Niemann-Pick disease type C

Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period), gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period), and ataxia not unfrequently following initial psychiatric disturbances (adult form). The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families) or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes) after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype). Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential diagnosis may include other lipidoses; idiopathic neonatal hepatitis and other causes of cholestatic icterus should be considered in neonates, and conditions with cerebellar ataxia, dystonia, cataplexy and supranuclear gaze palsy in older children and adults. Symptomatic management of patients is crucial. A first product, miglustat, has been granted marketing authorization in Europe and several other countries for specific treatment of the neurological manifestations. The prognosis largely correlates with the age at onset of the neurological manifestations

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Policies and clinical practices relating to the management of gestational diabetes mellitus in the public health sector, South Africa – a qualitative study

BACKGROUND: Women with a prior gestational diabetes have an increased lifetime risk of developing type 2 diabetes. Although post-partum follow-up for GDM women is essential to prevent progression to type 2 diabetes, it is poorly attended. The need for health systems interventions to support postpartum follow-up for GDM women is evident, but there is little knowledge of actual current practice. The aim of this study was to explore current policies and clinical practices relating to antenatal and post-natal care for women with GDM in South Africa, as well as health sector stakeholders’ perspectives on the barriers to – and opportunities for – delivering an integrated mother - baby health service that extends beyond the first week post-partum, to the infant’s first year of life. METHODS: Following a document review of policy and clinical practice guidelines, in-depth interviews were conducted with 11 key informants who were key policy makers, health service managers and clinicians working in the public health services in South Africa’s two major cities (Johannesburg and Cape Town). Data were analysed using qualitative content analysis procedures. RESULTS: The document review and interviews established that it is policy that health services adhere to international guidelines for GDM diagnosis and management, in addition to locally developed guidelines and protocols for clinical practice. All key informants confirmed that lack of postpartum follow-up for GDM women is a significant problem. Health systems barriers include fragmentation of care and the absence of standardised postnatal care for post-GDM women. Key informants also raised patient - related challenges including lack of perceived future risk of developing type 2 diabetes and non-attendance for postpartum follow up, as barriers to postnatal care for GDM women. All participants supported integrated primary health services but cautioned against overloading health workers. CONCLUSION: Although there is alignment between international guidelines, local policy and reported clinical practice in the management of GDM, there is a gap in continuation of care in the postpartum period. Health systems interventions that support and facilitate active follow-up for women with prior GDM are needed if high rates of progression to type 2 diabetes are to be avoided

Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: Novel markers in biological classification

10.1007/s10549-011-1555-6Breast Cancer Research and Treatment1321143-151BCTR