bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in MAGEL2 and L1CAM Are Associated With Congenital Hypopituitarism and Arthrogryposis
Authors: Gregory Louise C , Shah Pratik , Sanner Juliane R F , Arancibia Monica , Hurst Jane , Jones Wendy D , Spoudeas Helen , Le Quesne Stabej Polona , Williams Hywel J , Ocaka Louise A , Loureiro Carolina , Martinez-Aguayo Alejandro , Dattani Mehul T 
Published: August 2019

AbstractContextCongenital hypopituitarism (CH) is rarely observed in combination with severe joint contractures (arthrogryposis). Schaaf-Yang syndrome (SHFYNG) phenotypically overlaps with Prader-Willi syndrome, with patients also manifesting arthrogryposis. L1 syndrome, a group of X-linked disorders that include hydrocephalus and lower limb spasticity, also rarely presents with arthrogryposis.ObjectiveWe investigated the molecular basis underlying the combination of CH and arthrogryposis in five patients.PatientsThe heterozygous p.Q666fs*47 mutation in the maternally imprinted MAGEL2 gene, previously described in multiple patients with SHFYNG, was identified in patients 1 to 4, all of whom manifested growth hormone deficiency and variable SHFYNG features, including dysmorphism, developmental delay, sleep apnea, and visual problems. Nonidentical twins (patients 2 and 3) had diabetes insipidus and macrocephaly, and patient 4 presented with ACTH insufficiency. The hemizygous L1CAM variant p.G452R, previously implicated in patients with L1 syndrome, was identified in patient 5, who presented with antenatal hydrocephalus.ResultsHuman embryonic expression analysis revealed MAGEL2 transcripts in the developing hypothalamus and ventral diencephalon at Carnegie stages (CSs) 19, 20, and 23 and in the Rathke pouch at CS20 and CS23. L1CAM was expressed in the developing hypothalamus, ventral diencephalon, and hindbrain (CS19, CS20, CS23), but not in the Rathke pouch.ConclusionWe report MAGEL2 and L1CAM mutations in four pedigrees with variable CH and arthrogryposis. Patients presenting early in life with this combined phenotype should be examined for features of SHFYNG and/or L1 syndrome. This study highlights the association of hypothalamo-pituitary disease with MAGEL2 and L1CAM mutations.
Circulating Oxytocin Is Genetically Determined and Associated With Obesity and Impaired Glucose Tolerance
Authors: Weingarten Mark Florian Joachim , Scholz Markus , Wohland Tobias , Horn Katrin , Stumvoll Michael , Kovacs Peter , Tönjes Anke 
Published: August 2019

AbstractContextDespite the emerging evidence on the role of oxytocin (OXT) in metabolic diseases, there is a lack of well-powered studies addressing the relationship of circulating OXT with obesity and diabetes.Objectives and DesignHere, we measured OXT in a study cohort (n = 721; 396 women, 325 men; mean age ± SD, 47.7 ± 15.2 years) with subphenotypes related to obesity, including anthropometric traits such as body mass index [BMI (mean ± SD), 26.8 ± 4.6 kg/m2], waist-to-hip ratio (WHR; 0.88 ± 0.09), blood parameters (glucose, 5.32 ± 0.50 mmol/L; insulin, 5.3 ± 3.3 µU/mL), and oral glucose tolerance test to clarify the association with OXT. We also tested in a genome-wide association study (GWAS) whether the interindividual variation in OXT serum levels might be explained by genetic variation.ResultsThe OXT concentration was increased in subjects with elevated BMI and positively correlated with WHR, waist circumference, and triglyceride levels. The OXT concentration in subjects with BMI <25 kg/m2 was significantly lower (n = 256; 78.6 pg/mL) than in subjects with a BMI between 25 and 30 kg/m2 (n = 314; 98.5 pg/mL, P = 6 × 10−6) and with BMI >30 kg/m2 (n = 137; 106.4 pg/mL, P = 8 × 10−6). OXT levels were also positively correlated with plasma glucose and insulin and were elevated in subjects with impaired glucose tolerance (P = 4.6 × 10−3). Heritability of OXT was estimated at 12.8%. In a GWAS, two hits in linkage disequilibrium close (19 kb) to the OXT reached genome-wide significant association (top-hit rs12625893, P = 3.1 × 10−8, explained variance 3%).ConclusionsOur data show that OXT is genetically affected by a variant near OXT and is associated with obesity and impaired glucose tolerance.
Effects of Nicotinamide Riboside on Endocrine Pancreatic Function and Incretin Hormones in Nondiabetic Men With Obesity
Authors: Dollerup Ole L , Trammell Samuel A J , Hartmann Bolette , Holst Jens J , Christensen Britt , Møller Niels , Gillum Matthew P , Treebak Jonas T , Jessen Niels 
Published: August 2019

