoperative predictors of noncompliance with postoperative cataract surgery care in an urban teaching hospital. It found that one in four patients was noncompliant with cataract surgery postoperative care and that age 50 years or less was a key predictor of non-compliance.