bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between diagonal earlobe creases and coronary artery disease as determined via angiography
Authors: Wang Yong , Mao Li-Hua , Jia En-Zhi , Li Zhao-Yang , Ding Xiao-Qing , Ge Peng-Cheng , Liu Zhe , Zhu Tie-Bing , Wang Lian-Sheng , Li Chun-Jian , Ma Wen-Zhu , Yang Zhi-Jian
Published: February 2016

Objective

This study was designed to examine the prevalence of unilateral and bilateral diagonal earlobe creases (DELCs) with respect to the diagnosis of coronary heart disease (CHD).

Methods

A total of 558 consecutive participants (402 males and 156 females) aged 36–91 years who underwent coronary angiography were enrolled in this study. The participants were classified as being without a DELC, having a unilateral DELC and having bilateral DELCs; participants with either a unilateral DELC or bilateral DELCs were defined as participants with DELCs. Significant CHD was defined as at least one major vessel with >50% stenosis, and coronary atherosclerosis severity was defined using the Gensini scoring system.

Results

In the present study, bilateral DELCs were more frequently among male (p=0.001), CHD (p=0.000), older people (p=0.000) and those with more severe coronary artery atherosclerosis (p=0.000). The results of the multiple regression analyses indicated that DELCs (OR, 4.861; 95% CI 3.093 to 7.642, p=0.000) remained independently associated with a risk of CHD. It was assumed that participants without a DELC have a certain background risk for CHD (OR is assumed to be 1); the results of the multivariate logistic regression indicated that the relative risk of CHD among participants with bilateral DELCs was 5.690 among all participants (OR, 5.690; 95% CI 3.450 to 9.384, p=0.000), 5.436 among male participants (OR, 5.436; 95% CI 2.808 to 10.523, p=0.000) and 7.148 among female participants (OR, 7.148; 95% CI 3.184 to 16.049, p=0.000). Moreover, a positive association between DELC and age (SI=1.21, SIM=1.65, AP =0.132), gender (SI=2.09, SIM=0.81, AP=0.49) and smoking status (SI=1.49, SIM=0.73, AP=0.29) was found, respectively.

Conclusions

The results of the present study indicated that DELCs are a simple and a feasible means of identifying CHD. However, the exact mechanism underlying the relationship between DELCs and CHD warrants further study.
What is a medical decision? A taxonomy based on physician statements in hospital encounters: a qualitative study
Authors: Ofstad Eirik H , Frich Jan C , Schei Edvin , Frankel Richard M , Gulbrandsen Pål
Published: February 2016

Objective

The medical literature lacks a comprehensive taxonomy of decisions made by physicians in medical encounters. Such a taxonomy might be useful in understanding the physician-centred, patient-centred and shared decision-making in clinical settings. We aimed to identify and classify all decisions emerging in conversations between patients and physicians.

Design

Qualitative study of video recorded patient–physician encounters.

Participants and setting

380 patients in consultations with 59 physicians from 17 clinical specialties and three different settings (emergency room, ward round, outpatient clinic) in a Norwegian teaching hospital. A randomised sample of 30 encounters from internal medicine was used to identify and classify decisions, a maximum variation sample of 20 encounters was used for reliability assessments, and the remaining encounters were analysed to test for applicability across specialties.

Results

On the basis of physician statements in our material, we developed a taxonomy of clinical decisions—the Decision Identification and Classification Taxonomy for Use in Medicine (DICTUM). We categorised decisions into 10 mutually exclusive categories: gathering additional information, evaluating test results, defining problem, drug-related, therapeutic procedure-related, legal and insurance-related, contact-related, advice and precaution, treatment goal, and deferment. Four-coder inter-rater reliability using Krippendorff's α was 0.79.

Conclusions

DICTUM represents a precise, detailed and comprehensive taxonomy of medical decisions communicated within patient–physician encounters. Compared to previous normative frameworks, the taxonomy is descriptive, substantially broader and offers new categories to the variety of clinical decisions. The taxonomy could prove helpful in studies on the quality of medical work, use of time and resources, and understanding of why, when and how patients are or are not involved in decisions.
Impact of high ambient temperature on unintentional injuries in high-income countries: a narrative systematic literature review
Authors: Otte im Kampe Eveline , Kovats Sari , Hajat Shakoor
Published: February 2016

Objectives

Given the likelihood of increased hot weather due to climate change, it is crucial to have prevention measures in place to reduce the health burden of high temperatures and heat waves. The aim of this review is to summarise and evaluate the evidence on the effects of summertime weather on unintentional injuries in high-income countries.

Design

3 databases (Global Public Health, EMBASE and MEDLINE) were searched by using related keywords and their truncations in the title and abstract, and reference lists of key studies were scanned. Studies reporting heatstroke and intentional injuries were excluded.

