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1.
J Infect Dis ; 224(12 Suppl 2): S890-S900, 2021 12 20.
Article in English | MEDLINE | ID: mdl-34718638

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 (N = 140) and postintervention (N = 124) evaluation. RESULTS: Mean overall (61.1 to 69.3; P < .0001) and domain-specific knowledge scores for etiology/spread (5.4 to 8.1; P < .0001), management (6.4 to 7.2; P < .0001), and oral rehydration solution ([ORS] 5.7 to 6.5; P < .0001) increased significantly (at α = 0.05) after intervention and were well retained. Impact on knowledge regarding etiology/spread (adjusted odds ratio [aOR] = 5.6; P < .0001), cholera (aOR = 2.0; P = .0041), management (aOR = 3.1; P < .0001), ORS (aOR = 2.3; P = .0008), and overall (aOR = 4.3; P < .0001) were significant. Intervention worked better for IHPs who practiced for ≥10 years (aOR = 3.2; P < .0001), untrained IHPs (aOR = 4.8; P < .0001), and pharmacists (aOR = 8.3; P < .0001). Irrational practices like empirical antibiotic use for every cholera case (aOR = 0.3; P < .0001) and investigation for every diarrhea case (aOR = 0.4; P = .0003) were reduced. Rationality of testing (aOR = 4.2; P < .0001) and antibiotic use (aOR = 1.8; P = .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 Supply
2.
J Neuroinflammation ; 14(1): 155, 2017 08 03.
Article in English | MEDLINE | ID: mdl-28774347

ABSTRACT

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.


Subject(s)
Gene Expression Regulation/physiology , MicroRNAs/metabolism , Neurons/metabolism , Peptides/toxicity , STAT1 Transcription Factor/metabolism , TATA-Box Binding Protein/metabolism , Animals , Cell Line, Tumor , Gene Expression Regulation/genetics , Interferon-gamma/genetics , Interferon-gamma/metabolism , Mice , MicroRNAs/genetics , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neuroblastoma/pathology , Neurons/drug effects , Peptides/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , STAT1 Transcription Factor/genetics , TATA-Box Binding Protein/genetics , Time Factors , Transfection
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