A Comparison of Changes in the Mean Arterial Blood Pressure and Mean Uterine Artery Pulsatility Index from 11-14 to 19-24 + 6 Gestation Weeks in Low-Risk and High-Risk Asian Indian Pregnant Women.

Aim The aim of this study was to determine the changes in the mean arterial blood pressure (MAP) and mean uterine artery (UtA) pulsatility index (PI) from 11-14 to 19-24 + 6 gestation weeks in Asian Indian pregnant women. Methods Clinical and demographic details, MAP, and mean UtA PI measures were ascertained for pregnant women at 11 to 14 gestation weeks and 19-24 + 6 gestation weeks. Women were categorized as a high-or-low risk for preterm preeclampsia using the Fetal Medicine Foundation algorithm and 1 in 150 cutoff. High-risk pregnant women were recommended low-dose aspirin 150 mg daily at bedtime. Changes in MAP and mean UtA PI were compared for gestational age intervals and high-and-low risk women using nonparametric tests. Results The study analyzed the results of 1,163 pregnant women. Both MAP (mean difference: 5.14, p < 0.001) and mean UtA PI (mean difference: 0.14, p < 0.001) remained significantly higher at the second-trimester assessment in high-risk pregnant women compared to low-risk pregnant women. Seventy-seven (35.16%) of the 219 pregnant women with abnormal mean UtA PI in the first trimester had an abnormal mean UtA PI in the second-trimester assessment. One hundred (10.59%) of the 944 pregnant women with normal mean UtA PI in the first trimester had an abnormal mean UtA PI in the 19-24 + 6 weeks assessment. Seventy-seven pregnant women (6.62% of 1,163 women, 95% confidence interval: 5.33, 8.20) had an abnormal mean UtA PI at both gestation age intervals. High-risk pregnant women taking low-dose aspirin daily showed a larger reduction in mean UtA PI compared to high-risk pregnant women that did not report the use of low-dose aspirin (0.89 vs. 0.62, p <0.001) Conclusion MAP and mean UtA PI decreased significantly from the first to the second trimester of pregnancy. Sequential assessment of the MAP and mean UtA PI in the first and second trimesters of pregnancy will be useful for fetal radiologists in India to identify a subgroup of women with abnormal mean UtA PI at both trimesters that may need more intense surveillance and follow-up till childbirth.

Diagnostic Effectiveness of Third-Trimester Fetal Doppler Studies in Pregnancy to Predict Late-and-Term Stillbirth and Neonatal Mortality in the Samrakshan Program in India.

Aim To determine the diagnostic effectiveness of third-trimester fetal Doppler studies in pregnancy for stillbirths and neonatal mortality in the Samrakshan program of the Indian Radiological and Imaging Association (IRIA). Methods The mean uterine artery (UtA) pulsatility index (PI) > 95th percentile, umbilical artery PI > 95th percentile, middle cerebral artery (MCA) PI < 5th percentile, and/or cerebroplacental ratio (CPR) < 5th percentile in the third trimester fetal Doppler study was considered as abnormal. The results of the fetal Doppler study closest to childbirth were considered for analysis. Late stillbirth (SB) was defined as a fetal loss between 28 and 36 gestation weeks and the term SB was defined as a fetal loss at ≥ 37 gestation weeks. Neonatal death was defined as the demise of a live-born baby within the first 28 days of life. Parameters of diagnostic effectiveness such as sensitivity, specificity, positive and negative predictive values and likelihood ratios, diagnostic odds ratio, and the area under receiver operator characteristic (AUROC) curve were assessed. Results Screening of 1,326 pregnant women in the third trimester of pregnancy between September 2019 and February 2022, identified 308 (23.23%) abnormal Doppler studies, 11 (0.83%) SB, and 11 (0.84%) neonatal deaths. An abnormal Doppler study was significantly associated with late stillbirths (OR 37.2, 95% CI: 2.05, 674) but not with term SB (OR: 3.38, 95% CI: 0.76, 15) or neonatal deaths (OR 1.39, 95% CI: 0.40, 4.87). Mean UtA PI, umbilical artery PI, MCA PI, and CPR were significantly associated with late SB and not term SB. The AUROC of Doppler measures was excellent for late SB but did not show discriminatory ability for term SB or neonatal deaths. Conclusion Integration of fetal Doppler with routine third-trimester antenatal scans can help identify pregnant women at high risk for late SB. The effectiveness of fetal Doppler to identify pregnant women at high risk for term SB and neonatal deaths needs further study on a larger sample size.

