bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral Doppler Interrogation of Mitral Regurgitation —Spot Diagnosis
Authors: Fadel Bahaa M. , Bakarman Hatem , Dahdouh Ziad , Di Salvo Giovanni , Mohty Dania
Published: January 2015

Mitral regurgitation (MR) is one of the most common valvular lesions that are readily identified by transthoracic echocardiography. Color Doppler imaging is the modality of choice for the recognition of MR, and it plays an important role in the assessment of regurgitation severity. Continuous wave (CW) Doppler is commonly used to interrogate the MR signal, and this modality can provide highly useful data regarding several physiological and pathological parameters. In this manuscript, we present a series of cases that illustrate the various hemodynamic parameters that can be derived from analysis of the CW Doppler signal of MR.
Retracted: Quercetin induces endoplasmic reticulum stress to enhance cDDP cytotoxicity in ovarian cancer: involvement of STAT3 signaling
Authors: Yang Zongyuan , Liu Yi , Liao Jing , Gong Cheng , Sun Chaoyang , Zhou Xiaoshui , Wei Xiao , Zhang Taoran , Gao Qinglei , Ma Ding , Chen Gang
Published: January 2015

There is an urgent need to make cisplatin (cDDP) more effective and less toxic in the treatment of ovarian cancer for its systemic side effects and high resistance rate. In this study, we investigated the effect of quercetin (Qu) pretreatment on the potentiation of cDDP in ovarian cancer. We found that Qu pretreatment significantly enhanced cDDP cytotoxicity in an ovarian cancer cell line and primary cancer cells. In addition, we demonstrated that Qu elicited obvious endoplasmic reticulum stress (ERS) and activated all three branches of ERS in ovarian cancer. Specific inhibitors of each ERS pathway, as well as the general ERS stabilizer tauroursodeoxycholic acid, notably diminished such enhancing effects. Furthermore, Qu notably suppressed STAT3 phosphorylation, leading to downregulation of the BCL‐2 gene downstream of STAT3. Moreover, blocking ERS restored the protein levels of phosphorylated STAT3 as well as BCL‐2 expression, thus abolishing the chemosensitization potency of Qu; these results revealed that Qu affected the STAT3 pathway to enhance cDDP cytotoxicity, and this effect involved ERS signaling. In a xenograft mouse model of ovarian cancer, Qu enhanced the antitumor effect of cDDP. Tumors from mice treated with cDDP in combination with Qu pretreatment had repressed STAT3 phosphorylation, lower BCL‐2 and higher apoptosis levels compared with those from the other groups. Meanwhile, Qu markedly reduced the elevation of blood creatinine during cDDP intervention. These data indicate that Qu pretreatment potentiates the antitumor effects of cDDP in ovarian cancer while protecting the kidneys against damage. Therefore the strategy of Qu pretreatment may be beneficial in enhancing the therapeutic efficacy of cDDP against ovarian cancer.
Study based on the analysis of valence electron structure for adiabatic shear sensitivity of 30CrMnMo and C45E4 steel in process of high‐speed penetration
Authors: Li J. Q. , Wang Y. , Chen L. , Huang S. T.
Published: January 2015

In this paper, the influence of valence electron structure parameters on the adiabatic shearing sensitivity has been studied for two grade steels (30CrMnMo and C45E4) as a function of covalent pair number and lattice electron number by empirical electron theory of solids and molecules in high‐speed penetration process. The research shows that the adiabatic shearing sensitivity increases with the increase of the covalent electron pair number nA, decreases with the increase of the lattice electron number nl. The nA of each structure unit in 30CrMnMo steel is larger than that in C45E4steel, the nl of each structure unit in 30CrMnMo steel is smaller than that in C45E4steel. Therefore, the adiabatic shearing sensitivity is higher for 30CrMnMo targets damaged by adiabatic shear failure, and yet C45E4 targets were damaged by ductile fracture without any adiabatic shear band. The basis can be provided for appropriately selecting and designing materials with different adiabatic shearing sensitivity by studying the specific alloy elements on the influence of adiabatic shearing sensitivity in valence electron structure level.
Borderline personality disorder and childhood maltreatment: a genome‐wide methylation analysis
Authors: Prados J. , Stenz L. , Courtet P. , Prada P. , Nicastro R. , Adouan W. , Guillaume S. , Olié E. , Aubry J.‐M. , Dayer A. , Perroud N.
Published: January 2015

Early life adversity plays a critical role in the emergence of borderline personality disorder (BPD) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole‐genome methylation scan of BPD subjects. Using the Illumina Infinium® HumanMethylation450 BeadChip, global methylation status of DNA extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 BPD subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (MDD) and reporting a low rate of child maltreatment. Several CpGs within or near the following genes (IL17RA, miR124‐3, KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A and SPSB2) were found to be differently methylated, either in BPD compared with MDD or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to miR124‐3 that was significantly associated with BPD and severity of childhood maltreatment. miR124‐3 codes for a microRNA (miRNA) targeting several genes previously found to be associated with BPD such as NR3C1. Our results highlight the potentially important role played by miRNAs in the etiology of neuropsychiatric disorders such as BPD and the usefulness of using methylome‐wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.
Potential for long‐term transfer of dissolved organic carbon from riparian zones to streams in boreal catchments
Authors: Ledesma José L. J. , Grabs Thomas , Bishop Kevin H. , Schiff Sherry L. , Köhler Stephan J.
Published: January 2015

