bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonsteroidal Anti-Inflammatory Drug and Aspirin Use in Relation to Lung Cancer Risk among Postmenopausal Women
Authors: Baik Christina S. , Brasky Theodore M. , Pettinger Mary , Luo Juhua , Gong Zhihong , Wactawski-Wende Jean , Prentice Ross L.
Published: February 2015

Background: Results from prospective studies suggest that nonsteroidal anti-inflammatory drugs (NSAID) may decrease lung cancer risk; however, any protective effect appears to be most evident in men.

Methods: We evaluated the associations between NSAID use and lung cancer incidence in postmenopausal women in the Women's Health Initiative (WHI) adjusting for female-specific potential confounders such as hormone therapy in addition to smoking histories and other potential confounders. We identified 143,841 women from ages 50 to 79 and 1,902 centrally confirmed lung cancer cases were included in the analysis. We used Cox regression models to estimate HRs and their 95% confidence intervals (CI).

Results: Compared with nonuse, regular NSAID use was not associated with overall lung cancer incidence (NSAID use >10 years HR 0.87; 95% CI, 0.71–1.08, Ptrend = 0.13). No statistically significant associations were found when examined by histologic subtypes and although there was a trend of decreased risk with longer duration of NSAID use in the adenocarcinoma subtype, this was not statistically significant (NSAID use >10 years HR 0.80; 95% CI, 0.58–1.10; Ptrend = 0.07).

Conclusion: Our study did not show that NSAID use is associated with lung cancer risk in women even after adjusting for female-specific confounders. There was a trend of decreased risk in the adenocarcinoma subtype; however, this was not statistically significant.

Impact: Future studies will need to take in account the various molecular subtypes of non–small cell lung cancer to further elucidate the role of NSAIDs in lung cancer, especially for the adenocarcinoma subtype. Cancer Epidemiol Biomarkers Prev; 24(5); 790–7. ©2015 AACR.
13C-MR Spectroscopic Imaging with Hyperpolarized [1-13C]pyruvate Detects Early Response to Radiotherapy in SCC Tumors and HT-29 Tumors
Authors: Saito Keita , Matsumoto Shingo , Takakusagi Yoichi , Matsuo Masayuki , Morris H. Douglas , Lizak Martin J. , Munasinghe Jeeva P. , Devasahayam Nallathamby , Subramanian Sankaran , Mitchell James B. , Krishna Murali C.
Published: February 2015

Purpose: X-ray irradiation of tumors causes diverse effects on the tumor microenvironment, including metabolism. Recent developments of hyperpolarized 13C-MRI enabled detecting metabolic changes in tumors using a tracer [1-13C]pyruvate, which participates in important bioenergetic processes that are altered in cancers. Here, we investigated the effects of X-ray irradiation on pyruvate metabolism in squamous cell carcinoma (SCCVII) and colon cancer (HT-29) using hyperpolarized 13C-MRI.

Experimental Design: SCCVII and HT-29 tumors were grown by injecting tumor cells into the hind legs of mice. [1-13C]pyruvate was hyperpolarized and injected intravenously into tumor-bearing mice, and 13C-MR signals were acquired using a 4.7 T scanner.

Results: [1-13C]pyruvate and [1-13C]lactate were detected in the tumor-bearing legs immediately after hyperpolarized [1-13C]pyruvate administration. The [1-13C]lactate to [1-13C]pyruvate ratio (Lac/Pyr) increased as the tumors grew in nonirradiated SCCVII tumors. The increase in Lac/Pyr was suppressed modestly with a single 10 Gy of irradiation, but it significantly decreased by further irradiation (10 Gy × 3). Similar results were obtained in HT-29; Lac/Pyr significantly dropped with fractionated 30 Gy irradiation. Independent ex vivo measurements revealed that the lactate dehydrogenase (LDH) activity and protein level were significantly smaller in the irradiated SCCVII tumors compared with the nonirradiated tumors, indicating that a decrease in LDH activity was one of the main factors responsible for the decrease of Lac/Pyr observed on 13C-MRI.

Conclusions: Robust changes of Lac/Pyr observed in the HT-29 after the radiation suggested that lactate conversion from pyruvate monitored with hyperpolarized 13C-MRI could be useful for the evaluation of early response to radiotherapy. Clin Cancer Res; 21(22); 5073–81. ©2015 AACR.

See related commentary by Lai et al., p. 4996
Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors
Authors: Sinha Sutapa , Boysen Justin , Nelson Michael , Secreto Charla , Warner Steven L. , Bearss David J. , Lesnick Connie , Shanafelt Tait D. , Kay Neil E. , Ghosh Asish K.
Published: February 2015

Purpose: B-cell chronic lymphocytic leukemia (CLL) is an incurable disease despite aggressive therapeutic approaches. We previously found that Axl receptor tyrosine kinase (RTK) plays a critical role in CLL B-cell survival. Here, we explored the possibility of using a high-affinity Axl inhibitor as a single agent or in combination with Bruton's tyrosine kinase (BTK) inhibitors for future clinical trial to treat patients with CLL.

Experimental Design: Expression/activation status of other members of the TAM (e.g., Tyro3, Axl, and MER) family of RTKs in CLL B cells was evaluated. Cells were treated with a high-affinity orally bioavailable Axl inhibitor TP-0903 with or without the presence of CLL bone marrow stromal cells (BMSCs). Inhibitory effects of TP-0903 on the Axl signaling pathway were also evaluated in CLL B cells. Finally, cells were exposed to TP-0903 in combination with BTK inhibitors to determine any synergistic/additive effects of the combination.

