bluuebunny/crossref_metadata_2025_split huggingface dataset:
Slower lower limb blood pooling in young women with orthostatic intolerance
Authors: Lindenberger Marcus , Länne Toste 
Published: November 2014

New Findings
What is the central question of this study?
Orthostatic stress is mostly caused by venous blood pooling in the lower limbs. Venous distension elicits sympathetic responses, and increased distension speed enhances the cardiovascular response. We examine whether lower limb blood pooling rate during lower body negative pressure is linked to orthostatic intolerance.

What is the main finding and its importance?
A similar amount of blood was pooled in the lower limb, but at a slower rate in women who developed signs of orthostatic intolerance. The difference in blood pooling rate increased with orthostatic stress and was most prominent at a presyncope‐inducing level of lower body negative pressure. The findings have implications for the pathophysiology as well as treatment of orthostatic intolerance.

Vasovagal syncope is common in young women, but its aetiology remains elusive. Orthostatic stress‐induced lower limb blood pooling is linked with central hypovolaemia and baroreceptor unloading. Venous distension in the arm elicits a sympathetic response, which is enhanced with more rapid distension. Our aim was to study both the amount and the speed of lower limb pooling during orthostatic stress and its effects on compensatory mechanisms to maintain cardiovascular homeostasis in women with orthostatic intolerance. Twenty‐seven healthy women, aged 20–27 years, were subjected to a lower body negative pressure (LBNP) of 11–44 mmHg. Five women developed symptoms of vasovagal syncope (orthostatic intolerant) and were compared with the remaining women, who tolerated LBNP well (orthostatic tolerant). Lower limb blood pooling, blood flow and compensatory mobilization of venous capacitance blood were measured. Lower body negative pressure induced equal lower limb blood pooling in both groups, but at a slower rate in orthostatic intolerant women (e.g. time to 50% of total blood pooling, orthostatic intolerant 44 ± 7 s and orthostatic tolerant 26 ± 2 s; P < 0.001). At presyncope‐inducing LBNP, the mobilization of venous capacitance blood was both reduced (P < 0.05) and much slower in orthostatic intolerant women (P = 0.0007). Orthostatic intolerant women elicited blunted arterial vasoconstriction at low‐grade LBNP, activating only cardiopulmonary baroreceptors, while orthostatic tolerant women responded with apparent vasoconstriction (P < 0.0001). In conclusion, slower lower limb blood pooling could contribute to orthostatic intolerance in women. Mobilization of venous capacitance blood from the peripheral to the central circulation was both slower and decreased; furthermore, reduced cardiopulmonary baroreceptor sensitivity was found in women who developed orthostatic intolerance. Further studies including women who experience syncope in daily life are needed.
Modulating Endoplasmic Reticulum-Golgi Cargo Receptors for Improving Secretion of Carrier-Fused Heterologous Proteins in the Filamentous Fungus Aspergillus oryzae
Authors: Hoang Huy-Dung , Maruyama Jun-ichi , Kitamoto Katsuhiko 
Published: November 2014

ABSTRACT

Filamentous fungi are excellent hosts for industrial protein production due to their superior secretory capacity; however, the yield of heterologous eukaryotic proteins is generally lower than that of fungal or endogenous proteins. Although activating protein folding machinery in the endoplasmic reticulum (ER) improves the yield, the importance of intracellular transport machinery for heterologous protein secretion is poorly understood. Here, using
Aspergillus oryzae
as a model filamentous fungus, we studied the involvement of two putative lectin-like cargo receptors,
A. oryzae
Vip36 (AoVip36) and AoEmp47, in the secretion of heterologous proteins expressed in fusion with the endogenous enzyme α-amylase as the carrier. Fluorescence microscopy revealed that mDsRed-tagged AoVip36 localized in the Golgi compartment, whereas AoEmp47 showed localization in both the ER and the Golgi compartment. Deletion of AoVip36 and AoEmp47 improved heterologous protein secretion, but only AoVip36 deletion had a negative effect on the secretion of α-amylase. Analysis of ER-enriched cell fractions revealed that AoVip36 and AoEmp47 were involved in the retention of heterologous proteins in the ER. However, the overexpression of each cargo receptor had a different effect on heterologous protein secretion: AoVip36 enhanced the secretion, whereas AoEmp47 promoted the intracellular retention. Taken together, our data suggest that AoVip36 and AoEmp47 hinder the secretion of heterologous proteins by promoting their retention in the ER but that AoVip36 also promotes the secretion of heterologous proteins. Moreover, we found that genetic deletion of these putative ER-Golgi cargo receptors significantly improves heterologous protein production. The present study is the first to propose that ER-Golgi transport is a bottleneck for heterologous protein production in filamentous fungi.
Intra- and Interindividual Variations Mask Interspecies Variation in the Microbiota of Sympatric Peromyscus Populations
Authors: Baxter Nielson T. , Wan Judy J. , Schubert Alyxandria M. , Jenior Matthew L. , Myers Philip , Schloss Patrick D. 
Published: November 2014

