bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostate Tumor Cell–Derived IL1β Induces an Inflammatory Phenotype in Bone Marrow Adipocytes and Reduces Sensitivity to Docetaxel via Lipolysis-Dependent Mechanisms
Authors: Herroon Mackenzie K. , Diedrich Jonathan D. , Rajagurubandara Erandi , Martin Carly , Maddipati Krishna R. , Kim Seongho , Heath Elisabeth I. , Granneman James , Podgorski Izabela
Published: September 2019

Adipocyte–tumor cell cross-talk is one of the critical mediators of tumor progression and an emerging facilitator of therapy evasion. Tumor cells that metastasize to adipocyte-rich bone marrow take advantage of the interplay between metabolic and inflammatory pathways to activate prosurvival mechanisms that allow them to thrive and escape therapy. Using in vitro and in vivo models of marrow adiposity, we demonstrate that metastatic prostate carcinoma cells engage bone marrow adipocytes in a functional cross-talk that promotes IL1β expression in tumor cells. Tumor-supplied IL1β contributes to adipocyte lipolysis and regulates a proinflammatory phenotype in adipocytes via upregulation of COX-2 and MCP-1. We further show that the enhanced activity of the IL1β/COX-2/MCP-1 axis and a resulting increase in PGE2 production by adipocytes coincide with augmented hypoxia signaling and activation of prosurvival pathways in tumor cells, revealing a potential mechanism of chemoresistance. The major consequence of this interplay is the reduced response of prostate cancer cells to docetaxel, a phenomenon sensitive to the inhibition of lipolysis.

Implications:

Studies presented herein highlight adipocyte lipolysis as a tumor-regulated metabolic event that engages proinflammatory cross-talk in the microenvironment to promote prostate cancer progression in bone. Understanding the impact of bone marrow adipose tissue on tumor adaptation, survival, and chemotherapy response is fundamentally important, as current treatment options for metastatic prostate cancer are palliative.
Phonetic Transcription for Speech-Language Pathology in the 21st Century
Authors: Stemberger Joseph Paul , Bernhardt Barbara May
Published: September 2019

The past few decades have seen rapid changes in speech-language pathology in terms of technology, information on speech production and perception, and increasing levels of multilingualism in communities. This tutorial provides an overview of phonetic transcription for the modern world, both for work with clients, and for research and training. The authors draw on their backgrounds in phonetics, phonology and speech-language pathology, and their crosslinguistic project in the phonological acquisition of children with typical versus protracted phonological development. Challenges and solutions are presented, as well as resources for further training of students, clinicians and researchers.
Hydrogen Sulfide Ameliorates Cognitive Dysfunction in Formaldehyde-Exposed Rats: Involvement in the Upregulation of Brain-Derived Neurotrophic Factor
Authors: Li Xiang , Zhuang Yuan-Yuan , Wu Lei , Xie Ming , Gu Hong-Feng , Wang Bo , Tang Xiao-Qing
Published: September 2019

Objective: To investigate whether hydrogen sulfide (H2S) counteracts formaldehyde (FA)-induced cognitive defects and whether the underlying mechanism is involved in the upregulation of hippocampal brain-derived neurotrophic factor (BDNF) expression. Methods: The cognitive function of rats was evaluated by the Morris water maze (MWM) test and the novel object recognition test. The content of superoxide dismutase (SOD) and malondialdehyde (MDA) in the hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The neuronal apoptosis in the hippocampal CA1 region was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end (TUNEL) staining. The expression of the BDNF protein was detected by Western blot and immunohistochemistry. Results: We found that sodium hydrosulfide (NaHS, a donor of H2S) significantly reversed the impairment in the function of learning and memory in the MWM test and the novel objective recognition task induced by intracerebroventricular injection of FA. We also showed that NaHS significantly reduced the level of MDA, elevated the level of SOD, and decreased the amount of TUNEL-positive neurons in the hippocampus of FA-exposed rats. Moreover, NaHS markedly increased the expression of hippocampal BDNF in FA-exposed rats. Conclusions: H2S attenuates FA-induced dysfunction of cognition and the underlying mechanism is involved in the reduction of hippocampal oxidative damage and apoptosis as well as upregulation of hippocampal BDNF.
Isoproterenol Disrupts Intestinal Barriers Activating Gut-Liver-Axis: Effects on Intestinal Mucus and Vascular Barrier as Entry Sites
Authors: Sorribas Marcel , de Gottardi Andrea , Moghadamrad Sheida , Hassan Mohsin , Spadoni I. , Rescigno M. , Wiest Reiner
Published: September 2019