Results: CLL B cells overexpress Tyro3, but not MER. Of interest, Tyro3 remains as constitutively phosphorylated and forms a complex with Axl in CLL B cells. TP-0903 induces massive apoptosis in CLL B cells with LD50 values of nanomolar ranges. Importantly, CLL BMSCs could not protect the leukemic B cells from TP-0903–induced apoptosis. A marked reduction of the antiapoptotic proteins Mcl-1, Bcl-2, and XIAP and upregulation of the proapoptotic protein BIM in CLL B cells was detected as a result of Axl inhibition. Finally, combination of TP-0903 with BTK inhibitors augments CLL B-cell apoptosis.

Conclusions: Administration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating patients with CLL. Clin Cancer Res; 21(9); 2115–26. ©2015 AACR.
Introducing the Quill™ Device for Modified Sleeve Circumcision with Subcutaneous Suture: A Retrospective Study of 70 Cases
Authors: Gu Chaohui , Tian Fengyan , Jia Zhankui , Li Guanru , Meng Zhenglei , Xing Weizhi , Ding Yafei , Jin Zhibo , Kan Quancheng , Yang Jinjian
Published: February 2015

Objective: The purpose of the study was to evaluate the safety and feasibility of treatment for male circumcision using modified sleeve circumcision and subcuticular suture with the Quill™ device. Methods: From May 2011 to March 2012, 70 consecutive cases of male circumcision were performed using an alternative technique with the Quill™ device by a single surgeon in our institution. The inclusion and exclusion criteria for the selection process of this procedure were the same as for conventional circumcision. We evaluated the indications and perioperative outcomes. The circumcisions were performed as day-case procedures under local anesthesia. Results: All patients were followed up for a minimum of 3-6 months. The ages ranged from 8 to 68 (mean = 27.0 years, SD = 10). The indications for surgery were either cosmetic (n = 16, 22.9%) or medical [redundant prepuce (n = 36, 51.4%), phimosis (n = 5, 7.1%), paraphimosis (n = 2, 2.9%), balanoposthitis (n = 9, 12.9%), melanoma (n = 1, 1.4%), and condyloma acuminata (n = 1, 1.4%)] (n = 54, 77.1%). The mean operation time in this group was 29 min (19-38 min) when the Quill™ device was used. In all, 3 cases developed complications (4.3%). The final cosmetic result was satisfactory for both the patients and their spouses or parents. Conclusion: This study showed that modified sleeve circumcision and subcuticular suture were safe and reliable surgical methods of circumcision that provide a better cosmetic result.
Absence of Hydrogen Sulfide-Induced Hypometabolism in Pigs: A Mechanistic Explanation in Relation to Small Nonhibernating Mammals
Authors: Dirkes Marcel C. , Milstein Dan M.J. , Heger Michal , van Gulik Thomas M.
Published: February 2015

Artificially induced hypometabolism in nonhibernating mammals may have considerable clinical implications. Numerous studies in small rodent models have demonstrated that hydrogen sulfide (H2S) induces hypometabolism, supposedly as a result of histotoxic hypoxia. However, the induction of hypometabolism is absent in large animals following H2S administration. To determine the cause of this animal size-dependent discrepancy in H2S pharmacodynamics, the effects of sodium H2S (NaSH; 5 mg/kg/h, 4-hour intravenous administration) on systemic, pneumocardial, hematological, biochemical, microvascular (sublingual), and histological parameters were investigated in pigs. After 4 h, no differences were observed between the NaSH and control group with respect to systemic, pneumocardial, hematological, biochemical, and histological parameters. However, NaSH triggered significant hyperperfusion in the sublingual microcirculation, as evidenced by an increased blood vessel diameter (154 ± 16 and 85 ± 25% vs. baseline for NaSH and NaCl, respectively), total vessel density (139 ± 18 and 98 ± 13%, respectively), and perfused vessel density (139 ± 18 and 99 ± 13%, respectively). These phenomena are consistent with microvascular changes that occur during a panting response, an important heat loss mechanism (i.e., thermoregulatory effector) in pigs that is controlled by the thermoneutral zone (Ztn). On the basis of our findings and the literature, a mechanistic explanation is provided for the differential manifestation of hypometabolism between small and large animals. In large animals, H2S does not act via histotoxic hypoxia but likely triggers carotid bodies to transmit a hypoxic signal, which subsequently lowers the Ztn and activates heat loss mechanisms (e.g., panting) to align ATP consumption with ATP production through hypothermia. Since large animals have a small surface:size ratio, the cooling rate is too inefficient to accommodate hypothermia and subsequent hypometabolism. This is why large animals do not exhibit hypometabolism, despite the activation of thermoregulatory effectors. This is also a reason for the poor translatability of artificial hypometabolism to the clinical setting.
Feasibility and Accuracy of Molecular Testing in Specimens Obtained with Small Biopsy Forceps: Comparison with the Results of Surgical Specimens
Authors: Oki Masahide , Yatabe Yasushi , Saka Hideo , Kitagawa Chiyoe , Kogure Yoshihito , Ichihara Shu , Moritani Suzuko
Published: February 2015

