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Background: The herbal preparation, STW5‐II, improves upper gastrointestinal symptoms, including abdominal fullness, early satiation, and epigastric pain, in patients with functional dyspepsia, and in preclinical models decreases fundic tone and increases antral contractility. The effects of STW5‐II on esophago‐gastric junction pressure, proximal gastric tone and antropyloroduodenal pressures, disturbances of which may contribute to symptoms associated with disorders of gut–brain interaction, including functional dyspepsia, in humans, have, hitherto, not been evaluated. Methods: STW5‐II or placebo (matched for color, aroma, and alcohol content) were each administered orally, at the recommended dose (20 drops), to healthy male and female volunteers (age: 27 ± 1 years) in a double‐blind, randomized fashion, on two separate occasions, separated by 3–7 days, to evaluate effects on (i) esophago‐gastric junction pressures following a standardized meal using solid‐state high‐resolution manometry (part 1, n = 16), (ii) proximal gastric volume using a barostat (part 2, n = 16), and (iii) antropyloroduodenal pressures assessed by high‐resolution manometry (part 3, n = 18), for 120 min (part 1) or 180 min (parts 2, 3). Key Results: STW5‐II increased maximum intrabag volume (ml; STW5‐II: 340 ± 38, placebo: 251 ± 30; p = 0.007) and intrabag volume between t = 120 and 180 min (p = 0.011), and the motility index of antral pressure waves between t = 60 and 120 min (p = 0.032), but had no effect on esophago‐gastric junction, pyloric, or duodenal pressures. Conclusions & Inferences: STW5‐II has marked region‐specific effects on gastric motility in humans, which may contribute to its therapeutic efficacy in functional dyspepsia. [ABSTRACT FROM AUTHOR]

Aim: To perform a direct, double‐blind, randomised, crossover comparison of subcutaneous and intravenous glucagon‐like peptide‐1 (GLP‐1) in hyperglycaemic subjects with type 2 diabetes naïve to GLP‐1‐based therapy. Materials and Methods: Ten fasted, hyperglycaemic subjects (1 female, age 63 ± 10 years [mean ± SD], glycated haemoglobin 73.5 ± 22.0 mmol/mol [8.9% ± 2.0%], both mean ± SD) received subcutaneous GLP‐1 and intravenous saline, or intravenous GLP‐1 and subcutaneous saline. Infusion rates were doubled every 120 min (1.2, 2.4, 4.8 and 9.6 pmol·kg−1·min−1 for subcutaneous, and 0.3, 0.6, 1.2 and 2.4 pmol·kg−1·min−1 for intravenous). Plasma glucose, total and intact GLP‐1, insulin, C‐peptide, glucagon and gastrointestinal symptoms were evaluated over 8 h. The results are presented as mean ± SEM. Results: Plasma glucose decreased more with intravenous (by ~8.0 mmol/L [144 mg/dL]) than subcutaneous GLP‐1 (by ~5.6 mmol/L [100 mg/dL]; p < 0.001). Plasma GLP‐1 increased dose‐dependently, but more with intravenous than subcutaneous for both total (∆max 154.2 ± 3.9 pmol/L vs. 85.1 ± 3.8 pmol/L; p < 0.001), and intact GLP‐1 (∆max 44.2 ± 2.2 pmol/L vs. 12.8 ± 2.2 pmol/L; p < 0.001). Total and intact GLP‐1 clearance was higher for subcutaneous than intravenous GLP‐1 (p < 0.001 and p = 0.002, respectively). The increase in insulin secretion was greater, and glucagon was suppressed more with intravenous GLP‐1 (p < 0.05 each). Gastrointestinal symptoms did not differ (p > 0.05 each). Conclusions: Subcutaneous GLP‐1 administration is much less efficient than intravenous GLP‐1 in lowering fasting plasma glucose, with less stimulation of insulin and suppression of glucagon, and much less bioavailability, even at fourfold higher infusion rates. [ABSTRACT FROM AUTHOR]

Aim: To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). Methods: In cohort 1, 70 newly diagnosed, treatment‐naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75‐g glucose drink containing 150 mg 13C‐acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi‐solid mashed potato meal, labelled with 100 μl 13C‐octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). Results: Gastric emptying was slower in female than male subjects in both cohorts (both p <.01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p <.05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p <.001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p <.05). Conclusions: Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume‐adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D. [ABSTRACT FROM AUTHOR]

Aim: To evaluate gastric emptying (GE) and the glycaemic response to a 75‐g oral glucose load in newly diagnosed, treatment‐naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12–15 months after insulin pump therapy. Materials and Methods: Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75‐g glucose drink containing 150 mg 13C‐acetate, to determine the gastric half‐emptying time, and underwent assessment of plasma glucose and serum insulin, C‐peptide and glucagon‐like peptide‐1 (GLP‐1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re‐assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12–15 months, GE was re‐measured in 14 of the T2D participants. Results: At baseline, participants with T2D exhibited substantially augmented fasting and post‐glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP‐1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP‐1 secretion was attenuated, fasting and post‐glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12–15 months of follow‐up. Conclusions: In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short‐term insulin pump therapy. The effect on GE is maintained for at least 12 months. [ABSTRACT FROM AUTHOR]

The article discusses the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on blood pressure. GLP-1 receptor agonists have been shown to have cardiovascular and renal protective effects, independent of their glucose-lowering properties. While these drugs have been found to reduce systolic blood pressure in hypertensive individuals, they have little effect on diastolic blood pressure or normotensive individuals. The article also highlights the importance of accurately measuring blood pressure, including postprandial blood pressure, and suggests that further research is needed to optimize the assessment of the effects of GLP-1 receptor agonists on blood pressure. [Extracted from the article]

Background: Intensive care unit (ICU) survivors have reduced oral intake; it is unknown whether intake and associated barriers are unique to this group. Objective: To quantify energy intake and potential barriers in ICU survivors compared with general medical (GM) patients and healthy volunteers. Design: A descriptive cohort study in ICU survivors, GM patients, and healthy volunteers. Following an overnight fast, participants consumed a 200 ml test‐meal (213 kcal) and 180 min later an ad libitum meal to measure energy intake (primary outcome). Secondary outcomes; taste recognition, nutrition‐impacting symptoms, malnutrition, and quality of life (QoL). Data are mean ± SD, median (interquartile range [IQR]) or number [percentage]). Results: Twelve ICU survivors (57 ± 17 years, BMI: 30 ± 6), eight GM patients (69 ± 19 years, BMI: 30 ± 6), and 25 healthy volunteers (58 ± 27 years, BMI: 25 ± 4) were included. Recruitment ceased early because of slow recruitment and SARS‐CoV‐2. Energy intake was lower in both patient groups than in health (ICU: 289 [288, 809], GM: 426 [336, 592], health: 815 [654, 1165] kcal). Loss of appetite was most common (ICU: 78%, GM: 67%). For ICU survivors, GM patients and healthy volunteers, respectively, severe malnutrition prevalence; 40%, 14%, and 0%; taste identification; 8.5 [7.0, 11.0], 8.5 [7.0, 9.5], and 8.0 [6.0, 11.0]; and QoL; 60 [40–65], 50 [31–55], and 90 [81–95] out of 100. Conclusions: Energy intake at a buffet meal is lower in hospital patients than in healthy volunteers but similar between ICU survivors and GM patients. Appetite loss potentially contributes to reduced energy intake. [ABSTRACT FROM AUTHOR]

