bluuebunny/crossref_metadata_2025 huggingface dataset:
Value of homocysteine levels, troponin I, and score for neonatal acute physiology and perinatal extension II as early predictors of morbidity
Authors: Usluer Hale , Turker Gulcan , Gokalp Ayşe Sevim
Published: September 2011

Background:  Although the effects of cardiac troponin I (cTnI) have been documented in infants, the associations among the value of maternal and cord blood total homocysteine (Hcy) levels, cord blood cTnI and the score for neonatal acute physiology and perinatal extension II (SNAPPE‐II) values in infants have not been documented. The aim of this study was to determine the value of maternal total Hcy (mtHcy) and cord blood total Hcy (ctHcy) levels, cTnI and SNAPPE‐II as predictive factors of morbidity in newborns.

Methods:  Maternal and cord blood samples were routinely collected for analysis from all prospective participating volunteers. In this case–control study, both hospitalized (n= 71) and non‐hospitalized (n= 148) newborns were identified and followed until discharge.

Results:  Regression analysis revealed that pre‐eclampsia, gestational age, mtHcy and SNAPPE‐II values were significantly and independently associated with morbidity. Cord blood pH, ctHcy levels, SNAPPE‐II values, and pre‐eclampsia were associated with mtHcy levels. A similar association was found among cTnI, cord blood pH, mtHcy levels and ctHcy levels. The specificity and sensitivity values of mtHcy in predicting newborn morbidity were 62% and 78%, respectively, while the specificity and sensitivity values of SNAPPE‐II in predicting newborn morbidity were 96% and 97%, respectively.

Conclusions:  Elevated mtHcy levels were associated with cTnI, SNAPPE‐II values, cord blood gas, and neonatal morbidities. These results suggest that SNAPPE‐II may be an early predictor of morbidity after delivery and that elevated mtHcy levels may be an early prenatal biomarker of morbidity in newborns.
On the culture‐independent assessment of the diversity and distribution of Prochlorococcus
Authors: Mühling Martin
Published: September 2011

Much of our current knowledge on Prochlorococcus has derived from research on various genetic strains that have successfully been brought into culture. In particular, analyses of the complete genomes of 12 of those isolates have revealed the extent to which these strains differ from each other and the genetic means by which they are adapted to specific environmental niches. However, based on culture‐independent studies it is now clear that the strains currently available in diverse culture collections do not represent the true diversity of Prochlorococcus geno‐ and phenotypes. Potential alternatives to overcome the limitations caused by difficulties in isolating Prochlorococcus may be provided by the whole‐genome amplification of flow cytometrically isolated individual cells. The new information obtained in this way on various genetic types would, in turn, facilitate the correct identification of Prochlorococcus‐derived sequences within metagenomic sequence data sets. However, culture‐independent molecular population genetic approaches have also greatly furthered our understanding of the ecology and physiological capability of Prochlorococcus genetic groups. Based on this, I support the notion that such population genetic approaches to reveal the Prochlorococcus microdiversity are still of great value if appropriate marker genes providing a high genetic resolution are used. The comparison of the results from those culture‐independent analyses of environmental marine samples with those from the measurement of relevant environmental and biotic parameters still has potential to uncover further parameters that control Prochlorococcus diversity and distribution. In this context, I will discuss those markers that have so far been used in population genetic studies of Prochlorococcus, which is followed by outlining a general approach to evaluate their use for resolving microbial microdiversity and for phylogenetic identification.
Collie eye anomaly in Hokkaido dogs: case study
Authors: Mizukami Keijiro , Chang Hye‐Sook , Ota Mitsuharu , Yabuki Akira , Hossain Mohammand A. , Rahman Mohammad M. , Uddin Mohammad M. , Yamato Osamu
Published: September 2011

Objective  To describe a Hokkaido dog, one of the traditional Japanese breeds that was affected by Collie eye anomaly (CEA), and to report the genotype of this dog and the Hokkaido dog allelic frequency of the CEA‐associated mutation.

