bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological demands of mountain rescue work
Authors: Callender Nigel , Ellerton John , Macdonald Jamie Hugo 
Published: September 2011

ObjectiveTo characterise the physical fitness of mountain rescue (MR) volunteers and the physical demands of a typical MR callout.MethodsEight MR volunteers (age ± SD: 45.5 ± 8.9 years) completed a laboratory-based treadmill exercise test to exhaustion. One week later subjects completed a field-based simulated callout to retrieve a casualty by stretcher. In both studies exercise intensity was evaluated by determination of oxygen uptake and other cardiovascular measures.ResultsThe maximal oxygen uptake of the participants was 53 ml/kg/min (95% CI 45 to 60). In an unassisted callout, a typical rucksack load was 17% of body mass. Ascent time was 56 min (95% CI 40 to 72), of which 82% (95% CI 66% to 98%) was completed at hard or very hard intensity (above the respiratory compensation point). Descent time with a stretcher was 58 min (95% CI 52 to 64), of which only 6% (95% CI −4% to 16%) was completed at hard or very hard intensity. Correlations between heart rate and oxygen uptake were similar (p=0.254 by analysis of variance) during laboratory (r=0.72) and field testing, especially for the ascent (r=0.75).ConclusionsMountain rescuers generally have high levels of physical fitness and are required to perform at very hard intensity for the majority of the ascent to a casualty. Heart rate is a simple yet valid measure of exercise intensity in MR personnel. These findings highlight important information on the unique physical demands faced by MR volunteers and provide direction for future research, volunteer selection and training.
Activation of T Lymphocytes in Atherosclerotic Plaques
Authors: Grivel Jean-Charles , Ivanova Oxana , Pinegina Natalia , Blank Paul S. , Shpektor Alexander , Margolis Leonid B. , Vasilieva Elena 
Published: September 2011

Objective—
To decipher the immunologic mechanisms of plaque maturation and rupture, it is necessary to analyze the phenotypes and distribution of individual lymphocytes that migrate to the plaques, as well as their activation at different stages of plaque formation.

Methods and Results—

We developed a protocol to isolate plaque-residing immune cells and analyze their status using polychromatic flow cytometry. We found that the composition and phenotype of T lymphocytes in the plaques differs from that in blood. CD4 and, in particular, CD8
+
T cells in plaques are highly activated; the fraction of CD8 T cells coexpressing CD25 and human leukocyte antigen-D related in plaques was 6 times as large as in blood.

Conclusion—
The first flow-cytoanalysis of individual T cells in atherosclerotic plaques indicates that plaques represent a separate immunologic compartment from blood with lymphocytes characterized by a high level of T-cell activation, which is compatible with the presence of antigen(s) that trigger infiltration activation of these cells. The ability to isolate and characterize these cells may lead to the identification of such antigens.
α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Attenuates Early Brain Injury in a Perforation Model of Subarachnoid Hemorrhage in Rats
Authors: Duris Kamil , Manaenko Anatol , Suzuki Hidenori , Rolland William B. , Krafft Paul R. , Zhang John H. 
Published: September 2011

Background and Purpose—
Early brain injury is an important pathological process after subarachnoid hemorrhage (SAH). The goal of this study was to evaluate whether the α7 nicotinic acetylcholine receptor (α7nAChR) agonist PNU-282987 attenuates early brain injury after SAH and whether α7nAChR stimulation is associated with down-regulation of caspase activity via phosphatidylinositol 3-kinase-Akt signaling.

Methods—
The perforation model of SAH was performed, and neurological score, body weight loss, and brain water content were evaluated 24 and 72 hours after surgery. Western blot and immunohistochemistry were used for quantification and localization of phosphorylated Akt and cleaved caspase 3. Neuronal cell death was quantified with TUNEL staining. α7nAChR antagonist methylcaconitine and phosphatidylinositol 3-kinase inhibitor wortmannin were used to manipulate the proposed pathway, and results were quantified with Western blot.

Results—
PNU-282987 improved neurological deficits both 24 and 72 hours after surgery and reduced brain water content in left hemispheres 24 hours after surgery. PNU-282987 significantly increased phosphorylated Akt levels and significantly decreased cleaved caspase 3 levels in ipsilateral hemispheres after SAH. Methylcaconitine and wortmannin reversed effects of treatment. Phosphorylated Akt and cleaved caspase 3 were colocalized to neurons in the ipsilateral basal cortex. Phosphorylated Akt was mainly localized in TUNEL-negative cells. PNU-282987 significantly reduced neuronal cell death in the ipsilateral basal cortex.