ABSTRACTUsing populations of two sympatricPeromyscusspecies, we characterized the importance of the host species, physiology, environment, diet, and other factors in shaping the structure and dynamics of their gut microbiota. We performed a capture-mark-release experiment in which we obtained 16S rRNA gene sequence data from 49 animals at multiple time points. In addition, we performed 18S rRNA gene sequencing of the same samples to characterize the diet of each individual. Our analysis could not distinguish between the two species ofPeromyscuson the basis of the structures of their microbiotas. However, we did observe a set of bacterial populations that were found in every animal. Most notable were abundant representatives of the generaLactobacillusandHelicobacter. When we combined the 16S and 18S rRNA gene sequence analyses, we were unable to distinguish the communities on the basis of the animal's diet. Furthermore, there were no discernible differences in the structure of the gut communities based on the capture site or their developmental or physiological status. Finally, in contrast to humans, where each individual has a unique microbiota when sampled over years, among the animals captured in this study, the uniqueness of each microbiota was lost within a week of the original sampling. Wild populations provide an opportunity to study host-microbiota interactions as they originally evolved, and the ability to perform natural experiments will facilitate a greater understanding of the factors that shape the structure and function of the gut microbiota.
Quaternary Ammonium Biocides: Efficacy in Application
Authors: Gerba Charles P. 
Published: November 2014

ABSTRACT
Quaternary ammonium compounds (QACs) are among the most commonly used disinfectants. There has been concern that their widespread use will lead to the development of resistant organisms, and it has been suggested that limits should be place on their use. While increases in tolerance to QACs have been observed, there is no clear evidence to support the development of resistance to QACs. Since efflux pumps are believe to account for at least some of the increased tolerance found in bacteria, there has been concern that this will enhance the resistance of bacteria to certain antibiotics. QACs are membrane-active agents interacting with the cytoplasmic membrane of bacteria and lipids of viruses. The wide variety of chemical structures possible has seen an evolution in their effectiveness and expansion of applications over the last century, including non-lipid-containing viruses (i.e., noroviruses). Selection of formulations and methods of application have been shown to affect the efficacy of QACs. While numerous laboratory studies on the efficacy of QACs are available, relatively few studies have been conducted to assess their efficacy in practice. Better standardized tests for assessing and defining the differences between increases in tolerance versus resistance are needed. The ecological dynamics of microbial communities where QACs are a main line of defense against exposure to pathogens need to be better understood in terms of sublethal doses and antibiotic resistance.
Nonribosomal Peptide Synthase Gene Clusters for Lipopeptide Biosynthesis in Bacillus subtilis 916 and Their Phenotypic Functions
Authors: Luo Chuping , Liu Xuehui , Zhou Huafei , Wang Xiaoyu , Chen Zhiyi 
Published: November 2014

ABSTRACT

Bacillus
cyclic lipopeptides (LPs) have been well studied for their phytopathogen-antagonistic activities. Recently, research has shown that these LPs also contribute to the phenotypic features of
Bacillus
strains, such as hemolytic activity, swarming motility, biofilm formation, and colony morphology.
Bacillus subtilis
916 not only coproduces the three families of well-known LPs, i.e., surfactins, bacillomycin Ls (iturin family), and fengycins, but also produces a new family of LP called locillomycins. The genome of
B. subtilis
916 contains four nonribosomal peptide synthase (NRPS) gene clusters,
srf
,
bmy
,
fen
, and
loc
, which are responsible for the biosynthesis of surfactins, bacillomycin Ls, fengycins, and locillomycins, respectively. By studying
B. subtilis
916 mutants lacking production of one, two, or three LPs, we attempted to unveil the connections between LPs and phenotypic features. We demonstrated that bacillomycin Ls and fengycins contribute mainly to antifungal activity. Although surfactins have weak antifungal activity
in vitro
, the strain mutated in
srfAA
had significantly decreased antifungal activity. This may be due to the impaired productions of fengycins and bacillomycin Ls. We also found that the disruption of any LP gene cluster other than
fen
resulted in a change in colony morphology. While surfactins and bacillomycin Ls play very important roles in hemolytic activity, swarming motility, and biofilm formation, the fengycins and locillomycins had little influence on these phenotypic features. In conclusion,
B. subtilis
916 coproduces four families of LPs which contribute to the phenotypic features of
B. subtilis
916 in an intricate way.
Pathogenicity of Salmonella Strains Isolated from Egg Shells and the Layer Farm Environment in Australia
Authors: McWhorter Andrea R. , Davos Dianne , Chousalkar K. K. 
Published: November 2014

