bluuebunny/crossref_metadata_2025 huggingface dataset:
Clear Cell Adenocarcinoma of the Urethra: Review of the Literature
Authors: Venyo Anthony Kodzo-Grey
Published: January 2015

Background.Clear cell adenocarcinoma of the urethra (CCAU) is extremely rare and a number of clinicians may be unfamiliar with its diagnosis and biological behaviour.Aims.To review the literature on CCAU.Methods.Various internet databases were used.Results/Literature Review.(i) CCAU occurs in adults and in women in the great majority of cases. (ii) It has a particular association with urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; and probably does not arise by malignant transformation of nephrogenic adenoma. (iii) It is usually, readily distinguished from nephrogenic adenoma because of greater cytological a-typicality and mitotic activity and does not stain for prostate-specific antigen or prostatic acid phosphatase. (iv) It has been treated by anterior exenteration in women and cystoprostatectomy in men and at times by radiotherapy; chemotherapy has rarely been given. (v) CCAU is aggressive with low 5-year survival rates. (vi) There is no consensus opinion of treatment options that would improve the prognosis.Conclusions.Few cases of CCAU have been reported. Urologists, gynaecologists, pathologists, and oncologists should report cases of CCAU they encounter and enter them into a multicentric trial to determine the best treatment options that would improve the prognosis.
Tumor-Derived Osteopontin Reprograms Normal Mammary Fibroblasts to Promote Inflammation and Tumor Growth in Breast Cancer
Authors: Sharon Yoray , Raz Yael , Cohen Noam , Ben-Shmuel Amir , Schwartz Hila , Geiger Tamar , Erez Neta
Published: January 2015

Breast tumors are characterized by an extensive desmoplastic stroma, abundantly populated by fibroblasts. Cancer-associated fibroblasts (CAF) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. CAF also orchestrate tumor-promoting inflammation in multiple tumor types, including breast cancer. However, the mechanisms through which normal tissue fibroblasts are reprogrammed to tumor-promoting CAFs are mainly obscure. Here, we show that mammary fibroblasts can be educated by breast cancer cells to become activated to a proinflammatory state that supports malignant progression. Proteomic analysis of breast cancer cell–secreted factors identified the secreted proinflammatory mediator osteopontin, which has been implicated in inflammation, tumor progression, and metastasis. Osteopontin was highly secreted by mouse and human breast cancer cells, and tumor cell–secreted osteopontin activated a CAF phenotypes in normal mammary fibroblasts in vitro and in vivo. Osteopontin was sufficient to induce fibroblast reprogramming and neutralizing antibodies against osteopontin-blocked fibroblast activation induced by tumor cells. The ability of secreted osteopontin to activate mammary fibroblasts relied upon its known receptors CD44 and αVβ3 integrin. Strikingly, osteopontin silencing in tumor cells in vivo attenuated stromal activation and inhibited tumor growth. Our findings establish a critical functional role for paracrine signaling by tumor-derived osteopontin in reprograming normal fibroblasts into tumor-promoting CAFs. Cancer Res; 75(6); 963–73. ©2015 AACR.
TLR2 Limits Development of Hepatocellular Carcinoma by Reducing IL18-Mediated Immunosuppression
Authors: Li Shinan , Sun Rui , Chen Yongyan , Wei Haiming , Tian Zhigang
Published: January 2015

Immune mechanisms underlying hepatocellular carcinoma (HCC) are not well understood. Here, we show that the Toll-like receptor TLR2 inhibits production of the proinflammatory cytokine IL18 and protects mice from DEN-induced liver carcinogenesis. On this protocol, Tlr2−/− mice exhibited more aggressive HCC development associated with impaired CD8+ T-cell function. Furthermore, Ly6ChighIL18Rα+ myeloid-derived suppressor cells (MDSC) were increased in number in the livers of Tlr2−/− mice before tumor onset. MDSC in this setting exhibited higher iNOS levels that could inhibit IFNγ production and CD8+ T-cell proliferation in vitro. Notably, Tlr2−/− hepatocytes produced more mature IL18 after DEN treatment that was sufficient to drive MDSC accumulation there. IL18 adminstration was sufficient to induce accumulation of MDSC, whereas hepatocyte-specific silencing of IL18 in Tlr2−/− mice decreased the proportion of MDSC, increased the proportion of functional CD8+ T cells, and alleviated HCC progression. IL18 production was mediated by caspase-8 insofar as the decrease in its silencing was sufficient to attenuate levels of mature IL18 in Tlr2−/− mice. Furthermore, the TLR2 agonist Pam3CSK4 inhibited both caspase-8 and IL18 expression, decreasing MDSC, increasing CD8+ T-cell function, and promoting HCC regression. Overall, our findings show how TLR2 deficiency accelerates IL18-mediated immunosuppression during liver carcinogenesis, providing new insights into immune control that may assist the design of effective immunotherapies to treat HCC. Cancer Res; 75(6); 986–95. ©2015 AACR.
Clinical Efficacy and Tolerability of a Novel Selective Corticosteroid in Atopic Dermatitis - Two Randomised Controlled Trials
Authors: Dölle Sabine , Hielscher Nadine , Bareille Philippe Jean , Hardes Kelly , Robertson Jonathan , Worm Margitta
Published: January 2015

