Risk Factors Associated with Default among New Smear Positive TB Patients Treated Under DOTS in India

Background

Poor treatment adherence leading to risk of drug resistance, treatment failure, relapse, death and persistent infectiousness remains an impediment to the tuberculosis control programmes. The objective of the study was to identify predictors of default among new smear positive TB patients registered for treatment to suggest possible interventions to set right the problems to sustain and enhance the programme performance.

Methodology & Principal Findings

Twenty districts selected from six states were assigned to six strata formed, considering the geographic, socio-cultural and demographic setup of the area. New smear positive patients registered for treatment in two consecutive quarters during III quarter 2004 to III quarter 2005 formed the retrospective study cohort. Case control analysis was done including defaulted patients as “cases” and equal number of age and sex matched patients completing treatment as “controls”. The presence and degree of association between default and determinant factors was computed through univariate and multivariate logistic regression analysis. Data collection was through patient interviews using pre-tested semi structured questionnaire and review of treatment related records. Information on a wide range of socio demographic and patient related factors was obtained. Among the 687 defaulted and equal numbers of patients in completed group, 389 and 540 patients respectively were satisfactorily interviewed. In the logistic regression analysis, factors independently associated with default were alcoholism [AOR-1.72 (1.23–2.44)], illiteracy [AOR-1.40 (1.03–1.92)], having other commitments during treatment [AOR-3.22 (1.1–9.09)], inadequate knowledge of TB [AOR-1.88(1.35–2.63)], poor patient provider interaction [AOR-1.72(1.23–2.44)], lack of support from health staff [AOR-1.93(1.41–2.64)], having instances of missed doses [AOR-2.56(1.82–3.57)], side effects to anti TB drugs [AOR-2.55 (1.87–3.47)] and dissatisfaction with services provided [AOR-1.73 (1.14–2.6)].

Conclusion

Majority of risk factors for default were treatment and provider oriented and rectifiable with appropriate interventions, which would help in sustaining the good programme performance.     

Effect of sesamol on radiation-induced cytotoxicity in Swiss albino mice

The radio-protective ability of sesamol (SM) at various doses viz., 0, 10, 25, 40, 50, 70 and 100 mg/kg bw, administered intraperitoneally 30 min prior to 9.5 Gy whole-body γ-irradiation was studied in Swiss albino mice. Radiation toxicity and mortality were observed during a period of 30 days and the percentage mortality was calculated. SM pretreatment with 50 mg/kg bw was found to be the most effective dose in maintaining body weight and in reducing the percentage mortality, while 100 mg/kg bw was found to be more effective in maintaining the spleen index and in stimulation of endogenous spleen colony-forming units. Pretreatment with SM (50 mg/kg bw) in mice irradiated with 15 Gy significantly reduced dead, inflammatory, mitotic and goblet cells in irradiated jejunum. SM at 50 mg/kg bw also increased crypt cells, maintained villus height, and prevented mucosal erosion. Nuclear enlargement in epithelial cells was found less in SM-treated mice compared with the irradiated control. The radiation-induced decrease in endogenous antioxidant enzymes (GSH, GST, catalase) and the increase in lipid peroxidation were also reduced by pretreatment with SM [50 and 100 mg/kg bw] at all monitored post-irradiation intervals. There was no protection at a dose less than 25 mg/kg bw.     

Postendocytotic trafficking of the follicle-stimulating hormone (FSH)-FSH receptor complex

Although the fates of the internalized hormone-receptor complexes formed by the lutropin/choriogonadotropin and the TSH receptors have been examined in some detail, much less is known about the fate of the internalized FSH-FSH receptor (FSHR) complex.Using biochemical and imaging approaches we show here that the majority of the internalized FSH-FSHR complex accumulates in endosomes and subsequently recycles back to the cell surface where the bound, intact hormone dissociates back into the medium. Only small amounts of FSH and the FSHR are routed to a lysosomal degradation pathway, and the extent of FSH-induced down-regulation of the cell surface and total FSHR is minimal. This pathway was detected in heterologous (human kidney 293T) cells transfected with the rat (r) or human (h) FSHR as well as in a mouse Sertoli cell line (MSC-1) or a mouse granulosa cell line (KK-1) transfected with the rFSHR.Additional experiments using a series of C-terminal deletions of the rFSHR and the hFSHR showed that the recycling of the internalized FSH-FSHR complex and the extent of hFSH-induced down-regulation is dictated by a short stretch of amino acids present at the extreme C-terminal end of the receptor.We conclude that most of the internalized FSH-FSHR complex is recycled back to the cell surface, that this recycling pathway is highly dependent on amino acid residues present near the C terminus of the FSHR, and that it is an important determinant of the extent of down-regulation of the FSHR.     

