An update on transcriptional and post-translational regulation of brain voltage-gated sodium channels

Voltage-gated sodium channels are essential proteins in brain physiology, as they generate the sodium currents that initiate neuronal action potentials. Voltage-gated sodium channels expression, localisation and function are regulated by a range of transcriptional and post-translational mechanisms. Here, we review our understanding of regulation of brain voltage-gated sodium channels, in particular SCN1A (Naᵥ1.1), SCN2A (Naᵥ1.2), SCN3A (Naᵥ1.3) and SCN8A (Naᵥ1.6), by transcription factors, by alternative splicing, and by post-translational modifications. Our focus is strongly centred on recent research lines, and newly generated knowledge

Using the Physical Activity Kit (PAK) to Get People Moving.

Presented at: Administration for Children and Families Tribal/Native American Grantee Conference; June 6-8; Alexandria, VA.https://digitalrepository.unm.edu/prc-posters-presentations/1061/thumbnail.jp

Clinicians’ understanding of ICD-10 diagnostic criteria for F62.0 enduring personality change after catastrophic experience

ICD-10 has included a diagnostic category of "enduring personality change after catastrophic experience" (EPCACE). Preliminary investigation suggests there is considerable endorsement in principle for this new category amongst experts in the field of intentional human trauma, yet many aspects of the diagnosis remain contentious. Criticisms leveled at EPCACE raised issues that question the reliability, validity and clinical utility of this diagnostic category. ICD-10 has two sets of documents describing EPCACE criteria. These are diagnostic criteria for research (DCR) and clinical description and diagnostic guidelines (CDDG). My aim in this research is to clarify EPCACE criteria by examining how clinicians described the symptoms which conform to or exceed the criteria of EPCACE that they observed in their clients. No other published research has yet emerged examining the descriptive validity of this category. I employed a qualitative approach from a social phenomenology and applied policy research perspectives to gather the views and experiences of clinicians. Twenty four clinicians working in the area of torture and refugee trauma, war trauma and sexual assault trauma were interviewed in depth for this study. Using the CDDG, clinicians recognize personality change as a consequence of trauma. Clinicians’ understanding of the manifestations of symptoms of EPCACE resulted in a composite interpretative description of the symptom criteria of EPCACE. Hostility or mistrust was identified as a core symptom. Somatization, self injurious behaviours, sexual dysfunction and enduring guilt are additional features that are not encompassed by current EPCACE criteria. Hypothesized relationships between symptoms are suggested. This study contributes to the descriptive validity of EPCACE. It demonstrates the utility of a qualitative approach to descriptive validation of diagnostic criteria. Participation of clinicians as members of working parties in the development and review of diagnostic criteria is a firm recommendation arising from this study. The symptom descriptors generated from this study could be used to enhance the CDDG. Similarities and differences between the DCR and CDDG highlighted issues that have implications in clinical practice. Research opportunities have been identified to further enhance the validity and clinical utility of EPCACE

Are Computers Good for Children? The Effects of Home Computers on Educational Outcomes

Although computers are universal in the classroom, nearly twenty million children in the United States do not have computers in their homes. Surprisingly, only a few previous studies explore the role of home computers in the educational process. Home computers might be very useful for completing school assignments, but they might also represent a distraction for teenagers. We use several identification strategies and panel data from the two main U.S. datasets that include recent information on computer ownership among children -- the 2000-2003 CPS Computer and Internet Use Supplements (CIUS) matched to the CPS Basic Monthly Files and the National Longitudinal Survey of Youth 1997 -- to explore the causal relationship between computer ownership and high school graduation and other educational outcomes. Teenagers who have access to home computers are 6 to 8 percentage points more likely to graduate from high school than teenagers who do not have home computers after controlling for individual, parental, and family characteristics. We generally find evidence of positive relationships between home computers and educational outcomes using several identification strategies, including controlling for typically unobservable home environment and extracurricular activities in the NLSY97, fixed effects models, instrumental variables, and including future computer ownership and falsification tests. Home computers may increase high school graduation by reducing non-productive activities, such as truancy and crime, among children in addition to making it easier to complete school assignments.technology, computers, education

Regularity of fractional maximal functions through Fourier multipliers

We prove endpoint bounds for derivatives of fractional maximal functions with either smooth convolution kernel or lacunary set of radii in dimensions $n \geq 2$. We also show that the spherical fractional maximal function maps $L^p$ into a first order Sobolev space in dimensions $n \geq 5$

Microwave-assisted synthesis of 3-aminobenzo[b]thiophene scaffolds for the preparation of kinase inhibitors

Microwave irradiation of 2-halobenzonitriles and methyl thioglycolate in the presence of triethylamine in DMSO at 130 °C provides rapid access to 3-aminobenzo[b]thiophenes in 58–96% yield. This transformation has been applied in the synthesis of the thieno[2,3-b]pyridine core motif of LIMK1 inhibitors, the benzo[4,5]thieno[3,2-e][1,4]diazepin-5(2H)-one scaffold of MK2 inhibitors and a benzo[4,5]thieno[3,2-d]pyrimidin-4-one inhibitor of the PIM kinases