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Background: Multidrug-resistant tuberculosis (MDR-TB) increases the risk of depression, lowers treatment compliance leading to poor outcomes. Objectives: To (1) document the prevalence of depression among MDR-TB cases registered at tuberculosis units (TUs) of Ahmedabad city and (2) assess determinants of depression. Methodology: Adult MDR-TB patients registered at all (23) TUs of Ahmedabad city, were studied using semi-structured questionnaire along with Gujarati translated version of the Hamilton Depression Rating Scale (HAM-D) to assess the severity of depression based on 17 items. The sample size at 95% level of significance, was 251. Probability proportional to size sampling was adopted for selecting participants from each of the 23 TUs. Proportions and odds ratio with confidence interval with probability value were calculated. Results: Of 251, only 185 (73.7%) cases could be contacted. Mortality proportion among selected cases was 18.7%. More than one-fifth (22%) had ≥1 comorbidity and 9.7% had another active TB case in the family. 161 (87.1) experienced ≥1 adverse event. Financial, social, or psychological stressors were reported by 22% of cases. Based on the HAM-D scale, 16.2% suffered from depression, determinants of depression by univariate analysis showed significant association with recent family issues, discrimination, financial/other troubling issues, and the presence of adverse drug event. Conclusion: MDR-TB cases are more vulnerable for developing depression as the prevalence was 16.2% among them. Hence, cases need to be monitored closely for depression at TU as well at community level.
RESUMO
Background: Under Rashtriya Bal Swasthya Karyakram (RBSK), children (0-18 years) are screened for a spectrum of 30 health conditions, categorized under 4D's namely defect (birth), disease (chronic), deficiency disorders, and developmental delay, and referred for treatment at higher centers. The aim of this study is to document demographic, clinical profile of children detected with any of 4D's during 2018-20 at one Urban Primary health center to assess their Quality of Life (QOL) and client satisfaction. Materials and Methods: A total of 102 children <18 years were selected as per Probability Proportionate to Size for different 4D's; within each category required participants were selected randomly. Information was gathered on designed semi-structured proforma. For QOL, customized World Health organization Quality of Life Brief (WHO-BREF) Questionnaire tool was used. Client satisfaction about the RBSK was assessed among RBSK users (N = 46) with Likert scale. Result: Out of 102 cases, 97 were covered including 8 with more than 1 type of 4Ds. Majority beneficiaries were male (53.1%), from 5 to 10 years age (43.8%), and middle social class (52%). Congenital defects (48.5%) especially heart defects were the most common followed by deficiency disorders (40.2%) mostly severe anemia and/or severe acute malnutrition. Out of 46 who availed RBSK services, 82.6% rated service as very good or good. Most children (81.7%) had good QOL. Conclusion: Most detected 4D's belonged to school going age and middle class. They rated program as very good or good. Congenital defects, specifically heart defects were the most common. Overall, most children (81.7%) had good QOL.
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Leucine-rich repeat kinase 2 (LRRK2) and tau have been identified as risk factors of Parkinson's disease (PD). As LRRK2 is a kinase and tau is hyperphosphorylated in some LRRK2 mutation carriers of PD patients, the obvious hypothesis is that tau could be a substrate of LRRK2. Previous reports that LRRK2 phosphorylates free tau or tubulin-associated tau provide direct support for this proposition. By comparing LRRK2 with cdk5, we show that wild-type LRRK2 and the G2019S mutant phosphorylate free recombinant full-length tau protein with specific activity 480- and 250-fold lower than cdk5, respectively. More strikingly tau binds to wt LRRK2 or the G2019S mutant 140- or 200-fold more strongly than cdk5. The extremely low activity of LRRK2 but strong binding affinity with tau suggests that LRRK2 may facilitate tau phosphorylation as a scaffold protein rather than as a major tau kinase. This hypothesis is further supported by the observation that (i) cdk5 or tau coimmunoprecipitates with endogenous LRRK2 in SH-SY5Y cells, in mouse brain tissue, and in human PBMCs; (ii) knocking down endogenous LRRK2 by its siRNA in SH-SY5Y cells reduces tau phosphorylation at Ser396 and Ser404; (iii) inhibiting LRRK2 kinase activity by its inhibitors has no effect on tau phosphorylation at these two sites; and (iv) overexpressing wt LRRK2, the G2019S mutant, or the D1994A kinase-dead mutant in SH-SY5Y cells has no effect on tau phosphorylation. Our results suggest that LRRK2 facilitates tau phosphorylation indirectly by recruiting tau or cdk5 rather than by directly phosphorylating tau.
