bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycoplasma suis infection results endothelial cell damage and activation: new insight into the cell tropism and pathogenicity of hemotrophic mycoplasma
Authors: Sokoli Albina , Groebel Katrin , Hoelzle Katharina , Amselgruber Werner M , Mateos José M , Schneider Mårten KJ , Ziegler Urs , Felder Kathrin M , Hoelzle Ludwig E
Published: February 2013

Hemotrophic mycoplasmas (HM) are highly specialized red blood cell parasites that cause infectious anemia in a variety of mammals, including humans. To date, no in vitro cultivation systems for HM have been available, resulting in relatively little information about the pathogenesis of HM infection. In pigs,Mycoplasma suis-induced infectious anemia is associated with hemorrhagic diathesis, and coagulation dysfunction. However, intravasal coagulation and subsequent consumption coagulopathy can only partly explain the sequence of events leading to hemorrhagic diathesis manifesting as cyanosis, petechial bleeding, and ecchymosis, and to disseminated coagulation. The involvement of endothelial activation and damage inM. suis-associated pathogenesis was investigated using light and electron microscopy, immunohistochemistry, and cell sorting.M. suisinteracted directly with endothelial cells in vitro and in vivo. Endothelial activation, widespread endothelial damage, and adherence of red blood cells to the endothelium were evident inM. suis-infected pigs. These alterations of the endothelium were accompanied by hemorrhage, intravascular coagulation, vascular occlusion, and massive morphological changes within the parenchyma.M. suisbiofilm-like microcolonies formed on the surface of endothelial cells, and may represent a putative persistence mechanism ofM. suis. In vitro analysis demonstrated thatM. suisinteracted with the endothelial cytoskeletal protein actin, and induced actin condensation and activation of endothelial cells, as determined by the up-regulation of ICAM, PECAM, E-selectin, and P-selectin. These findings demonstrate an additional cell tropism of HM for endothelial cells and suggest thatM. suisinterferes with the protective function of the endothelium, resulting in hemorrhagic diathesis.
Antigen dose and humoral immune response correspond with protection for inactivated infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L)
Authors: Munang’andu Hetron Mweemba , Fredriksen Børge Nilsen , Mutoloki Stephen , Dalmo Roy Ambli , Evensen Øystein
Published: February 2013

An enduring challenge in the vaccinology of infectious pancreatic necrosis virus (IPNV) is the lack of correlation between neutralizing antibodies and protection against mortality. To better understand the immunological basis of vaccine protection, an efficacy trial including Atlantic salmon (Salmo salar L.) vaccinated with a high antigen (HiAg) or low antigen (LoAg) dose vaccine was carried out in a cohabitation challenge model using the highly virulent Norwegian Sp strain NVI015. To pinpoint the immunological basis of vaccine protection, pathogenic mechanisms of IPNV were unraveled in control fish while obtaining feedback on mechanisms of protection in the vaccinated fish. During the incubation period, infection rates were highest in control fish, followed by the LoAg group with the lowest infections being in the HiAg group. Although both the liver and pancreas are target organs prone to tissue damage, infection in the liver was delayed until acute infection in most fish. A correlate of pathology determined as the cutoff threshold of viral copy numbers linked to tissue damage in target organs was estimated at ≥ 107.0, which corresponded with an increase in mortality. The kinetics of IFNα and Mx expression suggests that these genes can be used as biomarkers of IPNV infection progression. Mechanisms of vaccine protection involved reducing infection rates, preventing infection of the liver and reducing virus replication in target organs to levels below the correlate of pathology. Overall, the study shows that antigen dose corresponds with vaccine efficacy and that antibody levels can be used as a signature of protective immunity against pathological disease and mortality.
Sputum mediator profiling and relationship to airway wall geometry imaging in severe asthma
Authors: Desai Dhananjay , Gupta Sumit , Siddiqui Salman , Singapuri Amisha , Monteiro William , Entwisle James , Visvanathan Sudha , Parmar Harsukh , Kajekar Radhika , Brightling Christopher E
Published: February 2013

Background

Severe asthma is a heterogeneous disease and the relationship between airway inflammation and airway remodelling is poorly understood. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts.

Methods

In a single centre cross-sectional observational study we recruited 59 subjects with severe asthma that underwent sputum induction and thoracic CT. Quantitative CT analysis of the apical segment of the right upper lobe (RB1) was performed. Forty-one mediators in sputum samples were measured of which 21 mediators that were assessable in >50% of samples were included in the analyses.

Results

Independent of airway geometry, sputum MMP9 and IL-1β were elevated in those groups with a high sputum neutrophil count while sputum ICAM was elevated in those subjects with a low sputum neutrophil count. In contrast, sputum CCL11, IL-1α and fibrinogen were different in groups stratified by both sputum neutrophil count and airway geometry. Sputum CCL11 concentration was elevated in subjects with a low sputum neutrophil count and high luminal and total RB1 area, whereas sputum IL1α was increased in subjects with a high sputum neutrophil count and low total RB1 area. Sputum fibrinogen was elevated in those subjects with RB1 luminal narrowing and in those subjects with neutrophilic inflammation without luminal narrowing.