Boreal regions store most of the global terrestrial carbon, which can be transferred as dissolved organic carbon (DOC) to inland waters with implications for both aquatic ecology and carbon budgets. Headwater riparian zones (RZ) are important sources of DOC, and often just a narrow ‘dominant source layer’ (DSL) within the riparian profile is responsible for most of the DOC export. Two important questions arise: how long boreal RZ could sustain lateral DOC fluxes as the sole source of exported carbon and how its hydromorphological variability influences this role. We estimate theoretical turnover times by comparing carbon pools and lateral exports in the DSL of 13 riparian profiles distributed over a 69 km2 catchment in northern Sweden. The thickness of the DSL was 36 ± 18 (average ± SD) cm. Thus, only about one‐third of the 1‐m‐deep riparian profile contributed 90% of the lateral DOC flux. The 13 RZ exported 8.7 ± 6.5 g C m−2 year−1, covering the whole range of boreal stream DOC exports. The variation could be explained by local hydromorphological characteristics including RZ width (R2 = 0.90). The estimated theoretical turnover times were hundreds to a few thousands of years, that is there is a potential long‐lasting supply of DOC. Estimates of net ecosystem production in the RZ suggest that lateral fluxes, including both organic and inorganic C, could be maintained without drawing down the riparian pools. This was supported by measurements of stream DO14C that indicated modern carbon as the predominant fraction exported, including streams disturbed by ditching. The transfer of DOC into boreal inland waters from new and old carbon sources has a major influence on surface water quality and global carbon balances. This study highlights the importance of local variations in RZ hydromorphology and DSL extent for future DOC fluxes under a changing climate.
Association between knee pain and gait speed decline in rural Japanese community‐dwelling older adults: 1‐year prospective cohort study
Authors: Kitayuguchi Jun , Kamada Masamitsu , Hamano Tsuyoshi , Nabika Toru , Shiwaku Kuninori , Kamioka Hiroharu , Okada Shimpei , Mutoh Yoshiteru
Published: January 2015

Aim

The present study examined whether knee pain was associated with decline in maximum gait speed (MGS) in a rural mountainous region.

Methods

This was a population‐based 1‐year prospective cohort study. A total of 658 men and women aged 60 years and older participated in the baseline survey in 2006, and 400 individuals participated in the follow‐up survey in 2007. We compared the incidence of meaningful decline in gait speed (≥0.1 m/s) in older adults with different knee pain levels (none, mild, severe), estimating incidence rate ratio (IRR) by multivariable‐adjusted Poisson regression model.

Results

Meaningful decline in MGS presented in 24.3% of participants, especially in men (30.3%). Baseline knee pain level was significantly related to meaningful decline in MGS after adjustment of potential confounders (IRR 1.79 for mild pain, 1.84 for severe pain; P for trend <0.01). In sensitivity analyses with change in MGS as the continuous variable, the association was not significant, but a similar negative association with knee pain was confirmed (mild pain β = −0.040, severe pain β = −0.088; P for trend = 0.104). In addition, older adults with knee pain at both baseline and follow up had a higher risk of meaningful decline in MGS (IRR 2.33, 95% CI 1.59–3.40) compared with those who had no pain at baseline or follow up.

Conclusions

Knee pain was associated with a decline in gait speed at 1‐year follow up. Prevention and treatment of knee pain might be important for suppression of decline in physical function in older adults. Geriatr Gerontol Int 2016; 16: 55–64.
Effect of inulin on growth and bacteriocin production by Lactobacillus plantarum in stationary and shaken cultures
Authors: da Silva Sabo Sabrina , Converti Attilio , Todorov Svetoslav Dimitrov , Domínguez José Manuel , de Souza Oliveira Ricardo Pinheiro
Published: January 2015

The prebiotic effect of inulin added to MRS medium on growth and bacteriocin production by L. plantarum ST16 Pa was investigated in stationary cultures in anaerobic jars with medium containing 0.025% sodium thioglycolate or in flasks shaken at 100 rpm. In the presence of 1% inulin in anaerobic stationary cultures, this strain produced lactic acid at a level that was 36.5% higher than in the absence of the polysaccharide. In shaken cultures without inulin, cell count was 54% higher than in the stationary ones. Under stationary conditions in anaerobic jars, the addition of inulin increased the maximum specific growth rate from 0.37 to 0.49 h−1 and reduced the generation time from 1.85 h to 1.40 h. Consequently, the exponential phase was shortened from 12 to 9 h when the cells were grown in stationary cultures with the oxygen scavenger. Despite this effect of inulin on growth rate, stationary cultures without inulin displayed higher antimicrobial activity against Listeria monocytogenes L104 (3200 AU/mL) than cultures with inulin (1600 AU/mL); therefore, inulin behaved as a compound able to accelerate growth rather than to stimulate bacteriocin production. The results presented in this study are very promising, as L. monocytogenes is a well‐known foodborne pathogenic microorganism. Moreover, L. plantarum ST16 Pa has proven to be a potential producer of a natural food preservative at an industrial level.
An integrative review of experiences of patients with rheumatoid arthritis
Authors: Poh L.W. , He H.‐G. , Lee C.S.C. , Cheung P.P. , Chan W.‐C.S.
Published: January 2015

Aim

To provide an overview of evidence on the experiences and needs of adults living with rheumatoid arthritis (RA).

Background

Many research have studied the impact of RA on one's quality of life, but no reviews have examined the overall experiences of patients living with RA.

Methods

An integrative review was performed to synthesize the experiences and/or needs of adult patients with RA based on articles retrieved from databases of CINAHL, Scopus, PubMed, PsycINFO and Web of Science, and published between January 2003 and March 2014 in English.

