bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a best practice pathway to support improvements in Indigenous Australians’ mental health and well-being: a qualitative study
Authors: Hinton Rachael , Kavanagh David J , Barclay Lesley , Chenhall Richard , Nagel Tricia
Published: August 2015

Objective

There is a need to adapt pathways to care to promote access to mental health services for Indigenous people in Australia. This study explored Indigenous community and service provider perspectives of well-being and ways to promote access to care for Indigenous people at risk of depressive illness.

Design

A participatory action research framework was used to inform the development of an agreed early intervention pathway; thematic analysis

Setting

2 remote communities in the Northern Territory.

Participants

Using snowball and purposive sampling, 27 service providers and community members with knowledge of the local context and the diverse needs of those at risk of depression were interviewed. 30% of participants were Indigenous. The proposed pathway to care was adapted in response to participant feedback.

Results

The study found that Indigenous mental health and well-being is perceived as multifaceted and strongly linked to cultural identity. It also confirms that there is broad support for promotion of a clear pathway to early intervention. Key identified components of this pathway were the health centre, visiting and community-based services, and local community resources including elders, cultural activities and families. Enablers to early intervention were reported. Significant barriers to the detection and treatment of those at risk of depression were identified, including insufficient resources, negative attitudes and stigma, and limited awareness of support options.

Conclusions

Successful early intervention for well-being concerns requires improved understanding of Indigenous well-being perspectives and a systematic change in service delivery that promotes integration, flexibility and collaboration between services and the community, and recognises the importance of social determinants in health promotion and the healing process. Such changes require policy support, targeted training and education, and ongoing promotion.
Accuracy of administrative data for surveillance of healthcare-associated infections: a systematic review
Authors: van Mourik Maaike S M , van Duijn Pleun Joppe , Moons Karel G M , Bonten Marc J M , Lee Grace M
Published: August 2015

Objective

Measuring the incidence of healthcare-associated infections (HAI) is of increasing importance in current healthcare delivery systems. Administrative data algorithms, including (combinations of) diagnosis codes, are commonly used to determine the occurrence of HAI, either to support within-hospital surveillance programmes or as free-standing quality indicators. We conducted a systematic review evaluating the diagnostic accuracy of administrative data for the detection of HAI.

Methods

Systematic search of Medline, Embase, CINAHL and Cochrane for relevant studies (1995–2013). Methodological quality assessment was performed using QUADAS-2 criteria; diagnostic accuracy estimates were stratified by HAI type and key study characteristics.

Results

57 studies were included, the majority aiming to detect surgical site or bloodstream infections. Study designs were very diverse regarding the specification of their administrative data algorithm (code selections, follow-up) and definitions of HAI presence. One-third of studies had important methodological limitations including differential or incomplete HAI ascertainment or lack of blinding of assessors. Observed sensitivity and positive predictive values of administrative data algorithms for HAI detection were very heterogeneous and generally modest at best, both for within-hospital algorithms and for formal quality indicators; accuracy was particularly poor for the identification of device-associated HAI such as central line associated bloodstream infections. The large heterogeneity in study designs across the included studies precluded formal calculation of summary diagnostic accuracy estimates in most instances.

Conclusions

Administrative data had limited and highly variable accuracy for the detection of HAI, and their judicious use for internal surveillance efforts and external quality assessment is recommended. If hospitals and policymakers choose to rely on administrative data for HAI surveillance, continued improvements to existing algorithms and their robust validation are imperative.
Recognition and differentiation of species in the Passiflora sidifolia complex
Authors: Nardin Carla Fernanda , Bernacci Luís Carlos , Plotze Rodrigo O. , Bruno Odemir M. , Shepherd George J.
Published: August 2015

The variation in leaf morphology observed in Passifloraceae is one of the most extreme cases in the Angiosperms, allowing some species within this family to be distinguished by their leaves. Nevertheless, other species in this family are difficult to recognize based solely on leaf morphology, or by floral and molecular characteristics. Aiming to verify the similarities and differences between the Passiflora species Passiflora actinia Hook., Passiflora elegans Mast., Passiflora sidifolia M.Roem., and Passiflora watsoniana Mast., detailed analyses were conducted regarding the morphological traits of the leaf blade, specifically shape and venation, and the flower. The data were composed of continuous and qualitative values, using the Gower coefficient. A principal coordinates analysis (PCoA) and cluster analysis were performed. Features that have not previously been used for the Passifloraceae, such as leaf venation, were important for the distinction of P. watsoniana from the other species. The analyses including only the species P. actinia, P. sidifolia, and P. elegans showed a clear differentiation between them. Despite the wide variability observed in P. elegans, the analysis revealed that the different populations from different regions had more similarities with each other than with any other species.
Fluctuating asymmetry in an extreme morphological adaptation in the Chilean bee Xeromelissa rozeni (Hymenoptera: Colletidae)
Authors: Miklasevskaja Margarita , Packer Laurence
Published: August 2015

