bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood and Adult Social Conditions and Risk of Stroke
Authors: Grau Armin J. , Ling Paul , Palm Frederik , Urbanek Christian , Becher Heiko , Buggle Florian
Published: April 2012

Background: Socioeconomic conditions may strongly influence the risk of stroke. We tested the hypotheses that indexes of social status in different life periods including childhood are inversely associated with stroke risk and that there is a cumulative effect of social conditions during lifetime on the risk of stroke. Furthermore, we investigated whether social advancement compared to the parental generation is associated with reduced stroke risk. Methods: In a case-control study, we assessed parental professional status, highest school degree, professional education and the last professional activity in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack [TIA; age 60.7 ± 12.8 years (mean ± standard deviation); 31.1% women] and 370 age- and sex-matched control subjects randomly selected from the general population of the same area. Results: Higher level of school exams [odds ratio (OR) 0.58, 95% confidence interval (CI) 0.39–0.86], university or polytechnic high school degrees (OR 0.39, 95% CI 0.24–0.63), nonmanual (last or current) professional activity (OR 0.51, 95% CI 0.37–0.71) and father’s nonmanual professional activity (OR 0.64, 95% 0.43–0.97) were associated with a lower risk of stroke/TIA. Adjustment for vascular risk factors including current smoking and alcohol consumption reduced the strength of these associations and rendered them nonsignificant except for university or polytechnic high school degrees (OR 0.49, 95% CI 0.27–0.87). Additional adjustment for regular sports activity further attenuated the association between academic degrees and risk of stroke/TIA (OR 0.56, 95% CI 0.31–1.02). A score summarizing 4 lifetime social indexes was not independently associated with stroke risk (OR 0.67, 95% CI 0.39–1.16). Social advancement as assessed by changes from paternal manual work to nonmanual work in the index generation was more common among control subjects (23.5%) than patients (15.3%; p = 0.0097), but such advancement was not independently associated with stroke/TIA after adjustment for all covariables (OR 0.82, 95% CI 0.50–1.33). Conclusions: Socioeconomic conditions were inversely linked to the risk of stroke/TIA. These associations were strongly influenced by lifestyle factors such as smoking, alcohol consumption and mainly sports activity. Stroke preventive strategies may have a particularly large potential if they focus on such lifestyle habits in socially disadvantaged groups.
Hemodiafiltration Improves Plasma 25-Hepcidin Levels: A Prospective, Randomized, Blinded, Cross-Over Study Comparing Hemodialysis and Hemodiafiltration
Authors: Stefánsson Bergur V. , Abramson Mats , Nilsson Ulf , Haraldsson Börje
Published: April 2012

Background/Aims: Data from studies comparing the effect of hemodiafiltration (HDF) and conventional hemodialysis (HD) on clinically important outcomes are insufficient to support superiority of HDF. None of these studies has been participant-blinded. Methods: We performed a prospective, randomized, and patient-blinded cross-over study. Twenty patients on chronic HD received either HD for 2 months followed by post-dilution HDF for 2 months or in opposite order. A range of clinical parameters, as well as markers of inflammation, oxidative stress and iron metabolism was measured. Results: The two treatments were similar with respect to dialysis-related complications, quality of life, and the biomarkers of oxidative stress and inflammation. Compared to HD, 25-hepcidin and β2-microglobulin were 38 and 32%, respectively, lower after 60 days of HDF (p < 0.001 and p < 0.01, respectively). The consumption of ESA (erythropoietin-stimulating agent) and LMWH (low-molecular-weight heparin) was significantly higher with HDF. Conclusion: In short term, HDF is not superior to HD regarding dialysis-related complications. The higher ESA consumption observed with HDF can be explained by blood clotting in tubing and dialyzers, as more anticoagulation was needed with post-dilution HDF. In a longer perspective, lowering serum hepcidin levels may improve pathological iron homeostasis.
Science and the Sources of Hype
Authors: Caulfield T. , Condit C.
Published: April 2012

It has been suggested that genomic research is frequently inappropriately hyped, in both the popular press and the scientific literature, and that this hype has the potential to create a range of social concerns. This paper maps the complex array of social forces that contribute to the phenomenon of hype, including the pressure to publish, the increasingly intense commercialization agenda, the messaging emanating from research institutions, the news media and, even, the public itself. These numerous and interrelated factors create a ‘hype pipeline’ that will be difficult to counter without the utilization of a wide range of policy strategies.
Influence of Smoking Combined with Another Risk Factor on the Risk of Mortality from Coronary Heart Disease and Stroke: Pooled Analysis of 10 Japanese Cohort Studies
Authors: Nakamura Koshi , Nakagawa Hideaki , Sakurai Masaru , Murakami Yoshitaka , Irie Fujiko , Fujiyoshi Akira , Okamura Tomonori , Miura Katsuyuki , Ueshima Hirotsugu ,   The EPOCH-JAPAN Research Group
Published: April 2012

