Search

Funder: British Heart Foundation; Id: http://dx.doi.org/10.13039/501100000274, Insufficient oxygen supply (hypoxia) during fetal development leads to cardiac remodeling and a predisposition to cardiovascular disease in later life. Previous work has shown hypoxia causes oxidative stress in the fetal heart and alters the activity and expression of mitochondrial proteins in a sex-dependent manner. However, the functional effects of these modifications on mitochondrial respiration remain unknown. Furthermore, while maternal antioxidant treatments are emerging as a promising new strategy to protect the hypoxic fetus, whether these treatments convey similar protection to cardiac mitochondria in the male or female fetus has not been investigated. Therefore, using an established rat model, we measured the sex-dependent effects of gestational hypoxia and maternal melatonin treatment on fetal cardiac mitochondrial respiration, reactive oxygen species (ROS) production, and lipid peroxidation. Pregnant Wistar rats were subjected to normoxia or hypoxia (13% oxygen) during gestational days (GDs) 6-20 (term ~22 days) with or without melatonin treatment (5 µg/ml in maternal drinking water). On GD 20, mitochondrial aerobic respiration and H2 O2 production were measured in fetal heart tissue, together with lipid peroxidation and citrate synthase (CS) activity. Gestational hypoxia reduced maternal body weight gain (p < .01) and increased placental weight (p < .05) but had no effect on fetal weight or litter size. Cardiac mitochondria from male but not female fetuses of hypoxic pregnancy had reduced respiratory capacity at Complex II (CII) (p < .05), and an increase in H2 O2 production/O2 consumption (p < .05) without any changes in lipid peroxidation. CS activity was also unchanged in both sexes. Despite maternal melatonin treatment increasing maternal and fetal plasma melatonin concentration (p < .001), melatonin treatment had no effect on any of the mitochondrial parameters investigated. To conclude, we show that gestational hypoxia leads to ROS generation from the mitochondrial electron transport chain and affects fetal cardiac mitochondrial respiration in a sex-dependent manner. We also show that maternal melatonin treatment had no effect on these relationships, which has implications for the development of future therapies for hypoxic pregnancies.

Introduction Colorectal cancer is the second leading cause of cancer deaths in Latinos in the U.S., but it is unclear, from previous research, whether Latinos have differing rates of colorectal cancer screening methods from those of non-Hispanic Whites. Methods This study used electronic health records from 686 community health centers across 21 states in the Accelerating Data Value Across a National Community Health Center of the National Patient-Centered Clinical Research Network. Records from English-preferring Latinos, Spanish-preferring Latinos, and non-Hispanic Whites aged 50-75 years were included. A total of 5 outcomes were compared between 2012 and 2017 to provide a comprehensive view of colorectal cancer screening: (1) any colorectal cancer screening, (2) stool-based screening, (3) annual rates of stool testing, (4) any referral for lower gastrointestinal endoscopy, and (5) endoscopy referral among patients with a positive stool-based screening. Results In this study (N=204,243), Spanish-preferring Latinos had higher odds of any colorectal cancer screening (OR=1.44, 95% CI=1.23, 1.68) and stool-based testing (OR=1.82, 95% CI=1.55, 2.13) than non-Hispanic Whites. English- and Spanish-preferring Latinos had lower odds of having ever had a referral for endoscopy in the study period than non-Hispanic Whites (English: OR=0.23, 95% CI=0.15, 0.34; Spanish: OR=0.55, 95% CI=0.40, 0.74), even with a positive stool-based screening (English: OR=0.14, 95% CI=0.06, 0.33; Spanish: OR=0.33, 95% CI=0.19, 0.57). Conclusions In a multistate network of community health centers, Latino patients aged >50 years were more likely to receive stool-based screening tests for colorectal cancer than non-Hispanic Whites but were less likely to receive endoscopy referrals than non-Hispanic Whites, even when experiencing a positive stool-based screening test. Initiatives to improve Latino colorectal cancer outcomes should encourage indicated referrals for lower gastrointestinal endoscopy.

The RECOVERY (Randomised Evaluation of COVid‐19 thERapY) trial found that dexamethasone 6 mg once per day for 10 days reduced deaths by one‐third in ventilated patients and by one‐fifth in other patients, receiving oxygen therapy. This equates to the prevention of one death in around eight ventilated patients, or one in around 25 patients requiring oxygen.

During the early stages of the COVID‐19 pandemic, hospitals in London, the UK epicentre, reported an unusually high number of people presenting with COVID‐19 disease developing diabetic ketoacidosis, hyperosmolar hyperglycaemic state, or a combination of both. Very high doses of insulin were often needed to manage the hyperglycaemia. It has been proposed that these metabolic disturbances may result from severe insulin resistance combined with decreased insulin secretion due to beta cell dysfunction.

The UK National Diabetes Inpatient COVID Response Group was formed at the end of March 2020 to support the provision of diabetes inpatient care during the COVID pandemic. It was formed in response to two emerging needs. First to ensure that basic diabetes services are secured and maintained at a time when there was a call for re-deployment to support the need for general medical expertise across secondary care services. The second was to provide simple safe diabetes guidelines for use by specialists and non-specialists treating inpatients with or suspected of COVID-19 infection. To date the group, comprising UK-based specialists in diabetes, pharmacy and psychology, have produced two sets of guidelines which will be continually revised as new evidence emerges. It is supported by Diabetes UK, the Association of British Clinical Diabetologists and NHS England.

Maternal hypertension is associated with increased rates of pregnancy pathologies, including fetal growth restriction, due at least in part to reductions in nitric oxide (NO) bioavailability and associated vascular dysfunction. Dietary nitrate supplementation, from beetroot juice (BRJ), has been shown to increase NO bioavailability and improve cardiovascular function in both preclinical and clinical studies. This study is the first to investigate effects of dietary nitrate supplementation in a pregnant animal model. Importantly, the effects of nitrate-containing BRJ were compared with both 'placebo' (nitrate-depleted) BRJ as well as water to control for potential nitrate-independent effects. Our data show novel, nitrate-independent effects of BRJ to lower blood pressure and improve vascular function in endothelial nitric oxide synthase knockout (eNOSMaternal hypertension is associated with adverse pregnancy outcomes, including fetal growth restriction (FGR), due in part to reductions in nitric oxide (NO) bioavailability. We hypothesized that maternal dietary nitrate administration would increase NO bioavailability to reduce systolic blood pressure (SBP), improve vascular function and increase fetal growth in pregnant endothelial NO synthase knockout (eNOS

Objectives To investigate inter-examiner variability in gonioscopic evaluation of pectinate ligament abnormality in dogs and to assess level of inter-examiner agreement for four different gonioscopy grading schemes. Materials and Methods Two examiners performed gonioscopy in 98 eyes of 49 Welsh springer spaniel dogs and estimated the percentage circumference of iridocorneal angle affected by pectinate ligament abnormality to the nearest 5%. Percentage scores assigned to each eye by the two examiners were compared. Inter-examiner agreement was assessed following assignment of the percentage scores to each of four grading schemes by Cohen's kappa statistic. Results There was a strong positive correlation between the results of the two examiners (R=0·91). In general, Examiner 1 scored individual eyes higher than Examiner 2, especially for eyes in which both examiners diagnosed pectinate ligament abnormality. A “good” level of agreement could only be achieved with a gonioscopy grading scheme of no more than three categories and with a relatively large intermediate bandwidth (κ=0·68). Clinical Significance A three-tiered grading scheme might represent an improvement on hereditary eye disease schemes which simply classify dogs to be either “affected” or “unaffected” for pectinate ligament abnormality. However, the large intermediate bandwidth of this scheme would only allow for the additional detection of those dogs with marked progression of pectinate ligament abnormality which would be considered most at risk of primary closed-angle glaucoma.

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown. This study aimed to assess the effect of antenatal SC treatment on metabolic and cardiovascular health in offspring by assessing postnatal weight gain, glucose tolerance, systolic blood pressure, and resistance artery function in a mouse model of FGR, the placental-specific insulin-like growth factor 2 (PO) knockout mouse. SC was administered subcutaneously (10 mg/kg) daily from embryonic day (E)12.5. Antenatal SC treatment did not alter fetal weight or viability but increased postnatal weight gain in wild-type (WT) female offspring (P < 0.05) and reduced glucose sensitivity in both WT (P < 0.01) and P0 (P < 0.05) female offspring compared with controls. Antenatal SC treatment increased systolic blood pressure in both male (WT vs. WT-SC: 117 ± 2 vs. 140 ± 3 mmHg, P < 0.0001; P0 vs. P0-SC: 113 ± 3 vs. 140 ± 4 mmHg, P < 0.0001; means ± SE) and female (WT vs. WT-SC: 121 ± 2 vs. 140 ± 2 mmHg, P < 0.0001; P0 vs. P0-SC: 117 ± 2 vs. 144 ± 4 mmHg, P < 0.0001) offspring at 8 and 13 wk of age. Increased systolic blood pressure was not attributed to altered mesenteric artery function. In utero exposure to SC may result in metabolic dysfunction and elevated blood pressure in later life. NEW & NOTEWORTHY Sildenafil citrate (SC) is currently used to treat fetal growth restriction (FGR). We demonstrate that SC is ineffective at treating FGR, and leads to a substantial increase systolic blood pressure and alterations in glucose homeostasis in offspring. We therefore urge caution and suggest that further studies are required to assess the safety and efficacy of SC in utero, in addition to the implications on long-term health.

The structural norm approach was combined with the Potential for Conflict Index (PCI2) to examine differences in normative tolerances for varying levels of people at one time (PAOT) both within and between scuba divers and snorkelers. Data were obtained from scuba divers (n = 975) and snorkelers (n = 609) in the Florida keys. Each group evaluated their encounter norms for seeing 0, 5, 10, 15, 20, 25, and >25 scuba divers (and snorkelers) at one time on scales from “extremely unacceptable” to “extremely acceptable.” Both groups rated 0 in-group PAOT less positively than 5 PAOT, perhaps a function of safety. In general, however, as the number of scuba divers or snorkelers increased, mean acceptance decreased. Scuba divers could tolerate about 10 other divers or snorkelers. Snorkelers could tolerate more snorkelers (about 17) than divers (about 10). PCI2 values suggested that there was greatest consensus that 25 or more PAOT was unacceptable and 5 PAOT was most acceptable. Combining the structural norm approach with PCI2 facilitates understanding research findings and formulating management standards.

Scientific integrity cannot be adequately ensured by appeals to the ethical principles of individual researchers. Research fraud has become a public scandal, exacerbated by our inability accurately to judge its extent. Current reliance on peer review of articles ready for publication as the sole means to control the quality and integrity of the majority of research has been shown to be inadequate, partly because faults in the research process may be concealed and partly because anonymous peer review is itself imperfect. Consequently, the scientific literature is mixed, with the reader unable always to distinguish the good articles from the bad. Scientific research is subject to market forces that will always provide a motivation for a range of misdemeanours. This has led to a ‘market for lemons’. Regulations, and sanctions against miscreants, need to be modelled on those historically found necessary to limit financial fraud. Practical and effective systems of process control and audit have already been devised to ensure the integrity of clinical and pre-clinical research. These should be adapted for use in a much wider range of research activities.

We systematically reviewed interventions substituting sucrose for other macronutrients in apparently healthy adults to assess impact on cardiometabolic risk indicators. Multiple databases were searched to January 2012 and abstracts assessed by 2 reviewers. Twenty-five studies (29 papers) met inclusion criteria but varied in quality and duration. Weaknesses included small subject numbers, unclear reporting of allocation, unusual dietary regimes, differences in energy intake, fat composition or fibre between conditions, unhealthy subjects, heterogeneity of results, and selective reporting. Insufficient data were available to draw reliable conclusions except with regard to the substitution of sucrose for starch, where effects on plasma lipids were inconsistent, mostly explicable by other factors, or nonsignificant. Based on fewer studies, there was little evidence for significant effects on plasma glucose or insulin. Sucrose substitution for starch up to 25% energy does not appear to have adverse effects on cardiometabolic risk indicators in apparently healthy adults. Furthermore, there is no consistent evidence that restricting sucrose in an isoenergetic diet would affect risk indicators, except perhaps in people with certain preexisting metabolic abnormalities. Larger, high-quality studies, lasting several months and studying a wider range of outcomes, are needed in order to provide evidence on which to base public health initiatives.

To investigate inter-examiner variability in gonioscopic evaluation of pectinate ligament abnormality in dogs and to assess level of inter-examiner agreement for four different gonioscopy grading schemes.Two examiners performed gonioscopy in 98 eyes of 49 Welsh springer spaniel dogs and estimated the percentage circumference of iridocorneal angle affected by pectinate ligament abnormality to the nearest 5%. Percentage scores assigned to each eye by the two examiners were compared. Inter-examiner agreement was assessed following assignment of the percentage scores to each of four grading schemes by Cohen's kappa statistic.There was a strong positive correlation between the results of the two examiners (R=0·91). In general, Examiner 1 scored individual eyes higher than Examiner 2, especially for eyes in which both examiners diagnosed pectinate ligament abnormality. A "good" level of agreement could only be achieved with a gonioscopy grading scheme of no more than three categories and with a relatively large intermediate bandwidth (κ=0·68).A three-tiered grading scheme might represent an improvement on hereditary eye disease schemes which simply classify dogs to be either "affected" or "unaffected" for pectinate ligament abnormality. However, the large intermediate bandwidth of this scheme would only allow for the additional detection of those dogs with marked progression of pectinate ligament abnormality which would be considered most at risk of primary closed-angle glaucoma.

The ability to monitor arterial blood pressure continuously with unobtrusive body worn sensors may provide a unique and potentially valuable assessment of a patient's cardiovascular health. Pulse wave velocity (PWV) offers an attractive method to continuously monitoring blood pressure. However, PWV technologies based on timing measurements between the ECG and a distal PPG suffer from inaccuracies on mobile patients due to the confounding influence of pre-ejection period (PEP). In this paper, we presented a wearable, continuous blood pressure monitor (ViSi Mobile) that can measure and track changes in PEP. PEP is determined from precordial vibrations captured by an accelerometer coupled to the patient's sternum. The performance of the PEP measurements was evaluated on test subjects with postural change and patient activity. Results showed potential to improve cNIBP accuracy in active patients.

OBJECTIVE. Nephrogenic systemic fibrosis (NSF) is a rare multisystemic fibrosing disorder that principally affects the skin but may affect other organs of patients with renal insufficiency. The purpose of our study was to identify any common risk factors and determine whether IV gadodiamide is associated with the development of NSF.MATERIALS AND METHODS. A retrospective chart review was performed for all 12 patients diagnosed with NSF at our institution between 2000 and 2006 to identify the clinical manifestations, timing, and dose of gadodiamide administration; dialysis records; concurrent medications; comorbid conditions and surgeries; laboratory findings; imaging findings; and clinical outcome. A review of the dialysis and MR records between 2000 and 2006 showed 559 MRI examinations on 168 dialysis patients (including 301 contrast-enhanced examinations).RESULTS. NSF was diagnosed by clinical findings and tissue diagnosis. All 12 patients had renal insufficiency—eight with dialysis-dependent chronic ren...

Summary The food industry must take an interest in nutrition research prioritisation both for short- and long-term commercial reasons and to fulfil its social responsibilities towards its customers. It should be emphasised, however, that these responsibilities are necessarily limited by practical considerations. Research priorities should take account of strategic goals as well as the technical capability of the nutrition research community at any particular point in time. Important strategic needs for research in nutrition require techniques that have yet to be developed. Whether or not the outcome of research may be commercially exploitable may significantly influence the enthusiasm of companies to provide funding but should not be the main criterion in setting priorities for publicly funded research. Opportunities for co-operation in research funding should be sought only after the object of the research, the methods to be used and the principal researchers have been chosen. Programmes that place too great an emphasis on co-operation tend to distort and trivialise the subjects given priority. A number of areas of research into the common ‘nutrition-related’ diseases of our time (cardiovascular disease, cancer, obesity, anaemia, osteoporosis and dental caries) fulfil strategic needs, are practical and timely, are commercially exploitable and also offer opportunities for co-operative funding. These areas should be prime targets for research funding from both public and private sources.

