bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Cholecystokinin and its Receptors in the Intestinal Tract of Type 2 Diabetes Patients and Healthy Controls
Authors: Gilliam-Vigh Hannah , Jorsal Tina , Rehfeld Jens F , Pedersen Jens , Poulsen Steen S , Vilsbøll Tina , Knop Filip K 
Published: May 2021

Abstract

Background
Cholecystokinin (CCK) is a gut hormone originally known for its effects on gallbladder contraction and release of digestive enzymes. CCK, however, also mediates satiety and stimulate insulin secretion. Knowledge of the distribution of CCK-producing enteroendocrine cells (I cells) in humans is sparse. The general notion, based on animal data, is that I cells are present mainly in the proximal small intestine. We examined the occurrence of I cells (immunohistochemically) and the expression of CCK messenger RNA (mRNA) as well as CCK1 and CCK2 receptor mRNA along the intestines in healthy individuals and patients with type 2 diabetes.

Methods
Mucosal biopsies collected with 30-cm intervals in the small intestine and from seven anatomical locations in the large intestine (using double-balloon enteroscopy) from 12 patients with type 2 diabetes and 12 gender-, age-, and body mass index–matched healthy individuals were analyzed using mRNA sequencing and immunohistochemical staining.

Results
We observed a gradual decrease in CCK mRNA expression and density of CCK-immunoreactive cells from duodenum to ileum. Very few CCK-immunoreactive cells and nearly undetectable CCK mRNA expression were found in the large intestine. No significant differences were seen between the groups. Expression of CCK receptors was observed in the duodenum of both groups.

Conclusions
Both density of CCK cells and expression of CCK mRNA decreased through the small intestine in both groups with low levels in the large intestine. Patients with type 2 diabetes did not have altered density of CCK cells or expression of CCK mRNA in intestinal mucosa.
Cardiac Phenotype and Tissue Sodium Content in Adolescents With Defects in the Melanocortin System
Authors: Puder Lia , Roth Sophie , Krabusch Philipp , Wiegand Susanna , Opitz Robert , Bald Martin , Flück Christa , Schulz Esther , Voss Egbert , Markó Lajos , Linz Peter , Berger Felix , Müller Dominik N , Kuehne Titus , Litt Michael J , Cone Roger D , Kühnen Peter , Kelm Marcus 
Published: May 2021

Abstract

Context
Pro-opiomelanocortin (POMC) and the melanocortin-4 receptor (MC4R) play a pivotal role in the leptin–melanocortin pathway. Mutations in these genes lead to monogenic types of obesity due to severe hyperphagia. In addition to dietary-induced obesity, a cardiac phenotype without hypertrophy has been identified in MC4R knockout mice.

Objective
We aimed to characterize cardiac morphology and function as well as tissue Na+ content in humans with mutations in POMC and MC4R genes.

Methods
A cohort of 42 patients (5 patients with bi-allelic POMC mutations, 6 heterozygous MC4R mutation carriers, 19 obese controls without known monogenic cause, and 12 normal weight controls) underwent cardiac magnetic resonance (CMR) imaging and 23Na-MRI.

Results
Monogenic obese patients with POMC or MC4R mutation respectively had a significantly lower left ventricular mass/body surface area (BSA) than nonmonogenic obese patients. Left ventricular end-diastolic volume/BSA was significantly lower in POMC- and MC4R-deficient patients than in nonmonogenic obese patients. Subcutaneous fat and skin Na+ content was significantly higher in POMC- and MC4R-deficient patients than in nonmonogenic obese patients. In these compartments, the water content was significantly higher in patients with POMC and MC4R mutation than in control groups.

Conclusion
Patients with POMC or MC4R mutations carriers had a lack of transition to hypertrophy, significantly lower cardiac muscle mass/BSA, and stored more Na+ within the subcutaneous fat tissue than nonmonogenic obese patients. The results point towards the role of the melanocortin pathway for cardiac function and tissue Na+ storage and the importance of including cardiologic assessments into the diagnostic work-up of these patients.
Association Between Visit-to-Visit Fasting Plasma Glucose Variability and Osteoporotic Fractures in Nondiabetic Subjects
Authors: Kim Jung A , Sung Lee Ji , Song Eyun , Roh Eun , Hee Yu Ji , Hoon Kim Nam , Jin Yoo Hye , Seo Ji A , Gon Kim Sin , Hee Kim Nan , Hyun Baik Sei , Mook Choi Kyung 
Published: May 2021

Abstract

Context
Although long-term glucose variability has been reported to be a risk factor associated with osteoporosis, there have been no previous studies between the relationship of glucose variability and fractures in people without diabetes.

