Comprehensive Update on Synthetic Aspects of Bosentan Derivatives.

Bosentan and its analogues were first reported as endothelin (ET) receptor antagonists in US patent No. 5, 292,740 in 1994. Bosentan synthesis has been reported by employing different methods from the reaction between (4,6-dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine and 4- (tert-butyl) benzenesulfonamide and 4-(tert-butyl)-N-(6-chloro-5-(2-methoxyphenoxy)-[2,2'- bipyrimidin]-4-yl) benzenesulfonamide in the form of different salts like potassium salt, ammonium salt, sodium salt, and free, on its reaction with ethylene glycol. Several changes have been observed in the chemistry of the involved intermediate synthesis, particularly coupling chemistry, to produce bosentan derivatives with high purity and yield.

Effectiveness of 13-valent pneumococcal conjugate vaccine on radiological primary end-point pneumonia among cases of severe community acquired pneumonia in children: A prospective multi-site hospital-based test-negative study in Northern India.

INTRODUCTION: Community acquired pneumonia (CAP) is a leading cause of under-five mortality in India and Streptococcus pneumoniae is the main bacterial pathogen for it. Pneumococcal Conjugate Vaccine 13 (PCV13) has been introduced in a phased manner, in the national immunization program of India since 2017/2018. The primary objective of this study was to evaluate the effectiveness of PCV13 on chest radiograph (CXR)-confirmed pneumonia, in children hospitalized with WHO-defined severe CAP. METHODS: This prospective, multi-site test-negative study was conducted in a hospital-network situated in three districts of Northern India where PCV13 had been introduced. Children aged 2-23 months, hospitalized with severe CAP and with interpretable CXR were included after parental consent. Clinical data was extracted from hospital records. CXRs were interpreted by a panel of three independent blinded trained radiologists. Exposure to PCV13 was defined as ≥2 doses of PCV13 in children aged ≤ 12 months and ≥ 1 dose(s) in children > 12 months of age. Our outcome measures were CXR finding of primary endpoint pneumonia with or without other infiltrates (PEP±OI); vaccine effectiveness (VE) and hospital mortality. RESULTS: From 1st June 2017-30th April 2021, among 2711 children included, 678 (25.0%) were exposed to PCV1. CXR positive for PEP±OI on CXR was found in 579 (21.4%), of which 103 (17.8%) were exposed to PCV. Adjusted odds ratio (AOR) for PEP±OI among the exposed group was 0.69 (95% CI, 0.54-0.89, p = 0.004). Adjusted VE was 31.0% (95% CI: 11.0-44.0) for PEP±OI. AOR for hospital mortality with PEP±OI was 2.65 (95% CI: 1.27-5.53, p = 0.01). CONCLUSION: In severe CAP, children exposed to PCV13 had significantly reduced odds of having PEP±OI. Since PEP±OI had increased odds of hospital mortality due to CAP, countrywide coverage with PCV13 is an essential priority.

Hospital-Based Retrospective Cross-sectional Study to Analyse the Causes of Maternal Deaths at a Tertiary Health Care Facility.

Context: Maternal mortality is considered a key health indicator of Maternal and Child Health. Considering the fact that complications are preventable and most of them are modifiable, the study has been planned to analyse maternal deaths in order to suggest recommendations for preventing it. There are various delays according to the three-delay model at primary and secondary level; therefore, interventions are needed at those levels to prevent maternal deaths. Aims: To determine the various direct and indirect causes of maternal deaths, analyse the association of medical and social factors with maternal deaths and ^to determine the predictors of maternal deaths. Settings and Design: Hospital-based retrospective cross-sectional study of all the maternal deaths occurring in the last 4 years at a tertiary health care facility. Methods and Material: Data were collected from the Facility Based Maternal Death Review forms. Statistical Analysis Used: Data were entered and analysed by IBM SPSS version 25.0 software. Results: For maternal deaths, direct obstetric causes were responsible in 128 (74.4%) and indirect causes in 45 (26.2%) cases followed by unspecified causes in 78 (45.3%) and 1 (0.6%) coincidental cause. Statistically significant associations were observed between maternal death and period of gestation, mode of delivery and outcome of delivery (P = 0.12, P = 0.04 and P < 0.001, respectively). Conclusions: The health professionals of primary and secondary level should be well equipped to diagnose the complications and to manage it as early as possible. Thus, maternal mortality rates can be decreased to significant level.