Addressing a paucity of large‐scale studies about women academics maternity experiences of leave in academia and under‐theorizing the influence of neoliberalism on this phenomenon, this research provides one of the largest studies of women's experiences of maternity leave in the academic sector. Secondary analysis of a subset of data from a global online mixed method survey with 553 women academics (82% UK, 18% international) was undertaken to explore experiences and implications of maternity leave for women. The findings reveal that women academics continued to undertake core academic work duties during maternity leave such as writing grant applications and journal articles, supervising doctoral students, teaching, and responding to emails. We document four distinct orientations adopted by women during maternity leave that characterize neoliberal subjectivity and use Foucauldian governmentality to unmask the inculcation of such norms. Our analysis shows how neoliberal ideology has gained a hegemonic position in academia that leaves little space for maternity leave, resulting in many women effectively relinquishing their maternity rights to sustain academic productivity. We argue that neoliberalism and new managerialism within the academy undermine policies to support women's maternity rights. The findings of this study will be of interest to scholars and Human Resources professionals, academic mothers, managers, and policymakers who are championing change in the sector. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the performance of machine learning algorithms for the prediction of discharge within 12 and 24 h to produce a measure of readiness for discharge after general surgery. Methods: Consecutive general surgery patients at two tertiary hospitals, over a 2‐year period, were included. Observation and laboratory parameter data were stratified into training, testing and validation datasets. Random forest, XGBoost and logistic regression models were evaluated. Each ward round note time was taken as a different event. Primary outcome was classification accuracy of the algorithmic model able to predict discharge within the next 12 h on the validation data set. Results: 42 572 ward round note timings were included from 8826 general surgery patients. Discharge occurred within 12 h for 8800 times (20.7%), and within 24 h for 9885 (23.2%). For predicting discharge within 12 h, model classification accuracies for derivation and validation data sets were: 0.84 and 0.85 random forest, 0.84 and 0.83 XGBoost, 0.80 and 0.81 logistic regression. For predicting discharge within 24 h, model classification accuracies for derivation and validation data sets were: 0.83 and 0.84 random forest, 0.82 and 0.81 XGBoost, 0.78 and 0.79 logistic regression. Algorithms generated a continuous number between 0 and 1 (or 0 and 100), representing readiness for discharge after general surgery. Conclusions: A derived artificial intelligence measure (the Adelaide Score) successfully predicts discharge within the next 12 and 24 h in general surgery patients. This may be useful for both treating teams and allied health staff within surgical systems. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of gastric distension, induced using a gastric 'barostat', on the secretion of glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) in the presence and absence of small intestinal nutrients in healthy individuals. Materials and Methods: Eight healthy participants (two females, six males, mean age 69.3 ± 1.2 years, body mass index 23.5 ± 0.8 kg/m2) were each studied on four occasions when they received an intraduodenal infusion of either (i) 0.9% saline or (ii) glucose delivered at a rate of 3 kcal/min both with, and without, an intragastric balloon with the pressure set to 8 mmHg above the intragastric minimum distending pressure. Results: Following intraduodenal saline or glucose infusion, there was no difference in plasma GLP‐1 with or without gastric distension (P = 1.00 for both saline and glucose infusions). There was also no difference in plasma GIP with or without gastric distension (P = 1.00 for saline infusion and P =.99 for glucose infusion). Conclusions: Gastric distension, either alone or during small intestinal glucose exposure, does not stimulate incretin hormone secretion significantly in healthy humans. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether co‐ingestion of dietary protein with, or before, carbohydrate may be a useful strategy to reduce postprandial hyperglycaemia in older men with type 2 diabetes (T2D). Materials and Methods: Blood glucose, plasma insulin and glucagon concentrations were measured for 180 minutes following ingestion of a drink containing 30 g of glucose (G; 120 kcal), 30 g of whey protein (120 kcal), 30 g of glucose plus 30 g of whey protein (GP; 240 kcal), or control (~2 kcal) in older men with T2D (n = 10, 77 ± 1 years; 31 ± 1.7 kg/m2) and without T2D (n = 10, 78 ± 2 years; 27 ± 1.4 kg/m2). Mixed model analysis was used. Results: GP versus G markedly reduced the increase in blood glucose concentrations (P <.001) and had a synergistic effect on the increase in insulin concentrations (P <.001), in men both with and without T2D. Glucose concentrations were higher in men with T2D compared with those without T2D, whereas insulin and glucagon concentrations were largely unaffected by the presence of T2D. Gastric emptying was faster in men with T2D than in those without T2D. Conclusions: The ability of whey protein to reduce carbohydrate‐induced, postprandial hyperglycaemia is retained in older men with T2D compared with those without T2D, and whey protein supplementation may be a useful strategy in the prevention and management of T2D in older people. [ABSTRACT FROM AUTHOR]

This paper examines the relationship between the prevalence of the urgent and emergency care vanguard (UEC) at the local authority level and their delayed transfers of care (DTOC) rates in England. We created a novel measure of exposure to UEC vanguards based on the residence of patients who used UEC partner hospitals, and we group it by the level of exposure (high, medium, low, none). We use this measure to estimate the effect of UEC vanguards on DTOC rates and then on DTOC rates by sector and a range of reasons associated with the delay. The analysis was run at the local authority level (LA) using quarterly data from NHS England for 150 English LAs from the years 2012–2017. We find a statistically significant UEC exposure effect of around 0.3% reduction in total DTOC to a 1% increase of UEC exposure (equivalent to 775 DTOC days per local authority per quarter in high UEC exposure areas), a result robust to various specification checks. Nonacute sector DTOC was found to be more responsive to UEC vanguards in comparison to acute sector DTOC (0.4% and 0.3% reductions, respectively, to every 1% of UEC exposure). DTOC due to social care was particularly responsive to UEC exposure (0.7% reduction to 1% exposure). DTOC reasons associated with the highest impact of UEC exposure were as follows: awaiting a care package at own home, waiting for further NHS nonacute care, and completion of assessment (reductions of 0.5%, 0.3%, and 0.3% to 1% exposure, respectively). All three reasons were originally associated with the largest number of DTOC days. These findings further advocate for UEC vanguards having been successful at alleviating the pressure on hospitals related to DTOC. [ABSTRACT FROM AUTHOR]

Unnecessarily prolonged stays in hospitals can have negative impacts on patients and present avoidable costs to health and social care systems. This paper presents the qualitative findings of a multi‐methods study of the social care causes of delayed transfers of care (DTOC) for older people in England. The quantitative strand of this study found that DTOC are significantly affected by homecare supply. In this paper, we explore in depth how and why social care capacity factors lead to delays, from the perspectives of those working within the system. We examined the local transfer arrangements in six English local authority (LA) sites that were purposively sampled to include a range of DTOC performance and LA characteristics. Between March and December 2018, 52 professionals involved in arranging or facilitating discharge from hospitals in these sites provided qualitative data, primarily through semi‐structured interviews. Topics included discharge teams and processes, strategic issues and perceived causes of delays. The thematic analysis uncovered the nuances behind the causes of DTOC previously categorised broadly as 'provider capacity' and 'patient choice'. In particular, our analysis highlights the lack of fit between available provision and the needs of people leaving hospital (theme 1); workforce inconsistencies (theme 2) and a myth of patient choice (theme 3). We are now at a turning point in the development of policy to reduce DTOC in the English system, with the full implications of a new national discharge to assess programme yet to be seen. Our research shows the significance of the alignment of service capacity, including the type and location of provision, with the needs and preferences of those leaving hospital. As the new system becomes established, attendance to such nuances behind blockages in the system will be more important than ever. [ABSTRACT FROM AUTHOR]

