bluuebunny/crossref_metadata_2025 huggingface dataset:
Management stock ownership and corporate debt: evidence from an emerging market
Authors: Farhangdoust Shayan , Salehi Mahdi , Molavi Homa
Published: April 2020

Purpose

The purpose of the present paper is to examine the trade-off relationship between managerial ownership and corporate debts and whether this relationship is moderated by ownership structure and corporate tax rates, particularly in a transition and emerging market whose unique institutional characteristics considerably differ from those prevailing both in the West and East markets.

Design/methodology/approach

This research is semi-empirical in terms of method and practical in terms of purpose. The authors test their hypotheses by using simultaneous equations system methodology with two- and three-stages least squares regression (2SLS and 3SLS) and panel data technics on a sample of 952 listed companies on the Tehran Stock Exchange during 2011-2018.

Findings

The findings indicate that, contrary to the current line of research, there is no trade-off relationship between managerial ownership and debt concerning the reduction of agency costs. Likewise, the study finds no convincing evidence that either the controlling shareholder or the corporate tax rate could influence or moderate this interrelationship. The conjecture lies in the fact that the fundamental environmental variations between the Tehran Stock Exchange and the institutional assumptions underpinning the Western models have led to the formation of such unexpected results.

Research limitations/implications

The implications drawn from this study are constrained by two primary limitations. First, the present study is conducted in an Iranian setting; therefore, the data used for the study only contain companies listed on the Tehran Stock Exchange. The utilization of listed companies on the Tehran Stock Exchange is likely to affect the generalizability of the study in an international context. Second, in this study, we were unable to extend the sample time period because of some major deficiencies in the Tehran Stock Exchange library and its supplementary software. The usage of an extended time period could have provided more generalizable results. However, extended time period, per se, may impair the validity of the results as well.

Originality/value

Because the fundamental institutional assumptions underpinning the Western and even East Asia capital structure models are not valid in the institutional environment of Iran, the findings of this study could provide substantial implications for the understanding of agency costs and capital structure literature. These significant institutional and ownership differences are the factors affecting firms’ leverage and capital choice decisions. Indeed, this study has laid some groundwork upon which a more detailed evaluation of the Iranian firms’ capital structure could be based. In addition, the examination of such relations may provide the ground for sound decision-making by various interested users of financial and accounting information.
Reduction of bisphenol A by Lactobacillus acidophilus and Lactobacillus plantarum in yoghurt
Authors: Taghizadeh Moghaddam Sara , Javadi Afshin , Matin Amir Abbas
Published: April 2020

The present study aimed to evaluate the effects of Lactobacillus acidophilus and L. plantarum on the concentration of bisphenol A in yoghurt as a food model. The bisphenol A was extracted from samples using a  hollow fibre liquid‐phase microextraction method, followed by analysis using HPLC. The concentration of bisphenol A was also analysed during four weeks of yoghurt storage. L. plantarum and L. acidophilus decreased the level of bisphenol A in yoghurt by 82.8% and 43.44%, respectively. At the end of the storage period, the reduction level of bisphenol A by L. plantarum (95.30%) was higher than that of L. acidophilus (90.77%).
Emulsification properties of sodium caseinate‐based conjugates with selected polysaccharides
Authors: Kumar Sathish M H , Sabikhi Latha , Lamba Heena
Published: April 2020

Sodium caseinate (SC) was conjugated with polysaccharides, viz. maltodextrin (MD), pectin (P) and gum arabic (GA) at protein:polysaccharide weight ratio of 1:2, 1:1 and 2:1. The emulsifying properties and other relevant chemical properties of these conjugates were compared. The visible colour change, SDS‐PAGE analysis and available reducing groups confirmed greater conjugation in SC‐MD conjugate than the SC‐GA and SC‐P conjugates. SC‐P conjugate at the weight ratio of 1:2 exhibited the best emulsifying properties (emulsifying activity – 46.7%, emulsion stability – 7 days at 5 ± 1 °C storage) and had better solubility (33.5%) near the iso‐electric pH.
Eco‐Schemes and Private Sustainability Initiatives: Creating Synergies
Authors: Poppe Krijn , Koutstaal Hannah
Published: April 2020

The eco‐schemes proposed by the European Commission for the new Common Agricultural Policy (CAP) have the potential to make agriculture more sustainable and climate smart. Based on Dutch policy advice we suggest basing the implementation on food systems thinking and to align public eco‐schemes with private initiatives. Dutch policy seeks to create a circular agricultural system by 2030. As such, policy measures must contribute towards ‘closing leakages in material flows, cutting emissions and reducing wastage of biomass throughout the whole food system’. This corresponds with the objectives of the new CAP. Member States can transfer budget from the basic income support to the eco‐schemes relatively easily, but the one year contracts proposed by the Commission would not ensure continuity for farmers. Farmers are incentivised first and foremost by markets and other food chain actors and it would therefore be more attractive to couple eco‐schemes with private labelling systems, via a common integrated points system with performance indicators. Providers of sustainability schemes could apply for equivalence with eco‐schemes. Farmers participating in an approved sustainability scheme would then, under the principle of compliance by default, automatically be given the possibility to take part in the equivalent eco‐scheme. Management and oversight of compliance would be the responsibility of the organisation offering the sustainability scheme. This would have the benefit of reducing administrative costs.
Mesenteric lymphadenopathy is a key to diagnosis of radiologically challenging pulmonary lymphoma
Authors: Lu Pei‐Hsuan , Huang Chung‐Yao , Jhou Zong‐Yi , Huang Wei‐Ming , Chen Chia‐Hung , Huang Chun‐Chao
Published: April 2020

Extranodal marginal zone B‐cell lymphoma (EMZBL), previously known as mucosa‐associated lymphoid tissue lymphoma, is the most common type of marginal zone B‐cell lymphomas. Primary pulmonary lymphomas only constitute 0.5% of primary lung cancer, but 90% of these are EMZBLs. Primary pulmonary lymphomas share similar imaging features with secondary pulmonary lymphomas. Imaging diagnosis is challenging because many benign and other malignant lung lesions can display similar features. Here, we demonstrate a 70‐year‐old male case with lung tumors and only mesenteric lymphadenopathy, which was eventually diagnosed as advanced pulmonary EMZBL with involvement of the mesenteric lymph nodes and bone marrow. Pulmonary masses have a wide differential diagnosis, but concurrent isolated mesenteric lymphadenopathy might be a radiological clue to pulmonary lymphoma.

