Neonatal mortality among preterm infants admitted to neonatal intensive care units in India and Pakistan: A prospective study.

OBJECTIVE: To explore potential reasons for differences in preterm neonatal mortality in neonatal intensive care units (NICUs) in India and Pakistan. DESIGN: A prospective observational study, the Project to Understand and Research Stillbirth and Preterms in Southeast Asia (PURPOSe) was conducted July 2018 to February 2020. SETTING: Three hospitals in Davangere, India, and a large public hospital in Karachi, Pakistan. POPULATION: Of a total of 3,202 preterm infants enrolled, 1,512 were admitted to a study NICU. METHODS: We collected data for neonates, including length of stay, diagnoses, and diagnostic tests. MAIN OUTCOME MEASURES: Neonatal mortality, tests performed, diagnoses ascertained. RESULTS: For infants of equivalent weights and gestational ages, neonatal mortality in Pakistan was twice that in the Indian NICU. The mean newborn length of stay in Pakistan was 2 days compared with 10 days for India. Fewer diagnostics and other investigations were used to determine neonatal condition or guide treatment in the Pakistani NICU. Because of limited information from testing in Pakistan concerning clinical respiratory distress, respiratory distress syndrome appeared to be over-diagnosed, whereas other conditions including pneumonia, sepsis, necrotising entercolitis and intraventricular haemorrhage were rarely diagnosed. CONCLUSION: In the Pakistani site, the limited resources available to the NICU appeared related to a shorter length of stay and decreased diagnostic testing, likely explaining the higher mortality. With improved care, reduction in mortality among preterm neonates should be achievable.

The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study.

BACKGROUND: Preterm birth remains the major cause of neonatal death worldwide. South Asia contributes disproportionately to deaths among preterm births worldwide, yet few population-based studies have assessed the underlying causes of deaths. Novel evaluations, including histological and bacteriological assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of preterm deaths. We sought to assess underlying and contributing causes of preterm neonatal deaths in India and Pakistan. METHODS: The project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe) was a prospective cohort study done in three hospitals in Davangere, India, and two hospitals in Karachi, Pakistan. All pregnant females older than 14 years were screened at the time of presentation for delivery, and those with an expected or known preterm birth, defined as less than 37 weeks of gestation, were enrolled. Liveborn neonates with a weight of 1000 g or more who died by 28 days after birth were included in analyses. Placentas were collected and histologically evaluated. In addition, among all neonatal deaths, with consent, minimally invasive tissue sampling was performed for histological analyses. PCR testing was performed to assess microbial pathogens in the placental, blood, and fetal tissues collected. An independent panel reviewed available data, including clinical description of the case and all clinical maternal, fetal, and placental findings, and results of PCR bacteriological investigation and minimally invasive tissue sampling histology, from all eligible preterm neonates to determine the primary and contributing maternal, placental, and neonatal causes of death. FINDINGS: Between July 1, 2018, and March 26, 2020, of the 3470 preterm neonates enrolled, 804 (23%) died by 28 days after birth, and, of those, 615 were eligible and had their cases reviewed by the panel. Primary maternal causes of neonatal death were hypertensive disease (204 [33%] of 615 cases), followed by maternal complication of pregnancy (76 [12%]) and preterm labour (76 [11%]), whereas the primary placental causes were maternal and fetal vascular malperfusion (172 [28%] of 615) and chorioamnionitis, funisitis, or both (149 [26%]). The primary neonatal cause of death was intrauterine hypoxia (212 [34%] of 615) followed by congenital infections (126 [20%]), neonatal infections (122 [20%]), and respiratory distress syndrome (126 [20%]). INTERPRETATION: In south Asia, intrauterine hypoxia and congenital infections were the major causes of neonatal death among preterm babies. Maternal hypertensive disorders and placental disorders, especially maternal and fetal vascular malperfusion and placental abruption, substantially contributed to these deaths. FUNDING: Bill & Melinda Gates Foundation.

Genome-wide association mapping identifies an SNF4 ortholog that impacts biomass and sugar yield in sorghum and sugarcane.

Sorghum is a feed/industrial crop in developed countries and a staple food elsewhere in the world. This study evaluated the sorghum mini core collection for days to 50% flowering (DF), biomass, plant height (PH), soluble solid content (SSC), and juice weight (JW), and the sorghum reference set for DF and PH, in 7-12 testing environments. We also performed genome-wide association mapping with 6 094 317 and 265 500 single nucleotide polymorphism markers in the mini core collection and the reference set, respectively. In the mini core panel we identified three quantitative trait loci for DF, two for JW, one for PH, and one for biomass. In the reference set panel we identified another quantitative trait locus for PH on chromosome 6 that was also associated with biomass, DF, JW, and SSC in the mini core panel. Transgenic studies of three genes selected from the locus revealed that Sobic.006G061100 (SbSNF4-2) increased biomass, SSC, JW, and PH when overexpressed in both sorghum and sugarcane, and delayed flowering in transgenic sorghum. SbSNF4-2 encodes a γ subunit of the evolutionarily conserved AMPK/SNF1/SnRK1 heterotrimeric complexes. SbSNF4-2 and its orthologs will be valuable in genetic enhancement of biomass and sugar yield in plants.