Results

13 studies met our inclusion criteria. 11 out of 13 studies showed that the risk of unintentional injuries increases with increasing ambient temperatures. On days with moderate temperatures, the increased risk varied between 0.4% and 5.3% for each 1°C increase in ambient temperature. On extreme temperature days, the risk of injuries decreased. 2 out of 3 studies on occupational accidents found an increase in work-related accidents during high temperatures. For trauma hospital admissions, 6 studies reported an increase during hot weather, whereas 1 study found no association. The evidence for impacts on injuries by subgroups such as children, the elderly and drug users was limited and inconsistent.

Conclusions

The present review describes a broader range of types of unintentional fatal and non-fatal injuries (occupational, trauma hospital admissions, traffic, fire entrapments, poisoning and drug overdose) than has previously been reported. Our review confirms that hot weather can increase the risk of unintentional injuries and accidents in high-income countries. The results are useful for injury prevention strategies.
Paid family leave's effect on hospital admissions for pediatric abusive head trauma
Authors: Klevens Joanne , Luo Feijun , Xu Likang , Peterson Cora , Latzman Natasha E
Published: February 2016

Paediatric abusive head trauma (AHT) is a leading cause of fatal child maltreatment among young children. Current prevention efforts have not been consistently effective. Policies such as paid parental leave could potentially prevent AHT, given its impacts on risk factors for child maltreatment. To explore associations between California's 2004 paid family leave (PFL) policy and hospital admissions for AHT, we used difference-in-difference analyses of 1995–2011 US state-level data before and after the policy in California and seven comparison states. Compared with seven states with no PFL policies, California's 2004 PFL showed a significant decrease in AHT admissions in both <1 and <2-year-olds. Analyses using additional data years and comparators could yield different results.
Association between maternal education and objectively measured physical activity and sedentary time in adolescents
Authors: Sherar Lauren B , Griffin Tom P , Ekelund Ulf , Cooper Ashley R , Esliger Dale W , van Sluijs Esther M F , Bo Andersen Lars , Cardon Greet , Davey Rachel , Froberg Karsten , Hallal Pedro C , Janz Kathleen F , Kordas Katarzyna , Kriemler Susi , Pate Russell R , Puder Jardena J , Sardinha Luis B , Timperio Anna F , Page Angie S
Published: February 2016

Background

Investigating socioeconomic variation in physical activity (PA) and sedentary time is important as it may represent a pathway by which socioeconomic position (SEP) leads to ill health. Findings on the association between children's SEP and objectively assessed PA and/or sedentary time are mixed, and few studies have included international samples.

Objective

Examine the associations between maternal education and adolescent's objectively assessed PA and sedentary time.

Methods

This is an observational study of 12 770 adolescents (10–18 years) pooled from 10 studies from Europe, Australia, Brazil and the USA. Original PA data were collected between 1997 and 2009. The associations between maternal education and accelerometer variables were examined using robust multivariable regression, adjusted for a priori confounders (ie, body mass index, monitor wear time, season, age and sex) and regression coefficients combined across studies using random effects meta-analyses. Analyses were conducted in March 2014.

Results

Adolescents of university educated mothers spent more time sedentary (9.5 min/day, p=0.005) and less time in light activity (10 min/day, p<0.001) compared with adolescents of high school educated mothers. Pooled analysis across two studies from Brazil and Portugal (analysed separately because of the different coding of maternal education) showed that children of higher educated mothers (tertiary vs primary/secondary) spent less time in moderate to vigorous PA (MVPA) (6.6 min/day, p=0.001) and in light PA (39.2 min/day: p<0.001), and more time sedentary (45.9 min/day, p<0.001).

Conclusions

Across a number of international samples, adolescents of mothers with lower education may not be at a disadvantage in terms of overall objectively measured PA.
Prion protein genotype survey confirms low frequency of scrapie‐resistant K222 allele in British goat herds
Authors: Goldmann W. , Marier E. , Stewart P. , Konold T. , Street S. , Langeveld J. , Windl O. , Ortiz‐Pelaez A.
Published: February 2016

