How can we keep impaired glucose tolerance and impaired fasting glucose from progressing to diabetes?

Lifestyle interventions aimed at weight loss of 5% to 10% of body weight along with moderate aerobic exercise such as brisk walking for 150 minutes a week are the most effective means to prevent impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) from progressing to diabetes (strength of recommendation [SOR]: A, several meta-analyses, including a recent Cochrane review)

Routine antenatal ultrasound in low- And Middle-income Countries: First look - A cluster randomised trial

Objective: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centers in resource-limited countries.Design: Cluster randomized trial.Settings: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan and Zambia).Methods: Clusters were randomized to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds.Main Outcome Measures: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality.Results: During the 24-month trial, 28 intervention and 28 control clusters had 24,263 and 23,160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa and abnormal lie were within expected ranges. 9% were referred for an ultrasound-diagnosed condition and 71% attended the referral. The ANC (RR 1·0 95% CI 1·00, 1·01) and hospital delivery rates for complicated pregnancies (RR 1·03 95% CI 0·89, 1·20) did not differ between intervention and control clusters nor did the composite outcome (RR 1·09 95% CI 0·97, 1·23) or its individual components.Conclusions: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome as well as the individual components were not reduced. This article is protected by copyright. All rights reserved

Oligohydramnios: a prospective study of fetal, neonatal and maternal outcomes in low-middle income countries

BACKGROUND: Oligohydramnios is a condition of abnormally low amniotic fluid volume that has been associated with poor pregnancy outcomes. To date, the prevalence of this condition and its outcomes has not been well described in low and low-middle income countries (LMIC) where ultrasound use to diagnose this condition in pregnancy is limited. As part of a prospective trial of ultrasound at antenatal care in LMICs, we sought to evaluate the incidence of and the adverse maternal, fetal and neonatal outcomes associated with oligohydramnios. METHODS: We included data in this report from all pregnant women in community settings in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo (DRC) who received a third trimester ultrasound as part of the First Look Study, a randomized trial to assess the value of ultrasound at antenatal care. Using these data, we conducted a planned secondary analysis to compare pregnancy outcomes of women with to those without oligohydramnios. Oligohydramnios was defined as measurement of an Amniotic Fluid Index less than 5 cm in at least one ultrasound in the third trimester. The outcomes assessed included maternal morbidity and fetal and neonatal mortality, preterm birth and low-birthweight. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models using general estimating equations to account for the correlation of outcomes within cluster. RESULTS: Of 12,940 women enrolled in the clusters in Guatemala, Pakistan, Zambia and the DRC in the First Look Study who had a third trimester ultrasound examination, 87 women were diagnosed with oligohydramnios, equivalent to 0.7% of those studied. Prevalence of detected oligohydramnios varied among study sites; from the lowest of 0.2% in Zambia and the DRC to the highest of 1.5% in Pakistan. Women diagnosed with oligohydramnios had higher rates of hemorrhage, fetal malposition, and cesarean delivery than women without oligohydramnios. We also found unfavorable fetal and neonatal outcomes associated with oligohydramnios including stillbirths (OR 5.16, 95%CI 2.07, 12.85), neonatal deaths \u3c 28 days (OR 3.18, 95% CI 1.18, 8.57), low birth weight (OR 2.10, 95% CI 1.44, 3.07) and preterm births (OR 2.73, 95%CI 1.76, 4.23). The mean birth weight was 162 g less (95% CI -288.6, - 35.9) with oligohydramnios. CONCLUSIONS: Oligohydramnos was associated with worse neonatal, fetal and maternal outcomes in LMIC. Further research is needed to assess effective interventions to diagnose and ultimately to reduce poor outcomes in these settings

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Investigating Immune Profiles in Differentiated Thyroid Cancer by Multiplex Immunofluorescence

BACKGROUND: As the most common endocrine malignancy in the United States (U.S.), differentiated thyroid cancer (DTC) accounts for 3.8% of all cancers in the U.S., with roughly 10% of cases progressing to distant metastatic DTC, which is associated with a poor five year survival outcome despite conventional management, including surgery and radioactive iodine ablation. Recently, novel immunotherapies have garnered attention as a viable therapeutic resource for patients with advanced DTC. However, the response to therapy has been variable and unpredictable, which may be associated with an immune suppressive circulating phenotype. Nonetheless, the intra-tumoral immune infiltrate remains to be elucidated, demonstrating a critical need to address the gap in understanding in order to better prognosticate the disease. OBJECTIVE: To identify and compare tumor-infiltrating immune markers with those present in the adjacent normal thyroid tissue, and collate these immune infiltrates with tumor characteristics. METHODS: Twenty-nine adult tissue samples containing tumor and stromal regions were collected from patients with DTC. The samples were analyzed using multiplex immunofluorescence (MxIF) with antibodies against cell-surface molecules CD56, PD-1, PD-L1, FOXP3, CD3, CD8, CD4, CD45, CD68, CD163, INOS, HLA-DR, CD33, and CD19. 17 of the specimens were analyzed using HALO and a positive threshold was assigned based on review by a trained researcher. RESULTS: In evaluating the immune profiles, important differences in the immune infiltrates between different stages of the cancer were observed. Generally, PD-1 and PD-L1 were highly expressed within the tumor, despite variability in lymphocyte infiltration, indicating the importance of PD-1 and PD-L1 as potential predictive biomarkers for the aggressiveness of thyroid cancer. Tumor from patients with distant metastases demonstrated higher T cell infiltration, T regulatory cells, macrophages and PD-L1 positive cells as compared to localized tumor. CONCLUSION: Immune profiling demonstrated significant differences between tumor and adjacent healthy regions, particularly in terms of PD-1 and PD-L1 expression and lymphocyte infiltration, indicating that higher intratumor infiltration of T regulatory cells, macrophages and PD-1/PD-L1 positive cells may be associated with advanced thyroid cancer. Therefore, the data demonstrates the efficacy of MxIF in gathering valuable information regarding the tumor microenvironment, which will have major implications in guiding the selection of patients for immunotherapy.https://digitalcommons.unmc.edu/surp2021/1042/thumbnail.jp