Results

A total of 38 studies were reviewed. RA has adverse effects on patients' quality of life due to its negative impacts in their physical and psychosocial aspects of health. Patients with RA cope with these impacts using various methods and are frequent users of healthcare services. However, few studies have evaluated patients' further needs in coping or the effectiveness of their coping mechanisms, and patients' experiences with health care.

Conclusion

This review provides evidence for healthcare professionals to gain a better understanding of RA patients' experiences and needs. Future studies can explore interventions that will enhance the quality of current healthcare practices and ultimately improve patients' quality of life.

Implications for nursing and health policy

Establishing a positive healthcare professional–patient relationship is crucial and healthcare professionals are in a position to provide greater informational and emotional support to patients. Policy makers and healthcare organizations need to look into ways to enhance the healthcare services to better suit RA patients' needs.
Enhancement of Thermoelectric Performance in Hierarchical Mesoscopic Oxide Composites of Ca3Co4O9 and La0.8Sr0.2CoO3
Authors: Butt Sajid , Xu Wei , Farooq Muhammad U. , Ren Guang K. , Mohmed Fida , Lin Yuanhua , Nan Ce‐Wen
Published: January 2015

The natural contradiction in enhancing electrical conductivity and thermopower in thermoelectric oxides makes it hard to improve the performance of a single thermoelectric oxide material. We report a facile method to construct a unique architecture of thermoelectric oxides that is promising to realize a simultaneous improvement of overall electrical conductivity and thermopower. Here, a series of two‐phase nanocomposites comprising of Ca3Co4O9 (CCO) and La0.8Sr0.2CoO3 (LSCO) has been synthesized through ball milling followed by spark plasma sintering (SPS) method. The electron microscope images reveal that the two constituents form the unique composites while retaining their individual crystalline and morphological identities. Owing to the hierarchical mesoscopic structure with nanoscale particles and submicrometer scale grain boundaries, an external strain is induced into the CCO grains by the LSCO nanoparticles to enhance the thermopower. The mesoscopic structure is also favorable for improving the electrical conductivity. Moreover, the long‐wavelength phonons can be scattered effectively from LSCO nanoparticles and the thermal conductivity is further suppressed. With compromises between power factor and thermal conductivity, the largest ZT achieved is up to 0.41 at 1000 K for the composites with 25 wt% of LSCO.
Emergence and Extinction of a New Phase During On–Off Experiments Related to Flash Sintering of 3YSZ
Authors: Lebrun Jean‐Marie , Morrissey Timothy G. , Francis John S. C. , Seymour Kevin C. , Kriven Waltraud M. , Raj Rishi
Published: January 2015

The flash phenomenon occurs when oxide ceramics are heated above a threshold temperature under an applied electric field. It is defined as an abrupt increase in the conductivity of the specimen. The specimen then can be held in this state of high conductivity by switching the power supply from voltage to current control. Here, we report on the emergence of new X‐ray diffraction peaks in 3 mol% yttria‐stabilized zirconia (3YSZ) when the specimen is held in this current controlled state. These peaks are indexed as a pseudocubic phase of zirconia. The peaks extinguish and reappear when the field is turned off and on. The specimen temperature in the flash state is measured from the thermal expansion of platinum, which is placed as a thin film on a small portion of the specimen surface. Experiments without the electric field, at even higher temperatures than those measured with the platinum standard, do not show any change of phase, thus ruling out Joule heating as the cause of this phenomenon. The time dependency of the growth and dissolution of the pseudo cubic phase is reported. These in situ experiments were carried out at the Advanced Photon Source Synchrotron at the Argonne National Laboratory.
Aggregation Bias in Estimates of Conditional Conservatism: Theory and Evidence
Authors: Cano‐Rodríguez Manuel , Núñez‐Nickel Manuel
Published: January 2015

This paper documents a study about the influence of the aggregation effect on the estimates of models based on the original Basu model – specifically the Ball, Kothari and Nikolaev model (Ball et al., 2013b). We provide an analytical study of the effect, showing that it can produce two biases: an omitted‐variable bias and a truncated‐sample bias. Using separate proxies for good and bad news for each company and year, we estimate the empirical sign and magnitude of those biases. Our results show that the estimates of conditional conservatism based on regressions of (unexpected) earnings on (unexpected) returns, as in the paper by Ball et al., are contaminated by substantial aggregation bias. More specifically, the aggregation effect causes these models to underestimate good‐news timeliness and overestimate bad‐news timeliness, thereby overestimating differential timeliness. Moreover, when we use proxies that provide better control for the aggregation effect, the differential timeliness coefficient tends to 0, showing that the influence of conditional conservatism on the returns–earnings relationship is, at best, marginal.
Improvements in patient‐reported outcomes in patients with psoriasis receiving etanercept plus topical therapies: results from REFINE
Authors: Papp K.A. , Barber K. , Bissonnette R. , Bourcier M. , Lynde C.W. , Poulin Y. , Shelton J. , Garces K. , Toole J. , Poulin‐Costello M.
Published: January 2015

Background

The REFINE study examined the efficacy and safety of adding topical corticosteroid therapy to etanercept when stepping down from the initial dose of etanercept to the maintenance dose. Clinical responses were shown to be similar in patients who remained on etanercept 50 mg twice weekly (BIW) and those who received etanercept 50 mg once weekly (QW) plus topical therapies through week 24.

Objective

The purpose of this analysis was to evaluate the effect of treatment on health‐related quality of life (HRQoL) for patients in REFINE.