Fluctuating asymmetry (FA), random deviations from perfect symmetry in bilateral traits, is a common inverse measure of developmental stability (DS), which is related to one’s ability to buffer against environmental and genetic perturbations. There is a widespread hypothesis that heterozygosity grants an increased ability to compensate for developmental errors caused by genetic and environmental factors, rendering homozygous individuals less symmetric than heterozygous ones. In addition, if natural selection on FA is common, nonessential traits should exhibit higher asymmetry than functionally essential traits. This is especially well tested in haplodiploid organisms, which present a clear distinction between “homo”zygosity (males) and heterozygosity (females). Relatively few FA studies looked at this relationship in hymenopterans or in haplodiploid organisms in general and the results are rather inconsistent. This study compares FA measurements of seven parts of the maxillary palpus, with sclerotized and membranous parts scored separately, and two wing venation characters for males and females of the Chilean bee Xeromelissa rozeni (Toro and Moldenke, 1979). The results of this study suggest that there is an equally strong selection force for maxillary palp symmetry in both males and females leading to a relatively low FA in both sexes, and that less functional traits exhibit higher FA due to relaxation of selection. Lastly, we stress the importance of testing a larger number of independent traits.
Quasi-black holes: General features and purely field configurations
Authors: Bronnikov K. A. , Zaslavskii O. B.
Published: August 2015

Objects that are on the threshold of forming the horizon but never collapse are called quasi-black holes (QBHs). We discuss the properties of the general spherically symmetric QBH metric without addressing its material source, including its limiting cases as the corresponding small parameter tends to zero. We then show that QBHs can exist among self-gravitating configurations of electromagnetic and dilatonic scalar fields without matter. These general results are illustrated by explicit examples of exact solutions.
Maximal acceleration and radiative processes
Authors: Papini Giorgio
Published: August 2015

We derive the radiation characteristics of an accelerated, charged particle in a model due to Caianiello in which the proper acceleration of a particle of mass [Formula: see text] has the upper limit [Formula: see text]. We find two power laws, one applicable to lower accelerations, the other more suitable for accelerations closer to [Formula: see text] and to the related physical singularity in the Ricci scalar. Geometrical constraints and power spectra are also discussed. By comparing the power laws due to the maximal acceleration (MA) with that for particles in gravitational fields, we find that the model of Caianiello allows, in principle, the use of charged particles as tools to distinguish inertial from gravitational fields locally.
Determination of the relative phase in ψ′ and J/ψ decays into baryon and antibaryon
Authors: Zhu Kai , Mo Xiao-Hu , Yuan Chang-Zheng
Published: August 2015

With the recent measurements of [Formula: see text] and [Formula: see text] decay into octet-baryon pairs, we study the relative phase between the strong and the electromagnetic amplitudes, and find a large phase by fitting the present data. The fits take into account the details of experimental effects, including energy spread and initial state radiation. We also predict some branching fractions of [Formula: see text] decays and the continuum production rates at the [Formula: see text] mass based on the relative phase and absolute amplitudes obtained from the fits.
The highest precision proof of CPT invariance in the “nuclear binding masses”
Authors: Akindinov A. , Alici A. , Antonioli P. , Arcelli S. , Bellini F. , Cara Romeo G. , Carnesecchi F. , Chiarini M. , Cifarelli L. , Colocci M. , De Caro A. , Contin A. , De Gruttola D. , De Pasquale S. , Fusco Girard M. , Guerzoni B. , Hatzifotiadou D. , Kim D. W. , Kim J. S. , Kiselev S. , Lee S. C. , Malkevich D. , Margotti A. , Meninno E. , Nania R. , Nedosekin A. , Noferini F. , Pagano P. , Pesci A. , Pinazza O. , Preghenella R. , Scapparone E. , Scioli G. , Voloshin K. , Wenninger H. , Williams M. C. S. , Zampolli C. , Zichichi A.
Published: August 2015

The validity of CPT invariance in the field of “nuclear binding masses” has been studied for nuclei (antinuclei) with two and three nucleons (antinucleons): [Formula: see text] and [Formula: see text]. It is discussed the importance of investigating the transition from the world where gluons and quarks carry their QCD colors (QGCW) to the world where gluons and quarks exist only with zero-QCD-color (QGZCW).
Role of dark excitations in the nonequilibrium condensation of exciton polaritons in optically-pumped organic single crystal microcavities
Authors: Zaster Svitlana , Bittner Eric R.
Published: August 2015

We present a reaction/diffusion model for the formation of a lower polariton condensate in a microcavity containing an organic semiconducting molecular crystalline film. Our model–based upon an anthracene film sandwiched between two reflecting dielectric mirrors–consists of three coupled fields corresponding to a gas of excitons created by an external driving pulse, a reservoir of dark states formed by the nonemissive decay of excitons in to nearby electronic states, and a lower polariton condensate. We show that at finite temperature, the presence of the dark reservoir can augment the exciton population such that a lower critical pumping threshold is required to achieve the critical exciton densities required to sustain a stable condensate population. Using linear-stability analysis, we show that a variety of dynamical regimes can emerge depending upon the characteristics of the cavity and the lattice temperature.
Rickart modules relative to singular submodule and dual Goldie torsion theory
Authors: Ungor Burcu , Halicioglu Sait , Harmanci Abdullah
Published: August 2015

Let [Formula: see text] be an arbitrary ring with identity and [Formula: see text] a right [Formula: see text]-module with the ring [Formula: see text] End[Formula: see text] of endomorphisms of [Formula: see text]. The notion of an [Formula: see text]-inverse split module [Formula: see text], where [Formula: see text] is a fully invariant submodule of [Formula: see text], is defined and studied by the present authors. This concept produces Rickart submodules of modules in the sense of Lee, Rizvi and Roman. In this paper, we consider the submodule [Formula: see text] of [Formula: see text] as [Formula: see text] and [Formula: see text], and investigate some properties of [Formula: see text]-inverse split modules and [Formula: see text]-inverse split modules [Formula: see text]. Results are applied to characterize rings [Formula: see text] for which every free (projective) right [Formula: see text]-module [Formula: see text] is [Formula: see text]-inverse split for the preradicals such as [Formula: see text] and [Formula: see text].
CFD MODELING OF HIGH SPEED LIQUID JETS FROM AN AIR-POWERED NEEDLE-FREE INJECTION SYSTEM
Authors: NAKAYAMA HARUKA , PORTARO ROCCO , KIYANDA CHARLES BASENGA , NG HOI DICK
Published: August 2015