Background: The gut-liver-axis presents the pathophysiological hallmark for multiple liver diseases and has been proposed to be modulated during stress and shock. Access to the gut-liver-axis needs crossing of the mucus and gut-vascular barrier. The role of β-adrenoreceptor-activation for both barriers has not been defined and is characterized here. Methods: Splanchnic β-adrenergic stimulation was achieved by chronic intraperitoneal application of isoproterenol via alzet-pump in vivo. The intestinal permeability and gut-vascular barrier function was assessed in ileal loop experiments. The extravasation of predefined sizes of fluorescence isothiocyanate (FITC)-dextran molecules in ileal microcirculation was evaluated by intravital confocal laser endomicroscopy in vivo. Mucus parameters thickness, goblet cell count and mucin-expression were assessed by stereomicroscopy, immunostaining and RNA-sequencing respectively. Ileal lamina propria (LP) as well as mesenteric lymph node mononuclear cells was assessed by FACS. Results: Healthy mice lack translocation of 4 kDa-FITC-dextran from the small intestine to the liver, whereas isoproterenol-treated mice demonstrate pathological translocation (PBT). Mucus layer is reduced in thickness with loss of goblet-cells and mucin-2-staining and -expression in isoproterenol-treated animals under standardized gnotobiotic conditions. Isoproterenol disrupts the gut vascular barrier displaying Ileal extravasation of large-sized 70- and 150 kDa-FITC-dextran. This pathological endothelial permeability and accessibility induced by isoproterenol associates with an augmented expression of plasmalemmal-vesicle-associated-protein-1 in intestinal vessel. Ileal LP after isoproterenol treatment contains more CD11c+-dendritic cells (DC) with increased appearance of CCR7+ DC in mesenteric lymph nodes. Conclusions: Isoproterenol impairs the intestinal muco-epithelial and endothelial-vascular barrier promoting PBT to the liver. This barrier dysfunction on multiple levels potentially can contribute to liver injury induced by catecholamines during states of increased β-adrenergic drive.
Reduction in Heart Rate Variability in Autosomal Dominant Polycystic Kidney Disease
Authors: Lai Silvia , Mangiulli Marco , Perrotta Adolfo M. , Di Lazzaro Giraldi Gianluca , Testorio Massimo , Rosato Edoardo , Cianci Rosario , Gigante Antonietta
Published: September 2019

Introduction: Cardiovascular disease is one of the main causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Autonomic dysfunction is associated with an increased risk for all cardiovascular events in the general population and can be evaluated with heart rate variability (HRV). Objective: To evaluate HRV in ADPKD patients with mild hypertension versus hypertensive patients with organ damage and healthy controls (HC). Materials and Methods: We have enrolled 65 patients: 21 ADPKD patients (10 males), 20 patients with hypertension (14 males), and 24 HC (10 males). Biochemical analysis, clinical evaluation, anthropometric data, intima-media thickness, 24-h ECG Holter recording, and echocardiography were investigated at the time of enrollment. Results: No significant differences in HRV parameters were found between ADPKD with mild hypertension and hypertensive patients with organ damage. The median of HRV variables in time domain as SDNN (global autonomic activity) was significantly lower in ADPKD and hypertensive patients than HC (p < 0.05). In the frequency domain analysis, low frequency (LF), which mainly reflects the sympathetic component, showed higher values in ADPKD and hypertensive patients than HC during the night (p < 0.01). During the night, the sympathovagal balance, LF/high frequency (HF), showed higher values in ADPKD and hypertensive patients than HC (p < 0.0001). Conversely, LF day was lower in ADPKD and hypertensive patients than HC (p < 0.01). HF, which mainly reflects the parasympathetic component, was lower in ADPKD and hypertensive patients during the night than HC (p < 0.0001). Conclusions: HRV reduction is present in ADPKD patients with mild hypertension in the absence of organ damage. The evaluation of sympathovagal balance can provide novel information on the cardiovascular risk in ADPKD patients in addition to classical risk factors.
Red Blood Cell Lifespan Shortening in Patients with Early-Stage Chronic Kidney Disease
Authors: Li Jiu-Hong , Luo Jun-Feng , Jiang Ying , Ma Yong-Jian , Ji Yong-Qiang , Zhu Guo-Liang , Zhou Cong , Chu Hong-Wei , Zhang Hou-De
Published: September 2019

Background: Although reduced red blood cell (RBC) lifespan has been reported to be a contributory factor to anemia in patients with end-stage chronic kidney disease (CKD), there are limited data regarding RBC lifespan in early-stage CKD. Serum erythropoietin (EPO) is considered a primary causative factor of renal anemia. The aims of this study were to compare the RBC lifespan, serum EPO levels, and other renal anemia indicators across CKD-stage groups of patients and to analyze the impacts of etiological factors on renal anemia. Methods: A cohort of 74 non-smoking patients with CKD were enrolled, including 15 in stage 1, 18 in stage 2, 15 in stage 3, 15 in stage 4, and 11 in stage 5. RBC lifespan was determined by CO breath tests. Potential correlations of hemoglobin (Hb) concentration with RBC lifespan, reticulocyte count (Ret), and levels of EPO, ferritin, folic acid, and vitamin B12 were analyzed. Results: CKD progression was associated with decreases in (Hb) and RBC lifespan. RBC lifespan durations in CKD stages 1–5 were 122 ± 50, 112 ± 26, 90 ± 32, 88 ± 28, and 60 ± 24 days, respectively. RBC lifespan means for the stage 3, 4 and 5 groups were significantly shorter than those for the stage 1 and 2 groups. Serum EPO did not differ significantly between the CKD stage groups. (Hb) correlated directly with RBC lifespan (r = 0.372, p = 0.002) and Ret (r = 0.308, p = 0.011), but did not correlate with serum EPO, ferritin, folic acid, or vitamin B12 levels. Conclusions: Reduced RBC lifespan in early-stage CKD, demonstrated in this study, suggests that increased RBC destruction may play a more important etiological role in renal anemia than other indicators in patients with CKD.
Breast Cancer: Reimbursement Policies and Adoption of New Therapeutic Agents by National Health Systems
Authors: Trapani Dario , Curigliano Giuseppe , Eniu Alexandru
Published: September 2019