ABSTRACT

In Australia, the egg industry is periodically implicated during outbreaks of
Salmonella
food poisoning.
Salmonella enterica
serovar Typhimurium and other nontyphoidal
Salmonella
spp., in particular, are a major concern for Australian public health. Several definitive types of
Salmonella
Typhimurium strains, but primarily
Salmonella
Typhimurium definitive type 9 (DT9), have been frequently reported during egg-related food poisoning outbreaks in Australia. The aim of the present study was to generate a pathogenicity profile of nontyphoidal
Salmonella
isolates obtained from Australian egg farms. To achieve this, we assessed the capacity of
Salmonella
isolates to cause gastrointestinal disease using both
in vitro
and
in vivo
model systems. Data from
in vitro
experiments demonstrated that the invasion capacity of
Salmonella
serovars cultured to stationary phase (liquid phase) in LB medium was between 90- and 300-fold higher than bacterial suspensions in normal saline (cultured in solid phase). During the
in vivo
infection trial, clinical signs of infection and mortality were observed only for mice infected with either 10
3
or 10
5
CFU of
S
. Typhimurium DT9. No mortality was observed for mice infected with
Salmonella
serovars with medium or low invasive capacity in Caco-2 cells. Pathogenicity gene profiles were also generated for all serovars included in this study. The majority of serovars tested were positive for selected virulence genes. No relationship between the presence or absence of virulence genes by PCR and either
in vitro
invasive capacity or
in vivo
pathogenicity was detected. Our data expand the knowledge of strain-to-strain variation in the pathogenicity of Australian egg industry-related
Salmonella
spp.
Is iron treatment beneficial in, iron-deficient but non-anaemic (IDNA) endurance athletes? A systematic review and meta-analysis
Authors: Burden Richard J , Morton Katie , Richards Toby , Whyte Gregory P , Pedlar Charles R 
Published: November 2014

PurposeThe aim of this study was to determine whether iron treatments improve the iron status and aerobic capacity of iron deficient non-anaemic endurance athletes.MethodA meta-analysis of studies that investigated the effects of iron treatment on serum ferritin (sFer), serum iron (sFe), transferrin saturation (Tsat), haemoglobin concentration ([Hb]) and (). Seventeen eligible studies were identified from online databases.ResultsAnalysis of pooled data indicated that iron treatments had a large effect on improving sFer (Hedges’ g=1.088, 95% CI 0.914 to 1.263, p<0.001), sFe (Hedges’ g=1.004, 95% CI 0.828 to 1.181, p<0.001) and Tsat (Hedges g=0.741, 95% CI 0.564 to 0.919, p<0.001) and a moderate effect on improving [Hb] (Hedges’ g=0.695, 95% CI 0.533 to 0.836, p<0.001) and(Hedges’ g=0.610, 95% CI 0.399 to 0.821,p<0.001). Regression analysis revealed a significant interaction between the effect of iron treatment on sFer and treatment duration, suggesting treatments that lasted beyond 80 days appear to have the least effect on sFer.ConclusionsThese results indicate iron treatments improve the iron status and aerobic capacity of iron deficient non-anaemic endurance athletes.
Alcohol-related hospitalisations of trauma patients in Southern Taiwan: a cross-sectional study based on a trauma registry system
Authors: Rau Cheng-Shyuan , Liu Hang-Tsung , Hsu Shiun-Yuan , Cho Tzu-Yu , Hsieh Ching-Hua 
Published: November 2014