Stimulation of vitellogenin production by methoprene in prepupae and pupae of manduca sexta

Denaturing electrophoresis of hemolymph from prepupae of M. sexta showed trace amounts of polypeptides with mobilities corresponding to those of vitellogenin (Vg) apoproteins from adult females. Absence of the polypeptides in allatectomized insects suggested regulation by juvenile hormone (JH). Daily administration of 10 μg of the JH analog methoprene from day 4 of the fifth stage to day 0 of the pupal stage caused accumulation of these polypeptides. They were identified as apovitellogenins (apoVgs) immunochemically with Vg antiserum. Stimulation of Vg in response to methoprene varied with age. In all cases, day 0 female pupae were highly responsive. Vg synthesis was not stimulated when pupae were injected with 20-hydroxyecdysone (20-HE) in addition to methoprene. Methoprene-stimulated Vg synthesis was also abolished by inhibitors of mRNA or protein synthesis (α-amanitin, actinomycin, cycloheximide). This result indicated that methoprene-stimulated Vg accumulation requires gene expression. A Vg cDNA (2.1 kb) obtained by immunoscreening of the λgt 11 library, when used as a radiolabelled probe, hybridized with a 5.1 kb mRNA from total RNA of female fat body. It also hybridized with fat body RNA of normal prepupae and methoprene treated day 0 pupae but not with that of early fifth instars or solvent control pupae. The results indicate that the trace amounts of Vg found in prepupal stages are due to a weak expression of the Vg gene, which is stimulated by JH and repressed by 20-HE. © 1994 Wiley-Liss, Inc.     

Factors associated with excess all-cause mortality in the first wave of the COVID-19 pandemic in the UK: A time series analysis using the Clinical Practice Research Datalink

BackgroundExcess mortality captures the total effect of the Coronavirus Disease 2019 (COVID-19) pandemic on mortality and is not affected by misspecification of cause of death. We aimed to describe how health and demographic factors were associated with excess mortality during, compared to before, the pandemic.Methods and findingsWe analysed a time series dataset including 9,635,613 adults (≥40 years old) registered at United Kingdom general practices contributing to the Clinical Practice Research Datalink. We extracted weekly numbers of deaths and numbers at risk between March 2015 and July 2020, stratified by individual-level factors. Excess mortality during Wave 1 of the UK pandemic (5 March to 27 May 2020) compared to the prepandemic period was estimated using seasonally adjusted negative binomial regression models. Relative rates (RRs) of death for a range of factors were estimated before and during Wave 1 by including interaction terms. We found that all-cause mortality increased by 43% (95% CI 40% to 47%) during Wave 1 compared with prepandemic. Changes to the RR of death associated with most sociodemographic and clinical characteristics were small during Wave 1 compared with prepandemic. However, the mortality RR associated with dementia markedly increased (RR for dementia versus no dementia prepandemic: 3.5, 95% CI 3.4 to 3.5; RR during Wave 1: 5.1, 4.9 to 5.3); a similar pattern was seen for learning disabilities (RR prepandemic: 3.6, 3.4 to 3.5; during Wave 1: 4.8, 4.4 to 5.3), for black or South Asian ethnicity compared to white, and for London compared to other regions. Relative risks for morbidities were stable in multiple sensitivity analyses. However, a limitation of the study is that we cannot assume that the risks observed during Wave 1 would apply to other waves due to changes in population behaviour, virus transmission, and risk perception.ConclusionsThe first wave of the UK COVID-19 pandemic appeared to amplify baseline mortality risk to approximately the same relative degree for most population subgroups. However, disproportionate increases in mortality were seen for those with dementia, learning disabilities, non-white ethnicity, or living in London.

Helen Strongman and colleagues investigate the health and demographic factors associated with excess mortality during, as compared to before, the COVID-19 pandemic.     

Involvement of secondary metabolites and extracellular lytic enzymes produced by Pseudomonas fluorescens in inhibition of Rhizoctonia solani, the rice sheath blight pathogen

Fourteen strains of Pseudomonas fluorescens isolated from rhizosphere soil of rice were tested for their antagonistic effect towards Rhizoctonia solani, the rice sheath blight fungus. Among them, PfMDU2 was the most effective in inhibiting mycelial growth of R. solani in vitro. Production of chitinase, beta-1,3-glucanase, siderophores, salicylic acid (SA) and hydrogen cyanide (HCN) by P. fluorescens strains was evaluated. The highest beta-1,3-glucanase activity, siderophore production, SA production and HCN production were recorded with PfMDU2. A significant relationship between the antagonistic potential of P. fluorescens against R. solani and its level of beta-1,3-glucanase, SA and HCN was observed.     