Methods

All patients received etanercept 50 mg BIW for 12 weeks and were then randomized to etanercept 50 mg BIW or etanercept 50 mg QW plus topical corticosteroid as required to clear through week 24. HRQoL measures included the Dermatology Life Quality Index (DLQI), Treatment Satisfaction Questionnaire for Medication (TSQM) and the Economic Implications of Psoriasis Patient Questionnaire. No comparative testing was performed for this descriptive analysis. Missing data were imputed using the last observation carried forward.

Results

For 287 randomized patients (144 etanercept; 143 etanercept plus topical), the mean change [standard deviation (SD)] in DLQI from baseline to week 24 was 10.7 (7.8) for etanercept and 9.9 (6.9) for etanercept plus topical. Mean change (SD) in TSQM effectiveness, convenience, side‐effects and global satisfaction was 27.1 (36.1), 14.8 (25.9), −0.7 (22.0) and 26.7 (32.5) for the etanercept arm and 32.5 (40.3), 18.5 (29.0), 1.3 (19.4) and 28.4 (35.9) for etanercept plus topical. Economic implications, including healthcare visits, employment status, work productivity, ability to perform daily activities and out‐of‐pocket expenses were similar between treatment arms.

Conclusion

At week 24 of REFINE, measures of HRQoL were numerically similar in patients who stayed on etanercept 50 mg BIW and patients who received etanercept 50 mg QW plus topical therapies.
Prevalence of abnormal glycometabolism in treatment‐naive patients with hepatitis C virus infection in a Chinese Han population
Authors: Rao Huiying , Wei Lai , Li Hong , Yang Ruifeng , Zhang Haiying , Shang Jia , Chen Hong , Li Jun , Xie Qing , Gao Zhiliang , Wang Lei , Wei Jia , Jiang Jianning , Sun Yongtao ,   CCgenos Study Group
Published: January 2015

Background and Aim

The hepatitis C virus (HCV) may promote pancreatic β‐cell apoptosis‐like cell death through a caspase 3‐dependent pathway, initiating the onset of type 2 diabetes mellitus (T2DM); however, the risk factors for development of T2DM and other abnormal glycometabolic factors in HCV patients of the Chinese Han ethnicity have been poorly explored.

Methods

A total of 947 patients Chinese Han patients with confirmed HCV infection were enrolled in a multicenter study in order to examine the genetic and physiological parameters associated with the onset of abnormal glycometabolic conditions, including T2DM and prediabetes.

Results

HCV genotype 1b and host interleukin‐28B CC genotype were most commonly observed. A total of 145 (15.3%) patients were diagnosed with T2DM and prediabetes. Elevated age, waist circumference, smoking duration, and systolic and diastolic blood pressure were shown to increase risks for abnormal glycometabolism. Liver dysfunction was shown to have positive correlations with abnormal glycometabolism in HCV patients. Genome‐wide association studies indicated that certain genetic encoding inosine triphosphatase polymorphs (rs6051702) were associated with elevated risks for abnormal glycometabolism. Coupled with previous research data, it is likely that abnormal glycometabolism may be a useful predictor of risk for poor response to antiviral therapies and treatment‐induced complications, such as anemia, in treatment naïve patients.

Conclusions

Abnormal glycometabolism and other such complications of HCV and HCV treatment may share critical metabolic and genetic pathways, providing potentially novel targets for future antiviral therapies for treatment resistant HCV genotypes.
Impaired induction of interleukin 28B and expression of interferon λ 4 associated with nonresponse to interferon‐based therapy in chronic hepatitis C
Authors: Murakawa Miyako , Asahina Yasuhiro , Nakagawa Mina , Sakamoto Naoya , Nitta Sayuri , Kusano‐Kitazume Akiko , Watanabe Takako , Kawai‐Kitahata Fukiko , Otani Satoshi , Taniguchi Miki , Goto Fumio , Nishimura‐Sakurai Yuki , Itsui Yasuhiro , Azuma Seishin , Kakinuma Sei , Watanabe Mamoru
Published: January 2015

Background and Aim

Interferon (IFN) λ plays an important role in innate immunity to protect against hepatitis C viral (HCV) infection. Single nucleotide polymorphisms (SNPs) near IL28B (IFNλ3) are strongly associated with treatment response to IFNα therapy in chronic hepatitis C (CHC) patients. Recently, IFNλ4 related to IL28B‐unfavorable allele was discovered. However, the impact of IFNλs on CHC is unknown. We aimed to investigate the mechanism underlying responsiveness to IFN‐based therapy in CHC associated with SNPs near IL28B.

Methods

We evaluated the basal mRNA levels and ex‐vivo induction of IFNλ expression including IFNλ4 in peripheral blood mononuclear cells (PBMCs) from 50 CHC patients treated with pegylated‐IFNα/RBV. Furthermore, we investigated the effect of IFNλ4 on induction of IL28B in vitro.

Results

When PBMCs were stimulated with IFNα and polyinosinic–polycytidylic acid, IL28B induction was significantly lower in patients with IL28B‐unfavorable genotype (rs12979860 CT/TT) than those with IL28B‐favorable genotype (rs12979860 CC; P = 0.049). IL28B induction was lower in nonresponders than in relapsers (P = 0.04), and it was also lower in nonsustained virological responder patients for triple therapy including NS3 protease inhibitors. IFNλ4 mRNA was detected in 12 of 26 patients with IL28B‐unfavorable SNP, and IFNλ4 expression was associated with lower IL28B induction in patients with IL28B‐unfavorable genotype (P = 0.04) and nonresponse to IFNα therapy (P = 0.003). Overexpression of IFNλ4 suppressed IL28B induction and promoter activation.