Topical corticosteroids remain the first-line therapy for atopic dermatitis (AD). Hence, we investigated the efficacy and safety profile of a novel selective corticosteroid, GW870086. We performed 2 randomised, double-blind, controlled studies with 25 AD patients and 20 healthy subjects. The changes in the Three-Item Severity (TIS) score and the skin thickness were the primary end points, respectively. The adjusted TIS score (day 22) shows that the novel corticosteroid resulted in a non-significant, but dose-dependent reduction compared to placebo (GW870086 0.2% vs. placebo = -0.38, GW870086 2% vs. placebo = -0.89). Significant skin thinning was observed in the second study on days 14 and 21 when patients were treated with the comparator but not with the novel corticosteroid compared to placebo. The clinical efficacy of the new selective corticosteroid was not superior to placebo, although a dose-dependent improvement upon treatment was noticed without the onset of skin thinning.
The Ankle-Brachial Index Is Related to Left Ventricular Ejection Fraction in Bonnet Macaques
Authors: Liu Yang , Bapat Manasi , Kamran Haroon , Salciccioli Louis , Rozenboym Anna , Coplan Jeremy , Lazar Jason M.
Published: January 2015

Low ankle-brachial index (ABI) is a marker of peripheral arterial disease associated with higher cardiovascular risk. ABI has been found to be influenced by left ventricular ejection fraction (LVEF), but this relation is confounded by atherosclerosis. Objectives: Since nonhuman primates have a low incidence of atherosclerosis, we sought to evaluate the effect of LVEF on ABI in 24 healthy female bonnet macaques (age 83 ± 21 months). Methods: LVEF was determined by echocardiography during anesthesia with ketamine. ABI was determined using automatic blood pressure cuff. Results: Mean LVEF was 73 ± 6%. Mean ABI was 1.03 (range 0.78-1.17) with similar right and left lower limb values (p = 0.78). On univariate analysis, mean ABI was significantly correlated with LVEF (r = 0.58, p = 0.003) but not with age, crown-rump length or weight. Mean LVEF increased in a stepwise manner from lowest to highest ABI tertile (68 ± 6 vs. 73 ± 4 vs. 77 ± 5%, p = 0.008). On ordinal regression and forced multivariate linear analyses, ABI status was independently related to LVEF. Conclusions: ABI is influenced by left ventricular systolic function but not age, height, weight or mass index in bonnet macaques. Left ventricular systolic function should be accounted for when considering ABI measurements.
Pulmonary Shunt Fraction Measurement Compared to Contrast Echocardiography in Hereditary Haemorrhagic Telangiectasia Patients: Time to Abandon the 100% Oxygen Method?
Authors: Velthuis Sebastiaan , Vorselaars Veronique M.M. , Westermann Cornelis J.J. , Snijder Repke J. , Mager Johannes J. , Post Martijn C.
Published: January 2015

Background: The presence of pulmonary right-to-left shunting (RLS) is associated with severe neurological complications from paradoxical embolisation in patients with hereditary haemorrhagic telangiectasia (HHT) and screening is warranted. Pulmonary shunt fraction measurement with the 100% oxygen method can be used for the detection and quantification of functional pulmonary RLS, although transthoracic contrast echocardiography (TTCE) has emerged as the gold standard over the last few years. Objective: The aim of this study was to determine the true diagnostic accuracy of the established 100% oxygen method in detecting pulmonary RLS, as compared to TTCE. Methods: We analysed 628 persons screened for HHT between 2004 and 2010, all of whom underwent TTCE. A quantitative 3-point grading scale was used to differentiate between minimal, moderate or extensive pulmonary RLS on TTCE (grade 1-3, respectively). Additional shunt fraction measurement with the 100% oxygen method was pursued in cases of pO2 <13 or <12 kPa in patients younger or older than 30 years, respectively. A shunt fraction >5% was considered pathological. Results: Both TTCE and the 100% oxygen method were performed in 210 subjects. Although the presence of a pathological shunt fraction correlated with an increased pulmonary shunt grade on TTCE, the 100% oxygen method confirmed a >5% shunt fraction in only 51% of patients with pulmonary RLS on TTCE (14, 20 and 72% for grade 1, 2 and 3, respectively). Conclusion: Pulmonary shunt fraction measurement with the 100% oxygen method is not a useful screening technique for the detection of pulmonary RLS in HHT as its sensitivity is too low and large pulmonary shunts on TTCE may remain undetected using this method.
Acute Effects of Biventricular Pacing in Heart Failure Patients with a Normal Ejection Fraction and Mechanical Dyssynchrony
Authors: Wang Yi-Chih , Yu Chih-Chieh , Chiu Fu-Chun , Splett Vincent , Klepfer Ruth , Hilpisch Kathryn , Tsai Chia-Ti , Lai Ling-Ping , Hwang Juey-Jen , Lin Jiunn-Lee
Published: January 2015