Purine metabolites can indicate diabetes progression.

AIM: To find the association between purine metabolites and diabetic complications in rats. MATERIALS AND METHODS: Alloxan was administered to induce diabetes in rats. After 30 days, the levels of uric acid, inosine, xanthine, hypoxanthine and AMP were assessed in both plasma and liver tissues using HPLC technique. RESULTS: A significant increase in xanthine, hypoxanthine, AMP levels (p < .001 and t-value 2.78) and inosine in plasma and liver tissues (p < .05 and t-value 2.11) with a concomitant increase in uric acid levels (p < .001 and t-value 2.80) was observed in diabetic group. CONCLUSION: Purine metabolites like uric acid and other intermediate products of purine metabolism are increased in diabetes. These results can be used in addition or separately in evaluating the progression of diabetes.

Genome-Wide Association Mapping Identifies Novel Panicle Morphology Loci and Candidate Genes in Sorghum.

Panicle morphology is an important trait in racial classification and can determine grain yield and other agronomic traits in sorghum. In this study, we performed association mapping of panicle length, panicle width, panicle compactness, and peduncle recurving in the sorghum mini core panel measured in multiple environments with 6,094,317 single nucleotide polymorphism (SNP) markers. We mapped one locus each on chromosomes 7 and 9 to recurving peduncles and eight loci for panicle length, panicle width, and panicle compactness. Because panicle length was positively correlated with panicle width, all loci for panicle length and width were colocalized. Among the eight loci, two each were on chromosomes 1, 2, and 6, and one each on chromosomes 8 and 10. The two loci on chromosome 2, i.e., Pm 2-1 and Pm 2-2, were detected in 7 and 5 out of 11 testing environments, respectively. Pm 2-2 colocalized with panicle compactness. Candidate genes were identified from both loci. The rice Erect Panicle2 (EP2) ortholog was among the candidate genes in Pm 2-2. EP2 regulates panicle erectness and panicle length in rice and encodes a novel plant-specific protein with unknown functions. The results of this study may facilitate the molecular identification of panicle morphology-related genes and the enhancement of yield and adaptation in sorghum.

Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade.

Inflammation can support or restrain cancer progression and the response to therapy. Here, we searched for primary regulators of cancer-inhibitory inflammation through deep profiling of inflammatory tumor microenvironments (TMEs) linked to immune-dependent control in mice. We found that early intratumoral accumulation of interferon gamma (IFN-γ)-producing natural killer (NK) cells induced a profound remodeling of the TME and unleashed cytotoxic T cell (CTL)-mediated tumor eradication. Mechanistically, tumor-derived prostaglandin E2 (PGE2) acted selectively on EP2 and EP4 receptors on NK cells, hampered the TME switch, and enabled immune evasion. Analysis of patient datasets across human cancers revealed distinct inflammatory TME phenotypes resembling those associated with cancer immune control versus escape in mice. This allowed us to generate a gene-expression signature that integrated opposing inflammatory factors and predicted patient survival and response to immune checkpoint blockade. Our findings identify features of the tumor inflammatory milieu associated with immune control of cancer and establish a strategy to predict immunotherapy outcomes.

Selective Estrogen Receptor Modulator and prostimulatory effects of phytoestrogen ß-ecdysone in Tinospora cordifolia on osteoblast cells.

BACKGROUND: Indian ethnomedicine acclaims Tinosporacordifolia as a bone strengthening agent and prescribes it for the treatment of bone fractures, gout and other inflammatory diseases of the bone. OBJECTIVE: (a) To understand the potential of T. cordifolia to act as a Selective Estrogen Receptor Modulator (SERM) on in vitro models. (b) To understand the toxic effects (if any) of T. cordifolia in vivo. (c) To understand the effects of ß-ecdysone (proposed osteoprotective principle of T. cordifolia) on the growth of human osteoblast-like cells MG-63 and rat primary culture of osteoblasts. (d) To conduct phytochemical analysis on T. cordifolia extract to confirm the presence of ß-ecdysone. MATERIALS AND METHODS: The role of T. cordifolia as SERM was analyzed by investigating the effect of the extract on the growth of MCF-7 and HeLa cells. The effects of T. cordifolia in vivo was studied by biochemical (Liver function and renal function tests) and histopathological (Hematoxylin/Eosin staining) analysis. Phytochemical analysis of T.cordifolia was carried out by performing FT-IR and LC-ESI-MS analysis. RESULTS: (a) T. cordifolia extract exerted non-estrogenic effects on MCF-7 and HeLa cells implicating its role as SERM. (b) High doses of T. cordifolia extract (750 and 1000 mg/kg body wt.) showed impairment of hepatic and renal function, induced pathological alterations in hepatic and renal architecture in albino rats. (c) ß-ecdysone an ecdysteroid proposed as the osteoprotective principle of T. cordifolia exhibited significant prostimulatory effects on osteoblast cells and rat primary osteoblasts. (d) Phytochemical analysis confirmed the presence of ß-ecdysone in alcoholic extract of T. cordifolia extract substantiating its role as the osteoprotective principle of T. cordifolia. CONCLUSION: (a) T. cordifolia could function as SERM and can have applications in the therapy of osteoporosis. (b) ß-ecdysone is the osteoprotective principle of T. cordifolia.