Metabolic and transcriptomic study of pennycress natural variation identifies targets for oil improvement

Article describes how, although pennycress, a winter annual, could be grown as a dedicated bioenergy crop, an increase in its seed oil content is required to improve its economic competitiveness. In this work, the authors combined biomass composition with metabolomic and transcriptomic studies of developing embryos from 22 pennycress natural variants to identify targets for oil improvement

Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain

<p>Abstract</p> <p>Background</p> <p>Gap junction proteins, connexins, are expressed in most endocrine and exocrine glands in the body and are at least in some glands crucial for the hormonal secretion. To what extent connexins are expressed in neurons releasing hormones or neuropeptides from or within the central nervous system is, however, unknown. Previous studies provide indirect evidence for gap junction coupling between subsets of neuropeptide-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Here we employ double labeling and retrograde tracing methods to investigate to what extent neuroendocrine and neuropeptide-containing neurons of the hypothalamus and brainstem express the neuronal gap junction protein connexin 36.</p> <p>Results</p> <p>Western blot analysis showed that connexin 36 is expressed in the PVN. In bacterial artificial chromosome transgenic mice, which specifically express the reporter gene Enhanced Green Fluorescent Protein (EGFP) under the control of the connexin 36 gene promoter, EGFP expression was detected in magnocellular (neuroendocrine) and in parvocellular neurons of the PVN. Although no EGFP/connexin36 expression was seen in neurons containing oxytocin or vasopressin, EGFP/connexin36 was found in subsets of PVN neurons containing corticotropin-releasing hormone (CRH), and in somatostatin neurons located along the third ventricle. Moreover, CRH neurons in brainstem areas, including the lateral parabrachial nucleus, also expressed EGFP/connexin 36.</p> <p>Conclusion</p> <p>Our data indicate that connexin 36 is expressed in subsets of neuroendocrine and CRH neurons in specific nuclei of the hypothalamus and brainstem.</p

Search for new physics in events with same-sign dileptons and jets in pp collisions at √s = 8 TeV

Chatrchyan, S. et al.A search for new physics is performed based on events with jets and a pair of isolated, same-sign leptons. The results are obtained using a sample of proton-proton collision data collected by the CMS experiment at a centre-of-mass energy of 8 TeV at the LHC, corresponding to an integrated luminosity of 19.5 fb−1. In order to be sensitive to a wide variety of possible signals beyond the standard model, multiple search regions defined by the missing transverse energy, the hadronic energy, the number of jets and b-quark jets, and the transverse momenta of the leptons in the events are considered. No excess above the standard model background expectation is observed and constraints are set on a number of models for new physics, as well as on the same-sign top-quark pair and quadruple-top-quark production cross sections. Information on event selection efficiencies is also provided, so that the results can be used to confront an even broader class of new physics models.We thank the technical and administrative staff at CERN and other CMS institutes, and acknowledge support from: FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); MSI (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MON, RosAtom, RAS and RFBR (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie programme and the European Research Council and EPLANET(EuropeanUnion); the Leventis Foundation; the A.P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dansl’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschapen Technologie (IWT-Belgium); the Ministry of Education, Youth and Sports(MEYS) of Czech Republic; the Council of Science and Industrial Research, India; the Compagnia di San Paolo(Torino); the HOMINGPLUS programme of Foundation for PolishScience, cofinanced by EU,Re-gional Development Fund; and the Thalis and Aristeia programmes cofinanced byEU-ESFand the Greek NSRF.Peer reviewe

Erratum: Search for anomalous tt¯ production in the highly-boosted all-hadronic final state

Chatrchyan, S. et al.The uncertainties on the mistagged NTMJ background include the statis- tical uncertainty on the sample after loose selection, to which the mistag probability is applied; the statistical uncertainty on the mistag proba- bility itself, ranging from < 1% at 1 TeV /c 2 to ≈ 10% at 3 TeV /c 2 ; and the systematic uncertainty on the mistag probability application, as de- scribed in section 3.3, which is in the range of 1 to 5% depending on the t ̄ t mass. The total background uncertainty is ≈ 5% for the low-mass region, dominated by the systematic uncertainty, and ≈ 100% for the high-mass region, dominated by statistical uncertainty associated with the sample after loose selection.Peer reviewe

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts