bluuebunny/crossref_metadata_2025 huggingface dataset:
Body mapping of cutaneous wetness perception across the human torso during thermo-neutral and warm environmental exposures
Authors: Filingeri Davide , Fournet Damien , Hodder Simon , Havenith George
Published: August 2014

Sensing skin wetness is linked to inputs arising from cutaneous cold-sensitive afferents. As thermosensitivity to cold varies significantly across the torso, we investigated whether similar regional differences in wetness perception exist. We also investigated the regional differences in thermal pleasantness and whether these sensory patterns are influenced by ambient temperature. Sixteen males (20 ± 2 yr) underwent a quantitative sensory test under thermo-neutral [air temperature (Tair) = 22°C; relative humidity (RH) = 50%] and warm conditions (Tair = 33°C; RH = 50%). Twelve regions of the torso were stimulated with a dry thermal probe (25 cm2) with a temperature of 15°C below local skin temperature (Tsk). Variations in Tsk, thermal, wetness, and pleasantness sensations were recorded. As a result of the same cold-dry stimulus, the skin-cooling response varied significantly by location ( P = 0.003). The lateral chest showed the greatest cooling (−5 ± 0.4°C), whereas the lower back showed the smallest (−1.9 ± 0.4°C). Thermal sensations varied significantly by location and independently from regional variations in skin cooling with colder sensations reported on the lateral abdomen and lower back. Similarly, the frequency of perceived skin wetness was significantly greater on the lateral and lower back as opposed to the medial chest. Overall wetness perception was slightly higher under warm conditions. Significantly more unpleasant sensations were recorded when the lateral abdomen and lateral and lower back were stimulated. We conclude that humans present regional differences in skin wetness perception across the torso, with a pattern similar to the regional differences in thermosensitivity to cold. These findings indicate the presence of a heterogeneous distribution of cold-sensitive thermo-afferent information.
AMPK-α2is involved in exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following high-fat diet
Authors: Abbott Marcia J. , Turcotte Lorraine P.
Published: August 2014

AMP-activated protein kinase (AMPK) has been studied extensively and postulated to be a target for the treatment and/or prevention of metabolic disorders such as insulin resistance. Exercise training has been deemed a beneficial treatment for obesity and insulin resistance. Furthermore, exercise is a feasible method to combat high-fat diet (HFD)-induced alterations in insulin sensitivity. The purpose of this study was to determine whether AMPK-α2activity is required to gain beneficial effects of exercise training with high-fat feeding. Wild-type (WT) and AMPK-α2dominant-negative (DN) male mice were fed standard diet (SD), underwent voluntary wheel running (TR), fed HFD, or trained with HFD (TR + HFD). By week 6, TR, irrespective of genotype, decreased blood glucose and increased citrate synthase activity in both diet groups and decreased insulin levels in HFD groups. Hindlimb perfusions were performed, and, in WT mice with SD, TR increased insulin-mediated palmitate uptake (76.7%) and oxidation (>2-fold). These training-induced changes were not observed in the DN mice. With HFD, TR decreased palmitate oxidation (61–64%) in both WT and DN and increased palmitate uptake (112%) in the WT with no effects on palmitate uptake in the DN. With SD, TR increased ERK1/2 and JNK1/2 phosphorylation, regardless of genotype. With HFD, TR reduced JNK1/2 phosphorylation, regardless of genotype, carnitine palmitoyltransferase 1 expression in WT, and CD36 expression in both DN and WT. These data suggest that low AMPK-α2signaling disrupts, in part, the exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following HFD.
Variation in Mutation Spectrum Partly Explains Regional Differences in the Breast Cancer Risk of Female BRCA Mutation Carriers in the Netherlands
Authors: Vos Janet R. , Teixeira Natalia , van der Kolk Dorina M. , Mourits Marian J.E. , Rookus Matti A. , van Leeuwen Flora E. , Collée Margriet , van Asperen Christi J. , Mensenkamp Arjen R. , Ausems Margreet G.E.M. , van Os Theo A.M. , Meijers-Heijboer Hanne E.J. , Gómez-Garcia Encarna B. , Vasen Hans F. , Brohet Richard M. ,   on behalf of the Hereditary Breast and Ovarian Cancer Research Group Netherlands, van der Hout Annemarie H. , Jansen Liesbeth , Oosterwijk Jan C. , de Bock Geertruida H.
Published: August 2014

Background: We aimed to quantify previously observed relatively high cancer risks in BRCA2 mutation carriers (BRCA2 carriers) older than 60 in the Northern Netherlands, and to analyze whether these could be explained by mutation spectrum or population background risk.

Methods: This consecutive cohort study included all known pathogenic BRCA1/2 carriers in the Northern Netherlands (N = 1,050). Carrier and general reference populations were: BRCA1/2 carriers in the rest of the Netherlands (N = 2,013) and the general population in both regions. Regional differences were assessed with HRs and ORs. HRs were adjusted for birth year and mutation spectrum.

Results: All BRCA1 carriers and BRCA2 carriers younger than 60 had a significantly lower breast cancer risk in the Northern Netherlands; HRs were 0.66 and 0.64, respectively. Above age 60, the breast cancer risk in BRCA2 carriers in the Northern Netherlands was higher than in the rest of the Netherlands [HR, 3.99; 95% confidence interval (CI), 1.11–14.35]. Adjustment for mutational spectrum changed the HRs for BRCA1, BRCA2 <60, and BRCA2 ≥60 years by −3%, +32%, and +11% to 0.75, 0.50, and 2.61, respectively. There was no difference in background breast cancer incidence between the two regions (OR, 1.03; 95% CI, 0.97–1.09).

Conclusions: Differences in mutation spectrum only partly explain the regional differences in breast cancer risk in BRCA2 carriers, and for an even smaller part in BRCA1 carriers.

Impact: The increased risk in BRCA2 carriers older than 60 may warrant extension of intensive breast screening beyond age 60. Cancer Epidemiol Biomarkers Prev; 23(11); 2482–91. ©2014 AACR.
A Prospective Study of Physical Activity and Breast Cancer Incidence in African-American Women
Authors: Rosenberg Lynn , Palmer Julie R. , Bethea Traci N. , Ban Yulun , Kipping-Ruane Kristen , Adams-Campbell Lucile L.
Published: August 2014

Background: Physical activity has been associated with reduced risk of breast cancer. Evidence on the association in African Americans is limited.

Methods: With prospective data from the Black Women's Health Study, we assessed vigorous exercise and walking in relation to incidence of invasive breast cancer overall (n = 1,364), estrogen receptor–positive (ER+, n = 688) cancer, and estrogen receptor–negative (ER−, n = 405) cancer, based on 307,672 person-years of follow-up of 44,708 African-American women ages 30 years or older at enrollment. Cox proportional hazards models estimated incidence rate ratios (IRR) and 95% confidence intervals (CI).

Results: Vigorous exercise at baseline was inversely associated with overall breast cancer incidence (Ptrend = 0.05): the IRR for ≥7 h/wk relative to <1 h/wk was 0.74 (95% CI, 0.57–0.96). The association did not differ by ER status. Brisk walking for ≥7 h/wk was associated with a reduction similar to that for vigorous exercise. Vigorous exercise at the age of 30 years, 21 years, or in high school was not associated with breast cancer incidence. Sitting for long periods at work or watching TV was not significantly associated with breast cancer incidence.

Conclusion: High levels of vigorous exercise or brisk walking may be associated with a reduction in incidence of breast cancer in African-American women.

Impact: These results provide informative data on a potential modifiable risk factor, exercise, for breast cancer in African-American women. Cancer Epidemiol Biomarkers Prev; 23(11); 2522–31. ©2014 AACR.
Cancer Prevention and Control Interventions Using Social Media: User-Generated Approaches
Authors: Cavallo David N. , Chou Wen-Ying Sylvia , McQueen Amy , Ramirez Amelie , Riley William T.
Published: August 2014

Social media are now used by a majority of American internet users. Social media platforms encourage participants to share information with their online social connections and exchange user-generated content. Significant numbers of people are already using social media to share health-related information. As such, social media provide an opportunity for “user-generated” cancer control and prevention interventions that employ users' behavior, knowledge, and existing social networks for the creation and dissemination of interventions. These interventions also enable novel data collection techniques and research designs that will allow investigators to examine real-time behavioral responses to interventions. Emerging social media-based interventions for modifying cancer-related behaviors have been applied to such domains as tobacco use, diet, physical activity, and sexual practices, and several examples are discussed for illustration purposes. Despite some promising early findings, challenges including inadequate user engagement, privacy concerns, and lack of internet access among some groups need to be addressed in future research. Recommendations for advancing the field include stronger partnerships with commercial technology companies, utilization of rapid and adaptive designs to identify successful strategies for user engagement, rigorous and iterative efficacy testing of these strategies, and inclusive methods for intervention dissemination. Cancer Epidemiol Biomarkers Prev; 23(9); 1953–6. ©2014 AACR.
TGFβ Induces “BRCAness” and Sensitivity to PARP Inhibition in Breast Cancer by Regulating DNA-Repair Genes
Authors: Liu Liang , Zhou Weiying , Cheng Chun-Ting , Ren Xiubao , Somlo George , Fong Miranda Y. , Chin Andrew R. , Li Hui , Yu Yang , Xu Yang , O'Connor Sean Timothy Francis , O'Connor Timothy R. , Ann David K. , Stark Jeremy M. , Wang Shizhen Emily
Published: August 2014

Transforming growth factor beta (TGFβ) proteins are multitasking cytokines, in which high levels at tumor sites generally correlate with poor prognosis in human patients with cancer. Previously, it was reported that TGFβ downregulates the expression of ataxia telangiectasia–mutated (ATM) and mutS homolog 2 (MSH2) in breast cancer cells through an miRNA-mediated mechanism. In this study, expression of a panel of DNA-repair genes was examined, identifying breast cancer 1, early onset (BRCA1) as a target downregulated by TGFβ through the miR181 family. Correlations between the expression levels of TGFβ1 and the miR181/BRCA1 axis were observed in primary breast tumor specimens. By downregulating BRCA1, ATM, and MSH2, TGFβ orchestrates DNA damage response in certain breast cancer cells to induce a “BRCAness” phenotype, including impaired DNA-repair efficiency and synthetic lethality to the inhibition of poly (ADP-ribose) polymerase (PARP). Xenograft tumors with active TGFβ signaling exhibited resistance to the DNA-damaging agent doxorubicin but increased sensitivity to the PARP inhibitor ABT-888. Combination of doxorubicin with ABT-888 significantly improved the treatment efficacy in TGFβ-active tumors. Thus, TGFβ can induce “BRCAness” in certain breast cancers carrying wild-type BRCA genes and enhance the responsiveness to PARP inhibition, and the molecular mechanism behind this is characterized.

Implications: These findings enable better selection of patients with sporadic breast cancer for PARP interventions, which have exhibited beneficial effects in patients carrying BRCA mutations. Mol Cancer Res; 12(11); 1597–609. ©2014 AACR.
Caffeic Acid Directly Targets ERK1/2 to Attenuate Solar UV-Induced Skin Carcinogenesis
Authors: Yang Ge , Fu Yang , Malakhova Margarita , Kurinov Igor , Zhu Feng , Yao Ke , Li Haitao , Chen Hanyong , Li Wei , Lim Do Young , Sheng Yuqiao , Bode Ann M. , Dong Ziming , Dong Zigang
Published: August 2014

Caffeic acid (3,4-dihydroxycinnamic acid) is a well-known phenolic phytochemical present in coffee and reportedly has anticancer activities. However, the underlying molecular mechanisms and targeted proteins involved in the suppression of carcinogenesis by caffeic acid are not fully understood. In this study, we report that caffeic acid significantly inhibits colony formation of human skin cancer cells and EGF-induced neoplastic transformation of HaCaT cells dose-dependently. Caffeic acid topically applied to dorsal mouse skin significantly suppressed tumor incidence and volume in a solar UV (SUV)–induced skin carcinogenesis mouse model. A substantial reduction of phosphorylation in mitogen-activated protein kinase signaling was observed in mice treated with caffeic acid either before or after SUV exposure. Caffeic acid directly interacted with ERK1/2 and inhibited ERK1/2 activities in vitro. Importantly, we resolved the cocrystal structure of ERK2 complexed with caffeic acid. Caffeic acid interacted directly with ERK2 at amino acid residues Q105, D106, and M108. Moreover, A431 cells expressing knockdown of ERK2 lost sensitivity to caffeic acid in a skin cancer xenograft mouse model. Taken together, our results suggest that caffeic acid exerts chemopreventive activity against SUV-induced skin carcinogenesis by targeting ERK1 and 2. Cancer Prev Res; 7(10); 1056–66. ©2014 AACR.
Nature of Tumor Control by Permanently and Transiently Modified GD2 Chimeric Antigen Receptor T Cells in Xenograft Models of Neuroblastoma
Authors: Singh Nathan , Liu Xiaojun , Hulitt Jessica , Jiang Shuguang , June Carl H. , Grupp Stephan A. , Barrett David M. , Zhao Yangbing
Published: August 2014

Chimeric antigen receptor (CAR) therapy has begun to demonstrate success as a novel treatment modality for hematologic malignancies. The success observed thus far has been with T cells permanently engineered to express chimeric receptors. T cells engineered using RNA electroporation represent an alternative with the potential for similar efficacy and greater safety when initially targeting novel antigens. Neuroblastoma is a common pediatric solid tumor with the potential to be targeted using immunotherapy. We performed xenograft studies in NSG mice in which we assessed the efficacy of both permanently modified and transiently modified CAR T cells directed against the neuroblastoma antigen GD2 in both local and disseminated disease models. Disease response was monitored by tumor volume measurement and histologic examination, as well as in vivo bioluminescence. RNA-modified GD2 CAR T cells mediated rapid tumor destruction when delivered locally. A single infusion of lentivirally modified GD2 CAR T cells resulted in long-term control of disseminated disease. Multiple infusions of RNA GD2 CAR T cells slowed the progression of disseminated disease and improved survival, but did not result in long-term disease control. Histologic examination revealed that the transiently modified cells were unable to significantly penetrate the tumor environment when delivered systemically, despite multiple infusions of CAR T cells. Thus, we demonstrate that RNA-modified GD2 CAR T cells can mediate effective antitumor responses in vivo, and permanently modified cells are able to control disseminated neuroblastoma in xenograft mice. Lack of long-term disease control by RNA-engineered cells resulted from an inability to penetrate the tumor microenvironment. Cancer Immunol Res; 2(11); 1059–70. ©2014 AACR.
Experience Using a Rapid Assay for Aneuploidy and Microdeletion/Microduplication Detection in over 2,900 Prenatal Specimens
Authors: Rosenfeld Jill A. , Morton S. Anne , Hummel Cathryn , Sulpizio Scott G. , McDaniel Lisa D. , Schultz Roger A. , Torchia Beth S. , Ravnan J. Britt , Ellison Jay W. , Fisher Allan J.
Published: August 2014

Background: While microarray testing can identify chromosomal abnormalities missed by karyotyping, its prenatal use is often avoided in low-risk pregnancies due to the possible identification of variants of uncertain significance (VOUS). Methods: We tested 2,970 prenatal samples of all referral indications using a rapid BACs-on-Beads-based assay with probes for sex chromosomes, common autosomal aneuploidies, and 20 microdeletion/microduplication syndromes, designed as an alternative to microarray in low-risk pregnancies and an alternative to rapid aneuploidy testing in pregnancies also undergoing microarray analysis. Results: Interpretable results were obtained in 2,940 cases (99.0%), with 89% receiving results in 1 day. Aneuploidies were detected in 7.3% and partial chromosome abnormalities in 0.45% (n = 13), including 5 referred for maternal age, abnormal maternal serum screen, or isolated ultrasound markers. The added detection above karyotype was 1 in 745 in lower-risk cases with normal ultrasounds or isolated ultrasound markers/increased nuchal measurements and 1 in 165 for fetuses with structural/growth abnormalities. Neither false negatives nor false positives were found within test limitations. Female polyploidy could not be detected, while polyploidies with Y chromosomes were suspected and confirmed through additional analysis. Conclusion: When combined with karyotyping, this assay provides increased interrogation of specific chromosomal regions, while limiting VOUS identification.
Laparoscopic Ureteral Reimplantation underneath Broad Ligament Tunnel for Female Vesicoureteral Stenosis: A Technical Innovation
Authors: Xu Chuangliang , Zeng Shuxiong , Zhang Zhensheng , Zhou Tie , Li Huizhen , Li Haihang , Wei Rongchao , Song Ruixiang , Yang Qingsong , Yu Xiaowen , Sun Yinghao
Published: August 2014

Introduction: In order to anatomically reconstruct ureteral stenosis, we present a novel technique for laparoscopic ureteral reimplantation. Patients and Methods: Three young females, who were diagnosed with hydroureteronephrosis caused by congenital vesicoureteral junction obstruction, were treated by laparoscopic ureteral reimplantation with a tunnel underneath the broad ligament. Results: Surgery was performed successfully without conversion to open surgery. No major intra- or postoperative complications occurred. Postoperative follow-up was 38, 33 and 26 months, respectively. The operative time was between 220 and 260 min. The mean estimated blood loss was less than 20 ml. Subsequent imaging performed 3 months after surgery revealed relief of hydroureteronephrosis for all patients. The patients all gave birth to healthy neonates and showed normal urinary tract sonogram and urine analysis during the gestation period. Conclusion: Laparoscopic ureteral reimplantation with broad ligament tunnel is safe and effective, allowing for anatomical reconstruction of ureter defects. However, a larger clinical sample and longer follow-up period will be needed.
Pyonephrosis Caused by Salmonella Typhi: A Case Report
Authors: Batista da Costa José , Cornu Jean-Nicolas , Levgraverend Dorian , Cordel Hugues , Ridel Christophe , Letendre Julien , Traxer Olivier , Tligui Mohamed , Haab François
Published: August 2014

Introduction: Salmonella is a rare cause of urinary tract infections. We report here a unique case of pyonephrosis due to Salmonella Typhi (S. Typhi) complication, a stone-related obstructive pyelonephritis. Case Report: A 47-year-old man, without any history of typhoid fever or gastrointestinal symptoms, presented with a pyonephrosis and life-threatening bacteremia following an acute obstructive right pyelonephritis caused by S. Typhi. The patient was treated by urinary drainage (ureteral stent), antibiotics, and delayed right nephrectomy. We postulated that urolithiasis could explain asymptomatic chronic urinary carriage of S. Typhi. Conclusion:S. Typhi is one possible cause of life-threatening urinary tract infection, especially in the context of urolithiasis.
A MAVS/TICAM-1-Independent Interferon-Inducing Pathway Contributes to Regulation of Hepatitis B Virus Replication in the Mouse Hydrodynamic Injection Model
Authors: Leong Chean Ring , Oshiumi Hiroyuki , Okamoto Masaaki , Azuma Masahiro , Takaki Hiromi , Matsumoto Misako , Chayama Kazuaki , Seya Tsukasa
Published: August 2014

Toll-like receptors (TLRs) and cytoplasmic RNA sensors have been reported to be involved in the regulation of hepatitis B virus (HBV) replication, but remain controversial due to the lack of a natural infectious model. Our current study sets out to characterize aspects of the role of the innate immune system in eliminating HBV using hydrodynamic-based injection of HBV replicative plasmid and knockout mice deficient in specific pathways of the innate system. The evidence indicated that viral replication was not affected by MAVS or TICAM-1 knockout, but absence of interferon regulatory factor 3 (IRF-3) and IRF-7 transcription factors, as well as the interferon (IFN) receptor, had an adverse effect on the inhibition of HBV replication, demonstrating the dispensability of MAVS and TICAM-1 pathways in the early innate response against HBV. Myd88-/- mice did not have a significant increase in the initial viremia, but substantial viral antigen persisted in the mice sera, a response similar to Rag2-/- mice, suggesting that the MyD88-dependent pathway participated in evoking an adaptive immune response against the clearance of intrahepatic HBV. Taken together, we show that the RNA-sensing pathways do not participate in the regulation of HBV replication in a mouse model; meanwhile MyD88 is implicated in the HBV clearance.
Experiences and Results from Cochlear Implantation in Patients with Long Duration of Deafness
Authors: Lundin Karin , Stillesjö Fredrik , Rask-Andersen Helge
Published: August 2014

Objective: The aim of the present study was to gauge factors that influence the outcome of cochlear implants (CI) in patients who have been deaf for an extended period. Patients and Methods: Twelve adult cases (13 ears) were operated on at the CI unit in Uppsala during the period of 2002-2013. These patients had a deafness duration ranging between 20 and 72 years in the implanted ear and severe to profound hearing loss or deafness in the other ear. Data concerning pre- and postoperative speech perception, deafness duration, hearing/deafness duration in the contralateral ear, age at implantation, intraoperative electrophysiological measurements, cause of deafness, and user status were collected. Results: Eleven of 12 patients (13 ears) benefitted from CI treatment. Conclusion: The overall hearing experience, deafness duration, and age at onset of deafness are important issues to consider prior to CI.
Cooperation between human fibrocytes and endothelial colony-forming cells increases angiogenesis via the CXCR4 pathway
Authors: Dorfmüller Peter , Guerin Coralie , Bieche Ivan , Badoual Cécile , Boscolo Elisa , Kambouchner Marianne , Cazes Aurélie , Mercier Olaf , Humbert Marc , Gaussem Pascale , Bischoff Joyce , Israël-Biet Dominique , Smadja David
Published: August 2014

Fibrotic diseases of the lung are associated with a vascular remodelling process. Fibrocytes (Fy) are a distinct population of blood-borne cells that co-express haematopoietic cell antigens and fibroblast markers, and have been shown to contribute to organ fibrosis. The purpose of this study was to determine whether fibrocytes cooperate with endothelial colony-forming cells (ECFC) to induce angiogenesis. We isolated fibrocytes from blood of patient with idiopathic pulmonary fibrosis (IPF) and characterised them by flow cytometry, quantitative reverse transcriptase PCR (RTQ-PCR), and confocal microscopy. We then investigated the angiogenic interaction between fibrocytes and cordblood- derived ECFC, both in vitro and in an in vivo Matrigel implant model. Compared to fibroblast culture medium, fibrocyte culture medium increased ECFC proliferation and differentiation via the SDF- 1/CXCR4 pathway. IPF-Fy co-implanted with human ECFC in Matrigel plugs in immunodeficient mice formed functional microvascular beds, whereas fibroblasts did not. Evaluation of implants after two weeks revealed an extensive network of erythrocyte-containing blood vessels. CXCR4 blockade significantly inhibited this blood vessel formation. The clinical relevance of these data was confirmed by strong CXCR4 expression in vessels close to fibrotic areas in biopsy specimens from patients with IPF, by comparison with control lungs. In conclusion, circulating fibrocytes might contribute to the intense remodelling of the pulmonary vasculature in patients with idiopathic pulmonary fibrosis.
Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression
Authors: Davidova Alzbeta , Mörgelin Matthias , Linder Adam , Larsen Michael , Qvortrup Klaus , Nordenfelt Pontus , Shannon Oonagh , Dzupova Olga , Holub Michal , Malmström Johan , Herwald Heiko , Malmström Erik
Published: August 2014

Early diagnosis of severe infectious diseases is essential for timely implementation of lifesaving therapies. In a search for novel biomarkers in sepsis diagnosis we focused on polymorphonuclear neutrophils (PMNs). Notably, PMNs have their protein cargo readily stored in granules and following systemic stimulation, an immediate increase of neutrophil-borne proteins can be observed into the circulation of sepsis patients. We applied a combination of mass spectrometry (MS) based approaches, LC-MS/MS and selected reaction monitoring (SRM), to characterise and quantify the neutrophil proteome in healthy or disease conditions. With this approach we identified a neutrophil- derived protein abundance pattern in blood plasma consisting of 20 proteins that can be used as a protein signature for severe infectious diseases. Our results also show that SRM is highly sensitive, specific, and reproducible and, thus, a promising technology to study a complex, dynamic and multifactorial disease such as sepsis.
Bleeding diathesis and gastro-duodenal ulcers in inherited cytosolic phospholipase-A2 alpha deficiency
Authors: Faioni Elena , Razzari Cristina , Zulueta Aida , Femia Eti , Fenu Lara , Trinchera Marco , Podda Gian Marco , Pugliano Mariateresa , Marongiu Francesco , Cattaneo Marco
Published: August 2014

Arachidonic acid (AA), when cleaved from phospholipids by cytosolic phospholipase A2 alpha (cPLA2a), generates eicosanoids, with pro-hemostatic, pro-inflammatory, vasoactive and gastro-protective functions. We describe a patient (27-year-old man) and his twin-sister with early-onset bleeding diathesis and recurrent gastro-intestinal (GI) ulcers. Platelet aggregation/δ-granules secretion by collagen was impaired, but normal by AA; serum levels of thromboxane (Tx) B2 and 12-hydroxyeicosatetraenoic acid, and urinary levels of 11-dehydro- TxB2 were extremely low. Patients were homozygous for 1723G>C transition in PLA2G4A gene, which changed the codon for Asp575 to His. GI ulcers affected 5/14 heterozygous (< 40 years) and 1/16 wildtype homozygous (> 60 years) family members; none had bleeding diathesis. The proband, his sister and mother also had mildly reduced factor XI levels. Platelet messenger RNA expression did not differ among subjects with different PLA2G4A genotypes. Conversely, platelet cPLA2a was undetectable by Western Blotting in the proband and his sister, and decreased in 1723G>C heterozygous subjects, suggesting that the variant is transcribed, but not translated or translated into an unstable protein. We described a syndromic form of deficiency of cPLA2a , characterised by recurrent GI ulcers and bleeding diathesis, associated with mild inherited deficiency of factor XI. Unlike other reported patients with cPLA2a deficiency, these patients had extremely low levels of platelet TxA2 biosynthesis.
Rosuvastatin Activates ATP-Binding Cassette Transporter A1–Dependent Efflux Ex Vivo and Promotes Reverse Cholesterol Transport in Macrophage Cells in Mice Fed a High-Fat Diet
Authors: Shimizu Tomohiko , Miura Shin-ichiro , Tanigawa Hiroyuki , Kuwano Takashi , Zhang Bo , Uehara Yoshinari , Saku Keijiro
Published: August 2014

Objective—

It is controversial whether statins improve high-density lipoprotein (HDL) function, which plays an important role in reverse cholesterol transport in vivo. The aim of the present study was to clarify the effects of rosuvastatin and atorvastatin on reverse cholesterol transport in macrophage cells in vivo and their underlying mechanisms.

Approach and Results—

Male C57BL mice were divided into 3 groups (rosuvastatin, atorvastatin, and control groups) and orally administered rosuvastatin, atorvastatin, or placebo for 6 weeks under feeding with a 0.5% cholesterol+10% coconut oil diet. After administration, although there were no changes in plasma HDL cholesterol levels among the groups, plasma from the rosuvastatin group showed an increased ability to promote ATP-binding cassette transporter A1–mediated cholesterol efflux ex vivo. In addition, capillary electrophoresis revealed a shift in HDL toward the pre-β HDL fraction only in the rosuvastatin group. Mice in all 3 groups were intraperitoneally injected with
3
H-cholesterol–labeled and cholesterol-loaded macrophages and then were monitored for the appearance of
3
H-tracer in plasma and feces. The amount of
3
H-tracer excreted into feces during 48 hours in the rosuvastatin group was greater than that in the control group. Finally,
3
H-cholesteryl oleate-HDL was intravenously injected into all groups, blood samples were taken, and the count of
3
H-cholesterol was analyzed. Plasma
3
H-cholesteryl oleate-HDL changed similarly, and no differences in fractional catabolic rates were observed.