Scrapie in goats is a transmissible, fatal prion disease, which is endemic in the British goat population. The recent success in defining caprine PRNP gene variants that provide resistance to experimental and natural classical scrapie has prompted the authors to conduct a survey of PRNP genotypes in 10 goat breeds and 52 herds to find goats with the resistant K222 allele. They report here the frequencies in 1236 tested animals of the resistance‐associated K222 and several other alleles by breed and herd. Eight animals were found to be heterozygous QK222 goats (0.64 per cent genotype frequency, 95 per cent CI 0.28 to 1.27 per cent) but no homozygous KK222 goats were detected. The K222 allele was found in Saanen, Toggenburg and Anglo‐Nubian goats. The fact that only a few goats with the K222 allele have been identified does not preclude the possibility to design and implement successful breeding programmes at national level.
Prophylactic effects of pomegranate (Punica granatum) juice on sodium fluoride induced oxidative damage in liver and erythrocytes of rats
Authors: Bouasla Asma , Bouasla Ihcène , Boumendjel Amel , Abdennour Cherif , El Feki Abdelfattah , Messarah Mahfoud
Published: February 2016

The objective of this study was to investigate the protective effects of pomegranate (Punica granatum) juice (PGJ) on oxidative damages in liver tissue and erythrocytes of rats intoxicated by sodium fluoride (NaF). Rats were randomly divided into two groups: group I received standard diet and group II received orally 1 mL of PGJ. After 5 weeks of pretreatment, each group was divided again into two subgroups and treated for another 3 weeks as follows: group I was subdivided into a control group and a group that was treated with 100 ppm of NaF (in drinking water); group II was subdivided into one group that was treated daily with both 100 ppm NaF and PGJ (1 mL orally) and one that received daily 1 mL of pomegranate juice. Exposure to NaF decreased hematological parameters, changed the total protein, albumin, bilirubin levels, and increased the activities of hepatic marker enzymes. We also noted an increase in lipid peroxidation contents, accompanied by a decrease of reduced glutathione levels. Antioxidant enzyme activities in both tissues were modified in the NaF group compared with the control group. However, the administration of PGJ juice caused an amelioration of the previous parameters. Our results indicated the potential effects of NaF to induce oxidative damage in tissues and the ability of PGJ to attenuate NaF-induced oxidative injury.
The myosin activator omecamtiv mecarbil: a promising new inotropic agent
Authors: Nánási Péter , Váczi Krisztina , Papp Zoltán
Published: February 2016

Heart failure became a leading cause of mortality in the past few decades with a progressively increasing prevalence. Its current therapy is restricted largely to the suppression of the sympathetic activity and the renin–angiotensin system in combination with diuretics. This restrictive strategy is due to the potential long-term adverse effects of inotropic agents despite their effective influence on cardiac function when employed for short durations. Positive inotropes include inhibitors of the Na+/K+ pump, β-receptor agonists, and phosphodiesterase inhibitors. Theoretically, Ca2+ sensitizers may also increase cardiac contractility without resulting in Ca2+ overload; nevertheless, their mechanism of action is frequently complicated by other pleiotropic effects. Recently, a new positive inotropic agent, the myosin activator omecamtiv mecarbil, has been developed. Omecamtiv mecarbil binds directly to β-myosin heavy chain and enhances cardiac contractility by increasing the number of the active force-generating cross-bridges, presumably without major off-target effects. This review focuses on recent in vivo and in vitro results obtained with omecamtiv mecarbil, and discusses its mechanism of action at a molecular level. Based on clinical data, omecamtiv mecarbil is a promising new tool in the treatment of systolic heart failure.
TAM receptor tyrosine kinase function and the immunopathology of liver disease
Authors: Mukherjee S. K. , Wilhelm A. , Antoniades C. G.
Published: February 2016

Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus on its impact upon hepatic inflammatory pathology.
Nitric oxide-mediated vascular function in sepsis using passive leg movement as a novel assessment: a cross-sectional study
Authors: Nelson Ashley D. , Rossman Matthew J. , Witman Melissa A. , Barrett-O'Keefe Zachary , Groot H. Jonathan , Garten Ryan S. , Richardson Russell S.
Published: February 2016

Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 ± 1.7% vs. 6.8 ± 1.3%; values are means ± SD). In terms of PLM, baseline LBF (196 ± 33 ml/min vs. 328 ± 20 ml/min), peak change in LBF from baseline (133 ± 28 ml/min vs. 483 ± 86 ml/min), and the LBF area under the curve (16 ± 8.3 vs. 143 ± 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis.
A Survey on the Application of Evolutionary Algorithms for Mobile Multihop Ad Hoc Network Optimization Problems
Authors: Reina D. G. , Ruiz P. , Ciobanu R. , Toral S. L. , Dorronsoro B. , Dobre C.
Published: February 2016