Background: Breast cancer is a cause of morbidity for more than half a million of patients in Europe, resulting in broad societal impacts that affect patients, families, and societies from a human, emotional, economic, and financial perspective. Expenditure for cancer medicines represents one of the principal driving costs of healthcare. The aim of this review is to describe the European policy and regulatory landscape of innovation uptake in breast oncology – with emphasis on value in cancer healthcare. Summary: In Europe, several reimbursement models or policy tools have been developed by countries to compose their benefit packages. The most commonly applied scheme is the product-specific eligibility model, prioritizing selected medicines and their indications. Mixed models are commonly developed, addressing the protection of more vulnerable people, ensuring protection from impoverishment caused by cancer and containing disparities. However, the risk to incur significant out-of-pocket expenses for essential or newer medicines for cancer is still substantial in Europe, especially in low- and middle-income countries, determining greater financial distress and poorer outcome for patients. Value-based priority setting is an essential mechanism to ensure timely access to the most valuable medicines for breast cancer patients. Estimations of the value of medicines can be provided within health technology assessment services and networks and informed by benefit scales and tools. Key Messages: There is ample room for reciprocal support across the diverse cultural and legal realities in Europe. The aim is common: save cancer patients from premature death by ensuring the timely access to the best care, protecting from financial hardships and distress to leave no cancer patient behind in poverty. Steps are to be taken to promote value-based priority setting, paving the way toward universal health coverage in Europe, where health of people is protected, and affordable best quality care is the only standard pursued and acceptable.
High Risk of Sudden Sensorineural Hearing Loss in Several Autoimmune Diseases according to a Population-Based National Sample Cohort Study
Authors: Jeong Junhui , Lim Hyunsun , Lee Kyuin , Hong Chang Eui , Choi Hyun Seung
Published: September 2019

Objective: We investigated the risk of sudden sensorineural hearing loss (SSNHL) in patients with autoimmune diseases compared with a control group in a population-based study using a National Health Insurance Service National Sample Cohort data from Korea. Methods:We enrolled autoimmune-disease patients who were ≥20 years of age in 2006 into the autoimmune-disease group, and selected a control group with similar demographic characteristics. We tracked the 2 groups from 2006 to 2015 and compared the proportions of patients who developed SSNHL. Results: Of 13,250 patients in the autoimmune-disease group, 145 experienced an SSNHL event (1.09%). Of the 66,250 in the control group, 484 experienced an SSNHL event (0.73%). The SSNHL risk was significantly higher in the autoimmune-disease group than in the control group. SSNHL incidence was significantly higher among patients with antiphospholipid syndrome (APS), multiple sclerosis (MS), rheumatoid arthritis (RA), and connective-tissue diseases including Sjögren syndrome and Behçet disease. In detailed stratified analyses using reinforced additional diagnostic codes, only RA patients had a significantly higher SSNHL incidence than the control group. Conclusion: The association of several autoimmune diseases with SSNHL was evaluated in this large-scale, population-based, big-data study. The risk of SSNHL was significantly higher in patients with APS, MS, RA, and connective-tissue diseases including Sjögren syndrome and Behçet disease than in patients without autoimmune diseases. SSNHL, in particular, was significantly associated with RA according to detailed analyses using reinforced additional diagnostic codes.
Needs Around Dialysis Treatment from Different Perspectives (NADIP): Results of the Exploratory German Multicenter Survey
Authors: Biggar Patrick , Hidde Dennis , Ketteler Markus
Published: September 2019

Background/Aims: In 2015, approximately 70,000 patients with end-stage renal disease were treated chronically with dialysis in Germany. However, there is only sparse information regarding subjective appreciation of the different aspects of extracorporeal renal replacement therapies. This study was performed to gain insight into the needs and appreciation of services in dialysis centers in Germany including the views not only of the patients but also of the caregivers, physicians, and nurses. Methods: A cross-sectional written voluntary questionnaire survey based on the international RAND Kidney Disease Quality of Life Short Form (version 1.3) comprising 510 adult dialysis patients, 274 caregivers, 29 physicians, and 60 nurses in 30 dialysis centers across Germany. Results: Although patients were mostly satisfied with present treatment options, room for improvement exists. Patients were less critical of services than doctors and nurses. Factors such as trustworthy contact with staff at the centers as well as information exchange with other patients and among caregivers play a significant role in the patients’ perception of a high-quality dialysis treatment facility. Therefore, continued cost saving, in particular regarding personnel, may subjectively counteract the objective technical improvements of dialysis. Conclusions: High-quality technical standards are essential for successful dialysis therapy; however, additionally, we recommend an array of communicative and social tools employed by all stakeholders to convey and exchange information and also support subjective well-being. This survey represents one of the largest evaluations to date. The data are also of potential international relevance for non-German health management systems.
Safety of Imatinib Mesylate in a Multicenter Expanded Access Program in Adult Patients with Gastrointestinal Stromal Tumors in the Adjuvant Setting
Authors: Reichardt Peter , Schlemmer Marcus , Delgado Perez Juan R. , Papai Zsuzsanna , Prausova Jana , Melichar Bohuslav , Fumagalli Elena , Barone Carlo , Bauer Sebastian , Pustowka Anette , Crippa Stefania , Castellana Ramon , Quiering Claudia , Le Cesne Axel
Published: September 2019

