Synthesis of benzothiazolopyrazoloisonicotinohydrazide derivatives and their nitro regioisomers for antitubercular activity

1388-1399The history of incessant struggle and the current global burden associated with emerging infectious disease especially tuberculosis, guided us to define the scope of this research project, and to identify research gaps in synthesizing some heterocyclic compounds for anti-tubercular activity. In this research project, we have synthesized a series of novel heterocyclic (benzothiazoles) compounds viz N'-((1-(7-chloro-6-fluorobenzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazol-4-yl) methylene)isonicotinohydrazide 12a-c their 5-nitro 15a-c and 4-nitro 18a-c derivatives, by a series of reactions of their respective synthons. The completion of reaction and the purity of the synthesized compounds have been established by chromatographic analysis. All the newly synthesized compounds satisfactorily show acceptable analysis for their anticipated structures, which have been confirmed based on physicochemical and spectral data. These newly synthesized compounds have been primarily evaluated for their in vitro anti-tubercular activity by Ziehl-Neelsen stain method. Compounds 15a, 15b, 15c, 18b and 18c have shown 100% inhibition at 25 mg/ mL and MIC values of around 45 nM against M. tuberculosis H37Rv (ATCC 27294). Cytotoxicity on THP-1 cell line shows that all the tested compounds are safe

Synthesis of benzothiazolopyrazoloisonicotinohydrazide derivatives and their nitro regioisomers for antitubercular activity

The history of incessant struggle and the current global burden associated with emerging infectious disease especially tuberculosis, guided us to define the scope of this research project, and to identify research gaps in synthesizing some heterocyclic compounds for anti-tubercular activity. In this research project, we have synthesized a series of novel heterocyclic (benzothiazoles) compounds viz N'-((1-(7-chloro-6-fluorobenzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazol-4-yl) methylene)isonicotinohydrazide 12a-c their 5-nitro 15a-c and 4-nitro 18a-c derivatives, by a series of reactions of their respective synthons. The completion of reaction and the purity of the synthesized compounds have been established by chromatographic analysis. All the newly synthesized compounds satisfactorily show acceptable analysis for their anticipated structures, which have been confirmed based on physicochemical and spectral data. These newly synthesized compounds have been primarily evaluated for their in vitro anti-tubercular activity by Ziehl-Neelsen stain method. Compounds 15a, 15b, 15c, 18b and 18c have shown 100% inhibition at 25 mg/ mL and MIC values of around 45 nM against M. tuberculosis H37Rv (ATCC 27294). Cytotoxicity on THP-1 cell line shows that all the tested compounds are safe.

NITROGEN, PHOSPHORUS, AND POTASSIUM RANGE OF VERMICOMPOST USING EISENIA FETIDA AND PERIONYX EXCAVATUS

The aim of the presentation is to produce vermicomposting from organic kitchen solid wastes using two types of earthworms such as Eisenia fetida and Perionyx excavatus and check the nitrogen, phosphorus, and potassium level between E. fetida and P. excavatus. This study examines the potential of the E. fetida and P. excavatus in the vermicompost of kitchen waste. As kitchen waste is rich in organic material. Physical and biochemical parameters were analyzed during the period of 60 days. Pre-decomposition is 15 days and subsequent vermicomposting is 60 days indicates, the rule of these species of vermitechnology increase was found in all the parameters such as total nitrogen (%), available phosphorus (%), and exchangeable potassium (%) while a decrease was found in pH and carbon-to-nitrogen ratio in E. fetida as the timing of vermicomposting increased from 0 days to 60 days

Fear of Birth Defects Is a Major Barrier to Soil-Transmitted Helminth Treatment (STH) for Pregnant Women in the Philippines

