Ru(II)/Ru(IV)-catalyzed C(sp2)-H allylation with alkene difunctionalization to access isochroman-1-imines.

Merging C(sp2)-H allylation and alkene difunctionalization events to access isochroman-1-imines, using N-aroyl aminoesters, MBH acetates, and NBS, under Ru(II)/Ru(IV) catalysis has been developed. Using 1H NMR, ESI-MS, HRMS, control reactions, deuterium labeling experiments, and DFT analysis, the allyl transfer (redox) process was proven to involve in C-H allylation rather than olefin insertion. Scale-up and synthetic transformations demonstrated the sustainability of this method.

Gender differences in COVID-19 knowledge, risk perception, and public stigma among the general community: Findings from a nationwide cross-sectional study in India.

Introduction: Individual and community characteristics predictive of knowledge, perception, and attitude on COVID-19, specifically on gender, have not been adequately explored. Objective: To examine the gender differences in COVID-19 knowledge, self-risk perception and public stigma among the general community and to understand other socio-demographic factors which were predictive of them. Method: A nationally representative cross-sectional multi-centric survey was conducted among adult individuals(≥18 yrs) from the community member (N = 1978) from six states and one union territory of India between August 2020 to February 2021. The participants were selected using systematic random sampling. The data were collected telephonically using pilot-tested structured questionnaires and were analyzed using STATA. Gender-segregated multivariable analysis was conducted to identify statistically significant predictors (p < 0.05) of COVID-19-related knowledge, risk perception, and public stigma in the community. Results: Study identified significant differences between males and females in their self-risk perception (22.0% & 18.2% respectively) and stigmatizing attitude (55.3% & 47.1% respectively). Highly educated males and females had higher odds of having COVID-19 knowledge (aOR: 16.83: p < 0.05) than illiterates. Highly educated women had higher odds of having self-risk perception (aOR: 2.6; p < 0.05) but lower public stigma [aOR: 0.57; p < 0.05]. Male rural residents had lower odds of having self-risk perception and knowledge [aOR: 0.55; p < 0.05 & aOR: 0.72; p < 0.05] and female rural residents had higher odds of having public stigma [aOR: 1.36; p < 0.05]. Conclusion: Our study findings suggest the importance of considering thegender differentials and their background, education status and residential status in designing effective interventions to improve knowledge and reduce risk perception and stigma in the community about COVID-19.

Molecular detection of spotted fever group of Rickettsiae in acute encephalitis syndrome cases from eastern Uttar Pradesh region of India.

The Eastern Uttar Pradesh region of India is known for its endemicity of acute encephalitis syndrome (AES). Decades of research have established that Orientia tsutsugamushi, a causative of scrub typhus, is a substantial contributor (>60%) for the AES cases besides other aetiology, but additional factors in the remaining proportion are still unidentified. Rickettsial infections are challenging to diagnose in clinical settings due to overlapping clinical symptoms, the absence of definitive indicators, a low index of suspicion, and the lack of low-cost, rapid diagnostic tools. Hence, the present study was designed to determine the load of rickettsial infections among AES cases. Furthermore, we aim to find out the prevalent rickettsial species in AES cases as well as in the vector population at this location. The study included the whole blood/cerebrospinal fluid of AES patients and arthropod specimens from rodents. The molecular identification was performed using the 23S-5S intergenic spacer region and ompB gene with genomic DNA obtained from studied specimens. We detected 5.34% (62/1160) of rickettsial infection in AES cases. Among these, phylogenetic analysis confirmed the presence of 54.8% Rickettsia conorii (n = 34) and 16.1% of Rickettsia felis (n = 10), while the rest proportion of the isolates was unidentified at the species level. Furthermore, R. felis was identified in one CSF sample from AES patients and three flea samples from Xenopsylla cheopis. Rickettsia spp. was also confirmed in one Ornithonyssus bacoti mite sample. The results of this investigation concluded the presence of spotted fever group Rickettsia spp. among AES identified cases as well as in the mite and flea vectors that infest rodents.