Key points

Concurrent isolated mesenteric lymphadenopathy might be a radiological clue to pulmonary lymphoma.

For nonspecific lung tumors, additional abdominal computed tomography (CT) scan might be helpful for diagnosis of possible lymphoma.
Restoration of functional sperm production in irradiated pubertal rhesus monkeys by spermatogonial stem cell transplantation
Authors: Shetty Gunapala , Mitchell Jennifer M. , Meyer Jennifer M. , Wu Zhuang , Lam Truong N.A. , Phan Thien T. , Zhang Jie , Hill Lorraine , Tailor Ramesh C. , Peters Karen A. , Penedo Maria C. , Hanna Carol , Orwig Kyle E. , Meistrich Marvin L.
Published: April 2020

Background

In male pre‐pubertal cancer patients, radiation and chemotherapy impact future fertility by eradication of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but only a small percentage of spermatozoa produced were of donor origin. Transient hormone suppression with a GnRH antagonist (GnRH‐ant) enhanced spermatogenic recovery from transplanted SSCs.

Objectives

To evaluate donor‐derived and endogenous spermatogenic recovery after SSC transplantation into irradiated monkeys and to test whether hormone suppression around the time of transplantation facilitates spermatogenic recovery.

Materials and methods

Testes of 15 adult rhesus monkeys were irradiated with 7 Gy and 4 months later transplanted, to one of the testes, with cryopreserved testicular cells containing SSCs from unrelated monkeys. Monkeys were either treated with GnRH‐ant for 8 weeks before transplantation, GnRH‐ant from 4 weeks before to 4 weeks after transplantation, or with no GnRH‐ant. Tissues were harvested 10 months after transplantation.

Results

Two of the 15 monkeys, a control and a pre‐transplantation GnRH‐ant–treated, showed substantially higher levels of testicular spermatogenesis and epididymal sperm output in the transplanted side as compared to the untransplanted. Over 84% of epididymal spermatozoa on the transplanted side had the donor genotype and were capable of fertilizing eggs after intracytoplasmic sperm injection forming morulae of the donor paternal origin. Low levels of donor spermatozoa (~1%) were also identified in the epididymis of three additional monkeys. Transplantation also appeared to enhance endogenous spermatogenesis.

Discussion and conclusion

We confirmed that SSC transplantation can be used for restoration of fertility in male cancer survivors exposed to irradiation as a therapeutic agent. The success rate of this procedure, however, is low. The success of filling the tubules with the cell suspension, but not the GnRH‐ant treatment, was related to the level of colonization by transplanted cells.
Assessing heart rate variability in type 1 diabetes mellitus—Psychosocial stress a possible confounder
Authors: Kristiansen Eva , Wanby Pär , Åkesson Karin , Blomstrand Peter , Brudin Lars , Thegerström Johanna
Published: April 2020

Background

Autonomic neuropathy (AN) commonly arises as a long‐term complication in diabetes mellitus and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram recordings. Psychosocial stress also affects HRV and could be one of several confounders for cardiac AN. The present work investigated the impact of psychosocial stress on HRV in individuals with type 1 diabetes mellitus (T1DM) and assessed the use of salivary cortisol as a biomarker for psychosocial stress in this context.

Methods

A total of 167 individuals 6–60 years old (113 with T1DM and 54 healthy controls) underwent 24‐hr ECG recordings with HRV analysis. Salivary cortisol was sampled thrice during the registration day. Perceived psychosocial stress along with other factors of possible importance for the interpretation of HRV was documented in a diary.

Results

Heart rate variability (high‐frequency power during sleep) was reduced (p < .05) with older age, longer diabetes duration, higher mean glucose levels, physical inactivity, and perceived psychosocial stress. Salivary cortisol levels in the evening were increased (p < .05) in women in ovulation phase, in individuals with preceding hypoglycemia or with hyperglycemia. The amplitude of salivary cortisol was reduced (p < .05) with the presence of perceived psychosocial stress, but only in adult healthy controls, not in individuals with diabetes.

Conclusion

Psychosocial stress might be a confounder for reduced HRV when diagnosing cardiac AN in T1DM. Salivary cortisol is, however, not a useful biomarker for psychosocial stress in diabetes since the physiological stress of both hypoglycemia and hyperglycemia seems to overrule the effect of psychosocial stress on cortisol.
Impact of a digital medicine programme on hepatitis C treatment adherence and efficacy in adults at high risk for non‐adherence
Authors: Sulkowski Mark , Luetkemeyer Annie F. , Wyles David L. , Martorell Claudia , Muir Andrew , Weisberg Ilan , Gordon Stuart C. , McLain Richard , Huhn Gregory
Published: April 2020

Background

Direct‐acting anti‐virals (DAA) are highly effective for hepatitis C virus (HCV) treatment, but perceived risks of medication non‐adherence may restrict access to care. Digital medicine programme (DMP) has improved adherence and outcomes for some conditions.