Conclusions—
α7nAChR stimulation decreased neuronal cell death and brain edema and improved neurological status in a rat perforation model of SAH. α7nAChR stimulation is associated with increasing phosphorylation of Akt and decreasing cleaved caspase 3 levels in neurons.
Reduced Efficacy of Circulating Costimulatory Cells After Focal Cerebral Ischemia
Authors: Hug Andreas , Liesz Arthur , Muerle Bettina , Zhou Wei , Ehrenheim Julia , Lorenz Alexander , Dalpke Alexander , Veltkamp Roland 
Published: September 2011

Background and Purpose—
Cerebral ischemia is ensued by a cellular immune depression syndrome. The postischemic functional capacity of T lymphocytes is controversial, and interactions between leukocyte subsets are largely unknown. Understanding the immunologic interplay between antigen-presenting cells and lymphocytes as well as between distinct lymphocyte subsets after stroke might be of clinical/therapeutic significance because animal data argue for a cerebroprotective effect of, for example, CD4+CD25+ regulatory T cells.

Methods—
Ex vivo CD4+ T cell proliferation was analyzed in experimental and human stroke using fluorescence activated cell sorter analysis. To investigate suppressive effects of CD4+CD25+ regulatory T cells as well as the influence of costimulatory cells on CD4+ T cell proliferation, subsets were magnetically sorted before proliferation assay setup.

Results—

After stroke: (1) proliferation of mouse and human CD4+ T cells on T cell receptor stimulation was unaltered; (2) the suppressive effect of CD4+CD25+ regulatory T cells in mouse and man was unaltered; and (3) efficacy of circulating costimulatory cells from stroke animals was reduced by a mean of 0.6 (SEM 0.1,
P
=0.001) CD4+ T cell division numbers compared with sham-treated animals.

Conclusions—
Reduced costimulatory efficacy of circulating costimulatory cells in mice is an important feature of stroke-induced immunodepression. Understanding the interplay of costimulatory cells and responder T cells (eg, CD4+ T cells or CD4+CD25+ regulatory T cells) after stroke may offer new insights into the prevention of secondary inflammatory damage to the brain and help to guide new therapeutic strategies.
Velocity Criteria for Intracranial Stenosis Revisited
Authors: Zhao Limin , Barlinn Kristian , Sharma Vijay K. , Tsivgoulis Georgios , Cava Luis F. , Vasdekis Spyros N. , Teoh Hock Luen , Triantafyllou Nikos , Chan Bernard P.L. , Sharma Arvind , Voumvourakis Konstantinos , Stamboulis Elefterios , Saqqur Maher , Harrigan Mark R. , Albright Karen C. , Alexandrov Andrei V. 
Published: September 2011

Background and Purpose—
Intracranial atherosclerotic disease is associated with a high risk of stroke recurrence. We aimed to determine accuracy of transcranial Doppler screening at laboratories that share the same standardized scanning protocol.

Methods—
Patients with symptoms of cerebral ischemia were prospectively studied. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) criteria were used for identification of ≥50% stenosis. We determined velocity cutoffs for ≥70% stenosis on digital subtraction angiography by Warfarin–Aspirin Symptomatic Intracranial Disease criteria and evaluated novel stenotic/prestenotic ratio and low-velocity criteria.

Results—

A total of 102 patients with intracranial atherosclerotic disease (age 57±13 years; 72% men; median National Institutes of Health Stroke Scale 3, interquartile range 6) provided 690 transcranial Doppler/digital subtraction angiography vessel pairs. On digital subtraction angiography, ≥50% stenosis was found in 97 and ≥70% stenosis in 62 arteries. Predictive values for transcranial Doppler SONIA criteria were similar (
P
>0.9) between middle cerebral artery (sensitivity 78%, specificity 93%, positive predictive value 73%, negative predictive value 94%, and overall accuracy 90%) and vertebral artery/basilar artery (69%, 98%, 88%, 93%, and 92%). As a single velocity criterion, most sensitive mean flow velocity thresholds for ≥70% stenosis were: middle cerebral artery >120 cm/s (71%) and vertebral artery/basilar artery >110 cm/s (55%). Optimal combined criteria for ≥70% stenosis were: middle cerebral artery >120 cm/s, or stenotic/prestenotic ratio ≥3, or low velocity (sensitivity 91%, specificity 80%, receiver operating characteristic 0.858), and vertebral artery/basilar artery >110 cm/s or stenotic/prestenotic ratio ≥3 (60%, 95%, 0.769, respectively).