Challenges in Accessing and Delivering Maternal and Child Health Services during the COVID-19 Pandemic: A Cross-Sectional Rapid Survey from Six States of India.

BACKGROUND/OBJECTIVES: Globally, the COVID-19 pandemic and its prevention and control policies have impacted maternal and child health (MCH) services. This study documents the challenges faced by patients in accessing MCH services, and the experiences of health care providers in delivering those services during the COVID-19 outbreak, explicitly focusing on the lockdown period in India. METHODS: A cross-sectional study (rapid survey) was conducted in 18 districts from 6 states of India during March to June, 2020. The sample size included 540 MCH patients, 18 gynaecologists, 18 paediatricians, 18 district immunisation officers and 108 frontline health workers. Bivariate analysis and multivariable analysis were used to assess the association between sociodemographic characteristics, and challenges faced by the patients. RESULTS: More than one-third of patients (n = 212; 39%) reported that accessing MCH services was a challenge during the lockdown period, with major challenges being transportation-related difficulties (n = 99; 46%) unavailability of hospital-based services (n = 54; 23%) and interrupted outreach health services (n = 39; 18.4%). The supply-side challenges mainly included lack of infrastructural preparedness for outbreak situations, and a shortage of human resources. CONCLUSIONS/RECOMMENDATIONS: A holistic approach is required that focuses on both preparedness and response to the outbreak, as well reassignment and reinforcement of health care professionals to continue catering to and maintaining essential MCH services during the pandemic.

Duration of seroprotection of the live attenuated SA-14-14-2 Japanese encephalitis vaccine in children in India.

BACKGROUND: Acute encephalitis syndrome (AES) is a major public health concern in India, and the Japanese Encephalitis (JE) virus is the most common cause of viral encephalitis in Asia affecting children under the age of 15 years. In India, despite the introduction of the JE vaccine (SA-14-14-2) in the immunization programme, JE continues to account for 15-20% of AES cases to date. This study evaluates the immunogenicity of live attenuated SA-14-14-2 JE vaccine in terms of persistence of the humoral response after two doses. METHODS: A cross-sectional study was conducted among 266 children belonging to one of the JE endemic regions of Uttar Pradesh, India. Blood samples were taken from children (2-10 years) and grouped according to the duration (in years) after two doses of the vaccine (5 groups with a class interval of 2 years). Informed written consent was obtained from the parents/guardians. All the samples collected were tested for the presence of anti-JEV-specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and further confirmed by micro neutralization test (MNT) and immunofluorescence assays. RESULTS: Of the 266 samples tested by ELISA for anti-JEV-specific IgG antibodies, 260 (97.74%) were negative and 6 (2.26%) were equivocal. The geometric mean immune status ratio across the five groups, 0-2 years (n = 59), 2-4 years (n = 73), 4-6 years (n = 65), 6-8 years (n = 48) and 8-10 years (n = 21) post-two doses of SA-14-14-2 JE vaccine was 1.143, 1.059, 1.138, 1.075 and 1.130, respectively, and the geometric mean titre obtained from MNT across the five groups was 10.77, 8.400, 8.453, 9.517 and 9.674, respectively. CONCLUSION: The study showed a decreasing trend of anti-JEV specific IgG antibody titres across the five groups based on the duration following two doses of SA-14-14-2 vaccine. The results emphasize the significance of booster doses of vaccine for children living in endemic areas.

Factors associated with COVID-19 stigma during the onset of the global pandemic in India: A cross-sectional study.