Aims

To conduct a prospective, single‐arm, open‐label study across the United States to assess the impact of DMP on adherence and efficacy in adults with chronic HCV infection at high risk for non‐adherence.

Methods

Eligible participants were placed on the DMP to evaluate real‐time adherence; primary outcome was sustained virological response (SVR) at ≥10 weeks post‐treatment.

Results

Between August 2017 and April 2019, 288 participants (Medicaid, 64.9%; psychiatric disorders, 61.1%; homeless, 9.4%) received DAAs for 8‐12 weeks (sofosbuvir/velpatasvir or ledipasvir, 45%; glecaprevir/pibrentasvir, 55%). SVR was achieved in 99.1% of 218 participants who had HCV RNA assessed at ≥10 weeks post‐treatment; of the 70 participants who did not have SVR assessed, 17 had SVR4 with HCV RNA assessed at a median (IQR; interquartile range) 5.6 weeks (4.1, 7.9) post‐treatment; one completed treatment but did not have HCV RNA assessed, and 52 discontinued treatment early without assessment. Overall, the primary analysed participants (n = 218) actively used the DMP for median (range) 92.9% (12.5%, 100%) of their prescribed treatment time, and overall pill‐taking adherence was 95.0% (57.1%, 100%). Participants reported the programme was useful and easy to use through satisfaction surveys.

Conclusions

HCV treatment with DMP was accepted by patients and clinicians and may support HCV treatment outcomes among patients at high risk for treatment non‐adherence (Clinical trials.gov NCT03164902).
DNA methylation level in blood and relations to breast cancer, risk factors and environmental exposure in Greenlandic Inuit women
Authors: Wielsøe Maria , Tarantini Letizia , Bollati Valentina , Long Manhai , Bonefeld‐Jørgensen Eva Cecilie
Published: April 2020

Several studies have found aberrant DNA methylation levels in breast cancer cases, but factors influencing DNA methylation patterns and the mechanisms are not well understood. This case–control study evaluated blood methylation level of two repetitive elements and selected breast cancer‐related genes in relation to breast cancer risk, and the associations with serum level of persistent organic pollutants (POPs) and breast cancer risk factors in Greenlandic Inuit. DNA methylation was determined using bisulphite pyrosequencing in blood from 74 breast cancer cases and 80 controls. Using first tertile as reference, the following was observed. Positive associations for ATM in second tertile (OR: 2.33, 95% CI: 1.04; 5.23) and ESR2 in third tertile (OR: 2.22, 95% CI: 0.97; 5.05) suggest an increased breast cancer risk with high DNA methylation. LINE‐1 methylation was lower in cases than controls. In third tertile (OR: 0.42, 95% CI: 0.18; 0.98), associations suggest in accordance with the literature an increased risk of breast cancer with LINE‐1 hypomethylation. Among controls, significant associations between methylation levels and serum level of POPs and breast cancer risk factors (age, body mass index, cotinine level) were found. Thus, breast cancer risk factors and POPs may alter the risk through changes in methylation levels; further studies are needed to elucidate the mechanisms.
Prognostic value of indoleamine 2,3 dioxygenase in patients with higher‐risk myelodysplastic syndromes treated with azacytidine
Authors: Müller‐Thomas Catharina , Heider Michael , Piontek Guido , Schlensog Martin , Bassermann Florian , Kirchner Thomas , Germing Ulrich , Götze Katharina S. , Rudelius Martina
Published: April 2020

Hypomethylating agents (HMAs) are widely used in patients with higher‐risk myelodysplastic syndromes (MDS) not eligible for stem cell transplantation; however, the response rate is <50%. Reliable predictors of response are still missing, and it is a major challenge to develop new treatment strategies. One current approach is the combination of azacytidine (AZA) with checkpoint inhibitors; however, the potential benefit of targeting the immunomodulator indoleamine‐2,3‐dioxygenase (IDO‐1) has not yet been evaluated. We observed moderate to strong IDO‐1 expression in 37% of patients with high‐risk MDS. IDO‐1 positivity was predictive of treatment failure and shorter overall survival. Moreover, IDO‐1 positivity correlated inversely with the number of infiltrating CD8+ T cells, and IDO‐1+ patients failed to show an increase in CD8+ T cells under AZA treatment. In vitro experiments confirmed tryptophan catabolism and depletion of CD8+ T cells in IDO‐1+ MDS, suggesting that IDO‐1 expression induces an immunosuppressive microenvironment in MDS, thereby leading to treatment failure under AZA treatment. In conclusion, IDO‐1 is expressed in more than one‐third of patients with higher‐risk MDS, and is predictive of treatment failure and shorter overall survival. Therefore, IDO‐1 is emerging as a promising predictor and therapeutic target, especially for combination therapies with HMAs or checkpoint inhibitors.
Gene expression of HIF‐1α and VEGF in response to hypoxia in sickle cell anaemia: Influence of hydroxycarbamide
Authors: Pedrosa Alano M. , Lemes Romélia P. G.
Published: April 2020

Hypoxia and hemoglobin S polymerization are two triggers responsible for initiating erythrocyte sickling and the consequent clinical sickle cell anemia (SCA) events. The objective of this study was to investigate the expression of hypoxia‐responsive genes in SCA, testing for correlation with the clinical–laboratorial characteristics of the patient and hydroxyurea therapy. Our results showed, for the first time, a significantly increased expression of HIF‐1α and VEGF genes in patients with SCA and an inverse dose–response relationship with hydroxyurea therapy. These results suggest that hypoxic stress may be involved in both the severity of SCA and its response to treatment.
Accurate quantification of urinary metabolites for predictive models manifest clinicopathology of renal cell carcinoma
Authors: Sato Tomonori , Kawasaki Yoshihide , Maekawa Masamitsu , Takasaki Shinya , Shimada Shuichi , Morozumi Kento , Sato Masahiko , Kawamorita Naoki , Yamashita Shinichi , Mitsuzuka Koji , Mano Nariyasu , Ito Akihiro
Published: April 2020