Background: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors most often caused by activating mutations of the KIT gene. KIT tyrosine kinase inhibitors provide targeted therapy for the underlying genetic mutation, and adjuvant therapy is indicated for patients who are at significant risk of relapse following GIST resection. This is a report of the safety of imatinib in patients with GIST in the adjuvant setting in an expanded access program. Methods: In this multicenter, open-label, single-arm trial, safety was assessed based on the frequency of adverse events (AEs). Results: Three hundred patients were treated and analyzed; 40 patients discontinued treatment. Median overall exposure during the program was 181 days (range 9–420); most patients (260/300 treated) completed the study. Six patients had disease recurrence, 4 of whom discontinued. In line with previously published reports, the most frequent AEs were nausea, diarrhea, and periorbital edema. The AEs were mild to moderate in most cases (76%). Conclusions: These findings are in agreement with the known safety profile of imatinib and confirm the safety of imatinib at 400 mg/day in the adjuvant setting. The incidence of severe AEs was low.
Brush Cytology Performance for the Assessment of Biliopancreatic Strictures
Authors: Pereira Pedro , Morais Rui , Vilas-Boas Filipe , Rodrigues-Pinto Eduardo , Lopes Joanne , Carneiro Fátima , Macedo Guilherme
Published: September 2019

Introduction: Brush cytology is commonly used during endoscopic retrograde cholangiopancreatography for the diagnostic evaluation of biliopancreatic strictures. However, since the overall sensitivity of brush cytology is poor, the exclusion of malignancy is difficult. Recognition of factors related to the patient, technique or lesion may help improve the diagnostic yield of brush cytology. The objective of this study was to evaluate the diagnostic yield of brush cytology in the assessment of biliopancreatic strictures and identify predictive factors associated with a positive diagnosis of malignancy. Methods: Retrospective study that evaluated all consecutive patients that underwent brush cytology for the investigation of biliopancreatic strictures in a tertiary center, between January 2012 and January 2018. Results: One hundred and sixty-five patients that underwent 182 procedures were included. A diagnosis of malignancy was confirmed in 110 patients (66.7%), of whom 62 had positive brush cytology (sensitivity 53.7%, specificity 98.5%, accuracy 69.8%). On the multivariate analysis, age ≥68 years (OR 4.83, 95% CI 1.04–22.37) and lesions suspicious of metastasis on cross-sectional imaging (OR 8.58, 95% CI 1.70–43.38) were independently associated with a positive result. Subanalysis of the patients presenting with these two factors (n = 26) revealed an increase in the diagnostic yield (sensitivity 80.8%). Conclusion: Age ≥68 years and lesions suspicious of metastasis on cross-sectional imaging are independent factors associated with a positive result. Patient selection taking these factors into account may increase the diagnostic yield of brush cytology.
A Clinico-Radiological Study of Cerebral Amyloid Angiopathy-Related Inflammation
Authors: Coulette Sarah , Renard Dimitri , Lehmann Sylvain , Raposo Nicolas , Arquizan Caroline , Charif Mahmoud , Thouvenot Eric , Wacongne Anne , Viguier Alain , Bonneville Fabrice , Allou Thibaut , Boukriche Yassine , Chiper Laura , Blanchet Fourcade Genevieve , Gabelle Audrey , Ducros Anne , Duflos Claire , Labauge Pierre , Menjot de Champfleur Nicolas , Ayrignac Xavier
Published: September 2019

Objective: To describe the clinico-radiological features and long-term prognosis in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri). Methods: Twenty-eight CAA-ri patients were recruited retrospectively from 6 neurological centers. We recorded the clinico-radiological and biological data, at baseline and during follow-up. Baseline characteristics associated with relapse risk and prognosis were assessed. Results: Five patients had pathologically confirmed CAA-ri whereas 23 had probable (n = 21) or possible (n = 2) CAA-ri. The mean age was 72 years; main clinical symptoms included confusion (54%), hemiparesis (36%), and aphasia (29%). Cerebral MRI disclosed a brain parenchymal lesion (89%), which was usually multifocal (82%) and bilateral (89%). It was associated with gadolinium enhancement (84%), small ischemic lesions (39%), cortical superficial siderosis (CSS; 50%), and a high number of microbleeds (mean 240 ± 277). An isolated leptomeningeal involvement was observed in 3 patients with pathological confirmation. Despite a favorable initial evolution after treatment, we observed a 42% risk of relapse, mostly within the first year (83%). After a mean follow-up of 2 years, 29% died and 25% had a marked disability. Disseminated CSS was associated with death. Conclusion: Despite an apparently favorable initial evolution, CAA-ri is characterized by a poor prognosis. Diagnostic criteria should consider patients with isolated leptomeningeal involvement.
Autotaxin Inhibitor Protects from Chronic Allograft Injury in Rat Kidney Allotransplantation
Authors: Cortinovis Monica , Aiello Sistiana , Mister Marilena , Conde-Knape Karin , Noris Marina , Novelli Rubina , Solini Samantha , Rodriguez Ordonez Pamela Y. , Benigni Ariela , Remuzzi Giuseppe
Published: September 2019