Objective: To assess factors associated with COVID-19 stigmatizing attitudes in the community and stigma experiences of COVID-19 recovered individuals during first wave of COVID-19 pandemic in India. Methods: A cross-sectional study was conducted in 18 districts located in 7 States in India during September 2020 to January 2021 among adults > 18 years of age selected through systematic random sampling. Data on socio demographic and COVID-19 knowledge were collected from 303 COVID-19 recovered and 1,976 non-COVID-19 infected individuals from community using a survey questionnaire. Stigma was assessed using COVID-19 Stigma Scale and Community COVID-19 Stigma Scale developed for the study. Informed consent was sought from the participants. Univariate and multivariate binary logistic regression analysis were conducted. Results: Half of the participants (51.3%) from the community reported prevalence of severe stigmatizing attitudes toward COVID-19 infected while 38.6% of COVID-19 recovered participants reported experiencing severe stigma. Participants from the community were more likely to report stigmatizing attitudes toward COVID-19 infected if they were residents of high prevalent COVID-19 zone (AOR: 1.5; CI: 1.2-1.9), staying in rural areas (AOR: 1.5; CI:1.1-1.9), belonged to the age group of 18-30 years (AOR: 1.6; CI 1.2-2.0), were male (AOR: 1.6; CI: 1.3-1.9), illiterate (AOR: 2.7; CI: 1.8-4.2), or living in Maharashtra (AOR: 7.4; CI: 4.8-11.3). COVID-19 recovered participants had higher odds of experiencing stigma if they had poor knowledge about COVID-19 transmission (AOR: 2.8; CI: 1.3-6.3), were staying for 6-15 years (AOR: 3.24; CI: 1.1-9.4) in the current place of residence or belonged to Delhi (AOR: 5.3; CI: 1.04-26.7). Conclusion: Findings indicated presence of stigmatizing attitudes in the community as well as experienced stigma among COVID-19 recovered across selected study sites in India during the first wave of COVID-19 pandemic. Study recommends timely dissemination of factual information to populations vulnerable to misinformation and psychosocial interventions for individuals affected by stigma.

Development & validation of scales to assess stigma related to COVID-19 in India.

Background & objectives: COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community. Methods: COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability. Results: Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement. Interpretation & conclusions: Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.

Comparison of the Rapid Antigen Testing Method With RT-qPCR for the Diagnosis of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has till now affected about 110 million people globally. It has not spared any country and has led to 24 lakh deaths. As a result, the testing had to be increased manifold leading to depletion in the number of the quantitative reverse transcription polymerase chain reaction (RT-qPCR) kits. Point-of-care rapid antigen-based tests were developed in order to meet the increasing demands. The objective of this study was to compare the performance of a rapid chromatographic test (index test) with a gold standard test (RT-qPCR). METHODS: A retrospective analysis was done at a tertiary care teaching hospital in Eastern Uttar Pradesh, India. Paired samples were taken from all patients reporting to the clinic for antigen-based rapid diagnostic testing (RDT) and RT-qPCR. The sensitivity and specificity were calculated to evaluate the performance of the RDT. RESULTS: The overall sensitivity and specificity of the RDT were observed to be 53.6% (39.7-67.0) and 97.35% (94.6-98.9), respectively. In symptomatic individuals, the sensitivity was higher 61.0% (44.5-75.8). The test positivity rates of RDT were found to be higher at a ​​cycle threshold value ≤20. CONCLUSION: RDT can be used as a screening test to rule in the infection especially in symptomatic patients who are more prone to spread the disease. It is an important weapon in the armamentarium of public healthcare for the containment of COVID-19.

Abundance of Ticks (Acari: Ixodidae) and Presence of Rickettsia and Anaplasma in Ticks Infesting Domestic Animals From Northern India.