A liquid jet injector is a biomedical device intended for drug delivery. Medication is delivered through a fluid stream that penetrates the skin. This small diameter liquid stream is created by a piston forcing a fluid column through a nozzle. These devices can be powered by springs or compressed gas. In this study, a CFD simulation is carried out to investigate the fluid mechanics and performance of needle free injectors powered specifically by compressed air. The motion of the internal mechanisms of the injector which propels a liquid jet through an orifice is simulated by the moving boundary method and the fluid dynamics is modeled using LES/VOF techniques. In this paper, numerical results are discussed by comparing the fluid stagnation pressures of the liquid jet with previously published experimental measurements obtained using a custom-built prototype of the air-powered needle free liquid injector. Performance plots as a function of various injector parameters are presented and explained.
MODVOLC: 14 years of autonomous observations of effusive volcanism from space
Authors: Wright Robert
Published: August 2015

During the period 28 February 2000–31 December 2013, the MODVOLC system (
http://modis.higp.hawaii.edu
) autonomously analysed almost 9 trillion (i.e. 9×10
12
) pixels contained within almost 3 million MODIS images, searching for evidence of high-temperature thermal signatures associated with volcanic eruptions. Thermal unrest, mainly associated with active lava, be it in the form of flows, domes, lakes or confined to vents, was detected at 93 volcanoes during this period of time. The first part of this paper describes the physical basis and operational implementation of the MODVOLC algorithm. The second part presents data to detail the nature of the thermal emission from these 93 volcanoes over the past 14 years.
Trapping and escaping processes of Yangtze River-derived sediments to the East China Sea
Authors: Wu Jiaxue , Ren Jie , Liu Huan , Qiu Chunhua , Cui Yongsheng , Zhang Qianjiang
Published: August 2015

Contour-parallel sediment dispersal from the Yangtze Estuary into the East China Sea develops a large-scale mud belt on the inner shelf. The sediment dynamics of long-distance dispersal is, however, still an open question. This was investigated by field observations in the 2013 wet season. To clarify the physics of the large-scale mud belt, we examined: (a) shelf circulation currents and their interaction with the Yangtze River; (b) small-/meso-scale processes including bottom boundary-layer flows, stratification and mixing, upwelling, and fronts; and (c) river-borne sediment gravity and contour currents. Field observations demonstrated that estuarine turbidity maxima can trap benthic concentrated suspensions in the near-bed layer and move these downslope of the subaqueous delta, forming sediment gravity currents supported by tidal currents. Compared with near-bed sediment transports, the buoyant coastal current cannot be a controlling factor in the mud belt formation. A constant along-shelf flux of near-bed sediment transport is responsible for the long-distance dispersal of the large-scale mud belt on the East China Sea inner shelf. The upwelling events provide more turbulent energy to sediment suspension under unstably stratified boundary flow. Our recognition of a contour-parallel ‘sediment channel’ has deep implications for understanding this inner-shelf mud belt and ancient mud deposits.
“Store-operated” cAMP signaling contributes to Ca2+-activated Cl−secretion in T84 colonic cells
Authors: Nichols Jonathan M. , Maiellaro Isabella , Abi-Jaoude Joanne , Curci Silvana , Hofer Aldebaran M.
Published: August 2015

Apical cAMP-dependent CFTR Cl−channels are essential for efficient vectorial movement of ions and fluid into the lumen of the colon. It is well known that Ca2+-mobilizing agonists also stimulate colonic anion secretion. However, CFTR is apparently not activated directly by Ca2+, and the existence of apical Ca2+-dependent Cl−channels in the native colonic epithelium is controversial, leaving the identity of the Ca2+-activated component unresolved. We recently showed that decreasing free Ca2+concentration ([Ca2+]) within the endoplasmic reticulum (ER) lumen elicits a rise in intracellular cAMP. This process, which we termed “store-operated cAMP signaling” (SOcAMPS), requires the luminal ER Ca2+sensor STIM1 and does not depend on changes in cytosolic Ca2+. Here we assessed the degree to which SOcAMPS participates in Ca2+-activated Cl−transport as measured by transepithelial short-circuit current ( Isc) in polarized T84 monolayers in parallel with imaging of cAMP and PKA activity using fluorescence resonance energy transfer (FRET)-based reporters in single cells. In Ca2+-free conditions, the Ca2+-releasing agonist carbachol and Ca2+ionophore increased Isc, cAMP, and PKA activity. These responses persisted in cells loaded with the Ca2+chelator BAPTA-AM. The effect on Iscwas enhanced in the presence of the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), inhibited by the CFTR inhibitor CFTRinh-172 and the PKA inhibitor H-89, and unaffected by Ba2+or flufenamic acid. We propose that a discrete component of the “Ca2+-dependent” secretory activity in the colon derives from cAMP generated through SOcAMPS. This alternative mode of cAMP production could contribute to the actions of diverse xenobiotic agents that disrupt ER Ca2+homeostasis, leading to diarrhea.
Variants in pancreatic carboxypeptidase genesCPA2andCPB1are not associated with chronic pancreatitis
Authors: Nakano Eriko , Geisz Andrea , Masamune Atsushi , Niihori Tetsuya , Hamada Shin , Kume Kiyoshi , Kakuta Yoichi , Aoki Yoko , Matsubara Yoichi , Ebert Karolin , Ludwig Maren , Braun Markus , Groneberg David A. , Shimosegawa Tooru , Sahin-Tóth Miklós , Witt Heiko
Published: August 2015