Objective
We assessed visit-to-visit variations in fasting plasma glucose (FPG) as a prognostic factor in predicting osteoporotic fractures in individuals without diabetes.

Methods
Using a nationwide cohort database, we examined the impact of FPG on the development of osteoporotic fractures in men and women (aged ≥50 years). The primary outcomes were the number of total fractures and vertebral fractures. FPG variability was measured using standard deviation (FPG-SD), coefficient of variation (FPG-CV), and variability independent of the mean (FPG-VIM).

Results
Of the 92 929 participants, 5262 (5.7%) developed osteoporotic fractures during the mean follow-up of 8.4 years. Individuals in the highest quartile of FPG-SD showed an 11% and 16% increase in risk of total and vertebral fractures, respectively, compared with those in the lowest quartile after adjustment for mean FPG and other risk factors. Analyses using FPG-CV and FPG-VIM demonstrated similar results. Subgroup analyses and sensitivity analyses to explore potential heterogeneity showed consistent results.

Conclusion
FPG variability may be a novel risk factor for osteoporotic fractures independent of risk factors in the general population without diabetes.
Sex-specific Disruption of the Prairie Vole Hypothalamus by Developmental Exposure to a Flame Retardant Mixture
Authors: Gillera Sagi Enicole A , Marinello William P , Cao Kevin T , Horman Brian M , Stapleton Heather M , Patisaul Heather B 
Published: May 2021

Abstract
Prevalence of neurodevelopmental disorders (NDDs) with social deficits is conspicuously rising, particularly in boys. Flame retardants (FRs) have long been associated with increased risk, and prior work by us and others in multiple species has shown that developmental exposure to the common FR mixture Firemaster 550 (FM 550) sex-specifically alters socioemotional behaviors including anxiety and pair bond formation. In rats, FRs have also been shown to impair aspects of osmoregulation. Because vasopressin (AVP) plays a role in both socioemotional behavior and osmotic balance we hypothesized that AVP and its related nonapeptide oxytocin (OT) would be vulnerable to developmental FM 550 exposure. We used the prairie vole (Microtus ochrogaste) to test this because it is spontaneously prosocial. Using siblings of prairie voles used in a prior study that assessed behavioral deficits resulting from developmental FM 550 exposure across 3 doses, here we tested the hypothesis that FM 550 sex-specifically alters AVP and OT neuronal populations in critical nuclei, such as the paraventricular nucleus (PVN), that coordinate those behaviors, as well as related dopaminergic (determined by tyrosine hydroxylase (TH) immunolabeling) populations. Exposed females had fewer AVP neurons in the anterior PVN and more A13 TH neurons in the zona incerta than controls. By contrast, in FM 550 males, A13 TH neuron numbers in the zona incerta were decreased but only in 1 dose group. These results expand on previous work showing evidence of endocrine disruption of OT/AVP pathways, including to subpopulations of PVN AVP neurons that coordinate osmoregulatory functions in the periphery.
Neuroendocrine Basis for Disrupted Ovarian Cyclicity in Female Mice During Chronic Undernutrition
Authors: Kreisman Michael J , Tadrousse Kirollos S , McCosh Richard B , Breen Kellie M 
Published: May 2021

AbstractChronic undernutrition is a type of metabolic stress that impairs reproduction in multiple species. Although energy balance and female reproductive capacity is recognized as tightly coupled, the neuroendocrine loci and molecular mechanisms that mediate ovarian cycle dysfunction during chronic undernutrition in adult females remain poorly understood. Here, we present a series of studies in which we tested the hypothesis that inhibition of kisspeptin (Kiss1) neurons, which are critical for controlling luteinizing hormone (LH) pulses and the preovulatory LH surge in females, underlies the impairment of the ovarian cycle by undernutrition. We first investigated the effect of chronic undernutrition (70% of unrestricted feed intake) on estrous cyclicity in intact female c57bl6 mice. Undernutrition caused a rapid cessation of ovarian cyclicity during the 2-week treatment, suppressing ovarian steroidogenesis and inhibiting ovulation. Using 2 well-defined estradiol-replacement paradigms, we directly tested the hypothesis that undernutrition inhibits Kiss1 neurons in the arcuate nucleus (ARCKiss1), which are required for LH pulses and in the anteroventral periventricular nucleus (AVPVKiss1), which are necessary for LH surge secretion. Undernutrition prevented LH pulses and impaired ARCKiss1 neuronal activation, using c-Fos as a marker, in ovariectomized females subcutaneously implanted with a pellet containing a diestrus-like level of estradiol. In addition, undernutrition completely blocked the estradiol-induced LH surge and diminished Kiss1 messenger RNA abundance, without decreasing estradiol receptor α (Erα), in micropunches of the AVPV. Collectively, these studies demonstrate that undernutrition disrupts ovarian cyclicity in females via impairment both of ARCKiss1 control of LH pulses and AVPVKiss1 induction of the LH surge.
Endothelial Insulin Receptors Promote VEGF-A Signaling via ERK1/2 and Sprouting Angiogenesis
Authors: Walker Andrew M N , Warmke Nele , Mercer Ben , Watt Nicole T , Mughal Romana , Smith Jessica , Galloway Stacey , Haywood Natalie J , Soomro Taha , Griffin Kathryn J , Wheatcroft Stephen B , Yuldasheva Nadira Y , Beech David J , Carmeliet Peter , Kearney Mark T , Cubbon Richard M 
Published: May 2021

AbstractEndothelial insulin receptors (Insr) promote sprouting angiogenesis, although the underpinning cellular and molecular mechanisms are unknown. Comparing mice with whole-body insulin receptor haploinsufficiency (Insr+/-) against littermate controls, we found impaired limb perfusion and muscle capillary density after inducing hind-limb ischemia; this was in spite of increased expression of the proangiogenic growth factor Vegfa. Insr+/- neonatal retinas exhibited reduced tip cell number and branching complexity during developmental angiogenesis, which was also found in separate studies of mice with endothelium-restricted Insr haploinsufficiency. Functional responses to vascular endothelial growth factor A (VEGF-A), including in vitro angiogenesis, were also impaired in aortic rings and pulmonary endothelial cells from Insr+/- mice. Human umbilical vein endothelial cells with shRNA-mediated knockdown of Insr also demonstrated impaired functional angiogenic responses to VEGF-A. VEGF-A signaling to Akt and endothelial nitric oxide synthase was intact, but downstream signaling to extracellular signal-reduced kinase 1/2 (ERK1/2) was impaired, as was VEGF receptor-2 (VEGFR-2) internalization, which is required specifically for signaling to ERK1/2. Hence, endothelial insulin receptors facilitate the functional response to VEGF-A during angiogenic sprouting and are required for appropriate signal transduction from VEGFR-2 to ERK1/2.
Does Cardiopulmonary Testing Help Predict Long-Term Survival After Esophagectomy?
Authors: Chmelo Jakub , Khaw Rachel A. , Sinclair Rhona C. F. , Navidi Maziar , Phillips Alexander W. 
Published: May 2021

Abstract
Background
Esophagectomy is associated with a high rate of morbidity and mortality. Preoperative cardiopulmonary fitness has been correlated with outcomes of major surgery. Variables derived from cardiopulmonary exercise testing (CPET) have been associated with postoperative outcomes. It is unclear whether preoperative cardiorespiratory fitness of patients undergoing esophagectomy is associated with long-term survival. This study aimed to evaluate whether any of the CPET variables routinely derived from patients with esophageal cancer may aid in predicting long-term survival after esophagectomy.

Methods
Patients undergoing CPET followed by trans-thoracic esophagectomy for esophageal cancer with curative intent between January 2013 and January 2017 from single high-volume center were retrospectively analyzed. The relationship between predictive co-variables, including CPET variables and survival, was studied with a Cox proportional hazard model. Receiver operation curve (ROC) analysis was performed to find cutoff values for CPET variables predictive of 3-year survival.

Results
The study analyzed 313 patients. The ventilatory equivalent for carbon dioxide (VE/VCO2) at the anerobic threshold was the only CPET variable independently predictive of long-term survival in the multivariable analysis (hazard ratio [HR], 1.049; 95% confidence interval [CI], 1.011–1.088; p = 0.011). Pathologic stages 3 and 4 disease was the other co-variable found to be independently predictive of survival. An ROC analysis of the VE/VCO2 failed to demonstrate a predictive cutoff value of 3-year survival (area under the curve, 0.564; 95% CI, 0.499–0.629; p = 0.056).