Abstract

Objective
Augmenting nicotinamide adenine dinucleotide (NAD+) metabolism through dietary provision of NAD+ precursor vitamins translates to improved glucose handling in rodent models of obesity and diabetes. Preclinical evidence suggests that the NAD+/SIRT1 axis may be implicated in modulating important gut-related aspects of glucose regulation. We sought to test whether NAD+ precursor supplementation with nicotinamide riboside (NR) affects β-cell function, α-cell function, and incretin hormone secretion as well as circulating bile acid levels in humans.

Design
A 12-week randomized, double-blind, placebo-controlled, parallel-group trial in 40 males with obesity and insulin resistance allocated to NR at 1000 mg twice daily (n = 20) or placebo (n = 20). Two-hour 75-g oral glucose tolerance tests were performed before and after the intervention, and plasma concentrations of glucose, insulin, C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were determined. β-Cell function indices were calculated based on glucose, insulin, and C-peptide measurements. Fasting plasma concentrations of bile acids were determined.

Results
NR supplementation during 12 weeks did not affect fasting or postglucose challenge concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, or GIP, and β-cell function did not respond to the intervention. Additionally, no changes in circulating adipsin or bile acids were observed following NR supplementation.

Conclusion
The current study does not provide evidence to support that dietary supplementation with the NAD+ precursor NR serves to impact glucose tolerance, β-cell secretory capacity, α-cell function, and incretin hormone secretion in nondiabetic males with obesity. Moreover, bile acid levels in plasma did not change in response to NR supplementation.
Higher Serum Sex Hormone–Binding Globulin Levels Are Associated With Incident Cardiovascular Disease in Men
Authors: Gyawali Prabin , Martin Sean A , Heilbronn Leonie K , Vincent Andrew D , Jenkins Alicia J , Januszewski Andrzej S , Adams Robert J T , O’Loughlin Peter D , Wittert Gary A 
Published: August 2019

AbstractContextSex hormone–binding globulin (SHBG) levels are associated with cardiovascular disease (CVD) risk factors. However, prospective data on the association between SHBG levels and CVD events are sparse, with conflicting results.ObjectivesTo examine associations between serum SHBG, total testosterone (TT), and incident CVD and CVD-related mortality in middle-aged to elderly men.Design and MethodsData on 2563 community-dwelling men (35 to 80 years) were obtained from participants in the Men Androgen Inflammation Lifestyle Environment and Stress cohort. The analytic sample included 1492 men without baseline (2002 to 2007) CVD and with fasted morning serum SHBG and TT available at both baseline and follow-up (2007 to 2010) and without medications affecting TT or SHBG. Associations of baseline SHBG and TT, with incident CVD and CVD mortality, were analyzed using logistic regression for incident CVD and Cox proportional hazard regression for CVD mortality, adjusting for established CVD risk factors.ResultsIn multivariable models, elevated baseline SHBG and lower baseline TT were independently associated with incident CVD (SHBG: OR, 1.54; 95% CI, 1.15 to 2.06 per SD increase in SHBG, P = 0.003; TT: OR, 0.71; 95% CI, 0.52 to 0.97 per SD decrease in TT; P = 0.03). A decrease in TT between time points was associated with incident CVD (OR, 0.72; 95% CI, 0.56 to 0.92; P = 0.01). Neither SHBG nor TT was significantly associated with all-age CVD mortality [hazard ratio (HR), 0.69; 95% CI, 0.29 to 1.63; P = 0.40; and HR, 0.60; 95% CI, 0.28 to 1.26; P = 0.18, respectively].ConclusionsAmong all men and men >65 years, elevated SHBG and lower TT were independently associated with both a greater risk of CVD and an increased CVD mortality risk.
Androgens During the Reproductive Years: What Is Normal for Women?
Authors: Skiba Marina A , Bell Robin J , Islam Rakibul M , Handelsman David J , Desai Reena , Davis Susan R 
Published: August 2019

AbstractObjectiveWhether serum androgen levels can identify women with “androgen insufficiency” or “androgen excess” is unresolved; thus, what constitutes “normal” remains uncertain. We sought to determine whether androgens, including 11-oxygenated C19 steroids, vary with age, menstrual cycle, or body mass index (BMI), during the reproductive years.Design and SettingCross-sectional study recruited from eastern Australian states.ParticipantsA total of 588 women, aged 18 to 39 years, who were not pregnant, lactating, or using systemic hormone therapy, with regular menstrual cycles and no previous diagnosis of polycystic ovarian syndrome.Main Outcome MeasuresSex steroids measured using liquid chromatography-tandem mass spectrometry.ResultsTestosterone and androstenedione concentrations were significantly higher during the menstrual cycle mid- and luteal phases than in the early follicular phase, with median values across the cycle of 0.34 nmol/L (range, 0.04 to 1.01) and 1.97 nmol/L (range, 0.53 to 7.89), respectively. No cyclical variations were found in dehydroepiandrosterone (DHEA; 4.91 nmol/L; range, 0.08 to 23.51), 11-ketoandrostenedione (11KA; 7.99 nmol/L; range, 0.07 to 31.67), or 11-ketotestosterone (11KT; 1.27 nmol/L; range, 0.03 to 7.61). Overweight women had lower median testosterone (P < 0.05), DHEA (P < 0.05), and 11KA (P < 0.01) levels than normal-weight women. All C19 steroids were significantly lower (P < 0.01) in those aged 35 to 39 years than in those aged 18 to 25 years. The median 11KA/androstenedione (4.3:1) and 11KT/testosterone (3.9:1) ratios did not change with age, after adjustment for BMI and cycle stage.ConclusionsWe have demonstrated that 11KA and 11KT are stable across the menstrual cycle and make major quantitative contributions to the circulating androgen pool. All C19 androgens declined with age before menopause; hence, age-specific reference ranges are required for the interpretation of androgen levels in premenopausal women.
Diagnostic Accuracy of the Aldosterone–to–Active Renin Ratio for Detecting Primary Aldosteronism
Authors: Pilz Stefan , Keppel Martin H , Trummer Christian , Theiler-Schwetz Verena , Pandis Marlene , Borzan Valentin , Pittrof Matthias , Obermayer-Pietsch Barbara , Grübler Martin R , Verheyen Nicolas , Stepan Vinzenz , Meinitzer Andreas , Voelkl Jakob , März Winfried , Tomaschitz Andreas 
Published: August 2019

Abstract

Context
The aldosterone–to–active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but prospective study data on its sensitivity and specificity are sparse.

Objective
To investigate the diagnostic accuracy of the AARR for detecting PA.

Design
Prospective diagnostic accuracy study.

Setting
This study was conducted from February 2009 to August 2015 at the outpatient clinic of the Department of Endocrinology and Diabetology of the Medical University of Graz, Austria.

Participants
Four hundred patients with arterial hypertension who were referred to a tertiary care center for screening for endocrine hypertension.

Intervention
Participants had a determination of the AARR (index test) and a second AARR determination followed by a saline infusion test (SIT) after 2 to 6 weeks. PA was diagnosed in individuals with any AARR ≥3.7 ng/dL/µU/mL [including a plasma aldosterone concentration (PAC) of ≥9 ng/dL] who had a PAC ≥10 ng/dL after the SIT. We did not substantially alter antihypertensive drug intake.

Main Outcome Measures
Primary outcome was the receiver-operating characteristic (ROC) curve of the AARR in diagnosing PA.

Results
A total of 382 participants were eligible for analyses; PA was diagnosed in 18 (4.7%) patients. The area under the ROC curve of the AARR in detecting PA was 0.973 (95% CI, 0.956 to 0.990). Sensitivity and specificity for a positive AARR in diagnosing PA were 100% (95% CI, 81.5% to 100.0%) and 89.6% (95% CI, 86.0% to 92.5%), respectively.

Conclusions
The AARR has good diagnostic accuracy for detecting PA.
Higher C-Peptide Level During Glucose Clamp Is Associated With Muscle Insulin Resistance in Nonobese Japanese Men
Authors: Kaga Hideyoshi , Tamura Yoshifumi , Takeno Kageumi , Kakehi Saori , Someya Yuki , Funayama Takashi , Furukawa Yasuhiko , Suzuki Ruriko , Sugimoto Daisuke , Kadowaki Satoshi , Nishitani-Yokoyama Miho , Shimada Kazunori , Daida Hiroyuki , Aoki Shigeki , Giacca Adria , Kanazawa Akio , Kawamori Ryuzo , Watada Hirotaka 
Published: August 2019

Abstract

Context
Circulating C-peptide is generally suppressed by exogenous insulin infusion. However, steady-state serum C-peptide (SSSC) levels during hyperinsulinemic-euglycemic clamp in obese subjects are higher than in healthy subjects, which may contribute to hyperinsulinemia to compensate for insulin resistance. Even in healthy subjects, interindividual variations in SSSC levels are present; however, the characteristics of subjects with high SSSC levels in those populations have not been fully elucidated.