Genetic alterations in the carboxypeptidase A1 gene ( CPA1) are associated with early onset chronic pancreatitis (CP). Besides CPA1, there are two other human pancreatic carboxypeptidases (CPA2 and CPB1). Here we examined whether CPA2 and CPB1 alterations are associated with CP in Japan and Germany. All exons and flanking introns of CPA2 and CPB1 were sequenced in 477 Japanese patients with CP (234 alcoholic, 243 nonalcoholic) and in 497 German patients with nonalcoholic CP by targeted next-generation sequencing and/or Sanger sequencing. Secretion and enzymatic activity of CPA2 and CPB1 variants were determined after transfection into HEK 293T cells. We identified six nonsynonymous CPA2 variants (p.V67I, p.G166R, p.D168E, p.D173H, p.R237W, and p.G388S), eight nonsynonymous CPB1 alterations (p.S65G, p.N120S, p.D172E, p.R195H, p.D208N, p.F232L, p.A317V, and p.D364Y), and one splice-site variant (c.687+1G>T) in CPB1. Functional analysis revealed essentially complete loss of function in CPA2 variants p.R237W and p.G388S and CPB1 variants p.R110H and p.D364Y. None of the CPA2 or CPB1 variants, including those resulting in a marked loss of function, were overrepresented in patients with CP. In conclusion, CPA2 and CPB1 variants are not associated with CP.
Macrophage depletion lowers blood pressure and restores sympathetic nerve α2-adrenergic receptor function in mesenteric arteries of DOCA-salt hypertensive rats
Authors: Thang Loc V. , Demel Stacie L. , Crawford Robert , Kaminski Norbert E. , Swain Greg M. , Van Rooijen Nico , Galligan James J.
Published: August 2015

We tested the hypothesis that vascular macrophage infiltration and O2− release impairs sympathetic nerve α2-adrenergic autoreceptor (α2AR) function in mesenteric arteries (MAs) of DOCA-salt hypertensive rats. Male rats were uninephrectomized or sham operated (sham). DOCA pellets were implanted subcutaneously in uninephrectomized rats who were provided high-salt drinking water or high-salt water with apocynin. Sham rats received tap water. Blood pressure was measured using radiotelemetry. Treatment of sham and DOCA-salt rats with liposome-encapsulated clodronate was used to deplete macrophages. After 3–5, 10–13, and 18–21 days of DOCA-salt treatment, MAs and peritoneal fluid were harvested from euthanized rats. Norepinephrine (NE) release from periarterial sympathetic nerves was measured in vitro using amperometry with microelectrodes. Macrophage infiltration into MAs as well as TNF-α and p22 phox were measured using immunohistochemistry. Peritoneal macrophage activation was measured by flow cytometry. O2− was measured using dihydroethidium staining. Hypertension developed over 28 days, and apocynin reduced blood pressure on days 18–21. O2− and macrophage infiltration were greater in DOCA-salt MAs compared with sham MAs after day 10. Peritoneal macrophage activation occurred after day 10 in DOCA-salt rats. Macrophages expressing TNF-α and p22 phox were localized near sympathetic nerves. Impaired α2AR function and increased NE release from sympathetic nerves occurred in MAs from DOCA-salt rats after day 18. Macrophage depletion reduced blood pressure and vascular O2− while restoring α2AR function in DOCA-salt rats. Macrophage infiltration into the vascular adventitia contributes to increased blood pressure in DOCA-salt rats by releasing O2−, which disrupts α2AR function, causing enhanced NE release from sympathetic nerves.
Interaction of endothelial nitric oxide synthase with mitochondria regulates oxidative stress and function in fetal pulmonary artery endothelial cells
Authors: Konduri Girija G. , Afolayan Adeleye J. , Eis Annie , Pritchard Kirkwood A. , Teng Ru-Jeng
Published: August 2015

An increase in oxygen tension at birth is one of the key signals that initiate pulmonary vasodilation in the fetal lung. We investigated the hypothesis that targeting endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane regulates reactive oxygen species (ROS) formation in the fetal pulmonary artery endothelial cells (PAEC) during this transition. We isolated PAEC and pulmonary arteries from 137-day gestation fetal lambs (term = 144 days). We exposed PAEC to a simulated transition from fetal to (3% O2) to normoxic (21%) or hyperoxic (95% O2) postnatal Po2 or to the nitric oxide synthase (NOS) agonist ATP. We assessed the effect of O2 and ATP on eNOS interactions with the mitochondrial outer membrane protein porin and with the chaperone hsp90. We also investigated the effect of decoy peptides that blocked eNOS interactions with porin or hsp90 on PAEC angiogenesis and vasodilator function of pulmonary arteries. Transition of fetal PAEC from 3 to 21% O2 but not to 95% O2 or exposure to ATP increased eNOS association with hsp90 and porin. Decoy peptides that blocked eNOS interactions decreased NO release, increased O2 consumption and mitochondrial ROS levels, and impaired PAEC angiogenesis. Decoy peptides also inhibited the relaxation responses of pulmonary artery rings and dilation of resistance size pulmonary arteries to ATP. The mitochondrial-antioxidant mito-ubiquinone restored the response to ATP in decoy peptide-treated pulmonary arteries. These data indicate that targeting eNOS to mitochondria decreases endothelial oxidative stress and facilitates vasodilation in fetal pulmonary circulation at birth.
Explained variance in the thermoregulatory responses to exercise: the independent roles of biophysical and fitness/fatness-related factors
Authors: Cramer Matthew N. , Jay Ollie
Published: August 2015