Conclusions

Impaired induction of IL28B, related to IFNλ4 expression in PBMCs of IL28B‐unfavorable patients, is associated with nonresponse to IFNα‐based therapy for hepatitis C viral infection.
Occurrence of Giardia and Cryptosporidium in captive chimpanzees (Pan troglodytes), mandrills (Mandrillus sphinx) and wild Zanzibar red colobus monkeys (Procolobus kirkii)
Authors: Debenham John J. , Atencia Rebeca , Midtgaard Fred , Robertson Lucy J.
Published: January 2015

Background

The aim of this study was to investigate the occurrence of Giardia duodenalis and Cryptosporidium spp. in primates and determine their zoonotic or anthropozoonotic potential.

Methods

Direct immunofluorescence was used to identify Giardia and Cryptosporidium from faecal samples. PCR and DNA sequencing was performed on positive results.

Results

Giardia cysts were identified from 5.5% (5/90) of captive chimpanzees and 0% (0/11) of captive mandrills in the Republic of Congo; 0% (0/10) of captive chimpanzees in Norway; and 0% of faecal samples (n = 49) from wild Zanzibar red colobus monkeys. Two Giardia positive samples were also positive on PCR, and sequencing revealed identical isolates of Assemblage B. Cryptosporidium oocysts were not detected in any of the samples.

Conclusions

In these primate groups, in which interactions with humans and human environments are quite substantial, Giardia and Cryptosporidium are rare pathogens. In chimpanzees, Giardia may have a zoonotic or anthropozoonotic potential.
Immunogenetic characterization of a captive colony of sooty mangabeys (Cercocebus atys) used for SIV research
Authors: Smith Geary R. , Bauer Liesel , Crane Maria M. , Johnson Zachary P.
Published: January 2015

Background

African non‐human primates are SIV natural hosts and do not develop disease following infection. Understanding disease avoidance mechanisms in these species is important for HIV vaccine development. The largest captive population of sooty mangabeys, a SIV natural host species, resides at the Yerkes National Primate Research Center.

Methods

Thirteen primer sets that amplify polymorphic microsatellite loci within the MHC region were used to genotype 144 animals. Immunogenetic Management Software (IMS) was used to identify MHC haplotypes and organize data.

Results

Seventy‐three haplotypes were identified. Limited haplotype diversity was observed in this population with 88.2% of included animals carrying one of 18 haplotypes. Differences in haplotype frequency were observed between SIV (+) and SIV (−) populations.

Conclusions

We have developed a novel tool for others to use in the analysis of the role of the MHC in a natural host non‐human primate model species used for SIV research.
Embedded Synaptic Feedback in the Neuroendocrine Stress Axis
Authors: Wamsteeker Cusulin J. I. , Bains J. S.
Published: January 2015

Neural regulation of blood glucocorticoid levels is critical for defence of homeostasis during physiological or psychoemotional challenges. In mammals, this function is carried out by the neuroendocrine stress axis, coordinated by parvocellular neuroendocrine cells (PNCs) of the paraventricular hypothalamic nucleus. Feedback regulation of PNCs by glucocorticoids provides complex experience‐dependent shaping of neuroendocrine responses. We review recent evidence for metaplastic actions of glucocorticoids as ‘circuit breakers’ at synapses directly regulating PNC excitability and explore how such mechanisms may serve as substrates for stress adaptation.
Immunoregulatory actions of melatonin and zinc during chronic Trypanosoma cruzi infection
Authors: Brazão Vânia , Santello Fabricia Helena , Filipin Marina Del Vecchio , Azevedo Angela Palamin , Toldo Míriam Paula Alonso , de Morais Fabiana Rossetto , Prado José Clóvis do
Published: January 2015

After one century of the discovery of Chagas' disease and the development of an efficient drug with amplitude of actions both in the acute and chronic phase is still a challenge. Alternative immune modulators have been exhaustively used. For that purpose, melatonin and zinc were administered during chronic Trypanosoma cruzi‐infected Wistar rats and several endpoints were assessed. Melatonin has a remarkable functional versatility, being associated with important antioxidant, anti‐inflammatory, and anti‐apoptotic effects. The cross‐talk between zinc and the immune system includes its ability to influence the production and signaling of numerous inflammatory cytokines in a variety of cell types. Our study showed that zinc triggered a decrease in the generation of IFN‐γ for TCD4+ cells. Reduced percentage of CD4+T cells producing TNF‐α was observed in control melatonin or zinc‐and‐melatonin‐treated animals as compared with untreated rats. On the other hand, a significant increase in the percentage of IL‐4 from CD4+ and CD8+ T lymphocytes producers was observed 60 days after infection, for all zinc‐treated animals, whether infected or not. Melatonin and zinc therapies increased the percentages of CD4+ and CD8+ T lymphocytes IL‐10 producers. CD4+CD25highFoxp3+ T cells were also elevated in zinc‐ and melatonin‐treated animals. The modulation of the immune system influenced by these molecules affected cytokine production and the inflammatory process during chronic T. cruzi infection. Elucidation of the interplay between cytokine balance and the pathogenesis of Chagas’ disease is extremely relevant not only for the comprehension of the immune mechanisms and clinical forms but, most importantly, also for the implementation of efficient and adequate therapies.
Higher melatonin secretion is associated with lower leukocyte and platelet counts in the general elderly population: the HEIJO‐KYO cohort
Authors: Obayashi Kenji , Saeki Keigo , Kurumatani Norio
Published: January 2015