People with dementia and their carers are a growing subgroup of people who use community‐based social care. These services are designed to maintain people's quality of life while living at home. The ASCOT measure of social care‐related quality of life (SCRQoL), designed to evaluate quality and effectiveness of social care, has been adapted for proxy‐report when someone is unable to self‐report. The ASCOT‐Carer has been developed to measure carer's own SCRQoL. This study sought to establish the factors related to SCRQoL of people living with dementia (PLWD, proxy‐reported by carers) and their carers. Data were collected via a self‐administered postal or online survey of 313 carers in England, from January 2020 to April 2021. Carers were eligible if they supported someone living with dementia at home, who was unable to self‐complete questionnaires. The person living with dementia or their carer had to use at least one social care service, e.g. home care. We recruited participants via an online volunteer panel and NHS sites. Multiple regression was applied to explore the factors significantly related to ASCOT SCRQoL by self‐ and proxy‐report. Key influences on carers' own SCRQoL were their health, financial difficulties associated with caring, and satisfaction with social care support. Inadequate home design was significantly negatively associated with SCRQoL for PLWD. The latter stages of the pandemic‐related restrictions (the tier system from 2nd December 2020 to study end, April 2021) were associated with significantly worse SCRQoL for PLWD, but not for carers. The study offers insight into the factors associated with SCRQoL. In particular, the findings highlight the importance of adequate home design for people with dementia; satisfactory social care support and limiting any adverse financial impact of caring are important for carers. The findings indicate a negative effect of COVID restrictions on SCRQoL of people with dementia. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to assess the impact of a National Reporting Indicator (NRI) on rates of reporting of suspected adverse drug reactions using the Yellow Card scheme following the introduction of the NRI in Wales (UK) in April 2014. Methods: Yellow Card reporting data for general practitioners and other reporting groups in Wales and England for the financial years 2014–15 (study period 1) and 2015–16 (study period 2) were obtained from the Medicines and Healthcare Products Regulatory Agency and compared with those for 2013–14 (pre‐NRI control period). Results: The numbers of Yellow Cards submitted by general practitioners in Wales were 271, 665 and 870 in the control period, study period 1 and study period 2, respectively. This is equivalent to an increase of 145% in study period 1 and 221% in study period 2 compared with the 12‐month control period (2013–14). Corresponding increases in England were 17% and 37%, respectively (P <.001 chi–squared test). The numbers of Yellow Cards submitted by other groups in Wales were 906, 795 and 947 in each of the study periods. Conclusions: Introduction of the NRI corresponded with a significant increase in the number of Yellow Cards submitted by general practitioners in Wales. General practitioner reporting rates continued to increase year on year through to 2018–19 with the NRI still in place. No concomitant change was found in reporting rates by other groups in the health boards in Wales. [ABSTRACT FROM AUTHOR]

Cholecystectomy has been reported to be associated with increased risk of diabetes in cross‐sectional studies. In the current study, we performed both cross‐sectional and prospective analyses to examine the association between cholecystectomy and dysglycaemia in Chinese community‐dwelling adults. A total of 1612 participants (n = 1564 without cholecystectomy and n = 48 with cholecystectomy) were evaluated for glycaemic status (according to the World Health Organization (WHO) 1999 criteria) and then followed up over ~3.2 years. Percent changes (Δ) in fasting blood glucose and HbA1c from baseline at the follow‐up visit were calculated to define glycaemic control as stable (−10% ≤ Δ < 10%), improved (Δ < −10%), or worsened (Δ ≥ 10%). The baseline cross‐sectional analyses indicated that cholecystectomy was associated with an increased risk of both prediabetes and diabetes, while the prospective analysis indicated that cholecystectomy was also associated with a greater risk of deterioration in glycaemic control (ΔFPG ≥10% and ΔHbA1c ≥10%) (P < 0.05 for each, both before and after adjusting for potential confounding covariates). These observations suggest that individuals in the Chinese community‐dwelling population who have undergone cholecystectomy are at increased risk of dysglycaemia. Further studies are warranted to both delineate the underlying mechanisms and to clarify whether more intense surveillance for future development of diabetes is needed in this group. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to evaluate the comparative effects of low‐carbohydrate (LC), full‐strength (FS), and low‐alcohol (LA) beer on gastric emptying (GE), ethanol absorption, glycaemia and insulinaemia in health. Methods: Eight subjects (four male, four female; age: 20.4 ± 0.4 years; BMI 22.7 ± 0.4 kg/m2) had concurrent measurements of GE, plasma ethanol, blood glucose and plasma insulin for 180 min on three separate occasions after ingesting 600 mL of (i) FS beer (5.0% w/v, 246 kcal, 19.2 g carbohydrate), (ii) LC beer (4.6% w/v, 180 kcal, 5.4 g carbohydrate) and (iii) LA beer (2.6% w/v, 162 kcal, 17.4 g carbohydrate) labelled with 20 MBq 99mTc‐calcium phytate, in random order. Results: There was no difference in the gastric 50% emptying time (T50) (FS: 89.0 ± 13.5 min vs LC: 79.5 ± 12.9 min vs LA: 74.6 ± 12.4 min; P =.39). Plasma ethanol was less after LA than LC (P <.001) and FS (P <.001), with no difference between LC and FS (P = 1.0). There was an inverse relationship between plasma ethanol at 15 min and GE after LA (r = −0.87, P <.01) and a trend for inverse relationships after LC (r = −0.67, P =.07) and FS (r = −0.69, P =.06). The AUC 0–180 min for blood glucose was greater for LA than LC (P <.001), with no difference between LA and FS (P =.40) or LC and FS (P = 1.0). Conclusion: In healthy young subjects, GE of FS, LC and LA beer is comparable and a determinant of the plasma ethanol response. [ABSTRACT FROM AUTHOR]

Aim: To determine the serum bile acid (BA) response to 75‐g oral glucose in individuals without diabetes, and whether this is attenuated in patients with 'early' type 2 diabetes (T2D) and related to the glycaemic response at 2 hours in either group. Methods: Forty newly diagnosed, treatment‐naïve Han Chinese T2D subjects and 40 age‐, gender‐, and body mass index‐matched controls without T2D ingested a 75‐g glucose drink after an overnight fast. Plasma glucose and serum concentrations of total and individual BAs, fibroblast growth factor‐19 (FGF‐19), total glucagon‐like peptide‐1 (GLP‐1), and insulin, were measured before and 2 hours after oral glucose. Results: Fasting total BA levels were higher in T2D than control subjects (P <.05). At 2 hours, the BA profile exhibited a shift from baseline in both groups, with increases in conjugated BAs and/or decreases in unconjugated BAs. There were increases in total BA and FGF‐19 levels in control (both P <.05), but not T2D, subjects. Plasma glucose concentrations at 2 hours related inversely to serum total BA levels in control subjects (r = −0.42, P =.006). Total GLP‐1 and the insulin/glucose ratio were increased at 2 hours in both groups, and the magnitude of the increase was greater in control subjects. Conclusions: The serum BA response to a 75‐g oral glucose load is attenuated in patients with 'early' T2D, as is the secretion of FGF‐19 and GLP‐1, while in individuals without T2D it correlates with 2‐hour plasma glucose levels. These observations support a role for BAs in the regulation of postprandial glucose metabolism. [ABSTRACT FROM AUTHOR]