Rickettsia and Anaplasma are bacteria that can be transmitted by hematophagous arthropods such as ticks infesting animals in close proximity to humans. The main objective of the present study was to investigate abundance of common tick species infesting domestic animals and presence of Rickettsia and Anaplasma in tick populations. Adult ticks were collected from domestic animals in rural areas and screened by molecular detection of bacterial DNA for these two genera of bacteria. A total of 1,778 adult ixodid tick specimens were collected from 200 cattle, 200 buffaloes, 200 goats, and 40 dogs. The collection consisted of four species of ixodid ticks, Rhipicephalus (Boophilus) microplus (Canestrini) (83.8%), Hyalomma kumari (Sharif) (7.1%), Rhipicephalus sanguineus (Latreille) (6.4%), and Dermacentor auratus (Supino) (2.7%) infesting the domestic animals. The prevalence of all the collected tick species was highest in the month of October. Anaplasma spp. was the most frequently identified bacteria (3.3%) in tested ticks. Of 17 positive tick pools for Anaplasma spp., 14 pools were from ticks infesting cattle, 2 pools of ticks collected from buffalo, and the remaining pool were ticks infesting a goat at the time of collection. Although 1.6% tick pools of R. microplus collected from cattle tested positive for Rickettsia spp., present investigation provides evidence of the most prevalent ixodid ticks infesting domestic animals and the presence of obligate intracellular bacteria, Rickettsia and Anaplasma, in these ticks collected in the Gorakhpur division of Northern India.

Effectiveness of Presumptive Treatment of Acute Febrile Illness With Doxycycline or Azithromycin in Preventing Acute Encephalitis Syndrome in Gorakhpur, India: A Cohort Study.

OBJECTIVE: To estimate effectiveness of presumptive doxycycline or azithromycin treatment in preventing progression of Acute Febrile Illness to Acute Encephalitis Syndrome in Gorakhpur. STUDY DESIGN: Prospective cohort study. STUDY SETTING: Primary healthcare centers and Community healthcare centers of Gorakhpur district, Uttar Pradesh. PARTICIPANTS: Children aged 1 year to less than 15 years with fever of 3 days to less than 15 days duration attending three selected peripheral health facilities in Gorakhpur during August to October, 2018. PROCEDURE: 35 medical officers in three selected Primary Healthcare Centers/Community Healthcare centers were sensitized on the treatment strategy. After sensitization, study participants were enrolled and information about prescription of doxycycline or azithromycin was collected. Participants were telephonically followed-up to know their progression status from AFI to AES. MAIN OUTCOME MEASURE: Incidence of acute encephalitis syndrome among acute failure illness patients who received presumptive doxycycline or azithromycin treatment and those who did not receive this treatment. RESULTS: Of the enrolled 930 AFI patients, 801 (86%) were prescribed doxycycline or azithromycin and 725 (78%) could be telephonically followed-up. Progression to acute encephalitis syndrome was seen in 6 of the 621 patients who received presumptive treatment, and 5 of the 104 who did not receive the treatment. The relative risk of developing acute encephalitis syndrome among acute febrile illness patients who were prescribed presumptive treatment with doxycycline or azithromycin was 0.20 (95% CI: 0.06-0.65). The effectiveness of presumptive treatment with doxycycline or azithromycin strategy was 79.9% (95% CI: 35.4-94). CONCLUSIONS: PDA treatment to children presenting with fever in peripheral health facilities of the study blocks in Gorakhpur during August-November, 2018 had good effectiveness in preventing progression of acute febrile illness to acute encephalitis syndrome.

MR neurography in Parsonage-Turner syndrome.

BACKGROUND AND AIMS: Parsonage Turner Syndrome is a well known clinical entity. Several excellent articles have succinctly described Magnetic Resonance Imaging (MRI) findings in PTS. However, these articles have inferred neural involvement in PTS based on the patterns of denervation of muscles in the shoulder region. The aim of this study is to directly visualize the distribution and extent of abnormality in MR Neurography (MRN) of the brachial plexus in known cases of brachial plexus neuritis or Parsonage-Turner Syndrome (PTS). METHODS: 15 patients who were diagnosed with PTS based on clinical and electrophysiological findings participated in the study. MRN of the brachial plexus was done in a 1.5T system using a combination of T1W (T1-weighted), T2W (T2-weighted) fat-saturated, STIR (Short Tau Inversion Recovery), 3D STIR SPACE (Sampling Perfection with Application Optimized Contrasts) and 3D T2W SPACE sequences. Findings were recorded and assessed. RESULTS: The age range of our patients was 7-65 years (mean 37.87 years). Most of the patients had unilateral symptoms. All patients had weakness in shoulder abduction. Other common associated complaints included pain in the shoulder/neck/arm and preceding fever. MRN revealed the percentage of involvement of roots, trunks, cords and terminal branches was 53.3%, 46.7%, 40% and 13.3% respectively. Evidence of muscle denervation in the form of edema, fatty infiltration and atrophy was noted in 8 (53.3%) patients. CONCLUSION: Most of the patients in this study had unilateral involvement on MRN. The roots were the commonest site of involvement followed by the trunks, cords and terminal branches. C5 was the most commonly involved root.

