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Polydextrose is a randomly bonded polysaccharide produced by the bulk melt polycondensation of glucose and sorbitol in vacuo. It has been used as a bulking and texturizing agent and soluble fiber ingredient in many food products worldwide for over two decades. Because of its atypical linkages between glucose moieties, polydextrose resists digestion by mammalian gastrointestinal enzymes. It is minimally absorbed in the small intestine and partially fermented in the large intestine producing volatile fatty acids, with approximately 50% of the ingested dose being excreted undigested. In this it is similar to many other poorly digested soluble fiber ingredients. Numerous energy balance and isotope-label disposition studies have been conducted in animals and man to investigate the caloric availability of polydextrose. The weight of available experimental evidence in the 14 studies described herein shows that polydextrose has a caloric value of approximately 1 kcal/g.

Polydextrose is a randomly bonded polysaccharide produced by the bulk melt polycondensation of glucose and sorbitol in vacuo. It has been used as a bulking and texturizing agent and soluble fiber ingredient in many food products worldwide for over two decades. Because of its atypical linkages between glucose moieties, polydextrose resists digestion by mammalian gastrointestinal enzymes. It is minimally absorbed in the small intestine and partially fermented in the large intestine producing volatile fatty acids, with approximately 50% of the ingested dose being excreted undigested. In this it is similar to many other poorly digested soluble fiber ingredients. Numerous energy balance and isotope-label disposition studies have been conducted in animals and man to investigate the caloric availability of polydextrose. The weight of available experimental evidence in the 14 studies described herein shows that polydextrose has a caloric value of approximately 1 kcal/g.

To understand the consequences of functional cardiac stress testing among patients considering noncardiac nonophthalmologic surgery. A retrospective cohort study of 118,552 patients who made 159,795 visits to a dedicated preoperative risk assessment and optimization clinic between 2008 and 2018. A large integrated health system. Patients who visited a dedicated preoperative risk assessment and optimization clinic before noncardiac nonophthalmologic surgery. To assess changes to care delivered, we measured the probability of completing additional cardiac testing, cardiac surgery, or noncardiac surgery. To assess outcomes, we measured time-to-mortality and total one-year mortality. In causal inference models, preoperative stress testing was associated with increased likelihood of coronary angiography (relative risk: 8.6, 95% CI 6.1–12.1), increased likelihood of percutaneous coronary intervention (RR: 4.1, 95% CI: 1.8–9.2), increased likelihood of cardiac surgery (RR: 6.8, 95% CI 4.9–9.4), decreased likelihood of noncardiac surgery (RR: 0.77, 95% CI 0.75–0.79), and delayed noncardiac surgery for patients completing noncardiac surgery (mean 28.3 days, 95% CI: 23.1–33.6). The base rate of downstream cardiac testing was low, and absolute risk increases were small. Stress testing was associated with higher mortality in unadjusted analysis but was not associated with mortality in causal inference analyses. Preoperative cardiac stress testing likely induces coronary angiography and cardiac interventions while decreasing use of noncardiac surgery and delaying surgery for patients who ultimately proceed to noncardiac surgery. Despite changes to processes of care, our results do not support a causal relationship between stress testing and postoperative mortality. Analyses of care cascades should consider care that is avoided or substituted in addition to care that is induced. •Cardiac stress testing probably leads to higher rates of cardiac testing and interventions (a “care cascade”)•However, stress testing also decreases the likelihood that patients will complete surgery•Stress testing probably does not change mortality in the short- or long-term•Health datasets rarely capture care that is considered but not completed; many care cascades might instead be substitutions