Conclusions

We have demonstrated that sputum mediator profiling reveals a number of associations with airway geometry. Whether these findings reflect important biological phenotypes that might inform stratified medicine approaches requires further investigation.
Preliminary characterizations of a serum biomarker for sarcoidosis by comparative proteomic approach with tandem-mass spectrometry in ethnic Han Chinese patients
Authors: Zhang Yuan , Chen Xianqiu , Hu Yang , Du Shanshan , Shen Li , He Yifan , Zhang Yuxuan , Zhang Xia , Li Huiping , Yung Rex C
Published: February 2013

Background

The diagnosis of sarcoidosis is still a significant challenge in China because of the need to exclude other diseases including granulomatous infections and malignancies that may be clinically and radiographically similar. The specific aim of the study is to search for serum protein biomarkers of sarcoidosis and to validate their clinical usefulness in differential diagnosis.

Methods

Serum samples were collected from patients with sarcoidosis (n = 37), and compared to those from patients with tuberculosis (n = 20), other pulmonary diseases (n = 20), and healthy volunteers (n = 20) for determination of sarcoidosis-specific or -associated protein expression profiles. The first part of this study focused on proteomic analysis of serum from patients with sarcoidosis to identify a pattern of peptides capable of differentiating the studied populations using the ClinProt profiling technology based on mass spectrometry. Enzyme Linked Immunosorbent Assay (ELISA) was then used to verify corresponding elevation of the serum protein concentration of the potential biomarkers in the same patients sets. Receiver operating characteristic curve (ROC) analyses was performed to determine the optimal cutoff value for diagnosis. Immunohistochemistry was carried out to further confirm the protein expression patterns of the biomarkers in lung tissue.

Results

An unique protein peak of M/Z 3,210 Daltons (Da) was found to be differentially expressed between the sarcoidosis and control groups and was identified as the N-terminal peptide of 29 amino acids (94-122) of serum amyloid A (SAA). ELISA confirmed that the serum SAA level was significantly higher in the sarcoidosis group than that of the other 3 control groups (p < 0.05). The cutoff for serum SAA concentration determined by ROC analysis was 101.98 ng/ml, with the sensitivity and specificity of 96.3% and 52.5%, respectively. Immunohistochemical staining showed that the SAA depositions in lung tissue of the sarcoidosis patients were also significantly more intense than in non-sarcoid lung tissue (p < 0.05).

Conclusion

This is the first study to investigate serum protein markers in Chinese subjects with sarcoidosis. This study shows that the serum SAA expression profiles were different between the sarcoidosis and non-sarcoidosis groups. SAA may be a potential serum biomarker for ruling-out the diagnosis of sarcoidosis in Chinese subjects.
Horizontal gene transfer of epigenetic machinery and evolution of parasitism in the malaria parasite Plasmodium falciparum and other apicomplexans
Authors: Kishore Sandeep P , Stiller John W , Deitsch Kirk W
Published: February 2013

Background

The acquisition of complex transcriptional regulatory abilities and epigenetic machinery facilitated the transition of the ancestor of apicomplexans from a free-living organism to an obligate parasite. The ability to control sophisticated gene expression patterns enabled these ancient organisms to evolve several differentiated forms, invade multiple hosts and evade host immunity. How these abilities were acquired remains an outstanding question in protistan biology.

Results

In this work, we study SET domain bearing genes that are implicated in mediating immune evasion, invasion and cytoadhesion pathways of modern apicomplexans, including malaria parasites. We provide the first conclusive evidence of a horizontal gene transfer of a Histone H4 Lysine 20 (H4K20) modifier, Set8, from an animal host to the ancestor of apicomplexans. Set8 is known to contribute to the coordinated expression of genes involved in immune evasion in modern apicomplexans. We also show the likely transfer of a H3K36 methyltransferase (Ashr3 from plants), possibly derived from algal endosymbionts. These transfers appear to date to the transition from free-living organisms to parasitism and coincide with the proposed horizontal acquisition of cytoadhesion domains, the O-glycosyltransferase that modifies these domains, and the primary family of transcription factors found in apicomplexan parasites. Notably, phylogenetic support for these conclusions is robust and the genes clearly are dissimilar to SET sequences found in the closely related parasite Perkinsus marinus, and in ciliates, the nearest free-living organisms with complete genome sequences available.

Conclusions

Animal and plant sources of epigenetic machinery provide new insights into the evolution of parasitism in apicomplexans. Along with the horizontal transfer of cytoadhesive domains, O-linked glycosylation and key transcription factors, the acquisition of SET domain methyltransferases marks a key transitional event in the evolution to parasitism in this important protozoan lineage.
Efficacy of pulmonary rehabilitation in patients with moderate chronic obstructive pulmonary disease: a randomized controlled trial
Authors: Román Miguel , Larraz Concepción , Gómez Amalia , Ripoll Joana , Mir Isabel , Miranda Eduardo Z , Macho Ana , Thomas Vicenç , Esteva Magdalena
Published: February 2013

Background

Pulmonary Rehabilitation for moderate Chronic Obstructive Pulmonary Disease in primary care could improve patients’ quality of life.

Methods

This study aimed to assess the efficacy of a 3-month Pulmonary Rehabilitation (PR) program with a further 9 months of maintenance (RHBM group) compared with both PR for 3 months without further maintenance (RHB group) and usual care in improving the quality of life of patients with moderate COPD.

We conducted a parallel-group, randomized clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups. Health outcomes were quality of life, exercise capacity, pulmonary function and exacerbations.

Results

We found statistically and clinically significant differences in the three groups at 3 months in the emotion dimension (0.53; 95%CI0.06-1.01) in the usual care group, (0.72; 95%CI0.26-1.18) the RHB group (0.87; 95%CI 0.44-1.30) and the RHBM group as well as in fatigue (0.47; 95%CI 0.17-0.78) in the RHBM group. After 1 year, these differences favored the long-term rehabilitation group in the domains of fatigue (0.56; 95%CI 0.22-0.91), mastery (0.79; 95%CI 0.03-1.55) and emotion (0.75; 95%CI 0.17-1.33). Between-group analysis only showed statistically and clinically significant differences between the RHB group and control group in the dyspnea dimension (0.79 95%CI 0.05-1.52). No differences were found for exacerbations, pulmonary function or exercise capacity.

Conclusions

We found that patients with moderate COPD and low level of impairment did not show meaningful changes in QoL, exercise tolerance, pulmonary function or exacerbation after a one-year, community based rehabilitation program. However, long-term improvements in the emotional, fatigue and mastery dimensions (within intervention groups) were identified.

Trial registration

ISRCTN94514482
Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis
Authors: Kelso Joel K , Halder Nilimesh , Milne George J
Published: February 2013

Background

A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided.

Methods

A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed.

Results

Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and increased rates of vaccination further improved effectiveness and cost effectiveness.

Conclusions

The effectiveness and cost effectiveness consequences of the time-critical interplay of pandemic dynamics, vaccine availability and intervention timing has been quantified. For moderate and extreme pandemics, vaccination combined with rapidly activated antiviral and social distancing interventions of sufficient duration is cost effective from the perspective of life years saved.
Gremlin induces cell proliferation and extra cellular matrix accumulation in mouse mesangial cells exposed to high glucose via the ERK1/2 pathway
Authors: Huang Haixia , Huang Haiying , Li Ying , Liu Maodong , Shi Yonghong , Chi Yanqing , Zhang Tao
Published: February 2013

Background

Gremlin, a bone morphogenetic protein antagonist, plays an important role in the pathogenesis of diabetic nephropathy (DN). However, the specific molecular mechanism underlying Gremlin’s involvement in DN has not been fully elucidated. In the present study, we investigated the role of Gremlin on cell proliferation and accumulation of extracellular matrix (ECM) in mouse mesangial cells (MMCs), and explored the relationship between Gremlin and the ERK1/2 pathway.

Methods

To determine expression of Gremlin in MMCs after high glucose (HG) exposure, Gremlin mRNA and protein expression were evaluated using real-time polymerase chain reaction and western blot analysis, respectively. To determine the role of Gremlin on cell proliferation and accumulation of ECM, western blot analysis was used to assess expression of pERK1/2, transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF). Cell proliferation was examined by bromodeoxyuridine (BrdU) ELISA, and accumulation of collagen IV was measured using a radioimmunoassay. This enabled the relationship between Gremlin and ERK1/2 pathway activation to be investigated.

Results

HG exposure induced expression of Gremlin, which peaked 12 h after HG exposure. HG exposure alone or transfection of normal-glucose (NG) exposed MMCs with Gremlin plasmid (NG + P) increased cell proliferation. Transfection with Gremlin plasmid into MMCs previously exposed to HG (HG + P) significantly increased this HG-induced phenomenon. HG and NG + P conditions up-regulated protein levels of TGF-β1, CTGF and collagen IV accumulation, while HG + P significantly increased levels of these further. Inhibition of Gremlin with Gremlin siRNA plasmid reversed the HG-induced phenomena. These data indicate that Gremlin can induce cell proliferation and accumulation of ECM in MMCs. HG also induced the activation of the ERK1/2 pathway, which peaked 24 h after HG exposure. HG and NG + P conditions induced overexpression of pERK1/2, whilst HG + P significantly induced levels further. Inhibition of Gremlin by Gremlin siRNA plasmid reversed the HG-induced phenomena. This indicates Gremlin can induce activation of the ERK1/2 pathway in MMCs.

Conclusion

Culture of MMCs in the presence of HG up-regulates expression of Gremlin. Gremlin induces cell proliferation and accumulation of ECM in MMCs. and enhances activation of the ERK1/2 pathway.
Intracellular calcium release modulates polycystin-2 trafficking
Authors: Miyakawa Ayako , Ibarra Cristián , Malmersjö Seth , Aperia Anita , Wiklund Peter , Uhlén Per
Published: February 2013

Background

Polycystin-2 (PC2), encoded by the gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD), functions as a calcium (Ca2+) permeable ion channel. Considerable controversy remains regarding the subcellular localization and signaling function of PC2 in kidney cells.

Methods

We investigated the subcellular PC2 localization by immunocytochemistry and confocal microscopy in primary cultures of human and rat proximal tubule cells after stimulating cytosolic Ca2+ signaling. Plasma membrane (PM) Ca2+ permeability was evaluated by Fura-2 manganese quenching using time-lapse fluorescence microscopy.

Results

We demonstrated that PC2 exhibits a dynamic subcellular localization pattern. In unstimulated human or rat proximal tubule cells, PC2 exhibited a cytosolic/reticular distribution. Treatments with agents that in various ways affect the Ca2+ signaling machinery, those being ATP, bradykinin, ionomycin, CPA or thapsigargin, resulted in increased PC2 immunostaining in the PM. Exposing cells to the steroid hormone ouabain, known to trigger Ca2+ oscillations in kidney cells, caused increased PC2 in the PM and increased PM Ca2+ permeability. Intracellular Ca2+ buffering with BAPTA, inositol 1,4,5-trisphosphate receptor (InsP3R) inhibition with 2-aminoethoxydiphenyl borate (2-APB) or Ca2+/Calmodulin-dependent kinase inhibition with KN-93 completely abolished ouabain-stimulated PC2 translocation to the PM.

Conclusions

These novel findings demonstrate intracellular Ca2+-dependent PC2 trafficking in human and rat kidney cells, which may provide new insight into cyst formations in ADPKD.
Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the diabetes heart study
Authors: Adams Jeremy N , Cox Amanda J , Freedman Barry I , Langefeld Carl D , Carr J Jeffrey , Bowden Donald W
Published: February 2013

Background

Haptoglobin (HP) is an acute phase protein that binds to freely circulating hemoglobin. HP exists as two distinct forms, HP1 and HP2. The longer HP2 form has been associated with cardiovascular (CVD) events and mortality in individuals with type 2 diabetes (T2DM).

Methods

This study examined the association of HP genotypes with subclinical CVD, T2DM risk, and associated risk factors in a T2DM-enriched sample. Haptoglobin genotypes were determined in 1208 European Americans (EA) from 473 Diabetes Heart Study (DHS) families via PCR. Three promoter SNPs (rs5467, rs5470, and rs5471) were also genotyped.

Results

Analyses revealed association between HP2-2 duplication and increased carotid intima-media thickness (IMT; p = 0.001). No association between HP and measures of calcified arterial plaque were observed, but the HP polymorphism was associated with triglyceride concentrations (p = 0.005) and CVD mortality (p = 0.04). We found that the HP2-2 genotype was associated with increased T2DM risk with an odds ratio (OR) of 1.49 (95% CI 1.18-1.86, p = 6.59x10-4). Promoter SNPs were not associated with any traits.

Conclusions

This study suggests association between the HP duplication and IMT, triglycerides, CVD mortality, and T2DM in an EA population enriched for T2DM. Lack of association with atherosclerotic calcified plaque likely reflect differences in the pathogenesis of these CVD phenotypes. HP variation may contribute to the heritable risk for CVD complications in T2DM.
Prognostic value of early in-hospital glycemic excursion in elderly patients with acute myocardial infarction
Authors: Su Gong , Mi Shu-hua , Li Zhao , Tao Hong , Yang Hong-xia , Zheng Hong
Published: February 2013

Background

Acute phase hyperglycemia has been associated with increased mortality in patients with acute myocardial infarction (AMI). However, the predictive value of glycemic excursion for adverse outcome in elderly AMI patients is not clear. The aim of this study is to investigate the prognostic value of early in-hospital glycemic excursion and hemoglobin A1c (HbA1c) for one-year major adverse cardiac event (MACE) in elderly patients with AMI.

Methods

We studied 186 elderly AMI patients, whose clinical data were collected and the Global Registry of Acute Coronary Events (GRACE) risk score were calculated on admission. The fluctuations of blood glucose in patients were measured by a continuous glucose monitoring system (CGMS) for 72 hours. Participants were grouped into tertiles of mean amplitude of glycemic excursions (MAGE) and grouped into HbA1c levels (as ≥6.5% or <6.5%). The MACE of patients, including new-onset myocardial infarction, acute heart failure and cardiac death, was documented during one year follow-up. The relationship of MAGE and HbA1c to the incidence of MACE in elderly AMI patients was analyzed.

Results

In all participants, a higher MAGE level was associated with the higher GRACE score (r = 0.335, p < 0.001). The rate of MACE by MAGE tertiles (>3.94 mmol/L, 2.55-3.94 mmol/L or <2.55 mmol/L) was 30.2% vs. 14.8% vs. 8.1%, respectively (p = 0.004); by HbA1c category (≥6.5% vs. <6.5%) was 22.7% vs. 14.4%, respectively (p = 0.148). Elderly AMI patients with a higher MAGE level had a significantly higher cardiac mortality. In multivariable analysis, high MAGE level was significantly associated with incidence of MACE (HR 3.107, 95% CI 1.190-8.117, p = 0.021) even after adjusting for GRACE risk score, but HbA1c was not.

Conclusions

The early in-hospital intraday glycemic excursion may be an important predictor of mortality and MACE even stronger than HbA1c in elderly patients after AMI.
Upper torso and pelvis linear velocity during the downswing of elite golfers
Authors: Beak Seung-Hui , Choi Ahnryul , Choi Seung-Wook , Oh Seung Eel , Mun Joung Hwan , Yang Heegoo , Sim Taeyong , Song Hae-Ryong
Published: February 2013

Background

During a golf swing, analysis of the movement in upper torso and pelvis is a key step to determine a motion control strategy for accurate and consistent shots. However, a majority of previous studies that have evaluated this movement limited their analysis only to the rotational movement of segments, and translational motions were not examined. Therefore, in this study, correlations between translational motions in the 3 axes, which occur between the upper torso and pelvis, were also examined.

Methods

The experiments were carried out with 14 male pro-golfers (age: 29 ± 8 years, career: 8.2 ± 4.8years) who registered in the Korea Professional Golf Association (KPGA). Six infrared cameras (VICON; Oxford Metrics, Oxford, UK) and SB-Clinc software (SWINGBANK Ltd, Korea) were used to collect optical marker trajectories. The center of mass (CoM) of each segment was calculated based on kinematic principal. In addition, peak value of CoM velocity and the time that each peak occurred in each segment during downswing was calculated. Also, using cross-correlation analysis, the degree of coupling and time lags of peak values occurred between and within segments (pelvis and upper torso) were investigated.

Results

As a result, a high coupling strength between upper torso and pelvis with an average correlation coefficient = 0.86 was observed, and the coupling between segments was higher than that within segments (correlation coefficient = 0.81 and 0.77, respectively).

Conclusions

Such a high coupling at the upper torso and pelvis can be used to reduce the degree of motion control in the central nervous system and maintain consistent patterns in the movement. The result of this study provides important information for the development of optimal golf swing movement control strategies in the future.
Phytanic acid stimulates glucose uptake in a model of skeletal muscles, the primary porcine myotubes
Authors: Che Brita N , Oksbjerg Niels , Hellgren Lars I , Nielsen Jacob H , Young Jette F
Published: February 2013

Background

Phytanic acid (PA) is a chlorophyll metabolite with potentials in regulating glucose metabolism, as it is a natural ligand of the peroxisome proliferator-activated receptor (PPAR) that is known to regulate hepatic glucose homeostasis. This study aimed to establish primary porcine myotubes as a model for measuring glucose uptake and glycogen synthesis, and to examine the impact of physiological amounts of PA on glucose uptake and glycogen synthesis either alone or in combination with insulin.

Methods

Porcine satellite cells were cultured into differentiated myotubes and tritiated 2-deoxyglucose (2-DOG) was used to measure glucose uptake, in relation to PA and 2-DOG exposure times and also in relation to PA and insulin concentrations. The MIXED procedure model of SAS was used for statistical analysis of data.

Results

PA increased glucose uptake by approximately 35%, and the presence of insulin further increased the uptake, but this further increase in uptake was non- additive and less pronounced at high insulin concentrations. There was no effect of PA alone on glycogen synthesis, while the insulin stimulation of glycogen was increased by 20% in the presence of PA. PA neither stimulated glucose uptake nor glycogen synthesis in insulin-resistant myotubes generated by excess glucose exposure.

Conclusions

Primary porcine myotubes were established as a model of skeletal muscles for measuring glucose uptake and glycogen synthesis, and we showed that PA can play a role in stimulating glucose uptake at no or inadequate insulin concentrations.
Modulating the inflammatory properties of activated microglia with Docosahexaenoic acid and Aspirin
Authors: Pettit Lauren K , Varsanyi Christopher , Tadros James , Vassiliou Evros
Published: February 2013

Background

Microglia are considered the “resident macrophages” of the brain. When in their resting state, microglia perform routine maintenance and immune surveillance. Once activated, either by injury or an immune stimulus, microglia secrete a variety of pro-inflammatory molecules, such as Nitric Oxide, superoxide, and inflammatory cytokines. Up-regulation of pro-inflammatory molecules is transient, and does not cause neurodegeneration. However, if up-regulation lasts for an extended period of time, neurodegeneration ensues.

Many neurodegenerative diseases are characterized by chronic inflammation due to microglial activation. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been proposed as possible preventative treatments for neurodegenerative diseases, due to their anti-inflammatory properties. Docosahexaenoic Acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that has potent anti-inflammatory properties. This research work sought to elucidate whether microglial activation can be modulated by combining Aspirin, a classical NSAID, with Docosahexaenoic Acid, a natural anti-inflammatory agent. The combined ability of Aspirin and DHA to modulate microglial activation was determined in the context of pro-inflammatory cytokines, Nitric Oxide levels, as well as total Glutathione levels.

Results

Docosahexaenoic Acid increased total Glutathione levels in microglia cells and enhanced their anti-oxidative capacity. It reduced production of the pro-inflammatory cytokines TNF-α and IL-6 induced through TLR-3 and TLR-4 activation. Furthermore, it reduced production of Nitric Oxide. Aspirin showed similar anti-inflammatory effects with respect to TNF-α during TLR-3 and TLR-7 stimulation. Aspirin did not show any redection in terms of Nitric Oxide production. Combination of Aspirin and Docosahexaenoic Acid showed augmentation in total Glutathione production during TLR-7 stimulation as well as a reduction in IL-6, TNF-α and Nitric Oxide.

Conclusions

Collectively, these findings highlight the combination of Docosahexaenoic Acid and Aspirin as a possible measure against inflammation of the nervous system, thus leading to protection against neurodegenerative diseases with an inflammatory etiology.
The role of angiogenic factors and their soluble receptors in acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) associated with critical illness
Authors: Wada Takeshi , Jesmin Subrina , Gando Satoshi , Yanagida Yuichiro , Mizugaki Asumi , Sultana Sayeeda Nusrat , Zaedi Sohel , Yokota Hiroyuki
Published: February 2013

Background

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by a disruption of the endothelium and alveolar epithelial barriers involving increased microvascular permeability, thus resulting in the set of protein-rich pulmonary edema. Angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)/VEGF-receptor (VEGFR) and the angiopoietin (Ang)/Tie2 signaling pathways, play pivotal roles in both angiogenesis and microvascular permeability. The aim of the study was to assess the relationship between angiogenic factors, their soluble receptors and ALI/ARDS associated with critically ill patients, including sepsis, severe trauma, and post-cardiac arrest syndrome (PCAS).