Conclusions—

Rosuvastatin enhanced the ATP-binding cassette transporter A1–dependent HDL efflux function of reverse cholesterol transport, and this finding highlights the potential of rosuvastatin for the regression of atherosclerosis.
Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease
Authors: Wannamethee S. Goya , Welsh Paul , Papacosta Olia , Lennon Lucy , Whincup Peter H. , Sattar Naveed
Published: August 2014

Background—

Hyperparathyroidism and low vitamin D status have been implicated in the pathogenesis of heart failure (HF). We examined the prospective associations between parathyroid hormone (PTH), circulating 25-hydroxyvitamin D, and markers of mineral metabolism and risk of incident HF in older men with and without established cardiovascular disease.

Methods and Results—

Prospective study of 3731 men aged 60 to 79 years with no prevalent HF followed up for a mean period of 13 years, in whom there were 287 incident HF cases. Elevated PTH (≥55.6 pg/mL; top quarter) was associated with significantly higher risk of incident HF after adjustment for lifestyle characteristics, diabetes mellitus, blood lipids, blood pressure, lung function, heart rate, renal dysfunction, atrial fibrillation, forced expiratory volume in 1 second, and C-reactive protein (hazards ratio, 1.66; 95% confidence interval, 1.30–2.13). The increased risk was seen in both men with and without previous myocardial infarction or stroke (hazards ratio, 1.72; 95% confidence interval, 1.07–2.76; hazards ratio, 1.70; 95% confidence interval, 1.25–2.30, respectively). Elevated PTH was significantly associated with N-terminal probrain natriuretic peptide, a marker of left ventricular wall stress. By contrast, 25-hydroxyvitamin D and other markers of mineral metabolism including serum calcium and phosphate showed no significant association with incident HF after adjustment for age.

Conclusions—

Elevated PTH, but not 25-hydroxyvitamin D or other markers of mineral metabolism, is associated with increased risk of HF in both older men with and without myocardial infarction/stroke. This increased risk was not explained by its association with known risk factors for HF. Further studies are now needed to elucidate the mechanisms underlying this association.
Short‐term Changes in Ambient Particulate Matter and Risk of Stroke: A Systematic Review and Meta‐analysis
Authors: Wang Yi , Eliot Melissa N. , Wellenius Gregory A.
Published: August 2014

Background

Stroke is a leading cause of death and long‐term disability in the United States. There is a well‐documented association between ambient particulate matter air pollution (
PM
) and cardiovascular disease morbidity and mortality. Given the pathophysiologic mechanisms of these effects, short‐term elevations in
PM
may also increase the risk of ischemic and/or hemorrhagic stroke morbidity and mortality, but the evidence has not been systematically reviewed.

Methods and Results

We provide a comprehensive review of all observational human studies (January 1966 to January 2014) on the association between short‐term changes in ambient
PM
levels and cerebrovascular events. We also performed meta‐analyses to evaluate the evidence for an association between each
PM
size fraction (
PM
2.5
,
PM
10
,
PM
2.5‐10
) and each outcome (total cerebrovascular disease, ischemic stroke/transient ischemic attack, hemorrhagic stroke) separately for mortality and hospital admission. We used a random‐effects model to estimate the summary percent change in relative risk of the outcome per 10‐μg/m
3
increase in
PM
.

Conclusions

We found that
PM
2.5
and
PM
10
are associated with a 1.4% (95%
CI
0.9% to 1.9%) and 0.5% (95%
CI
0.3% to 0.7%) higher total cerebrovascular disease mortality, respectively, with evidence of inconsistent, nonsignificant associations for hospital admission for total cerebrovascular disease or ischemic or hemorrhagic stroke. Current limited evidence does not suggest an association between
PM
2.5‐10
and cerebrovascular mortality or morbidity. We discuss the potential sources of variability in results across studies, highlight some observations, and identify gaps in literature and make recommendations for future studies.
On cockroaches of the subfamily Epilamprinae (Dictyoptera: Blaberidae) from South India and Sri Lanka, with descriptions of new taxa
Authors: ANISYUTKIN LEONID N.
Published: August 2014

The new genus Indoapterolampra, gen. nov. and two new species (I. rugosiuscula sp. nov. and Morphna lucida sp. nov.) are described. Rhabdoblatta praecipua (Walker, 1868) is removed from the synonymy with 'Polyzosteria' terranea Walker, 1868. The latter species is considered Epilamprinae gen. sp. The lectotype of Phoraspis (Thorax) porcellana Saussure, 1862 is designated. A key for the genera of Epilamprinae from South India and Sri Lanka is provided. Detailed morphological descriptions of the studied taxa are given. The structure of the male genitalia of I. rugosiuscula sp. nov., M. lucida sp. nov., M. plana (Brunner von Wattenwyl, 1865), M. decolyi (Bolivar, 1897) and R. praecipua and that of the female genital complex of M. decolyi, P. (T.) porcellana and Phlebonotus anomalus (Saussure, 1863) are described for the first time. Some aspects of the cockroach evolution are briefly discussed.
Cymatodera ochlera Barr, a junior synonym of Cymatodera wolcotti Barr, with a comparison to similar species (Coleoptera: Cleridae)
Authors: BURKE ALAN F. , ZOLNEROWICH GREGORY
Published: August 2014