Circulating white blood cell (WBC) and platelet (PLT) counts are widely available and inexpensive cellular biomarkers of systemic inflammation and have been associated with a risk of cardiovascular disease, cancer, and mortality. Melatonin may reduce systemic inflammation through its direct and indirect antioxidative effect; however, the associations of melatonin secretion with systemic inflammation remain unclear. In this cross‐sectional study on 1088 elderly individuals (mean age, 71.8 years), we measured overnight urinary 6‐sulfatoxymelatonin excretion (UME) and WBC and PLT counts as indices of melatonin secretion and systemic inflammation, respectively. UME was naturally log‐transformed for linear regression models because of skewed distribution (median, 6.8 μg; interquartile range, 4.1–10.6 μg). Univariate models revealed that higher log‐transformed UME levels were significantly associated with lower WBC and PLT counts (P = 0.046 and 0.018). After adjusting for potential confounding factors significantly associated with WBC or PLT counts, higher log‐transformed UME levels were significantly associated with lower WBC and PLT counts (WBC: β, −0.143; 95% confidence interval, −0.267 to −0.020; P = 0.023; PLT: β, −6.786; 95% confidence interval, −12.047 to −1.525; P = 0.012). Furthermore, the adjusted mean differences in WBC and PLT counts between the lowest and highest UME tertile groups were 0.225 × 109/L and 9.480 × 109/L, respectively. In conclusion, melatonin secretion was significantly and inversely associated with WBC and PLT counts in the general elderly population. The associations were independent of several major causes of systemic inflammation, including aging, obesity, smoking, hypertension, diabetes, and physical inactivity.
Bootstrapping Robust Statistics for Markovian Data Applications to Regenerative R‐Statistics and L‐Statistics
Authors: Bertail Patrice , Clémençon Stéphan , Tressou Jessica
Published: January 2015

This article is devoted to extending the notion of robustness in the context of Markovian data, based on their (pseudo‐)regenerative properties and by studying its impact on the regenerative block‐bootstrap (RBB). Precisely, it is shown how to possibly define the ‘influence function’ in this framework, so as to measure the impact of (pseudo‐)regeneration data blocks on the statistic of interest. We also define the concept of regeneration‐based signed linear rank statistic and L‐statistic, as specific functionals of the regeneration blocks, which can be made robust against outliers in this sense. The asymptotic validity of the approximate RBB (ARBB), is established here, when applied to such statistics. For illustration purpose, we compare (A)RBB confidence intervals for the mean, the median and some L‐statistics related to the (supposedly existing) stationary probability distribution μ(dx) of the chain observed and for their robustified versions as well. Copyright © 2015 Wiley Publishing Ltd
Structural Break Inference Using Information Criteria in Models Estimated by Two‐Stage Least Squares
Authors: Hall Alastair R. , Osborn Denise R. , Sakkas Nikolaos
Published: January 2015

This paper makes two contributions in relation to the use of information criteria for inference on structural breaks when the coefficients of a linear model with endogenous regressors may experience multiple changes. First, we show that suitably defined information criteria yield consistent estimators of the number of breaks, when employed in the second stage of a two‐stage least squares (2SLS) procedure with breaks in the reduced form taken into account in the first stage. Second, a Monte Carlo analysis investigates the finite sample performance of a range of criteria based on Bayesian information criterion (BIC), Hannan–Quinn information criterion (HQIC) and Akaike information criterion (AIC) for equations estimated by 2SLS. Versions of the consistent criteria BIC and HQIC perform well overall when the penalty term weights estimation of each break point more heavily than estimation of each coefficient, while AIC is inconsistent and badly over‐estimates the number of true breaks.
Clinical course of chronic hepatitis B (CHB) presented with normal ALT in Asian American patients
Authors: Nguyen K. , Pan C. , Xia V. , Hu J. , Hu K.‐Q.
Published: January 2015

The clinical course for chronic hepatitis B (CHB) patients with normal ALT and with or without minimal histologic activity remains unclear. We assessed frequency, amplitude, disease activities, and associated factors of ALT and/or AST flares in this subpopulation. Forty‐seven consecutive treatment naïve Asian patients with CHB were enrolled from two liver clinics between December 2003 and January 2013, who had normal baseline ALT by routine clinical biochemical testing performed 6 weeks before or after the liver biopsy. We defined a flare as elevation of ALT/AST above the upper limit of normal of ALT/AST. The mean follow‐up was 37.6 (CI = 12, 88) months, and the mean age at entry into the study was 43.3 (CI = 19, 65); 22/47 (46.8%) were males; 15/45 (33.3%), HBeAg+; 68.1% had stage 0–1 fibrosis; 63.8% had grade 0–1 inflammation. During follow‐up, 13/47 (27.7%) cases developed ALT flare at least once in a mean of 13.5 (CI = 2, 43) months after liver biopsy; ALT flare was not associated with baseline ALT level, fibrosis stage, inflammation grade, hepatitis B virus (HBV) DNA load, HBeAg status, HBV genotype, HBV precore and basal core promoter mutations. 11/13 (84/6%) of ALT flares resolved during follow‐up. 13/13 (100%) of ALT flares met AASLD treatment criteria, but only 6/13 (46.2%) were on HBV treatment. Serum ALT and/or AST flares occur frequently in CHB carriers who initially presented with normal ALT during pretreatment period. Thus, regular follow‐up is warranted despite status of ALT/AST. No clinical factors were found to be associated with ALT flares.
HCV genotype 3 and squamous cell carcinoma antigen (SCCA)‐IgM are independently associated with histological features of NASH in HCV‐infected patients
Authors: Martini A. , Fattovich G. , Guido M. , Bugianesi E. , Biasiolo A. , Ieluzzi D. , Gallotta A. , Fassina G. , Merkel C. , Gatta A. , Negro F. , Pontisso P.
Published: January 2015