Evolutionary algorithms are metaheuristic algorithms that provide quasioptimal solutions in a reasonable time. They have been applied to many optimization problems in a high number of scientific areas. In this survey paper, we focus on the application of evolutionary algorithms to solve optimization problems related to a type of complex network like mobile multihop ad hoc networks. Since its origin, mobile multihop ad hoc network has evolved causing new types of multihop networks to appear such as vehicular ad hoc networks and delay tolerant networks, leading to the solution of new issues and optimization problems. In this survey, we review the main work presented for each type of mobile multihop ad hoc network and we also present some innovative ideas and open challenges to guide further research in this topic.
Metabolism Is Central to Tolerogenic Dendritic Cell Function
Authors: Sim Wen Jing , Ahl Patricia Jennifer , Connolly John Edward
Published: February 2016

Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.
The Role ofγδT Cells in Systemic Lupus Erythematosus
Authors: Wu Meng , Yang Jinhua , Li Xiaofeng , Chen Junwei
Published: February 2016

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the overproduction of autoantibodies against an array of nuclear and cytoplasmic antigens and affects multiple organs, such as the skin, joints, kidneys, and neuronal tissues. T cells have been recognized as important players in the development of SLE due to their functions in cytokine secretion, antigen presentation, and supporting B cells for antibody production.γδT cells are a minor population of T cells that play important roles in infection and tumor-associated disease. In recent years, the role ofγδT cells in autoimmune diseases has been investigated. In this review, we discussed the role ofγδT cells in the pathogenesis of SLE.
A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome
Authors: Blondonnet Raiko , Constantin Jean-Michel , Sapin Vincent , Jabaudon Matthieu
Published: February 2016

Acute respiratory distress syndrome (ARDS) is an acute-onset hypoxic condition with radiographic bilateral lung infiltration. It is characterized by an acute exudative phase combining diffuse alveolar damage and lung edema followed by a later fibroproliferative phase. Despite an improved understanding of ARDS pathobiology, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. After a short description of ARDS pathobiology, here, we review the scientific evidence that supports the value of various ARDS biomarkers with regard to their major biological roles in ARDS-associated lung injury and/or repair. Ongoing research aims at identifying and characterizing novel biomarkers, in order to highlight relevant mechanistic explorations of lung injury and repair, and to ultimately develop innovative therapeutic approaches for ARDS patients. This review will focus on the pathophysiologic, diagnostic, and therapeutic implications of biomarkers in ARDS and on their utility to ultimately improve patient care.
Prospective Study of Human Polyomaviruses and Risk of Cutaneous Squamous Cell Carcinoma in the United States
Authors: Gossai Anala , Waterboer Tim , Nelson Heather H. , Doherty Jennifer A. , Michel Angelika , Willhauck-Fleckenstein Martina , Farzan Shohreh F. , Christensen Brock C. , Hoen Anne G. , Perry Ann E. , Pawlita Michael , Karagas Margaret R.
Published: February 2016

Background: Merkel cell polyomavirus (PyV) is causally related to Merkel cell carcinoma, a rare skin malignancy. Little is known about the serostability of other PyVs over time or associations with cutaneous squamous cell carcinoma (SCC).

Methods: As part of a U.S. nested case–control study, antibody response against the PyV VP1 capsid proteins of BK and John Cunningham virus (JC) was measured using multiplex serology on 113 SCC cases and 229 gender, age, and study center–matched controls who had a prior keratinocyte cancer. Repeated serum samples from controls and both pre and postdiagnosis samples from a subset of SCC cases were also tested. Odds ratios (OR) for SCC associated with seropositivity to each PyV type were estimated using conditional logistic regression.

Results: Among controls, BK and JC seroreactivity was stable over time, with intraclass correlation coefficients of 0.86 for BK and 0.94 for JC. Among cases, there was little evidence of seroconversion following SCC diagnosis. JC seropositivity prior to diagnosis was associated with an elevated risk of SCC (OR = 2.54; 95% CI, 1.23–5.25), and SCC risk increased with increasing quartiles of JC (Ptrend = 0.004) and BK (Ptrend = 0.02) seroreactivity.

Conclusions: PyV antibody levels were stable over time and following an SCC diagnosis. A history of PyV infection may be involved in the occurrence of SCC in a population at high risk for this malignancy.

Impact: A single measure of PyV seroreactivity appears a reliable indicator of long-term antibody status, and PyV exposure may be a risk factor for subsequent SCC. Cancer Epidemiol Biomarkers Prev; 25(5); 736–44. ©2016 AACR.
New Strategies in Breast Cancer: Immunotherapy
Authors: Pusztai Lajos , Karn Thomas , Safonov Anton , Abu-Khalaf Maysa M. , Bianchini Giampaolo
Published: February 2016