Conclusions—
At laboratories with a standardized scanning protocol, SONIA mean flow velocity criteria remain reliably predictive of ≥50% stenosis. Novel velocity/ratio criteria for ≥70% stenosis increased sensitivity and showed good agreement with invasive angiography.
Low-Dose Intravenous Recombinant Tissue-Type Plasminogen Activator Therapy for Patients With Stroke Outside European Indications
Authors: Koga Masatoshi , Shiokawa Yoshiaki , Nakagawara Jyoji , Furui Eisuke , Kimura Kazumi , Yamagami Hiroshi , Okada Yasushi , Hasegawa Yasuhiro , Kario Kazuomi , Okuda Satoshi , Endo Kaoru , Miyagi Tetsuya , Osaki Masato , Minematsu Kazuo , Toyoda Kazunori 
Published: September 2011

Background and Purpose—
The purpose of this study was to determine the safety and efficacy of intravenous recombinant tissue-type plasminogen activator (0.6 mg/kg alteplase) within 3 hours of stroke onset in Japanese patients outside the indications in the European license.

Methods—
Of the 600 patients who were treated with recombinant tissue-type plasminogen activator, 422 met the inclusion criteria of the European license (IN group) and 178 did not (OUT group).

Results—
The OUT group was inversely associated with any intracerebral hemorrhage (adjusted OR, 0.50; 95% CI, 0.29–0.84), positively associated with an unfavorable outcome (2.48; 1.55–3.94) and mortality (2.04; 1.02–4.04), and not associated with symptomatic intracerebral hemorrhage (0.53; 0.11–1.79) or complete independency (0.65; 0.40–1.03) after multivariate adjustment.

Conclusions—
Functional and vital outcomes 3 months after low-dose recombinant tissue-type plasminogen activator in patients outside the European indications were less favorable compared with those included in the indications; however, the risk of intracerebral hemorrhage was not.
Inhibition of TLR8- and TLR4-induced Type I IFN induction by alcohol is different from its effects on inflammatory cytokine production in monocytes
Authors: Pang Maoyin , Bala Shashi , Kodys Karen , Catalano Donna , Szabo Gyongyi 
Published: September 2011

AbstractBackgroundProlonged alcohol consumption is a significant co-factor in the progression of chronic viral infections including hepatitis C and HIV, which are both single-stranded RNA viruses. Toll like receptor 8 (TLR8), a pattern recognition receptor expressed in monocytes, senses viral single stranded RNA as a danger signal and leads to the induction of Type I interferon (IFN) as well as the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha). Lipopolysaccharide (LPS), a Toll like receptor 4 (TLR4) ligand, was shown to affect inflammatory cell activation after alcohol consumption and in HIV and HCV infections. Here we hypothesized that alcohol exposure modulates TLR8- and TLR4-ligand-induced monocyte activation and affects both type I IFN and inflammatory cytokine induction.ResultsThe TLR8 ligand, CL075, as well as the TLR4 ligand, LPS, resulted in a significant induction of TNF alpha both at the mRNA and protein levels in human monocytes. We found that both acute and prolonged alcohol treatment resulted in inhibition of type I IFN induction by either TLR8 or TLR4 ligands in human monocytes at the protein and mRNA levels. In contrast to Type I IFN production, the effects of acute and prolonged alcohol were different on inflammatory cytokine activation after TLR8 or TLR4 ligand stimulation. Acute alcohol inhibited TLR8- or TLR4-induced TNF alpha protein and mRNA induction while it augmented IL-10 production in monocytes. In contrast, prolonged alcohol treatment augmented TNF alpha without affecting IL-10 production significantly in response to either TLR8 or TLR4 ligand stimulation.ConclusionsThese novel results suggest first, that alcohol has a profound inhibitory effect on Type I IFN induction regardless of intracellular (TLR8) or cell surface-derived (TLR4) danger signals. Second, both acute and prolonged alcohol exposure can inhibit antiviral Type I IFN pathway activation. Third, the opposite effects of acute (inhibitory) and prolonged alcohol (augmentation) treatment on pro-inflammatory cytokine activation extend to TLR8-induced signals beyond the previously shown TLR4/LPS pathway.
Comparison of PCR ribotyping and multilocus variable-number tandem-repeat analysis (MLVA) for improved detection of Clostridium difficile
Authors: Wei Hsiao L , Kao Chun Wei , Wei Sung H , Tzen Jason TC , Chiou Chien S 
Published: September 2011

Abstract

Background
Polymerase chain reaction (PCR) ribotyping is one of the globally accepted techniques for defining epidemic clones of Clostridium difficile and tracing virulence-related strains. However, the ambiguous data generated by this technique makes it difficult to compare data attained from different laboratories; therefore, a portable technique that could supersede or supplement PCR ribotyping should be developed. The current study attempted to use a new multilocus variable-number tandem-repeat analysis (MLVA) panel to detect PCR-ribotype groups. In addition, various MLVA panels using different numbers of variable-number tandem-repeat (VNTR) loci were evaluated for their power to discriminate C. difficile clinical isolates.