Cymatodera ochlera Barr 1972 has been considered to be very similar to but distinct from C. wolcotti Barr 1950. We present evidence to show that these two species are conspecific and C. ochlera should be treated as a junior synonym of C. wolcotti. Cymatodera wolcotti is compared to C. balteata and C. undulata, two species remarkably similar to C. wolcotti. Morphological characters of significant value are presented that confirm C. balteata and C. undulata are separate species. Images of all characters discussed are provided.
Two new species and a new synonym of the genus Paederus Fabricius (Coleoptera: Staphylinidae: Paederinae) from China
Authors: LI XIAO-YAN , SOLODOVNIKOV ALEXEY , ZHOU HONG-ZHANG
Published: August 2014

Two new species of the genus Paederus Fabricius, 1775 from mainland China are described: Paederus (Harpopaederus) brevior sp. nov. (Shaanxi) and P. (H.) multidenticulatus sp. nov. (Hubei). One new synonym is proposed: Paederus parvidenticulatus Li, Zhou & Solodovnikov, 2013 = Paederus symmetricus Li, Zhou & Solodovnikov, 2013 syn. nov.
A Unified Convection Scheme (UNICON). Part I: Formulation
Authors: Park Sungsu
Published: August 2014

The author develops a unified convection scheme (UNICON) that parameterizes relative (i.e., with respect to the grid-mean vertical flow) subgrid vertical transport by nonlocal asymmetric turbulent eddies. UNICON is a process-based model of subgrid convective plumes and mesoscale organized flow without relying on any quasi-equilibrium assumptions such as convective available potential energy (CAPE) or convective inhibition (CIN) closures. In combination with a relative subgrid vertical transport scheme by local symmetric turbulent eddies and a grid-scale advection scheme, UNICON simulates vertical transport of water species and conservative scalars without double counting at any horizontal resolution.

UNICON simulates all dry–moist, forced–free, and shallow–deep convection within a single framework in a seamless, consistent, and unified way. It diagnoses the vertical profiles of the macrophysics (fractional area, plume radius, and number density) as well as the microphysics (production and evaporation rates of convective precipitation) and the dynamics (mass flux and vertical velocity) of multiple convective updraft and downdraft plumes. UNICON also prognoses subgrid cold pool and mesoscale organized flow within the planetary boundary layer (PBL) that is forced by evaporation of convective precipitation and accompanying convective downdrafts but damped by surface flux and entrainment at the PBL top. The combined subgrid parameterization of diagnostic convective updraft and downdraft plumes, prognostic subgrid mesoscale organized flow, and the feedback among them remedies the weakness of conventional quasi-steady diagnostic plume models—the lack of plume memory across the time step—allowing UNICON to successfully simulate various transitional phenomena associated with convection (e.g., the diurnal cycle of precipitation and the Madden–Julian oscillation).
Energetics of East Pacific Easterly Waves during Intraseasonal Events
Authors: Rydbeck Adam V. , Maloney Eric D.
Published: August 2014

The background atmospheric state of the east Pacific warm pool in which easterly waves develop varies dramatically on intraseasonal time scales. East Pacific intraseasonal variability is well known to modulate local convective and circulation patterns. Westerly (easterly) intraseasonal phases are associated with westerly (easterly) low-level wind and positive (negative) convective anomalies. This study investigates the perturbation available potential energy (PAPE) and perturbation kinetic energy (PKE) budgets of easterly waves composited during westerly, easterly, and neutral intraseasonal phases, respectively. The mechanisms, magnitudes, locations, and vertical structures of easterly waves are shown to strongly vary as a function of intraseasonal phase. Easterly waves draw energy from low-level barotropic conversion, regardless of phase, although the location and magnitude of the conversion varies strongly. During neutral and westerly intraseasonal phases, the generation of PAPE associated with perturbation diabatic heating that is subsequently converted to PKE is the dominant energy source for easterly waves. A novel and previously unrecognized result is the detection of strong barotropic generation of PKE at midlevels during westerly intraseasonal phases. This previously unidentified source of PKE at midlevels is in part due to strong intraseasonal modulation of the background midlevel winds.
Parameter Tuning and Calibration of RegCM3 with MIT–Emanuel Cumulus Parameterization Scheme over CORDEX East Asia Domain
Authors: Zou Liwei , Qian Yun , Zhou Tianjun , Yang Ben
Published: August 2014

In this study, the authors calibrated the performance of the Regional Climate Model, version 3 (RegCM3), with the Massachusetts Institute of Technology (MIT)–Emanuel cumulus parameterization scheme over the Coordinated Regional Climate Downscaling Experiment (CORDEX) East Asia domain by tuning seven selected parameters based on the multiple very fast simulated annealing (MVFSA) approach. The seven parameters were selected based on previous studies using RegCM3 with the MIT–Emanuel convection scheme. The results show the simulated spatial pattern of rainfall, and the probability density function distribution of daily rainfall rates is significantly improved in the optimal simulation. Sensitivity analysis suggests that the parameter relative humidity criteria (RHC) has the largest effect on the model results. Followed by an increase of RHC, an increase of total rainfall is found over the northern equatorial western Pacific, mainly contributed by the increase of explicit rainfall. The increases of the convergence of low-level water vapor transport and the associated increases in cloud water favor the increase of explicit rainfall. The identified optimal parameters constrained by total rainfall have positive effects on the low-level circulation and surface air temperature. Furthermore, the optimized parameters based on the chosen extreme case are transferable to a normal case and the model’s new version with a mixed convection scheme.
Investigation of Discrepancies in Satellite Rainfall Estimates over Ethiopia
Authors: Young Matthew P. , Williams Charles J. R. , Chiu J. Christine , Maidment Ross I. , Chen Shu-Hua
Published: August 2014