To assess the incremental contribution of preoperative stress test results toward a diagnosis of obstructive coronary artery disease (CAD), prediction of mortality, or prediction of perioperative myocardial infarction in patients considering noncardiac, nonophthalmologic surgery. A retrospective cohort study of visits to a preoperative risk assessment and optimization clinic in a large health system between 2008 and 2018. To assess diagnostic information of preoperative stress testing, we used the Begg and Greenes method to calculate test characteristics adjusted for referral bias, with a gold standard of angiography. To assess prognostic information, we first created multiply-imputed logistic regression models to predict 90-day mortality and perioperative myocardial infarction (MI), starting with two tools commonly used to assess perioperative cardiac risk, Revised Cardiac Risk Index (RCRI) and Myocardial Infarction or Cardiac Arrest (MICA). We then added stress test results and compared the discrimination for models with and without stress test results. Among 136,935 visits by patients without an existing diagnosis of CAD, the decision to obtain preoperative stress testing identified around 4.0% of likely new diagnoses. Stress testing increased the likelihood of CAD (likelihood ratio: 1.31), but for over 99% of patients, stress testing should not change a decision on whether to proceed to angiography. In 117,445 visits with subsequent noncardiac surgery, stress test results failed to improve predictions of either perioperative MI or 90-day mortality. Reweighting the models and adding hemoglobin improved the prediction of both outcomes. Cardiac stress testing before noncardiac, nonophthalmologic surgery does not improve predictions of either perioperative mortality or myocardial infarction. Very few patients considering noncardiac, nonophthalmologic surgery have a pretest probability of CAD in a range where stress testing could usefully select patients for angiography. Better use of existing patient data could improve predictions of perioperative adverse events without additional patient testing. •The pretest probability of obstructive coronary artery disease is very low in patients considering noncardiac surgery.•Even with careful patient selection, stress testing can't efficiently diagnose CAD or select patients for angiography.•Stress test results don't improve predictions of death or myocardial infarction beyond commonly-used risk scores.•Prediction models that make better use of existing data could improve predictions of adverse operative events.

Extreme, expedition, and wilderness medicine are modern and rapidly evolving specialties that address the spirit of adventure and exploration. The relevance of and interest in these specialties are changing rapidly to match the underlying activities, which include global exploration, adventure travel, and military deployments. Extreme, expedition, and wilderness medicine share themes of providing best available medical care in the outdoors, especially in austere or remote settings. Early clinical and logistics decision making can often have important effects on subsequent outcomes. There are lessons to be learned from out-of-hospital care, military medicine, humanitarian medicine, and disaster medicine that can inform in-hospital medicine, and vice-versa. The future of extreme, expedition, and wilderness medicine will be defined by both recipients and practitioners, and empirical observations will be transformed by evidence-based practice.

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage 1 – 3 . The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes 4 – 7 . Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas 8 (SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus 9 (HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53 loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage. Defective DNA interstrand crosslink repair in Fanconi anaemia drives extensive genomic rearrangements, thereby substantially increasing the risk of cancer development.

ObjectivesTo describe variation in and drivers of contemporary preoperative cardiac stress testing.SettingA dedicated preoperative risk assessment and optimisation clinic at a large integrated medical centre from 2008 through 2018.ParticipantsA cohort of 118 552 adult patients seen by 104 physicians across 159 795 visits to a preoperative risk assessment and optimisation clinic.Main outcomeReferral for stress testing before major surgery, including nuclear, echocardiographic or electrocardiographic-only stress testing, within 30 days after a clinic visit.ResultsA total of 8303 visits (5.2%) resulted in referral for preoperative stress testing. Key patient factors associated with preoperative stress testing included predicted surgical risk, patient functional status, a previous diagnosis of ischaemic heart disease, tobacco use and body mass index. Patients living in either the most-deprived or least-deprived census block groups were more likely to be tested. Patients were tested more frequently before aortic, peripheral vascular or urologic interventions than before other surgical subcategories. Even after fully adjusting for patient and surgical factors, provider effects remained important: marginal testing rates differed by a factor-of-three in relative terms and around 2.5% in absolute terms between the 5th and 95th percentile physicians. Stress testing frequency decreased over the time period; controlling for patient and physician predictors, a visit in 2008 would have resulted in stress testing approximately 3.5% of the time, while a visit in 2018 would have resulted in stress testing approximately 1.3% of the time.ConclusionsIn this large cohort of patients seen for preoperative risk assessment at a single health system, decisions to refer patients for preoperative stress testing are influenced by various factors other than estimated perioperative risk and functional status, the key considerations in current guidelines. The frequency of preoperative stress testing has decreased over time, but remains highly provider-dependent.