Methods

One hundred fifty-nine critically ill patients, including 50 patients with sepsis, 57 patients with severe trauma and 52 resuscitated after out-of-hospital cardiac arrest, were divided into three subgroups: including 25 ALI patients, 101 ARDS patients and 22 non-ALI/ARDS patients. The serum levels of angiogenic factors were measured at the time of admission (day 1), as well as day 3 and day 5 and then were compared among the ALI, ARDS and non-ALI/ARDS groups. Their predictive values for developing ALI/ARDS and 28-day mortality were evaluated.

Results

Higher levels of sVEGFR1 and Ang2 were observed in the ALI and ARDS patients than in the non-ALI/ARDS patients during the entire study period. The Ang2/Ang1 ratio in the ARDS group was also significantly higher than that in the non-ALI/ADRS group. The sVEGFR2 levels in the ARDS group on day 1 were significantly lower than those of the non-ALI/ADRS group. In addition, significant positive correlations were seen between the sVEGFR1, Ang2, Ang2/Ang1, and the development of ALI/ARDS in critical illness. There were also significant negative correlations between the minimal value of sVEGFR2, the maximal value of Ang1 and the ALI/ARDS group. In particular, sVEGFR2 and Ang2 were independent predictors of developing ALI/ARDS. Moreover, Ang2 and sVEGFR2 also independently predicted the mortality in ALI/ARDS patients.

Conclusions

Angiogenic factors and their soluble receptors, particularly sVEGFR2 and Ang2, are thus considered to be valuable predictive biomarkers in the development of ALI/ARDS associated with critical illness and mortality in ALI/ARDS patients.
Prognostication of prostate cancer based on TOP2A protein and gene assessment: TOP2A in prostate cancer
Authors: de Resende Marina França , Vieira Samantha , Chinen Ludmilla Thomé Domingos , Chiappelli Francesco , da Fonseca Francisco Paulo , Guimarães Gustavo Cardoso , Soares Fernando Augusto , Neves Ivan , Pagotty Simone , Pellionisz Peter A , Barkhordarian Andre , Brant Xenia , Rocha Rafael Malagoli
Published: February 2013

Background

TOP2A encodes for topoisomerase IIα, a nuclear enzyme that controls DNA topological structure and cell cycle progression. This enzyme is a marker of cell proliferation in normal and neoplastic tissues; however, little information is available about its expression in prostate cancer (PCa).

Methods

Immunohistochemistry (IHC) was automated using mouse monoclonal antibody against TOP2A (clone SWT3D1; DAKO, Carpenteria, CA, USA) at dilution 1:800 and Flex Plus detection system in autostainer 48Ultra (DAKO). FISH was performed using TOP2A (17q21)/ CEP17 probe kit (Kreateck Biotechnology, San Diego, CA, USA). Biochemical and pathological data from 193 patients with PCa were retrieved for the analysis, whose significance was considered when p < 0.05. Also, fractal analysis was performed in a subset of 20 randomly selected cases.

Results

TOP2A protein expression correlated with higher Gleason scores and higher levels of preoperative PSA (p = 0.018 and p = 0.011). Patients with higher levels of TOP2A presented shorter biochemical recurrence-free survival (BRFS) (p = 0.001). In multivariate analysis, we found that TOP2A remained an independent prognostic factor of BRFS, with a relative risk of 1.98 (p = 0.001; 95% CI, 1.338–2.93); thus, cases that expressed high levels of this enzyme had a shorter BRFS compared with TOP2A-negative or TOP2A-low cases. No alterations in TOP2A gene status nor correlation between FISH and IHC results were observed. Concerning fractal analysis, patients who expressed higher levels of TOP2A have angiolymphatic invasion and presented higher Gleason scores (p = 0.033 and p = 0.025, respectively). Also, patients with higher expression of TOP2A presented shorter BRFS (p = 0.001).

Conclusions

This is the first study to perform TOP2A protein and gene digital assessment and fractal analysis in association with BRFS in a large series of PCa. Also, we show that TOP2A gene copy number alterations are not observed in this type of tumor. So, higher protein expression of TOP2A is not related to gene amplification in PCa. Furthermore, TOP2A protein assessment has prognostic importance and, due to its relation with poor outcome, TOP2A IHC evaluation in the biopsy can represent an important tool for selecting the most suitable surgical and clinical approach for patients with PCa.
Efficient PbS/CdS co-sensitized solar cells based on TiO2 nanorod arrays
Authors: Li Yitan , Wei Lin , Chen Xiya , Zhang Ruizi , Sui Xing , Chen Yanxue , Jiao Jun , Mei Liangmo
Published: February 2013