Individual variation in the thermoregulatory responses to exercise is notoriously large. Although aerobic fitness (V̇o2 max) and body fatness are traditionally considered important predictors of individual core temperature and sweating responses, recent evidence indicates potentially important and independent roles for biophysical factors. Using stepwise regression, we examined the proportion of individual variability in rectal temperature changes (ΔTre), whole body sweat loss (WBSL), and steady-state local sweat rate (LSRss) independently described by 1) biophysical factors associated with metabolic heat production (Hprod) and evaporative heat balance requirements (Ereq) relative to body size and 2) factors independently related to V̇o2 max and body fatness. In a total of 69 trials, 28 males of wide-ranging morphological traits and V̇o2 max values cycled at workloads corresponding to a range of absolute Hprod (410–898 W) and relative intensities (32.2–82.0% V̇o2 max) for 60 min in 24.8 ± 0.7°C and 33.4 ± 12.2% relative humidity. Hprod (in W/kg total body mass) alone described ∼50% of the variability in ΔTre (adjusted to r2 = 0.496; P < 0.001), whereas surface area-to-mass ratio and body fat percentage (BF%) explained an additional 4.3 and 2.3% of variability, respectively. For WBSL, Ereq (in W) alone explained ∼71% of variance (adjusted to r2 = 0.713, P < 0.001), and the inclusion of BF% explained an additional 1.3%. Similarly, Ereq (in W/m2) correlated significantly with LSRss (adjusted to r2 = 0.603, P < 0.001), whereas %V̇o2 max described an additional ∼4% of total variance. In conclusion, biophysical parameters related to Hprod, Ereq, and body size explain 54–71% of the individual variability in ΔTre, WBSL, and LSRss, and only 1–4% of additional variance is explained by factors related to fitness or fatness.
The Effect of Change in Body Mass Index on Volumetric Measures of Mammographic Density
Authors: Hart Vicki , Reeves Katherine W. , Sturgeon Susan R. , Reich Nicholas G. , Sievert Lynnette Leidy , Kerlikowske Karla , Ma Lin , Shepherd John , Tice Jeffrey A. , Mahmoudzadeh Amir Pasha , Malkov Serghei , Sprague Brian L.
Published: August 2015

Background: Understanding how changes in body mass index (BMI) relate to changes in mammographic density is necessary to evaluate adjustment for BMI gain/loss in studies of change in density and breast cancer risk. Increase in BMI has been associated with a decrease in percent density, but the effect on change in absolute dense area or volume is unclear.

Methods: We examined the association between change in BMI and change in volumetric breast density among 24,556 women in the San Francisco Mammography Registry from 2007 to 2013. Height and weight were self-reported at the time of mammography. Breast density was assessed using single x-ray absorptiometry measurements. Cross-sectional and longitudinal associations between BMI and dense volume (DV), non-dense volume (NDV), and percent dense volume (PDV) were assessed using multivariable linear regression models, adjusted for demographics, risk factors, and reproductive history.

Results: In cross-sectional analysis, BMI was positively associated with DV [β, 2.95 cm3; 95% confidence interval (CI), 2.69–3.21] and inversely associated with PDV (β, −2.03%; 95% CI, −2.09, −1.98). In contrast, increasing BMI was longitudinally associated with a decrease in both DV (β, −1.01 cm3; 95% CI, −1.59, −0.42) and PDV (β, −1.17%; 95% CI, −1.31, −1.04). These findings were consistent for both pre- and postmenopausal women.

Conclusion: Our findings support an inverse association between change in BMI and change in PDV. The association between increasing BMI and decreasing DV requires confirmation.

Impact: Longitudinal studies of PDV and breast cancer risk, or those using PDV as an indicator of breast cancer risk, should evaluate adjustment for change in BMI. Cancer Epidemiol Biomarkers Prev; 24(11); 1724–30. ©2015 AACR.
Aspirin Use and Risk of Breast Cancer: Systematic Review and Meta-analysis of Observational Studies
Authors: Zhong Shanliang , Chen Lin , Zhang Xiaohui , Yu Dandan , Tang Jinhai , Zhao Jianhua
Published: August 2015

Previous studies concerning the association between aspirin use and breast cancer risk yielded inconsistent results. We aimed to investigate the association by meta-analysis. PubMed and EMBASE were searched for relevant studies. We calculated the summary relative risks (RR) and 95% confidence intervals (CI) using random-effects models. Seventeen cohort studies and 15 case–control studies were included. The overall result showed that aspirin use decreased risk of breast cancer (RR, 0.90; 95% CI, 0.85–0.95). However, there was evidence of publication bias and heterogeneity and the association disappeared after correction using the trim-and-fill method. When stratified by study design, a significant benefit for aspirin users was only found in population-based and hospital-based case–control studies but not in cohort or nest case–control studies. Further subgroup analyses showed that aspirin use could decrease risk of in situ breast tumors or hormone receptor–positive tumors and reduce risk of breast cancer in postmenopausal women. Aspirin use may not affect overall risk of breast cancer, but decrease risk of in situ breast tumors or hormone receptor–positive tumors and reduce risk of breast cancer in postmenopausal women. Considering between-study significant heterogeneity and publication bias, confirmation in future studies is also essential. Cancer Epidemiol Biomarkers Prev; 24(11); 1645–55. ©2015 AACR.
The Search for New Agonists to P2X7R for Clinical Use: Tuberculosis as a Possible Target
Authors: Soares-Bezerra Rômulo J. , Pinho Rosa T. , Bisaggio Rodrigo da C. , Benévolo-de-Andrade Thereza Christina , Alves Luiz A.
Published: August 2015