ObjectivesTo provide an overview of the demographic characteristics of patients with positive blood alcohol concentration (BAC) and to investigate the performance of brain CT scans in these patients.DesignCross-sectional study.SettingTaiwan.Participants2192 patients who had undergone a test for blood alcohol of 13 233 patients registered in the Trauma Registry System between 1 January 2009 and 31 December 2012. A BAC level of 50 mg/dL was defined as the cut-off value. Detailed information was retrieved from the patients with positive BAC (n=793) and was compared with information from those with a negative BAC (n=1399).Main outcome measuresGlasgow Coma Scale (GCS) and Injury Severity Score (ISS) as well as the performance and findings of obtained brain CT scans.ResultsPatients with positive BAC had a higher rate of face injury, but a lower GCS score, a lower rate of head and neck injury, a lower ISS and New Injury Severity Score. Alcohol use was associated with a shorter length of hospital stay (8.6 vs 11.4 days, p=0.000) in patients with an ISS of <16. Of 496 patients with positive BAC who underwent brain CT, 164 (33.1%) showed positive findings on CT scan. In contrast, of 891 patients with negative BAC who underwent brain CT, 389 (43.7%) had positive findings on CT scan. The lower percentage of positive CT scan findings in patients with positive BAC was particularly evident in patients with an ISS <16 (18.0% vs 28.8%, p=0.001).ConclusionsPatients who consumed alcohol tended to have a low GCS score and injuries that were less severe. However, given the significantly low percentage of positive findings, brain CT might be overused in these patients with less severe injuries.
Quality of medicines in Canada: a retrospective review of risk communication documents (2005–2013)
Authors: Almuzaini Tariq , Sammons Helen , Choonara Imti 
Published: November 2014

ObjectiveTo explore the quality and safety of medicines in Canada.DesignA retrospective review of drug recalls and risk communication documents conveying issues relating to defective (ie, substandard and falsified) medicines.SettingThe Health Canada website search for drug recalls and risk communication documents issued between 2005 and 2013.Eligibility criteriaDrug recalls and risk communication documents related to quality defect in medicinal products.Main outcome measureRelevant data about defective medicines reported in drug recalls and risk communication documents, including description of the defect, type of formulation, year of the recall and category of the recall or the document.ResultsThere were 653 defective medicines of which 649 were substandard. The number of defective medicines reported by Health Canada increased from 42 in 2005 to 143 in 2013. The two most frequently reported types of defects were stability (205 incidents) and contamination issues (139 incidents). Some of these defects were found to be more prominent and repetitive over other types within some manufacturers. Tablet formulation (251 incidents) was the formulation most frequently compromised. No significant differences were observed between the manufacturers and distributors in the number of substandard medicines reported under each defect type. There were only four falsified medicines reported over the 9-year period.ConclusionsSubstandard medicines are a problem in Canada and have resulted in an increasing number of recalled medicines. Most of the failures were related to stability issues, raising the need to investigate the root causes and for stringent preventative measures to be implemented by manufacturers.
High and Interrelated Rates of PD-L1+CD14+ Antigen-Presenting Cells and Regulatory T Cells Mark the Microenvironment of Metastatic Lymph Nodes from Patients with Cervical Cancer
Authors: Heeren A. Marijne , Koster Bas D. , Samuels Sanne , Ferns Debbie M. , Chondronasiou Dafni , Kenter Gemma G. , Jordanova Ekaterina S. , de Gruijl Tanja D. 
Published: November 2014

AbstractA better understanding of the microenvironment in relation to lymph node metastasis is essential for the development of effective immunotherapeutic strategies against cervical cancer. In the present study, we investigated the microenvironment of tumor-draining lymph nodes of patients with cervical cancer by comprehensive flow cytometry–based phenotyping and enumeration of immune-cell subsets in tumor-negative (LN−, n = 20) versus tumor-positive lymph nodes (LN+, n = 8), and by the study of cytokine release profiles (n = 4 for both LN− and LN+). We found significantly lower CD4+ and higher CD8+ T-cell frequencies in LN+ samples, accompanied by increased surface levels of activation markers (HLA-DR; ICOS; PD-1; CTLA-4) and the memory marker CD45RO. Furthermore, in LN+, we found increased rates of a potentially regulatory antigen-presenting cell (APC) subset (CD11chiCD14+PD-L1+) and of myeloid-derived suppressor cell subsets; the LN+ APC subset correlated with significantly elevated frequencies of FoxP3+ regulatory T cells (Treg). After in vitro stimulation with different Toll-like receptor (TLR) ligands (PGN; Poly-IC; R848), we observed higher production levels of IL6, IL10, and TNFα but lower levels of IFNγ in LN+ samples. We conclude that, despite increased T-cell differentiation and activation, a switch to a profound immune-suppressive microenvironment in LN+ of patients with cervical cancer will enable immune escape. Our data indicate that the CD14+PD-L1+ APC/Treg axis is a particularly attractive and relevant therapeutic target to specifically tackle microenvironmental immune suppression and thus enhances the efficacy of immunotherapy in patients with metastasized cervical cancer. Cancer Immunol Res; 3(1); 48–58. ©2014 AACR.
An integrated genomic-transcriptomic approach supports a role for the proto-oncogene BCL3 in atherosclerosis
Authors: Marchetti Giovanna , Girelli Domenico , Zerbinati Carlotta , Lunghi Barbara , Friso Simonetta , Meneghetti Silvia , Coen Matteo , Gagliano Teresa , Guastella Giuseppe , Bochaton-Piallat Marie-Luce , Pizzolo Francesca , Mascoli Francesco , Malerba Giovanni , Bovolenta Matteo , Ferracin Manuela , Olivieri Oliviero , Bernardi Francesco , Martinelli Nicola 
Published: November 2014