Effectiveness of the First Trimester Samrakshan Protocol for the Identification of Pregnant Women at High Risk for Preterm Pre-eclampsia.

Aim To determine the effectiveness of the first trimester Samrakshan protocol for the identification of pregnant women at high risk for preterm pre-eclampsia (PE). Methods Samrakshan uses a protocol that integrates routine first-trimester ultrasound assessment at 11 to 14 gestation weeks with the measurement of mean arterial blood pressure and mean uterine artery pulsatility index assessment to determine a customized risk for preterm PE and fetal growth restriction. Based on the risk assessment, pregnant women are classified as high or low risk. Results The protocol had a high specificity (90.4%, 95% CI: 89.4%, 91.2%) and negative predictive value (98.1%, 95% CI: 97.6%, 99%) for preterm PE. The odds ratio and positive likelihood ratio for preterm PE were 16.7 (95% CI: 12.3, 22.6) and 6.64 (95% CI: 5.77, 7.63), respectively. Conclusions The positive likelihood ratio and odds ratios indicate that pregnant women identified as high risk for preterm PE using the first-trimester protocol of Samrakshan are significantly more likely to develop preterm PE than low-risk women.

Impact of the Community-Integrated Model of Samrakshan on Perinatal Mortality and Morbidity in Guna District of Central India.

Aim The aim of this study was to assess the impact of the community-integrated Samrakshan model on perinatal mortality and morbidity in the Guna district of Central India Methods The trimester-specific Samrakshan protocols were used to screen pregnant women in the first, second, and third trimesters of pregnancy and to stratify risk for preterm preeclampsia (PE) and fetal growth restriction (FGR) in the screened population. Low-dose aspirin was recommended for women identified at high risk in the first trimester screening. Fifty training programs were conducted over the duration of the program for district health workers including Anganwadi workers, Accredited Social Health Activist (ASHA) personnel, and women and child health staff. Data on the development of PE, stages of FGR, preterm births (PTBs), birthweight, neonatal mortality, and perinatal mortality were collected and compared with the baseline year to assess trends. Results The program covered 168 Anganwadi centers and screened 1,021 women in the first trimester, 870 women in the second trimester, and 811 women in the third trimester of pregnancy from 2019 to 2022 and obtained details on childbirth outcomes from 1,219 women. PE did not occur in 71.58% of pregnant women identified at high risk for PE and occurred in only 2.37% of pregnant women identified at low risk for PE. The incidence of PE reduced from 9.36 to 1.61%, stage 1 FGR from 18.71 to 11.83%, PTB from 19.49 to 11.25%, and birthweight less than 2,500 g from 33.66 to 21.46% from 2019 to 2022. The neonatal mortality rate reduced from 26 to 7.47/1,000 live births from 2019 to 2022 and the perinatal mortality rate reduced from 33.90 to 18.87/1,000 childbirths from 2019 to 2022 in the Samrakshan program area at Guna. Conclusion The community-integrated model of Samrakshan in the Guna district has led to a significant reduction in perinatal morbidity and mortality in the program area.

Prioritizing Fetal Structural Abnormalities Over Risk for Pre-Eclampsia and Fetal Growth Restriction in the 20-24 Gestation Week Assessment in India: Missing the Woods for the Trees?

Aim To compare the magnitude of fetuses with congenital anomalies, pregnant women identified at high risk for preterm pre-eclampsia (PE) or with preterm PE, and with early fetal growth restriction (FGR) or high risk for FGR at the second trimester assessment at 20 to 24 weeks of gestation. Methods A standardized trimester-specific protocol that included clinical and demographic details, fetal biometry, estimated fetal weight (EFW), fetal abdominal circumference (FAC), mean arterial blood pressure and fetal Doppler studies was used to identify high risk for preterm PE and FGR. The Targeted Imaging for Fetal Anomalies (TIFFA) scan was used to identify congenital anomalies. In addition, 95% confidence intervals of the point estimates were derived, and the p -value was estimated to assess the statistical significance of the difference in proportions. Results Analysis of the data of 4,572 pregnant women screened between 20 and 24 gestation weeks showed a significantly lower prevalence ( p < 0.001) of congenital abnormalities (3.81%) compared to women diagnosed with early PE (2.71%) or with a high risk for PE (4.00%) and women (6.80%) with early FGR or at higher risk for fetal growth restriction with both EFW and FAC < 10th percentile. Conclusion The data on prevalence from Samrakshan show that the second-trimester assessment of pregnant women in India must expand its scope from the TIFFA scan to also focus on screening to identify women at high risk for preterm PE and FGR.