Background: Tissue fibrosis is the final common phase of chronic allograft injury, the leading cause of late graft loss in kidney transplantation. Preclinical evidence points to the involvement of lysophosphatidic acid (LPA), a bioactive phospholipid, in the development of renal fibrosis. Objectives: We assessed whether treatment with an orally available inhibitor of autotaxin (ATXi), the main LPA-producing enzyme, could slow the progression of chronic allograft injury in a fully major histocompatibility complex-mismatched rat kidney transplant model and compared its effects with those of the angiotensin-converting enzyme inhibitor lisinopril. Methods: Kidney allograft recipients were given ciclosporin for the first 15 postoperative days to prevent early acute rejection. Thereafter, they received either no treatment or ATXi or lisinopril and were followed for 180 days after transplantation. Results: Renal LPA levels were increased in allograft rats, providing the rationale for using ATXi in this model. Chronic treatment with ATXi or lisinopril limited progressive proteinuria and ameliorated tubulointerstitial fibrosis compared with allograft rats, although the effects were more robust under ATX inhibition. The administration of ATXi, but not lisinopril, attenuated systemic hypertension, reduced intragraft T cell infiltration, and eventually improved renal graft survival. Conclusions: In summary, ATXi had protective effects on indices of chronic allograft injury and could be of therapeutic add-on value in the kidney transplant setting. Notably, an ATX inhibitor is currently being investigated in 2 large phase 3 studies in idiopathic pulmonary fibrosis, underscoring the clinical relevance of our findings.
Blood Microbiota Modification After Myocardial Infarction Depends Upon Low‐Density Lipoprotein Cholesterol Levels
Authors: Amar Jacques , Lelouvier Benjamin , Servant Florence , Lluch Jérôme , Burcelin Rémy , Bongard Vanina , Elbaz Meyer
Published: September 2019

Background

The role of bacteria on the onset of cardiovascular disease has been suggested. Reciprocally, increased intestinal bacterial translocation and bloodstream infection are common comorbidities associated with heart failure and myocardial infarction (
MI
). In this context, the aim of this study was to analyze the blood microbiome in patients shortly after acute myocardial infarction.

Methods and Results

We carried out a case control study comparing 103 patients at high cardiovascular risk but free of coronary disease and 99 patients who had an
MI
. The blood microbiome was analyzed both quantitatively by 16S quantitative polymerase chain reaction and qualitatively by 16S targeted metagenomic sequencing specifically optimized for blood samples. A significant increase in blood bacterial 16S
rDNA
concentration was observed in patients admitted for
MI
. This increase in blood bacterial
DNA
concentration was independent of post‐
MI
left ventricular function and was more marked in patients with low‐density lipoprotein cholesterol ≥1 g/L. In addition, differences in the proportion of numerous bacterial taxa in blood were significantly modified with the onset of
MI
, thus defining a blood microbiota signature of
MI
. Among the bacterial taxa whose proportions are decreased in patients with
MI
, at least 6 are known to include species able to metabolize cholesterol.

Conclusions

These results could provide the basis for the identification of blood microbiome‐based biomarkers for the stratification of
MI
patients. Furthermore, these findings should provide insight into the mechanism underlying the negative correlation reported between low‐density lipoprotein cholesterol concentration and the prognosis at the acute onset of
MI
and mortality.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02405468.
Association Between Serum Leptin Level and Calcific Aortic Valve Disease
Authors: Liu Yehong , Gu Yuying , Shen Ying , Lin Bowen , Li Ying , He Xiaoyan , Zhang Yibo , Lu Lin , Shen Weifeng , Zhang Qi , Yang Ke
Published: September 2019

Background

The pathophysiological process of calcific aortic valve disease (
CAVD
) is similar to that of atherosclerosis. Leptin accelerates the process of atherosclerosis. We sought to examine the relationship between leptin and
CAVD
.

Methods and Results

Serum leptin was measured in 397 consecutive patients undergoing standard transthoracic echocardiography and Doppler flow imaging. Multiple logistic regression analyses were used to assess the association between leptin and
CAVD
. Western blotting was performed to detect the expression of phosphorylated and total extracellular signal‐regulated kinase. Serum leptin (median) was higher in 200 patients with
CAVD
than that in 197 non‐
CAVD
controls (20.07 versus 9.03 ng/
mL
;
P
<0.01). Leptin correlated positively with age (
r
=0.37,
P
<0.01) and negatively with estimated glomerular filtration rate (
r
=−0.37,
P
<0.01). Multivariate analysis indicated that elevated leptin was an independent determinant for the presence of
CAVD
(
P
<0.01). Receiver‐operating characteristic curve analysis of leptin to detect the presence of
CAVD
showed that the area under the curve was 0.74 (95%
CI
, 0.69–0.79;
P
<0.01). The diagnostic value of leptin for the detection of
CAVD
was higher among younger patients (aged ≤65 years) or those with at least mildly reduced renal function (estimated glomerular filtration rate ≤82.06
mL
/min per 1.73 m
2
). The activation of extracellular signal‐regulated kinase 1/2 was stronger in calcific aortic valves than in normal aortic valves.

Conclusions

Elevated leptin is associated with the presence of
CAVD
, especially among younger patients or those with renal dysfunction.
Joint Associations of Obesity and NT‐proBNP With the Incidence of Atrial Fibrillation in the ARIC Study
Authors: Almuwaqqat Zakaria , O'Neal Wesley T. , Norby Faye L. , Lutsey Pamela L. , Selvin Elizabeth , Soliman Elsayed Z. , Chen Lin Y. , Alonso Alvaro
Published: September 2019

Background

Circulating
NT
‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels, a well‐known indicator of atrial wall stress and remodeling, inversely correlate with body mass index. Both are strongly predictive of atrial fibrillation (
AF
). Their potential interaction in relation to incident AF, however, has not been explored.

