Post-partum follow-up of women with gestational diabetes mellitus: Effectiveness, determinants, and barriers

Background: Despite the recommendations for postpartum blood glucose monitoring post gestational diabetes mellitus (GDM); scientific evidence reveals that these recommendations may not be fully complied to. This study aimed to follow-up women up to 2 years post-delivery with pregnancies complicated by GDM and healthy controls to assess this fact.Methods: Women with GDM (n = 78) and normal glucose tolerant (n = 89) delivered in 2014 were followed up for 2 years. They were informed and enquired via telephone about their blood glucose screening, physical activity, postpartum complications, and current weight status of mother and baby.Results: Women with previous GDM were older and reported higher body weight 2 years post-delivery. At the 2 year follow-up, n = 11 (14.1%) participants had developed diabetes, all with previous GDM. Both weight at birth (3.8 ± 0.5 kg) and at 2-year (10.7 ± 2.3 kg) for the babies born to GDM mothers was significantly higher than the NGT group babies (2.6 ± 0.63 and 7.1 ± 1.4 kg; p \u3c .05). Only 27 women regularly opted for T2DM screening via monitoring blood glucose or HbA1c levels postpartum. The top reason for failed screening included: believing that GDM would disappear after delivery, and being occupied with the baby.Conclusions: The high incidence of T2DM in women with previous GDM is an alarming finding. Given this trend, systematic follow-up programs are needed to reduce obesity and diabetes risk

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Identification of a Novel TGFβ/PKA Signaling Transduceome in Mediating Control of Cell Survival and Metastasis in Colon Cancer

Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown.Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site. This work demonstrates for the first time that TGFβ receptor reconstitution leads to decreased metastatic colonization. Moreover, we have identified a novel TGFβ/PKA tumor suppressor pathway that acts directly on a known cell survival mechanism that responds to stress with the survivin/XIAP dependent inhibition of caspases that effect apoptosis. The linkage between the TGFβ/PKA transduceome signaling and control of metastasis through induction of cell death was shown by TGFβ receptor restoration with reactivation of the TGFβ/PKA pathway in receptor deficient metastatic colon cancer cells leading to control of aberrant cell survival.This work impacts our understanding of the possible mechanisms that are critical to the growth and maintenance of metastases as well as understanding of a novel TGFβ function as a metastatic suppressor. These results raise the possibility that regeneration of attenuated TGFβ signaling would be an effective target in the treatment of metastasis. Our work indicates the clinical potential for developing anti-metastasis therapy based on inhibition of this very important aberrant cell survival mechanism by the multifaceted TGFβ/PKA transduceome induced pathway. Development of effective treatments for metastatic disease is a pressing need since metastases are the major cause of death in solid tumors

Effects of chirality on the intracellular localization of binuclear ruthenium(II) polypyridyl complexes

Interest in binuclear ruthenium(II) polypyridyl complexes as luminescent cellular imaging agents and for biomedical applications is increasing rapidly. We have investigated the cellular localization, uptake, and biomolecular interactions of the pure enantiomers of two structural isomers of [μ-bipb(phen)4Ru2]4+ (bipb is bis(imidazo[4,5-f]-1,10-phenanthrolin-2-yl)benzene and phen is 1,10-phenanthroline) using confocal laser scanning microscopy, emission spectroscopy, and linear dichroism. Both complexes display distinct enantiomeric differences in the staining pattern of fixed cells, which are concluded to arise from chiral discrimination in the binding to intracellular components. Uptake of complexes in live cells is efficient and nontoxic at 5 μM, and occurs through an energy-dependent mechanism. No differences in uptake are observed between the structural isomers or the enantiomers, suggesting that the interactions triggering uptake are rather insensitive to structural variations. Altogether, these findings show that the complexes investigated are promising for future applications as cellular imaging probes. In addition, linear dichroism shows that the complexes exhibit DNA-condensing properties, making them interesting as potential gene delivery vectors

First measurement of the |t|-dependence of coherent J/ψ photonuclear production

The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3. The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio

Global, regional, and national burden of upper respiratory infections and otitis media, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021

Background Upper respiratory infections (URIs) are the leading cause of acute disease incidence worldwide and contribute to a substantial health-care burden. Although acute otitis media is a common complication of URIs, the combined global burden of URIs and otitis media has not been studied comprehensively. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to explore the fatal and non-fatal burden of the two diseases across all age groups, including a granular analysis of children younger than 5 years, in 204 countries and territories from 1990 to 2021. Methods Mortality due to URIs and otitis media was estimated with use of vital registration and sample-based vital registration data, which are used as inputs to the Cause of Death Ensemble model to separately model URIs and otitis media mortality by age and sex. Morbidity was modelled with a Bayesian meta-regression tool using data from published studies identified via systematic reviews, population-based survey data, and cause-specific URI and otitis media mortality estimates. Additionally, we assessed and compared the burden of otitis media as it relates to URIs and examined the collective burden and contributing risk factors of both diseases. Findings The global number of new episodes of URIs was 12·8 billion (95% uncertainty interval 11·4 to 14·5) for all ages across males and females in 2021. The global all-age incidence rate of URIs decreased by 10·1% (–12·0 to –8·1) from 1990 to 2019. From 2019 to 2021, the global all-age incidence rate fell by 0·5% (–0·8 to –0·1). Globally, the incidence rate of URIs was 162 484·8 per 100 000 population (144 834·0 to 183 289·4) in 2021, a decrease of 10·5% (–12·4 to –8·4) from 1990, when the incidence rate was 181 552·5 per 100 000 population (160 827·4 to 206 214·7). The highest incidence rates of URIs were seen in children younger than 2 years in 2021, and the largest number of episodes was in children aged 5–9 years. The number of new episodes of otitis media globally for all ages was 391 million (292 to 525) in 2021. The global incidence rate of otitis media was 4958·9 per 100 000 (3705·4 to 6658·6) in 2021, a decrease of 16·3% (–18·1 to –14·0) from 1990, when the incidence rate was 5925·5 per 100 000 (4371·8 to 8097·9). The incidence rate of otitis media in 2021 was highest in children younger than 2 years, and the largest number of episodes was in children aged 2–4 years. The mortality rate of URIs in 2021 was 0·2 per 100 000 (0·1 to 0·5), a decrease of 64·2% (–84·6 to –43·4) from 1990, when the mortality rate was 0·7 per 100 000 (0·2 to 1·1). In both 1990 and 2021, the mortality rate of otitis media was less than 0·1 per 100 000. Together, the combined burden accounted for by URIs and otitis media in 2021 was 6·86 million (4·24 to 10·4) years lived with disability and 8·16 million (4·99 to 12·0) disability-adjusted life-years (DALYs) for all ages across males and females. Globally, the all-age DALY rate of URIs and otitis media combined in 2021 was 103 per 100 000 (63 to 152). Infants aged 1–5 months had the highest combined DALY rate in 2021 (647 per 100 000 [189 to 1412]), followed by early neonates (aged 0–6 days; 582 per 100 000 [176 to 1297]) and late neonates (aged 7–24 days; 482 per 100 000 [161 to 1052]). Interpretation The findings of this study highlight the widespread burden posed by URIs and otitis media across all age groups and both sexes. There is a continued need for surveillance, prevention, and management to better understand and reduce the burden associated with URIs and otitis media, and research is needed to assess their impacts on individuals, communities, economies, and health-care systems worldwide. Funding Bill & Melinda Gates Foundation

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions