Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

AIMS: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes. MATERIALS AND METHODS: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up. RESULTS: Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035-1.531) p = 0.0213), albuminuria (OR 1.277 (1.124-1.454), p = 0.0002; HR 1.608 (1.208-2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p = 0.0068; HR 1.324 (1.089-1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p = 0.0109). CONCLUSIONS: Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.

Diet shapes the metabolite profile in the intact human ileum, which affects PYY release.

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites, and appetite hormone release remains unclear owing to limited access to intact human ileum. In a randomized crossover trial (ISRCTN11327221; isrctn.com), we investigated the role of human ileum in GLP-1 and PYY release by giving healthy volunteers diets differing in fiber and food structure: high-fiber (intact or disrupted food structures) or low-fiber disrupted food structures. We used nasoenteric tubes to sample chyme from the intact distal ileum lumina of humans in the fasted state and every 60 min for 480 min postprandially. We demonstrate the highly dynamic, wide-ranging molecular environment of the ileum over time, with a substantial decrease in ileum bacterial numbers and bacterial metabolites after food intake. We also show that high-fiber diets, independent of food structure, increased PYY release compared with a low-fiber diet during 0 to 240 min postprandially. High-fiber diets also increased ileal stachyose, and a disrupted high-fiber diet increased certain ileal amino acids. Treatment of human ileal organoids with ileal fluids or an amino acid and stachyose mixture stimulated PYY expression in a similar profile to blood PYY concentrations, confirming the role of ileal metabolites in PYY release. Our study demonstrates the diet-induced changes over time in the metabolite environment of intact human ileum, which play a role in PYY release.

Reliability, validity and acceptability of an online clinical reasoning simulator for medical students: An international pilot.

INTRODUCTION: Clinical reasoning skills are essential for decision-making. Current assessment methods are limited when testing clinical reasoning and management of uncertainty. This study evaluates the reliability, validity and acceptability of Practicum Script, an online simulation-based programme, for developing medical students' clinical reasoning skills using real-life cases. METHODS: In 2020, we conducted an international, multicentre pilot study using 20 clinical cases with 2457 final-year medical students from 21 schools worldwide. Psychometric analysis was performed (n = 1502 students completing at least 80% of cases). Classical estimates of reliability for three test domains (hypothesis generation, hypothesis argumentation and knowledge application) were calculated using Cronbach's alpha and McDonald's omega coefficients. Validity evidence was obtained by confirmatory factor analysis (CFA) and measurement alignment (MA). Items from the knowledge application domain were analysed using cognitive diagnostic modelling (CDM). Acceptability was evaluated by an anonymous student survey. RESULTS: Reliability estimates were high with narrow confidence intervals. CFA revealed acceptable goodness-of-fit indices for the proposed three-factor model. CDM analysis demonstrated good absolute test fit and high classification accuracy estimates. Student survey responses showed high levels of acceptability. CONCLUSION: Our findings suggest that Practicum Script is a useful resource for strengthening students' clinical reasoning skills and ability to manage uncertainty.

The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake.

Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.

Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry.

The Scientific Investigation Committee of the American Academy of Restorative Dentistry offers this review of the 2022 dental literature to briefly touch on several topics of interest to modern restorative dentistry. Each committee member brings discipline-specific expertise in their subject areas that include (in order of the appearance in this report): prosthodontics; periodontics, alveolar bone, and peri-implant tissues; dental materials and therapeutics; occlusion and temporomandibular disorders; sleep-related breathing disorders; oral medicine and oral and maxillofacial surgery; and dental caries and cariology. The authors focused their efforts on reporting information likely to influence the daily dental treatment decisions of the reader with an emphasis on innovations, new materials and processes, and future trends in dentistry. With the tremendous volume of literature published daily in dentistry and related disciplines, this review cannot be comprehensive. Instead, its purpose is to update interested readers and provide valuable resource material for those willing to subsequently pursue greater detail on their own. Our intent remains to assist colleagues in navigating the tremendous volume of newly minted information produced annually. Finally, we hope that readers find this work helpful in managing patients.

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.

Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice.

Coupling the release of pituitary hormones to the developmental stage of the oocyte is essential for female fertility. It requires estrogen to restrain kisspeptin (KISS1)-neuron pulsatility in the arcuate hypothalamic nucleus, while also exerting a surge-like effect on KISS1-neuron activity in the AVPV hypothalamic nucleus. However, a mechanistic basis for this region-specific effect has remained elusive. Our genomic analysis in female mice demonstrate that some processes, such as restraint of KISS1-neuron activity in the arcuate nucleus, may be explained by region-specific estrogen receptor alpha (ERα) DNA binding at gene regulatory regions. Furthermore, we find that the Kiss1-locus is uniquely regulated in these hypothalamic nuclei, and that the nuclear receptor co-repressor NR0B1 (DAX1) restrains its transcription specifically in the arcuate nucleus. These studies provide mechanistic insight into how ERα may control the KISS1-neuron, and Kiss1 gene expression, to couple gonadotropin release to the developmental stage of the oocyte.

The Power of Suggestion: Subjective Satiety Is Affected by Nutrient and Health-Focused Food Labelling with No Effect on Physiological Gut Hormone Release.

Health claims on food labelling can influence peoples' perception of food without them actually eating it, for example driving a belief that a particular food will make them feel fuller. The aim of this study was to investigate whether nutrient and health claims on food labelling can influence self-reported, and physiological indicators of, satiation. A total of 50 participants attended two visits where they were asked to consume a 380 kcal breakfast (granola and yogurt) labelled as a 500 kcal 'indulgent' breakfast at one visit and as a 250 kcal 'sensible' breakfast at the other. The order of the breakfast descriptions was randomly allocated. Participants were unaware that the two breakfasts were the same product and that only the food labels differed. At each visit blood samples were collected to measure gut hormone levels (acylated ghrelin, peptide tyrosine-tyrosine and glucagon-like peptide-1) at three time points: 20 min after arrival (baseline), after 60 min (anticipatory, immediately prior to consumption) and after 90 min (post-consumption). Visual analogue scales measuring appetite (hunger, satiety, fullness, quantity and desire to eat) were completed prior to each sample. Between 60 and 90 min, participants consumed the breakfast and rated its sensory appeal. Participants reported a higher mean change in self-reported fullness for the 'indulgent' than the 'sensible' breakfast from anticipatory to post-consumption (mean difference: 7.19 [95% CI: 0.73, 13.6]; p = 0.030). This change was not observed for the other appetite measures at the other time points or gut hormone levels. This study suggests that nutrient and health claims on food labels may influence satiation as measured by self-reported fullness. It also suggests that the observed differences in satiety scores are not due to changes in the main appetite regulating gut hormones, but are more likely centrally mediated. More high-quality trials are required to confirm these findings.

Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss.

Glucagon analogs show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular, its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analog, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a pre-requisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics.

Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry.

The Scientific Investigation Committee of the American Academy of Restorative Dentistry offers this review of the 2021 dental literature in restorative dentistry to inform busy dentists regarding noteworthy scientific and clinical progress over the past year. Each member of the committee brings discipline-specific expertise to coverage of this broad topical area. Specific subject areas addressed, in order of the appearance in this report, include COVID-19 and the dental profession (new); prosthodontics; periodontics, alveolar bone, and peri-implant tissues; implant dentistry; dental materials and therapeutics; occlusion and temporomandibular disorders; sleep-related breathing disorders; oral medicine and oral and maxillofacial surgery; and dental caries and cariology. The authors focused their efforts on reporting information likely to influence daily dental treatment decisions with an emphasis on future trends in dentistry. With the tremendous volume of dentistry and related literature being published daily, this review cannot possibly be comprehensive. Rather, its purpose is to update interested readers and provide important resource material for those interested in pursuing greater details on their own. It remains our intent to assist colleagues in negotiating the extensive volume of important information being published annually. It is our hope that readers find this work useful in successfully managing the patients and dental problems they encounter.

The acute effect of glucagon on components of energy balance and glucose homoeostasis in adults without diabetes: a systematic review and meta-analysis.

OBJECTIVE: Using a systematic review and meta-analysis, we aimed to estimate the mean effect of acute glucagon administration on components of energy balance and glucose homoeostasis in adults without diabetes. METHODS: CENTRAL, CINAHL, Embase, MEDLINE, PubMed, and Scopus databases were searched from inception to May 2021. To be included, papers had to be a randomised, crossover, single- or double-blind study, measuring ad libitum meal energy intake, energy expenditure, subjective appetite, glucose, and/or insulin following acute administration of glucagon and an appropriate comparator in adults without diabetes. Risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Randomized trials with additional considerations for cross-over trials. Certainty of evidence was assessed using the GRADE approach. Random-effect meta-analyses were performed for outcomes with at least five studies. This study is registered on PROSPERO (CRD42021269623). RESULTS: In total, 13 papers (15 studies) were considered eligible: energy intake (5 studies, 77 participants); energy expenditure (5 studies, 59 participants); subjective appetite (3 studies, 39 participants); glucose (13 studies, 159 participants); insulin (12 studies, 147 participants). All studies had some concerns with regards to risk of bias. Mean intervention effect of acute glucagon administration on energy intake was small (standardised mean difference [SMD]: -0.19; 95% CI, -0.59 to 0.21; P = 0.345). Mean intervention effect of acute glucagon administration on energy expenditure (SMD: 0.72; 95% CI, 0.37-1.08; P < 0.001), glucose (SMD: 1.11; 95% CI, 0.60-1.62; P < 0.001), and insulin (SMD: 1.33; 95% CI, 0.88-1.77; P < 0.001) was moderate to large. CONCLUSIONS: Acute glucagon administration produces substantial increases in energy expenditure, and in circulating insulin and glucose concentrations. However, the effect of acute glucagon administration on energy intake is unclear. Insufficient evidence was available to evaluate the acute effect of glucagon on subjective appetite.

BMAT's predictive validity for medical school performance: A retrospective cohort study.

BACKGROUND: Although used widely, there is limited evidence of the BioMedical Admissions Test's (BMAT) predictive validity and incremental validity over prior educational attainment (PEA). We investigated BMAT's predictive and incremental validity for performance in two undergraduate medical schools, Imperial College School of Medicine (ICSM), UK, and Lee Kong Chian School of Medicine (LKCMedicine), Singapore. Our secondary goal was to compare the evidence collected with published evidence relating to comparable tools. METHODS: This was a retrospective cohort study of four ICSM (1188 students, entering 2010-2013) and three LKCMedicine cohorts (222 students, 2013-2015). We investigated associations between BMAT Section 1 ('Thinking Skills'), Section 2 ('Scientific Knowledge and Applications') and Section 3a ('Writing Task') scores, with written and clinical assessment performance across all programme years. Incremental validity was investigated over PEA (A-levels) in a subset of ICSM students. RESULTS: When BMAT sections were investigated independently, Section 2 scores predicted performance on all written assessments in both institutions with mainly small effect sizes (standardised coefficient ranges: ICSM: 0.08-0.19; LKCMedicine: 0.22-0.36). Section 1 scores predicted Years 5 and 6 written assessment performance at ICSM (0.09-0.14) but nothing at LKCMedicine. Section 3a scores only predicted Year 5 clinical assessment performance at ICSM with a coefficient <0.1. There were no positive associations with standardised coefficients >0.1 between BMAT performance and clinical assessment performance. Multivariable regressions confirmed that Section 2 scores were the most predictive. We found no clear evidence of incremental validity for any BMAT section scores over A-level grades. DISCUSSION: Schools who wish to assess scientific knowledge independently of A-levels may find BMAT Section 2 useful. Comparison with previous studies indicates that, overall, BMAT seems less useful than comparable tools. Larger scale studies are needed. Broader questions regarding why institutions adopt certain admissions tests, including those with little evidence, need consideration.

Higher dietary fibre intake is associated with increased skeletal muscle mass and strength in adults aged 40 years and older.

BACKGROUND: Skeletal muscle mass begins to decline from 40 years of age. Limited data suggest that dietary fibre may modify lean body mass (BM), of which skeletal muscle is the largest and most malleable component. We investigated the relationship between dietary fibre intake, skeletal muscle mass and associated metabolic and functional parameters in adults aged 40 years and older. METHODS: We analysed cross-sectional data from the US National Health and Nutrition Examination Survey between 2011 and 2018 from adults aged 40 years and older. Covariate-adjusted multiple linear regression analyses were used to evaluate the association between dietary fibre intake and BM components (BM, body mass index [BMI], total lean mass, appendicular lean mass, bone mineral content, total fat, trunk fat; n = 6454), glucose homeostasis (fasting glucose, fasting insulin, HOMA2-IR; n = 5032) and skeletal muscle strength (combined grip strength; n = 5326). BM components and skeletal muscle strength were expressed relative to BM (per kg of BM). RESULTS: Higher intakes of dietary fibre were significantly associated with increased relative total lean mass (ß: 0.69 g/kg BM; 95% CI, 0.48-0.89 g/kg BM; P < 0.001), relative appendicular lean mass (ß: 0.34 g/kg BM; 95% CI, 0.23-0.45 g/kg BM; P < 0.001), relative bone mineral content (ß: 0.05 g/kg BM; 95% CI, 0.02-0.07 g/kg BM; P < 0.001) and relative combined grip strength (ß: 0.002 kg/kg BM; 95% CI, 0.001-0.003 kg/kg BM; P < 0.001). Conversely, higher dietary fibre intakes were significantly associated with a lower BM (ß: -0.20; 95% CI, -0.28 to -0.11 kg; P < 0.001), BMI (ß: -0.08 kg/m2 ; 95%CI, -0.10 to -0.05 kg/m2 ), relative total fat (ß: -0.68 g/kg BM; 95% CI, -0.89 to -0.47 g/kg BM; P < 0.001), relative trunk fat (ß: -0.48 g/kg BM; 95%CI, -0.63 to -0.33 g/kg; P < 0.001), fasting glucose (ß: -0.01 mmol/L; 95% CI, -0.02 to -0.00 mmol/L; P = 0.017), fasting insulin (ß: -0.71 pmol/L; 95% CI, -1.01 to -0.41 pmol/L; P < 0.001) and HOMA2-IR (ß: -0.02 AU; 95% CI, -0.02 to -0.01 AU; P < 0.001). CONCLUSIONS: Higher dietary fibre intakes are associated with a lower BM and enhanced body composition, characterized by a reduction in fat mass and an increase in lean mass. Higher dietary fibre intakes were also associated with improvements in glucose homeostasis and skeletal muscle strength. Increasing dietary fibre intake may be a viable strategy to prevent age-associated declines in skeletal muscle mass.

Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry.

The Scientific Investigation Committee of the American Academy of Restorative Dentistry offers this review of the 2020 professional literature in restorative dentistry to inform busy dentists regarding noteworthy scientific and clinical progress over the past year. Each member of the committee brings discipline-specific expertise to this work to cover this broad topic. Specific subject areas addressed include prosthodontics; periodontics, alveolar bone, and peri-implant tissues; implant dentistry; dental materials and therapeutics; occlusion and temporomandibular disorders (TMDs); sleep-related breathing disorders; oral medicine and oral and maxillofacial surgery; and dental caries and cariology. The authors focused their efforts on reporting information likely to influence day-to-day dental treatment decisions with a keen eye on future trends in the profession. With the tremendous volume of dentistry and related literature being published today, this review cannot possibly be comprehensive. The purpose is to update interested readers and provide important resource material for those interested in pursuing greater detail. It remains our intent to assist colleagues in navigating the extensive volume of important information being published annually. It is our hope that readers find this work useful in successfully managing the dental patients they encounter.

The Effect of a Single Bout of Continuous Aerobic Exercise on Glucose, Insulin and Glucagon Concentrations Compared to Resting Conditions in Healthy Adults: A Systematic Review, Meta-Analysis and Meta-Regression.

BACKGROUND: Elevated glucose and insulin levels are major risk factors in the development of cardiometabolic disease. Aerobic exercise is widely recommended to improve glycaemic control, yet its acute effect on glycaemia and glucoregulatory hormones has not been systematically reviewed and analysed in healthy adults. OBJECTIVE: To determine the effect of a single bout of continuous aerobic exercise on circulating glucose, insulin, and glucagon concentrations in healthy adults. METHODS: CENTRAL, CINAHL, Embase, Global Health, HMIC, Medline, PubMed, PsycINFO, ScienceDirect, Scopus and Web of Science databases were searched from inception to May 2020. Papers were included if they reported a randomised, crossover study measuring glucose and/or insulin and/or glucagon concentrations before and immediately after a single bout of continuous aerobic exercise (≥ 30 min) compared to a time-matched, resting control arm in healthy adults. The risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Tool and GRADE approach, respectively. Random-effects meta-analyses were performed for glucose, insulin, and glucagon. Sub-group meta-analyses and meta-regression were performed for categorical (metabolic state [postprandial or fasted], exercise mode [cycle ergometer or treadmill]) and continuous (age, body mass index, % males, maximal aerobic capacity, exercise duration, exercise intensity) covariates, respectively. RESULTS: 42 papers (51 studies) were considered eligible: glucose (45 studies, 391 participants), insulin (38 studies, 377 participants) and glucagon (5 studies, 47 participants). Acute aerobic exercise had no significant effect on glucose concentrations (mean difference: - 0.05 mmol/L; 95% CI, - 0.22 to 0.13 mmol/L; P = 0.589; I2: 91.08%, large heterogeneity; moderate-quality evidence). Acute aerobic exercise significantly decreased insulin concentrations (mean difference: - 18.07 pmol/L; 95% CI, - 30.47 to - 5.66 pmol/L; P = 0.004; I2: 95.39%, large heterogeneity; moderate-quality evidence) and significantly increased glucagon concentrations (mean difference: 24.60 ng/L; 95% CI, 16.25 to 32.95 ng/L; P < 0.001; I2: 79.36%, large heterogeneity; moderate-quality evidence). Sub-group meta-analyses identified that metabolic state modified glucose and insulin responses, in which aerobic exercise significantly decreased glucose (mean difference: - 0.27 mmol/L; 95% CI, - 0.55 to - 0.00 mmol/L; P = 0.049; I2: 89.72%, large heterogeneity) and insulin (mean difference: - 42.63 pmol/L; 95% CI, - 66.18 to - 19.09 pmol/L; P < 0.001; I2: 81.29%, large heterogeneity) concentrations in the postprandial but not fasted state. Meta-regression revealed that the glucose concentrations were also moderated by exercise duration and maximal aerobic capacity. CONCLUSIONS: Acute aerobic exercise performed in the postprandial state decreases glucose and insulin concentrations in healthy adults. Acute aerobic exercise also increases glucagon concentrations irrespective of metabolic state. Therefore, aerobic exercise undertaken in the postprandial state is an effective strategy to improve acute glycaemic control in healthy adults, supporting the role of aerobic exercise in reducing cardiometabolic disease incidence. PROSPERO REGISTRATION NUMBER: CRD42020191345.

Differential effects of L- and D-phenylalanine on pancreatic and gastrointestinal hormone release in humans: A randomized crossover study.

AIM: To investigate the effects of L-phenylalanine on gastroenteropancreatic hormone release, glucose levels, subjective appetite and energy intake in humans, and to determine whether these effects were stereoisomer-specific by comparing them with D-phenylalanine. MATERIALS AND METHODS: A dose-finding, non-randomized, unblinded, crossover study was conducted during October-December 2017 at the NIHR Imperial Clinical Research Facility in five participants, in which the tolerability of escalating doses of oral L-phenylalanine was assessed (0, 3, 6 and 10 g). Also, an acute, randomized, double-blind, placebo-controlled crossover study was conducted during January-May 2018 at the NIHR Imperial Clinical Research Facility in 11 participants, in which the effects of oral 10 g L-phenylalanine relative to D-phenylalanine and placebo on gastroenteropancreatic hormone (insulin, glucagon, glucose-dependent insulinotropic polypeptide [GIP], peptide tyrosine tyrosine [PYY], glucagon-like peptide-1) and glucose concentrations, visual analogue scales for subjective appetite and energy intake at an ad libitum meal served 70 minutes postingestion, were investigated. RESULTS: L-phenylalanine was well-tolerated and increased insulin and glucagon concentrations prior to meal ingestion at several time points relative to placebo and D-phenylalanine (P < .05). L-phenylalanine also increased GIP concentrations relative to D-phenylalanine (P = .0420) and placebo (P = .0249) 70 minutes following ingestion. L-phenylalanine reduced postprandial glucose area under the curve (AUC)70-150mins relative to placebo (P = .0317) but did not affect subjective appetite or energy intake (P > .05). D-phenylalanine increased postprandial PYY AUC70-150mins concentrations relative to placebo (P = .0002). CONCLUSIONS: Ingestion of L-phenylalanine, but not D-phenylalanine, increases insulin, glucagon and GIP concentrations without appearing to have a marked effect on appetite.

Baclofen: To Screen or Not to Screen in Postmortem Blood?

Baclofen (BLF) has been prescribed in the UK since 1972 for the alleviation of spasticity. However, evidence suggests BLF is also recreationally misused. It has been associated with ethanol, gamma-hydroxybutyric acid (GHB), pregabalin (PGL) and gabapentin (GBP) use/abuse, and deaths have been reported. With current postmortem (PM) toxicological screening approaches, BLF is not routinely included in the general drugs screen and is only screened for if specifically mentioned in the case documents. The extent of BLF misuse is thus unclear. This study was carried out to determine the prevalence and concentrations of BLF in Coroners' toxicology, to investigate whether BLF misuse with ethanol, GHB, PGL and GBP is causing death and to determine the potential extent of the underreporting of BLF-associated deaths. Between 1 January 2016 and 31 December 2017, 3,750 PM femoral vein bloods were screened for BLF; all positive cases were quantified. Only 0.56% of samples screened positive for BLF, with concentration ranging from 0.08 to 102.00 µg/mL (median = 0.28). It was determined that if routine analysis without additional screening of BLF had been performed, 43% of BLF positives cases would have been missed. However, given the low incidence of detection, this only represents 0.25% of the cohort. Likely illicit use of BLF with GHB was seen in one case only. Death from the recreational use of BLF with PGL and GBP was not observed. Only two cases positive for BLF had an ethanol concentration of ≥50 mg%. Two cases of presumed intentional overdose of BLF were observed. This study highlights that although BLF abuse may be occurring, deaths are rare. It is therefore not cost- or time-effective to screen for BLF in all PM cases. With BLF currently being investigated for the treatment of alcoholism and withdrawal symptoms of illicit drug use, BLF-related deaths may rise in the future.

Annual review of selected scientific literature: A report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry.

This comprehensive review of the 2019 restorative dental literature is offered to inform busy dentists regarding remarkable publications and noteworthy progress made in the profession. Developed by the Scientific Investigation Committee of the American Academy of Restorative Dentistry, each author brings discipline-specific expertise to 1 of 8 sections of the report: (1) prosthodontics; (2) periodontics, alveolar bone, and peri-implant tissues; (3) implant dentistry; (4) dental materials and therapeutics; (5) occlusion and temporomandibular disorders; (6) sleep-related breathing disorders; (7) oral medicine and oral and maxillofacial surgery; and (8) dental caries and cariology. The report targets important information likely to influence day-to-day dental treatment decisions. Each review is not intended to stand alone but to update interested readers so that they may visit source material when greater detail is desired. As the profession moves toward evidence-based clinical decision-making, an incredible volume of potentially valuable dental literature continues to increase. It is the intention of this review and its authors to provide assistance in negotiating the extensive dental literature published in 2019. It is our hope that readers find this work useful in the clinical management of dental patients.