Conclusions
A high VE/VCO2 before esophagectomy for malignant disease is an independent predictor of long-term survival and may be an important variable for clinicians to consider when counseling patients.
Using administrative health data for palliative and end of life care research in Ireland: potential and challenges
Authors: Kelly Maria , O'Brien Katie M , Hannigan Ailish 
Published: May 2021

Background: This study aims to examine the potential of currently available administrative health and social care data for palliative and end-of-life care (PEoLC) research in Ireland. Objectives include to i) identify data sources for PEoLC research ii) describe the challenges and opportunities of using these and iii) evaluate the impact of recent health system reforms and changes to data protection laws. Methods: The 2017 Health Information and Quality Authority catalogue of health and social care datasets was cross-referenced with a recognised list of diseases with associated palliative care needs. Criteria to assess the datasets included population coverage, data collected, data dictionary and data model availability, and mechanisms for data access. Results: Nine datasets with potential for PEoLC research were identified, including death certificate data, hospital episode data, pharmacy claims data, one national survey, four disease registries (cancer, cystic fibrosis, motor neurone and interstitial lung disease) and a national renal transplant registry. The ad hoc development of the health system in Ireland has resulted in i) a fragmented information infrastructure resulting in gaps in data collections particularly in the primary and community care sector where much palliative care is delivered, ii) ill-defined data governance arrangements across service providers, many of whom are not part of the publically funded health service and iii) systemic and temporal issues that affect data quality. Initiatives to improve data collections include introduction of i) patient unique identifiers, ii) health entity identifiers and iii) integration of the Eircode postcodes. Recently enacted general data protection and health research regulations will clarify legal and ethical requirements for data use. Conclusions: Ongoing reform initiatives and recent changes to data privacy laws combined with detailed knowledge of the datasets, appropriate permissions, and good study design will facilitate future use of administrative health and social care data for PEoLC research in Ireland.
Framing superbugs - testing whether advocacy frames change attitudes, intention or behaviour using an online randomised control experiment
Authors: Metcalfe Daniel , Aldalooj Esraa , Thakur Matthew , Clements Lara 
Published: May 2021

Background: Antimicrobial resistance (AMR) presents a significant threat to global health, requiring multifaceted action by individuals and policymakers. Advocates must persuade others to act. Making communication about AMR more effective could plausibly increase support for action. The Wellcome Trust-funded ‘Reframing Resistance’ project used communications research to develop framing recommendations for the language practitioners use to describe AMR. The aim of this study was to explore how this language influenced attitudes and behaviours towards AMR. Methods: This study was a randomised trial to evaluate the effects of different styles of AMR framing language upon attitudinal and behavioural measures. Participants (n=1,934) were recruited in October 2019 using an on-line tool called “Prolific” and randomly assigned to review five variations of AMR narratives: four experimental frames which incorporated different combinations of language recommended by the framing guidelines, or a control frame without these features, taken from UN AMR communications. Participants were then asked a series of attitudinal and behavioural questions in relation to the AMR narrative they reviewed. Attitudes were measured using five-point Likert-type scales and behaviours were measured using binary variables. Descriptive analysis was used to explore respondents’ characteristics and multivariable logistic regression models were used to establish independent associations between AMR frames and respondents’ attitudes and behaviours. Results: Participants who reviewed narratives that followed framing language guidelines were more likely to donate money or sign a petition, and rated narratives as more usable and important than participants who reviewed the control framing. Conclusions: While larger trials with more diverse participants are needed to confirm generalisability, these results suggest that applying framing to communications could help advocates of AMR to drive action. Furthermore, the study reinforces the value of randomised studies to empirically test the impact of frames upon behaviour and indicates the potential for a more extensive programme of research.
Indicadores antropométricos y consumo alimentario de personal de salud según su turno laboral, cronotipo y calidad del sueño
Authors: Hernández Rangel Arlene Jamín , Rivera Macías Lorena Guadalupe , López Ortiz María Montserrat 
Published: May 2021