More than 70% of breast cancers contain lymphocytic infiltration in the stroma, and preclinical studies suggest that immunoediting and partial control of cancer progression by the local immune microenvironment operate in most breast cancers. Consistent with this hypothesis, a large number of studies demonstrated a favorable prognostic and chemotherapy response predictive role for immune infiltration in breast cancer. The evidence is particularly strong for triple-negative and HER2-positive cancers. The development of clinically effective immune checkpoint inhibitors now provides an opportunity to test the therapeutic potential of augmenting the local antitumor immune response. Several phase I clinical trials using single-agent anti–PD-1 and anti–PD-L1 antibodies demonstrated objective tumor response rates, with remarkably durable responses, in heavily pretreated, metastatic, triple-negative cancers and somewhat lower responses in estrogen receptor–positive cancers. Currently, close to 50 ongoing, or soon to open, clinical trials evaluate the role of this new treatment modality in breast cancer. Clin Cancer Res; 22(9); 2105–10. ©2016 AACR.
Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation
Authors: Nelson Katelyn N. , Meyer April N. , Siari Asma , Campos Alexandre R. , Motamedchaboki Khatereh , Donoghue Daniel J.
Published: February 2016

Fibroblast growth factor receptors (FGFR) are critical for cell proliferation and differentiation. Mutation and/or translocation of FGFRs lead to aberrant signaling that often results in developmental syndromes or cancer growth. As sequencing of human tumors becomes more frequent, so does the detection of FGFR translocations and fusion proteins. The research conducted in this article examines a frequently identified fusion protein between FGFR3 and transforming acidic coiled-coil containing protein 3 (TACC3), frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Using titanium dioxide–based phosphopeptide enrichment (TiO2)-liquid chromatography (LC)-high mass accuracy tandem mass spectrometry (MS/MS), it was demonstrated that the fused coiled-coil TACC3 domain results in constitutive phosphorylation of key activating FGFR3 tyrosine residues. The presence of the TACC coiled-coil domain leads to increased and altered levels of FGFR3 activation, fusion protein phosphorylation, MAPK pathway activation, nuclear localization, cellular transformation, and IL3-independent proliferation. Introduction of K508R FGFR3 kinase-dead mutation abrogates these effects, except for nuclear localization which is due solely to the TACC3 domain.

Implications: These results demonstrate that FGFR3 kinase activity is essential for the oncogenic effects of the FGFR3-TACC3 fusion protein and could serve as a therapeutic target, but that phosphorylated tyrosine residues within the TACC3-derived portion are not critical for activity. Mol Cancer Res; 14(5); 458–69. ©2016 AACR.
Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice
Authors: Rossi Emily L. , de Angel Rebecca E. , Bowers Laura W. , Khatib Subreen A. , Smith Laura A. , Van Buren Eric , Bhardwaj Priya , Giri Dilip , Estecio Marcos R. , Troester Melissa A. , Hair Brionna Y. , Kirk Erin L. , Gong Ting , Shen Jianjun , Dannenberg Andrew J. , Hursting Stephen D.
Published: February 2016

Using a murine model of basal-like breast cancer, we tested the hypothesis that chronic obesity, an established breast cancer risk and progression factor in women, induces mammary gland epigenetic reprogramming and increases mammary tumor growth. Moreover, we assessed whether the obesity-induced epigenetic and protumor effects are reversed by weight normalization. Ovariectomized female C57BL/6 mice were fed a control diet or diet-induced obesity (DIO) regimen for 17 weeks, resulting in a normal weight or obese phenotype, respectively. Mice on the DIO regimen were then randomized to continue the DIO diet or were switched to the control diet, resulting in formerly obese (FOb) mice with weights comparable with control mice. At week 24, all mice were orthotopically injected with MMTV-Wnt-1 mouse mammary tumor cells. Mean tumor volume, serum IL6 levels, expression of proinflammatory genes in the mammary fat pad, and mammary DNA methylation profiles were similar in DIO and FOb mice and higher than in controls. Many of the genes found to have obesity-associated hypermethylation in mice were also found to be hypermethylated in the normal breast tissue of obese versus nonobese human subjects, and nearly all of these concordant genes remained hypermethylated after significant weight loss in the FOb mice. Our findings suggest that weight normalization may not be sufficient to reverse the effects of chronic obesity on epigenetic reprogramming and inflammatory signals in the microenvironment that are associated with breast cancer progression. Cancer Prev Res; 9(5); 339–48. ©2016 AACR.
The Level of Anxiety and Depression in Dialysis Patients Undertaking Regular Physical Exercise Training - a Preliminary Study
Authors: Dziubek Wioletta , Kowalska Joanna , Kusztal Mariusz , Rogowski Łukasz , Gołębiowski Tomasz , Nikifur Małgorzata , Szczepańska-Gieracha Joanna , Zembroń-Łacny Agnieszka , Klinger Marian , Woźniewski Marek
Published: February 2016