Background: In spite of the importance of a multifactorial approach to preventing cardiovascular disease in smokers, most information on the combined adverse effects of smoking and hypertension or high serum cholesterol on cardiovascular disease has been derived from Western populations, and coronary heart disease was often used as the only endpoint. Therefore, the present large-scale pooled analysis attempted to provide reliable information on the adverse effects of the coexistence of smoking and hypertension or high serum cholesterol on the risk of mortality from coronary heart disease and stroke in both, individuals and the entire population in Japan. Methods: A total of 27,385 male and 39,207 female participants aged 40–89 years were enrolled from 10 well-qualified Japanese cohort studies with a mean follow-up of 10.1 years. Hazard ratios and their corresponding 95% confidence intervals in smokers who had hypertension or high serum cholesterol were estimated for men and women separately using a Cox proportional hazards regression model that included age, body mass index, cohort and either serum total cholesterol or systolic blood pressure as covariates. Fractions of deaths attributable to the coexistence of these risk factors were also calculated. Results: The multivariate-adjusted hazard ratios in male and female current smokers with hypertension, compared with those with neither factor were 2.57 (95% confidence intervals, 1.51–4.38) and 6.14 (3.49–10.79) for coronary heart disease, and 3.28 (1.89–5.71) and 1.61 (0.81–3.18) for cerebral infarction, respectively. The fractions of deaths attributable to the coexistence of current smoking and hypertension in men and women were 24.6 and 9.6% for coronary heart disease and 28.1 and 2.0% for cerebral infarction, respectively. Smokers with high serum cholesterol were broadly comparable to hypertensive smokers only with respect to coronary mortality risk; the hazard ratios, compared with those with neither factor were 4.19 (2.33–7.53) for men and 3.90 (1.57–9.67) for women. The fraction of coronary deaths attributable to the coexistence of current smoking and high serum cholesterol was 6.3% in men and 2.2% in women. There was no interaction between smoking habit and blood pressure or serum total cholesterol for these two subtypes in both men and women. Conclusions: Particular attention should be given to smokers who have concomitant hypertension or high serum cholesterol for preventing deaths due to cardiovascular disease. From a public health perspective in Japan, priority should be given to hypertensive smokers, since this group makes a large contribution to the burden of both coronary and cerebral infarction deaths.
First-Line Bevacizumab-Containing Therapy for Triple-Negative Breast Cancer: Analysis of 585 Patients Treated in the ATHENA Study
Authors: Thomssen Christoph , Pierga Jean-Yves , Pritchard Kathleen I. , Biganzoli Laura , Cortes-Funes Hernan , Petráková Katarína , Kaufman Bella , Duenne Anja , Smith Ian
Published: April 2012

Background: The prognosis for patients with triple-negative breast cancer (TNBC) is poor and treatment options are limited. Bevacizumab improves the efficacy of standard first-line therapy in locally recurrent/metastatic breast cancer (LR/mBC). The benefit of bevacizumab seen in patients with TNBC appears similar to that observed in the overall population. We conducted an exploratory analysis of patients with TNBC treated in the single-arm routine oncology practice ATHENA study. Methods: Patients with previously untreated LR/mBC received standard first-line chemotherapy combined with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks, until progression, unacceptable toxicity, or patient/physician decision). Results: Of 2,264 patients treated in ATHENA, 585 (26%) had TNBC. Most patients received single-agent taxane with bevacizumab. In the TNBC subgroup, the overall response rate was 49%, including complete responses in 10%; only 16% had primary resistant disease. Median time to progression was 7.2 months (95% CI 6.6–7.8) and median overall survival was 18.3 months (95% CI 16.4–19.7). The 1-year overall survival rate was 60%. The safety profile in TNBC was consistent with results in the overall population. Conclusion: This exploratory subgroup analysis suggests that first-line chemotherapy in combination with bevacizumab is an active regimen in patients with metastatic TNBC.
Penetration of Experimental Infiltrants with Different Penetration Coefficients and Ethanol Addition into Natural Caries Lesions in Primary Molars
Authors: Paris S. , Soviero V.M. , Chatzidakis A.J. , Meyer-Lueckel H.
Published: April 2012

This study evaluated the influence of the penetration coefficient (PC) and ethanol addition on the penetration depth (PD) of experimental infiltrants into proximal caries lesions in primary molars. Caries lesions (n = 45) were randomly treated with 1 of 4 experimental infiltrants (PC63; PC185; PC204; PC391) for 5 min. Lesion depths and PDs were analysed using dual fluorescence confocal microscopy. Lesions were almost completely infiltrated in all groups. Median PDs and percentage penetrations were not significantly different between groups (p > 0.05). When applied for 5 min, all tested infiltrants were able to infiltrate proximal caries in primary molars nearly completely.
Cross-Linked Poly(Gamma-Glutamic Acid) Attenuates Pleural and Chest Wall Adhesions in a Mouse Thoracotomy Model
Authors: Izumi Y. , Takahashi Y. , Kohno M. , Nomori H.
Published: April 2012

Background: Cross-linked poly(gamma-glutamic acid) (XL) is derived from a naturally occurring biodegradable polymer produced by Bacillus subtilis. In the present study, we compared the efficacy of XL in preventing adhesion formation after thoracotomy in mice with Seprafilm (SEP), which is currently the most commonly applied adhesion prevention material. Methods: Left thoracotomy was done. Adhesion between the lung and the thoracotomy site (Lu groups), or between the thoracotomy site and the overlying chest muscles (Mu groups), was evaluated in separate groups of animals. In the Lu-XL group (n = 12) and the Mu-XL group (n = 12), approximately 20 mg of XL was applied as powder. In the Lu-SEP group (n = 12) and Mu-SEP group (n = 12), a 5 × 3 mm SEP sheet was applied. Nothing was applied in the Lu-NON group (n = 12) and the Mu-NON group (n = 12). After 7 and 14 days, the respective adhesions were scored and compared. Results: The adhesion score was significantly lower in the Lu-XL group (0.5 ± 0.9) in comparison to the Lu-NON group (3.8 ± 0.5) and the Lu-SEP group (2.2 ± 0.8; p < 0.002), and in the Mu-XL group (0.8 ± 0.7) in comparison to the Mu-NON group (3.8 ± 0.4) and the Mu-SEP group (2.5 ± 0.8; p < 0.001). These differences were similar also at 14 days. Conclusion: It was suggested that the antiadhesive effect of XL was superior to SEP in this particular model of thoracotomy in mice.
Enhancement of the Antitumor Effect on Combination Therapy of an Anticancer Drug and Its Antibody against Carcinoembryonic Antigen
Authors: Shibaguchi Hirotomo , Tsuru Hirofumi , Kuroki Motomu , Kuroki Masahide
Published: April 2012

Background: Carcinoembryonic antigen (CEA) is frequently overexpressed in various types of human cancers and is associated with cell adhesion. There are three possible mechanisms of cancer therapy that employ anti-CEA antibody (Ab): Ab-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) or the prevention of CEA interaction with the extracellular matrix and/or intercellular adhesion molecules resulting in anoikis. In this study, the effect of C2-74, a human anti-CEA monoclonal Ab was evaluated. Methods: ADCC, CDC and anoikis assays in combination with C2-74 and an anticancer drug (5-fluorouracil or cisplatin) were investigated using tumor cell lines (MKN-45, MKN-74 and KATO III). In the anoikis assay, other human anti-CEA Abs and mouse anti-CEA-related cell adhesion molecule 6 Abs were also investigated using HLC-1 cells. Results: Additive cytotoxicity was observed when the anticancer drug and C2-74 on tumor cells were combined in the CDC assays, whereas in the anoikis assay, no such additive effect was observed. Anti-CEA-related cell adhesion molecule 6 Abs, but not anti-CEA Abs, accelerated anoikis in HLC-1 cells. Conclusion: A mechanism for the additive antitumor effect when an anticancer drug and C2-74 are combined is indicated mainly by CDC activity but is irrelevant to anoikis in tumor cells.
Mastoid Obliteration with Concha Cartilage Graft and Temporal Muscle Fascia
Authors: Maniu A. , Cosgarea M.
Published: April 2012

Aim: The aim of our study was to describe an effective technique for mastoid cavity obliteration in canal wall down tympanomastoidectomy for chronic otitis media and to review its efficacy in producing a dry, low-maintenance, small mastoid cavity. Material and Method: A retrospective clinical study of 56 consecutive patients undergoing procedures for active chronic otitis media with cholesteatoma has been carried out. All surgical interventions involved partial mastoid obliteration and restoration of the middle ear space by use of cartilage reconstruction of the tympanic membrane. Ossicular reconstruction was achieved with either a partial or total ossicular replacement prosthesis. Results: A completely dry cavity was achieved in 49 of 56 patients (approx. 88%, 95% confidence interval 77–95%). An overall statistically significant improvement in hearing (p < 0.05) was obtained, with the mean pure-tone average air-bone gap decreasing from 33.4 ± 8.2 dB (average ± SD) to 18.3 ± 9.7 dB. There were no residual or recurrent cholesteatomas. Conclusion: Cartilage reconstruction of the tympanic membrane proved to be a useful adjunct in the surgical management of the chronically draining cavity.
Genistein Attenuated Allergic Airway Inflammation by Modulating the Transcription Factors T-bet, GATA-3 and STAT-6 in a Murine Model of Asthma
Authors: Gao Fei , Wei Dong , Bian Tao , Xie Ping , Zou Jian , Mu Huijun , Zhang Bin , Zhou Xiaoyan
Published: April 2012

Background: Genistein, a flavonoid in legumes and some herbal medicines, has various biological actions. Previous studies have shown that genistein decreased airway inflammation in allergic asthma. However, studies on how genistein affects immunoreactions in asthma are very limited. Objective: It was the aim of this study to investigate the effect of genistein on T helper 1 (Th1)/Th2 cytokines in a murine asthma model and to explore its underlying mechanisms. Methods: The asthma model was set up both in vivo and in vitro: the mice were divided into four groups in vivo, i.e. control group, ovalbumin-sensitized (OVA) group, Gen20 group (20 mg/kg genistein) and Gen40 group (40 mg/kg genistein), and into three groups in vitro, i.e. control group, OVA group, genistein group. Changes in lung histology were observed and concentrations of interleukin-4, interleukin-5 and interferon-γ in bronchoalveolar lavage fluid and serum were measured by enzyme-linked immunosorbent assay. The mRNA expression of GATA binding protein 3 (GATA-3), signal transducer and activator of transcription 6 (STAT-6) and T-box transcription factor (T-bet) in the lungs and CD4+ T cells of each group were detected by real-time PCR and the corresponding proteins were detected by Western blot. Results: The results showed that genistein attenuated OVA-induced airway inflammation, decreased Th2-type cytokines and increased Th1-type cytokines. Additionally, our data suggested that genistein may modulate the Th1/Th2 reaction by inhibiting GATA-3 and STAT-6 production while increasing T-bet production. Conclusion: Genistein may modulate the immunomodulatory actions caused by Th1/Th2 cytokines in asthma, at least partially, by the down-regulation of GATA-3 and STAT-6 and the up-regulation of T-bet.
Pharmaceutical Countermeasures Have Opposite Effects on the Utricles and Semicircular Canals in Man
Authors: Weerts Aurélie P. , De Meyer Guido , Pauwels Griet , Vanspauwen Robby , Dornhoffer John L. , Van de Heyning Paul H. , Wuyts Floris L.
Published: April 2012