(1997). Roger Nash Baldwin, the National Civil Liberties Bureau, and Military Intelligence During World War I. The Historian: Vol. 60, No. 1, pp. 87-106.

Initial sticking probabilities for D2 dissociative chemisorption at a Ag(111) surface have been measured for translational energies in the range Ei=220–500 meV, as a function of incident angle θi and gas temperature, using seeded molecular beams. Sticking probabilities are dependent on the D2 internal state distribution and scale with the normal component of the translational energy. The data has been fit by assuming that dissociation is independent of molecular rotation, being the sum of contributions from molecules in different vibrational states v with a sticking function S0(Ei,θi,v)=A/2{1+tanh[Ei cos2 θi−E0(v)]/w(v)}, in a manner similar to the behavior on copper. Sticking parameters E0, the translational energy required for S0 to reach half of its maximum value, are determined with good precision (±25 meV) for levels v=3 (328 meV) and v=4 (170 meV) with width parameters w=54 and 63 meV, respectively, while the barriers for levels v=1 and 2 are close to the upper limit of the sticking data and E0 is e...

We have observed efficient translational to rotational energy transfer for ${\mathrm{H}}_{2}$ $(\ensuremath{\upsilon}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1,J\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2\ensuremath{\leftarrow}0)$ scattered from Cu(111), the cross section increasing rapidly from near threshold to reach a maximum at a translational energy of 140 meV. Above this energy a change in the behavior of the ${\mathrm{H}}_{2}$ $(\ensuremath{\upsilon}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1,J\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2\ensuremath{\leftarrow}0)$ cross section was seen, coinciding with the abrupt onset of ${\mathrm{H}}_{2}$ $(\ensuremath{\upsilon}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1,J)$ removal by coupling of translational and vibrational coordinates. Vibrational relaxation competes with rotational excitation, both processes occurring preferentially at the same impact sites and geometry.

The six major ginsenosides, Rg1, Re, Rb1, Rc, Rb2, and Rd, in roots and leaves of American ginseng have been isolated and quantified by high-performance liquid chromatography. In 4-year-old roots, the main ginsenosides were Re and Rb1, and together they accounted for >75% of the total ginsenosides. In leaves, the concentration and composition of ginsenosides varied with the maturity of the leaf tissue. One-month-old leaves contained 1.33−2.64 g ginsenoside/100 g dry weight, and the ginsenoside Re accounted for >50% of the total concentration. In mature, 4-month-old leaves, the total ginsenoside content ranged from 4.14 to 5.58 g/100 g dry weight, and the ginsenosides Re and Rd each accounted for ∼40% of the total ginsenosides. The production site of ginseng influenced the ginsenoside contents of roots and leaves. However, few significant correlations were found between root and leaf ginsenosides and between ginsenoside levels and mineral composition of the leaves and soil. Keywords: Panax quinquefolium; s...