Narrow bandgap PbS nanoparticles, which may expand the light absorption range to the near-infrared region, were deposited on TiO2 nanorod arrays by successive ionic layer adsorption and reaction method to make a photoanode for quantum dot-sensitized solar cells (QDSCs). The thicknesses of PbS nanoparticles were optimized to enhance the photovoltaic performance of PbS QDSCs. A uniform CdS layer was directly coated on previously grown PbS-TiO2 photoanode to protect the PbS from the chemical attack of polysulfide electrolytes. A remarkable short-circuit photocurrent density (approximately 10.4 mA/cm2) for PbS/CdS co-sensitized solar cell was recorded while the photocurrent density of only PbS-sensitized solar cells was lower than 3 mA/cm2. The power conversion efficiency of the PbS/CdS co-sensitized solar cell reached 1.3%, which was beyond the arithmetic addition of the efficiencies of single constituents (PbS and CdS). These results indicate that the synergistic combination of PbS with CdS may provide a stable and effective sensitizer for practical solar cell applications.
Room temperature-synthesized vertically aligned InSb nanowires: electrical transport and field emission characteristics
Authors: Kuo Cheng-Hsiang , Wu Jyh-Ming , Lin Su-Jien
Published: February 2013

Vertically aligned single-crystal InSb nanowires were synthesized via the electrochemical method at room temperature. The characteristics of Fourier transform infrared spectrum revealed that in the syntheses of InSb nanowires, energy bandgap shifts towards the short wavelength with the occurrence of an electron accumulation layer. The current–voltage curve, based on the metal–semiconductor–metal model, showed a high electron carrier concentration of 2.0 × 1017 cm−3 and a high electron mobility of 446.42 cm2 V−1 s−1. Additionally, the high carrier concentration of the InSb semiconductor with the surface accumulation layer induced a downward band bending effect that reduces the electron tunneling barrier. Consequently, the InSb nanowires exhibit significant field emission properties with an extremely low turn-on field of 1.84 V μm−1 and an estimative threshold field of 3.36 V μm−1.
Theory of fractional hybrid differential equations with linear perturbations of second type
Authors: Lu Hongling , Sun Shurong , Yang Dianwu , Teng Houshan
Published: February 2013

In this paper, we develop the theory of fractional hybrid differential equations with linear perturbations of second type involving Riemann-Liouville differential operators of order

0
<
q
<
1

. An existence theorem for fractional hybrid differential equations is proved under the φ-Lipschitz condition. Some fundamental fractional differential inequalities which are utilized to prove the existence of extremal solutions are also established. Necessary tools are considered and the comparison principle which will be useful for further study of qualitative behavior of solutions is proved.

MSC:34A40, 34A12, 34A99.
Winner and loser effects are modulated by hormonal states
Authors: Earley Ryan L , Lu Chung-Kai , Lee I-Han , Wong Stephanie C , Hsu Yuying
Published: February 2013

Introduction

Many animals use information acquired from recent experiences to modify their responses to new situations. Animals’ decisions in contests also depend on their previous experience: after recent victories individuals tend to behave more aggressively and after defeats more submissively. Although these winner and/or loser effects have been reported for animals of different taxa, they have only recently been shown to be flexible traits, which can be influenced by extrinsic factors. In a mangrove killifish (Kryptolebias marmoratus), for instance, individuals which lost an earlier contest were more likely than others to alter contest decisions after a recent win/loss. This result suggests that individuals perceiving themselves to have worse fighting abilities are more inclined to adjust contest strategy based on new information. If this is the case, an individual’s propensity to modify behaviour after a win/loss might also be modulated by intrinsic mechanisms related to its ability to fight. Stress and sex steroid hormones are often associated with an individual’s contest behaviour and performance, so, in this study, we tested the hypothesis that an individual’s propensity to change behaviour after wins or losses also depends on its hormonal state.

Results

Our results show that an individual’s propensity to adjust contest decisions after wins and losses does depend on its hormonal state: individuals with lower levels of cortisol (F), testosterone (T) and 11-ketotestosterone (KT) are more receptive than others to the influence of recent contest experiences, especially losing experiences, and the influences last longer. Furthermore, although winning and losing experiences resulted in significant changes in behaviour, they did not bring about a significant change in the levels of F, T, KT or oestradiol (E2).

Conclusions

This study shows that an individual’s receptivity to the influence of recent wins and losses is modulated by its internal state, as well as by extrinsic factors. Individuals with hormonal profiles corresponding to lower aggressiveness and a reduced likelihood of winning were more likely to alter contest decisions after a recent win/loss. The results also suggest that F, T, KT and E2 are not the primary physiological mechanisms mediating winner-loser effects in this fish.
Australian families living with rare disease: experiences of diagnosis, health services use and needs for psychosocial support
Authors: Anderson Matilda , Elliott Elizabeth J , Zurynski Yvonne A
Published: February 2013

Background

Families of children living with a rare disease report significant health and social burden, however, few studies have systematically examined family needs by using validated tools to assess the scope and extent of this burden. Our aim was to develop a comprehensive survey to assess health, psychosocial and financial impacts on Australian families caring for a child with a rare disease.

Methods

We developed a self-administered survey for parents/carers incorporating pre-validated tools. The survey included questions about experiences of diagnosis, health services use and needs, needs for peer and financial supports. Forty-seven families attending the state-wide Genetic Metabolic Disorders Service at the Children’s Hospital at Westmead, Sydney were invited to participate.