Treatment for tuberculosis is effective with the use of proper antibiotics, but the number of drug-resistant cases is increasing. Drug resistance occurred in 650,000 cases of the 20 million patients in treatment worldwide in 2011, which demonstrates the necessity of finding new therapeutic approaches. In this context, the search for new medicines and immunomodulators could help reduce the prevalence and incidence of multi-drug-resistant tuberculosis cases. Thus several preclinical studies demonstrate the involvement of the P2X7 receptor (P2X7R) in the control of Mycobacterium tuberculosis (MTB) infection. Adenosine triphosphate (ATP), a natural agonist for P2X7R, promotes MTB death and the induction of apoptosis in monocytes and macrophages infected with MTB via activation of P2X7R by extracellular ATP. In addition, P2X7R activation in the presence of ATP increases the expression of major histocompatibility complex (MHC) class II by macrophages infected with Mycobacterium bovis (BCG) or MTB, which contributes to the generation of the antimicrobial immune response via T cells. Nevertheless, one idea that seems overlooked by the “purinergic community” is the use of the high-conductance channel associated with P2X7R to increase the passage of hydrophilic drugs to the cytoplasm of cells that express the P2X7 pore, a potential method for a drug delivery system. In this work, we propose the use of P2X7 agonists in conjunction with low molecular weight anti-tuberculosis medicines for the treatment of multi-drug-resistant tuberculosis.
Concentration-Dependent Diversifcation Effects of Free Cholesterol Loading on Macrophage Viability and Polarization
Authors: Xu Xiaoyang , Zhang Aolin , Li Ningjun , Li Pin-Lan , Zhang Fan
Published: August 2015

Background/Aims: The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implication of excess free cholesterol loading in the pathophysiology of atherosclerosis across a broad concentration range from (in µg/ml) 0 to 60. Methods: Macrophage viability was determined by measuring formazan formation and flow cytometry viable cell counting. The polarization of M1 and M2 macrophages was differentiated by FACS (Fluorescence-Activated Cell Sorting) assay. The secretion of IL-1β in macrophage culture medium was measured by ELISA kit. Macrophage apoptosis was detected by flow cytometry using a TUNEL kit. Results: Macrophage viability was increased at the treatment of lower concentrations of free cholesterol from (in µg/ml) 0 to 20, but gradually decreased at higher concentrations from 20 to 60. Lower free cholesterol loading induced anti-inflammatory M2 macrophage polarization. The activation of the PPARγ (Peroxisome Proliferator-Activated Receptor gamma) nuclear factor underscored the stimulation of this M2 phenotype. Nevertheless, higher levels of free cholesterol resulted in pro-inflammatory M1 activation. Moreover, with the application of higher free cholesterol concentrations, macrophage apoptosis and secretion of the inflammatory cytokine IL-1β increased significantly. Conclusion: These results for the first time demonstrate that free cholesterol could render concentration-dependent diversification effects on macrophage viability, polarization, apoptosis and inflammatory cytokine secretions, thereby reconciling the pros and cons of free cholesterol buildup in macrophages to the pathophysiology of atherosclerosis.
Lithium-Associated Hyperparathyroidism: A Pooled Analysis
Authors: Ibrahim Yasin , Mohamed Salah Edin , Deniwar Ahmed , Al-Qurayshi Zaid H. , Kandil Emad
Published: August 2015

Background: Lithium treatment has been associated with hyperparathyroidism (HPT). However, there are conflicting data regarding the rate of single- (SGD) versus multiple-gland disease (MGD) as well as the optimum surgical approach in these cases. Methods: Published data were identified through systematic electronic literature searches. Studies that fulfilled the preset inclusion criteria were analyzed (n = 12). Results: These studies documented 210 lithium-associated HPT (LAH) cases. Of these, 103 (49%) were due to SGD and 107 (51%) due to MGD. The unadjusted odds ratio of having multiple LAH compared to sporadic HPT was 3.44 (95% confidence interval 2.5907-4.5633; p < 0.0001). The sensitivity of preoperative sestamibi and sonography for SGD was 66-100 and 75-82%, respectively. The sensitivity for MGD was 9-67% for both. Intraoperative parathyroid hormone monitoring was utilized in 6 studies. Three studies recommended minimally invasive parathyroidectomy (MIP), while the other 3 recommended bilateral exploration. Conclusion: LAH is a relatively frequent condition among patients on lithium, and calcium monitoring should be performed initially and longitudinally. Almost half of the LAH cases are due to SGD. MIP should be the optimum surgical approach.
Salvage Procedures after Total Necrosis of a Free Jejunal Graft
Authors: Ni Song , Zhu Yiming , Wang Jian , Li Dezhi , Zhang Bin , Xu Zhengang , Liu Shaoyan
Published: August 2015