Preterm Birth Rates after Initiating the Third-Trimester Screening Protocol of Samrakshan in India: Initial Results.

Aim To determine the trends in preterm birth (PTB) rates in Samrakshan after initiating a third-trimester screening protocol. Methods The Samrakshan program of IRIA focused on clinical stage-based management of fetal growth restriction (FGR) in the third trimester integrating fetal Doppler studies with routine trimester-specific antenatal scans. Mean uterine artery pulsatility index (PI), umbilical artery PI, middle cerebral artery PI, and cerebroplacental ratio were assessed for all third-trimester pregnant women in the program. Results From 2019 to 2022, 249 (18.33%, 95% CI: 16.34, 20.54) women had PTB with 221 (16.67%, 95% CI: 14.73, 18.75) PTBs between 34 and 37 gestation weeks and 22 (1.66%, 95% CI: 1.10, 2.50) PTBs at gestation < 34 weeks. The overall preterm birth rates showed a significant (chi-square p < 0.001) declining trend each year from 23.18% ( n = 121) in 2019-2020 to 16.81% ( n = 99) in 2020-2021 and 10.75% ( n = 23) in 2021-2022. Conclusion The declining trend of PTB rates in the Samrakshan program shows that the reduction of PTB is an added benefit of the integration of fetal Doppler studies in the third trimester of pregnancy.

Reducing Perinatal Mortality in India: Two-Years Results of the IRIA Fetal Radiology Samrakshan Program.

Aim The aim of the study is to determine improvements in perinatal mortality at the end of the first 2 years from the initiation of the Samrakshan program of the Indian Radiological and Imaging Association. Methods Samrakshan is a screening program of pregnant women that uses trimester-specific risk assessment protocols including maternal demographics, mean arterial pressure, and fetal Doppler studies to classify women as high risk or low risk for preterm preeclampsia (PE) and fetal growth restriction (FGR). Low dose aspirin 150 mg daily once at bedtime was started for pregnant women identified as high risk in the 11-13 6/7 weeks screening. The third-trimester screening focused on the staging of FGR and protocol-based management for childbirth and risk assessment for PE. Outcomes of childbirth including gestational age at delivery, development of PE, and perinatal mortality outcomes were collected. Results Radiologists from 38 districts of 16 states of India participated in the Samrakshan program that screened 2,816 first trimester, 3,267 second trimester, and 3,272 third trimester pregnant women, respectively. At 2 years, preterm PE was identified in 2.76%, preterm births in 19.28%, abnormal Doppler study in 25.76% of third trimester pregnancies, and 75.32% of stage 1 FGR delivered at term. The neonatal mortality rate was 9.86/1,000 live births, perinatal mortality rate was 18.97/1,000 childbirths, and maternal mortality was 58/100,000 live births compared with 29.5, 36, and 113, respectively in 2016. Conclusion Fetal Doppler integrated antenatal ultrasound studies in Samrakshan led to a significant reduction in preterm PE rates, preterm birth rates, and a significant improvement in mean birth weights. Perinatal, neonatal, and maternal mortality rates are significantly better than the targets for 2030 set by the Sustainable Development Goals-3.

The Sela macaque (Macaca selai) is a distinct phylogenetic species that evolved from the Arunachal macaque following allopatric speciation.

Arunachal macaque (M. munzala) is an endangered and recently discovered cercopithecine primate from Western Arunachal Pradesh, India. On genetic analyses of Arunachal macaques, we observed spatially distributed substantial inter-species genetic divergence among the samples collected from Arunachal Pradesh. The results suggested that Arunachal macaque evolved into two phylogenetic species about 1.96 mya following allopatric speciation by means of Sela mountain pass in Arunachal Pradesh, India. We describe - Sela macaque (M. selai) as a new macaque species that interestingly exhibited high intra-specific genetic variation and also harbors at least two conservation units. Further, we report the past demographic trajectories and quantify genetic variation required for taxonomic clarification. The present study also identifies gap areas for undertaking surveys to document the relic and unknown trans-boundary populations of macaques through multinational, multi-lateral cross border collaboration.

The Discovery and Development of Thienopyrimidines as Inhibitors of Helicobacter pylori That Act through Inhibition of the Respiratory Complex I.