Each NH coordinated with the CDC's Pharmacy Partnership of Long-Term Care Program to provide COVID-19 mRNA (Moderna) vaccine clinics to vaccinate residents and staff. Moderna and Pfizer-BioNTech messenger RNA (mRNA) COVID-19 vaccines are highly effective and safe in preventing severe COVID-19 disease.1-3 Consequently, NH residents and staff were vaccinated through the CDC's Pharmacy Partnership of Long-Term Care Program4 clinics. Coronavirus 2019 (COVID-19) has disproportionately affected nursing home (NH) residents, accounting for at least one-third of COVID-19 deaths. NH staff completed the vaccine side effect data collection form for each resident and returned it to their NH leadership. [Extracted from the article]

Background: Energy-dense formulae are often provided to critically ill patients with enteral feed intolerance with the aim of increasing energy delivery, yet the effect on gastric emptying is unknown. The rate of gastric emptying of a standard compared with an energy-dense formula was quantified in critically ill patients.Methods: Mechanically ventilated adults were randomized to receive radiolabeled intragastric infusions of 200 mL standard (1 kcal/mL) or 100 mL energy-dense (2 kcal/mL) enteral formulae on consecutive days in this noninferiority, blinded, crossover trial. The primary outcome was scintigraphic measurement of gastric retention (percentage at 120 minutes). Other measures included area under the curve (AUC) for gastric retention and intestinal energy delivery (calculated from gastric retention of formulae over time), blood glucose (peak and AUC), and intestinal glucose absorption (using 3-O-methyl-D-gluco-pyranose [3-OMG] concentrations). Comparisons were undertaken using paired mixed-effects models. Data presented are mean ± SE.Results: Eighteen patients were studied (male/female, 14:4; age, 55.2 ± 5.3 years). Gastric retention at 120 minutes was greater with the energy-dense formula (standard, 17.0 ± 5.9 vs energy-dense, 32.5 ± 7.1; difference, 12.7% [90% confidence interval, 0.8%-30.1%]). Energy delivery (AUC120 , 13,038 ± 1119 vs 9763 ± 1346 kcal/120 minutes; P = 0.057), glucose control (peak glucose, 10.1 ± 0.3 vs 9.7 ± 0.3 mmol/L, P = 0.362; and glucose AUC120 8.7 ± 0.3 vs 8.5 ± 0.3 mmol/L.120 minutes, P = 0.661), and absorption (3-OMG AUC120 , 38.5 ± 4.0 vs 35.7 ± 4.0 mmol/L.120 minutes; P = .508) were not improved with the energy-dense formula.Conclusion: In critical illness, administration of an energy-dense formula does not reduce gastric retention, increase energy delivery to the small intestine, or improve glucose absorption or glucose control; instead, there is a signal for delayed gastric emptying. [ABSTRACT FROM AUTHOR]

Background: Postprandial falls in blood pressure (BP) are more common in older compared to younger individuals. The effects of protein compared to carbohydrates and fat on postprandial BP, and the relation to gastric emptying rates, are poorly studied. Objectives: To determine the effects of a whey protein compared to a control drink on systolic BP (SBP) and diastolic BP (DBP), and heart rate (HR) in healthy younger and older men, and to relate these effects to gastric emptying. Design: A pooled analyses of two randomized, double‐blind, cross‐over studies. Setting: Two acute clinical intervention studies with identical study design. Participants: Nineteen older (age: 74 ± 1 years, body mass index: 26 ± 1 kg/m2) and 13 younger (23 ± 1 years, 24 ± 1 kg/m2) healthy men. Intervention: A 70 g/280 kcal whey‐protein or control (water with diet cordial, ~2 kcal) drink (450 ml). Measurements: BP and HR were assessed with an automated device immediately before and at 3‐min intervals after drink ingestion (0–180 min). Gastric emptying of the drinks was measured using 3D ultrasonography (0–180 min). Results: Older versus younger men exhibited a greater fall in SBP (−23 ± 2 vs −15 ± 2 mmHg, p = 0.001) after whey‐protein versus control, as BP did not change after the two drinks in younger men (p > 0.05). The nadir in SBP occurred later in the older than younger men (114 ± 11 vs 62 ± 14 min; p < 0.001), with SBP still apparently declining 180 min after whey‐protein ingestion in the older men. The magnitude of the rise in HR was greater (p < 0.05) in the younger than older men. Conclusion: Following ingestion of 70 g whey protein, healthy older men exhibited a sustained fall in BP, despite an increase in HR, whereas in younger men there was no change in BP. BP may need to be monitored after high protein meals in older people at risk of postprandial hypotension. [ABSTRACT FROM AUTHOR]

In our routine use of RIA for glucagon analysis, we began seeing unexpected plasma glucagon responses to oral and enteral glucose loads in both healthy humans and patients with type 2 diabetes, which differed markedly from responses seen in similar subjects in earlier studies. The relationships between the integrated glucagon response relative to baseline measured by Millipore radioimmunoassay (RIA) and Mercodia ELISA kits were evaluated by linear regression analysis (C and F). Our data also suggest that the RIA kit manufactured prior to the change of antibody for glucagon was acceptable for evaluation of circulating glucagon levels in clinical settings (although suppression by glucose was not always clearly shown, when compared with more sensitive assays11). [Extracted from the article]

