A Longitudinal Analysis of Mosquito Net Ownership and Use in an Indigenous Batwa Population after a Targeted Distribution

Major efforts for malaria prevention programs have gone into scaling up ownership and use of insecticidal mosquito nets, particularly in sub-Saharan Africa where the malaria burden is high. Socioeconomic inequities in access to long lasting insecticidal nets (LLINs) are reduced with free distributions of nets. However, the relationship between social factors and retention of nets after a free distribution has been less studied, particularly using a longitudinal approach. Our research aimed to estimate the ownership and use of LLINs, and examine the determinants of LLIN retention, within an Indigenous Batwa population after a free LLIN distribution. Two LLINs were given free of charge to each Batwa household in Kanungu District, Uganda in November 2012. Surveyors collected data on LLIN ownership and use through six cross-sectional surveys pre- and post-distribution. Household retention, within household access, and individual use of LLINs were assessed over an 18-month period. Socioeconomic determinants of household retention of LLINs post-distribution were modelled longitudinally using logistic regression with random effects. Direct house-to-house distribution of free LLINs did not result in sustainable increases in the ownership and use of LLINs. Three months post-distribution, only 73% of households owned at least one LLIN and this period also saw the greatest reduction in ownership compared to other study periods. Eighteen-months post distribution, only a third of households still owned a LLIN. Self-reported age-specific use of LLINs was generally higher for children under five, declined for children aged 6–12, and was highest for older adults aged over 35. In the model, household wealth was a significant predictor of LLIN retention, controlling for time and other variables. This research highlights on-going socioeconomic inequities in access to malaria prevention measures among the Batwa in southwestern Uganda, even after free distribution of LLINs, and provides critical information to inform local malaria programs on possible intervention entry-points to increase access and use among this marginalized population

TNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice

Abstract\ud \ud Background\ud High fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-α, a cytokine that contributes to insulin resistance and vascular dysfunction. Considering that the enzyme phosphatase and tension homologue (PTEN), whose expression is increased by TNF-α, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-α-mediated vascular resistance to insulin induced by HFD. Mechanisms underlying PTEN effects were determined.\ud \ud \ud Methods\ud Mesenteric vascular beds were isolated from C57Bl/6J and TNF-α KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-α and PTEN contribute to vascular dysfunction.\ud \ud \ud Results\ud Vasodilation in response to insulin was decreased in HFD-fed mice and in ex vivo control arteries incubated with TNF-α. TNF-α receptors deficiency and TNF-α blockade with infliximab abolished the effects of HFD and TNF-α on insulin-induced vasodilation. PTEN vascular expression (total and phosphorylated isoforms) was increased in HFD-fed mice. Treatment with a PTEN inhibitor improved insulin-induced vasodilation in HFD-fed mice. TNF-α receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice.\ud \ud \ud Conclusion\ud TNF-α induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-α and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity-related conditions.This work was supported by grants from Fundação de Amparo à Pesquisa\ud do Estado de São Paulo (FAPESP 2013/08216-2-CRID), Coordenação de Aper‑\ud feiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de\ud Desenvolvimento Científico e Tecnológico (CNPq), Brazil

c-FLIP Maintains Tissue Homeostasis by Preventing Apoptosis and Programmed Necrosis

As a catalytically inactive homolog of caspase-8, a proapoptotic initiator caspase, c-FLIP blocks apoptosis by binding to and inhibiting caspase-8. The transcription factor nuclear factor κB (NF-κB) plays a pivotal role in maintaining the homeostasis of the intestine and the liver by preventing death receptor–induced apoptosis, and c-FLIP plays a role in the NF-κB–dependent protection of cells from death receptor signaling. Because c-Flip–deficient mice die in utero, we generated conditional c-Flip–deficient mice to investigate the contribution of c-FLIP to homeostasis of the intestine and the liver at developmental and postnatal stages. Intestinal epithelial cell (IEC)– or hepatocyte-specific deletion of c-Flip resulted in perinatal lethality as a result of the enhanced apoptosis and programmed necrosis of the IECs and the hepatocytes. Deficiency in the gene encoding tumor necrosis factor–α (TNF-α) receptor 1 (Tnfr1) partially rescued perinatal lethality and the development of colitis in IEC-specific c-Flip–deficient mice but did not rescue perinatal lethality in hepatocyte-specific c-Flip–deficient mice. Moreover, adult mice with interferon (IFN)– inducible deficiency in c-Flip died from hepatitis soon after depletion of c-FLIP. Pretreatment of IFN-inducible c-Flip–deficient mice with a mixture of neutralizing antibodies against TNF-α, Fas ligand (FasL), and TNF-related apoptosis-inducing ligand (TRAIL) prevented hepatitis. Together, these results suggest that c-FLIP controls the homeostasis of IECs and hepatocytes by preventing cell death induced by TNF-α, FasL, and TRAIL