The successful treatment of Helicobacter pylori infections is becoming increasingly difficult due to the rise of resistance against current broad spectrum triple therapy regimens. In the search for narrow-spectrum agents against H. pylori, a high-throughput screen identified two structurally related thienopyrimidine compounds that selectively inhibited H. pylori over commensal members of the gut microbiota. To develop the structure-activity relationship (SAR) of the thienopyrimidines against H. pylori, this study employed four series of modifications in which systematic substitution to the thienopyrimidine core was explored and ultimately side-chain elements optimized from the two original hits were merged into lead compounds. During the development of this series, the mode of action studies identified H. pylori's respiratory complex I subunit NuoD as the target for lead thienopyrimidines. As this enzyme complex is uniquely essential for ATP synthesis in H. pylori, a homology model of the H. pylori NuoB-NuoD binding interface was generated to help rationalize the SAR and guide further development of the series. From these studies, lead compounds emerged with increased potency against H. pylori, improved safety indices, and a good overall pharmacokinetic profile with the exception of high protein binding and poor solubility. Although lead compounds in the series demonstrated efficacy in an ex vivo infection model, the compounds had no efficacy in a mouse model of H. pylori infection. Additional optimization of pharmacological properties of the series to increase solubility and free-drug levels at the sequestered sites of H. pylori infection would potentially result in a gain of in vivo efficacy. The thienopyrimidine series developed in this study demonstrates that NuoB-NuoD of the respiratory complex I can be targeted for development of novel narrow spectrum agents against H. pylori and that thienopyrimines can serve as the basis for future advancement of these studies.

Discordant dating of pregnancy by LMP and ultrasound and its implications in perinatal statistics.

CONTEXT: High perinatal mortality in India may be caused by inaccurate dating of pregnancy resulting from suboptimal uptake of antenatal care and ultrasound services during pregnancy. AIM: To determine the discrepancy in the last menstrual period (LMP) assigned expected date of delivery (EDD) and ultrasound assigned EDD in pregnant women in a rural district of central India. METHODS: Data from an ongoing cross-sectional screening program providing fetal radiology imaging in Guna district of Madhya Pradesh from 2012-2019 was analyzed for recall of LMP and discordance between LMP and ultrasound assigned EDD. The discrepancy was present when EDD assigned by ultrasound differed by 3 or more days at gestational ages less than 8+6 weeks, 5-7 days at gestational ages 8+6 weeks till 14 weeks, and 7-10 days at gestational ages 14-20 weeks. RESULTS: The program screened 14,701 pregnant women of which 4,683 (31.86%, 95% CI: 31.11, 32.61) could not recall LMP. EDD assigned by LMP and ultrasound matched in 7,035 (70.22%, 95% CI: 69.32, 71.12) of the remaining 10,018 pregnant women. EDD was overestimated by LMP for 26.06% (95% CI: 25.21, 26.93) women; these foetuses were at risk of being misclassified as a term fetus. In 2018, the project had no maternal deaths, infant mortality rate of 24.7, low birth weight rate of 9.69%, and 100% antenatal coverage. CONCLUSION: Accurate dating of pregnancy and systematic follow-up integrating radiology imaging and obstetrics care for appropriate risk-based management of pregnant women can significantly improve perinatal statistics of India.

Samrakshan: An Indian Radiological and Imaging Association program to reduce perinatal mortality in India.

CONTEXT: India has a high perinatal mortality rate. The Indian Radiological and Imaging Association (IRIA) is supplementing efforts to address perinatal mortality in India through the Samrakshan program. AIMS: To describe various elements of the Samrakshan program that aims to reduce perinatal mortality in India. METHODS: Samrakshan focuses on two priority areas, preeclampsia (PE) and fetal growth restriction (FGR). Samrakshan aims at technical skill upgradation, specifically focused on improved interpretative ability, prognostic and therapeutic efficacy using Doppler studies, a free online learning platform and offline continuous medical educations (CMEs), building an evidence base from the program to develop policy and guidelines, and improving synergy with the RAKSHA program of IRIA and other fetal care stakeholders. RESULTS: Two courses on Doppler studies focused on first trimester and third trimester, supplemented by case discussions and journal articles, have started on the online platform with 230 registrants. The first statewide CME was held at Indore. Samrakshan screening identified 10 (17.24%, 95% CI: 8.59, 29.43) women at high risk for preterm PE and 29 (50.00%, 95% CI 36.58, 63.42) women at high risk for FGR in the first trimester. Ten fetuses (7.63%, 95% CI: 3.72, 13.59) including 9 with stage 1 FGR were identified in the third-trimester screening. CONCLUSIONS: Samrakshan is a flagship program of IRIA that aims to reduce perinatal mortality in India through a synergistic, holistic approach that complements and supplements existing efforts in India.