Background: Delayed gastric emptying is the leading cause of enteral feeding intolerance (EFI) in critical illness. This phase 2a study compared TAK‐954, a selective agonist of 5‐hydroxytryptamine type 4 receptors, with metoclopramide in critically ill patients with EFI (NCT01953081). Methods: A blinded, double‐dummy trial was conducted in mechanically ventilated patients with EFI (>200 mL gastric residual volume within 24 hours before randomization). Patients were randomized to receive either 0.5 mg intravenous TAK‐954 over 1 hour then 0.9% saline injection 4 times/d (sham metoclopramide) or the active comparator 10 mg intravenous metoclopramide 4 times/d and a 1‐hour 0.9% saline infusion. After initial dosing, participants received a radiolabeled meal of liquid nutrient (Ensure; 106 kcal), and gastric emptying was measured (scintigraphy). Adverse events (AEs) were recorded from the time of consent through to day 5; serious AEs were collected to day 30. Results: Thirteen patients (TAK‐954, n = 7; metoclopramide, n = 6) participated. Five patients in the TAK‐954 group and 4 in the metoclopramide group experienced AEs (2 and 3, respectively, were serious). All AEs except 1 (diarrhea in the metoclopramide group) were considered unrelated to study drug. Following treatment, a greater proportion of patients receiving TAK‐954 had normal gastric retention (<13% retention at 180 minutes) than those receiving metoclopramide (6/7 vs 3/6 patients, respectively). Conclusion: A single dose of 0.5 mg intravenous TAK‐954 appears to have at least similar efficacy in accelerating gastric emptying to multiple doses of 10 mg metoclopramide and was not associated with increased AEs. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: Almost half of deaths related to COVID‐19 in the United States are linked to nursing homes (NHs). We describe among short‐term and long‐term residents at three NHs in Michigan the outbreak identification process, universal testing, point prevalence of COVID‐19, and subsequent containment efforts, outcomes, and challenges. DESIGN: Outbreak investigation. SETTING: Three NHs in southeast Michigan. PARTICIPANTS: All residents (N = 215) at three NHs (total beds = 356) affiliated with a large academic healthcare system. METHODS: Upon detection of confirmed cases within the facility, each NH in collaboration and consultation with local hospital, public health officials, and parent corporation implemented immediate facility‐wide testing and the following intervention measures: cohorting of COVID‐19 positive residents; communication regarding testing and results with residents, healthcare professionals, and families; personal protective equipment reeducation and use throughout facilities; and dedicated staffing for infected patients cohorted in a dedicated COVID‐19 wing. We collected patient data regarding demographics, symptoms, comorbidities, hospitalization, and 14‐day outcomes. RESULTS: A total of 29 cases of COVID‐19 were identified at three participating NHs. Nineteen cases of COVID‐19 were identified through symptom‐triggered testing from March 23 to April 23, 2020; 10 (4.7%) additional cases were identified through universal testing of 215 residents conducted from April 7 to 15, 2020. The hospitalization rate was 37.9%. The case fatality rate was 20.7% (6/29); these patients had multiple comorbidities. No residents who tested positive through the point‐prevalence survey required hospitalization, and five were discharged home within 14 days. CONCLUSION: Proactive and coordinated steps between NH medical directors and administrators, referral hospitals including their laboratories, and local public health officials are necessary to rapidly respond to an outbreak and limit the transmission of COVID‐19. This coordinated public health approach may save lives, minimize the burden to the healthcare system, and reduce healthcare costs. See related editorial by Kathleen Unroe [ABSTRACT FROM AUTHOR]

Undergraduate biology laboratories emphasize hands‐on skills. Typically, descriptions of manual techniques are delivered via written instruction. Custom‐produced prelab instructional videos, which augment prelab instruction, have come into wider use in recent years. However, institutional and economic barriers can interfere with video production at all colleges and universities. In such cases, professionally produced laboratory instructional videos provide an attractive alternative. We hypothesized that students who watch short, professionally produced instructional videos before performing a laboratory would feel more confident and achieve greater learning gains than students whose prelab instruction was limited to handouts. For this proof of concept study, we investigated the value added when students watched a brief video, twice per lab, in an intermediate molecular biology course at a small, liberal arts university, and in a nonmajors biology course at a large, public research university. Both video and nonvideo comparison groups were administered a pre‐ and postlab exams. A postlab self‐efficacy survey was also administered to video groups. Our results reveal that in three out of the four laboratory classes, students who watched professional instruction videos performed significantly better in both pre‐ and postlab exams. For these students, we observed up to a two‐fold increase in test scores on scientific concepts and techniques. For all classes, most of the video group students reported that the video contributed to their confidence, comprehension of concepts, and understanding of how to conduct the lab. We conclude that professional instructional videos may address production barriers and have the potential to effectively enhance undergraduate science curricula and significantly improve students' performance. [ABSTRACT FROM AUTHOR]

Summary: Soybean cyst nematode (SCN, Heterodera glycines) is the most devastating pest affecting soybean production worldwide. SCN resistance requires both the GmSHMT08 and the GmSNAP18 in 'Peking'‐type resistance. Here, we describe the molecular interaction between GmSHMT08 and GmSNAP18, which is potentiated by a pathogenesis‐related protein GmPR08‐Bet VI. Like GmSNAP18 and GmSHMT08, GmPR08‐Bet VI expression was induced in response to SCN and its overexpression decreased SCN cysts by 65% in infected transgenic soybean roots. Overexpression of GmPR08‐Bet VI did not have an effect on SCN resistance when the two cytokinin‐binding sites in GmPR08‐Bet VI were mutated, indicating a new role of GmPR08‐Bet VI in SCN resistance. GmPR08‐Bet VI was mapped to a QTL for resistance to SCN using different mapping populations. GmSHMT08, GmSNAP18 and GmPR08‐Bet VI localize to the cytosol and plasma membrane. GmSNAP18 expression and localization hyper‐accumulated at the plasma membrane and was specific to the root cells surrounding the nematode in SCN‐resistant soybeans. Genes encoding key components of the salicylic acid signalling pathway were induced under SCN infection. GmSNAP18 and GmPR08‐Bet VI were also induced under salicylic acid and cytokinin exogenous treatments, while GmSHMT08 was induced only when the resistant GmSNAP18 was present, pointing to the presence of a molecular crosstalk between SCN‐resistant genes and defence genes. Expression analysis of GmSHMT08 and GmSNAP18 identified the need of a minimum expression requirement to trigger the SCN resistance reaction. These results provide insight into a new response mechanism towards plant nematode resistance involving haplotype compatibility, gene dosage and hormone signalling. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effects of 8 weeks' administration of exenatide (EXE) once weekly on gastric emptying of solids and liquids (using the "gold standard" technique, scintigraphy), glucose absorption and postprandial glycaemia in healthy people. Material and methods: A total of 32 healthy participants were randomized to receive either EXE once weekly (2 mg/wk subcutaneously; six men, 10 women, mean age 59.9 ± 0.9 years, mean body mass index [BMI] 29.6 ± 0.6 kg/m2) or matching placebo (PBO; six men, 10 women, mean age 60.6 ± 1.2 years, mean BMI 29.5 ± 1.0 kg/m2) for 8 weeks. Gastric emptying, nausea (visual analogue scale), and plasma glucose, insulin, C‐peptide and glucagon were measured for 120 min after a solid/liquid meal, comprising 100 g ground beef (radiolabelled with 20 MBq 99mTc‐sulphur colloid) and 150 mL 10% glucose (radiolabelled with 7 MBq 67Ga‐EDTA), and containing 5 g 3‐O‐methyl‐glucose (3‐OMG) as a marker of glucose absorption, at baseline and after 8 weeks' treatment. Results: The study treatments were well tolerated. Scores for nausea were consistently low, with no difference between the EXE once weekly and PBO groups. EXE once weekly slowed gastric emptying of solids (area under the curve [AUC]0–120min: P < 0.05) and liquids (AUC0–120min: P = 0.01) substantially, and attenuated glucose absorption (3‐OMG incremental AUC [iAUC]0–30min: P = 0.001) and the postprandial rise in plasma glucose (iAUC0–30min: P = 0.008). Plasma glucagon at 2 h was reduced by EXE once weekly (P = 0.001). The magnitude of the reduction in plasma glucose at t = 30 min from baseline to 8 weeks with EXE once weekly was related inversely to the 50% emptying time of the glucose drink (r = −0.55, P = 0.03). Conclusions: In healthy participants, 8 weeks' administration of the "long‐acting" glucagon‐like peptide‐1 receptor agonist EXE, slowed gastric emptying of solids and liquids substantially, with consequent reductions in glucose absorption and postprandial glycaemia. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of the dipeptidyl peptidase‐4 (DPP‐4) inhibitor vildagliptin on glycaemic and energy expenditure responses during intraduodenal fat infusion, as well as the contribution of endogenous glucagon‐like peptide‐1 (GLP‐1) signalling, in people with type 2 diabetes (T2DM). Methods: A total of 15 people with T2DM managed by diet and/or metformin (glycated haemoglobin 49.3 ± 2.1 mmol/mol) were studied on three occasions (two with vildagliptin and one with placebo) in a double‐blind, randomized, crossover fashion. On each day, vildagliptin 50 mg or placebo was given orally, followed by intravenous exendin (9–39) 600 pmol/kg/min, on one of the two vildagliptin treatment days, or 0.9% saline over 180 minutes. At between 0 and 120 minutes, a fat emulsion was infused intraduodenally at 2 kcal/min. Energy expenditure, plasma glucose and glucose‐regulatory hormones were evaluated. Results: Intraduodenal fat increased plasma GLP‐1 and glucose‐dependent insulinotropic polypeptide (GIP), insulin and glucagon, and energy expenditure, and decreased plasma glucose (all P < 0.05). On the two intravenous saline days, plasma glucose and glucagon were lower, plasma intact GLP‐1 was higher (all P < 0.05), and energy expenditure tended to be lower after vildagliptin (P = 0.08) than placebo. On the two vildagliptin days, plasma glucose, glucagon and GLP‐1 (both total and intact), and energy expenditure were higher during intravenous exendin (9–39) than saline (all P < 0.05). Conclusions: In well‐controlled T2DM during intraduodenal fat infusion, vildagliptin lowered plasma glucose and glucagon, and tended to decrease energy expenditure, effects that were mediated by endogenous GLP‐1. [ABSTRACT FROM AUTHOR]