Case  A nine‐month‐old intact female Hokkaido dog without any obvious visual disturbance was diagnosed ophthalmoscopically with CEA. Severe choroidal hypoplasia was observed in the bilateral temporal area adjacent to the optic nerve head, appearing as whitish areas. Therefore, the dog was suspected of possessing the CEA‐associated mutation that was previously reported as an intronic 7.8‐kilo base deletion in the canine NHEJ1 gene.

Procedures  SYBR Green‐based real‐time PCR with a melting curve analysis, conventional PCR with agarose gel electrophoresis, and direct DNA sequencing were carried out to determine the genotype of the dog. Furthermore, a preliminary genotyping survey was carried out in 17 Hokkaido dogs from three kennels using the real‐time PCR method, and the pedigree relationships were analyzed using their pedigree papers.

Results  The Hokkaido dog affected by CEA was proven to possess the CEA‐associated mutation. Of these 17 Hokkaido dogs, 12 dogs were heterozygous carriers and five dogs were affected by this mutation. The preliminary genotyping survey and pedigree analysis demonstrated that the allelic frequency of the CEA‐associated mutation is very high in Hokkaido dogs.

Conclusion  These data suggest that the Hokkaido breed is highly susceptible to CEA because of the known CEA‐associated mutation much like the Collie‐related breeds.
The effect of loading in regenerated bone in dehiscence defects following a combined approach of bone grafting and GBR
Authors: Zambon Riccardo , Mardas Nikos , Horvath Attilla , Petrie Aviva , Dard Michel , Donos Nikos
Published: September 2011

Objectives

To evaluate by histology the effect of loading on the regenerated bone at dehiscence type defects around implants when treated with a combined approach of bone grafting and guided bone regeneration (GBR).

Materials and methods

In twelve Göttingen mini‐pigs, the lower premolars and first molars were extracted and the alveolar process was reduced in width. After 3 months, two Straumann SLActive® (Straumann AG, Basel, Switzerland) implants were placed in each hemi‐mandible. Twelve implants were placed into the reduced alveolar ridge (group P) with no further defect or treatment on the site, while on 36 implants, buccal dehiscence defects were created and treated as follows: Group T1: synthetic bone substitute (Straumann Bone Ceramic®, SBC, Straumann AG). Group T2: SBC with a polyethylene glycol membrane (Straumann MembraGel®, Straumann AG); Group N: the dehiscence remained untreated. Three months following implantation, long, custom‐made, healing abutments were placed in one hemi‐mandible only to ensure functional loading. After 2 months, histological analysis was performed.

Results

A trend for lower residual defect height and higher bone‐to‐implant contact was observed in the loaded sites compared with non‐loaded sites in groups P, T1 and N. In group T2, the opposite effect was observed. In terms of bone formation, sites treated with SBC grafting and GBR (group T2) exhibited the largest surface area of regenerated bone followed by T1 and N. Significant resorption of the graft particles was noted in group T2 and the graft surface area occupied by SBC was significantly higher in group T1 compared with group T2 (P < 0.05).

Conclusions

Loading may have a positive effect on bone‐to‐implant contact in implants inserted in pristine bone or inserted in dehiscence sites and treated by grafting/no grafting.
Metal allergy and second‐generation metal‐on‐metal arthroplasties
Authors: Cousen Philippa J. , Gawkrodger David J.
Published: September 2011

There are concerns about the induction of metal allergy with second‐generation metal‐on‐metal prostheses, and the role that this may play in the development of complications such as ‘pseudotumours’ or failure of the implant. In this review, we attempt to set out the current knowledge on this subject. From a review of the literature, it is apparent that the first‐generation metal‐on‐metal replacement hips did cause metal sensitization, and that joint failure was associated with this, although it is still not clear which one led to the other. Highly engineered second‐generation metal‐on‐metal arthroplasties used in joint resurfacings are now increasingly employed. Several studies have recently shown an association between metal sensitization and peri‐implant hypersensitivity reactions and implant loosening and failure, although the overall risk appears to be low. The pragmatic approach adopted by most contact dermatologists for patients known to be allergic to nickel, cobalt or chromium and who require joint replacement is to recommend prostheses made of titanium‐based alloys. Patch testing continues to be a useful tool as laboratory investigations for metal hypersensitivity continue to emerge. The development of guidelines on the management of patients receiving metal‐on‐metal arthroplasties suspected of being metal‐allergic is desirable.
Effects of two weeks of daily apnea training on diving response, spleen contraction, and erythropoiesis in novel subjects
Authors: Engan H. , Richardson M. X. , Lodin‐Sundström A. , van Beekvelt M. , Schagatay E.
Published: September 2011