Introducción: alteraciones en el cronotipo y la calidad del sueño se han asociado con la desincronización del reloj circadiano, estudiadas como posible causa de la aparición de enfermedades crónicas como obesidad. El objetivo fue identificar la asociación entre los indicadores antropométricos, porcentaje de grasa corporal y consumo alimentario con el turno laboral, cronotipo y calidad del sueño de personal de salud de un hospital de segundo nivel de atención. Materiales y Métodos: se tomaron medidas antropométricas (peso, talla, circunferencia de cintura y pliegues cutáneos) para determinar IMC y porcentaje de grasa corporal total; se aplicó el Cuestionario de Cronotipo de Munich y el Índice de calidad del sueño de Pittsburg. Resultados: participaron 60 trabajadores, siendo el cronotipo nocturno el predominante (53%). El 80% tiene una moderada calidad del sueño; el 55% tenía sobrepeso y obesidad, y solo el 8.3% presenta porcentaje de grasa corporal normal. En el turno nocturno destacó la mala calidad de dormición (p=0.03) y adaptación de los cronotipos vespertino y nocturno (p=0.03). Los participantes de cronotipo vespertino mostraron los mayores valores de peso corporal (p=0.04). La calidad del sueño no mostró asociación significativa con los cambios en el peso o el porcentaje de grasa corporal. Discusión: los ritmos circadianos alterados incrementan el riesgo de obesidad y otros problemas de salud. Se observa una adaptación del cronotipo al turno en que laboran, moderada calidad del sueño y hábitos de alimentación inadecuada, considerados sincronizadores de los ciclos circadianos, ubicándolos como factores a tomar en cuenta para evitar enfermedades futuras.
An evaluation of medication optimisation following myocardial infarction within a cardiac rehabilitation service
Authors: Norman Jessica 
Published: May 2021

Background/Aims Managing patients' medical risk is a core component of cardiac rehabilitation. However, the optimisation of medical therapy for patients post myocardial infarction has frequently been found to be suboptimal. This article evaluates the evidence-based prescribing practice for patients post myocardial infarction who attended a local cardiac rehabilitation service that included an advanced cardiac rehabilitation nurse. The focus is on dose optimisation of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and beta-blocker therapies. Methods Data were collected retrospectively from 100 patient records at a cardiac rehabilitation service. Explored variables included demographic factors, prescribing rates at hospital discharge, left ventricular function, drug types and doses, and drug optimisation rates and timings. Data regarding the practitioner who carried out the optimisation and any documented reasons for not pursuing further dose titration were also collected. Results The advanced cardiac rehabilitation nurse was well placed to optimise pharmacotherapy post myocardial infarction, although the optimisation process was found to be complex, often requiring an overlapping multidisciplinary team approach. Conclusions Care should be taken not to overlook patients with normal left ventricular function or mild left ventricular impairment post myocardial infarction. More advanced practitioner roles are needed to allow the team to take responsibility for the medication optimisation of all patients post myocardial infarction within the cardiac rehabilitation service. The optimisation time target set by the National Institute for Health and Care Excellence was not always reached, as it was not always feasible to safely optimise medications so quickly.
Giving intravenous iron to patients with symptomatic heart failure is safe and cost effective
Authors: Redfern James , Goode Rachel , Leung Wing Yin , Quarterman Clare , Rao Archana 
Published: May 2021

Aims/Background Heart failure affects approximately 1 million people in the UK, adversely affecting quality of life, functional capacity and cognitive health. Iron deficiency complicates heart failure in approximately 50% of patients. Giving intravenous ferric carboxymaltose has been shown to improve quality of life in patients with heart failure (New York Heart Association class and Kansas City Cardiomyopathy Questionnaire). Methods A quality improvement project was designed to assess the feasibility, safety and cost implications of establishing an intravenous iron service in the authors' centre. Results Between July and December 2019 61 patients who were screened met the inclusion criteria and were administered intravenous ferric carboxymaltose. There were statistically significant improvements in ferritin levels (83.3 ug/litre to 433 ug/litre; P<0.0001), transferrin saturation (18% to 30% P<0.0001) and haemoglobin levels (126 g/litre to 135 g/litre; P<0.01). No demonstrable changes in New York Heart Association class or quality of life scores were noted. The overall financial impact for the trust was income generation of £14 665, a net income of £240 per patient. Conclusions Intravenous iron replacement with ferric carboxymaltose is safe and cost effective, and should be considered in eligible iron-deficient patients with symptomatic heart failure. Integration with another day case intravenous service represented the most logistically simple and economically viable method of service delivery.