Prevalence of high-risk pregnancy among pregnant women enrolled under Pradhan Mantri Surakshit Matritva Abhiyan in government health facilities of district Etawah, Uttar Pradesh: A cross-sectional study.

Background: According to the Sample Registration System report, India has reduced the maternal mortality rate from 130 per 100,000 live births in 2014-2016 to 113 per 100,000 live births in 2016-2018. The main purpose of antenatal care is to identify "high-risk" cases as early as possible from a large group of antenatal mothers and provide them skilled and appropriate care. Objective: To determine the prevalence of high-risk pregnancy (HRP) in pregnant females availing services under pradhan mantri surakshit matritva abhiyan (PMSMA) and to assess awareness of pregnant mothers about services provided under PMSMA in district Etawah of Uttar Pradesh. Material and Methods: Community-based cross-sectional study was carried out among 400 female beneficiaries who were registered under the PMSMA scheme and delivered their baby at any government health facility during one year of study period. Results: It was observed that from all the antenatal women visiting the community health center for HRP day under the PMSMA scheme, 162 (40.5%) were categorized as HRPs and 238 (59.6%) of them were nonhigh-risk pregnancies. A statistically significant association was observed (P-value = 0.005 at 95% CI) between the difference in the proportion of HRPs and the educational status of the pregnant mothers. Out of 400 beneficiaries, 167 (41.75%) were aware of the PMSMA scheme. Conclusion: Regular antenatal care (ANC) check-ups, early identification of HRP, health education, and timely screening are needed to reduce maternal mortality.

Are the labour rooms of primary healthcare facilities capable of providing basic delivery and newborn services? A cross-sectional study.

OBJECTIVES: The study aimed to assess the functionality of labour rooms by evaluating the labour room infrastructure with reference to the standard guidelines, the status of the availability of human resources, the availability of essential equipment and consumables in the labour room and by documenting the knowledge of the healthcare provider in terms of labour room practices. The study also explored the facility parameters associated with its delivery load taking the facility as a unit of analysis. DESIGN: A cross-sectional analytical study. SETTING: India has realised the importance of improving the quality of care in public health facilities, and steps are being taken to make healthcare more responsive to women's needs. With an increase in the proportion of institutional deliveries in India, the outcome of the delivery process can be improved by optimising the health facility components. PARTICIPANTS: The study was conducted in 52 health facilities and healthcare providers involved in the delivery process in the selected facilities. RESULTS: The infrastructure of the facilities was found to be the best for medical college followed by district hospitals, Community Health Centres (CHCs), Primary Health Centres (PHCs) and subcentres. Similar findings were observed in terms of the availability of equipment and consumables. Lack of healthcare providers was observed as only 20% of the posts for health personnel were fulfilled in CHCs followed by PHCs, subcentres and district hospitals where 43, 50 and 79% of the available vacancies were fulfilled. The level of knowledge of healthcare providers in terms of partograph, active management of the third stage of labour and post-partum haemorrhage ranged as per their designation. The specialists were the most knowledgeable while the Auxiliary Nurse Midwife (AMNs) were the least. All the components of structural capacity, i.e. infrastructure (r 2 = 0.377, P value < 0.001), equipment and consumable (r 2 = 0.606, P value < 0.001) and knowledge of healthcare providers (r 2 = 0.456, P value < 0.001) along with the overall facility score were positively correlated with the average delivery load of the health facility. The results from multivariate linear regression depict significant relation between the delivery load and availability of equipment and consumables (t = 4.015, P < 0.01) and with the knowledge of healthcare providers (t = 2.129, P = 0.039). CONCLUSIONS: The higher facilities were better equipped to provide delivery and newborn care. A higher delivery load was found at high-level facilities which can be attributed to better infrastructure, adequate supply of equipment and consumables and availability of trained human resources.

Morbidity Patterns among Menopausal Women in Rural Uttar Pradesh, India: A Cross-Sectional Study.

