7,306 research outputs found

    Updates to the World Health Organization's Recommendations for the Use of Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants

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    In July 2010, the World Health Organization (WHO) released new guidelines entitled, “Antiretroviral Drugs for Treating Pregnant Women and Preventing HIVInfection in Infants: Towards universal access.” Previewed in November 2009 in abridged form, the completed document highlights the key WHO recommendations for antiretroviral treatment (ART) and prophylaxis in pregnant women, and contains substantial changes from the 2006 guidelines. Of note, the new guidelines recommend ART for all pregnant women with a CD4 cell count (CD4) less than 350 cells/mm3, regardless of their clinical stage; includes tenofovir (TDF) as an acceptable alternative component of an ART regimen in pregnant and breastfeeding women; encourages initiation of both ART and antiretroviral (ARV) prophylaxis early in pregnancy; eliminates singledose nevirapine (sdNVP) per se as a prophylaxis option; lists three-drug ARV prophylaxis as an option for women who do not need ART for their own health; and introduces extended daily infant nevirapine (ED-NVP) as a strategy for prevention of breast milk transmission of HIV. This article reviews these new recommendations and their rationale, and highlights key implications and challenges to their implementation in the Zambian context.Keywords: Guidelines, HIV, prevention of mother to child transmission, antiretroviral, Zambi

    A Review of the 2010 WHO Adult Antiretroviral Therapy Guidelines: Implications and Realities of These Changes for Zambia

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    No AbstractKeywords: Guidelines, HIV, World Health Organization, antiretroviral, Zambi

    Proximal femoral excision with interposition myoplasty for cerebral palsy patients with painful chronic hip dislocation

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    Purpose: Proximal femoral excision is a salvage procedure for painful chronic hip dislocation in cerebral palsy (CP) patients. The primary objective of this article is to describe our experience of an amplified interposition myoplasty, with appropriate peri-operative pain and tone management strategies, in a cohort of non-ambulatory CP patients with painful chronic hip dislocation. Our secondary objective is to present the clinical outcomes of these patients. Methods: We describe our experience in 20 CP patients (25 procedures) at mean 54-month (range 27–169) follow-up with a surgical technique that includes an augmented interposition myoplasty and tone management. The indications for surgery were pain (21 hips), poor sitting tolerance (11) and difficulty with perineal care (8). Results: The mean age was 22 years (range 10–40) with 11 patients Gross Motor Function Classification Scale (GMFCS) IV and 9 patients GMFCS V. Mean length of stay was 13 days (3–35). One procedure required revision at 12 months. Mean pain score improved from 7.8 (5–10) pre-operatively to 2.8 (1–5) post-operatively (p  <  0.001). Sitting tolerance improved in all patients and in 75 % (15) perineal care was easier. Conclusions: Our interposition myoplasty technique with individualised pain/tone management has good outcomes in this cohort of patients with multiple co-morbidities

    Worldwide trends in mortality from biliary tract malignancies

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    BACKGROUND: Intrahepatic cholangiocarcinomas are malignant tumors arising from the intrahepatic biliary tract. The pathogenesis of these tumors remains unknown. Although there is a marked global variation in prevalence, some recent studies have suggested an increase in mortality from intrahepatic cholangiocarcinoma in several regions of low endemicity. As the study of mortality trends may yield clues to possible etiological factors, we analyzed worldwide time trends in mortality from biliary tract malignancies. METHODS: Annual age-standardized rates for individual countries were compiled for deaths from biliary tract malignancies using the WHO database. These data were used to analyze gender and site-specific trends in mortality rates. RESULTS: An increasing trend for mortality from intrahepatic cholangiocarcinoma was noted in most countries. The average estimated annual percentage change (EAPC) in mortality rates for males was 6.9 ± 1.5, and for females was 5.1 ± 1.0. Increased mortality rates were observed in all geographic regions. Within Europe, increases were higher in Western Europe than in Central or Northern Europe. In contrast, mortality rates for extrahepatic biliary tract malignancies showed a decreasing trend in most countries, with an overall average EAPC of -0.3 ± 0.4 for males, but -1.3 ± 0.4 for females. CONCLUSIONS: There has been a marked global increase in mortality from intrahepatic, but not extra-hepatic, biliary tract malignancies

    SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

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    Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

    Non-operative treatment of common finger injuries

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    Finger fractures are common injuries with a wide spectrum of presentation. Although a vast majority of these injuries may be treated non-operatively with gentle reduction, appropriate splinting, and careful follow-up, health care providers must recognize injury patterns that require more specialized care. Injuries involving unstable fracture patterns, intra-articular extension, or tendon function tend to have suboptimal outcomes with non-operative treatment. Other injuries including terminal extensor tendon injuries (mallet finger), stable non-articular fractures, and distal phalanx tuft fractures are readily treated by conservative means, and in general do quite well. Appropriate understanding of finger fracture patterns, treatment modalities, and injuries requiring referral is critical for optimal patient outcomes

    Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity.

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    Mutations in the Golgi SNARE (SNAP [soluble NSF attachment protein] receptor) protein Membrin (encoded by the GOSR2 gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitous and essential protein mediating ER-to-Golgi membrane fusion. Thus, it is unclear how mutations in Membrin result in a disorder restricted to the nervous system. Here, we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in Drosophila models of GOSR2-PME. Furthermore, we show that Membrin mutations cause fragmentation of the presynaptic cytoskeleton coupled with transsynaptic instability and hyperactive neurotransmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships in GOSR2-PME
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