Results

Of 46 families who received the survey, 30 (65%) completed it. Most (93%) found the survey acceptable and relevant (91%). Patients were 1–17 years old, 14 (47%) male, and 12 (40%) non-Caucasian. Eighteen (60%) had a lysosomal storage disease and 12(40%) had a mitochondrial disorder. Eleven (38%) saw 3–5 doctors and four (14%) saw 6–10 doctors before receiving the correct diagnosis; 43% felt diagnosis was delayed. Four (13%) were dissatisfied with the way diagnosis was given, due to insensitive style of communication, inadequate information and psychological support. Psychosocial impact was moderate to high for 90% of families and the level of impact was not dependent on the level of health functioning of the child. Twenty-six (87%) wanted, but only 13(43%) received, information about peer-support groups. The 30 children accounted for 168 visits to general practitioners and 260 visits to specialist doctors; 21 (70%) children had at least one admission to hospital, including one who had 16 admissions in the previous 12 months. Most families (77%) received financial assistance but 52% believed this was insufficient. Families benefited from a specialised multi-disciplinary clinic but called for patient-held electronic medical records.

Conclusions

Australian families caring for children with genetic metabolic disorders are adversely impacted by delays in diagnosis, lack of easy access to peer support groups and lack of psychological support. Further research is needed to estimate economic impact and to analyse health service delivery models for children with rare diseases in Australia.
Increased heart rate variability but no effect on blood pressure from 8 weeks of hatha yoga – a pilot study
Authors: Papp Marian E , Lindfors Petra , Storck Niklas , Wändell Per E
Published: February 2013

Background

Yoga exercises are known to decrease stress and restore autonomic balance. Yet knowledge about the physiological effects of inversion postures is limited. This study aimed to investigate the effects of inversion postures (head below the heart) on blood pressure (BP) and heart rate variability (HRV).

Methods

Twelve healthy women and men took part in an 8-week yoga program (60 min once a week). BP was measured with an automatic Omron mx3 oscillometric monitoring device and HRV with a Holter 24-hour ECG at baseline and 8 weeks after the intervention.

Results

There was no significant effect of inversion postures on BP. Nine out of 12 participants showed a significant increase in HRV (p < 0.05) at night (2 hours) on pNN50% (12.7 ± 12.5 to 18.2 ± 13.3). There were no significant changes in other HRV measures such as NN50, LF, HF, LF/HF ratio, LF normalized units (n.u.), HF n.u. and RMSSD.

Conclusion

Eight weeks of hatha yoga improved HRV significantly which suggests an increased vagal tone and reduced sympathetic activity.
Induction of long-lasting protective immunity against Toxoplasma gondii in BALB/c mice by recombinant surface antigen 1 protein encapsulated in poly (lactide-co-glycolide) microparticles
Authors: Chuang Shu-Chun , Ko Jing-Chun , Chen Chaio-Ping , Du Jia-Tze , Yang Chung-Da
Published: February 2013

Background

Current development efforts of subunit vaccines against Toxoplasma gondii, the etiological agent of toxoplasmosis, have been focused mainly on tachyzoite surface antigen 1 (SAG1). Since microparticles made from poly (lactide-co-glycolide) (PLG) polymers have been developed as safe, potent adjuvants or delivery systems, we aimed to encapsulate recombinant SAG1 (rSAG1) with the PLG polymers to prepare PLG-encapsulated rSAG1 (PLG-rSAG1) microparticles that would sustain rSAG1 release and generate long-lasting protective immunity against T. gondii in BALB/c mice.

Methods

In the present study, rSAG1 was encapsulated into PLG microparticles by the double emulsion method. PLG-rSAG1 microparticles were then intraperitoneally injected twice at a 14-day interval into BALB/c mice. We examined the ability of PLG-rSAG1 microparticles to induce and prolong effective anti-Toxoplasma immune responses, in comparison with rSAG1 formulated with a Vet L-10 adjuvant (rSAG1 (Vet L-10)). Eight weeks after the last immunization, protective activities were also evaluated after a lethal subcutaneous challenge of 1x104 live T. gondii tachyzoites.

Results

PLG-rSAG1 microparticles, 4.25~6.58 micrometers in diameter, showed 69%~81% entrapment efficiency. The amount of released rSAG1 protein from microparticles increased gradually over a 35-day period and the protein still retained native SAG1 antigenicity. Intraperitoneal vaccination of mice with the microparticles resulted in enhanced SAG1-specific IgG titers as well as lymphocyte proliferation and, more importantly, these enhanced activities were maintained for 10 weeks. In addition, eight weeks after the last immunization, maximum production of gamma interferon was detected in mice immunized with PLG-rSAG1 microparticles. Furthermore, 80% (8/10) of mice immunized with PLG-rSAG1 microparticles survived at least 28 days after a lethal subcutaneous tachyzoite challenge.

Conclusions

Encapsulation of rSAG1 into PLG microparticles preserves the native SAG1 antigenicity and sustains the release of rSAG1 from microparticles. PLG-rSAG1 microparticles can effectively induce not only significant long-lasting SAG1-specific humoral and cell-mediated immune responses but also high protection against T. gondii tachyzoite infection. Our study provides a valuable basis for developing long-lasting vaccines against T. gondii for future use in humans and animals.