We believe that the use of the paracetamol technique in isolation to evaluate the effects of GLP-1RAs on gastric emptying in humans should be abandoned and that scintigraphic measurement, using a standardized technique, should represent a mandatory regulatory requirement in the development of this drug class, including oral semaglutide. We have also pointed out that it is incorrect to suggest that a reduction in the AUC 0 to 1 hours, but not the AUC 0 to 5 hours, for paracetamol, indicates that an effect to slow gastric emptying is only sustained for 1 hour,2 simply because it may be anticipated that all the paracetamol will eventually be absorbed. [Extracted from the article]

Aims: To determine the effects of the dipeptidyl peptidase‐4 inhibitor, sitagliptin, on gastric emptying (GE) of a high‐carbohydrate meal and associated glycaemic and blood pressure (BP) responses in type 2 diabetes mellitus (T2DM). Materials and Methods: Fourteen patients with T2DM (nine men, five women; age 67.8 ± 1.5 years; body mass index 31.2 ± 0.9 kg/m2; T2DM duration: 4.2 ± 0.9 years; glycated haemoglobin: 46 ± 1.8 mmol/mol [6.4% ± 0.2%]), managed by diet and/or metformin, underwent concurrent measurements of GE, BP and plasma glucose for 240 minutes after ingestion of a radiolabelled mashed potato meal after receiving sitagliptin (100 mg) or placebo in randomized, double‐blind, crossover fashion on 2 consecutive days. Results: Sitagliptin reduced postprandial plasma glucose (P < .005) without affecting GE (P =.88). The magnitude of the glucose‐lowering effect (change in incremental area under the curve0–240 min from placebo to sitagliptin) was related to GE (kcal/min) on placebo (r = 0.68, P =.008) There was a comparable fall in systolic BP (P =.80) following the meal, with no difference between the 2 days. Conclusions: In T2DM, while sitagliptin has no effect on either GE or postprandial BP, its ability to lower postprandial glucose are dependent on the basal rate of GE. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency has been increasing concurrently with prevalence of autism spectrum disorders (ASD), and emerging evidence suggests vitamin D is involved in brain development. Most prior studies of ASD examined vitamin D levels in children already diagnosed, but a few examined levels during perinatal development, the more likely susceptibility period. Therefore, we examined newborn vitamin D levels in a case–control study conducted among births in 2000–2003 in southern California. Children with ASD (N = 563) or intellectual disability (ID) (N = 190) were identified from the Department of Developmental Services and compared to population controls (N = 436) identified from birth certificates. 25‐hydroxyvitamin D (25(OH)D) was measured in archived newborn dried blood spots by a sensitive assay and corrected to sera equivalents. We categorized 25(OH) D levels as deficient (<50 nmol/L), insufficient (50–74 nmol/L), and sufficient (≥75 nmol/L), and also examined continuous levels, using logistic regression. The adjusted odds ratios (AOR) and 95% confidence intervals for ASD were 0.96 (0.64–1.4) for 25(OH)D deficiency (14% of newborns) and 1.2 (0.86–1.6) for insufficiency (26% of newborns). The AORs for continuous 25(OH)D (per 25 nmol/L) were 1.0 (0.91–1.09) for ASD and 1.14 (1.0–1.30) for ID. Thus, in this relatively large study of measured newborn vitamin D levels, our results do not support the hypothesis of lower 25(OH)D being associated with higher risk of ASD (or ID), although we observed suggestion of interactions with sex and race/ethnicity. 25(OH)D levels were relatively high (median 84 nmol/L in controls), so results may differ in populations with higher prevalence of low vitamin D levels. Autism Res 2019, 12: 989–998. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: We studied whether vitamin D levels measured at birth were related to whether a child later developed autism (or low IQ). Our results did not show that children with autism, or low IQ, overall had lower vitamin D levels at birth than children without autism. Vitamin D levels were fairly high, on average, in these children born in Southern California. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of the prandial glucagon‐like peptide‐1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75‐g oral glucose load in healthy people and those with type 2 diabetes (T2DM). Materials and methods: Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ± SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75‐g glucose drink on two separate days. All participants received lixisenatide (10 μg subcutaneously) or placebo in a randomized, double‐blind, crossover fashion 30 minutes before the glucose drink. Results: Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0‐120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0‐120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001). Conclusions: In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension. [ABSTRACT FROM AUTHOR]