Methods and Results

In total, 9556 participants of the ARIC (Atherosclerosis Risk in Communities) study who had 2 measurements of
NT
‐pro
BNP
and no baseline
AF
or heart failure were followed from 1996 to 1998 through 2016 for the occurrence of incident
AF
. Participants were categorized as obese (body mass index ≥30) and nonobese (body mass index <30) and by
NT
‐pro
BNP
levels (using the median of 68.2 pg/
mL
as the cutoff). Over a median follow‐up of 18.3 years, we identified 1806 incident cases of
AF
. Analysis using multivariable Cox regression models showed that obese participants with high
NT
‐pro
BNP
levels at visit 4 had a higher adjusted risk of incident
AF
(hazard ratio: 3.64; 95% CI, 3.15–4.22) compared with nonobese individuals with low
NT
‐pro
BNP
levels. The association of obesity with
AF
risk was not modified by
NT
‐pro
BNP
levels (
P
=0.46 for interaction). Increasing
BNP
among participants from 1990–1992 to 1996–1998 was associated with increased
AF
risk. After further adjustment for clinical risk factors and medications, results were similar.

Conclusions

Individuals who had both elevated body mass index and
NT
‐pro
BNP
and were free of clinically recognized heart failure were at higher risk of
AF
development. Those who experienced an increase in
NT
‐pro
BNP
levels between visits 2 and 4 were at higher risk of
AF
.
Posttraumatic Stress Disorder and Risk for Early Incident Atrial Fibrillation: A Prospective Cohort Study of 1.1 Million Young Adults
Authors: Rosman Lindsey , Lampert Rachel , Ramsey Christine M. , Dziura James , Chui Phillip W. , Brandt Cynthia , Haskell Sally , Burg Matthew M.
Published: September 2019

Background

Acute psychological stress and negative emotions are known risk factors for atrial fibrillation (
AF
). Whether exposure to chronic stress syndromes, such as posttraumatic stress disorder (
PTSD
), also increases susceptibility to
AF
is unknown.

Methods and Results

We prospectively assessed the incidence of
AF
over a 13‐year period among 988 090 young and middle‐aged veterans (mean age, 30.29±9.19 years; 87.8% men, 64.5% white) who first accessed care through the Veterans Health Administration from October 2001 to November 2014 and were free of
AF
, atrial flutter, or atrial tachycardia at baseline. Time‐varying, multivariate Cox proportional hazard models were used to examine the independent contribution of
PTSD
to new
AF
. We also tested for effect modification by sex and controlled for healthcare use. During a mean follow‐up of 4.8 years, 2491 patients were diagnosed with
AF
. Patients with
PTSD
had a higher overall incidence of
AF
(
P
<0.0001) and were more likely to develop
AF
at a younger age than those without
PTSD
(
P
=0.004).
PTSD
was significantly associated with incident
AF
in unadjusted models (hazard ratio, 1.31; 95%
CI
, 1.19–1.43) and models that adjusted for demographics, lifestyle factors, cardiovascular risk factors, and depression (hazard ratio, 1.13; 95%
CI
, 1.02–1.24). The interaction with sex was nonsignificant (
P
=0.93).

Conclusions

PTSD
was associated increased risk for early incident
AF
after adjustment for established
AF
risk factors and depression in this cohort of young and middle‐aged veterans. Findings from this study require validation in more diverse populations to determine their generalizability.
Hemodialysis Procedure–Associated Autonomic Imbalance and Cardiac Arrhythmias: Insights From Continuous 14‐Day ECG Monitoring
Authors: Rogovoy Nichole M. , Howell Stacey J. , Lee Tiffany L. , Hamilton Christopher , Perez‐Alday Erick A. , Kabir Muammar M. , Zhang Yanwei , Kim Esther D. , Fitzpatrick Jessica , Monroy‐Trujillo Jose M. , Estrella Michelle M. , Sozio Stephen M. , Jaar Bernard G. , Parekh Rulan S. , Tereshchenko Larisa G.
Published: September 2019

Background

In patients with end‐stage kidney disease, sudden cardiac death is more frequent after a long interdialytic interval, within 6 hours after the end of a hemodialysis session. We hypothesized that the occurrence of paroxysmal arrhythmias is associated with changes in heart rate and heart rate variability in different phases of hemodialysis.

Methods and Results

We conducted a prospective ancillary study of the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease cohort. Continuous
ECG
monitoring was performed using an
ECG
patch, and short‐term heart rate variability was measured for 3 minutes every hour (by root mean square of the successive normal‐to‐normal intervals, spectral analysis, Poincaré plot, and entropy), up to 300 hours. Out of enrolled participants (n=28; age 54±13 years; 57% men; 96% black; 33% with a history of cardiovascular disease; left ventricular ejection fraction 70±9%), arrhythmias were detected in 13 (46%). Nonsustained ventricular tachycardia occurred more frequently during/posthemodialysis than pre‐/between hemodialysis (63% versus 37%,
P
=0.015). In adjusted for cardiovascular disease time‐series analysis, nonsustained ventricular tachycardia was preceded by a sudden heart rate increase (by 11.2 [95%
CI
10.1–12.3] beats per minute;
P
<0.0001). During every‐other‐day dialysis, root mean square of the successive normal‐to‐normal intervals had a significant circadian pattern (Mesor 10.6 [ 95%
CI
0.9–11.2] ms; amplitude 1.5 [95%
CI
1.0–3.1] ms; peak at 02:01 [95%
CI
20:22–03:16]
am
;
P
<0.0001), which was replaced by a steady worsening on the second day without dialysis (root mean square of the successive normal‐to‐normal intervals −1.41 [95%
CI
−1.67 to −1.15] ms/24 h;
P
<0.0001).