Nonalcoholic steatohepatitis (NASH) enhances the risk of progressive liver disease. In chronic hepatitis C (CHC), liver steatosis is frequent, especially in genotype 3, but its clinical significance is debated. As squamous cell carcinoma antigen (SCCA)‐IgM has been associated with advanced liver disease and risk of tumour development, we evaluated its occurrence in CHC and the possible relation with NASH at liver biopsy. Using a validated ELISA, serum SCCA‐IgM was measured in 91 patients with CHC at the time of liver biopsy performed before antiviral treatment, at the end of treatment and 6 months thereafter, and in 93 HCV‐negative patients with histological diagnosis of nonalcoholic fatty liver disease, as controls. SCCA‐IgM was detected in 33% of CHC patients and in 4% of controls. This biomarker was found more elevated in CHC patients with histological NASH, and at multivariate analysis, SCCA‐IgM and HCV genotype 3 were independently associated with NASH [OR (95% CI): 6.94 (1.21–40) and 27.02 (4.44–166.6)]. As predictors of NASH, HCV genotype 3 and SCCA‐IgM had a specificity and a sensitivity of 97% and 44%, and of 95% and 27%, respectively. PPV and NPV were 80% and 86% for HCV genotype 3 vs 73% and 72% for SCCA‐IgM. In patients with sustained virologic response to therapy, SCCA‐IgM levels decreased significantly, while these remained unchanged in nonresponders. In conclusion, SCCA‐IgM is detectable in one‐third of patients with CHC and significantly correlates with histological NASH.
Transposable elements as agents of rapid adaptation may explain the genetic paradox of invasive species
Authors: Stapley Jessica , Santure Anna W. , Dennis Stuart R.
Published: January 2015

Rapid adaptation of invasive species to novel habitats has puzzled evolutionary biologists for decades, especially as this often occurs in the face of limited genetic variability. Although some ecological traits common to invasive species have been identified, little is known about the possible genomic/genetic mechanisms that may underlie their success. A common scenario in many introductions is that small founder population sizes will often lead to reduced genetic diversity, but that invading populations experience large environmental perturbations, such as changes in habitat and environmental stress. Although sudden and intense stress is usually considered in a negative context, these perturbations may actually facilitate rapid adaptation by affecting genome structure, organization and function via interactions with transposable elements (TEs), especially in populations with low genetic diversity. Stress‐induced changes in TE activity can alter gene action and can promote structural variation that may facilitate the rapid adaptation observed in new environments. We focus here on the adaptive potential of TEs in relation to invasive species and highlight their role as powerful mutational forces that can rapidly create genetic diversity. We hypothesize that activity of transposable elements can explain rapid adaptation despite low genetic variation (the genetic paradox of invasive species), and provide a framework under which this hypothesis can be tested using recently developed and emerging genomic technologies.
Rot is a key regulator of Staphylococcus aureus biofilm formation
Authors: Mootz Joe M. , Benson Meredith A. , Heim Cortney E. , Crosby Heidi A. , Kavanaugh Jeffrey S. , Dunman Paul M. , Kielian Tammy , Torres Victor J. , Horswill Alexander R.
Published: January 2015

Staphylococcus aureus is a significant cause of chronic biofilm infections on medical implants. We investigated the biofilm regulatory cascade and discovered that the repressor of toxins (Rot) is part of this pathway. A USA300 community‐associated methicillin‐resistant S. aureus strain deficient in Rot was unable to form a biofilm using multiple different assays, and we found rot mutants in other strain lineages were also biofilm deficient. By performing a global analysis of transcripts and protein production controlled by Rot, we observed that all the secreted protease genes were up‐regulated in a rot mutant, and we hypothesized that this regulation could be responsible for the biofilm phenotype. To investigate this question, we determined that Rot bound to the protease promoters, and we observed that activity levels of these enzymes, in particular the cysteine proteases, were increased in a rot mutant. By inactivating these proteases, biofilm capacity was restored to the mutant, demonstrating they are responsible for the biofilm negative phenotype. Finally, we tested the rot mutant in a mouse catheter model of biofilm infection and observed a significant reduction in biofilm burden. Thus S. aureus uses the transcription factor Rot to repress secreted protease levels in order to build a biofilm.
Barnyard millet – a potential food and feed crop of future
Authors: Sood Salej , Khulbe Rajesh K. , Gupta Arun K. , Agrawal Pawan K. , Upadhyaya Hari D. , Bhatt Jagdish C.
Published: January 2015

The two species under genus Echinochloa, E. frumentacea (Indian barnyard millet) and E. esculenta (Japanese barnyard millet), are cultivated for food and fodder by hilly and tribal communities in Asia particularly in India, China and Japan. The crop has wide adaptability and occupies a special place in marginal rainfed areas because of its short life cycle. Although the area under the crop has come down drastically in last 50 years, the crop ability to survive under harsh conditions makes it a better choice during famine years. In the Indian Himalayan region, the crop was traditionally used as a substitute for rice. It has been identified as a suitable choice for climate‐resilient agriculture. High nutrient content and antioxidant effects make it to be considered as a functional food crop. Recently, the demand of the crop has increased due to its highly nutritious grains. Thus, it has the potential to provide both food and nutritional security particularly in hills where nutritional deficiencies are in abundance. Despite enormous potential, the crop has not gained the popularity among masses and is still considered as poor man's food. This work therefore is an attempt to compile the meagre information available on crop history, evolution, crop breeding and present status to make the crop competitive and revamp its cultivation.
Metabolic change in the right dorsolateral prefrontal cortex and its correlation with symptom severity in patients with generalized anxiety disorder: Proton magnetic resonance spectroscopy at 3 Tesla
Authors: Moon Chung‐Man , Kang Heoung‐Keun , Jeong Gwang‐Woo
Published: January 2015