The activity of a Cu 85 Pd 15 {110}surface towards dissociative chemisorption of D 2 has been investigated over a range of incident gas conditions using a molecular beam. Two different surfaces can be prepared, a disordered (1 × 1) surface with both Cu and Pd in the top layer and an ordered, reconstructed (2 × 1) surface with a top layer of pure Cu and a first layer with 1 2 monolayer of Pd in an ordered (2 × 1) array [D.J. Holmes et al., Surf. Sci. 227 (1990) 179; M.A. Newton et al., Surf. Sci. 259 (1991) 45]. The alloy shows a Pd derived feature in the density of states that shifts upwards towards the Fermi level with increasing Pd content [R.S. Rao et al., Phys. Rev. B 29 (1984) 1713]. Adsorption of D 2 on the Cu 85 Pd 15 {110}(2 × 1) surface is highly activated, rising from S 0 ≈ 1.5 × 10 −7 at an energy of 0.13 eV to ∼ 0.01 at 0.4 eV. This behaviour is similar to that of Cu{111}but S 0 is rather lower than that reported for Cu{110}. The changes to the filled d bands due in the Pd alloy have a minimal effect on the dissociative chemisorption probability, consistent with the absence of any d band density of states at the Fermi level. The disordered Cu 85 Pd 15 {110}(1 × 1) surface also shows activated dissociative chemisorption but with a much larger adsorption probability, S 0 ≈ 1 × 10 −3 . Annealing the surface has a dramatic effect on the sticking probability and is attributed to the dissolution of Pd clusters. This behaviour is contrasted with that of the pure materials in the light of the well characterised electronic structure of Cu 85 Pd 15 {110}.

The JET neutral beam injection system has proved to be both effective and reliable as a plasma heating device. The ion heating and plasma fuelling characteristics of the system are ideally suited to the production of high fusion performance plasmas while the flexibility in the choice of beam species (H, D, T, 3 He or 4 He) and the ability to inject into almost any JET plasma configuration allows a wide variety of related physics experiments to be carried out. The capability to inject (for the first time) tritium beams was essential to the successful execution of the first tritium experiments in which 1.7 MW of power from DT fusion reactions was generated.

Aim To identify effective approaches to recognize diabetes risk and prevent progression to Type 2 diabetes in vulnerable groups, whose diabetes risk may be difficult to identify or manage. Methods UK-based interventions that assess diabetes risk and/or target known risk factors were identified through four main sources: submissions to two calls for evidence by the National Institute for Health and Clinical Excellence; local practice examples collected via a targeted email questionnaire; selected electronic databases; and a focused search of relevant websites. No restriction was placed on the study type or evaluation methods used. Key themes and sub-themes on outcomes, as well as facilitators and barriers to successful delivery, are reported. Results Twenty-four interventions met all inclusion criteria: 15 included a risk identification element and 14 included preventative activities. A range of risk identification tools were used to improve diagnosis of unmet diabetes-related health needs and raise awareness of diabetes risk factors. All preventative interventions focused on lifestyle change. No interventions monitored blood glucose as an outcome and only one reported improvements in baseline risk scores. Facilitators included tailored and flexible programme design, outreach delivery in familiar locations and effective inter-agency working. Barriers included literacy and language difficulties, transient participant populations, low prioritization of diabetes prevention and cost. Conclusions It is possible to engage successfully with high-risk adults in vulnerable groups to achieve positive health outcomes relevant to the prevention of diabetes. However, more robust evidence on longer-term outcomes is required to ensure that programmes are targeted and delivered appropriately.

The hormone leptin, secreted predominantly from adipose tissue, plays a crucial role in the regulation of numerous neuroendocrine functions, from energy homeostasis to reproduction. Genetic deficiency as a consequence of leptin or leptin receptor mutations, although rare in humans, leads to early onset of chronic hyperphagia and massive obesity. In most human obesity, however, leptin levels are chronically elevated. Under these conditions of persistent hyperleptinaemia, and particularly when obesity is associated with a high-fat diet, leptin resistance develops, and signalling through the leptin receptor is curtailed, fuelling further weight gain. Here, we review the role of leptin receptors in the regulation of feeding and obesity development. Leptin receptors are found in each of the major components of the CNS "feeding" circuitry-the brainstem, hypothalamus and distributed reward centres. Through these receptors, leptin exerts influences on signalling and integration within these circuits to alter feeding behaviours. Although some progress is now being made with peptide analogues, the leptin receptor has not proved to be amenable to small molecule pharmacological intervention to date. Where clinical benefit from recombinant leptin administration has been achieved, this has been under circumstances of complete endogenous leptin deficiency or relative hypoleptinaemia such as in lipodystrophy.