Disruptions in local chromatin structure often indicate features of biological interest such as regulatory régions. We find that sonication of cross-linked chromatin, when combined with a sizeselection step and massively parallel short-read sequencing, can be used as a method (Sono-Seq) to map locations of high chromatin accessibility in promoter regions. Sono-Seq sites frequently correspond to actively transcribed promoter regions, as evidenced by their co-association with RNA Polymerase II ChIP régions, transcription start sites, histone H3 lysine 4 trimethylation (H3K4me3) marks, and CpG islands; signals over other sites, such as those bound by the CTCF insulator, are also observed. The pattern of breakage by Sono-Seq overlaps with, but is distinct from, that observed for FAIRE and DNase I hypersensitive sites. Our results demonstrate that Sono-Seq can be a useful and simple method by which to map many local alterations in chromatin structure. Furthermore, our results provide insights into the mapping of binding sites by using ChIP-Seq experiments and the value of référence samples that should be used in such experiments.

Background Heart failure is a prevalent health problem associated with costly hospital readmissions. Transitional care programs have been shown to reduce readmissions but are costly to implement. Evidence regarding the effectiveness of telemonitoring in managing the care of this chronic condition is mixed. The objective of this randomized controlled comparative effectiveness study is to evaluate the effectiveness of a care transition intervention that includes pre-discharge education about heart failure and post-discharge telephone nurse coaching combined with home telemonitoring of weight, blood pressure, heart rate, and symptoms in reducing all-cause 180-day hospital readmissions for older adults hospitalized with heart failure. Methods/Design A multi-center, randomized controlled trial is being conducted at six academic health systems in California. A total of 1,500 patients aged 50 years and older will be enrolled during a hospitalization for treatment of heart failure. Patients in the intervention group will receive intensive patient education using the ‘teach-back’ method and receive instruction in using the telemonitoring equipment. Following hospital discharge, they will receive a series of nine scheduled health coaching telephone calls over 6 months from nurses located in a centralized call center. The nurses also will call patients and patients’ physicians in response to alerts generated by the telemonitoring system, based on predetermined parameters. The primary outcome is readmission for any cause within 180 days. Secondary outcomes include 30-day readmission, mortality, hospital days, emergency department (ED) visits, hospital cost, and health-related quality of life. Discussion BEAT-HF is one of the largest randomized controlled trials of telemonitoring in patients with heart failure, and the first explicitly to adapt the care transition approach and combine it with remote telemonitoring. The study population also includes patients with a wide range of demographic and socioeconomic characteristics. Once completed, the study will be a rich resource of information on how best to use remote technology in the care management of patients with chronic heart failure. Trial registration ClinicalTrials.gov # NCT01360203 .

Background Anaemia is a worldwide problem and iron deficiency is the most common cause. In pregnancy, anaemia increases the risk of adverse maternal, foetal and neonatal outcomes. India’s anaemia rate is among the highest in the world with India’s National Family Health Survey indicating over 50% of pregnant women were affected by anaemia. India’s Anaemia Mukt Bharat-Intensified National Iron Plus Initiative aims to reduce the prevalence of anaemia among reproductive-age women, adolescents and children by 3% per year and facilitate the achievement of a Global World Health Assembly 2025 objective to achieve a 50% reduction of anaemia among women of reproductive age. However, preliminary results of the NFHS-5 survey completed in 2020 indicate that anaemia rates are increasing in some states and these targets are unlikely to be achieved. With oral iron being the first-line treatment for iron deficiency anaemia (IDA) in pregnancy, these results are likely to be impacted by the side effects, poor adherence to tablet ingestion and low therapeutic impact of oral iron. These reports suggest a new approach to treating IDA, specifically the importance of single-dose intravenous iron infusions, may be the key to India effectively reaching its targets for anaemia reduction. Methods This 3-arm, randomized controlled trial is powered to report two primary outcomes. The first is to assess whether a single dose of two different intravenous formulations administered early in the second trimester of pregnancy to women with moderate IDA will result in a higher percentage of participants achieving a normal for pregnancy Hb concentration at 30–34 weeks’ gestation or just prior to delivery when compared to participants taking standard doses of oral iron. The second is a clinical outcome of low birth weight (LBW) (< 2500 g), with a hypothesis that the risk of LBW delivery will be lower in the intravenous iron arms when compared to the oral iron arm. Discussion The RAPIDIRON trial will provide evidence to determine if a single-dose intravenous iron infusion is more effective and economically feasible in reducing IDA in pregnancy than the current standard of care. Trial registration Clinical Trials Registry – India CTRI/2020/09/027730. Registered on 10 September 2020, http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=46801&EncHid=&userName=anemia%20in%20pregnancy