Results
At first, 40 VNTR loci from the C. difficile genome were used to screen for the most suitable MLVA panel. MLVA and PCR ribotyping were implemented to identify 142 C. difficile isolates. Groupings of serial MLVA panels with different allelic diversity were compared with 47 PCR-ribotype groups. A MLVA panel using ten VNTR loci with limited allelic diversity (0.54-0.83), designated MLVA10, generated groups highly congruent (98%) with the PCR-ribotype groups. For comparison of discriminatory power, a MLVA panel using only four highly variable VNTR loci (allelic diversity: 0.94-0.96), designated MLVA4, was found to be the simplest MLVA panel that retained high discriminatory power. The MLVA10 and MLVA4 were combined and used to detect genetically closely related C. difficile strains.

Conclusions
For the epidemiological investigations of C. difficile, we recommend that MLVA10 be used in coordination with the PCR-ribotype groups to detect epidemic clones, and that the MLVA4 could be used to detect outbreak strains. MLVA10 and MLVA4 could be combined in four multiplex PCR reactions to save time and obtain distinguishable data.
Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya
Authors: Githinji Nyawira , Maleche-Obimbo Elizabeth , Nderitu Moses , Wamalwa Dalton C , Mbori-Ngacha Dorothy 
Published: September 2011

Abstract

Background
In resource-limited settings, such as Kenya, access to CD4 testing is limited. Therefore, evaluation of less expensive laboratory diagnostics is urgently needed to diagnose immuno-suppression in children.

Objectives
To evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4 count in HIV-infected children.

Methods
This was a hospital based retrospective study conducted in three HIV clinics in Kisumu and Nairobi in Kenya. TLC, CD4 count and CD4 percent data were abstracted from hospital records of 487 antiretroviral-naïve HIV-infected children aged 1 month - 12 years.

Results
TLC and CD4 count were positively correlated (r = 0.66, p < 0.001) with highest correlation seen in children with severe immuno-suppression (r = 0.72, p < 0.001) and children >59 months of age (r = 0.68, p < 0.001). Children were considered to have severe immuno-suppression if they met the following WHO set CD4 count thresholds: age below 12 months (CD4 counts < 1500 cells/mm3), age 12-35 months (CD4 count < 750 cells/mm3), age 36-59 months (CD4 count < 350 cells/mm3, and age above 59 months (CD4 count < 200 cells/mm3). WHO recommended TLC threshold values for severe immuno-suppression of 4000, 3000, 2500 and 2000 cells/mm3 for age categories <12, 12-35, 36-59 and >59 months had low sensitivity of 25%, 23%, 33% and 62% respectively in predicting severe immuno-suppression using CD4 count as gold standard. Raising TLC thresholds to 7000, 6000, 4500 and 3000 cells/mm3 for each of the stated age categories increased sensitivity to 71%, 64%, 56% and 86%, with positive predictive values of 85%, 61%, 37%, 68% respectively but reduced specificity to 73%, 62%, 54% and 68% with negative predictive values of 54%, 65%, 71% and 87% respectively.

Conclusion
TLC is positively correlated with absolute CD4 count in children but current WHO age-specific thresholds had low sensitivity to identify severely immunosuppressed Kenyan children. Sensitivity and therefore utility of TLC to identify immuno-suppressed children may be improved by raising the TLC cut off levels across the various age categories.
Elevated placenta growth factor predicts pneumonia in patients with chronic obstructive pulmonary disease under inhaled corticosteroids therapy
Authors: Cheng Shih-Lung , Wang Hao-Chien , Cheng Shih-Jung , Yu Chong-Jen 
Published: September 2011

Abstract

Background
An increased incidence of pneumonia in patients with chronic obstructive pulmonary disease (COPD) under inhaled corticosteroid (ICS) therapy was noticed in previous studies. We performed a prospective study to elucidate the risk factors for the development of pneumonia in this group of patients.