Three potentially protective responses to hypoxia have been reported to be enhanced in divers: (1) the diving response, (2) the blood‐boosting spleen contraction, and (3) a long‐term enhancement of hemoglobin concentration (Hb). Longitudinal studies, however, have been lacking except concerning the diving response. Ten untrained subjects followed a 2‐week training program with 10 maximal effort apneas per day, with pre‐ and posttraining measurements during three maximal duration apneas, and an additional post‐training series when the apneic duration was kept identical to that before training. Cardiorespiratory parameters and venous blood samples were collected across tests, and spleen diameters were measured via ultrasound imaging. Maximal apneic duration increased by 44 s (P < 0.05). Diving bradycardia developed 3 s earlier and was more pronounced after training (P < 0.05). Spleen contraction during apneas was similar during all tests. The arterial hemoglobin desaturation (SaO2) nadir after apnea was 84% pretraining and 89% after the duration‐mimicked apneas post‐training (P < 0.05), while it was 72% (P < 0.05) after maximal apneas post‐training. Baseline Hb remained unchanged after training, but reticulocyte count increased by 15% (P < 0.05). We concluded that the attenuated SaO2 decrease during mimic apneas was due mainly to the earlier and more pronounced diving bradycardia, as no enhancement of spleen contraction or Hb had occurred. Increased reticulocyte count suggests augmented erythropoiesis.
First Principles Estimation of Shock Tube Tests on Nanoreinforced Composite Materials
Authors: Xu Weiping , Ervin Elizabeth K.
Published: September 2011

Extreme loads events can cause enormous human and infrastructure losses. Computer modeling is the key to reducing the high cost of dynamic monitoring and experimentation. Engineers in various fields have undertaken complicated modeling for structures under abnormal loads. However, an efficient and accurate model is necessary to more rapidly address dangerous shock problems. Composite materials have replaced metals in various applications thanks to their superior shock resistance properties. This investigation particularly relates to their usage on naval ships to achieve improved blast survivability with the additional benefit of lower cost. A relatively simple model is detailed for the approximate centerline response prediction of the specific complex case of composite materials tested in a shock tube. A modal analysis simulation of a beam is performed using gross properties as well as physical geometry and arbitrary shock. Closed form equations have been employed to derive the eigenproblem that generates mode shapes and natural frequencies, and the resulting responses are compared to experimental shock tube test results. The best outcome was generated by the simplest model consisting of a shock pressure pulse averaged in two divisions and applied over the entire beam span. For this case, the simulation and experimental responses had reasonable correlation for fractured E-glass/vinyl-ester composite specimens with both nanoclay and graphite platelet reinforcement. This model is also a conservative estimate for the transient test deflection range for all other specimens.
40 μm Silver Flip-Chip Interconnect Technology With Solid-State Bonding
Authors: Sha Chu-Hsuan , Lee Chin C.
Published: September 2011