Tropical Applications of Meteorology Using Satellite and Ground-Based Observations (TAMSAT) rainfall estimates are used extensively across Africa for operational rainfall monitoring and food security applications; thus, regional evaluations of TAMSAT are essential to ensure its reliability. This study assesses the performance of TAMSAT rainfall estimates, along with the African Rainfall Climatology (ARC), version 2; the Tropical Rainfall Measuring Mission (TRMM) 3B42 product; and the Climate Prediction Center morphing technique (CMORPH), against a dense rain gauge network over a mountainous region of Ethiopia. Overall, TAMSAT exhibits good skill in detecting rainy events but underestimates rainfall amount, while ARC underestimates both rainfall amount and rainy event frequency. Meanwhile, TRMM consistently performs best in detecting rainy events and capturing the mean rainfall and seasonal variability, while CMORPH tends to overdetect rainy events. Moreover, the mean difference in daily rainfall between the products and rain gauges shows increasing underestimation with increasing elevation. However, the distribution in satellite–gauge differences demonstrates that although 75% of retrievals underestimate rainfall, up to 25% overestimate rainfall over all elevations. Case studies using high-resolution simulations suggest underestimation in the satellite algorithms is likely due to shallow convection with warm cloud-top temperatures in addition to beam-filling effects in microwave-based retrievals from localized convective cells. The overestimation by IR-based algorithms is attributed to nonraining cirrus with cold cloud-top temperatures. These results stress the importance of understanding regional precipitation systems causing uncertainties in satellite rainfall estimates with a view toward using this knowledge to improve rainfall algorithms.
Comparison of Global and Seasonal Characteristics of Cloud Phase and Horizontal Ice Plates Derived from CALIPSO with MODIS and ECMWF
Authors: Hirakata Maki , Okamoto Hajime , Hagihara Yuichiro , Hayasaka Tadahiro , Oki Riko
Published: August 2014

This study analyzed the global and seasonal characteristics of cloud phase and ice crystal orientation (CTYPE-lidar) by using the Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) on board the Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO). A dataset from September 2006 to August 2007 was used to derive the seasonal characteristics. The discrimination scheme was originally developed by Yoshida et al., who classified clouds mainly into warm water, supercooled water, and randomly oriented ice crystals or horizontally oriented ice plates. This study used the following products for the comparison with CTYPE-lidar: (i) the vertical feature mask (VFM) of the National Aeronautics and Space Administration (NASA), (ii) the Moderate Resolution Imaging Spectroradiometer (MODIS), and (iii) European Centre for Medium-Range Weather Forecasts (ECMWF). Overall, the results showed that the CTYPE-lidar discrimination scheme was consistent with the outputs from VFM, MODIS, and ECMWF. The zonal mean water cloud cover in daytime from this study showed good agreement with that derived from MODIS; the slope of the linear regression was 1.06 and the offset was 0.002. The CTYPE-lidar ice cloud occurrence frequency and the ECMWF ice supersaturation occurrence frequency were also in good agreement; the slope of the linear regression of the two products was 1.02 in the temperature range −60°C ≤ T ≤ −30°C. The maximum occurrence frequencies in this study and ECMWF were recognized around −60°C of the equator, with their peak shifted from several degrees north (~9°N) in September–November (SON) to south (~9°S) in December–February (DJF) and back to north (~7°N) in March–May (MAM) and June–August (JJA).
Occupational Performance Coaching for stroke survivors: A pilot randomized controlled trial protocol
Authors: Kessler Dorothy E. , Egan Mary Y. , Dubouloz Claire-Jehanne , Graham Fiona P. , McEwen Sara E.
Published: August 2014

Background.

Many stroke survivors report participation challenges. Occupational Performance Coaching for stroke survivors (OPC-Stroke) is designed to assist stroke survivors to develop the ability to plan and manage engagement in occupation. This approach combines emotional support, individualized education, and goal-focused problem solving to promote occupational engagement.

Purpose.

This study will explore the potential efficacy of OPC-Stroke and the feasibility of the research methods for use in a larger trial.

Method.

A pilot randomized controlled trial will be undertaken. Participants will be randomly assigned to receive 10 sessions of OPC-Stroke or usual care. Participation, perceived goal performance, satisfaction and self-efficacy, emotional well-being, and cognition will be measured at three time points.

Implications.

This research will test the potential usefulness of OPC-Stroke as well as the study methods, and thereby inform the continuing development of OPC-Stroke and further studies to measure its effectiveness.
Simulation modeling framework for uncovering system behaviors in the biofuels supply chain network
Authors: Agusdinata Datu B , Lee Seokcheon , Zhao Fu , Thissen Wil
Published: August 2014

A full realization of alternative energy such as biofuels depends on the existence of a viable supply chain (SC) network. An agent-based simulation approach is pursued to understand the dynamics of the biofuels SC network. The interests of three SC actors are represented: users, biorefineries, and farmers. Each actor type has a binary decision option: adoption or non-adoption of biofuels. This SC network model is characterized by distributed control, time asynchrony, and resource contention among actors, who make decisions based on incomplete knowledge and delayed information. The decision dynamics of these actors are modeled using a computational ecosystem construct. A preliminary set of coupled payoff function for each actor type and each decision is developed to represent interdependencies among SC actors. The simulation model was used to evaluate three archetypes of subsidy policy. The SC network behavior is observed in terms of fraction of actors adopting the biofuel option. The SC network shows behaviors ranging from fixed point equilibrium under no delay and perfect knowledge to periodic and chaotic oscillations. The network behavior is very sensitive to the time delay parameter that partly influences the quality of information on which actors’ decisions are based. Several regions of SC behavior are identified. In particular, a chaotic behavior was observed. The work provides a methodological basis for further development, including identification of policies to control undesirable system behaviors.