Ethnomedicine based evaluation of osteoprotective properties of Tinospora cordifolia on in vitro and in vivo model systems.

Indian ethnomedicine acclaims the use of Tinospora cordifolia (TC) in the treatment of bone fractures and vat rakta (gout). The objective of the study is to investigate the effects of alcoholic extract of Tinospora cordifolia on bone remodeling (involving osteoblastic and osteoclastic actions) in vitro and protect against ovariectomy-induced bone loss in vivo. Human osteoblast-like cells MG-63 and primary osteoblast cells isolated from rat femur were used as osteoblast models and RAW macrophage cell line 264.7 induced to take up osteoclastic lineage using RANK ligand were used as osteoclast models in the current study. Sirius red staining, quantification of osteocalcin, cytopathological analysis by Hematoxylin/eosin staining and semiquantitative reverse transcription PCR (RT-PCR) was carried out to ascertain the effects of T. cordifolia extract on osteoblast cells. MTT assay was perfomed to understand the influence of T. cordifolia extract on osteoclast cells. Adult female Sprague-Dawley rats were used as in vivo models to study the effect of T. cordifolia on ovariectomy induced bone loss. Radiological (DEXA analysis), Biochemical (markers of bone formation and resorption), histopathological (Hematoxylin/eosin staining) and histomorphometric analysis of the bone was carried out. Treatment with T. cordifolia extract resulted in enhanced collagen deposition, increased levels of osteocalcin, increased expression of osteogenic genes all indicative of favourable osteoblastogenesis. Treatment with T. cordifolia extract did not exert any significant influence on the proliferation of osteoclasts. Pretreatment with T. cordifolia extract at a dose of 50mg/kg body wt/day orally for 21days followed by treatment for 12 weeks post ovariectomy was able to prevent ovariectomy-induced bone loss in vivo. Results of the study support the use of T. cordifolia in Indian ethnomedicine for the treatment of bone diseases and fractures.

New species, new records and re-description of spider mites (Acari: Tetranychidae) from India.

Two species of Tetranychidae (Acari), Oligonychus neotylus sp. nov. from Zea mays and Pennisetum purpureum (Poaceae) and Tetranychus hirsutus sp. nov. from Gymnema sylvestre R. Br. (Apocynaceae) are described from Karnataka state, south India. Tetranychus bambusae Wang and Ma is recorded for the first time from India and re-described. Four other species are reported for the first time from India viz., Oligonychus coniferarum (McGregor), Oligonychus duncombei Meyer, Tetranychus marianae McGregor and Tetranychus okinawanus Ehara from Cupressus sp., an undetermined grass, Centrosema pubescens and Adenium obesum, respectively.

Identification of candidate genes and natural allelic variants for QTLs governing plant height in chickpea.

In the present study, molecular mapping of high-resolution plant height QTLs was performed by integrating 3625 desi genome-derived GBS (genotyping-by-sequencing)-SNPs on an ultra-high resolution intra-specific chickpea genetic linkage map (dwarf/semi-dwarf desi cv. ICC12299 x tall kabuli cv. ICC8261). The identified six major genomic regions harboring six robust QTLs (11.5-21.3 PVE), associated with plant height, were mapped within <0.5 cM average marker intervals on six chromosomes. Five SNPs-containing genes tightly linked to the five plant height QTLs, were validated based upon their high potential for target trait association (12.9-20.8 PVE) in 65 desi and kabuli chickpea accessions. The vegetative tissue-specific expression, including higher differential up-regulation (>5-fold) of five genes especially in shoot, young leaf, shoot apical meristem of tall mapping parental accession (ICC8261) as compared to that of dwarf/semi-dwarf parent (ICC12299) was apparent. Overall, combining high-resolution QTL mapping with genetic association analysis and differential expression profiling, delineated natural allelic variants in five candidate genes (encoding cytochrome-c-biosynthesis protein, malic oxidoreductase, NADH dehydrogenase iron-sulfur protein, expressed protein and bZIP transcription factor) regulating plant height in chickpea. These molecular tags have potential to dissect complex plant height trait and accelerate marker-assisted genetic enhancement for developing cultivars with desirable plant height ideotypes in chickpea.