Loss of function in somatostatin receptor 5 has no impact on the growth of medaka fish due to compensation by the other paralogs.

Somatic growth in vertebrates is regulated endocrinologically by the somatotropic axis, headed by the growth hormone (GH) and the insulin growth factor-I (IGF-I). Somatostatin (Sst), a peptide hormone synthesized in the hypothalamus, modulates GH actions through its receptors (Sstr). Four Sstr subtypes (Sstr 1-3 and 5) have been identified in teleosts. However, little is known about whether they have a specific function or tissue expression. The aim of this study was to determine the role of sstr2 and sstr5 in the growth of the medaka (Oryzias latipes). The assessed expression pattern across diverse tissues highlighted greater prevalence of sstr1 and sstr3 in brain, intestine and muscle than in pituitary or liver. The expression of sstr2 was high in all the tissues tested, while sstr5 was predominantly expressed in the pituitary gland. A CRISPR/Cas9 sstr5 mutant with loss of function (sstr5-/-) was produced. Assessment of sstr5-/- indicated no significant difference with the wild type regarding growth parameters such as standard length, body depth, or peduncle depth. Furthermore, the functional loss of sstr5 had no impact on the response to a nutritional challenge. The fact that several sstr subtypes were upregulated in different tissues in sstr5-/- medaka suggests that in the mutant fish, there may be a compensatory effect on the different tissues, predominantly by sstr1 in the liver, brain and pituitary, with sstr2 being upregulated in pituitary and liver, and sstr3 only presenting differential expression in the brain. Analysis of the sstr subtype and the sstr5-/- fish showed that sstr5 was not the only somatostatin receptor responsible for Sst-mediated Gh regulation.

Differential Impact of Index Stroke on Dementia Risk in African-Americans Compared to Whites.

OBJECTIVE: To compare whites and African-Americans in terms of dementia risk following index stroke. METHODS: The data consisted of billing and International Classification of Diseases, Ninth Revision diagnosis codes from the South Carolina Revenue and Fiscal Affairs office on all hospital discharges within the state between 2000 and 2012. The sample consisted of 68,758 individuals with a diagnosis of ischemic stroke prior to 2010 (49,262 white [71.65%] and 19,496 African-Americans [28.35%]). We identified individuals in the dataset who were subsequently diagnosed with any of 5 categories of dementia and evaluated time to dementia diagnosis in Cox Proportional Hazards models. We plotted cumulative hazard curves to illustrate the effect of race on dementia risk after controlling for age, sex, and occurrence of intervening stroke. RESULTS: Age at index stroke was significantly different between the 2 groups, with African-Americans being younger on average (70.0 [SD 12.5] in whites versus 64.5 [SD 14.1] in African-Americans, P < .0001). Adjusted hazard ratios revealed that African-American race increased risk for all 5 categories of dementia following incident stroke, ranging from 1.37 for AD to 1.95 for vascular dementia. Age, female sex, and intervening stroke likewise increased risk for dementia. CONCLUSIONS: African-Americans are at higher risk for dementia than whites within 5 years of ischemic stroke, regardless of dementia subtype. Incident strokes may have a greater likelihood of precipitating dementia in African-Americans due to higher prevalence of nonstroke cerebrovascular disease or other metabolic or vascular factors that contribute to cognitive impairment.

The clinical course of sarcoidosis: presentation, diagnosis, and treatment in a large white and black cohort in the United States.

BACKGROUND: Although numerous reports have described the clinical features of sarcoidosis in various ethnic and racial groups, many have been limited by small size, homogenous populations, and relatively short follow-up periods. We report the clinical characteristics of a large, race-sex-age diverse cohort of sarcoidosis clinic patients followed in a large university medical center for an extended period of time. METHODS: This study included clinical data for sarcoidosis patients followed over a 12-year period at a sarcoidosis clinic at the Medical University of South Carolina. RESULTS: 1774 sarcoidosis patients were identified. Black females were more common (44%) than other race/gender combinations (p = 0.01). The diagnosis of sarcoidosis occurred > 3 months after the onset of symptoms in 48% of the cohort and > 1 year after the onset of symptoms in 25%. Anti-sarcoidosis treatment was required in 61% of the patients. Pulmonary function improved over time and the median corticosteroid requirement lessened. Compared to whites, blacks had more advanced radiographic stages of sarcoidosis (p < 0.0001), more organ involvement (p < 0.0001), and more frequently required anti-sarcoidosis medication (p < 0.0001). Compared to women, men had more advanced radiographic stages of sarcoidosis (p < 0.0001). CONCLUSIONS: The analysis indicates that sarcoidosis tends to improve over time in terms of pulmonary function and medication requirements. The disease was found to be more severe in blacks than whites. Treatment was not necessarily required. These results provide a comprehensive model of the course and treatment of sarcoidosis in the clinical setting.

Defining in Detail and Evaluating Reliability of DSM-5 Criteria for Autism Spectrum Disorder (ASD) Among Children.

This paper describes a process to define a comprehensive list of exemplars for seven core Diagnostic and Statistical Manual (DSM) diagnostic criteria for autism spectrum disorder (ASD), and report on interrater reliability in applying these exemplars to determine ASD case classification. Clinicians completed an iterative process to map specific exemplars from the CDC Autism and Developmental Disabilities Monitoring (ADDM) Network criteria for ASD surveillance, DSM-5 text, and diagnostic assessments to each of the core DSM-5 ASD criteria. Clinicians applied the diagnostic exemplars to child behavioral descriptions in existing evaluation records to establish initial reliability standards and then for blinded clinician review in one site (phase 1) and for two ADDM Network surveillance years (phase 2). Interrater reliability for each of the DSM-5 diagnostic categories and overall ASD classification was high (defined as very good .60-.79 to excellent ≥ .80 Kappa values) across sex, race/ethnicity, and cognitive levels for both phases. Classification of DSM-5 ASD by mapping specific exemplars from evaluation records by a diverse group of clinician raters is feasible and reliable. This framework provides confidence in the consistency of prevalence classifications of ASD and may be further applied to improve consistency of ASD diagnoses in clinical settings.