Metformin has been shown to modulate the cardiovascular response to intraduodenal glucose in patients with type 2 diabetes (T2DM), and may have the capacity to regulate postprandial blood pressure (BP), which is often inadequately compensated in T2DM, resulting in postprandial hypotension. In the present study, we evaluated the acute effects of metformin on the BP and heart rate (HR) responses to oral glucose in patients with T2DM. Ten diet‐controlled T2DM patients were evaluated on two occasions in a double‐blind, randomized, crossover design. Participants received either metformin 1 g or saline (control) intraduodenally 60 minutes before ingesting a 50 g glucose drink labelled with 150 mg 13C‐acetate. BP, HR, plasma glucagon‐like peptide‐1 (GLP‐1) and gastric emptying (breath test) were evaluated over 180 minutes. Systolic and diastolic BP decreased and HR increased after oral glucose (P < 0.001 for all) on both days. Metformin attenuated the fall in systolic BP (P < 0.001), increased plasma GLP‐1 concentrations (P < 0.05) and slowed gastric emptying (P < 0.05) without significantly affecting diastolic BP or HR. In conclusion, metformin acutely attenuates the hypotensive response to oral glucose, associated with augmented GLP‐1 secretion and delayed gastric emptying, effects potentially relevant to its favourable cardiovascular profile. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effects of 12 weeks of treatment with a whey/guar preload on gastric emptying, postprandial glycaemia and glycated haemoglobin (HbA1c) levels in people with type 2 diabetes (T2DM). Materials and methods: A total of 79 people with T2DM, managed on diet or metformin (HbA1c 49 ± 0.7 mmol/mol [6.6 ± 0.1%]), were randomized, in single‐blind fashion, to receive 150 mL flavoured preloads, containing either 17 g whey protein plus 5 g guar (n = 37) or flavoured placebo (n = 42), 15 minutes before two meals, each day for 12 weeks. Blood glucose and gastric emptying (breath test) were measured before and after a mashed potato meal at baseline (without preload), and after the preload at the beginning (week 1) and end (week 12) of treatment. HbA1c levels, energy intake, weight and body composition were also evaluated. Results: Gastric emptying was slower (P < 0.01) and postprandial blood glucose levels lower (P < 0.05) with the whey/guar preload compared to placebo preload, and the magnitude of reduction in glycaemia was related to the rate of gastric emptying at both week 1 (r = −0.54, P < 0.001) and week 12 (r = −0.54, P < 0.0001). At the end of treatment, there was a 1 mmol/mol [0.1%] reduction in HbA1c in the whey/guar group compared to the placebo group (49 ± 1.0 mmol/mol [6.6 ± 0.05%] vs. 50 ± 0.8 mmol/mol [6.7 ± 0.05%]; P < 0.05). There were no differences in energy intake, body weight, or lean or fat mass between the groups. Conclusions: In patients with well‐controlled T2DM, 12 weeks' treatment with a low‐dose whey/guar preload, taken twice daily before meals, had sustained effects of slowing gastric emptying and reducing postprandial blood glucose, which were associated with a modest reduction in HbA1c, without causing weight gain. [ABSTRACT FROM AUTHOR]

Hypoglycaemia is arguably the most important complication of insulin therapy in type 1 and type 2 diabetes. Counter‐regulation of hypoglycaemia is dependent on autonomic function and frequent hypoglycaemia may lead to reductions in both autonomic warning signals and the catecholamine response, the so‐called "impaired awareness of hypoglycaemia". It is now appreciated that gastric emptying is a major determinant of the glycaemic response to carbohydrate‐containing meals in both health and diabetes, that disordered (especially delayed) gastric emptying occurs frequently in diabetes, and that acute hypoglycaemia accelerates gastric emptying substantially. However, the potential relevance of gastric emptying to the predisposition to, and counter‐regulation of, hypoglycaemia has received little attention. In insulin‐treated patients, the rate of gastric emptying influences the timing of the postprandial insulin requirement, and gastroparesis is likely to predispose to postprandial hypoglycaemia. Conversely, the marked acceleration of gastric emptying induced by hypoglycaemia probably represents an important counter‐regulatory response to increase the rate of carbohydrate absorption. This review summarizes the current knowledge of the inter‐relationships between hypoglycaemia and gastric emptying, with a focus on clinical implications. [ABSTRACT FROM AUTHOR]

Aims: The gastrointestinal tract, particularly the lower gut, may be key to the anti‐diabetic action of metformin. We evaluated whether administration of metformin into the distal, vs the proximal, small intestine would be more effective in lowering plasma glucose by stimulating glucagon‐like pepetide‐1 (GLP‐1) and/or slowing gastric emptying (GE) in type 2 diabetes (T2DM). Materials and methods: Ten diet‐controlled T2DM patients were studied on three occasions. A transnasal catheter was positioned with proximal and distal infusion ports located 13 and 190 cm beyond the pylorus, respectively. Participants received infusions of (a) proximal + distal saline (control), (b) proximal metformin (1000 mg) + distal saline or (c) proximal saline + distal metformin (1000 mg) over 5 minutes, followed 60 minutes later by a glucose drink containing 50 g glucose and 150 mg 13C‐acetate. "Arterialized" venous blood and breath samples were collected over 3 hours for measurements of plasma glucose, GLP‐1, insulin and glucagon, and GE, respectively. Results: Compared with control, both proximal and distal metformin reduced plasma glucose and augmented GLP‐1 responses to oral glucose comparably (P < 0.05 each), without affecting plasma insulin or glucagon. GE was slower after proximal metformin than after control (P < 0.05) and tended to be slower after distal metformin, without any difference between proximal and distal metformin. Conclusions: In diet‐controlled T2DM patients, glucose‐lowering via a single dose of metformin administered to the upper and lower gut was comparable and was associated with stimulation of GLP‐1 and slowing of GE. These observations suggest that the site of gastrointestinal administration is not critical to the glucose‐lowering capacity of metformin. [ABSTRACT FROM AUTHOR]

However, in both studies, after continuous administration, gastric emptying was still slowed substantially by GLP-1.12,13 Recent studies, using scintigraphy, have established that the "long-acting" GLP-1RAs, exenatide once-weekly11 and liraglutide,14 do slow emptying with chronic administration, albeit probably less than "short-acting" GLP-1RAs. A study reported in abstract form, in which gastric emptying was measured by scintigraphy, suggests that dulaglutide has a sustained effect to slow gastric emptying in T2DM.18 The effects of subcutaneous and oral semaglutide on gastric emptying, regretfully, have only been assessed using the paracetamol test.19,20 In obese subjects given semaglutide (1 mg/week subcutaneous for 12 weeks), plasma paracetamol levels were 27% less in the first hour.19 It was suggested (we believe incorrectly) that the slowing of emptying is only modest. Dahl et al.20 reported, in abstract form, the effect of oral semaglutide (14 mg) on paracetamol absorption in T2DM; the AUC 0-1 h for plasma paracetamol was reduced by 31%; the AUC 0-5 h was not provided. The comprehensive study by Urva et al.2 evaluated the effect of the dual glucose-dependent insulinotropic polypeptide and GLP-1RA, tirzepatide, using the paracetamol technique, in humans with and without T2DM, and in comparison with the effects of semaglutide and dulaglutide. [Extracted from the article]

The article reports on the preparedness of nursing homes in Michigan to deal with the COVID-19 pandemic. It presents the results of a survey sent to nursing homes on their preparedness, compares these results to an influenza pandemic in 2007, and concludes that nursing homes are better prepared in 2020.