Using surgically resected tissue, we identified characteristic metabolites related to the diagnosis and malignant status of clear cell renal cell carcinoma (ccRCC). Specifically, we quantified these metabolites in urine samples to evaluate their potential as clinically useful noninvasive biomarkers of ccRCC. Between January 2016 and August 2018, we collected urine samples from 87 patients who had pathologically diagnosed ccRCC and from 60 controls who were patients with benign urological conditions. Metabolite concentrations in urine samples were investigated using liquid chromatography‐mass spectrometry with an internal standard and adjustment based on urinary creatinine levels. We analyzed the association between metabolite concentration and predictability of diagnosis and of malignant status by multiple logistic regression and receiver operating characteristic (ROC) curves to establish ccRCC predictive models. Of the 47 metabolites identified in our previous study, we quantified 33 metabolites in the urine samples. Multiple logistic regression analysis revealed 5 metabolites (l‐glutamic acid, lactate, d‐sedoheptulose 7‐phosphate, 2‐hydroxyglutarate, and myoinositol) for a diagnostic predictive model and 4 metabolites (l‐kynurenine, l‐glutamine, fructose 6‐phosphate, and butyrylcarnitine) for a predictive model for clinical stage III/IV. The sensitivity and specificity of the diagnostic predictive model were 93.1% and 95.0%, respectively, yielding an area under the ROC curve (AUC) of 0.966. The sensitivity and specificity of the predictive model for clinical stage were 88.5% and 75.4%, respectively, with an AUC of 0.837. In conclusion, quantitative analysis of urinary metabolites yielded predictive models for diagnosis and malignant status of ccRCC. Urinary metabolites have the potential to be clinically useful noninvasive biomarkers of ccRCC to improve patient outcomes.
A molecular dynamics approach on the Y393C variant of protein disulfide isomerase A1
Authors: Madero‐Ayala Pablo A. , Mares‐Alejandre Rosa E. , Ramos‐Ibarra Marco A.
Published: April 2020

Human protein disulfide isomerase A1 (PDIA1) shows both catalytic (i.e., oxidoreductase) and non‐catalytic (i.e., chaperone) activities and plays a crucial role in the oxidative folding of proteins within the endoplasmic reticulum. PDIA1 dysregulation is a common trait in numerous pathophysiological conditions, including neurodegenerative disorders and cancerous diseases. The 1178A>G mutation of the human PDIA1‐encoding gene is a non‐synonymous single nucleotide polymorphism detected in patients with Cole‐Carpenter syndrome type 1 (CSS1), a particularly rare bone disease. In vitro studies showed that the encoded variant (PDIA1 Y393C) exhibits limited oxidoreductase activity. To gain knowledge on the structure–function relationship, we undertook a molecular dynamics (MD) approach to examine the structural stability of PDIA1 Y393C. Results showed that significant conformational changes are the structural consequence of the amino acid substitution Tyr>Cys at position 393 of the PDIA1 protein. This structure‐based study provides further knowledge about the molecular origin of CCS1.
Changes in treatment needs of hypoparathyroidism during pregnancy and lactation: A case series
Authors: Hartogsohn Etki A. R. , Khan Aliya A. , Kjærsulf Line Underbjerg , Sikjaer Tanja , Hussain Sharjil , Rejnmark Lars
Published: April 2020

Objective

As only sparse data are available, we aimed to investigate whether needs for activated vitamin D and calcium supplements change in women with hypoparathyroidism during pregnancy and lactation and risk of pregnancy‐related complications.

Design

Retrospective review of medical records.

Patients

Twelve Danish and Canadian patients with chronic hypoparathyroidism who completed 17 pregnancies.

Measurements

Data were extracted on plasma levels of ionized calcium (P‐Ca2+) and doses of active vitamin D and calcium supplements during pregnancy (N = 14) and breastfeeding (N = 10). Data on pregnancy complications were available from all 17 pregnancies.

Results

Although average doses of active vitamin D (P = .91) and calcium supplements (P = .43) did not change during pregnancies, a more than 20% increase or decrease in dose of active vitamin D was needed in more than half of the pregnancies in order to maintain normocalcemia. Five women (36%) developed hypercalcaemia by the end of pregnancy or start of lactation. Median levels of P‐Ca2+ increased from 1.20 mmol/L in third trimester to 1.32 mmol/L in the post‐partum period (P < .03). Accordingly, the average dose of active vitamin D was significantly reduced (P = .01) during lactation compared to 3rd trimester. One woman developed severe pre‐eclampsia (6%). Further four pregnancies (24%) were complicated by polyhydramnios, dystocia and/or perinatal hypoxia. Ten pregnancies required caesarean delivery (59%) with four (24%) being performed as an emergency.