Objectives: We tested the acute effects of resynchronization in heart failure patients with a normal (>50%) left ventricular (LV) ejection fraction (HFNEF) and mechanical dyssynchrony. Methods: Twenty-four HFNEF patients (72 ± 6 years, 5 male) with mechanical dyssynchrony (standard deviation of electromechanical time delay among 12 LV segments >35 ms) were studied with temporary pacing catheters in the right atrium, LV, and right ventricle (RV), and high-fidelity catheters for pressure recording. Using selected atrioventricular (AV) intervals of 60, 90, 120, 150, and 180 ms to optimize transmitral flow during simultaneous biventricular pacing, the RV-LV (VV) interval was then evaluated at RV30, RV15, 0, LV15, LV30, and LV45 (RV or LV indicates which ventricle was paced first, the number indicates by how many ms). Results: During simultaneous pacing, longer AV intervals were associated with improved LV pressure-derivative minimums and increased aortic pressures (p < 0.05 vs. normal sinus rhythm). In the VV interval from RV30 to LV45, there was a graded increase in the aortic velocity time integral and a decrease in dyssynchrony during simultaneous or LV-first pacing (p < 0.05 vs. normal sinus rhythm). Conclusions: For HFNEF patients with mechanical dyssynchrony, acute simultaneous biventricular or LV-first pacing with longer AV intervals reduced mechanical dyssynchrony and improved diastolic and systolic hemodynamics.
Association of Lifestyle and Cardiovascular Risk Factors with Lung Function in a Sample of the Adult Italian Population: A Cross-Sectional Survey
Authors: Laurendi Giovanna , Donfrancesco Chiara , Palmieri Luigi , Vanuzzo Diego , Scalera Giselda , Giampaoli Simona ,   on behalf of the Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey 2008-2012
Published: January 2015

Background: Some epidemiological studies have identified high values of pulmonary functions as an indicator of good health. At present little is known about the distribution of these characteristics in the general adult population. Objective: The aim of this study is to describe pulmonary function in the Italian general population and to evaluate its association with some lifestyle and cardiovascular risk conditions using data of the OEC/HES (Cardiovascular Epidemiology Observatory/Health Examination Survey) Project, a cross-sectional survey based on the examination of random samples of the general population. Methods: A total of 9,108 men and women aged 35-79 years were examined between 2008 and 2012. Pulmonary function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured with a spirometer and anthropometric measurements and blood pressure were also recorded, whereas lifestyle (physical activity, smoking habits), health status and drug treatment were assessed by a questionnaire. FEV1 and FVC % predicted were also calculated. Univariate analysis and a multiple linear regression were performed in order to assess associations. Results: FVC and FEV1 percent predicted values were 98.0 (95% CI 97.4-98.6) and 107.3 (95% CI 106.6-107.9) for men and 108.7 (95% CI 107.9-109.4) and 113.3 (95% CI 112.6-114.1) for women. A lower mean FEV1 and FVC % predicted value was found in smokers, individuals physically inactive during their leisure time, diabetics, obese individuals and hypertensive patients. Multivariate linear regression models confirmed the independent association between risk factors and FEV1 and FVC levels. Conclusion: Our data confirm the inverse relationship existing between pulmonary function and cardiovascular risk factors, obesity, dyslipidemias and hypertension, all of which are conditions related to chronic diseases. An early public healthcare intervention on lifestyle could be useful to reduce the decline in pulmonary function.
Neuropsychiatric Symptoms in Primary Progressive Aphasia and Apraxia of Speech
Authors: Singh Tarun D. , Duffy Joseph R. , Strand Edythe A. , Machulda Mary M. , Whitwell Jennifer L. , Josephs Keith A.
Published: January 2015

Aim: To conduct a prospective analysis of the neuropsychiatric symptoms (NPS) across the three categories of primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS), compare the prevalence and nature of the symptoms, and look at which symptoms could be helpful to better differentiate these PPA and PAOS categories. Methods: A total of 106 consecutive patients with a diagnosis of semantic variant (n = 13), logopenic variant (n = 37), agrammatic variant (n = 15) or PAOS (n = 41) were included in this prospective study. The NPS were measured by the Neuropsychiatric Inventory Questionnaire. Results: There were 65 patients with PPA and 41 with PAOS diagnosis. The most distinguishing features between the two groups were anxiety, apathy, aberrant motor behavior and appetite, while among the subtypes of PPA they were disinhibition and appetite changes. PPA and PAOS patients initially exhibited depression, but with increased disease duration, PAOS patients showed apathy (55.5%) while PPA patients showed disinhibition (28.6%) and aberrant motor behavior (14.3%). Conclusion: Mood symptoms like anxiety and appetite changes are more likely to be present at initial stages of PPA, whereas behavioral symptoms like aberrant motor behavior and apathy are likely to occur early in PAOS. The NPS seem to evolve with the progression of the disease in both PPA and PAOS.
Calcifications in Benfluorex-Induced Valve Heart Disease: A Misknown Association
Authors: Plurien François , Bruneval Patrick , Jobic Yannick , Iung Bernard , Ennezat Pierre-Vladimir
Published: January 2015

Benfluorex, an anorexigenic agent, is recognized to induce noncalcified restrictive valvular regurgitation. We report a well-documented case of a 73-year-old patient who developed heart failure with aortic and mitral regurgitation following benfluorex intake. Echocardiography and peroperative analysis found large mitral annular calcifications and aortic subvalvular calcifications. Pathology confirmed drug-induced valve heart disease (DIVHD). The presence of valvular apparatus calcification should not lead to diagnosis of degenerative valvular disease and a priori preclude the diagnosis of DIVHD.
Bronchogenic Stress Cardiomyopathy: A Case Series
Authors: Rajwani Adil , Adam Zulfiquar , Hall James Anthony
Published: January 2015

Despite a growing awareness of stress (takotsubo) cardiomyopathy, the diversity in precipitants beyond emotional distress remains under-appreciated. Emerging data implicate a differential influence of precipitant type on the variable presentations of stress cardiomyopathy. We outline 5 cases of stress cardiomyopathy where the precipitant was an acute exacerbation of chronic obstructive pulmonary disease treated with high-dose bronchodilator therapy. In this setting, an atypical and insidious presentation of the stress cardiomyopathy was consistently observed that was difficult to distinguish from the acute airway exacerbation itself, with an absence of chest pain in particular. Scrutiny of published single-case reports reveals a similar atypical presentation; this supports the existence of a novel bronchogenic subgroup of stress cardiomyopathy. A key role of repeat ECG evaluation in distinguishing protracted but uncomplicated bronchospasm from bronchogenic stress cardiomyopathy is highlighted. Further data are now required to examine whether high-dose β-agonist therapy is implicated in this association.
Serum Visfatin and Leptin in Relation to Childhood Adiposity and Body Fat Distribution: The PIAMA Birth Cohort Study
Authors: Willers Saskia M. , Brunekreef Bert , Abrahamse-Berkeveld Marieke , van de Heijning Bert , van der Beek Eline , Postma Dirkje S. , Kerkhof Marjan , Smit Henriëtte A. , Wijga Alet H.
Published: January 2015

Background/Aims: Visfatin has been suggested as a marker of visceral adiposity. We hypothesized that visfatin, but not leptin, would be specifically associated with visceral adiposity. We investigated the relation of serum visfatin and leptin with measures of adiposity and body fat distribution in children. Methods: Serum leptin and visfatin levels were measured in 1,022 12-year-old children participating in the PIAMA birth cohort. BMI, waist, hip and upper arm circumference were available for all children. Multiple linear regression analyses were conducted to study associations between different anthropometric indices and log serum visfatin and leptin levels. Results: All anthropometric indices showed positive and strong dose-response relationships with serum leptin. Visfatin was increased only in children with a high waist-to-hip ratio. The effect size was small compared to those observed for leptin and the association was present in overweight children (n = 133) but not in normal weight children. Conclusion: Serum leptin levels strongly increased with increasing adiposity, but were not related to a specific type of fat distribution. In contrast, serum visfatin was associated only with high waist-to-hip ratio in overweight children. Based on our study we would currently not recommend visfatin as a marker of visceral adiposity in the general population of children.
Assessing the Discriminant Ability, Reliability, and Comparability of Multiple Short Forms of the Boston Naming Test in an Alzheimer's Disease Center Cohort
Authors: Katsumata Yuriko , Mathews Melissa , Abner Erin L. , Jicha Gregory A. , Caban-Holt Allison , Smith Charles D. , Nelson Peter T. , Kryscio Richard J. , Schmitt Frederick A. , Fardo David W.
Published: January 2015

Background: The Boston Naming Test (BNT) is a commonly used neuropsychological test of confrontation naming that aids in determining the presence and severity of dysnomia. Many short versions of the original 60-item test have been developed and are routinely administered in clinical/research settings. Because of the common need to translate similar measures within and across studies, it is important to evaluate the operating characteristics and agreement of different BNT versions. Methods: We analyzed longitudinal data of research volunteers (n = 681) from the University of Kentucky Alzheimer's Disease Center longitudinal cohort. Conclusions: With the notable exception of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) 15-item BNT, short forms were internally consistent and highly correlated with the full version; these measures varied by diagnosis and generally improved from normal to mild cognitive impairment (MCI) to dementia. All short forms retained the ability to discriminate between normal subjects and those with dementia. The ability to discriminate between normal and MCI subjects was less strong for the short forms than the full BNT, but they exhibited similar patterns. These results have important implications for researchers designing longitudinal studies, who must consider that the statistical properties of even closely related test forms may be quite different.
Spinocerebellar Ataxia Type 7: A Neurodegenerative Disorder with Peripheral Neuropathy
Authors: Salas-Vargas José , Mancera-Gervacio Jocelyn , Velázquez-Pérez Luis , Rodrígez-Labrada Roberto , Martínez-Cruz Emilio , Magaña Jonathan J. , Durand-Rivera Alfredo , Hernández-Hernández Oscar , Cisneros Bulmaro , Gonzalez-Piña Rigoberto
Published: January 2015

Background: Autosomal dominant spinocerebellar ataxias (SCA) are a group of inherited neurodegenerative disorders that typically show peripheral neuropathy. SCA7 is one of the rarest forms of SCA (<1/100,000 individuals). However, the disease shows a prevalence of ∼800/100,000 inhabitants in certain regions of Mexico. This low global prevalence may explain, at least in part, the isolated anecdotal and limited clinical data regarding peripheral neuropathy in SCA7 patients. Aim: To assess sensory and motor peripheral nerve action potentials in an SCA7 patients group and in healthy volunteers, and subsequently correlate the electrophysiological findings with clinical and genetic features. Materials and Methods: We enrolled in our study, 13 symptomatic SCA7 patients with a confirmed molecular and clinical diagnosis, and 19 healthy volunteers as the control group. Nerve conduction studies were carried out using standard electromyography recording methods. The sensory and motor latency, amplitude and conduction velocity were recorded in both experimental groups and analyzed using the Student's t-test. Results: SCA7 patients showed a significant prolongation of sensory nerve conduction latencies, as well as a decrease in sensory amplitudes. Decreases in motor amplitudes and peroneal conduction velocity were also observed. Finally, we found an association between CAG repeats and the severity of cerebellar and non-cerebellar symptoms with electrophysiological signs of demyelinization. Discussion: Our results reveal the existence of a critical sensorimotor peripheral neuropathy in SCA7 patients. Moreover, we show that using sensitive electrophysiological tools to evaluate nerve conduction can improve the diagnosis and design of therapeutic options based on pharmacological and rehabilitative strategies. Conclusion: These findings demonstrate that SCA7 is a disease that globally affects the peripheral nervous system.
Principles of Rehabilitation and Reactivation
Authors: Osadnik Christian R. , Rodrigues Fernanda M.M. , Camillo Carlos A. , Loeckx Matthias , Janssens Wim , Dooms Christophe , Troosters Thierry
Published: January 2015

Skeletal muscle dysfunction and physical inactivity are two clinically important features of a wide range of acute and chronic respiratory conditions. Optimisation of both of these features is important in order to improve physical function, prevent clinical deterioration and maximise community participation. One of the most potent and evidence-based interventions to address these physical deficits is pulmonary rehabilitation (PR). Whilst the majority of PR research has been conducted in patients with chronic obstructive pulmonary disease, there is widespread recognition that PR can benefit many other respiratory patient groups. These include patients with interstitial lung diseases, asthma, pulmonary hypertension, pre-/post-lung surgery (e.g. lung cancer, transplantation) and cystic fibrosis to name a few. Exercise training must be appropriately prescribed by a skilled healthcare professional with comprehensive knowledge of the pathology and physiology of these conditions, as well as a sound understanding of the exercise physiology and core principles of exercise prescription, monitoring and progression. It has also become increasingly recognised that people with respiratory conditions, particularly those with chronic disease, are considerably less active than those of good health. PR should therefore aim to induce behavioural change to facilitate the adoption and maintenance of an active lifestyle. In addition, PR should pay attention to the psychological well-being of patients and self-management of their lung disease in all its aspects. To that end, multidisciplinary individualised programs should be offered. This review sets the scene of PR principles for a series of papers that will focus on specific diseases other than chronic obstructive pulmonary disease where rehabilitation may offer a clinically important aspect of care over and above conventional pharmacological treatment.
Characteristic Features of Reproductive Hormone Profiles in Late Adolescent and Adult Females with Complete Androgen Insensitivity Syndrome
Authors: Doehnert Ulla , Bertelloni Silvano , Werner Ralf , Dati Eleonora , Hiort Olaf
Published: January 2015

Little is known about gonadotropins and sex steroid levels in postpubertal women with complete androgen insensitivity syndrome (CAIS). In order to define reproductive hormone profiles in women with CAIS and intact gonads, 42 postpubertal females with proven CAIS (age range 14-50 years) with testes in situ were examined. Reproductive hormone values [testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH)] were assessed by commercially available immunoassays. In women with CAIS, LH levels (median 18.5 IU/l, range 5.5-51.1 IU/l) were elevated above the usual adult reference ranges, whereas FSH values (3.5 IU/l, 0.4-16.3 IU/l) were not. Basal T (20 nmol/l, 6-52 nmol/l) and E2 values (113 pmol/l; 18-257 pmol/l) were found in the usual adult male reference ranges; SHBG levels (53 nmol/l, 15-180 nmol/l) were in the adult female reference range. Calculated free androgen indices (Tx10³/SHBG: 380, 114-863) and aromatization indices (E2/T: 0.052, 0.020-0.196) did not differ from the reference ranges for adult men given in the literature (Tx10³/SHBG: 315-936; E2/T: 0.03-0.07). Reproductive hormone profiles in women with CAIS do not follow the usual male/female pattern, suggesting a specific postpubertal hormone milieu. Albeit calculation of CAIS-specific reference ranges requires larger series and standardization of laboratory methods, these results may be a prerequisite for the identification of pathologic hormone patterns in women with CAIS and gonads in situ. The present data will also be useful to monitor hormone replacement therapy in individuals with removed gonads.
Effects of Continuous Positive Airway Pressure Treatment on Clinic and Ambulatory Blood Pressures in Patients With Obstructive Sleep Apnea and Resistant Hypertension
Authors: Muxfeldt Elizabeth S. , Margallo Victor , Costa Leonardo M.S. , Guimarães Gleison , Cavalcante Aline H. , Azevedo João C.M. , de Souza Fabio , Cardoso Claudia R.L. , Salles Gil F.
Published: January 2015

The effect of continuous positive airway pressure (CPAP) on blood pressures (BPs) in patients with resistant hypertension and obstructive sleep apnea is not established. We aimed to evaluate it in a randomized controlled clinical trial, with blinded assessment of outcomes. Four hundred thirty-four resistant hypertensive patients were screened and 117 patients with moderate/severe obstructive sleep apnea, defined by an apnea–hypopnea index ≥15 per hour, were randomized to 6-month CPAP treatment (57 patients) or no therapy (60 patients), while maintaining antihypertensive treatment. Clinic and 24-hour ambulatory BPs were obtained before and after 6-month treatment. Primary outcomes were changes in clinic and ambulatory BPs and in nocturnal BP fall patterns. Intention-to-treat and per-protocol (limited to those with uncontrolled ambulatory BPs) analyses were performed. Patients had mean (SD) 24-hour BP of 129(16)/75(12) mm Hg, and 59% had uncontrolled ambulatory BPs. Mean apnea–hypopnea index was 41 per hour and 58.5% had severe obstructive sleep apnea. On intention-to-treat analysis, there was no significant difference in any BP change, neither in nocturnal BP fall, between CPAP and control groups. The best effect of CPAP was on night-time systolic blood pressure in per-protocol analysis, with greater reduction of 4.7 mm Hg (95% confidence interval, −11.3 to +3.1 mm Hg;
P
=0.24) and an increase in nocturnal BP fall of 2.2% (95% confidence interval, −1.6% to +5.8%;
P
=0.25), in comparison with control group. In conclusion, CPAP treatment had no significant effect on clinic and ambulatory BPs in patients with resistant hypertension and moderate/severe obstructive sleep apnea, although a beneficial effect on night-time systolic blood pressure and on nocturnal BP fall might exist in patients with uncontrolled ambulatory BP levels.
Rhythmic Gamma Stimulation Affects Bistable Perception
Authors: Cabral-Calderin Yuranny , Schmidt-Samoa Carsten , Wilke Melanie
Published: January 2015

When our brain is confronted with ambiguous visual stimuli, perception spontaneously alternates between different possible interpretations although the physical stimulus remains the same. Both alpha (8–12 Hz) and gamma (>30 Hz) oscillations have been reported to correlate with such spontaneous perceptual reversals. However, whether these oscillations play a causal role in triggering perceptual switches remains unknown. To address this question, we applied transcranial alternating current stimulation (tACS) over the posterior cortex of healthy human participants to boost alpha and gamma oscillations. At the same time, participants were reporting their percepts of an ambiguous structure-from-motion stimulus. We found that tACS in the gamma band (60 Hz) increased the number of spontaneous perceptual reversals, whereas no significant effect was found for tACS in alpha (10 Hz) and higher gamma (80 Hz) frequencies. Our results suggest a mechanistic role of gamma but not alpha oscillations in the resolution of perceptual ambiguity.
Memristor Models for Machine Learning
Authors: Carbajal Juan Pablo , Dambre Joni , Hermans Michiel , Schrauwen Benjamin
Published: January 2015

In the quest for alternatives to traditional complementary metal-oxide-semiconductor, it is being suggested that digital computing efficiency and power can be improved by matching the precision to the application. Many applications do not need the high precision that is being used today. In particular, large gains in area and power efficiency could be achieved by dedicated analog realizations of approximate computing engines. In this work we explore the use of memristor networks for analog approximate computation, based on a machine learning framework called reservoir computing. Most experimental investigations on the dynamics of memristors focus on their nonvolatile behavior. Hence, the volatility that is present in the developed technologies is usually unwanted and is not included in simulation models. In contrast, in reservoir computing, volatility is not only desirable but necessary. Therefore, in this work, we propose two different ways to incorporate it into memristor simulation models. The first is an extension of Strukov’s model, and the second is an equivalent Wiener model approximation. We analyze and compare the dynamical properties of these models and discuss their implications for the memory and the nonlinear processing capacity of memristor networks. Our results indicate that device variability, increasingly causing problems in traditional computer design, is an asset in the context of reservoir computing. We conclude that although both models could lead to useful memristor-based reservoir computing systems, their computational performance will differ. Therefore, experimental modeling research is required for the development of accurate volatile memristor models.
Oscillator-Interference Models of Path Integration Do Not Require Theta Oscillations
Authors: Orchard Jeff
Published: January 2015

Navigation and path integration in rodents seems to involve place cells, grid cells, and theta oscillations (4–12 Hz) in the local field potential. Two main theories have been proposed to explain the neurological underpinnings of how these phenomena relate to navigation and to each other. Attractor network (AN) models revolve around the idea that local excitation and long-range inhibition connectivity can spontaneously generate grid-cell-like activity patterns. Oscillator interference (OI) models propose that spatial patterns of activity are caused by the interference patterns between neural oscillators. In rats, these oscillators have a frequency close to the theta frequency. Recent studies have shown that bats do not exhibit a theta cycle when they crawl, and yet they still have grid cells. This has been interpreted as a criticism of OI models. However, OI models do not require theta oscillations. We explain why the absence of theta oscillations does not contradict OI models and discuss how the two families of models might be distinguished experimentally.
A Balanced Protocol for Return to School for Children and Youth Following Concussive Injury
Authors: DeMatteo Carol , Stazyk Kathy , Giglia Lucy , Mahoney William , Singh Sheila K. , Hollenberg Robert , Harper Jessica A. , Missiuna Cheryl , Law Mary , McCauley Dayle , Randall Sarah
Published: January 2015

Background. Few protocols exist for returning children/youth to school after concussion. Childhood concussion can significantly affect school performance, which is vital to social development, academic learning, and preparation for future roles. The goal of this knowledge translation research was to develop evidence based materials to inform physicians about pediatric concussion. Methods. The Return to School (RTS) concussion protocol was developed following the National Institute for Health and Care Excellence procedures. Results. Based on a scoping review, and stakeholder opinions, an RTS protocol was developed for children/youth. This unique protocol focuses on school adaptation in 4 main areas: ( a) timetable/attendance, ( b) curriculum, ( c) environmental modifications, and ( d) activity modifications. Conclusion. A balance of cognitive rest and timely return to school need to be considered for returning any student to school after a concussion. Implementation of these new recommendations may be an important tool in prevention of prolonged absence from school and academic failure while supporting brain recovery.
Acculturation, Adaptation, and Mental Health Among Ladakhi College Students
Authors: Ozer Simon
Published: January 2015

The Indian region of Ladakh has recently undergone comprehensive sociocultural changes through the process of acculturation. The present study employs an acculturation psychological framework to assess how two groups of Ladakhi college students navigate through different degrees of exposure to acculturation and how this affects their mental health. Using mixed methods, 292 (age: M = 20.89, SD = 1.66; 64.4% females) respondents were included in the quantitative assessment and 12 participated in semistructured interviews. Analysis revealed that students with less acculturation exposure were more oriented toward ethnic culture and to a greater extent experienced impaired mental health when compared with the sample with more acculturation. Most prevalent among the students (34.2%) was a bicultural orientation, integrating both ethnic and mainstream culture. In general, acculturation orientation was not associated with quantitative measures of depression or anxiety. The qualitative analysis revealed agency and cultural identity to be pivotal factors in the process of reproducing culture and negotiating cultural change.
Communicating future overheating risks to building design practitioners: Using the Low Carbon Futures tool
Authors: Gul Mehreen Saleem , Jenkins DP , Patidar S , Menzies GF , Banfill PFG , Gibson GJ
Published: January 2015

The Low Carbon Futures tool provides a probabilistic assessment of future overheating risks and cooling demands for domestic and nondomestic buildings in the UK. The approach adopted for the development of the Low Carbon Futures tool includes academic rigour within the development of the calculation engine, and also practitioner feedback throughout the process. This paper discusses the journey of the tool from modelling and simulation to the practitioner engagement, which took place by means of a questionnaire, focus groups and interviews with building design professionals aimed at understanding how the issue of overheating in buildings is being addressed. Throughout these events, the synergies between designing for low-carbon targets and designing for a future climate were explored. A final dissemination event was held to identify output styles that could be generated by the Low Carbon Futures tool that would be more practical and useful for specific client types. The workshop discussions serve to shape the outputs from the tool, and the feedback gathered will be used to inform a number of output styles, based on client type.

Practical application: This paper outlines the development of the Low Carbon Futures tool for analysing overheating risks in buildings and discusses the practitioner feedback obtained from industry professionals on the use and applicability of the tool, in a final event hosted by the Low Carbon Futures research team in London. This event confirmed that practitioners need to be comfortable with the layout and format of the output in order to communicate its meaning and possible implications to a range of clients. A balanced output is required, which conveys some of the complexity of the underlying analysis, but which is easily understood and conveyed to a potentially lay audience.
A Survey on Characteristics of Japanese Academic Job Market and Evaluation
Authors: Domon Koji , Kitamura Yoshihiro
Published: January 2015

Background:

During the Meiji era, at the end of the 19th century, Japan introduced western systems into many fields, economically developing later than other industrially developed countries. Japan introduced a higher education system modeled on the German system, focusing not on education but on research. The historical background has shaped contemporary Japanese academia differently from that of the United States and the European Union. In addition, because of geographical and linguistic barriers in Asia, intercommunication with researchers in other developed countries has been much less than that between the United States and the European Union, leaving Japanese academia relatively isolated.

Method:

We survey the characteristics of the Japanese academic system in higher education, using the latest published data.

Result:

This article indicates a concentration of research at former imperial universities and a rigidity of movement among universities both internationally and domestically. Furthermore, small differences in salary levels have provided little incentive to perform research. However, while most universities in Japan have not introduced evaluation systems for promotion and salary that are heavily dependent on journal rankings, as in the European Union and United States, Japanese academic performance has not declined.

Conclusion:

This article suggests that in Japan, salary incentives, the impact factor, and so on have had little influence on academic performance. Even though cultural and historical differences between countries affect academic behaviors, we hope that this article might trigger consideration of other possible evaluation schemes for the future.
Role of endocannabinoid signalling in the dorsolateral periaqueductal grey in the modulation of distinct panic-like responses
Authors: Batista Luara A , Bastos Juliana R , Moreira Fabricio A
Published: January 2015

Panic attacks, a major feature of panic disorder, can be modelled in rats by exposing animals to stimuli that induce escape reactions, such as the elevated T-maze or the activation of the dorsolateral periaqueductal grey. Since the cannabinoid CB1 receptor modulates various types of aversive responses, this study tested the hypothesis that enhancement of endocannabinoid signalling in the dorsolateral periaqueductal grey inhibits panic-like reactions in rats. Local injection of the CB1 agonist, arachidonoyl 2-Chloroethylamide (0.005–0.5 pmol), attenuated the escape response from the open arm of the elevated T-maze, a panicolytic effect. The anandamide hydrolysis inhibitor, URB597 (0.3–3 nmol), did not induce consistent results. In the test of dorsolateral periaqueductal grey stimulation with d,l-homocysteic acid, arachidonoyl 2-Chloroethylamide, at the lowest dose, attenuated the escape reaction. The highest dose of URB597 also inhibited this response, contrary to the result obtained in the elevated T-maze. This effect was reversed by the CB1 antagonist, AM251 (100 pmol). The present results confirm the anti-aversive property of direct CB1 receptor activation in the dorsolateral periaqueductal grey. The effect of the anandamide hydrolysis inhibitor, however, could be detected only in a model employing direct stimulation of this structure. Altogether, these results suggest that anandamide signalling is recruited only under certain types of aversive stimuli.
Schizophrenia biomarkers: Translating the descriptive into the diagnostic
Authors: Pickard Benjamin S
Published: January 2015

While schizophrenia and mental health are qualitatively distinct at the level of clinical presentation, the specific molecular signatures that underlie, or associate with, illness are not. Biomarker identification in schizophrenia is intended to offer a number of important benefits to patient well-being including prediction of future illness, diagnostic clarity and a level of disease description that would guide treatment choice. However, the choice of sample and form of analysis used to produce useful biomarkers is still uncertain. In this review, advances from recent studies spanning the technical spectrum are presented together with comment on their comparative strengths and weaknesses. To date, these studies have aided our understanding of the pathological processes associated with illness much more than they have provided robust biomarkers. A number of reasons for this observation are suggested, as are new strategies for the extraction of biomarkers from large ‘-omics’ datasets.
Positive Parenting of Young Adolescents by Male Cohabiting Partners
Authors: Forehand Rex , Parent Justin , Golub Andrew , Reid Megan
Published: January 2015

Fathers have often been ignored in the parenting literature. The current study focused on male cohabiting partners (MCPs) who can serve as “social stepfathers” and examined the association of coparent support and conflict with their positive parenting behavior (i.e., acceptance, firm control, and monitoring) of adolescents. Participants were 121 low-income urban Black cohabiting stepfamilies (mother, MCP, adolescent). The mother and MCP completed measures on coparenting support and conflict, and the young adolescent completed measures on MCP parenting. Using structural equation modeling (SEM), support, but not conflict, was associated with positive parenting. Support and conflict did not interact to influence parenting. The findings suggest that fathering in these families is contextually sensitive and that support from a mother is central for MCPs to engage in positive parenting of adolescents.
Serum sCD95L concentration in patients with spinal cord injury
Authors: Biglari Bahram , Büchler Axel , Swing Tyler , Child Christopher , Biehl Elisabeth , Reitzel Tim , Bruckner Tom , Ferbert Thomas , Korff Sebastian , Rief Harald , Gerner Hans-Jürgen , Moghaddam Arash
Published: January 2015

Objective

To determine serum concentrations of soluble CD95 ligand (sCD95L) in patients with traumatic spinal cord injury.

Methods

Patients with traumatic spinal cord injury were recruited. Blood was collected on admission to hospital and at 4 h, 9 h, 12 h, 24 h, 3 days, 7 days, and 2, 4, 8 and 12 weeks postadmission. Serum concentrations of sCD95L were determined via immunoassay.

Result

The study included 23 patients. Mean sCD95L concentrations were significantly lower at 4 h, 9 h, 12 h and 24 h than at admission, and were significantly higher at 8 and 12 weeks, compared with admission.

Conclusion

The serum sCD95L concentration fell significantly during the first 24 h after traumatic spinal cord injury. Concentrations then rose, becoming significantly higher than admission levels at 8 weeks. sCD95L may represent a possible therapeutic target for traumatic spinal cord injury.
Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts
Authors: Wei Xiaomei , Yan Jin , Tillu Dipti , Asiedu Marina , Weinstein Nicole , Melemedjian Ohannes , Price Theodore , Dussor Gregory
Published: January 2015

Background

Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine.

Methods

NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model.

Results

Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6).

Conclusions

These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine.
The cultural form of György Márkus’s philosophy
Authors: Pickle Jonathan
Published: January 2015

György Márkus’s Culture, Science, Society: The Constitution of Cultural Modernity is the most sophisticated attempt among contemporary philosophies to proffer a radical critical theory of culture based upon a Marxian philosophical anthropology and an emphatically post-metaphysical re-interpretation of the paradigm of production. In this paper, I aim to evince how the content of Márkus’s published writings is related to the cultural form of his philosophical practice that he describes as ‘orientation in thought’. First, I provide an overview of several key features appertaining to Márkus’s heuristic conceptual framework. Second, I clarify the theoretical and practical horizons of his project through a schematic characterization of the three categories of studies that Márkus has not included in his theory of cultural modernity. In conclusion, I raise the question of the exclusion of religion from high culture and propose some counter-arguments.