Background/Aims: The aim of the study was to evaluate the effects of a six-month physical training undertaken by haemodialysis (HD) patients, on the depression and anxiety. Methods: Patients with end stage renal disease (ESRD) were recruited from the dialysis station at the Department of Nephrology and Transplantation Medicine in Wroclaw. Physical training took place at the beginning of the first 4-hours of dialysis, three times a week for six months. A personal questionnaire, Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) were used in the study. Results: A total of 28 patients completed the study: 20 were randomised to endurance training and 8 were randomised to resistance training. Statistical analysis of depression and anxiety at the initial (t1) and final examination (t2) indicated a significant reduction in depression and anxiety, particularly anxiety as a trait (X2) in the whole study group. The change in anxiety as a state correlated with the disease duration, duration of dialysis and the initial level of anxiety as a state (t1X1). The change in anxiety as a trait significantly correlated with age and the initial level of anxiety (t1X2). Conclusions: Undertaking physical training during dialysis by patients with ESRD is beneficial in reducing their levels of anxiety and depression. Both resistance and endurance training improves mood, but only endurance training additionally results in anxiety reduction.
Kidney Function and Cognitive Impairment in People Aged 80 Years and Over with Untreated Hypertension: A Cross-Sectional Survey
Authors: Wang Han , Liu Tao , Cai Ying-ying , Jiang Hui , Liu Han-xiong , Lin Cai
Published: February 2016

Background/Aims: Both kidney dysfunction and cognitive impairment are common problems in hypertensive patients. However, few studies have explored the association between these conditions in hypertensive patients aged 80 or over. The current study was undertaken to determine the impact of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) on cognitive impairment among an 80-year-old population with untreated hypertension in China. Methods: A total of 395 hypertensive patients aged 80 or over were assessed for the presence of cognitive impairment according to the 30-item Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a score below 24 on MMSE. eGFR was evaluated using the Chinese Modification of Diet in Renal Disease equation. CKD was defined according to categorical approach, which is based on “YES” (eGFR below 60 ml/min) or “NO” (eGFR above 60 ml/min). Results: The mean (SD) age was 83.0 ± 2.6 years for the sample, of whom 69.8% were female. There were 59 (14.9%) and 280 (71.1%) prevalent cases of CKD and cognitive impairment, respectively. CKD patients were older, had higher scores on Activity of Daily Living (ADL), and lower score on MMSE. After controlling for potential confounding, multiple logistic regressions demonstrated that both CKD and eGFR were associated with cognitive impairment in hypertensive patients aged 80 or over. Conclusion: Our study found that both CKD and eGFR were associated with cognitive impairment among hypertensive patients aged 80 or over in China. Therefore, targeted screening for cognitive impairment should be considered in these patients with CKD.
Use of Low-Cost Videomicroscopy versus Standard Videodermatoscopy in Trichoscopy: A Controlled, Blinded Noninferiority Trial
Authors: Verzì Anna Elisa , Lacarrubba Francesco , Micali Giuseppe
Published: February 2016

Affordable (USD ∼30) handheld USB digital microscopes, or videomicroscopes (VMs), that provide ×10-200 magnification are available on the web for nonmedical uses such as in botany, entomology, microelectronics or, recently, for hair/scalp evaluation. The aim of this study was to compare the reliability of low-cost VMs versus standard, medically marketed videodermatoscopes (VDs) in trichoscopy. Twenty-five patients affected by different types of hair loss were enrolled in a controlled, blinded noninferiority trial. All patients underwent examination by two low-cost VMs as well as by standard VD in order to evaluate any variability in the detection of common trichoscopic features. At the end of the study, the two low-cost VMs enabled a correct identification of all hair shaft alterations; as regards follicular and/or perifollicular examination, black dots were easily recognized by both equipments, but other follicular features, such as yellow dots, white dots and perifollicular scales, were not always adequately visualized because of low color quality and/or reduced brightness and/or resolution. In conclusion, our study suggests that the potential accuracy of low-cost VMs in the evaluation of hair loss may have some pitfalls. Therefore, a low-cost VM should not be routinely used for reliable scalp trichoscopy, unless supported by individual controlled noninferiority trials.
Meta-Analyses of Association Between BRAFV600E Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma
Authors: Zhang Qing , Liu Shao-zheng , Zhang Qing , Guan Yan-xing , Chen Qing-jie , Zhu Qin-yao
Published: February 2016

Background/Aims: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. Methods: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAFV600E mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. Results: Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAFV600E mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAFV600E mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAFV600E mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27). Conclusion: This meta-analysis confirmed significant associations between BRAFV600E mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAFV600Emutation for PTC prognosis.
Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling
Authors: Guida Mona Samy , El-Aal Ali Abd , Kafafy Yehya , Salama Safwat Farid , Badr Badr Mohamed , Badr Gamal
Published: February 2016