Conclusion

In chronic hypoparathyroidism, close medical monitoring of the mother with frequent adjustments in the dose of calcium and active vitamin D is required during pregnancy and lactation in order to maintain normocalcemia. Patients should be offered close obstetric care to handle potential perinatal complications. We recommend evaluating the neonate immediately after birth and notifying the paediatrician of the risks of hypocalcaemia as well as hypercalcaemia in the neonate.
Characteristics of adult‐ compared to childhood‐onset type 1 diabetes
Authors: Casu A. , Kanapka L. G. , Foster N. C. , Hirsch I. B. , Laffel L. M. , Shah V. N. , DeSalvo D. J. , Lyons S. K. , Vendrame F. , Aleppo G. , Mastrandrea L. D. , Pratley R. E. , Rickels M. R. , Peters A. L. ,   for the T1D Exchange Clinic Network
Published: April 2020

Aims

To compare diagnosis characteristics, diabetes management and comorbidities in a population diagnosed with type 1 diabetes in childhood with those in a similar population diagnosed in adulthood to identify disease differences related to the age of diabetes onset.

Methods

This analysis was performed using the T1D Exchange Clinic Registry, a cross‐sectional survivor cohort. Retrospectively collected characteristics were compared across the following age‐at‐diagnosis groups: <10, 10–17, 18–24, 25–39 and ≥40 years.

Results

The entire cohort included 20 660 participants [51% female, median (interquartile range) age 18 (14–36) years, 82% non‐Hispanic white]. Diabetic ketoacidosis at diagnosis was more common among those with onset in childhood. Participants diagnosed as adults were more likely to be overweight/obese at diagnosis and to have used oral agents preceding type 1 diabetes diagnosis (57%). Current insulin pump use was less frequent in participants diagnosed at older ages. Current glycaemic control, measured by HbA1c, insulin requirements and use of a continuous glucose monitor were not different by age at diagnosis. Coeliac disease was the only comorbidity that was observed to have a different frequency by age at diagnosis, being more common in the participants diagnosed at a younger age.

Conclusions

These results show differences and similarities between type 1 diabetes diagnosed in childhood vs adulthood; notably, there was a tendency for there was a higher frequency of diabetic ketoacidosis at onset in children and a higher frequency of use of oral antidiabetes agents in adults. The data indicate that there is little distinction between the clinical characteristics and outcomes of type 1 diabetes diagnosed in childhood vs adulthood. Optimizing glycaemic control remains a challenge in all age groups, with lower use of insulin pumps impacting those diagnosed as adults.
Student Predispositions as Predictors of Dissent Behaviors in Supply Chain Courses*
Authors: Johnson Laquanda Leaven , Kelly Stephanie
Published: April 2020

This study investigates how student dissent behaviors are affected by student predispositions (i.e., math anxiety and self‐efficacy) in supply chain related courses. The data support a model in which students’ vengeful dissent behaviors are indirectly induced by these predispositions through the mediation of perceived immediacy. It is critical for instructors to understand the relationship between these variables to help improve the classroom environment for students, which this study helps to accomplish. Instructors of quantitative courses may need to engage students with predispositions in communication outside of the classroom to foster effective relationship building away from an environment that triggers students’ anxiety.
Chemerin predicts carotid intima‐media thickening in severe obesity
Authors: Ministrini Stefano , Ricci Maria Anastasia , Nulli Migliola Elisa , De Vuono Stefano , D’Abbondanza Marco , Paganelli Maria Teresa , Vaudo Gaetano , Siepi Donatella , Lupattelli Graziana
Published: April 2020

Background and aims

Chemerin is an adipokine with an emerging role in the crosstalk between adipose tissue and immune system. It is overexpressed in severe obesity, affects adipogenesis and glucose homeostasis and it correlates with early vascular damage. The aim of this study is to investigate the correlation between circulating levels of chemerin and early vascular damage in subjects with severe obesity, before and after laparoscopic sleeve gastrectomy (LSG).

Methods

Fifty‐six obese subjects eligible for LSG were enrolled in the study. The following parameters were evaluated: body mass index (BMI), glycemia, insulinemia, glycated haemoglobin, lipid profile, plasma chemerin levels and carotid intima‐media thickness (cIMT). Fifty‐four subjects were evaluated 1 year after the intervention.

Results

Univariate analysis showed a direct and significant correlation between chemerin and waist circumference, insulin resistance, glycated haemoglobin and cIMT. Chemerin was a better predictor of intima‐media thickening than waist circumference and glycated haemoglobin at the ROC curve analysis, with a cut‐off value for chemerin of 140 ng/mL. The reduction of chemerin is independently associated with the reduction of cIMT and the improvement of insulin sensitivity after LSG.

Conclusion

Chemerin is involved in the development and progression of early vascular damage and insulin resistance in subjects with severe obesity, and in their healing after bariatric surgery. Chemerin could also have a role in the assessment of cardiovascular risk in subjects with severe obesity.
Dysregulation of astrocytic mitochondrial function following exposure to a dopamine metabolite: Implications for Parkinson's disease
Authors: Bagnoli Enrico , Diviney Tara , FitzGerald Una
Published: April 2020

The monoamine oxidase metabolite of dopamine, 3,4‐dihydroxyphenylacetaldehyde (DOPAL), is hypothesized to induce neurodegeneration in Parkinson's disease (PD). However, DOPAL's effect on astrocyte function is less well known. Furthermore, the conflicting protective and pathological roles of resting and reactive astrocytes in Parkinson's disease have led to astrocytes being characterized as a double‐edged sword in this disease. Using the Neu7 rat astrocyte cell line as a model of astrocyte behaviour, we aimed to evaluate the effect of DOPAL on astrocyte viability, reactivity and mitochondrial function. Astrocytic production of hydrogen peroxide and nitrite was indicative of reactivity. Mitochondrial function was assessed using extracellular flux analysis with the Seahorse extracellular flux analysis system and mitochondria membrane potential dye. We found that DOPAL significantly reduces Neu7 viability, induces apoptosis, decreases mitochondrial performance and increases oxidative and nitrative stress in a concentration‐dependent manner. This is the first in vitro study showing that DOPAL is directly toxic to astrocytes. We predict that the loss of astrocyte viability and the gain of neurotoxic effects, like the increase in oxidative stress, will have detrimental consequences to neuronal viability. This research supports the hypothesis that DOPAL is a contributing factor to PD progression and provides a basis for future research to elucidate the mechanism of DOPAL‐induced astrocyte toxicity in PD.
Severe psychological distress among patients with epilepsy during the COVID‐19 outbreak in southwest China
Authors: Hao Xiaoting , Zhou Dong , Li Zhe , Zeng Guojun , Hao Nanya , Li Enzhi , Li Wenjing , Deng Aiping , Lin Mintao , Yan Bo
Published: April 2020

