PPAR Gamma Receptor: A Novel Target to Improve Morbidity in Preterm Babies

Worldwide, three-quarters of a million babies are born extremely preterm (&lt;28 weeks gestation) with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopulmonary dysplasia (BPD), and 10% suffer from cerebral palsy. Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) agonist, may reduce the incidence of BPD and improve neurodevelopment in extreme preterm babies. Pioglitazone exerts an anti-inflammatory action mediated through Nuclear Factor-kappa B repression. PPARγ signalling is underactive in preterm babies as adiponectin remains low during the neonatal period. In newborn animal models, pioglitazone has been shown to be protective against BPD, necrotising enterocolitis, and lipopolysaccharide-induced brain injury. Single Nucleotide Polymorphisms of PPARγ are associated with inhibited preterm brain development and impaired neurodevelopment. Pioglitazone was well tolerated by the foetus in reproductive toxicology experiments. Bladder cancer, bone fractures, and macular oedema, seen rarely in adults, may be avoided with a short treatment course. The other effects of pioglitazone, including improved glycaemic control and lipid metabolism, may provide added benefit in the context of prematurity. Currently, there is no formulation of pioglitazone suitable for administration to preterm babies. A liquid formulation of pioglitazone needs to be developed before clinical trials. The potential benefits are likely to outweigh any anticipated safety concerns.</p

Studying Lobby Influence in the European Parliament

We present a method based on natural language processing (NLP), for studying the influence of interest groups (lobbies) in the law-making process in the European Parliament (EP). We collect and analyze novel datasets of lobbies' position papers and speeches made by members of the EP (MEPs). By comparing these texts on the basis of semantic similarity and entailment, we are able to discover interpretable links between MEPs and lobbies. In the absence of a ground-truth dataset of such links, we perform an indirect validation by comparing the discovered links with a dataset, which we curate, of retweet links between MEPs and lobbies, and with the publicly disclosed meetings of MEPs. Our best method achieves an AUC score of 0.77 and performs significantly better than several baselines. Moreover, an aggregate analysis of the discovered links, between groups of related lobbies and political groups of MEPs, correspond to the expectations from the ideology of the groups (e.g., center-left groups are associated with social causes). We believe that this work, which encompasses the methodology, datasets, and results, is a step towards enhancing the transparency of the intricate decision-making processes within democratic institutions.Comment: 11 pages, 5 figures. Under review for presentation at ICWSM 202

Watchful waiting versus pharmacological management of small-for-gestational-age infants with hyperinsulinemic hypoglycemia

IntroductionGiven that reports on severe diazoxide (DZX) toxicity are increasing, we aimed to understand if the short-term clinical outcomes of small-for-gestational-age (SGA) infants with hyperinsulinemic hypoglycemia (HH) managed primarily by supportive care, termed watchful waiting (WW), are different from those treated with DZX.MethodA real-life observational cohort study was conducted from 1 September 2014 to 30 September 2020. The WW or DZX management decision was based on clinical and biochemical criteria. We compared central line duration (CLD), postnatal length of stay (LOS), and total intervention days (TIDs) among SGA-HH infants treated with DZX versus those on a WW approach. Fasting studies determined the resolution of HH.ResultAmong 71,836 live births, 11,493 were SGA, and 51 SGA infants had HH. There were 26 and 25 SGA-HH infants in the DZX and WW groups, respectively. Clinical and biochemical parameters were similar between groups. The median day of DZX initiation was day 10 of life (range 4–32), at a median dose of 4 mg/kg/day (range 3–10). All infants underwent fasting studies. Median CLD [DZX, 15 days (6–27) vs. WW, 14 days (5–31), P = 0.582] and postnatal LOS [DZX, 23 days (11–49) vs. WW, 22 days (8–61), P = 0.915] were comparable. Median TID was &gt;3-fold longer in the DZX than the WW group [62.5 days (9–198) vs. 16 days (6–27), P &lt; 0.001].ConclusionCLD and LOS are comparable between WW and DZX groups. Since fasting studies determine the resolution of HH, physicians should be aware that clinical intervention of DZX-treated SGA-HH patients extends beyond the initial LOS

Abnormalities at chromosome region 3p12–14 characterize clear cell renal carcinoma

In an effort to determine whether or not any characteristic chromosomal abnormalities exist in renal cancer, cytogenetic findings were correlated with tumor histology in nine cases of renal adenocarcinoma. Metaphase preparations adequate for analysis were obtained from cultures harvested between day 3 and day 21. Model chromosome number was diploid in three cases, hypodiploid in three, and hyperdiploid in the remaining three. One clear cell adenocarcinoma failed to reveal any chromosomal abnormality. Two tumors, a tubular/papillary carcinoma and an acinar/papillary carcinima, showed the clonal abnormalities del(1)(p21),+2,+7,+8,+12,+13,+16,+17,-21 and t(2;lO)(q14-21;q26),+7q,+11q,-18, respectively. Interestingly, five of six clear cell tumors studied had clonal abnormalities affecting the short arm of chromosome #3 in the 3p12-21 region, and in the remaining case, of 15 karyotyped metaphases suitable for interpretation, one showed a deletion in 3p. These data indicate that clear cell carcinoma of the kidney may be associated with a nonrandom chromosomal abnormality involving the 3p12-14 region

