Behavioral and neurological effects of Vrk1 deficiency in zebrafish.

Vaccinia-related kinase 1 (VRK1) is a serine/threonine kinase, for which mutations have been reported cause to neurodegenerative diseases, including spinal muscular atrophy, characterized by microcephaly, motor dysfunction, and impaired cognitive function, in humans. Partial Vrk1 knockdown in mice has been associated with microcephaly and impaired motor function. However, the pathophysiological relationship between VRK1 and neurodegenerative disorders and the precise mechanism of VRK1-related microcephaly and motor function deficits have not been fully investigated. To address this, in this study, we established vrk1-deficient (vrk1-/-) zebrafish and found that they show mild microcephaly and impaired motor function with a low brain dopamine content. Furthermore, vrk1-/- zebrafish exhibited decreased cell proliferation, defects in nuclear envelope formation, and heterochromatin formation in the brain. To our knowledge, this is the first report demonstrating the important role of VRK1 in microcephaly and motor dysfunction in vivo using vrk1-/- zebrafish. These findings contribute to elucidating the pathophysiological mechanisms underlying VRK1-mediated neurodegenerative diseases associated with microcephaly.

Vrk2 deficiency elicits aggressive behavior in female zebrafish.

Vaccinia-related kinase 2 (VRK2) is a serine/threonine kinase initially identified in highly proliferative cells such as thymocytes and fetal liver cells, and it is involved in cell proliferation and survival. VRK2 is also expressed in the brain; however, its molecular function in the central nervous system is mostly unknown. Many genome-wide association studies (GWASs) have reported that VRK2 is a potential candidate molecule for neuropsychiatric diseases such as schizophrenia in humans. However, the pathophysiological relationship between VRK2 and neuropsychiatric disorders has not been fully investigated. In this study, we evaluated vrk2-deficient (vrk2-/- ) zebrafish and found that vrk2-/- female zebrafish showed aggressive behavior and different social preference compared with control (vrk2+/+ ) zebrafish, with low gamma-aminobutyric acid (GABA) content in the brain and high density of neuronal dendrites when compared to vrk2+/+ zebrafish. These findings suggest that female vrk2-/- zebrafish were indeed a model of malbehavior characterized by aggression and social interaction, which can be attributed to the low levels of GABA content in their brain.

Cocaine has some effect on neuromedin U expressing neurons related to the brain reward system.

Neuromedin U (NMU) is a bioactive neuropeptide, highly distributed in the gastrointestinal tract and the central nervous system. NMU has various physiological functions related to feeding behavior, energy metabolism, stress responses, circadian rhythmicity and inflammation. Recently, several reports indicate that the central NMU system plays an important role in the reward systems in the brain. However, the underlying molecular mechanisms are not yet fully defined. In this study, we found that some of cocaine-induced c-Fos immunoreactive cells were co-localized with NMU in the nucleus accumbens (NAc), caudate putamen (CPu), and basolateral amygdala (BLA), which are key brain regions associated with the brain reward system, in wild type mice. Whereas, a treatment with cocaine did not influence the kinetics of NMU or NMU receptors mRNA expression in these brain regions, and NMU-knockout mice did not show any higher preference for cocaine compared with their control mice. These results indicate that cocaine has some effect on NMU expressing neurons related to the brain reward system, and this suggests NMU system may have a role on the brain reward systems activated by cocaine.

Demographic and clinical characteristics of dominican adults admitted to a diabetic foot clinic in the Dominican Republic, 2015.

AIM: To identify the demographic and clinical characteristics of Dominican adults admitted to a diabetic foot clinic and compare these characteristics by sex to better characterize and understand the severity of diabetes in the Dominican Republic. METHODS: We conducted a retrospective medical chart review of Dominican adults admitted to the National Institute of Diabetes, Endocrinology, and Nutrition's (INDEN) diabetic foot clinic between January 1st, 2015 and December 31st, 2015. We generated descriptive statistics and compared results by sex. RESULTS: We assessed 447 medical charts of patients admitted in 2015. More men visited the clinic than women (65% vs. 35%). The average duration of diabetes was 14.4 ±â€¯8.9 years. Abscess was the most common foot problem (74% in men, 68% in women, p = 0.164). A slightly smaller proportion of men received amputations than women (46% vs. 51%, p = 0.390). Women were older (p < 0.001), less educated (p = 0.004), and less likely to be married (p < 0.001). Women also exhibited higher rates of obesity (p = 0.003), hypertension (p = 0.005), cardiovascular disease (p = 0.011), ischemic foot (p = 0.008), and above the knee amputations (p = 0.002). CONCLUSION: Implementation of diabetes education programs, introduction of proper foot care, and improved resources for lifestyle management are needed to increase awareness and subsequently decrease diabetes and its negative impact on the health and economy of the Dominican Republic. Our findings suggest that various risk factors and comorbidities important to the development of diabetes may be disproportionately affecting women. Interventions should focus on women and their behaviors that increase risk for diabetes.