Purpose of the Study: To determine the appropriate salvage method after total necrosis of a jejunal graft after reconstruction of total laryngopharyngoesophagectomy or a larynx-preserving operation, considering the complexity of medical service in China. Procedures: We reviewed 5 patients with a mean age of 61 years who developed total jejunal graft necrosis and underwent reconstruction of a free jejunal transfer in our hospital. The total number and choice of salvage procedures, the symptoms and the results of salvage for the 5 patients have been reviewed. Results: Four of the 5 patients survived. One of them underwent gastric pull-up reconstruction and recovered well. One patient died due to severe infection after the loss of the jejunal graft and secondary gastric pull-up reconstruction. A temporary external fistula was formed in 3 patients after the initial jejunal graft necrosis, 2 of which underwent fistula repair 6 and 5 months later, while one went on long-term gastric tube feeding. Conclusion: Our results suggest that a temporary external fistula formation is an optional secondary salvage procedure after total necrosis of an initial jejunal graft, considering the relatively low quality of medical service in China.
Reconstruction of Defects Involving the Nasal Ala and the Nasolabial Fold: The Role of the Microvascular Prehelical Rim Graft
Authors: Holzmann David , Forster Natasha A. , Vital Domenic , Giovanoli Pietro
Published: August 2015

Purpose: To demonstrate a surgical technique for reconstructing defects involving the triangle of the nasal ala, nasolabial fold and upper lip. Procedure: Retrospective survey with follow-up including 4 consecutive patients with extensive skin and soft tissue defects. Results: Successful reconstruction with good nasal function and acceptable cosmetic result was achieved in all patients. Conclusion: The microvascular helical rim graft offers a unique option to reconstruct defects in this specific triangular area of the face when standard techniques have failed.
A Prospective Observational Survey on the Long-Term Effect of LDL Apheresis on Drug-Resistant Nephrotic Syndrome
Authors: Muso Eri , Mune Masatoshi , Hirano Tsutomu , Hattori Motoshi , Kimura Kenjiro , Watanabe Tsuyoshi , Yokoyama Hitoshi , Sato Hiroshi , Uchida Shunya , Wada Takashi , Shoji Tetsuo , Takemura Tsukasa , Yuzawa Yukio , Ogahara Satoru , Sugiyama Satoshi , Iino Yasuhiko , Sakai Soichi , Ogura Yousuke , Yukawa Susumu , Nishizawa Yoshiki , Yorioka Noriaki , Imai Enyu , Matsuo Seiichi , Saito Takao
Published: August 2015

Background/Aims: LDL apheresis (LDL-A) is used for drug-resistant nephrotic syndrome (NS) as an alternative therapy to induce remission by improvement of hyperlipidemia. Several clinical studies have suggested the efficacy of LDL-A for refractory NS, but the level of evidence remains insufficient. A multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was conducted to evaluate its clinical efficacy with high-level evidence. Methods: Patients with NS who showed resistance to primary medication for at least 4 weeks were prospectively recruited to the study and treated with LDL-A. The long-term outcome was evaluated based on the rate of remission of NS 2 years after treatment. Factors affecting the outcome were also examined. Results: A total of 58 refractory NS patients from 40 facilities were recruited and enrolled as subjects of the POLARIS study. Of the 44 subjects followed for 2 years, 21 (47.7%) showed remission of NS based on a urinary protein (UP) level <1.0 g/day. The UP level immediately after LDL-A and the rates of improvement of UP, serum albumin, serum creatinine, eGFR, and total and LDL cholesterol after the treatment session significantly affected the outcome. Conclusions: Almost half of the cases of drug-resistant NS showed remission 2 years after LDL-A. Improvement of nephrotic parameters at termination of the LDL-A treatment was a predictor of a favorable outcome.
Upper Respiratory Infections and MRI Activity in Relapsing-Remitting Multiple Sclerosis
Authors: Kneider Maria , Lisovskaja Vera , Lycke Jan , Malmeström Clas , Jakobsen Johannes K. , Nerman Olle , Andersen Oluf
Published: August 2015

Background: Although clinical reports have suggested a relationship between systemic infections and multiple sclerosis (MS) relapses, MRI evidence supporting an association is conflicting. Here we evaluated the temporal relationship between upper respiratory infections (URIs) and MRI activity in relapsing-remitting (RR) MS. Methods: We combined individual data on URI with data on active lesions in pre-scheduled MRI examinations performed every 4 weeks for 28 weeks in 69 patients. A 4-week at-risk (AR) period started, by definition, 1 week before the onset of a URI. We recorded the relationship between the number of active lesions in each MRI with (1) the number of days of AR time in the immediately preceding 4-week period and (2) the number of days passed since the onset of a preceding URI. Results: Average MRI lesions/day showed no difference between AR (0.0764) and not-AR (0.0774) periods. The number of lesions in 483 pre-scheduled MRI examinations did not correlate with the AR proportion in the prior 4-week period (rho = -0.03), and time from URI onset did not correlate with lesion number on the next MRI examination (rho = 0.003). Conclusion: The occurrence of a URI did not increase the risk of MRI activity evaluated in an adjacent 4-week window in RRMS.
Evaluation of the Role of IgE Responses to Der p 1 and Der p 2 in Chinese House Dust Mite-Allergic Patients
Authors: Wang Hui-Ying , Gao Zhong-Shan , Zhou Xiang , Dai Yu , Yao Wo , Zhang Xiao-Feng , Yang Zhao-Wei , Wu Shan-Dong , Yu Chao-Hui , Yang Xu-Yan , van Ree Ronald
Published: August 2015