Objective

To compare the severity of psychological distress between patients with epilepsy and healthy controls during the COVID‐19 outbreak in southwest China, as well as identify potential risk factors of severe psychological distress among patients with epilepsy.

Methods

This cross‐sectional case‐control study examined a consecutive sample of patients older than 15 years treated at the epilepsy center of West China Hospital between February 1 and February 29, 2020. As controls, sex‐ and age‐matched healthy visitors of inpatients (unrelated to the patients) were also enrolled during the same period. Data on demographics and attention paid to COVID‐19 were collected by online questionnaire, data on epilepsy features were collected from electronic medical records, and psychological distress was evaluated using the 6‐item Kessler Psychological Distress Scale (K‐6). Potential risk factors of severe psychological distress were identified using multivariate logistic regression.

Results

The 252 patients and 252 controls in this study were similar along all demographic variables except family income. Patients with epilepsy showed significantly higher K‐6 scores than healthy controls and spent significantly more time following the COVID‐19 outbreak (bothP < .001). Univariate analyses associated both diagnosis of drug‐resistant epilepsy and time spent paying attention to COVID‐19 with severe psychological distress (defined as K‐6 score >12; bothP ≤ .001). Multivariate logistic regression identified two independent predictors of severe psychological distress: time spent paying attention to COVID‐19 (odds ratio [OR] = 1.172, 95% confidence interval [CI] = 1.073‐1.280) and diagnosis of drug‐resistant epilepsy (OR = 0.283, 95% CI = 0.128‐0.623).

Significance

During public health outbreaks, clinicians and caregivers should focus not only on seizure control but also on mental health of patients with epilepsy, especially those with drug‐resistant epilepsy. K‐6 scores > 12 indicate severe psychological distress. This may mean, for example, encouraging patients to engage in other activities instead of excessively following media coverage of the outbreak.
Barrier lipid composition and response to plasma lipids: A direct comparison of mouse dorsal back and ear skin
Authors: Martins Cardoso Renata , Absalah Samira , Van Eck Miranda , Bouwstra Joke A.
Published: April 2020

The skin of the ear and the back are frequently selected sites in skin research using mouse models. However, distinct responses to treatment have been described between these two sites in several studies. Despite the crucial role of the stratum corneum (SC) in the skin barrier function of both dorsal back and ear skin, it remains unclear whether differences in lipid composition might underlie altered responses. Here, we compared the skin morphology and the barrier lipid composition of the ear with the back skin of wild‐type mice. The ear contained more corneocyte layers in the SC and its barrier lipid composition was enriched with sphingosine ceramide subclasses, especially the short ones with a total chain length of 33‐34 carbons. The free fatty acid (FFA) profile in the ear skin shifted towards shorter chains, significantly reducing the mean chain length to 23.3 vs 24.7 carbons in the back skin. In line, FFA species in the ear displayed a twofold increase in unsaturation index (P < .001). Gene expression in the ear skin revealed low expression of genes involved in lipid synthesis and uptake, indicating a reduced metabolic activity. Finally, the effects of hypercholesterolaemia on SC FFA composition was compared in ear and back skin of apolipoprotein E knockout (APOE−/−) mice. Interestingly, the FFA profile inAPOE−/−ear skin was minimally affected, while the FFA composition in the back skin was markedly changed in response to hypercholesterolaemia. In conclusion, ear and back skin have distinct barrier lipids and respond differently to elevated plasma cholesterol.
Aberrant ETS‐1 signalling impedes the expression of cell adhesion molecules and matrix metalloproteinases in non‐segmental vitiligo
Authors: Srivastava Niharika , Bishnoi Anuradha , Mehta Sakshi , Rani Seema , Kumar Ravinder , Bhardwaj Supriya , Sendhil Kumaran Muthu , Keshavamurthy Vinay , Gupta Sarika , Parsad Davinder
Published: April 2020

Cell adhesion is a complex process that involves multiple molecules on the cell surface (ie cell adhesion molecules [CAMs]), surrounding cells and extracellular matrix (ECM). Repigmentation in vitiligo is dependent on the ECM remodelling and cellular migration, primarily attributed to the transcriptional activation of matrix metalloproteinases (MMPs). In this study, we aimed to demonstrate the role of ETS‐1 signalling in the regulation of MMPs and CAMs. Therefore, we studied the expression of ETS‐1, MMPs (MMP‐2, MMP‐9) and CAMs including E‐cadherin, ITGA‐1 and ICAM‐1 in vitiligo (both active and stable) ex vivo. Further, we compared melanocyte morphology and their adhesion towards collagen IV and laminin between control and vitiligo groups in vitro. Also, we silenced ETS‐1 in melanocytes cultured from control skin and observed post‐silencing effect on above‐mentioned MMPs and CAMs. We perceived absent ETS‐1 and significantly reduced CAMs and MMPs in vitiligo compared with normal skin. Scanning electron microscopy (SEM) revealed a translucent material surrounding individual melanocytes in stable vitiligo and controls, whereas active vitiligo melanocytes demonstrated loss of this extracellular substance. Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS‐1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absent ETS‐1 expression in both stable and active non‐segmental vitiligo seems to impede the expression of CAMs, apart from MMPs, probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease.
The Practice of Family Life Education: Toward an Implementation Framework
Authors: Ballard Sharon M.
Published: April 2020