Radiation protection by the ocimum flavonoids orientin and vicenin: mechanisms of action

In previous studies, flavonoids, orientin and vicenin, that were isolated from the leaf extract of Ocimum sanctum, were found to protect mice against radiation injury. Several flavonoids are known to be good antioxidants. Therefore, the effect of orientin and vicenin on radiation-induced lipid peroxidation in vivo and their antioxidant activity in vitro were studied. Adult mice were injected intraperitoneally with 50 microgram/kg of orientin or vicenin and exposed whole-body to 3 Gy of gamma radiation. Lipid peroxidation was measured in the liver 15 min to 8 h postirradiation. The antioxidant activity of orientin/vicenin (10-500 microM) was studied by measuring inhibition of hydroxyl radicals generated by the Fenton reaction (Fe(3+)-EDTA-ascorbic acid-H(2)O(2)) in vitro. The compounds were also tested for possible pro-oxidant and iron chelation activities at the above concentrations in the in vitro system. Orientin and vicenin provided almost equal protection against radiation-induced lipid peroxidation in mouse liver. Both compounds showed a significantly greater free radical-inhibiting activity in vitro than DMSO. Neither orientin nor vicenin showed any pro-oxidant activity at the concentrations tested. Both compounds inhibited free radical formation in the absence of EDTA. Free radical scavenging appears to be a likely mechanism of radiation protection by these flavonoids.     

Turbulent flow evaluation of the venous needle during hemodialysis

Arteriovenous (AV) grafts and fistulas used for hemodialysis frequently develop intimal hyperplasia (IH) at the venous anastomosis of the graft, leading to flow-limiting stenosis, and ultimately to graft failure due to thrombosis. Although the high AV access blood flow has been implicated in the pathogenesis of graft stenosis, the potential role of needle turbulence during hemodialysis is relatively unexplored. High turbulent stresses from the needle jet that reach the venous anastomosis may contribute to endothelial denudation and vessel wall injury. This may trigger the molecular and cellular cascade involving platelet activation and IH, leading to eventual graft failure. In an in-vitro graft/needle model dye injection flow visualization was used for qualitative study of flow patterns, whereas laser Doppler velocimetry was used to compare the levels of turbulence at the venous anastomosis in the presence and absence of a venous needle jet. Considerably higher turbulence was observed downstream of the venous needle, in comparison to graft flow alone without the needle. While turbulent RMS remained around 0.1 m/s for the graft flow alone, turbulent RMS fluctuations downstream of the needle soared to 0.4-0.7 m/s at 2 cm from the tip of the needle and maintained values higher than 0.1 m/s up to 7-8 cm downstream. Turbulent intensities were 5-6 times greater in the presence of the needle, in comparison with graft flow alone. Since hemodialysis patients are exposed to needle turbulence for four hours three times a week, the role of post-venous needle turbulence may be important in the pathogenesis of AV graft complications. A better understanding of the role of needle turbulence in the mechanisms of AV graft failure may lead to improved design of AV grafts and venous needles associated with reduced turbulence, and to pharmacological interventions that attenuate IH and graft failure resulting from turbulence.     

5-Aminosalicylic acid reverses endosulfan-induced testicular toxicity in male rats

Pre-treatment with 5-aminosalicylic acid (5-ASA) significantly reduced sperm-shape abnormalities in endosulfan-treated rats. The number of abnormal sperm in the epididymis was markedly increased by endosulfan treatment but pre-treatment with 5-ASA kept these values close to normal. Treatment with 5-ASA at a dose of 25 mg/kg bw was more effective in reducing sperm-shape abnormality and sperm count than at a dose of 50 mg/kg bw. Endosulfan significantly increased the level of lactate dehydrogenase (LDH) in rats but a marked decrease was observed upon pre-treatment with 25 mg/kg bw 5-ASA. Changes in plasma testosterone levels were not significantly correlated with 5-ASA pre-treatment but histopathological analysis of seminiferous tubules and Leydig cells showed significant protection from endosulfan-induced tissue damage such as necrosis. The population of Sertoli cells increased and the lumen of the seminiferous tubules contained a greater number of spermatids. There was a corresponding increase in the number of Leydig cells. A curative study with 5-ASA showed a similar protection from endosulfan-induced toxicity and cellular damage, but the extent of protection was significantly lower.