OBJECTIVES: The quality of life declines gradually as women enter menopause, owing to the various problems associated with estrogen deficiency and aging, which adds to their morbidities. This study aimed to investigate the patterns of morbidity among rural menopausal women and compare the morbidity patterns among menopausal transition group and post-menopausal women. METHODS: This community-based cross-sectional study included menopausal women aged 45-55 years from rural areas of the Etawah district, Uttar Pradesh, India. To select blocks and villages of the district, multistage random sampling was performed. According to a pretested, semistructured schedule, data were collected through interviews. RESULTS: A total of 315 women participated in the study. The most frequent complaints among the participants were of feeling tired and worn out (85.1%) and of muscle and joint pains (67.6%). Poor memory (P = 0.046) and diabetes (P = 0.024) were more common in women who were in the menopause transition phase than in those who were in the postmenopausal phase. CONCLUSIONS: This study showed that majority of the menopausal women suffered from physical problems. Lifestyle modification and awareness programs will be beneficial among women in menopausal transition, to reduce the morbidity later in post-menopausal stage. Behaviour change communication, family and community support are essential in post-menopausal women, to help them cope with various morbid conditions.

Yoga Therapy as an Adjuvant in Management of Asthma.

OBJECTIVE: To assess the effect of yoga on control of asthma in children with bronchial asthma. METHODS: This hospital-based interventional randomized controlled trial conducted in the Department of Pediatrics at a tertiary care center of North India from November 2017 to October 2018 enrolled 140 newly diagnosed cases of asthma of age 10-16 y who were randomly divided into two groups. Seventy children in the case group practiced yoga under supervision for a period of 3 mo in addition to pharmacological treatment. Seventy controls received only pharmacological treatment. Pulmonary-function tests were done at baseline, 6 wk, and 12 wk along with quality of life (QOL) assessment by Pediatric Asthma Quality of Life Questionnaire (PAQLQ). The outcome measures assessed were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and peak expiratory flow rate (PEFR). QOL evaluation was done in 3 domains: activity limitation, symptoms, and emotional function. RESULTS: The asthmatic children practicing yoga have shown significant improvement in FVC, FEV1, FEV1/FVC and PEFR which was better as compared to controls. Improvement was also noted in mean-PAQLQ score in cases which was statistically significantly better as compared to controls. CONCLUSION: Yoga appears to have significant positive effect on control of asthma measured by pulmonary-function test and QOL. Therefore yoga therapy can be recommended as an adjuvant in management of asthma along with standard pharmacological management.

Epidemiology of Hypoxic Community-Acquired Pneumonia in Children Under 5 Years of Age: An Observational Study in Northern India.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of under-five mortality in India. An increased risk of mortality has been reported in cases of hypoxic pneumonia. METHODS: The primary objective of this study was to assess the proportion of children aged 2-59 months, hospitalized with hypoxic CAP, as well as socio-demographic, clinical, and radiological features associated with it. The secondary objective was to determine the risk of mortality among hospitalized cases of hypoxic CAP. This prospective, observational study was conducted in four districts of Northern India, between January 2015 and April 2021. A hospital-based surveillance network was established. Inclusion criteria were as follows: (a) child between 2 and 59 months, (b) hospitalization with symptoms of WHO-defined CAP, (c) resident of project district, (d) illness of <14 days, and (e) child had neither been hospitalized for this illness nor recruited previously. Children whose chest x-rays (CXRs) were either unavailable/un-interpretable and those that received any dose of pneumococcal conjugate vaccine-13 were excluded. Hypoxic pneumonia was defined as oxygen saturation <90% on pulse oximetry or requiring oxygen supplementation during hospital stay. RESULTS: During the study period, 71.9% (7,196/10,006) children of severe pneumonia were eligible for inclusion, of whom 35.9% (2,580/7,196) were having hypoxic pneumonia. Female gender and use of biomass fuel for cooking increased the odds of hypoxic CAP. Clinical factors like wheezing, pallor, tachypnea, low pulse volume, presence of comorbidity, general danger signs, severe malnutrition, and radiological finding of primary end-point pneumonia ± other infiltrates (PEP±OI) also increased the odds of hypoxic CAP in a conditional logistic regression model. Adjusted odds ratio for mortality with hypoxia was 2.36 (95% CI: 1.42-3.92). CONCLUSION: Almost one-third of cases hospitalized with severe CAP had hypoxia, which increased chances of mortality. Besides known danger signs, certain newer clinical signs such as pallor and wheezing as well as PEP+OI were associated with hypoxic CAP. Therefore, objective assessment of oxygen saturation must be done by pulse oximetry in all cases of CAP at the time of diagnosis.

Anticancer Agents Based on Vulnerable Components in a Signalling Pathway.