Entrepreneurism is widely regarded as being one way in which women can sidestep the sexism of male‐dominated institutionalized work environments and enter into a world in which men and women operate on a level playing field. Yet, in a corpus of stories of female entrepreneurs’ experiences, we noted that being ignored by men was a constant theme. Taking a social constructionist and narrative approach to identity, we analyse the gendered identity work that female entrepreneurs do in these stories and we seek to explicate the process through which female entrepreneurs do not evaluate being ignored by men as sexism‐in‐action. Using positioning theory as an analytical tool, we analyse these stories at three different levels: the here‐and‐now interaction between interviewer and storyteller; the there‐and‐then identity work of the characters in the storyworld; and the wider societal Discourses that the storytellers enact, and which are enacted by such identity work. Findings indicate that despite making gendered difference, inferiority and lack of agency relevant, the stories are not evaluated as sexism‐in‐action because the female entrepreneurs enact a postfeminist and neoliberal Discourse of freedom, autonomy and choice, rather than a feminist Discourse of discrimination and sexism. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this descriptive study was to examine teacher instructional dilemmas and opportunities that emerged when students worked with interactive computer‐based simulation models during the High‐Adventure Science (HAS) project. The intervention included the HAS digital curriculum, designed for grades 7–12. Each curricular unit was framed to address scientific questions in earth and environmental science, currently being investigated by scientists. Instructional support was provided through a 2‐day professional development session and through reporting systems within the curriculum. During 1 academic year, data were collected from a cohort of 12 teachers, through baseline and postimplementation surveys. From a nine‐teacher cohort subset, observation, interview, and survey data were collected during the following year. Descriptive findings indicate that a designed digital curriculum with carefully sequenced interactive models has benefits but creates instructional challenges; teacher and student roles are often flipped during the implementation of such a curriculum; and teachers may need to shift their instructional approach and find new ways to make digital learning experiences relevant and compelling as they respond to both opportunities and challenges. [ABSTRACT FROM AUTHOR]

Meal consumption leads to an increase in sympathetic output to compensate for hemodynamic changes and maintain blood pressure (BP). Obesity is associated with a blunting of the sympathetic response to meal ingestion, but interpretation of studies investigating these responses is compromised by their failure to account for the rate of gastric emptying, which is an important determinant of postprandial cardiovascular and sympathetic responses and, in both health and obesity, exhibits a wide interindividual variation. We sought to determine the effects of intraduodenal glucose infusion, bypassing gastric emptying, on BP, heart rate (HR), and noradrenaline responses in obese and healthy control subjects. 12 obese subjects (age 36.6 ± 3.9 years, body mass index (BMI) 36.1 ± 1.3 kg/m2) and 23 controls (age 27.8 ± 2.4 years, BMI 22.4 ± 0.5 kg/m2) received intraduodenal infusions of glucose at 1 or 3 kcal/ min, or saline, for 60 min (t = 0–60 min), followed by intraduodenal saline (t = 60–120 min). BP and HR were measured with an automatic cuff, and blood samples collected for measurement of plasma noradrenaline. Intraduodenal glucose at 1 kcal/min was associated with a fall in diastolic BP in the control subjects only (P < 0.01), with no change in systolic BP, HR or noradrenaline in either group. In both groups, intraduodenal glucose at 3 kcal/min was associated with a fall in diastolic (P < 0.01), but not systolic, BP, and rises in HR (P < 0.001) and plasma noradrenaline (P < 0.01), with no difference in responses between the groups. We conclude that cardiovascular and sympathetic responses to intraduodenal glucose infusion are comparable between obese and control subjects, and dependent on the rate of glucose delivery. [ABSTRACT FROM AUTHOR]

Accordingly, this supports the concept of selecting GLP-1RA therapy, particularly for those individuals in whom gastric emptying is more rapid, which is often the case in both obesity [1] and uncomplicated type 2 diabetes [4]. However, stable isotope breath tests (which, unlike scintigraphy, are not associated with a radiation burden and which have been validated against scintigraphy) have been shown to be a suitable alternative, particularly in large-scale clinical trials [4]. [Extracted from the article]

Personal health budgets ( PHBs) in England have been viewed as a vehicle for developing a personalised patient-based strategy within the substance misuse care pathway. In 2009, the Department of Health announced a 3-year pilot programme of PHBs to explore opportunities offered by this new initiative across a number of long-term health conditions, and commissioned an independent evaluation to run alongside as well as a separate study involving two pilot sites that were implementing PHBs within the substance misuse service. The study included a quantitative and qualitative strand. The qualitative strand involved 20 semi-structured interviews among organisational representatives at two time points (10 at each time point) between 2011 and 2012 which are the focus for this current paper. Overall, organisational representatives believed that PHBs had a positive impact on budget-holders with a drug and/or alcohol misuse problem, their families and the health and social care system. However, a number of concerns were discussed, many of which seemed to stem from the initial change management process during the early implementation stage of the pilot programme. This study provides guidance on how to implement and offer PHBs within the substance misuse care pathway: individuals potentially would benefit from receiving their PHB post-detox rather than at a crisis point; PHBs have the potential to improve the link to after-care services, and direct payments can provide greater choice and control, but sufficient protocols are required. [ABSTRACT FROM AUTHOR]

A literary criticism of the book "The View From Here” by Jay Wallace is presented. It outlines the confusion related to two perspectives i.e. regret and affirmation. It also discussed the justification and the morals related to the respective decisions and human psychology and their attitudes towards attachments.

An introduction is presented in which the editor discusses topics including the use of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in treating type 2 diabetes, the symptoms of gastrointestinal (GI) tract disorders, and the effects of GLP-1 on the physiology.

In rodents, metformin slows intestinal glucose absorption, potentially increasing exposure of the distal gut to glucose to enhance postprandial glucagon-like peptide-1 ( GLP-1) secretion. We evaluated the effects of metformin on serum 3-O-methylglucose (3- OMG; a marker of glucose absorption) and plasma total GLP-1 concentrations during a standardized intraduodenal infusion of glucose and 3- OMG in patients with type 2 diabetes. A total of 12 patients, treated with metformin 850 mg twice daily or placebo for 7 days each in a double-blind, randomized, crossover design (14 days' washout between treatments), were evaluated on days 5 or 8 of each treatment (6 subjects each). On each study day, 30 minutes after ingesting 850 mg metformin or placebo, patients received an infusion of glucose (60 g + 5 g 3- OMG, dissolved in water to 240 mL) via an intraduodenal catheter over the course of 120 minutes. Compared with placebo, metformin was associated with lower serum 3- OMG ( P < .001) and higher plasma total GLP-1 ( P = .003) concentrations. The increment in plasma GLP-1 after metformin vs placebo was related to the reduction in serum 3- OMG concentrations ( P = .019). Accordingly, metformin inhibits small intestinal glucose absorption, which may contribute to augmented GLP-1 secretion in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Major surgery can result in severe sleep deprivation, so that stages 3 and 4 and rapid eye movement (REM) sleep are either severely, or completely suppressed.3 This is exacerbated by the surgical ward environment, where patients' sleep is frequently disturbed by both staff and technology. Further, general anaesthesia delays the onset of nocturnal melatonin secretion resulting in sleep dysfunction early in the postoperative course.4 Recent work has sought to determine the role of sleep in nociceptive pathways and subjective pain experience. [Extracted from the article]

This article considers the practice of taxidermy and its relationship to the 'golden age' of big game hunting, the science of natural history and the dramaturgical codes of empire by looking at the collecting exploits of one man, Major Percy Powell-Cotton (1866-1940), and his attempts to preserve the spoils of the hunt in the 'great indoors'. As various scholars have pointed out, taxidermy offers up a vivid and striking 'afterlife' of the animal with a unique (and some might say unsavoury) ability to elucidate our environmental and cultural relations with other species. As such, the reanimated animals of empire, posed on the walls of the country estate or arrested in museum cases, represent valuable historical artefacts ripe for unstitching. Drawing on the work of Garry Marvin, Sam Alberti and Merle Patchett, this article stalks Powell-Cotton's taxidermic project across various sites of capture, production and display (what I call necrogeographies) to illuminate the sinuous contours of imperial natural history and the stories of pursuit, production and performance lurking beneath the skin of the reanimated animal. [ABSTRACT FROM AUTHOR]