Formation of pure silver (Ag) flip-chip interconnect of silicon (Si) chips on copper (Cu) substrates is reported. Arrays of Ag columns, each 36 μm in height and 40 μm in diameter, are fabricated on 2-in. Si wafers which are first coated with chromium (Cr)/gold (Au) dual layers. The Si wafers are diced into 6 mm × 6 mm chips, each having 50 × 50 Ag columns. The Si chip with Ag columns is directly bonded to Cu substrate at 260 °C in 80 mTorr vacuum to inhibit oxidation. The static bonding pressure is as low as 680 psi (4.69 MPa), corresponding to a load of 0.021 oz (0.60 g) per column. During bonding, the Ag columns deform and conform to the Cu substrate. They are well bonded to the Cu. No molten phase is involved in the bonding process. The joints consist of pure Ag only. The ductile Ag joints are able to accommodate the thermal expansion mismatch between Si and Cu. It is well known that in nearly all soldering processes used in electronic industries, intermetallic compound (IMC) formation is essential to make a solder joint. In the pure Ag interconnect, no IMCs exist. Thus, reliability issues associated with IMCs are eliminated. Compared to tin-based lead-free solders, pure Ag joints have superior electrical and thermal properties.
Wireless Solar Water Splitting Using Silicon-Based Semiconductors and Earth-Abundant Catalysts
Authors: Reece Steven Y. , Hamel Jonathan A. , Sung Kimberly , Jarvi Thomas D. , Esswein Arthur J. , Pijpers Joep J. H. , Nocera Daniel G.
Published: September 2011

An artificial water-splitting system was built using abundant materials and sunlight.
Physiological demands of mountain rescue work
Authors: Callender Nigel , Ellerton John , Macdonald Jamie Hugo
Published: September 2011

Objective

To characterise the physical fitness of mountain rescue (MR) volunteers and the physical demands of a typical MR callout.

Methods

Eight 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.

Results

The 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).

Conclusions

Mountain 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.
MAPPINGS ON SOFT CLASSES
Authors: KHARAL ATHAR , AHMAD B.
Published: September 2011

In this paper, we define the notion of a mapping on soft classes and study several properties of images and inverse images of soft sets supported by examples and counterexamples. Finally, these notions have been applied to the problem of medical diagnosis in medical expert systems.
CLASSIFICATION OF SODAR DATA BY DNA COMPUTING
Authors: RAY KUMAR S. , MONDAL MANDRITA
Published: September 2011

In this paper, we propose a wet lab algorithm for classification of SODAR data by DNA computing. The concept of DNA computing is essentially exploited to generate the classifier algorithm in the wet lab. The classifier is based on a new concept of similarity-based fuzzy reasoning suitable for wet lab implementation. This new concept of similarity-based fuzzy reasoning is different from conventional approach to fuzzy reasoning based on similarity measure and also replaces the logical aspect of classical fuzzy reasoning by DNA chemistry. Thus, we add a new dimension to the existing forms of fuzzy reasoning by bringing it down to nanoscale. We exploit the concept of massive parallelism of DNA computing by designing this new classifier in the wet lab. This newly designed classifier is very much generalized in nature and apart from SODAR data, this methodology can be applied to other types of data also. To achieve our goal we first fuzzify the given SODAR data in a form of synthetic DNA sequence which is called fuzzy DNA and which handles the vague concept of human reasoning. In the present approach, we can avoid the tedious choice of a suitable implication operator (for a particular operation) necessary for the classical approach to fuzzy reasoning based on fuzzy logic. We adopt the basic notion of DNA computing based on standard DNA operations. We consider double stranded DNA sequences, whereas, most of the existing models of DNA computation are based on single stranded DNA sequences. In the present model, we consider double stranded DNA sequences with a specific aim of measuring similarity between two DNA sequences. Such similarity measure is essential for designing the classifier in the wet lab. Note that, we have developed a completely new measure of similarity based on base pair difference which is absolutely different from the existing measure of similarity and which is very much suitable for expert system approach to classifier design, using DNA computing. In the present model of DNA computing, the end result of the wet lab algorithm produces multi valued status which can be linguistically interpreted to match the perception of an expert.
Aging, visual information, and adaptation to task asymmetry in bimanual force coordination
Authors: Hu Xiaogang , Newell Karl M.
Published: September 2011