The World Health Organization recommends anthelminthic treatment for pregnant women after the first trimester in soil-transmitted helminth (STH) endemic regions to prevent adverse maternal-fetal consequences. Although studies have shown the high prevalence of infection in the Philippines, no research has evaluated deworming practices. We hypothesized that pregnant women are not receiving deworming treatment and we aimed to identify barriers to World Health Organization guideline implementation. We conducted key informant interviews with local Department of Health (DOH) administrators, focus group discussions with nurses, midwives, and health care workers, and knowledge, attitudes, and practices surveys with women of reproductive age to elicit perspectives about deworming during pregnancy. Key informant interviews revealed that healthcare workers were not deworming pregnant women due to inadequate drug supply, infrastructure and personnel as well as fear of teratogenicity. Focus group discussions showed that healthcare workers similarly had not implemented guidelines due to infrastructure challenges and concerns for fetal malformations. The majority of local women believed that STH treatment causes side effects (74.8%) as well as maternal harm (67.3%) and fetal harm (77.9%). Women who were willing to take anthelminthics while pregnant had significantly greater knowledge as demonstrated by higher Treatment Scores (mean rank 146.92 versus 103.1, z = −4.40, p<0.001) and higher Birth Defect Scores (mean rank 128.09 versus 108.65, z = −2.43, p = 0.015). This study concludes that World Health Organization guidelines are not being implemented in the Philippines. Infrastructure, specific protocols, and education for providers and patients regarding anthelminthic treatment are necessary for the successful prevention of STH morbidity and mortality among pregnant women

Increasing Compliance with Mass Drug Administration Programs for Lymphatic Filariasis in India through Education and Lymphedema Management Programs

Global elimination of lymphatic filariasis requires giving drugs at least annually to populations who live at risk of becoming infected with the parasite. At least 80% of people at risk need to take the drugs annually for 5 or more years to stop transmission of the infection. People suffering from the long-term effects of infection, such as swollen legs, benefit from programs that teach self-care of their affected limbs. In this study, we assessed the impact of an educational campaign that, after addressing previously identified predictors of compliance, significantly improved drug compliance. The specific factors improving compliance included knowing about the drug distribution in advance, knowing that everyone is at risk for acquiring the infection, knowing that the drug distribution was for lymphatic filariasis prevention, and knowing at least one component of leg care. We also found that areas with programs to assist people with swollen legs had greater increases in compliance. This research provides evidence that program evaluation can be used to improve drug compliance. In addition, our work shows for the first time that programs to benefit people with swollen legs caused by lymphatic filariasis also increase the participation of people without disease in drug treatment programs

A multicenter, community-based, mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasis

BackgroundMany countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA).Methodology/principal findingsTo assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9-36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1-34.3); Papua New Guinea 32.9 (95% CI: 31.9-33.8); Indonesia 30.6 (95% CI: 29.8-31.3); Haiti 28.6 (95% CI: 27.8-29.4); India 26.8 (95% CI: 25.6-28) (PConclusions/significanceIDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted

The Early Youth Engagement in first episode psychosis (EYE-2) study: pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement

Background: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium–long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. Method: The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14–35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. Discussion: The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. Trial registration: ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019

Overexpression of the Rieske FeS protein of the Cytochrome b 6 f complex increases C4 photosynthesis in Setaria viridis.

C4 photosynthesis is characterised by a CO2 concentrating mechanism that operates between mesophyll and bundle sheath cells increasing CO2 partial pressure at the site of Rubisco and photosynthetic efficiency. Electron transport chains in both cell types supply ATP and NADPH for C4 photosynthesis. Cytochrome b 6 f is a key control point of electron transport in C3 plants. To study whether C4 photosynthesis is limited by electron transport we constitutively overexpressed the Rieske FeS subunit in Setaria viridis. This resulted in a higher Cytochrome b 6 f content in mesophyll and bundle sheath cells without marked changes in the abundances of other photosynthetic proteins. Rieske overexpression plants showed better light conversion efficiency in both Photosystems and could generate higher proton-motive force across the thylakoid membrane underpinning an increase in CO2 assimilation rate at ambient and saturating CO2 and high light. Our results demonstrate that removing electron transport limitations can increase C4 photosynthesis