Background/Aims: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation-induced T cell imbalance, and on immune dysfunction induced by gamma-rays. Methods: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro-apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4+ and CD8+ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. Results: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-α and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro-inflammatory cytokine (TNF-α and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. Conclusions: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity.
Geographic Atrophy and Choroidal Neovascularization in the Same Eye: A Review
Authors: Kaszubski Patrick , Ben Ami Tal , Saade Celine , Smith R. Theodore
Published: February 2016

Geographic atrophy (GA) and choroidal neovascularization (CNV), the two late forms of age-related macular degeneration, are generally considered two distinct entities. However, GA and CNV can occur simultaneously in the same eye, with GA usually occurring first. The prevalence of this combined entity is higher in histological studies than in clinical studies. No distinct systemic or genetic risk characteristics are associated with the combined GA/CNV entity, although on clinical examination and retinal imaging it can feature drusen or subretinal drusenoid deposits. GA and CNV may exist within the spectrum of a single disease, or they may be two very different diseases. Therapy with antivascular endothelial growth factor (anti-VEGF) is often successful for CNV, but some evidence suggests increased rates of GA development in eyes treated with anti-VEGF. In this article, we review the current literature regarding the epidemiology, clinical presentation, and treatment options for patients with the combined GA/CNV entity.
A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer
Authors: Skakkebaek Niels E.
Published: February 2016

During the past few decades there has been a significantly increasing trend in germ cell tumours all over the world, particularly in countries with Caucasian populations. The changes in incidence have occurred so fast that only environmental factors can explain this development. This review focuses on the hypothesis that testicular germ cell cancer, which originates from germ cell neoplasia in situ, is of foetal origin and associated with other male reproductive problems through a testicular dysgenesis syndrome, also including foetal origin of impaired spermatogenesis, hypospadias and cryptorchidism. There is little doubt that environmental factors associated with modern lifestyles have - in a broad sense - had an adverse influence on male reproductive health. The hypothesis that exposure to endocrine-disrupting chemicals plays a fundamental role in this trend is plausible. This is based on evidence from animal studies that demonstrate adverse reproductive effects caused by a number of endocrine-disrupting chemicals to which humans are exposed as part of our modern lifestyle.
Umbilical Cord Blood Transplantation Is a Feasible Rescue Therapeutic Option for Patients Suffering from Graft Failure after Previous Hematopoietic Stem Cell Transplantation
Authors: Bojic Marija , Worel Nina , Sperr Wolfgang R. , Schellongowski Peter , Wohlfarth Philipp , Schwarzinger Ilse , Mitterbauer-Hohendanner Gerlinde , Fischer Gottfried , Dieckmann Karin Ute , Lamm Wolfgang , Leiner Michael , Schulenburg Axel , Mitterbauer Margit , Greinix Hildegard T. , Kalhs Peter , Rabitsch Werner
Published: February 2016

Objective: Umbilical cord blood (UCB) is an important graft source for hematopoietic stem cell transplantation (SCT). Due to less stringent human leukocyte antigen (HLA) matching criteria compared to bone marrow or peripheral blood stem cells, UCB enables patients lacking an HLA-matched donor to receive potentially curative SCT. Methods: We retrospectively analyzed the efficacy and safety of UCB transplantation (UCBT) at our center. Results: Between June 2009 and June 2015, 27 UCBT were performed in 25 patients. Reasons for the use of UCB were lack of adequate related or unrelated stem cell donor (n = 20) and graft failure after previous SCT (n = 7). Median time to neutrophil engraftment was 22 days. Four patients experienced primary graft failure. Thirteen patients developed acute graft-versus-host disease (GVHD), whereupon 6 subsequently also developed chronic GVHD. After a median follow-up time of 19 months, 9 patients relapsed and 12 patients died. Cause of death was relapse in 8 and transplant-related events in 4 patients. Median overall survival and progression-free survival have not been reached yet. Conclusion: In our experience, UCBT is an alternative graft source for patients lacking a suitable related or unrelated donor and a feasible treatment option for patients experiencing graft failure after previous SCT.
On the Classification and Grading of Medulloepithelioma of the Eye
Authors: Verdijk Robert M.
Published: February 2016

Medulloepithelioma is a rare congenital tumor of the ciliary body and iris. The current classification and grading of medulloepithelioma shows inconsistencies and does not reflect clinical behavior. This position paper discusses the backgrounds of the current classification and intends to initiate a discussion on an alternative classification and grading scheme.
Protective Effect of Naringenin against Lipopolysaccharide-Induced Acute Lung Injury in Rats
Authors: Fouad Amr A. , Albuali Waleed H. , Jresat Iyad
Published: February 2016