This study investigated the coordination and control strategies that the elderly adopt during a redundant finger force coordination task and how the amount of visual information regulates the coordination patterns. Three age groups (20–24, 65–69, and 75–79 yr) performed a bimanual asymmetric force task. Task asymmetry was manipulated via imposing different coefficients on the finger forces such that the weighted sum of the two index finger forces equaled the total force. The amount of visual information was manipulated by changing the visual information gain of the total force output. Two hypotheses were tested: the reduced adaptability hypothesis predicts that the elderly show less degree of force asymmetry between hands compared with young adults in the asymmetric coefficient conditions, whereas the compensatory hypothesis predicts that the elderly exhibit more asymmetric force coordination patterns with asymmetric coefficients. Under the compensatory hypothesis, two contrasting directions of force sharing strategies (i.e., more efficient coordination strategy and minimum variance strategy) are expected. A deteriorated task performance (high performance error and force variability) was found in the two elderly groups, but enhanced visual information improved the task performance in all age groups. With low visual information gain, the elderly showed reduced adaptability (i.e., less asymmetric forces between hands) to the unequal weighting coefficients, which supported the reduced adaptability hypothesis; however, the elderly revealed the same degree of adaptation as the young group under high visual gain. The findings are consistent with the notion that the age-related reorganization of force coordination and control patterns is mediated by visual information and, more generally, the interactive influence of multiple categories of constraints.
Microparticle enlargement and altered surface proteins after air decompression are associated with inflammatory vascular injuries
Authors: Yang Ming , Milovanova Tatyana N. , Bogush Marina , Uzun Günalp , Bhopale Veena M. , Thom Stephen R.
Published: September 2011

Studies in a murine model have shown that decompression stress triggers a progressive elevation in the number of circulating annexin V-coated microparticles derived from leukocytes, erythrocytes, platelets, and endothelial cells. We noted that some particles appeared to be larger than anticipated, and size continued to increase for ≥24 h postdecompression. These observations led to the hypothesis that inert gas bubbles caused the enlargement and particle size could be reduced by hydrostatic pressure. After demonstrating pressure-induced particle size reduction, we hypothesized that annexin V-positive particle changes associated with decompression contributed to their proinflammatory potential. Intravenous injection of naive mice with particles isolated from decompressed mice, but not control mice, caused intravascular neutrophil activation; perivascular neutrophil sequestration and tissue injuries were documented as elevations of vascular permeability and activated caspase-3. These changes were not observed if mice were injected with particles that had been subjected to hydrostatic recompression or particles that had been emulsified by incubation with polyethylene glycol telomere B surfactant. Hydrostatic pressure and surfactant incubation also altered the pattern of proteins expressed on the surface of particles. We conclude that proinflammatory events and vascular damage are due to enlargement of annexin V-coated particles and/or changes in surface marker protein pattern associated with provocative decompression. Injection of annexin V-coated particles from decompressed mice will recapitulate the pathophysiological vascular changes observed following decompression stress.
Comparison of Transepidermal Water Loss and Laser Scanning Microscopy Measurements to Assess Their Value in the Characterization of Cutaneous Barrier Defects
Authors: Czaika V. , Alborova A. , Richter H. , Sterry W. , Vergou T. , Antoniou C. , Lademann J. , Koch S.
Published: September 2011

The exact qualitative and quantitative analysis of wound healing processes is a decisive prerequisite for optimizing wound care and for therapy control. Transepidermal water loss (TEWL) measurements are considered to be the standard procedure for assessing the progress of epidermal wound healing. The damage to the stratum corneum correlates with an increased loss of water through the skin barrier. This method is highly susceptible to failure by environmental factors, in particular by temperature and moisture. This study was aimed at comparing TEWL measurements and in vivo laser scanning microscopy (LSM) for the characterization of the epidermal wound healing process. LSM is a high-resolution in vivo method permitting to analyze the kinetics and dynamics of wound healing at a cellular level. While the TEWL values for the individual volunteers showed a wide scattering, LSM permitted the wound healing process to be clearly characterized at the cellular level. However, a comparison between the two methods was very difficult, because the results provided by LSM were images and not numerical. Therefore, a scoring system was set up which evaluates the stages of wound healing. Thus, the healing process could be numerically described. This method is independent of any environmental factors. Providing morphologically qualitative and numerically quantitative analyses of the wound healing process and being far less vulnerable to failure, LSM is advantageous over TEWL.
Severe Hypernatremic Dehydration and Metabolic Acidosis due to Neonatal Intestinal Microvillus Inclusion Disease
Authors: Shahid Shaneela , Fraser Douglas D. , Driman David K. , Bax Kevin C.
Published: September 2011