Objective
To investigate the clinical parameters associated with interindividual variations in SSSC levels in apparently healthy, nonobese Japanese men.

Design and Participants
We studied 49 nonobese (BMI < 25 kg/m2), healthy Japanese men. We evaluated SSSC and insulin sensitivity using hyperinsulinemic-euglycemic clamp with tracer. Intrahepatic lipid (IHL) was measured using proton magnetic resonance spectroscopy.

Results
We divided subjects into high and low SSSC groups based on the median SSSC value and compared their clinical parameters. Compared with the low SSSC group, the high SSSC group had IHL accumulation, impaired muscle insulin sensitivity, reduced insulin clearance, and hyperinsulinemia during a 75-g oral glucose tolerance test (OGTT). All of these factors were significantly correlated with SSSC.

Conclusions
In healthy, nonobese men, higher SSSC was associated with impaired muscle insulin sensitivity, IHL accumulation, and hyperinsulinemia during OGTT. These findings suggest that higher endogenous insulin secretion during hyperinsulinemia, along with reduced insulin clearance, may be an early change to maintain metabolic status in the face of moderate muscle insulin resistance, even in healthy, nonobese men.
Testicular Vein Sampling Can Reveal Gonadotropin-Independent Unilateral Steroidogenesis Supporting Spermatogenesis
Authors: Antonio Leen , Albersen Maarten , Billen Jaak , Maleux Geert , Van Rompuy Anne-Sophie , Coremans Peter , Marcq Philippe , Jørgensen Niels , Vanderschueren Dirk 
Published: August 2019

Abstract
Suppressed gonadotropins combined with high-normal serum testosterone concentrations in oligozoospermic men suggest either use of exogenous testosterone or presence of a testosterone-producing tumor. We describe the case of a 31-year-old man referred for primary infertility. Gonadotropins were undetectably low, but testosterone and estradiol were in the high-normal range. Semen analysis showed oligoasthenospermia. He denied using exogenous testosterone. Scrotal ultrasound showed microlithiasis and millimetric hypolucent lesions in the left testis but no intratesticular mass. Human chorionic gonadotropin was low. To investigate unilateral hormone secretion, selective testicular venous sampling was performed. Testosterone and estradiol were clearly higher on the left side than on the right (130 vs 26 nmol/L and 1388 vs 62 pmol/L, respectively), with a left spermatic vein–to-periphery gradient of 4.3 for testosterone and 13 for estradiol; there were no similar gradients on the right side. This finding confirms that all sex steroid secretion came from the left testis. The patient was therefore referred for left orchidectomy. Histopathology revealed multifocal seminoma, germ cell neoplasia in situ, and Leydig cell hyperplasia but no choriocarcinoma. However, gonadotrophin levels increased after orchidectomy, indicating that the source of gonadotropin-independent sex steroid secretion was removed. Testosterone and estradiol decreased to the mid-normal range. Sperm concentration improved. This report thus shows that endogenous testosterone secretion in one testicle supports spermatogenesis without measurable levels of gonadotropins. Selective testicular venous sampling is useful to identify the site of unilateral secretion when the clinical picture is inconclusive. However, histopathology could not reveal the factor that stimulated Leydig cell steroidogenesis.
An acute decrease in plasma membrane tension induces macropinocytosis via PLD2 activation
Authors: Loh Julie , Chuang Mei-Chun , Lin Shan-Shan , Joseph Jophin , Su You-An , Hsieh Tsung-Lin , Chang Yu-Chen , Liu Allen P. , Liu Ya-Wen 
Published: August 2019