Conclusions

Sudden increase in heart rate during/posthemodialysis is associated with nonsustained ventricular tachycardia. Every‐other‐day hemodialysis preserves circadian rhythm, but a second day without dialysis is characterized by parasympathetic withdrawal.
Tracing and Assessing the Evolution of Clinical Guidelines
Authors: Arnett Donna K. , Claas Steven A.
Published: September 2019

See Article
DuBose‐Briski et al
Re-Viewing Western U.S. Rephotography in the Anthropocene
Authors: Handley William R.
Published: September 2019

In this paper, documentary and artistic pairings of nineteenth-century survey photographs with rephotographs from the 1970s-2000s of identical views of western U.S. sites are read within divergent temporal and historiographical paradigms about historical and geological change. Viewed and interpreted within the legacy of American technocratic “progress” and of debates about the “old” and “new” western histories, this juxtaposed work across a century speaks to shifts in historians’ paradigms about the meaning of western expansion, from optimism to tragedy, and to whether geologic and human history are continuous or discontinuous. The ecological rupture of the Anthropocene returns us to nineteenth-century debates, which in part motivated survey photographs, about whether changes in geological and life forms are gradual or catastrophic—or some uneasy combination of the two. What haunts these photographs today is both a lost ideological past and a precarious, humanly viable future that the Anthropocene exposes.
Dispute Settlement in the Law of the Sea: Survey for 2018
Authors: Churchill Robin
Published: September 2019

This is the latest in a series of annual surveys in this Journal reviewing dispute settlement in the law of the sea, both under Part XV of the UN Convention on the Law of the Sea and outside the framework of the Convention. It covers developments during 2018. The most significant developments during the year were the judgment of the International Court of Justice in Costa Rica v. Nicaragua, delimiting the maritime boundaries between the two States’ overlapping maritime zones in both the Caribbean Sea and the Pacific Ocean; the report of the Conciliation Commission concerning maritime boundary arrangements between Timor-Leste and Australia; and the findings of a dispute settlement body of the South Pacific Regional Fisheries Management Organization.
Compensability of Moral Damage in Islamic Contract Law: A Comparative Analysis of the Palestinian, Jordanian and Qatari Civil Codes
Authors: Dodeen Mahmoud M.
Published: September 2019

This study explores Islamic law’s position towards the compensation of natural and juridical persons for moral damage within the scope of contractual liability in view of divergent and unclear legal and judicial opinions in Arab countries. One line of argument makes a distinction in the approach to tort and contractual liability. As a result, courts have been influenced by these opinions. In contrast, other jurists have not taken great pains to reach a different discretion in search of the truth. To enrich this study, to ensure a sound interpretation of the true situation, and in an attempt to draw a closer link between the positions of Islamic law and Latin law, the study provides a comparison between the civil codes of three Arab countries: Palestine, Jordan and Qatar.
Gross Fraud in the UAE Civil Code: From Its Roots in Islamic Jurisprudence to Contemporary Proposals for Reform
Authors: Jadalhaq Iyad Mohammad
Published: September 2019

The regulations concerning gross fraud instituted by the United Arab Emirates (UAE) legislature in the UAE Civil Code are derived from provisions put forward by the Ḥanafī school of law. A general rule was put forward, and exceptions thereto were set. A certain remedy for gross fraud was instituted, namely, giving the defrauded party the right to terminate the contract. This article determines the comprehensiveness and adequacy of the legal texts dealing with the impact of gross fraud on contracts in the UAE Civil Code, the methods by which balance could be achieved between the interests of the contracting parties, and the means of protecting the defrauded contractor. Furthermore, shortcomings and defects in the existing legal texts that require amendment and reform are highlighted. This study concludes that the legislative treatment of the impact of gross fraud on contracts is insufficient, and advances possible recommendations.
State of the Climate in 2018
Authors: Blunden Jessica , Arndt Derek S.
Published: September 2019

Editor’s note: For easy download the posted pdf of the State of the Climate for 2019 is a low-resolution file. A high-resolution copy of the report is available by clicking here. Please be patient as it may take a few minutes for the high-resolution file to download.
Misinformation About Health: A Review of Health Communication and Misinformation Scholarship
Authors: Krishna Arunima , Thompson Teresa L.
Published: September 2019

As more people choose to get health information online, health-related topics continue to be the target of misinformation. From targeted misinformation campaigns about the safety of tobacco, the mainstreaming and subsequent adoption of scientifically flawed research about vaccines, to the misinformation-driven stigmatization of HIV, health communication as an academic discipline has been faced with the challenge of stemming the flow of misinformation and correcting individuals’ misinformed beliefs. To that end, scholars have devoted much time and effort to understand the antecedents and consequences of health-related misinformation, as well as strategies to correct misinformation and inoculate others from misinformation. In this essay, we review research on health-related misinformation, with a special emphasis on two major journals in the field, that is, Health Communication and the Journal of Health Communication, and interrogate the nature of health-related misinformation. We close this essay with a conceptualization of misinformed yet vocal health communicators, whom we term health misliterates.
Horner Syndrome from a Pediatric Otolaryngology Perspective
Authors: Folkert Kyra N. , de Beaufort Heather , Bauman Nancy M.
Published: September 2019

Introduction:

Horner syndrome is described as the clinical triad of miosis, ptosis, and anhidrosis. In pediatric patients the condition may be congenital or acquired from neoplastic, infectious or traumatic conditions, including birth trauma. Most cases of pediatric Horner syndrome present first to a pediatric ophthalmologist however since the neural pathways involve the cervical sympathetic chain otolaryngologists should understand the pathophysiology to avoid delay in management of potentially malignant cases.