Background: During bronchoscopy, small biopsy forceps are increasingly used for the diagnosis of peripheral pulmonary lesions. However, it is unclear whether the formalin-fixed paraffin-embedded specimens sampled with the small biopsy forceps are suitable for the determination of genotypes which become indispensable for the management decision regarding patients with non-small cell lung cancer. Objectives: The aim of this study was to evaluate the feasibility and accuracy of molecular testing in the specimens obtained with 1.5-mm small biopsy forceps. Methods: We examined specimens in 91 patients, who were enrolled in our previous 3 studies on the usefulness of thin bronchoscopes and given a diagnosis of non-small cell lung cancer by bronchoscopy with the 1.5-mm biopsy forceps, and then underwent surgical resection. An experienced pathologist examined paraffin-embedded specimens obtained by bronchoscopic biopsy or surgical resection in a blind fashion on epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements and KRAS mutations. Results: Twenty-five (27%), 2 (2%) and 5 (5%) patients had an EGFR mutation, ALK rearrangement and KRAS mutation, respectively, based on the results in surgical specimens. EGFR, ALK and KRAS testing with bronchoscopic specimens was feasible in 82 (90%), 86 (95%) and 83 (91%) patients, respectively. If molecular testing was feasible, the accuracy of EGFR, ALK and KRAS testing with bronchoscopic specimens for the results with surgical specimens was 98, 100 and 98%, respectively. Conclusion: The results of molecular testing in the formalin-fixed paraffin-embedded specimens obtained with the small forceps, in which the genotype could be evaluated, correlated well with those in surgically resected specimens.
Evaluation of a Possible Role of Stigmatella aurantiaca ACE in Aβ Peptide Degradation: A Molecular Modeling Approach
Authors: Jalkute Chidambar B. , Sonawane Kailas D.
Published: February 2015

Amyloid-β (Aβ)-degrading enzymes are known to degrade Aβ peptides, a causative agent of Alzheimer's disease. These enzymes are responsible for maintaining Aβ concentration. However, loss of such enzymes or their Aβ-degrading activity because of certain genetic as well as nongenetic reasons initiates the accumulation of Aβ peptides in the human brain. Considering the limitations of the human enzymes in clearing Aβ peptide, the search for microbial enzymes that could cleave Aβ is necessary. Hence, we built a three-dimensional model of angiotensin-converting enzyme (ACE) from Stigmatella aurantiaca using homology modeling technique. Molecular docking and molecular dynamics simulation techniques were used to outline the possible cleavage mechanism of Aβ peptide. These findings suggest that catalytic residue Glu 434 of the model could play a crucial role to degrade Aβ peptide between Asp 7 and Ser 8. Thus, ACE from S. aurantiaca might cleave Aβ peptides similar to human ACE and could be used to design new therapeutic strategies against Alzheimer's disease.
Influence of Mechanical Stress on Palmoplantar Erythrodysesthesia - a Case Report
Authors: Jung Sora , Sehouli Jalid , Patzelt Alexa , Lademann Jürgen
Published: February 2015

Background: Cutaneous adverse events can have an important negative influence on quality of life and compliance in affected patients. Palmoplantar erythrodysesthesia (PPE; hand-foot syndrome) is a cutaneous toxicity associated with chemotherapeutic treatment, which necessitates treatment interruption or dose reduction in severe cases. This case report of pegylated liposomal doxorubicin-induced PPE shows the influence of mechanical stress on the development of skin lesions in various locations and the importance of patient education and compliance. Case Report: We present the case of a 43-year-old female patient diagnosed with ovarian cancer and having undergone surgical and chemotherapeutic treatment. The development of extensive grade 3 PPE affecting numerous areas of the body particularly exposed to mechanical pressure necessitated dermatological treatment. The combination of local application of an antioxidant-containing ointment and the patient's compliance made it possible to continue chemotherapy without interruption or dose reduction. Conclusion: The development of PPE often limits the use of chemotherapeutic agents, and this case report can provide a possible therapeutic and preventive strategy for affected patients.
Nordic Walking Enhances Oxygen Uptake without Increasing the Rate of Perceived Exertion in Patients with Chronic Obstructive Pulmonary Disease
Authors: Barberan-Garcia Anael , Arbillaga-Etxarri Ane , Gimeno-Santos Elena , Rodríguez Diego Agustín , Torralba Yolanda , Roca Josep , Vilaró Jordi
Published: February 2015

Background: In healthy subjects, Nordic walking (NW) generates higher oxygen uptake (V˙O2) than standard walking at an equal rate of perceived exertion (RPE). The feasibility and positive outcomes of NW in patients with chronic obstructive pulmonary disease (COPD) have been reported. Objectives: The aim of the current study is to assess the physiological responses and RPE during NW in COPD patients. Methods: In 15 COPD patients [mean (SD) age 67 (9) years] with a forced expiratory volume in the 1st s of 55% (15)], V˙O2, minute ventilation and heart rate were measured with a portable system during the 6-min walking test (6MWT), incremental shuttle walking test (SWT), 6-min NW on solid ground (6mNWground) and 6-min NW on soft dry beach sand (6mNWsand). The RPE using a modified Borg scale was assessed after each test. Results: 6mNWground and 6mNWsand showed a higher V˙O2 plateau compared with the 6MWT and peak V˙O2 measured during SWT [mean (SD) V˙O2 21 (3), 22 (4), 18 (4) and 19 (5) ml·kg-1·min-1, respectively; p < 0.05 each]. However, no differences in RPE were observed among 6mNWground, 6MWT and SWT [modified Borg scale score for dyspnea 4.2 (2.0), 4.1 (1.8) and 4.3 (1.7), respectively; nonsignificant]. However, RPE in 6mNWsand was significantly higher than in all the other exercise protocols [modified Borg scale score for dyspnea 5.2 (2.2); p < 0.05]. Conclusions: In COPD patients, the use of Nordic poles generates higher V˙O2 than standard walking with no differences in the dyspnea score. The results indicate the potential to enhance community-based training programs in these patients.
Pili Annulati and Trichorrhexis Nodosa in the Same Patient: Cause or Coincidence?
Authors: Donati Aline , Andriolo Anna Cecília , Barletta Marina , Valente Neusa , Romiti Ricardo
Published: February 2015

Purpose: To determine the relationship between pili annulati (PA) and acquired trichorrhexis nodosa (TN) seen in the same patient, considering the two main theories evoked by previous studies: greater stiffness of darker PA bands or associated cuticular damage. Procedures: Light microscopy of hair shafts from different regions of the patient's scalp. Results: TN was not superimposed to dark bands of PA. Conclusions: Greater stiffness of darker PA bands was excluded as the cause of hair breakage. Hair breakage in PA patients might be related to cuticular abnormalities, as previously reported. Because weathering of long thin chemically treated hairs is extremely common, coincidence cannot be completely ruled out in this case.
Role of Titanium in the Development of Yellow Nail Syndrome
Authors: Decker Ashley , Daly Deborah , Scher Richard K.
Published: February 2015

Yellow nail syndrome (YNS) is characterized by the triad of nail changes, lymphedema and respiratory tract involvement. Several hypotheses have been postulated to explain the findings in YNS including lymphatic drainage abnormalities along with microvasculopathy. The most recent hypothesis, proposed by Berglund and Calmark [Biol Trace Elem Res 2011;143:1-7], suggests a role of titanium dioxide in the development of YNS. This study showed elevated titanium levels (ranging from 1.1 to 170 μg/g of nail plate) in nail clippings or pieces of shed nail from 30 patients with YNS. Titanium was not found in the nails of healthy patients. Complete resolution was seen in 4 patients after removal of their titanium implants. Titanium dioxide is commonly found in cosmetics, sunscreens, medications, confectionaries and joint implants. Exposure to titanium can lead to its ions being released by galvanic action of dental gold or amalgam through the oxidative stress of fluorides. It is hypothesized that this galvanic interaction may lead to the yellow discoloration. At this point, cause and effect is speculative, but titanium may play a role in a subgroup of patients with YNS.
Single Bilateral Dexamethasone Implant in Addition to Panretinal Photocoagulation and Oral Azathioprine Treatment in IRVAN Syndrome
Authors: Saatci Ali Osman , Ayhan Ziya , Takeş Ömer , Yaman Aylin , Söylev Bajin F. Meltem
Published: February 2015

The idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome is a disease characterized by multiple retinal macroaneurysms, neuroretinitis and peripheral capillary nonperfusion. Visual loss may result from either ischemia-related complications or macular involvement. Treatment is not always rewarding. We report a case with stage 2 IRVAN syndrome who was successfully treated with a single bilateral intravitreal dexamethasone implant in addition to panretinal photocoagulation and systemic azathioprine treatment.
Clinical Response to Sorafenib in a Patient with Metastatic Colorectal Cancer and FLT3 Amplification
Authors: Brandão Moreira Raphael , D''Alpino Peixoto Renata , Rocha de Sousa Cruz Marcelo
Published: February 2015

Background: A considerable number of patients with metastatic colorectal cancer progress after exhausting all approved standard therapies but maintain an adequate performance status and could be candidates for further treatment. We aim at reviewing our experience with sorafenib treatment of a patient with FLT3 mutation in refractory metastatic colorectal cancer. Methods: Treatment with sorafenib of a patient with metastatic colorectal cancer and FLT3 translocation who had previously been heavily treated. Results: The patient with metastatic colorectal cancer, aged 51 years, showed significant symptomatic and laboratory improvement with sorafenib treatment (400 mg twice daily). Conclusion: The presented case illustrates how an aggressive and refractory colorectal tumor may respond well to targeted therapy.
The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism
Authors: Rodabough Rebecca J. , Budrys Nicole , Johnson Karen C. , Berger Jeffrey S. , Shikany James M. , Raiesdana Azad , Heckbert Susan R , Manson JoAnn E. , LaCroix Andrea Z. , Siscovick David , Kestenbaum Bryan , Smith Nicholas L. , de Boer Ian H. , Blondon Marc
Published: February 2015

Experimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women’s Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years. This secondary analysis of the trial compared the incidence of VTE by treatment group using an intention-to-treat Cox regression analysis. The incidence of VTE did not differ between women randomised to calcium plus vitamin D and women randomised to placebo (320 vs 348 VTE events, respectively; hazard ratio (HR) 0.92, 95 % confidence interval (CI) 0.79-1.07). Results were not modified in an analysis using inverse-probability weights to take non-adherence into account (HR 0.94, 95 %CI 0.73-1.22) or in multiple subgroups. Whereas the risk of a non-idiopathic VTE was similar between groups, the risk of idiopathic VTE was lower in women randomised to calcium plus vitamin D (40 vs 65 events; HR 0.62, 95 %CI 0.42-0.92). In conclusion, daily supplementation with 1,000 mg of calcium and 400 IU of vitamin D did not reduce the overall incidence of VTE in generally healthy postmenopausal women. However, the observed reduced risk of idiopathic VTE in women randomised to calcium and vitamin D warrants further investigations.

Trial Registration: NCT00000611 (www.clinicaltrials.gov).
Dissociation of SERPINE1 mRNA from the translational repressor proteins Ago2 and TIA-1 upon platelet activation
Authors: Corduan Aurélie , Plé Hélène , Laffont Benoit , Wallon Thérèse , Plante Isabelle , Landry Patricia , Provost Patrick
Published: February 2015

Platelets play an important role in haemostasis, as well as in thrombosis and coagulation processes. They harbour a wide variety of messenger RNAs (mRNAs), that can template de novo protein synthesis, and an abundant array of microRNAs, which are known to mediate mRNA translational repression through proteins of the Argonaute (Ago) family. The relationship between platelet microRNAs and proteins capable of mediating translational repression, however, remains unclear. Here, we report that half of platelet microRNAs is associated to mRNA-regulatory Ago2 protein complexes, in various proportions. Associated to these Ago2 complexes are platelet mRNAs known to support de novo protein synthesis. Reporter gene activity assays confirmed the capacity of the platelet microRNAs, found to be associated to Ago2 complexes, to regulate translation of these platelet mRNAs through their 3’UTR. Neither the microRNA repertoire nor the microRNA composition of Ago2 complexes of human platelets changed upon activation with thrombin. However, under conditions favoring de novo synthesis of Plasminogen Activator Inhibitor-1 (PAI-1) protein, we documented a rapid dissociation of the encoding platelet SERPINE1 mRNA from Ago2 protein complexes as well as from the translational repressor protein T-cell-restricted intracellular antigen-1 (TIA-1). These findings are consistent with a scenario by which lifting of the repressive effects of Ago2 and TIA-1 protein complexes, involving a rearrangement of protein•mRNA complexes rather than disassembly of Ago2•microRNA complexes, would allow translation of SERPINE1 mRNA into PAI-1 in response to platelet activation.
Assessment of Regional Myocardial Work in Rats
Authors: Espe Emil K.S. , Aronsen Jan Magnus , Eriksen Guro S. , Zhang Lili , Smiseth Otto A. , Edvardsen Thor , Sjaastad Ivar , Eriksen Morten
Published: February 2015

Background—

Left ventricular (LV) motion and deformation is dependent on mechanical load and do therefore not reflect myocardial energy consumption directly. Regional myocardial work, however, constitutes a more complete assessment of myocardial function.

Methods and Results—

Strain was measured using high-resolution phase-contrast MRI in 9 adult male rats with myocardial infarction (MI) and in 5 sham-operated control animals. Timing of LV valvular events and LV dimensions were evaluated by cine MRI. A separate cohort of 14 animals (MI/sham=9/5) underwent measurement of LV pressure concurrent with identification of valvular events by Doppler-echocardiography for the purpose of generating a standard LV pressure curve, normalized to valvular events. The infarctions were localized to the anterolateral LV wall. Combining strain with timing of valvular events and a measurement of peak arterial pressure, regional myocardial work could be calculated by applying the standard LV pressure curves. Cardiac output and stroke work was preserved in the MI hearts, suggesting a compensatory redistribution of myocardial work from the infarcted region to the viable tissue. In the septum, regional work was indeed increased in MI rats compared with sham (median work per unit long-axis length in a mid-ventricular slice: 241.2 [224.1–271.2] versus 137.2 [127.0–143.8] mJ/m;
P
<0.001). Myocardial work in infarcted regions was zero. Additionally, eccentric work was increased in the MI hearts.

Conclusions—

Phase-contrast MRI, in combination with measurement of peak arterial pressure and MRI-derived timing of valvular events, represent a noninvasive approach for estimation of regional myocardial work in rodents.
Long Noncoding RNAs in Cardiovascular Diseases
Authors: Uchida Shizuka , Dimmeler Stefanie
Published: February 2015

In recent year, increasing evidence suggests that noncoding RNAs play important roles in the regulation of tissue homeostasis and pathophysiological conditions. Besides small noncoding RNAs (eg, microRNAs), >200-nucleotide long transcripts, namely long noncoding RNAs (lncRNAs), can interfere with gene expressions and signaling pathways at various stages. In the cardiovascular system, studies have detected and characterized the expression of lncRNAs under normal physiological condition and in disease states. Several lncRNAs are regulated during acute myocardial infarction (eg,
Novlnc6
) and heart failure (eg,
Mhrt
), whereas others control hypertrophy, mitochondrial function and apoptosis of cardiomyocytes. In the vascular system, the endothelial-expressed lncRNAs (eg, MALAT1 and Tie-1-AS) can regulate vessel growth and function, whereas the smooth-muscle–expressed lncRNA smooth muscle and endothelial cell–enriched migration/differentiation-associated long noncoding RNA was recently shown to control the contractile phenotype of smooth muscle cells. This review article summarizes the data on lncRNA expressions in mouse and human and highlights identified cardiovascular lncRNAs that might play a role in cardiovascular diseases. Although our understanding of lncRNAs is still in its infancy, these examples may provide helpful insights how lncRNAs interfere with cardiovascular diseases.
Cortical Selective Neuronal Loss, Impaired Behavior, and Normal Magnetic Resonance Imaging in a New Rat Model of True Transient Ischemic Attacks
Authors: Ejaz Sohail , Emmrich Julius V. , Sawiak Stephen J. , Williamson David J. , Baron Jean-Claude
Published: February 2015

Background and Purpose—

New-definition transient ischemic attacks (TIAs) are frequent but difficult to diagnose because magnetic resonance imaging (MRI)-negative by definition. However, hidden underlying cell damage might be present and account for the reported long-lasting cognitive impairment after TIAs. Most prior rodent models of true TIA targeted the striatum or have not been fully characterized. Here we present the MRI, behavioral, and quantitative cell changes characterizing a new rodent model of true TIA targeting the more behaviorally relevant cerebral cortex.

Methods—

Fifteen-minute distal middle cerebral artery occlusion was performed in 29 spontaneously hypertensive rats allowed to survive for 7 to 60 days. Behavior was assessed serially using both global neurological and fine sensorimotor tests. Diffusion- and T2-weighted MRI was obtained 20 min postreperfusion and again 7 to 60 days later, and then changes in neurons and microglia were quantified across the middle cerebral artery territory using immunohistochemistry.

Results—

No MRI changes or pan-necrosis were observed at any time point, but patchy cortical selective neuronal loss affected 28/29 rats, regardless of survival interval, together with topographically congruent microglial activation that gradually declined over time. The Neuroscore was unchanged, but there was marked contralateral sensorimotor impairment, still recovering by day 28.

Conclusions—

Our new rodent model mimicking true cortical TIA is characterized by normal MRI, but consistent cortical selective neuronal loss and microglial activation and long-lasting sensorimotor deficits. By causing selective neuronal loss, TIAs and silent microemboli might affect neuronal reserve, thereby increasing long-term cognitive impairment risk. Selective neuronal loss and microglial activation might represent novel therapeutic targets that could be detectable in vivo after TIAs using appropriate imaging tracers.
The Picture of Health
Authors: Betcher Sharon V.
Published: February 2015

We carry our most intimate view of nature within our pictures of health. These images of health, often more amenable to ablenationalism than to a world of intra-active becoming, inform not only neoliberal policy, but ecological vision, including ecospiritualities. Increasingly “the politics of health” constitutes something like a structure of exclusion, a “racism that is biological” (Foucault). Since these intimate images of nature—these “pictures of health”—may be aggravating the next great planetary divide, disability studies might differently shape what we make of the picture of health, the “nature” that informs it, and a religious response to it. This article uses critical disability studies to examine the ways in which the ideology of health, often motivating ecological concern and religious seeking, can coincidentally collude with neoliberal responsibilization and biotechnologically supported transhumanism, generating policy enclosures of the gen-rich against the “refuse/d” or “waste/d.”
Lead Me Beside Still Waters
Authors: Hickman Lisa Nichols
Published: February 2015

Artist Ena Swansea paints a provocative paradox in “One” from her “4 Seasons” quadtych: Is the child in the bathtub playfully holding a bubble, the orb of our global commons, or a crystal ball that portends an ominous future? As the viewer is confronted with the image of a child who, in the middle of an ordinary daily routine, is up to his armpits in a pool of blood red water, the question of water toxicity becomes central in the painting.

Working from that image, this paper explores the interaction between water toxicity and Trisomy 21, proposing the need for a “precautionary principle” to guide decision-making. The rationale for that principle is developed here through a study of communities with heightened links between water toxicity and Trisomy 21, a deepened theology of water across worldviews drawing on the work of John Hart’s Sacramental Commons, and a proposed model for “eco-social disability.” Because scientific studies linking toxic water and Trisomy 21 are inconclusive, the precautionary principle serves as a guide to prevent the potential disabling effects of toxic water causing unjust generation of disablement.
Sex and strife: post-conflict sexual contacts in bonobos
Authors: Clay Zanna , de Waal Frans B.M.
Published: February 2015

Sexual contacts are thought to play an important role in regulating social tension in bonobos (Pan paniscus), and are especially common following aggressive conflicts, either between former opponents or involving bystanders. Nevertheless, research on the factors determining post-conflict sexual contacts, their effectiveness in reducing social tension and the nature of post-conflict sexual behaviour is scarce. Here, we collected data on post-conflict affiliative contacts in bonobos occurring between former opponents (reconciliation) and offered by bystanders towards victims (consolation) to investigate the role of sexual contacts in the regulation of aggressive conflicts compared to non-sexual affiliation behaviours. We tested whether post-conflict sexual contacts: (1) alleviate stress, (2) confer reproductive benefits, (3) mediate food-related conflict and (4) repair valuable social bonds. Thirty-six semi-free bonobos of all ages were observed at the Lola ya Bonobo Sanctuary, DR Congo, using standardized Post-Conflict/Matched Control methods. Consolation and reconciliation were both marked by significant increases in the occurrence of sexual behaviours. Reconciliation was almost exclusively characterized by sexual contacts, although consolation was also characterized by increases in non-sexual behaviours, such as embrace. Adults were more likely to engage in post-conflict sexual contacts than younger bonobos. Consistent with the stress-alleviation hypothesis, victims receiving sexual consolatory contact showed significantly lower rates of self-scratching, a marker of stress in primates, compared to receiving non-sexual contact. Post-conflict sexual contacts were not targeted towards valuable social partners and they did not confer obvious reproductive benefits; nor were they used to mediate food-related conflicts. Overall, results highlight the role of sex in regulating tension and social conflicts in bonobos.
A comparative assessment of handedness and its potential neuroanatomical correlates in chimpanzees (Pan troglodytes) and bonobos (Pan paniscus)
Authors: Hopkins William D. , Schaeffer Jennifer , Russell Jamie L. , Bogart Stephanie L. , Meguerditchian Adrien , Coulon Olivier
Published: February 2015

The evolutionary origins of human right-handedness remain poorly understood. Some have hypothesized that tool use served as an important preadaptation for the eventual evolution of population-level right-handedness. In contrast, others have suggested that complex gestural and vocal communication served as prerequisite for the evolution of human right-handedness. In this study, we tested these competing hypotheses by comparing the handedness of bonobos and chimpanzees, two closely related species of Pan, on three different measures of hand use including simple reaching, manual gestures and coordinated bimanual actions. Chimpanzees are well known for their tool using abilities whereas bonobos rarely use tools in the wild. In contrast, many have suggested that bonobos have a more flexible gestural and vocal communication system than chimpanzees. The overall results showed that chimpanzees were significantly more right-handed than bonobos for all three measures suggesting that adaptations for tool use rather than communication may have led to the emergence of human right-handedness. We further show that species differences in handedness may be linked to variation in the size and asymmetry of the motor-hand area of the precentral gyrus. The results are discussed within the context of evolutionary theories of handedness, as well as some limitations in the approach to handedness measurement in nonhuman primates.
Experimental evidence that grooming and play are social currency in bonobos and chimpanzees
Authors: Schroepfer-Walker Kara , Wobber Victoria , Hare Brian
Published: February 2015

While natural observations show apes use grooming and play as social currency, no experimental manipulations have been carried out to measure the effects of these behaviours on relationship formation in apes. While previous experiments have demonstrated apes quickly learn the identity of individuals who will provide food in a variety of cooperative and non-cooperative situations, no experiment has ever examined how grooming and play might shape the preferences of apes for different individuals. We gave a group bonobos () and chimpanzees () a choice between an unfamiliar human who had recently groomed or played with them and one who had not. Both species showed a preference for the unfamiliar human that had interacted with them over the one who did not. The effect was largely driven by the males of both species while interacting with females showed little effect on their preferences for unfamiliar humans. Subjects showed this preference even though they only had social interactions with one of the unfamiliar humans for a few minutes before each trial and their choices were not rewarded with food differentially. Our results support the long held idea that grooming and play act as a form of social currency in great apes (and likely many other species) that can rapidly shape social relationships, particularly between unfamiliar individuals.
Mormonism and the World Religions Discourse
Authors: Wiles Lee
Published: February 2015

This article examines the ways in which the status of Mormonism within academic comparative religion discourses is quite different from that which has evolved among Latter-day Saint leaders and within the burgeoning field of Mormon studies. Whereas Mormonism is a quasi-Christian New Religious Movement in most world religions textbooks and reference works, some scholars of Mormonism have advanced the expanding Church of Jesus Christ of Latter-day Saints into the position of world religion. In doing so, they have adopted the terminology of a broader taxonomy largely without regard for maintaining its established demarcations. This classificatory tension, which will likely increase in the future, reveals some of the underlying logics, semantic confusions, and power dynamics of comparative religion discourses, ultimately problematizing the categories of Christianity, world religion, and New Religious Movement as currently constituted.
When Acceptance Reflects Disrespect
Authors: Ramey Steven
Published: February 2015

The late Hans Penner critiqued the Phenomenology of Religion 25 years ago for confusing the subject and its object. His critique remains relevant to contemporary methods that accept participant statements uncritically. Beginning with a detailed analysis of one lived religion article and expanding to a broader critique, this essay illustrates the contradictions that remain in lived religion methodologies and similar approaches to the study of religion. While reflecting respect for practitioners and expanding the concept of religion, these methods ignore the agency of participants to represent themselves strategically and reinforce common discourse on religion, only expanding the category at its safe margins. The agendas that drive various studies work at cross purposes because of the inherent contradictions, and the dichotomy between scholars (and people like scholars) and practitioners that often results contradicts the rhetoric of respect and treating everyone equally.
Living Wills in Italy: Ethical and Comparative Law Approaches
Authors: Veshi Denard , Neitzke Gerald
Published: February 2015

In this article, advance directives will be analysed through ethical and comparative law approaches. Their importance, the two different types of advance directives and the so-called three steps hierarchy, will be discussed. Living wills will be treated in detail, considering the criticism they have attracted, as well as their known benefits. A thorough examination of the latest version of Arts. 3 and 4 of Italian Bill No. 2350, as approved by the Italian Senate in March 2009 and then amended by the Chamber of Deputies in July 2011, is included. This bill grants advance directives advisory force, limits their application in time and does not allow the validity of oral declarations. This political decision limits autonomy. Furthermore, there are doubts about the constitutionality of this bill, especially with respect to Arts. 2, 13 and 32 of the Italian Constitution, related to the right of self-determination. Further, this article will include a comparative approach of the legal aspects, with particular attention to the French and German models. To conclude, some ethical principles that the Italian legislator must take into consideration are indicated. In addition, some possible modifications of this Bill are suggested based on the experience of other European legislation.
Epicharmus and Aeschylus on Stage in Syracuse in the 5th Century
Authors: Poehlmann Egert
Published: February 2015

New excavations give clear information about the Athenian Dionysus-Theatre of the 5th century b.c.; and the stage in Western Greece can now be reconstructed by analogy with it.

Vase paintings depict wooden theatres in Sicily from 400 b.c. onwards, mainly for comedy. Tragedies were performed only after 476/5 b.c., but the lively tradition of comedy since the late 6th century b.c. must have had a stage. For Epicharmus’ short comedies, which had no lyrics or chorus and were addressed to the elite of Hieron’s court, the small theatre carved into the slope of the Temenites rock was sufficient. But the performances of Aeschylus’ Aitnaiai and Persians were politically motivated productions addressed to the whole Syracusan demos; they required a chorus, and space for large audiences. The form of the theatre and its wooden stage building, designed by Damokopos Myrilla, can be hypothetically reconstructed by analogy with their Athenian counterparts.
Sur la distinction établie par Aristide Quintilien (i, 18) entre rythmiciens συμπλέκοντες et χωρίζοντες
Authors: Calvié Laurent
Published: February 2015

The distinction by Aristides Quintilianus (i, 18) between συμπλέκοντες and χωρίζοντες rhythmicians, does not draw a contrast between two rhythmical doctrines or between rhythmicians and metricians, but between the defenders of two methods of classifying rhythms according to two different rhythmical traditions. It is both exact and fruitful : it not only throws light on the lost part of Aristoxenus’ ῾Ρυθμικὰ στοιχεῖα (one of the main χωρίζοντες) and on the sources of Aristides Quintilianus’ rhythmical theory, but also enables us to classify almost mechanically all ancient testimonies about Greek and Roman rhythmics. Neither of these two traditions is homogeneous : among the χωρίζοντες, there are the canonicians (the mere arithmeticians), empiricists like Aristoxenus and the disciples of the dogmatic physician Herophilus; and, among the συμπλέκοντες, there are philosophers, rhetors, musicians and metricians. Finally, the orchestic tradition falls outside the dichotomy between χωρίζοντες and συμπλέκοντες.
Correcting ēthos and Purifying the Body. Musical Therapy in Iamblichus’ De vita pythagorica
Authors: Provenza Antonietta
Published: February 2015

The tradition relating to the Pythagoreans and music therapy is most widely attested in two Neoplatonic works, Porphyry’s The Life of Pythagoras, and Iamblichus’ On the Pythagorean Way of Life. Although the chronological distance from the early Pythagoreans makes their accounts controversial, they offer interesting evidence on the beneficial effects of music. Iamblichus, whose work will be focused on in this paper, describes the effects of music on health through the notion of catharsis, which he often links with musical ēthos. The latter is not in fact attested before Plato, but Iamblichus, presenting Pythagoras in Platonic terms, emphasizes the importance he gives to the improvement of the individual’s character and life by means of music, which is used as a proper pharmakon. In such respect, Iamblichus’ work shows some similarities with Aristides Quintilianus’ De Musica, especially in connection with the “mixture” of melodies as if they were medicines.
A new species of Allagoptera (Arecaceae) from the Cerrado of central Brazil
Authors: Martins Renata Corrêa , FILGUEIRAS TARCISO S. , GRACIANO-RIBEIRO DALVA , SOMAVILLA NÁDIA SÍLVIA
Published: February 2015

A new species of Allagoptera from the Cerrado of central Brazil is described. The new species is distinguished by its solitary habit, open crown, and very long inflorescence rachis conspicuously curved at maturity. The new species, A. robusta, is compared morphologically and anatomically with A. campestris and A. leucocalyx.
Lectotypifications of some Indian Ceropegia (Apocynaceae: Ceropegieae)
Authors: Singh Rajeev Kumar
Published: February 2015

Eight binomials of six recognized species of Ceropegia are lectotypified: C. albiflora Hooker f., C. fantastica Sedgwick, C. lanceolata Wight, C. mysorensis Wight, C. pubescens Wallich, C. pusilla Wight & Arnott, C. sphenanantha Wight, and C. walkerae Wight.
A new species of the hermit crab genus Pagurus Fabricius, 1775 (Crustacea: Decapoda: Anomura: Paguridae) from shallow coastal waters in Japan, with a checklist of the East Asian species of the genus
Authors: KOMAI TOMOYUKI , SAITO YUMA , MYORIN EIJI
Published: February 2015

A new species of hermit crab of the family Paguridae, Pagurus rectidactylus, is described and illustrated on the basis of material from inshore waters in the Seto Inland Sea and the Sea of Japan. It appears closest to P. quinquelineatus Komai, 2003, also known from Japan, but is easily distinguished from the latter by the dactylus of the right cheliped almost unarmed or armed only with a few tiny spines or tubercles, instead of dorsal and dorsomesial rows of conspicuous spines, and the more elongate and slender ambulatory legs with more numerous ventral corneous spines on dactyli and propodi. Housing is also different between the two species: the new species exclusively inhabits carcinoecia formed by a hydrozoan Stylactaria misakiensis (Iwasa, 1934), whereas P. quinquelineatus uses gastropod shells without association with coelenterates. A checklist of East Asian (Japanese Archipelago to Taiwan Island, Far Eastern Russia to northern China) species of Pagurus along with general geographical distributions is presented.