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C-H Allylation and [3+2] Dipolar Cycloaddition.

The ruthenium(II)-catalyzed C-H functionalization of (hetero)aryl azomethine imines with allylic acetals is described. The initial formation of allylidene(methyl)oxoniums from allylic acetals could trigger C(sp2 )-H allylation, and subsequent endo-type [3+2] dipolar cycloaddition of polar azomethine fragments to deliver valuable indenopyrazolopyrazolones. The utility of this method is showcased by the late-stage functionalization of bioactive molecules such as estrone and celecoxib. Combined experimental and computational investigations elucidate a plausible mechanism of this new tandem reaction. Notably, the reductive transformation of synthesized compounds into biologically relevant diazocine frameworks highlights the importance of the developed methodology.

A rare case of quadriparesis.

Snakebite is a public health problem. Common krait is nocturnally active with painless bite. Patients exhibit neuromuscular weakness.

Ruthenium(II)-Catalyzed Site-Selective Hydroxymethylation of Indolines with Paraformaldehyde.

The facile synthesis of hydroxymethylated indole derivatives is crucial for their further development as pharmaceutical compounds and other synthetic purposes. Herein, we describe the ruthenium(II)-catalyzed hydroxymethylation of indolines and other N-heterocycles using paraformaldehyde as an abundant C1 feedstock. A wide substrate scope range and high levels of site selectivity as well as functional group tolerance were observed.

Reductive C2-Alkylation of Pyridine and Quinoline N-Oxides Using Wittig Reagents.

The ability to alkylate pyridines and quinolines is important for their further development as pharmaceuticals and agrochemicals, and for other purposes. Herein we describe the unprecedented reductive alkylation of pyridine and quinoline N-oxides using Wittig reagents. A wide range of pyridine and quinoline N-oxides were converted into C2-alkylated pyridines and quinolines with excellent site selectivity and functional-group compatibility. Sequential C-H functionalization reactions of pyridine and quinoline N-oxides highlight the utility of the developed method. Detailed labeling experiments were performed to elucidate the mechanism of this process.

Synthesis of TMPA Derivatives through Sequential Ir(III)-Catalyzed C-H Alkylation and Their Antidiabetic Evaluation.

The synthesis and antidiabetic evaluation of ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl]acetate (TMPA) and its structural analogs are described. The construction of TMPA derivatives has been successfully achieved in only two steps, which involve the iridium(III)-catalyzed α-alkylation of acetophenones with alcohols and the ketone-directed iridium(III)- or rhodium(III)-catalyzed redox-neutral C-H alkylation of α-alkylated acetophenones using Meldrum's diazo compounds. This synthetic protocol efficiently provides a range of TMPA derivatives with site selectivity and functional group compatibility. In addition, the site-selective demethylation of TMPA derivative affords the naturally occurring phomopsin C in good yield. Moreover, all synthetic compounds were screened for in vitro adenosine 5'-monophosphate-activated protein kinase (AMPK) activation using HepG2 cells. Furthermore, TMPA (5ac) and 5cd showing the most potent AMPK activation were treated for the in vivo antidiabetic experiment. Notably, our synthetic compound 5cd was found to display the powerful antidiabetic effect, stronger than that of metformin and TMPA (5ac).