A special schedule of foliar application of nutrients for the tea fields under extensive mechanized harvesting

To overcome the problem of acute shortage of work force faced by the south Indian tea industry, UPASI Tea Research Institute recommends mechanized harvesting to cover large areas with high worker productivity. While adopting extensive mechanized harvesting, total leaf area of the maintenance foliage on the plucking surface is reduced. As a result growth of the crop shoots has been adversely affected leading to reduction in productivity. Excessive banji shoot formation and nutrient deficiency symptoms were also noticed. To overcome all these adverse impacts of extensive mechanization, foliar application of primary, secondary and micro-nutrients has been attempted. The practical utility of foliar feeding of all these nutrients when applied as a mixture after every harvest, except during continuous heavy rainy months, showed an increase in yield up to 21% compared to the current recommended practice, in spite of extensive harvesting using shears and machines. The problem of dwarfing of crop shoots due to extensive shear/machine harvesting could be minimized due to increase in internodal length by 0.87 cm and the dry weight of the crop shoots increased by 0.09 g/shoot. Excessive production of banji shoots also came down from 65 to 52%

EXTUBATE: A randomised controlled trial of nasal biphasic positive airway pressure vs. nasal continuous positive airway pressure following extubation in infants less than 30 weeks' gestation: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Respiratory distress syndrome remains a significant problem among premature infants. Mechanical ventilation through an endotracheal tube remains the mainstay of respiratory support but may be associated with lung injury and the development of chronic lung disease of prematurity. Efforts are needed to reduce the duration of mechanical ventilation in favour of less invasive forms of respiratory support and to improve rates of successful extubation.</p> <p>Non-invasive respiratory support has been demonstrated to be less injurious to the premature lung. Standard practice is to use nasal continuous positive airway pressure (n-CPAP) following extubation to support the baby's breathing. Many clinicians also use nasal biphasic positive airway pressure (n-BiPAP) in efforts to improve rates of successful extubation. However, there is currently no evidence that this confers any advantage over conventional nasal continuous positive airway pressure.</p> <p>Methods</p> <p>We propose an unblinded multi-centre randomised trial comparing n-CPAP with n-BiPAP in babies born before 30 weeks' gestation and less than two weeks old. Babies with congenital abnormalities and severe intra-ventricular haemorrhage will be excluded. 540 babies admitted to neonatal centres in England will be randomised at the time of first extubation attempt. The primary aim of this study is to compare the rate of extubation failure within 48 hours following the first attempt at extubation. The secondary aims are to compare the effect of n-BiPAP and n-CPAP on the following outcomes:</p> <p>1. Maintenance of successful extubation for 7 days post extubation</p> <p>2. Oxygen requirement at 28 days of age and at 36 weeks' corrected gestational age</p> <p>3. Total days on ventilator, n-CPAP/n-BiPAP</p> <p>4. Number of ventilator days following first extubation attempt</p> <p>5. pH and partial pressure of carbon dioxide in the first post extubation blood gas</p> <p>6. Duration of hospital stay</p> <p>7. Rate of abdominal distension requiring cessation of feeds</p> <p>8. Rate of apnoea and bradycardia</p> <p>9. The age at transfer back to referral centre in days</p> <p>The trial will determine whether n-BiPAP is safe and superior to n-CPAP in preventing extubation failure in babies born before 30 weeks' gestation and less than two weeks old.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN18921778">ISRCTN18921778</a></p

Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[ɑ]pyrene diol epoxide and DNA

We have synthesized, separated, and purified ≈10 mg of a deoxyundecanucleotide duplex containing a single centrally positioned covalent adduct between (+)-anti-benzo[a]pyrene (BP) diol epoxide and the exocyclic amino group of guanosine. Excellent proton NMR spectra are observed for the (+)-trans-anti-BP diol epoxide-N^2-dG adduct positioned opposite dC and flanked by G.C pairs in the d[C1-C2-A3-T4-C5-(BP)G6-C7-T8-A9-C10-C11].d[12- G13-T14-A15-G16-C17-G18-A19-T20-G 21-G22] duplex +ADdesignated (BP)G.C 11-mer+BD. We have determined the solution structure centered about the BP covalent adduct site in the (BP)G.C 11-mer duplex by incorporating intramolecular and intermolecular proton-proton distance bounds deduced from the NMR data sets as constraints in energy minimization computations. The BP ring is positioned in the minor groove and directed toward the 5' end of the modified strand. One face of the BP ring of (BP)G6 is stacked over the G18 and A19 sugar-phosphate backbone on the partner strand and the other face is exposed to solvent. A minimally perturbed B-DNA helix is observed for the d[T4-C5-(BP)G6-C7-T8].d[A15-G16-C17-G18-A19] segment centered about the adduct site with Watson-Crick alignment for both the (BP)G6.C17 pair and flanking G.C pairs. A widening of the minor groove at the adduct site is detected that accommodates the BP ring whose long axis makes an angle of ≈45° with the average direction of the DNA helix axis. Our study holds future promise for the characterization of other steroisomerically pure adducts of BP diol epoxides with DNA to elucidate the molecular basis of structure-activity relationships associated with the stereoisomer-dependent spectrum of mutational and carcinogenic activities