The practice of family life education (FLE) includes the methods and strategies that family life educators use when implementing programs, along with processes and contextual factors that influence effective program implementation. The focus of this article is on the evidence‐based practices (i.e., best practices) used in the effective delivery of FLE programs. These best practices are organized into an implementation framework designed to guide and support FLE practice and thereby improve program outcomes. The FLE Implementation Framework includes the following components: (a) program environment, (b) program participants, (c) program design and delivery, and (d) program facilitator. Best practices for each component, as well as guiding questions and evaluation strategies, are provided.
Serum glucose and phosphorus concentrations during continuous renal replacement therapy using commercial replacement solutions with or without phosphorus
Authors: Crowley Kaitlin E. , DeGrado Jeremy R. , Charytan David M.
Published: April 2020

Introduction

Continuous venovenous hemofiltration (CVVH) is a common practice in the intensive care unit often associated with electrolyte derangements. Recently, our institution added a phosphate dialysis solution, Phoxillum®, to our formulary as an option for CVVH fluid in addition to the bicarbonate‐based Prismasol® products available. We sought to evaluate the impact of Phoxillum in patients who required CVVH when compared to Prismasol with regard to phosphate and glucose management.

Methods

This was a single‐center, retrospective, observational cohort analysis approved by Partners Health Care System Institutional Review Board that included patients who received a minimum of 24 hours of either Prismasol 4/2.5 or Phoxillum for CVVH from February 2017 to November 2017. Phosphate and glucose levels were monitored daily while on CVVH. Prevalence of hypoglycemia (glucose <70 mg/dL), hyperglycemia (glucose >180 mg/dL), hypophosphatemia (phosphate <2.5 mg/dL), and hyperphosphatemia (phosphate >4.3 mg/dL) were collected in terms of days of occurrence while on CVVH. Oral and intravenous phosphate repletion requirements were collected for all patients.

Findings

Hypophosphatemia occurred more frequently while patients were receiving Prismasol as compared to Phoxillum (130 [24.9%] vs. 13 [6.2%], rate ratio [RR] 0.20 [95% confidence interval—CI = 0.10–0.42, P < 0.0001]), and consequently there was a numerically lower need for intravenous phosphorous repletion in the Phoxillum group (RR = 0.58, 95% CI [0.26, 1.30], P = 0.19]. There was a numerically higher incidence of hyperphosphatemia while patients were on Phoxillum therapy as compared to Prismasol (78 [37%] vs. 145 [27.7%], RR 1.25 [95% CI = 0.84, 1.86, P = 0.27]). There was no difference between the Phoxillum and Prismasol groups in terms of hypoglycemia or hyperglycemia. There was no notable difference in the cost found between the two therapies.

Discussion

The findings suggest that the use of Phoxillum for CVVH may be associated with decreased incidence of hypophosphatemia and a potentially decreased need for phosphate repletion in patients who require CVVH.
Effects of dielectric barrier discharge cold plasma treatments on degradation of anilazine fungicide and quality of tomato (Lycopersicon esculentum Mill) juice
Authors: Ali Murtaza , Cheng Jun‐Hu , Sun Da‐Wen
Published: April 2020

The effect of cold plasma (CP) treatment on the degradation of anilazine fungicide in tomato juice was investigated. Anilazine solution of 5 mg/L was added to tomato juice samples and treated using a dielectric barrier discharge (DBD) cold plasma (CP) system with exposure times of 0, 1, 2, 3, 4 and 5 min. The gas chromatography‐mass spectrometry (GC‐MS) results showed that the reduction in anilazine in the tomato juice achieved 47% and 65% after treatments for 4 min and 5 min, respectively. The concentration of anilazine decreased significantly (P ≤ 0.05) with an increase in treatment time. Analysis of the quality attributes of tomato juice treated for 5 min showed that the quality of the treated juice remained acceptable with a slight decrease in pH from 4.28 to 4.18, an increase in total soluble solids (TSS) from 5.70 to 6.70 ◦Brix, an increase in the browning index from 2.35 to 4.54, a very low (but within the acceptable limit) total colour difference, and only minor changes in antioxidant capacity, total flavonoid and total phenolic content, as compared with the control samples. These results indicated that DBD cold plasma treatment could be an effective and rapid technique to degrade pesticide residues for the fruit juice industry.
The relationship between pancreas steatosis and the risk of metabolic syndrome and insulin resistance in Chinese adolescents with concurrent obesity and non‐alcoholic fatty liver disease
Authors: Chiyanika Chileka , Chan Dorothy F. Y. , Hui Steve C. N. , So Hung‐kwan , Deng Min , Yeung David K. W. , Nelson E. Anthony S. , Chu Winnie C. W.
Published: April 2020

Background

The incidence of childhood obesity and associated comorbidities are on an increasing trend worldwide. More than 340 million children and adolescents aged between 5 and 19 years old were overweight or had obesity in 2016, from which over 124 million children and adolescents (6% of girls and 8% of boys) had obesity.

Objective

To describe the relationship between pancreas steatosis, body fat and the risk of metabolic syndrome, insulin resistance in Hong Kong Chinese adolescents with both obesity and non‐alcoholic fatty liver disease (NAFLD).