Reactivity of Morita-Baylis-Hillman Adducts in C-H Functionalization of (Hetero)aryl Nitrones: Access to Bridged Cycles and Carbazoles.

The rhodium(III)-catalyzed cross-coupling of (hetero)aryl nitrones with Morita-Baylis-Hillman (MBH) adducts is described. An allylated intermediate derived from aryl nitrones and MBH adducts allows the formation of bridged cyclic compounds via an exotype [3 + 2] cycloaddition. In sharp contrast, electron-rich indolinyl or aniline substrates were found to couple with MBH adducts to generate naphthalene or carbazole derivatives, respectively.

Synthesis of (2 H)-Indazoles through Rh(III)-Catalyzed Annulation Reaction of Azobenzenes with Sulfoxonium Ylides.

The rhodium(III)-catalyzed C-H functionalization followed by intramolecular annulation reactions between azobenzenes and sulfoxonium ylides is described. This protocol leads to the efficient formation of 3-acyl (2 H)-indazoles with a range of substrate scope. A high level of chemoselectivity and functional group tolerance of this transformation were also observed.

Scrub Typhus as an Etiology of Acute Febrile Illness in Gorakhpur, Uttar Pradesh, India, 2016.

Seasonal outbreaks of acute encephalitis syndrome (AES) with high mortality occur every year in Gorakhpur region of Uttar Pradesh, India. Earlier studies indicated the role of scrub typhus as the important etiology of AES in the region. AES cases were hospitalized late in the course of their illness. We established surveillance for acute febrile illness (AFI) (fever ≥ 4 days duration) in peripheral health facilities in Gorakhpur district to understand the relative contribution of scrub typhus. Of the 224 patients enrolled during the 3-month period corresponding to the peak of AES cases in the region, about one-fifth had immunoglobulin M (IgM) antibodies against Orientia tsutsugamushi. Dengue and leptospira accounted for 8% and 3% of febrile illness cases. Treating patients with AFI attending the peripheral health facilities with doxycycline could prevent development of AES and thereby reduce deaths due to AES in Gorakhpur region.

Coverage & missed opportunity for Japanese encephalitis vaccine, Gorakhpur division, Uttar Pradesh, India, 2015: Implications for Japanese encephalitis control.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) is an important aetiology of acute encephalitis syndrome in Gorakhpur division, Uttar Pradesh, India. Two doses of JE vaccine ( first during 9-12 months and second during 16-24 months of age) are administered under the Universal Immunization Programme. We conducted surveys to estimate the coverage of JE vaccine and magnitude of missed opportunity for vaccination (MoV) for JE in Gorakhpur division. METHODS: To estimate the JE vaccine coverage, cluster surveys were conducted in four districts of Gorakhpur division by selecting 30 clusters by probability proportional to size method in each district, seven children aged 25-36 months were selected from each cluster and their mothers were interviewed about JE vaccination. To estimate the magnitude of MoV, exit surveys were conducted in vaccination clinics in selected health facilities, mothers were interviewed about the vaccination status of their children and vaccines administered to the child on the day of interview. RESULTS: A total of 840 children were surveyed, 210 from each district. The coverages of one and two doses of JE vaccine in Gorakhpur division were 75 per cent [95% confidence interval (CI): 71.0-78.9] and 42.3 per cent (95% CI: 37.8-46.8), respectively. Facility-based exit survey indicated that 32.7 per cent of the eligible children missed JE vaccine. INTERPRETATION & CONCLUSIONS: The survey results showed that three of the four children aged 25-36 months in Gorakhpur division had received at least one dose of JE vaccine. The coverage of second dose of JE vaccine, however, was low. Failure to administer vaccination simultaneously was the most common reason for MoV for JE vaccine. Training vaccinators about correct vaccination schedule and removing their misconception about administering vaccines simultaneously would substantially improve JE vaccine coverage in Gorakhpur.