Introduction: Sensory conflicts in the vestibular system lead to motion sickness of which space motion sickness (SMS) is a special case. SMS affects up to 70% of the astronauts during the first 3 days in space. The search for effective countermeasures has led to several nonpharmacological and pharmacological approaches. The current study focuses on the effects of lorazepam (1 mg), meclizine (25 mg), promethazine (25 mg), and scopolamine (0.4 mg) on the vestibular system, with special focus on the canal and otolith functions separately. Methods: The study had a placebo-controlled, single blind, repeated measures design. Sixteen healthy volunteers were subjected to a total of 7 test sessions, the first and last being without intake of medication. Semicircular canal function was evaluated by means of electronystagmography and otolith function with unilateral centrifugation. The horizontal semicircular canal function was characterized by the vestibulo-ocular reflex (VOR) gain measured during earth vertical axis rotation as well as the total caloric response. The function of the utricles was represented by the utricular sensitivity, reflecting the ocular counter roll relative to the virtual induced head tilt. Results: Promethazine significantly decreased the semicircular canal and utricular parameters. Both scopolamine and lorazepam caused only a decrease in the utricular sensitivity, whereas meclizine only decreased the semicircular canal-induced VOR gain. Discussion: The results show that the drugs affected different areas of the vestibular system and that the effects can thus be attributed to the specific pharmacological properties of each drug. Meclizine, as an antihistaminergic and weak anticholinergic drug, only affected the VOR gain, suggesting a central action on the medial vestibular nucleus. The same site of action is suggested for the anticholinergic scopolamine since acetylcholine receptors are present and utricular fibers terminate here. The global vestibular suppression caused by promethazine is probably a consequence of its anticholinergic, antihistaminergic, and antidopaminergic properties. Based on the fact that lorazepam increased the affinity of gamma-aminobutyric acid (GABA) for the GABAA-receptor and its effects on the utriculi, the site of action seems to be the lateral vestibular nucleus. Conclusion: Meclizine, scopolamine, and lorazepam selectively suppress specific parts of the vestibular system. Selective suppression of different parts of the vestibular system may be more beneficial for alleviating (space) motion sickness than general suppressive agents. Additionally, this knowledge may help the clinician in his therapeutic management of patients with either semicircular canal or otolith dysfunction.
Association between Black Stains and Dental Caries in Primary Teeth: Findings from a Brazilian Population-Based Birth Cohort
Authors: França-Pinto C.C. , Cenci M.S. , Correa M.B. , Romano A.R. , Peres M.A. , Peres K.G. , Matijasevich A. , Santos I.S. , Barros A.J.D. , Demarco F.F.
Published: April 2012

Lower dental caries experience has been observed in children and teenagers with the presence of black stains on dental structures. However, none of the previous investigations were population-based studies or adjusted the analysis for potential confounders. This study assessed the prevalence of black stains at the age of 5 in a population-based birth cohort from Pelotas, Brazil and investigated the association between black stains and dental caries. A total of 1,129 children from the 2004 Pelotas birth cohort were examined at age 5, and their mothers were interviewed at their households. Dental examinations included a search for black stains and dental caries on the primary dentition through the dmf-s index. The mothers’ questionnaire comprised data on demographic, social, and behavior aspects. Prevalence of black stains was 3.5% (95% CI 2.5–4.7) and the prevalence of dental caries was 48.4% (95% CI 45.4–51.4). Multivariable logistic regression analysis was performed to assess the association between black stains and dental caries. Adjusted analysis revealed that the presence of black stains was associated with lower levels of dental caries (OR = 0.51; 95% CI 0.26–0.99). The results of the present study suggest that black stains are a protective factor for dental caries development.
Positive Correlation between Erythrocyte Levels of n–3 Polyunsaturated Fatty Acids and Bone Mass in Postmenopausal Korean Women with Osteoporosis
Authors: Moon Hyoun-Jung , Kim Tae-Hee , Byun Dong-Won , Park Yongsoon
Published: April 2012

Background: Osteoporosis, a major health problem among postmenopausal women, is influenced by dietary factors. The purpose of the present study was to evaluate the hypothesis that erythrocyte levels of n–3 polyunsaturated fatty acid (PUFA) and the dietary intake of fish are associated with risk of osteoporosis and correlate with bone mass in postmenopausal Korean women with the disease. Methods: Fifty cases and 100 controls were recruited. Osteoporosis was defined according to the International Society for Clinical Densitometry guideline as a score lower than –2.5 SD below the T-score for lumbar vertebrae L1–L4, femoral neck or femoral total. Results: The T-score of the femoral neck was positively correlated with erythrocyte levels of n–3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the intake of fish, and was negatively correlated with the ratio of n–6/n–3 PUFA after adjusting for age, years after menopause and height. In addition, the risk of osteoporosis was positively associated with erythrocyte levels of saturated fatty acids but negatively associated with EPA + DHA. Conclusions: Erythrocyte levels of n–3 PUFA and the intake of fish were positively correlated with bone mass. In particular, erythrocyte levels of EPA + DHA reduced the risk of osteoporosis in postmenopausal Korean women.
Infectious Risks and Optimal Strength of Maintenance Immunosuppressants in Rituximab-Treated Kidney Transplantation
Authors: Baek Chung Hee , Yang Won Seok , Park Kyung Sun , Han Duck Jong , Park Jae Berm , Park Su-Kil
Published: April 2012

Background: Rituximab, an anti-CD20 antibody, effectively depletes B lymphocytes. It is not clear whether the use of conventional doses of mycophenolate mofetil (MMF), methylprednisolone and tacrolimus as maintenance immunosuppression in rituximab-treated kidney transplantation is associated with increased risk. Methods: We retrospectively evaluated 67 patients who underwent HLA-sensitized or ABO-incompatible living donor kidney transplantation after one dose of rituximab (200 or 500 mg) (group 1). Eighty-seven kidney transplant recipients who did not require rituximab served as a control (group 2). Results: Cytomegalovirus infection (16.4 vs. 5.7%, p = 0.031) and pneumonia (9.0 vs. 1.1%, p = 0.043) occurred more often in group 1, and 2 patients of group 1 died of infection. The doses of methylprednisolone and tacrolimus levels of the two groups were not different. MMF dose was reduced when serious infection occurred. The doses of MMF (in grams/day) at the following times postoperatively were lower in group 1 than in group 2: 1 month: 1.26 ± 0.42 vs. 1.40 ± 0.39, p = 0.033; 3 months: 1.14 ± 0.51 vs. 1.36 ± 0.39, p = 0.011; 6 months: 1.07 ± 0.50 vs. 1.30 ± 0.42, p = 0.012; 1 year: 0.88 ± 0.52 vs. 1.19 ± 0.44, p = 0.009; 2 years: 0.69 ± 0.55 vs. 1.25 ± 0.49, p = 0.059, but the reduction of MMF doses did not increase the incidence of acute rejection in group 1 (4.5% in group 1 vs. 9.2% in group 2, p = 0.351). If patients who died with functioning graft were excluded, graft survival was 98.5% in group 1 and 100% in group 2. Conclusions: Serious infectious complications were increased in rituximab-treated kidney transplant recipients and it might be adequate to reduce the MMF dose from the early postoperative period.
Clinical Grand Rounds: Atypical Hemolytic Uremic Syndrome
Authors: Hodgkins Kavita S. , Bobrowski Amy E. , Lane Jerome C. , Langman Craig B.
Published: April 2012

Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.
Testosterone Supplementation in Heart Failure
Authors: Toma Mustafa , McAlister Finlay A. , Coglianese Erin E. , Vidi Venkatesan , Vasaiwala Samip , Bakal Jeffrey A. , Armstrong Paul W. , Ezekowitz Justin A.
Published: April 2012

Background—

Low testosterone is an independent predictor of reduced exercise capacity and poor clinical outcomes in patients with heart failure (HF). We sought to determine whether testosterone therapy improves exercise capacity in patients with stable chronic HF.

Methods and Results—

We searched Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (1980–2010). Eligible studies included randomized controlled trials (RCTs) reporting the effects of testosterone on exercise capacity in patients with HF. Reviewers determined the methodological quality of studies and collected descriptive, quality, and outcome data. Four trials (n=198; men, 84%; mean age, 67 years) were identified that reported the 6-minute walk test (2 RCTs), incremental shuttle walk test (2 RCTs), or peak oxygen consumption (2 RCTs) to assess exercise capacity after up to 52 weeks of treatment. Testosterone therapy was associated with a significant improvement in exercise capacity compared with placebo. The mean increase in the 6-minute walk test, incremental shuttle walk test, and peak oxygen consumption between the testosterone and placebo groups was 54.0 m (95% CI, 43.0–65.0 m), 46.7 m (95% CI, 12.6–80.9 m), and 2.70 mL/kg per min (95% CI, 2.68–2.72 mL/kg per min), respectively. Testosterone therapy was associated with a significant increase in exercise capacity as measured by units of pooled SDs (net effect, 0.52 SD; 95% CI, 0.10–0.94 SD). No significant adverse cardiovascular events were noted.

Conclusions—

Given the unmet clinical needs, testosterone appears to be a promising therapy to improve functional capacity in patients with HF. Adequately powered RCTs are required to assess the benefits of testosterone in this high-risk population with regard to quality of life, clinical events, and safety.
Rare, Nonsynonymous Variant in the Smooth Muscle-Specific Isoform of Myosin Heavy Chain,
MYH11
, R247C, Alters Force Generation in the Aorta and Phenotype of Smooth Muscle Cells
Authors: Kuang Shao-Qing , Kwartler Callie S. , Byanova Katerina L. , Pham John , Gong Limin , Prakash Siddharth K. , Huang Jian , Kamm Kristine E. , Stull James T. , Sweeney H. Lee , Milewicz Dianna M.
Published: April 2012

Rationale:

Mutations in myosin heavy chain (
MYH11
) cause autosomal dominant inheritance of thoracic aortic aneurysms and dissections. At the same time, rare, nonsynonymous variants in
MYH11
that are predicted to disrupt protein function but do not cause inherited aortic disease are common in the general population and the vascular disease risk associated with these variants is unknown.

Objective:

To determine the consequences of the recurrent
MYH11
rare variant, R247C, through functional studies in vitro and analysis of a knock-in mouse model with this specific variant, including assessment of aortic contraction, response to vascular injury, and phenotype of primary aortic smooth muscle cells (SMCs).

Methods and Results:

The steady state ATPase activity (actin-activated) and the rates of phosphate and ADP release were lower for the R247C mutant myosin than for the wild-type, as was the rate of actin filament sliding in an in vitro motility assay.
Myh11
R247C/R247C
mice exhibited normal growth, reproduction, and aortic histology but decreased aortic contraction. In response to vascular injury,
Myh11
R247C/R247C
mice showed significantly increased neointimal formation due to increased SMC proliferation when compared with the wild-type mice. Primary aortic SMCs explanted from the
Myh11
R247C/R247C
mice were dedifferentiated compared with wild-type SMCs based on increased proliferation and reduced expression of SMC contractile proteins. The mutant SMCs also displayed altered focal adhesions and decreased Rho activation, associated with decreased nuclear localization of myocardin-related transcription factor-A. Exposure of the
Myh11
R247C/R247C
SMCs to a Rho activator rescued the dedifferentiated phenotype of the SMCs.

Conclusions:

These results indicate that a rare variant in
MYH11
, R247C, alters myosin contractile function and SMC phenotype, leading to increased proliferation in vitro and in response to vascular injury.
Dynamin-Related Protein 1–Mediated Mitochondrial Mitotic Fission Permits Hyperproliferation of Vascular Smooth Muscle Cells and Offers a Novel Therapeutic Target in Pulmonary Hypertension
Authors: Marsboom Glenn , Toth Peter T. , Ryan John J. , Hong Zhigang , Wu Xichen , Fang Yong-Hu , Thenappan Thenappan , Piao Lin , Zhang Hannah J. , Pogoriler Jennifer , Chen Yimei , Morrow Erik , Weir E. Kenneth , Rehman Jalees , Archer Stephen L.
Published: April 2012

Rationale:

Pulmonary arterial hypertension (PAH) is a lethal syndrome characterized by pulmonary vascular obstruction caused, in part, by pulmonary artery smooth muscle cell (PASMC) hyperproliferation. Mitochondrial fragmentation and normoxic activation of hypoxia-inducible factor-1α (HIF-1α) have been observed in PAH PASMCs; however, their relationship and relevance to the development of PAH are unknown. Dynamin-related protein-1 (DRP1) is a GTPase that, when activated by kinases that phosphorylate serine 616, causes mitochondrial fission. It is, however, unknown whether mitochondrial fission is a prerequisite for proliferation.

Objective:

We hypothesize that DRP1 activation is responsible for increased mitochondrial fission in PAH PASMCs and that DRP1 inhibition may slow proliferation and have therapeutic potential.

Methods and Results:

Experiments were conducted using human control and PAH lungs (n=5) and PASMCs in culture. Parallel experiments were performed in rat lung sections and PASMCs and in rodent PAH models induced by the HIF-1α activator, cobalt, chronic hypoxia, and monocrotaline. HIF-1α activation in human PAH leads to mitochondrial fission by cyclin B1/CDK1–dependent phosphorylation of DRP1 at serine 616. In normal PASMCs, HIF-1α activation by CoCl
2
or desferrioxamine causes DRP1-mediated fission. HIF-1α inhibition reduces DRP1 activation, prevents fission, and reduces PASMC proliferation. Both the DRP1 inhibitor Mdivi-1 and siDRP1 prevent mitotic fission and arrest PAH PASMCs at the G2/M interphase. Mdivi-1 is antiproliferative in human PAH PASMCs and in rodent models. Mdivi-1 improves exercise capacity, right ventricular function, and hemodynamics in experimental PAH.

Conclusions:

DRP-1–mediated mitotic fission is a cell-cycle checkpoint that can be therapeutically targeted in hyperproliferative disorders such as PAH.
Asiatic Acid Attenuates Infarct Volume, Mitochondrial Dysfunction, and Matrix Metalloproteinase-9 Induction After Focal Cerebral Ischemia
Authors: Lee Ki Yong , Bae Ok-Nam , Serfozo Kelsey , Hejabian Siamk , Moussa Ahmad , Reeves Mathew , Rumbeiha Wilson , Fitzgerald Scott D. , Stein Gary , Baek Seung-Hoon , Goudreau John , Kassab Mounzer , Majid Arshad
Published: April 2012

Background and Purpose—

Asiatic acid (AA) has been shown to attenuate cerebral infarction in a mouse model of focal ischemia and shows promise as a neuroprotective stroke therapy. To facilitate translation of these findings to clinical studies, we determined pharmacokinetics, a dose–response relationship, the therapeutic time window, and efficacy using multiple stroke models. We also explored potential mechanisms of action.

Methods—

Escalating doses of intravenous AA were administered and serum concentrations were measured at multiple time points for the pharmacokinetic studies. Subsequently, a dose–response relationship was determined followed by administration at different intervals after the onset of ischemia to establish a therapeutic time window for neuroprotection. Outcome measurements included both histological and behavioral. Mitochondrial function and matrix metalloproteinase activity in controls and treated rats were also determined.

Results—

The pharmacokinetic studies showed that AA (75 mg/kg) has a half-life of 2.0 hours. AA significantly decreased infarct volume and improved neurological outcome even when administration was at time points up to 12 hours after the onset of ischemia. Infarct volume was also significantly decreased in female rats and spontaneously hypertensive rats. AA attenuated mitochondrial dysfunction and reduced matrix metalloproteinase-9 induction.

Conclusions—

Our study shows AA is effective against multiple models of focal ischemia, has a long therapeutic time window, and is also effective in females and hypertensive animals. AA may mediate neuroprotection by protecting mitochondria and inhibiting matrix metalloproteinase-9 induction and activation. Taken together these data suggest that AA is an excellent candidate for development as a stroke therapy.
Developing an Index to Measure Urban Heat Island Effect Using Satellite Land Skin Temperature and Land Cover Observations
Authors: Jin Menglin S.
Published: April 2012

A new index of calculating the intensity of urban heat island effects (UHI) for a city using satellite skin temperature and land cover observations is recommended. UHI, the temperature difference between urban and rural regions, is traditionally identified from the 2-m surface air temperatures (i.e., the screen-level temperature T2m) measured at a pair of weather stations sited in urban and rural locations. However, such screen-level UHI is affected by the location, distance, and geographic conditions of the pair of weather stations. For example, choosing a different pair of rural and city sites leads to a different UHI intensity for the same city, due to the high heterogeneity of the urban surface temperature. To avoid such uncertainty, satellite-observed surface skin temperature measurements (i.e., skin level temperature Tskin) is recommended to record UHI, known as skin-level UHI or UHIskin. This new index has advantages of high spatial resolution and aerial coverage to better record UHI intensity than T2m. An assessment of skin-level UHI from 10 yr of the National Aeronautics and Space Administration (NASA)’s Moderate Resolution Imaging Spectroradiometer (MODIS) observations reveals that skin-level UHI has a strong UHI signal during the day and at night. In addition, there are significant diurnal and seasonal variations in skin-level UHI. Furthermore, the skin-level UHI is stronger during the day and summer (July) than during nighttime and winter. This new index is important for more uniformly assessing UHIs over cities around the globe. Nevertheless, whether the seasonality and diurnal variations revealed in this work using skin-level UHI index are valid over desert cities, such as Phoenix, Arizona, need to be examined.
Measuring a Utility-Scale Turbine Wake Using the TTUKa Mobile Research Radars
Authors: Hirth Brian D. , Schroeder John L. , Gunter W. Scott , Guynes Jerry G.
Published: April 2012

Observations of the wake generated by a single utility-scale turbine and collected by the Texas Tech University Ka-band mobile research radars on 27 October 2011 are introduced. Remotely sensed turbine wake observations using lidar technology have proven effective; however, the presented radar capabilities provide a larger observational footprint and greater along-beam resolution than current scanning lidar systems. Plan-position indicator and range–height indicator scanning techniques are utilized to produce various wake analyses. Preliminary analyses confirm radial velocity and wind speed deficits immediately downwind of the turbine hub to be on the order of 50%. This introduction lays the groundwork for more in-depth analyses of wake structure and evolution using the Texas Tech University Ka-band radar systems, including wake meandering and wake-to-wake interaction in large wind park deployments.
Novel application of a fecal management system for vaginal use in radiotherapy- associated rectovaginal fistula
Authors: Sonoda Laura A , Rosenheck Rachel E , Tierney Katherine , Muderspach Laila I , Palmer Suzanne L , Senikowich Michael , Lin Yvonne G
Published: April 2012

While highly effective for treating certain gynecologic malignancies, radiotherapy carries known risks, including fistula formation. We report a 75-year-old female with advanced cervical carcinoma who was provided a vaginally placed fecal management system after developing a rectovaginal fistula following primary treatment with chemoradiation. This report presents and discusses a novel method to palliate symptomatic RVFs in advanced-stage cancer.
Statistical analysis of the influence of input process parameters on characteristics of weld bonds of Al 5052 H32 alloy using a Box–Behnken design
Authors: Mittal Mayank , Dwivedi Dheerendra K
Published: April 2012

This article presents a systematic study on the effect of input process parameters of the weld-bonding process, namely curing temperature, curing time, welding pressure, welding time and welding current, on the characteristics of the weld bonds, such as bond-line thickness, equivalent nugget diameter, corona size and ultimate shear tensile strength using a Box–Behnken design approach. The effect of overlap length and surface roughness on the shear tensile strength of weld bonds was studied by conducting pilot experiments using a single variable approach. Thereafter, effects of input process parameters, such as curing temperature, curing time, welding pressure, welding time and welding current, on various characteristics of weld bonds was studied by conducting the main experiments according to the Box–Behnken design and response surface methodology (RSM). Regression models were developed to study the influence of input process parameters of weld bonding on characteristics of weld bonds, i.e. bond-line thickness, equivalent nugget diameter, corona size and ultimate shear tensile strength. A combination of weld bonding process parameters for maximum shear tensile strength of the weld bond was obtained with the help of analysis. Further, efforts were made to correlate the bond-line thickness, equivalent nugget diameter and corona size with ultimate shear tensile strength of weld bonds. Developed regression models were validated by conducting confirmation experiments.
Dimensional analysis for the definition of the influence of process parameters in selective laser melting of Ti–6Al–4V alloy
Authors: Cardaropoli Francesco , Alfieri Vittorio , Caiazzo Fabrizia , Sergi Vincenzo
Published: April 2012

This article aims to use the methodology of dimensional analysis to determine the influence of process parameters in selective laser melting of metal powders. The complexity of the selective laser melting process, in fact, does not allow a full evaluation of a physical model, involving all the influencing variables. Through dimensional analysis, the article intends to find out an appropriate definition of a set of non-dimensional groups in order to represent the output parameters. The article, therefore, focuses on the impact of the most influential ones, referring to the production of samples made of Ti–6Al–4V powder using a laser sintering machine EOSINT M270. Specimens are examined in terms of their relative density, given its importance in the design and production of elements for dental implants. Adequate exposure strategies based on the results provided may allow careful designs in order to provide tailored porosity to enhance biological fixation and achieve long-term stability.
Health behaviours of community-treated patients with psychosis
Authors: Feiler Gabriel , Chen Roger Chih-Yu , Pantelis Christos , Lambert Timothy
Published: April 2012

Objective:

To assess physical health self-reports and health utilization behaviours of community dwelling persons with persistent psychosis.

Method:

A cross-sectional survey was conducted of 106 patients with persistent psychosis. Using self-reported measures, the prevalence of smoking, alcohol consumption and exercise, and body mass index were determined. Health utilization behaviour, especially with respect to general practice, was assessed. Data was compared with that derived from the general population and longitudinally with a historical cohort.

Results:

Compared with the general population, those with psychosis were more likely to be smokers, overweight or obese, and less likely to be non/ex-smokers. Compared with previous studies, smoking and obesity persisted as major modifiable risk factors. Over 7 years, some risks such as smoking increased, whereas moderating factors such as light exercise, improved. Three-quarters of patients would visit their GP if they had a physical illness but a third reported not having visited their GP or other doctor in the previous 12 months.

Conclusions:

Patients with persistent psychosis have increased rates of cardiometabolic risk yet seek medical attention infrequently. These findings have not improved despite an increased awareness of the enhanced risk of developing metabolic disease in this group.
Patterns of Self-Reported Alcohol Use, Depressive Symptoms, and Body Mass Index in a Family Sample: The Buffering Effects of Parentification
Authors: Hooper Lisa M. , Doehler Kirsten , Jankowski Peter J. , Tomek Sara E.
Published: April 2012

Although the impact of parentification on children and adolescents’ psychological health and outcomes has long been studied and well documented, little is known about the impact of parentification on children and adolescents’ physical health and medical outcomes. Moreover, the potential buffering effects of parentification have been examined very rarely. The data in the current study were collected from an understudied, high-priority adolescent population ( N = 51 rural adolescent–parent dyads). The authors examined the bivariate relations between parent health (alcohol use, depressive symptoms, and body mass index [BMI]), adolescent health (alcohol use, depressive symptoms, and BMI), and parentification. The effect size of the significant bivariate correlations ranged from small to large ( r = .29 to r = .62). Parentification was positively associated with parent BMI and adolescent depressive symptoms. Parent alcohol use was strongly associated with adolescent alcohol use. Regression analyses were performed to determine if parentification moderates the relation between parental health and adolescent health. Parentification was found to function as a buffer of the relation between parent alcohol use and adolescent alcohol use. Parentification did not function as a moderator of the relation between parent depressive symptoms and adolescent depressive symptoms nor in the relationship between parent BMI and adolescent BMI. However, parentification did moderate the association between parent alcohol use and adolescent depressive symptoms.
Counselors Called for Service: Impact of Parental Deployment on Preschool Children
Authors: Waliski Angie , Bokony Patti , Edlund Carrie N. , Kirchner JoAnn
Published: April 2012

Children and families often experience stress from the physical or emotional absence of a parent due to deployment. The health of the family system plays a vital role in the successful transition through deployment and redeployment phases. Even very young children show signs of behavioral problems, sleep disturbances, depressive symptoms, and anxiety from parental deployment. This article reviews the literature concerning the impact of parental deployment on preschool aged children and current interventions and discusses implications for counselors assisting military families.
The Case for “Living” Models
Authors: Creelman Valerie
Published: April 2012

How best to teach and compose negative messages is a topic that continues to challenge and spark debate among business communication educators and researchers. Even where business communications textbooks emphasize the importance of context and audience analysis to determine whether to adopt a direct or indirect arrangement when expressing bad news, many still favour an indirect approach. In reviewing 50 years of negative news research, this article highlights the major concerns that continue to influence the debate as educators challenge and question existing models for addressing this rhetorically complex message genre.
Basque L2 development in immersion school settings
Authors: Manterola Ibon , Almgren Margareta , Idiazabal Itziar
Published: April 2012

The aim of this article is to study the development of Basque L2 by Spanish L1 children who attend school in a total immersion programme where Basque is the vehicular language. Narratives based on an adult model produced at ages 5 and 8 are analysed in order to better understand the acquisition process of Basque L2 in an immersion school context. Basque L1 children who are also educated in Basque from preschool age constitute a reference group. The same subjects participate in the research at both ages, which gives a longitudinal as well as a cross-sectional approach to the study. The degree of narrative autonomy, the organisation of the narrative structure and features of nominal and verbal cohesion and some metalinguistic strategies are analysed. The results show similar skills in both groups, and the differences are not always in favour of the L1 subjects. On the whole, L2 subjects seem to reproduce the adult model more closely. This study contributes to a better understanding of L2 development in a school context, focussing on the positive effects of Basque immersion programmes.