Aims

A few neuroimaging studies have demonstrated the key brain areas associated with generalized anxiety disorder (GAD). However, the brain metabolic changes in the dorsolateral prefrontal cortex (DLPFC) of patients with GAD are unclear. This study utilized 3‐Tesla proton magnetic resonance spectroscopy (1H‐MRS) to assess the DLPFC metabolic change and its correlation with symptom severity in patients with GAD.

Methods

Patients with GAD diagnosed using the DSM‐IV‐TR and age‐matched healthy controls participated in this study. Brain metabolite concentrations were measured from a localized voxel on the DLPFC using 3‐Tesla 1H‐MRS. Also, the volumetric composition of the gray matter and white matter volumes was assessed using voxel‐based morphometry.

Results

The choline/creatine and choline/N‐acetylaspartate ratios were significantly lower in patients than in controls. However, there were no significant differences in other metabolite ratios between the two groups. Choline concentrations were negatively correlated with anxiety levels as measured by the Hamilton Anxiety Rating Scale and the Generalized Anxiety Disorder Scale 7. There was no significant difference in the gray matter and white matter volumes in the MRS voxel between the two groups.

Conclusions

The present study demonstrates that GAD is associated with low a level of choline/N‐acetylaspartate in the DLPFC, which is closely related with symptom severity and cognitive dysfunction. This finding will be useful for an understanding of the neural mechanism associated with GAD.
Making a Difference in Migrant Summer School: Testing a Healthy Weight Intervention
Authors: Kilanowski Jill F. , Gordon Nahida H.
Published: January 2015

Objective

Evaluate the effectiveness of a healthy weight intervention designed for children of migrant farmworkers embedded in a 7‐week summer Midwest Migrant Education Program (MEP) for changes in: weight; Body Mass Index (BMI); BMI‐percentiles (BMI‐p); muscle strength and muscle flexibility; nutrition knowledge; attitudes; and behaviors.

Design and Sample

This is a two‐group pre‐post quasi‐experimental study. Latino children of migrant farmworkers attending summer MEP in grades one through eight were enrolled (n = 171: comparison n = 33, intervention n = 138).

Measures

Weight, BMI, BMI‐p, muscle strength and flexibility, knowledge, and healthy behaviors.

Intervention

Classroom content included: food variety; increasing fruits and vegetables; healthy breakfasts; more family meals; increasing family time; decreasing TV and electronic game time; increasing physical activity; limiting sugar‐sweetened drinks; portion sizes; and food labels.

Results

Statistically significant were increase in comparison group mean weight, decrease in intervention group BMI‐p, and improvements in muscle flexibility and healthy behavior attitudes. The intervention students showed trends toward healthy BMI. The number of MEP days attended was significantly correlated in four outcomes.

Conclusion

Study findings have the potential to decrease incidence of unhealthy weight in Latino migrant children, reduce rates of premature adult diseases in these children, and a potential to decrease future health care costs.
Nanometal Surface Energy Transfer Optical Ruler for Measuring a Human Telomere Structure
Authors: Armstrong Rachel E. , Riskowski Ryan A. , Strouse Geoffrey F.
Published: January 2015

Nanometal surface energy transfer (NSET) techniques on gold nanoparticles (AuNPs) have become an essential tool in molecular biophysics to identify structural details at long‐range donor‐acceptor distances. The NSET mechanism is well described, but it has been suggested that the use of large AuNPs in NSET may manipulate natural biomolecular function. If, in fact, such nonspecific interactions with the AuNP surface can be quantified or contained, then NSET may offer more potential in tracking biomolecular folding than the most comprehensive methods in conformer determination (X‐ray crystallography, NMR, EPR). Here, we describe an NSET ruler capable of tracking Hybrid‐2 telomere quadruplex folding and we demonstrate that nucleic acid appendage to AuNPs up to 10 nm in diameter does not manipulate biomolecular function. The quadruplex folding of Hybrid‐2 sequences was tracked by monitoring the emission of a DY680 dye on selected basepairs in the telomere sequence when appended to the surface of AuNPs (5–10 nm). Emission‐derived distances extracted from NSET theory correlate well to reported NMR structures of the hybrid quadruplex. Moreover, NSET theory calculates identical donor‐acceptor distal points between DY680 and all sizes of AuNPs, indicating that the AuNP tether is not dominant or disruptive towards nucleic acid folding.
Is Knowledge of God a Cognitive Achievement?
Authors: Bolos Anthony
Published: January 2015

This essay considers whether reformed epistemology is compatible with the claim that knowledge is a cognitive achievement. It is argued that knowledge of God is not only compatible with a more general achievement claim, but is also compatible with a much stronger achievement claim – namely, the strong achievement thesis where achievements are characterized by the overcoming of some obstacle. With respect to reformed epistemology, then, it is argued that the obstacle that is overcome is an environment that is not conducive to belief in God given the cognitive consequence of sin. This essay suggests two ways in which the agent is involved in the process of overcoming this obstacle.