Methods

Fifty two adolescents with obesity and NAFLD were analysed (14‐18 years), stratified into fatty and non‐fatty pancreas groups using chemical shift encoded MRI‐pancreas proton density fat fraction ≥5%. Pancreatic, abdominal subcutaneous adipose tissue (SAT)/visceral adipose tissue (VAT) volumes, biochemical and anthropometric parameters were measured. Mann‐Whitney U test, multiple linear/binary logistic regression analyses and odds ratios were used.

Results

Fifty percent had fatty pancreas, 38% had metabolic syndrome and 81% had insulin resistance. Liver proton density fat fraction (PDFF) and VAT were independent predictors of insulin resistance (P = .006, .016). Pancreas and liver PDFF were both independent predictors of beta cells dysfunction (P = .015, .050) and metabolic syndrome (P = .021, .041). Presence of fatty pancreas in obesity was associated with insulin resistance (OR = 1.58, 95% CI = 0.39‐6.4) and metabolic syndrome (OR = 1.70, 95% CI = 0.53‐5.5).

Conclusion

A significant causal relationship exists between fatty pancreas, fatty liver, body fat and the risk of developing metabolic syndrome and insulin resistance.

Key Points

Fatty pancreas is a common finding in adolescents with obesity, with a prevalence rate of 50% in this study cohort.

Liver PDFF and VAT are independent predictors of insulin resistance while pancreas PDFF and liver PDFF are independent predictors of both beta cells dysfunction and metabolic syndrome.

Presence of fatty pancreas at imaging should not be considered as a benign finding but rather as an imaging biomarker of emerging pancreatic metabolic and endocrine dysfunction.
Low urine pH predicts new onset of diabetes mellitus during a 10‐year period in men: BOREAS‐DM1 study
Authors: Higashiura Yukimura , Tanaka Marenao , Furuhashi Masato , Koyama Masayuki , Ohnishi Hirofumi , Numata Keita , Hisasue Takashi , Hanawa Nagisa , Moniwa Norihito , Miura Tetsuji
Published: April 2020

Aims/Introduction

A low level of urine pH (U‐pH) has been reported to be associated with metabolic disorders. However, the relationship between the incidence of diabetes mellitus and U‐pH has not yet been fully addressed.

Materials and Methods

We investigated the relationship between U‐pH and the development of diabetes mellitus during a 10‐year period in a general population of individuals who received annual health examinations in 2006 (n = 28,990). After exclusion of individuals with missing data, and those with diabetes mellitus and/or chronic kidney disease at baseline, a total of 12,476 individuals (men/women: 8,027/4,449) who received health examinations at least once during the period from 2007 to 2016 were recruited. The recruited individuals were divided into four groups according to their U‐pH levels: groups of U‐pH ≤5.0, 5.5, 6.0 and ≥6.5.

Results

During a 10‐year period, 521 men (6.5%) and 132 women (3.0%) had new onset of diabetes mellitus. The cumulative incidence of diabetes mellitus was 7.5% (men/women: 9.3%/4.4%) per 100 person‐years. The hazard ratios (HRs) in the U‐pH ≤5.0 (HR 1.93) and U‐pH 5.5 groups (HR 1.46) were significantly higher than that in the U‐pH ≥6.5 group as a reference for men, but not for women. After adjustment of age, obesity, fasting glucose, smoking and alcohol drinking habits, family history of diabetes mellitus, and use of drugs for hypertension and dyslipidemia, HR in the U‐pH ≤5.0 group (HR 1.39) was significantly higher than that in the U‐pH ≥6.5 group for men, but not for women.

Conclusions

Low U‐pH predicts new onset of diabetes mellitus in a general population of men.
Skeletal muscle mass and risk of advanced adenoma in surveillance colonoscopy
Authors: Yoo Kyung Mo , Yang Hyo‐Joon , Park Soo‐Kyung , Jung Yoon Suk , Park Jung Ho , Park Dong Il , Sohn Chong Il
Published: April 2020

Background and Aim

Sarcopenia has been suggested to be associated with chronic inflammation and insulin resistance. This study aimed to evaluate whether low muscle mass is associated with the incidence and recurrence of advanced colorectal adenoma.

Methods

We conducted a cohort study including 14 701 participants who underwent first‐time screening colonoscopy between 2003 and 2012 and follow‐up colonoscopy until 2017. Skeletal muscle mass was measured using a bioelectrical impedance analyzer and divided by body weight to calculate the skeletal muscle mass index (SMI).

Results

During a median 47 (interquartile range, 35–58) months of follow‐up, overall and advanced adenoma developed in 2988 (20.3%) and 207 (1.41%) participants, respectively. In multivariate analysis using models adjusted for baseline adenoma risk, lifestyle factors, markers for insulin resistance and chronic inflammation, and metabolic syndrome, decreasing SMI quartiles were associated with increased risk of occurrence of advanced adenoma and overall adenoma. The adjusted hazard ratios (95% confidence intervals) comparing SMI quartiles 3, 2, and 1 to quartile 4 were 1.57 (1.03–2.41), 1.22 (0.78–1.92), and 1.77 (1.13–2.76), respectively, for advanced adenoma (Pfor trend = 0.049) and 1.05 (0.95–1.17), 1.09 (0.98–1.21), and 1.26 (1.13–1.41), respectively, for overall adenoma (Pfor trend < 0.001).

Conclusions

In this large cohort with long‐term colonoscopy follow‐up, low relative muscle mass was associated with increased risk of occurrence of advanced adenoma and overall adenoma at follow‐up colonoscopy, independent of metabolic and inflammatory markers. Timely and thorough surveillance colonoscopy may be emphasized in such populations.