Traditional cancer treatment includes surgery, chemotherapy, radiotherapy and immunotherapy that are clinically beneficial, but are associated with drawbacks such as drug resistance and side effects. In quest for better treatment, many new molecular targets have been introduced in the last few decades. Finding new molecular mechanisms encourages researchers to discover new anticancer agents. Exploring the mechanism of action also facilitates anticipation of potential resistance mechanisms and optimization of rational combination therapies. The write up describes the leading molecular mechanisms for cancer therapy, including mTOR, tyrosine Wee1 kinase (WEE1), Janus kinases, PI3K/mTOR signaling pathway, serine/threonine protein kinase AKT, checkpoint kinase 1 (Chk1), maternal embryonic leucine-zipper kinase (MELK), DNA methyltransferase I (DNMT1), poly (ADP-ribose) polymerase (PARP)-1/-2, sphingosine kinase-2 (SK2), pan-FGFR, inhibitor of apoptosis (IAP), murine double minute 2 (MDM2), Bcl-2 family protein and reactive oxygen species 1 (ROS1). Additionally, the manuscript reviews the anticancer drugs currently under clinical trials.

A Cross-Sectional Study to Assess the Quality of Life of Perimenopausal and Post menopausal Women in Rural Etawah, Uttar Pradesh, India.

BACKGROUND: Perimenopause is the period in a woman's life during which she passes from the reproductive to the nonreproductive stage. According to the 2008 estimates, the number of menopausal women in India was 43 million. Projected values in 2026 depict the menopausal population at 103 million. Due to the increasing life expectancy, improved quality of life is imperative to decrease the disability and frailty of a society. OBJECTIVES: To study the quality of life of perimenopausal women in rural areas of Etawah district, Uttar Pradesh, and the various factors associated with it. MATERIALS AND METHODS: This is a community-based cross-sectional study conducted in 4 villages in the Saifai block of Etawah district, Uttar Pradesh, India. One hundred and ninety-nine healthy, perimenopausal women of the age group 45-55 years were included in the study. Data were collected on sociodemographic variables, and Menopause Specific Quality of Life Questionnaire - Intervention version questionnaire was used to assess the quality of life. RESULTS: The mean age of attainment of menopause was 45.38 ± 3.58 years. Majority of the women experienced physical (100%) and psychosocial (94.5%) symptoms; the most common symptom being "decrease in physical strength" (86.4%) and being able to "accomplish less than previously" (80.4%). Women who handled stress poorly showed severe vasomotor (P = 0.047) and psychosocial (P = 0.014) symptoms. Postmenopausal women who regularly exercised were 52.6% less likely to have vasomotor symptoms (odd's ratio OR 0.474 (0.235-0.960), P = 0.038). CONCLUSION: The quality of life among the study population was affected by the physical and psychosocial problems they experienced. By taking appropriate preventive measures, these can be ameliorated, and further deterioration can be checked.

Recovery of combustibles from electrostatic precipitator discharge.

Coal is the main fuel for the direct reduced iron (DRI) plants of India, which are one of the major sources of fly ash generation. The generation of fly ash and its disposal has raised concern because of the environmental impacts. In the present study, two different fly ash samples were investigated to explore the scope of recovery of combustibles. One did not show any recovery potential. The second sample indicated that about 40% of material could be recovered, with 35% fixed carbon and 10,841 kJ kg(-1) gross calorific value. This can be used as a fuel blend in standard fluidised bed combustion boilers efficiently burning inferior coal. A process flowsheet has been suggested for the recovery purpose. It was estimated that for a small 0.2 million tonnes per year (Mtpy) capacity DRI plant, approximately 3.4 ha of land could thus annually be saved from dumping of the generated fly ash, while recovering 1.83 MW of electrical energy.

Isolation, characterisation and antibacterial activity of new compounds from methanolic extract of seeds of Caesalpinia crista L. (Caesalpinaceae).

Phytochemical study on the methanolic extract of Caesalpinia crista afforded two novel compounds, 2-hydroxytrideca-3,6-dienyl-pentanoate and octacosa-12,15-diene along with known compounds 3-O-methylellagic acid 3'O-α-rhamnopyranoside, ß-sitosterol and sucrose. Compound 3-O-methylellagic acid 3'O-α-rhamnopyranoside is reported for the first time from the plant. Molecular structures, of isolated compounds, were elucidated by using the NMR spectroscopy in combination with IR and mass spectral data. All isolated compounds, extract and fractions were evaluated for in vitro antibacterial activity against various Gram-positive and Gram-negative bacterial strains and found to be significantly active against Staphylococcus aureus and methicillin-resistant S. aureus (minimum inhibitory concentration: 64-512 µg mL(- 1)).