Background/Aims: Lipopolysaccharide (LPS) induces acute lung injury (ALI) through oxidative stress and inflammation. Naringenin exerts antioxidant and anti-inflammatory effects. The possible protective effect of naringenin was investigated against ALI induced by LPS in rats. Methods: Rats received a single injection of LPS (5 mg/kg, i.v.). Naringenin was given for 4 consecutive days, at 2 doses (50 and 100 mg/kg/day, p.o.), starting 3 days before LPS administration. Results: LPS significantly increased wet/dry lung weight ratio, malondialdehyde, nitric oxide (NO), interleukin-6, and myeloperoxidase activity in the lung tissues. Naringenin, particularly the higher dose, significantly ameliorated the LPS-induced changes in the measured parameters. Also, naringenin markedly reduced the histopathological lung tissue injury that resulted from LPS. Naringenin significantly decreased the LPS-induced expression of nuclear factor-κB, inducible NO synthase, tumor necrosis factor-a, caspase-3, and significantly increased heat shock protein 70 expression in the lungs. Conclusion: Naringenin significantly protected against LPS-induced ALI in rats through its anti-inflammatory, antioxidant, antinitrosative, and antiapoptotic effects.
Acute Ischemia of the Glans Penis after Circumcision Treated with Hyperbaric Therapy and Pentoxifylline: Case Report and Revision of the Literature
Authors: Migliorini Filippo , Bianconi Francesco , Bizzotto Leonardo , Porcaro Antonio Benito , Artibani Walter
Published: February 2016

Acute severe ischemia of glans penis after circumcision is a very rare event and, if not treated, can lead to irreversible necrosis with severe consequences such as loss of part of the penis. The possible causes for this condition could be blood-vessel binding or cauterization, dorsal penile nerve block (DPNB), local anesthesia with vasoconstricting agents and wound dressing compression. The aim of the treatment is to provide good blood supply and thus, oxygen delivery to the ischemic penis. The therapeutic options include hyperbaric therapy (HBOT), pentoxifylline (PTX), enoxaparina, iloprost, antiplatelet, corticosteroids and peridural anesthesia. We report the case of a 24-year-old male who developed an acute severe glans penis ischemia after circumcision done under DPNB. The patient was successfully treated with HBOT in combination with PTX.
Ocorrência de carrapatos em animais silvestres recebidos e atendidos pelo Parque Zoológico Municipal Quinzinho de Barros, Sorocaba, São Paulo, Brasil
Authors: Martins Thiago Fernandes , Teixeira Rodrigo Hidalgo Friciello , Labruna Marcelo Bahia
Published: February 2016

Os carrapatos são ectoparasitas da classe Arachnida que parasitam vertebrados terrestres, anfíbios, repteis, aves e mamíferos. O presente trabalho relata a ocorrência de carrapatos ixodídeos em animais silvestres recebidos e atendidos pelo Hospital Veterinário do Parque Zoológico Municipal Quinzinho de Barros, localizado no município de Sorocaba, estado de São Paulo, Brasil. De setembro de 1999 a maio de 2015, foram coletados carrapatos em animais silvestres da região de Sorocaba e de outros 20 municípios do interior do estado de São Paulo. Ao todo, foram identificados 43 larvas, 637 ninfas e 1.178 adultos (631 machos e 547 fêmeas), totalizando 1.858 exemplares de 14 espécies distintas de ixodídeos. Durante exames clínicos de rotina, foram inspecionadas duas espécies de repteis, uma espécie de ave e 11 espécies distintas de mamíferos de um total de 103 animais silvestres amostrados. Nos repteis foram identificados Amblyomma rotundatum, nas aves Amblyomma sculptum e nos mamíferos Amblyomma aureolatum, Amblyomma brasiliense, Amblyomma calcaratum, Amblyomma dubitatum, Amblyomma longirostre, Amblyomma nodosum, Amblyomma ovale, A. sculptum, Amblyomma varium, Ixodes aragaoi, Haemaphysalis juxtakochi, Rhipicephalus microplus e Dermacentor nitens. Este estudo relata os primeiros registros de fêmeas de A. rotundatum parasitando Hydromedusa tectifera e Oxyrhopus guibei, assim como ninfas de A. dubitatum e H. juxtakochi em Chrysocyon brachyurus, ninfas de A. brasiliense em Myrmecophaga tridactyla e Tamandua tetradactyla, além de ninfas de A. sculptum em Alouatta guariba e Sphiggurus villosus no país, demonstrando que os zoológicos são uma fonte de informação valiosa para o conhecimento parasitológico da fauna silvestre brasileira.