ABSTRACT
BACKGROUND: In the densely populated slums of Kolkata, informal healthcare providers' (IHP) diarrhea-related knowledge and rationality of practices should be improved to reduce risk of adverse outcome, expenditure, and antimicrobial resistance. METHODS: A multicomponent intervention was conducted among 140 representative IHPs in the slums of 8 wards in Kolkata to assess its impact on their diarrhea-related knowledge and practice. Six intervention modules in local languages were provided (1 per month) with baseline (Nâ =â 140) and postintervention (Nâ =â 124) evaluation. RESULTS: Mean overall (61.1 to 69.3; Pâ <â .0001) and domain-specific knowledge scores for etiology/spread (5.4 to 8.1; Pâ <â .0001), management (6.4 to 7.2; Pâ <â .0001), and oral rehydration solution ([ORS] 5.7 to 6.5; Pâ <â .0001) increased significantly (at αâ =â 0.05) after intervention and were well retained. Impact on knowledge regarding etiology/spread (adjusted odds ratio [aOR]â =â 5.6; Pâ <â .0001), cholera (aORâ =â 2.0; Pâ =â .0041), management (aORâ =â 3.1; Pâ <â .0001), ORS (aORâ =â 2.3; Pâ =â .0008), and overall (aORâ =â 4.3; Pâ <â .0001) were significant. Intervention worked better for IHPs who practiced for ≥10 years (aORâ =â 3.2; Pâ <â .0001), untrained IHPs (aORâ =â 4.8; Pâ <â .0001), and pharmacists (aORâ =â 8.3; Pâ <â .0001). Irrational practices like empirical antibiotic use for every cholera case (aORâ =â 0.3; Pâ <â .0001) and investigation for every diarrhea case (aORâ =â 0.4; Pâ =â .0003) were reduced. Rationality of testing (aORâ =â 4.2; Pâ <â .0001) and antibiotic use (aORâ =â 1.8; Pâ =â .0487) improved. CONCLUSIONS: Multicomponent educational intervention resulted in sustainable improvement in diarrhea-related knowledge and practices among IHPs in slums of Kolkata. Policy implications should be advocated along with implementation and scale-up.
Subject(s)
Cholera , Diarrhea , Health Knowledge, Attitudes, Practice , Poverty Areas , Cholera/diagnosis , Cholera/drug therapy , Cholera/prevention & control , Cost of Illness , Diarrhea/diagnosis , Diarrhea/drug therapy , Diarrhea/prevention & control , Humans , Hygiene , Sanitation , Water SupplyABSTRACT
BACKGROUND: Polyglutamine diseases constitute a class of neurodegenerative disorders associated with expansion of the cytosine-adenine-guanine (CAG) triplet, in protein coding genes. Expansion of a polyglutamine tract in the N-terminal of TBP is the causal mutation in SCA17. Brain sections of patients with spinocerebellar ataxia 17 (SCA17), a type of neurodegenerative disease, have been reported to contain protein aggregates of TATA-binding protein (TBP). It is also implicated in other neurodegenerative diseases like Huntington's disease, since the protein aggregates formed in such diseases also contain TBP. Dysregulation of miR-29a/b is another common feature of neurodegenerative diseases including Alzheimer's disease, Huntington's disease, and SCA17. Using a cellular model of SCA17, we identified key connections in the molecular pathway from protein aggregation to miRNA dysregulation. METHODS: Gene expression profiling was performed subsequent to the expression of TBP containing polyglutamine in a cellular model of SCA17. We studied the expression of STAT1 and other interferon-gamma dependent genes in neuronal apoptosis. The molecular pathway leading to the dysregulation of miRNA in response of protein aggregation and interferon release was investigated using RNAi-mediated knockdown of STAT1. RESULTS: We show that the accumulation of polyglutamine-TBP in the cells results in interferon-gamma release which in turn signals through STAT1 leading to downregulation of miR-29a/b. We propose that the release of interferons by cells harboring toxic protein aggregates may trigger a bystander effect resulting in loss of neurons. Interferon-gamma also led to upregulation of miR-322 although this effect is not mediated through STAT1. CONCLUSIONS: Our investigation shows that neuroinflammation could be an important player in mediating the transcriptional dysregulation of miRNA and the subsequent apoptotic effect of toxic polyglutamine-TBP. The involvement of immunomodulators in polyglutamine diseases holds special therapeutic relevance in the light of recent findings that interferon-gamma can modulate behavior.