Pragmatic perspective on conservation genetics and demographic history of the last surviving population of Kashmir red deer (Cervus elaphus hanglu) in India.

The hangul (Cervus elaphus hanglu) is of great conservation concern because it represents the easternmost and only hope for an Asiatic survivor of the red deer species in the Indian subcontinent. Despite the rigorous conservation efforts of the Department of Wildlife Protection in Jammu & Kashmir, the hangul population has experienced a severe decline in numbers and range contraction in the past few decades. The hangul population once abundant in the past has largely become confined to the Dachigam landscape, with a recent population estimate of 218 individuals. We investigated the genetic variability and demographic history of the hangul population and found that it has shown a relatively low diversity estimates when compared to other red deer populations of the world. Neutrality tests, which are used to evaluate demographic effects, did not support population expansion, and the multimodal pattern of mismatch distribution indicated that the hangul population is under demographic equilibrium. Furthermore, the hangul population did not exhibit any signature of bottleneck footprints in the past, and Coalescent Bayesian Skyline plot analysis revealed that the population had not experienced any dramatic changes in the effective population size over the last several thousand years. We observed a strong evidence of sub-structuring in the population, wherein the majority of individuals were assigned to different clusters in Bayesian cluster analysis. Population viability analysis demonstrated insignificant changes in the mean population size, with a positive growth rate projected for the next hundred years. We discuss the phylogenetic status of hangul for the first time among the other red deer subspecies of the world and strongly recommend to upgrade hangul conservation status under IUCN that should be discrete from the other red deer subspecies of the world to draw more conservation attention from national and international bodies.

Loss of genetic diversity and inbreeding in Kashmir red deer (Cervus elaphus hanglu) of Dachigam National Park, Jammu & Kashmir, India.

BACKGROUND: Hangul (Cervus elaphus hanglu), the eastern most subspecies of red deer, is now confined only to the mountains in the Kashmir region of Jammu & Kashmir State of India. It is of great conservation significance as this is the last and only hope for Asiatic survivor of the red deer species in India. Wild population of free ranging hangul deer inhabiting in and around Dachigam National Park was genetically assessed in order to account for constitutive genetic attributes of hangul population using microsatellite markers. RESULTS: In a pool of 36 multi-locus genotypes, 30 unique individuals were identified based on six microsatellite loci. The estimated cumulative probability of identity assuming all individuals were siblings (PID sibs) was 0.009 (9 in 1000). Altogether, 49 different alleles were observed with mean (± s.e.) allelic number of 8.17 ± 1.05, ranging from 5 to 11 per locus. The observed heterozygosity ranged between 0.08 and 0.83, with mean 0.40 ± 0.11 and the inbreeding coefficient ranged between -0.04 and 0.87 with mean 0.38 ± 0.15. Majority of loci (5/6) were found to be informative (PIC value > 0.5). All loci deviated from Hardy-Weinberg equilibrium except Ca-38 (P > 0.05) and none of the pairs of loci showed significant linkage disequilibrium except the single pair of Ca-30 and Ca-43 (P < 0.05). CONCLUSIONS: The preliminary findings revealed that hangul population is significantly inbred and exhibited a low genetic diversity in comparison to other deer populations of the world. We suggest prioritizing the potential individuals retaining high heterozygosity for ex situ conservation and genetic monitoring of the hangul population should be initiated covering the entire distribution range to ensure the long term survival of hangul. We speculate further ignoring genetics attributes may lead to a detrimental effect which can negatively influence the reproductive fitness and survivorship of the hangul population in the wild.

Discovery of novel antitubercular 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues.

In the present investigation, a series of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues were synthesized and were evaluated for antitubercular activity by two fold serial dilution technique. All the newly synthesized compounds showed low to high inhibitory activities against Mycobacterium tuberculosis H(37)Rv and INH resistant M. tuberculosis. The compound 3-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (4o) was found to be the most promising compound active against M. tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis with minimum inhibitory concentration 3.12 µM and 6.25 µM, respectively.