Background: The role of specific IgE (sIgE) against Der p 1 and Der p 2 in Chinese patients with house dust mite (HDM) allergy has not yet been well investigated. Methods: One hundred patients were enrolled, based on sensitization and doctor-diagnosed allergy to HDM. Questionnaires were administered to document demographic and clinical characteristics. Serum IgE reactivity to Dermatophagoides pteronyssinus (Dp) extract, Der p 1, Der p 2 and Der p 10 was measured by ImmunoCAP. Results: Almost all patients were sensitized to Der p 1 (95%) and Der p 2 (93%), with both allergens together being largely responsible for the total anti-HDM IgE response. No evidence for a significant role of Der p 10 was found. Overall, IgE responses to HDM and its 2 major allergens were higher in children than in adults in this cross-sectional study. With increasing age, IgE responses to Der p 2 become more important. A positive correlation was observed between the reaction of sIgE against Dp, Der p 1 and Der p 2 and the number of organs (including the eyes, nose, lungs and skin) that were affected in patients. Conclusions: In China, Der p 1 and Der p 2 are the dominant allergens in patients with HDM allergy. The relative importance of Der p 1 and Der p 2 changes with age, in favor of Der p 2. Overall, sIgE titers were positively associated with the number of organs affected.
Growth and Chemosensitivity of Gastric Adenocarcinoma and Non-Malignant Cell Lines in Response to Novel Anti-Cancer Drug Combinations
Authors: Weinreich Jürgen , Archid Rami , Bajaeifer Khaled , Hack Anita , Königsrainer Alfred , Schott Timm C.
Published: August 2015

Background: To design novel polychemotherapy regimens for gastric adenocarcinoma therapy with wider therapeutic windows using a novel duplex drug (D-D). Methods: Two gastric adenocarcinoma (MKN-45 and 23132/87) and 2 non-malignant (NHDF and CCL-241) cell lines were treated with different drug regimens that included different doses of the standard triple-drug combination epirubicin (E) + cisplatin (C) + 5-fluorouracil (5-FU, F), i.e. ECF, and a new D-D that combined 2′-deoxy-5-fluorouridine (5FdU) and 3′ethinylcytidine. The cells were cultured for 14 days and the effect of the drug combinations was evaluated using CASY cell counting technology. Results: Overall growth inhibition of the cell lines with ECF was not cancer cell line-specific. Replacing 5-FU in ECF with a D-D resulted in greater growth inhibition of cancer cells than of the non-malignant cell lines and the inversion of the chemosensitivity of MKN-45 and 23132/87 cells. The type and quantity of the combined drug regimen determined the cytotoxicity and chemosensitivity of the cell lines. Conclusion: The cytotoxicity and tumour-cell specificity of standard single drugs can be markedly changed and determined using multidrug combinations that include D-Ds.
Effects of Iron Chelators on Pulmonary Iron Overload and Oxidative Stress in β-Thalassemic Mice
Authors: Yatmark Paranee , Morales Noppawan Phumala , Chaisri Urai , Wichaiyo Surasak , Hemstapat Warinkarn , Srichairatanakool Somdet , Svasti Saovaros , Fucharoen Suthat
Published: August 2015

Aim: To evaluate the effect of iron chelators on iron-related pulmonary pathology and oxidative stress in an animal model of β-thalassemia. Methods: Pulmonary iron overload was induced in heterozygous β-globin knockout mice (muβth-3/+, BKO). Over a period of 2 weeks, 180 mg of iron/mouse was loaded by intraperitoneal injection of iron dextran, and subsequently treated daily via intraperitoneal with either deferoxamine (DF) or deferiprone (L1) at an equimolar concentration of iron binding (0.2 and 0.6 μmol/g body weight, respectively) for 7 days. Results: Iron loading resulted in iron deposition in peribronchial regions, septa and also in alveolar macrophages with a grading score of 3. This iron burden resulted in lung epithelial injuries, fibrosis and corresponded with increased lipid peroxidation and decreased tissue catalase activity. Treatment with DF or L1 resulted in a reduction of iron-laden alveolar macrophages and decreased oxidative stress and tissue damage, showing the iron mobilizing ability of both compounds. Conclusion: Iron chelation therapy, with DF and L1, may protect against pulmonary damage by sequestering catalytic iron and improving oxidative status. It may be beneficial in the prevention of pulmonary complications in thalassemia.
Chromosome Polymorphism in Microtus(Alexandromys)mujanensis (Arvicolinae, Rodentia)
Authors: Lemskaya Natalya A. , Kartavtseva Irina V. , Rubtsova Nadezhda V. , Golenishchev Fedor N. , Sheremetyeva Irina N. , Graphodatsky Alexander S.
Published: August 2015

The Muya Valley vole (Microtus mujanensis) has a constant diploid chromosome number of 2n = 38, but an unstable karyotype with polymorphic chromosome pairs. Here, we describe 4 karyotypic variants involving 2 polymorphic chromosome pairs, MMUJ8 and MMUJ14, in 6 animals from Buryatia using a combination of GTG-banding and chromosome painting with M. agrestis probes. We suggest that the polymorphic pairs MMUJ8 and MMUJ14 were formed through pericentric inversions that played a major role during karyotype evolution of the species. We also propose that the stable diploid number with some ongoing polymorphism in the number of chromosome arms indicates that this evolutionarily young endemic species of Russian Far East is on the way to karyotype and likely species stabilization.