Objectives:

To aid otolaryngologists in recognizing and managing pediatric Horner syndrome by describing 3 unique cases from malignant, traumatic and/or congenital causes.

Methods:

Case report of 3 pediatric patients with Horner syndrome presenting to our pediatric otolaryngology department.

Results:

Case #1 is 5-month-old female with ptosis and a left level II 1.5 cm neck mass. Magnetic resonance imaging showed the mass displacing the common carotid artery and excisional biopsy revealed a poorly differentiated neuroblastoma. Case #2 is a 9-year-old female with anisocoria appearing after suffering a severe playground injury. Case #3 is a 3-year-old-male who developed ptosis and anisocoria following re-excision of a recurrent cervical lymphatic malformation.

Conclusion:

Pediatric Horner syndrome may be a benign finding that is easily overlooked but may reflect a serious underlying condition. Otolaryngologists should be aware of the pathophysiology and differential diagnosis, including malignant causes, to appropriately manage patients.
Evaluating the differential effectiveness of social influence and personality-targeted alcohol prevention on mental health outcomes among high-risk youth: A novel cluster randomised controlled factorial design trial
Authors: Newton Nicola C , Stapinski Lexine , Teesson Maree , Slade Tim , Champion Katrina E , Barrett Emma L , Birrell Louise , Kelly Erin , Mather Marius , Conrod Patricia J
Published: September 2019

Objective:

This study examined the secondary mental health outcomes of two contrasting alcohol prevention approaches, whereby one intervention targets common underlying personality risk for alcohol use and mental health problems ( Preventure) and the other targets alcohol- and drug-related behaviours and cognitions ( Climate Schools).

Methods:

A 2 × 2 cluster randomised controlled factorial design trial was conducted in 26 Australian schools randomised to the following 4 conditions: Climate Schools ( n = 6), Preventure ( n = 7), combined Climate Schools and Preventure (CAP; n = 6) or treatment as usual (TAU; n = 7). Participants completed questionnaires at baseline, 6, 12, 24 and 36 months post-baseline including the Brief Symptom Inventory anxiety and depression scales and hyperactivity and conduct scales of the Strengths and Difficulties Questionnaire. Analyses focused on students who were at high-risk based on personality traits ( n = 947; Mage = 13.3). The effectiveness of each approach in reducing symptoms of internalising and externalising problems was assessed using multi-level mixed effects analysis.

Results:

Main effects for each intervention relative to not receiving that intervention revealed significant main effects of Preventure in reducing anxiety symptoms ( d = −0.27, 95% confidence interval [CI] = [−0.53, −0.01], p < 0.05) and a marginal effect in reducing depressive symptoms ( d = −0.24, 95% CI = [−0.49, 0.01], p = 0.06) over 3 years. Interaction effects revealed that when delivered alone, Preventure significantly reduced conduct problems ( d = −0.45, 95% CI = [−0.78, −0.11], p < 0.05) and hyperactivity symptoms ( d = −0.38, 95% CI = [−0.70,−0.07], p < 0.05) compared to TAU.

Conclusion:

This study is the first to report the effectiveness of personality-targeted alcohol prevention in reducing internalising and externalising symptoms relative to an active control, providing evidence in favour of its specificity in preventing concurrent substance use and mental health problems among high-risk youth.
Egoistic norms, organizational identification, and the perceived ethicality of unethical pro-organizational behavior: A moral maturation perspective
Authors: Graham Katrina A , Resick Christian J , Margolis Jaclyn A , Shao Ping , Hargis Michael B , Kiker Jason D
Published: September 2019

Do some employees engage in unethical behavior because they actually believe it is the right thing to do? We explore this question in this article. Unlike other forms of unethical behavior, unethical pro-organizational behavior (UPB) is aimed at benefiting the perpetrator’s organization. We propose that employees are increasingly likely to engage in UPB when they believe these acts are ethically appropriate, and that these ethicality beliefs are strongest among employees who work in departments with egoistic norms. Such norms lack guidance on the importance of protecting outside stakeholders’ interest, and provide limited moral knowledge about the broader implications of UPB. We further propose that organizational identification strengthens these effects. Across three field studies, we find support for the hypothesized effects. Ethical judgments of UPB were positively related to both self (Studies 1 and 3) and supervisor (Study 2) ratings of employee UPB. In turn, acts of UPB were judged more ethically appropriate in departments with egoistic norms, and these positive ethical judgments mediated the relationships between egoistic norms and employee UPB (Study 2). Finally, the indirect effects of egoistic norms were strongest among employees with high levels of organizational identification (Study 3). Implications for theory and research are discussed.
The Role of Indigenous Knowledge Systems in Rural Smallholder Farmers’ Response to Climate Change: Case Study of Nkomazi Local Municipality, Mpumalanga, South Africa
Authors: Ubisi Nomcebo R. , Kolanisi Unathi , Jiri Obert
Published: September 2019

Climate change and variability have direct negative impacts on rural smallholder farmers. These impacts involve extreme climatic events such as excessive temperatures, prolonged droughts and floods which affect people’s livelihoods. This study was conducted in Nkomazi Local Municipality, Mpumalanga, South Africa. The main objective of the study was to investigate indigenous weather and climate indicators used by smallholder farmers and the role of indigenous knowledge in their farming systems. The research used qualitative methods, including focus group discussions and key informant interviews. The findings indicated that farmers observed animal behaviour, plants, atmospheric indicators and human ailments to predict weather.