ABSTRACT
Internalization of macromolecules and membrane into cells through endocytosis is critical for cellular growth, signaling and plasma membrane (PM) tension homeostasis. Although endocytosis is responsive to both biochemical and physical stimuli, how physical cues modulate endocytic pathways is less understood. Contrary to the accumulating discoveries on the effects of increased PM tension on endocytosis, less is known about how a decrease of PM tension impacts on membrane trafficking. Here, we reveal that an acute decrease of PM tension results in phosphatidic acid (PA) production, F-actin and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2]-enriched dorsal membrane ruffling and subsequent macropinocytosis in myoblasts. The PA production induced by decreased PM tension depends on phospholipase D2 (PLD2) activation via PLD2 nanodomain disintegration. Furthermore, the ‘decreased PM tension–PLD2–macropinocytosis’ pathway is prominent in myotubes, reflecting a potential mechanism of PM tension homeostasis upon intensive muscle stretching and relaxation. Together, we identify a new mechanotransduction pathway that converts an acute decrease in PM tension into PA production and then initiates macropinocytosis via actin and PI(4,5)P2-mediated processes.
The relationship between body mass index before pregnancy and the amount of weight that should be gained during pregnancy: A cross-sectional study
Authors: Özdilek Resmiye , Aba Yılda Arzu , Aksoy Sena Dilek , Şık Bulat Aytek , Akpak Yaşam Kemal 
Published: August 2019

Objective: To investigate the adaptation of pregnant women to the recommended weight gain range according to body mass index (BMI) and to determine the factors affecting them.
Methods: This cross-sectional study was performed in a university hospital’s obstetrics and gynecology unit (tertiary center) in Turkey. This study was conducted between March 2018 and August 2018 (6 months) in pregnant women. Pregnant women with chronic disease and receiving treatment during antenatal follow-up, with twin pregnancy, with a fetus with a congenital abnormality, and nutritional disturbance were excluded from the study. Eight hundred twelve pregnant women with normal antenatal follow-up and who volunteered to participate were included in the study.
Results: The mean age of the participants was 27.66±5.05 years. The mean weight and BMI before pregnancy were near standard in all participants. The group with the highest rate of recommended weight gain according to BMI before pregnancy was the group with low weight pregnant women. The ideal weight gain rate in all groups was 32%.
Conclusions: The groups with overweight and obese pregnant women according to BMI before pregnancy had the highest rates of weight gain, above the recommended limits. BMI before pregnancy directly affects weight gain during pregnancy and the importance of pre-pregnancy counseling and weight loss is emphasized once again.
doi: https://doi.org/10.12669/pjms.35.5.133
How to cite this:Ozdilek R, Aba YA, Aksoy SD, Sik BA, Akpak YK. The relationship between body mass index before pregnancy and the amount of weight that should be gained during pregnancy: A cross-sectional study. Pak J Med Sci. 2019;35(5):1204-1209. doi: https://doi.org/10.12669/pjms.35.5.133
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Association of medication administration errors with interruption among nurses in public sector tertiary care hospitals
Authors: - Raja - , - Badil - , - Sajid Ali , - Shaheen Sherali 
Published: August 2019

Objectives: To determine the association of medication administration errors with interruption among nurses working at public sector tertiary care hospitals in Karachi, Pakistan.
Methods: An analytical cross-sectional study was accomplished at two public sector healthcare facilities Civil Hospital, and Dow University Hospital, Karachi. The study was carried out from October 2017 to July 2018 over a period of 10 months. The sample was calculated by using OpenEpi version 3.0. By taking 56.4% of medication administration errors, 5% margin of error and 95% confidence level. The calculated sample size was 204 of both genders. The subjects both male and female nurses having a valid license from Pakistan Nursing Council and one year of clinical experience were enrolled in the study. The subjects were approached by using non-probability purposive sampling method. Validated and adapted questionnaire utilized to gather the data. Data was entered and analyzed by using SPSS version 21.0.
Results: In this study, total 204 nurses were included, almost half (52%) of them were male. Majority of (82.3%) study participants had age between 25-35 years old. There were total 716 medications given by 204 nurses. Out of these, 295 (41.2%) were antibiotics, other common medications were acid-suppressive, analgesic and antiemetic 14.5%, 15.9% and 11.2% respectively. Among all 716 medications, 644 (89.9%) were given intravenously whereas only 6.7% drugs given orally. A significant association has been found between medication administration errors and interruption like talking with other health care personnel, patients or attendant queries, phone calls (p-value=<0.001). Nearly 91% of the study nurses who were interrupted during medication committed medication errors.
Conclusion: It is concluded that there is a significant association between medication administration errors with interruption among nurses.
doi: https://doi.org/10.12669/pjms.35.5.287
How to cite this:Raja, Badil, Ali S, Sherali S. Association of medication administration errors with interruption among nurses in public sector tertiary care hospitals. Pak J Med Sci. 2019;35(5):1318-1321. doi: https://doi.org/10.12669/pjms.35.5.287
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.