Neonatal microvillus inclusion disease (MID) is a congenital secretory diarrhea diagnosed by morphological enterocyte abnormalities on histology. The secretory diarrhea associated with MID occurs within the first few hours of birth and is exacerbated by enteral feeding. Affected newborns will die of dehydration and acid-base disturbances if MID is not rapidly recognized and treated with massive intravenous fluid replacement and gut rest. We report a case of a 4-day-old neonate presenting with 18% weight loss, hypernatremic dehydration and metabolic acidosis. Despite aggressive fluid resuscitation (206 ml/kg for the first 24 h), the dehydration and metabolic acidosis were only minimally improved. The diapers were found soaked with clear, non-odorous fluid on repeated examinations. Persistent secretory diarrhea was suspected. Stool electrolytes analyses showed a high NaCl content typical of secretory diarrhea and intestinal biopsy with electron microscopy was diagnostic of MID.
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.
Absence of Pharmacokinetic Interaction Between Intravenous Peramivir and Oral Oseltamivir or Rimantadine in Humans
Authors: Atiee George , Lasseter Kenneth , Baughman Sharon , McCullough Amy , Collis Phil , Hollister Alan , Hernandez Jaime
Published: September 2011

Peramivir, an intravenously administered neuraminidase inhibitor, may be used concomitantly with other influenza antivirals. Two studies were conducted to assess the potential for pharmacokinetic interactions of peramivir when coadministered with oseltamivir or rimantadine. Twenty‐one healthy subjects were enrolled in each randomized, open‐label, crossover study, and they received 1 intravenous dose of peramivir (600 mg), 1 oral dose of oseltamivir (75 mg) or rimantadine (100 mg), or a combination of peramivir with oseltamivir or rimantadine. Assessment of the 90% confidence interval for the geometric mean ratio of peramivir and oseltamivir carboxylate or rimantadine pharmacokinetic parameters showed no effect of oseltamivir or rimantadine on the pharmacokinetics of peramivir and no effect of peramivir on the pharmacokinetics of oseltamivir carboxylate or rimantadine. The drugs were well tolerated. These results suggest no reason to expect an effect of concomitant administration of oseltamivir or rimantadine on the safety profile of peramivir in patients with influenza.
Pharmacokinetics, Pharmacodynamics, and Safety of Ticagrelor in Volunteers With Severe Renal Impairment
Authors: Butler Kathleen , Teng Renli
Published: September 2011

Ticagrelor, a P2Y12 receptor antagonist, is approved in the European Union and the US for the prevention of thrombotic events in patients with acute coronary syndromes. Renal dysfunction potentially affects drug disposition. Ticagrelor pharmacokinetics, pharmacodynamics, and safety in renal impairment were assessed. A single 180‐mg ticagrelor dose was administered to volunteers with severe renal impairment (creatinine clearance [CrCL] < 30 mL/min) and normal renal function (CrCL ≥ 80 mL/min; n = 10/group). Severe renal impairment did not significantly affect ticagrelor's pharmacokinetics, pharmacodynamics, or safety. Ticagrelor absorption and AR‐C124910XX (active metabolite) formation were rapid. In renally impaired volunteers, ticagrelor mean maximum concentration (Cmax) and area under the plasma concentration‐time curve from zero to infinity were 20% lower and for AR‐C124910XX was 17% higher versus normal volunteers. Ticagrelor systemic exposure was low in 3 volunteers (CrCL < 20 mL/min), but data were variable. Onset and offset of final‐extent inhibition of platelet aggregation were comparable in both groups. Inhibition of platelet aggregation parameters and profiles were similar between groups, indicating that platelet sensitivity to ticagrelor was not affected by severe renal impairment. Ticagrelor was well tolerated in both groups with few adverse events. No ticagrelor dose adjustment is required for renally impaired patients.
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

Background

Prolonged 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.

Results

The 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.

Conclusions

These 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

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

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

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.