Summaryassociation studies of coronary artery disease (CAD), could include functionally relevant associations. We propose an integrated genomic and transcriptomic approach for unravelling new potential genetic signatures of atherosclerosis. Fifteen among 91 single nucleotide polymorphisms (SNPs) were first selected for association in a sex- and age-adjusted model by examining 510 patients with CAD and myocardial infarction and 388 subjects with normal coronary arteries (CAD-free) in the replication stages of a genome-wide association study. We investigated the expression of 71 genes proximal to the 15 tag-SNPs by two subsequent steps of microarray-based Mrna profiling, the former in vascular smooth muscle cell populations, isolated from non-atherosclerotic and atherosclerotic human carotid portions, and the latter in whole carotid specimens. BCL3 and PVRL2, contiguously located on chromosome 19, and ABCA1, extensively investigated before, were found to be differentially expressed. BCL3 and PVRL2 SNPs were genotyped within a second population of CAD patients (n=442) and compared with CAD-free subjects (n=393). The carriership of the BCL3 rs2965169 G allele was more represented among CAD patients and remained independently associated with CAD after adjustment for all the traditional cardiovascular risk factors (odds ratio=1.70 with 95% confidence interval 1.07–2.71), while the BCL3 rs8100239 A allele correlated with metabolic abnormalities. The upregulation of BCL3 mRNA levels in atherosclerotic tissue samples was consistent with BCL3 protein expression, which was detected by immunostaining in the intima-media of atherosclerotic specimens, but not within non-atherosclerotic ones. Our integrated approach suggests a role for BCL3 in cardiovascular diseases.
Angiotensin Receptor Neprilysin Inhibitor LCZ696 Attenuates Cardiac Remodeling and Dysfunction After Myocardial Infarction by Reducing Cardiac Fibrosis and Hypertrophy
Authors: von Lueder Thomas G. , Wang Bing H. , Kompa Andrew R. , Huang Li , Webb Randy , Jordaan Pierre , Atar Dan , Krum Henry 
Published: November 2014

Background—
Angiotensin receptor neprilysin inhibitors (ARNi), beyond blocking angiotensin II signaling, augment natriuretic peptides by inhibiting their breakdown by neprilysin. The myocardial effects of ARNi have been little studied until recently. We hypothesized that LCZ696 attenuates left ventricular (LV) remodeling after experimental myocardial infarction (MI), and that this may be contributed to by inhibition of hypertrophy and fibrosis in cardiac cells.

Methods and Results—

One week after MI, adult male Sprague–Dawley rats were randomized to treatment for 4 weeks with LCZ696 (68 mg/kg body weight perorally; MI-ARNi, n=11) or vehicle (MI-vehicle, n=6). Five weeks after MI, MI-ARNi versus MI-vehicle demonstrated lower LV end-diastolic diameter (by echocardiography; 9.7±0.2 versus 10.5±0.3 mm), higher LV ejection fraction (60±2 versus 47±5%), diastolic wall strain (0.23±0.02 versus 0.13±0.02), and circular strain (−9.8±0.5 versus −7.3±0.5%; all
P
<0.05). LV pressure–volume loops confirmed improved LV function. Despite similar infarct size, MI-ARNi versus MI-vehicle had lower cardiac weights (
P
<0.01) and markedly reduced fibrosis in peri-infarct and remote myocardium. Angiotensin II–stimulated incorporation of 3[H]leucine in cardiac myocytes and 3[H]proline in cardiac fibroblast was used to evaluate hypertrophy and fibrosis, respectively. The neprilysin inhibitor component of LCZ696, LBQ657, inhibited hypertrophy but not fibrosis. The angiotensin receptor blocker component of LCZ696, valsartan inhibited both hypertrophy and fibrosis. Dual valsartan+LBQ augmented the inhibitory effects of valsartan and the highest doses completely abrogated angiotensin II–mediated effects.

Conclusions—
LCZ696 attenuated cardiac remodeling and dysfunction after MI. This may be contributed to by superior inhibition of LCZ696 on cardiac fibrosis and cardiac hypertrophy than either stand-alone neprilysin inhibitor or angiotensin receptor blocker.