Methods
A prospective, non-randomized study with patients diagnosed as having COPD from 2007 to 2008 identified in the Far Eastern Memorial Hospital were recruited. We recorded data for all patients, including clinical features and signs, demographic data, lung function status, and medications. Bio-markers such as C-reactive protein (CRP) and placenta growth factor (PlGF) were checked at first diagnosis. Every acute exacerbation was also recorded, especially pneumonia events, which were confirmed by chest radiography. Multivariate analysis was performed with stepwise logistic regression for pneumonia risk factors.

Results
274 patients were diagnosed as having COPD during the study period and 29 patients suffered from pneumonia with a prevalence of 10.6%. The rate was significantly higher in patients with ICS therapy (20/125, 16%) compared with those without ICS (9/149, 6%) (p = 0.02). We stratified ICS therapy into medium dose (500-999 ug/day fluticasone equivalent, 71 patients) and high dose (1000 ug/day and higher fluticasone equivalent, 54 patients) group. There was no statistical difference in the incidence of pneumonia between these two group (medium dose: 13/71, 18.3% vs. high dose: 7/54, 12.9%, p = 0.47). Multivariate analysis was performed to identify the risk factors for developing pneumonia and included forced expiratory volume in one second (FEV1) less than 40% of predicted (odds ratio (OR) 2.2, 95% confidence interval (CI): 1.1-6.9), ICS prescription ((OR) 2.4, 95% (CI): 1.3-8.7), the presence of diabetes mellitus (DM) (OR 2.6, 95% CI: 1.2-9.4) and PlGF level over 40 pg/L (OR 4.1, 95% CI: 1.5-9.9).

Conclusion
ICS therapy in patients with COPD increased the risk of pneumonia. However, there was no relationship between the incidence of pneumonia and dosage of ICS. Additionally, advanced COPD status, DM and elevated PlGF level were independent risk factors for the development of pneumonia. PlGF would be a good novel biomarker for predicting pneumonia.
Changes in vector species composition and current vector biology and behaviour will favour malaria elimination in Santa Isabel Province, Solomon Islands
Authors: Bugoro Hugo , Iro'ofa Charlie , Mackenzie Donna O , Apairamo Allen , Hevalao Watson , Corcoran Sarah , Bobogare Albino , Beebe Nigel W , Russell Tanya L , Chen Cheng-Chen , Cooper Robert D 
Published: September 2011

AbstractBackgroundIn 2009, Santa Isabel Province in the Solomon Islands embarked on a malaria elimination programme. However, very little is known in the Province about the anopheline fauna, which species are vectors, their bionomics and how they may respond to intensified intervention measures. The purpose of this study was to provide baseline data on the malaria vectors and to ascertain the possibility of successfully eliminating malaria using the existing conventional vector control measures, such as indoor residual spraying (IRS) and long-lasting insecticidal nets (LLIN).MethodsEntomological surveys were undertaken during October 2009. To determine species composition and distribution larval surveys were conducted across on the whole island. For malaria transmission studies, adult anophelines were sampled using human landing catches from two villages - one coastal and one inland.ResultsFiveAnophelesspecies were found on Santa Isabel:Anopheles farauti, Anopheles hinesorum,Anopheles lungae, Anopheles solomonis, andAnopheles nataliae.Anopheles hinesorumwas the most widespread species.Anopheles farautiwas abundant, but found only on the coast.Anopheles punctulatusandAnopheles koliensiswere not found.Anopheles farautiwas the only species found biting in the coastal village, it was incriminated as a vector in this study; it fed early in the night but equally so indoors and outdoors, and had a low survival rate.Anopheles solomoniswas the main species biting humans in the inland village, it was extremely exophagic, with low survival rates, and readily fed on pigs.ConclusionThe disappearance of the two major vectors,An. punctulatusandAn. koliensis, from Santa Isabel and the predominance ofAn. hinesorum, a non-vector species may facilitate malaria elimination measures.Anopheles farautiwas identified as the main coastal vector withAn. solomonisas a possible inland vector. The behaviour ofAn. solomonisis novel as it has not been previously found biting humans in any numbers. Both species appear to be short-lived, a characteristic that will limit their transmission potential. The early night feeding behaviour and a degree of outdoor biting seen inAn. farautiand particularly inAn. solomoniswill require that their response to IRS and LLIN be closely monitored. In coastal villages, where large, favourable breeding sites allow for high numbers ofAn. farautimay require the addition of larval control to achieve elimination.