Recurrent cutaneous abscesses caused by PVL-MRSA.
A 41-year-old female presented with a superficial buttock abscess. In the preceding 6 months she had four other abscesses at different anatomical sites. Screening for diabetes and immunocompromise was negative. Review of microbiology revealed Methicillin resistant Staphylococcus aureus harbouring Panton-Valentine leukocidin (PVL) genes. PVL syndrome is an emerging disorder associated with recurrent necrotic skin lesions in the young, otherwise healthy population.


MLP in layer-wise form with applications to weight decay.
A simple and general calculus for the sensitivity analysis of a feedforward MLP network in a layer-wise form is presented. Based on the local optimality conditions, some consequences for the least-means-squares learning problem are stated and further discussed. Numerical experiments with formulation and comparison of different weight decay techniques are included.


The stabbed wounds as a cause of injuries of different parts of the body.
Only 171 patients with injuries that were caused as a result of stubbing treated in Jan Bozy Regional Hospital in Lublin in the years 1997-2000, were analysed. The injured people were mostly men aged 21-40. 142 people were treated in outpatient clinic, and 29 were hospitalized. The medium ime spent in hospital was about 7 days. Eleven of the hospitalized patients were operated on immediately. On the basis of the analysis of the research results it was estimated that: 1. The most frequent tool ausing stabbed wounds in the case of hospitalized patients was a knife, and in outpatients--a nail. 2. The circumstances in which the stabbed wounds were most often appearing were accidents (out-patient clinic) and in the case of hospitalized patients assaults by unknown culprits. 3. The most frequent localization of the stabbed wounds among the hospitalized patients was chest and among the outpatients an arm or a leg.


Narrative research in psychotherapy: a critical review.
This paper is a review of studies which utilise the notion of narrative to analyse psychotherapy. Its purpose is to systematically present this diverse field of research, to highlight common themes and divergences between different strands and to further the development and integration of narrative research in psychotherapy. The paper reviews studies which employ an applied textual analysis of narratives produced in the context of psychotherapy. Criteria for inclusion of studies are, firstly, the analysis of therapeutic and therapy-related texts and, secondly, the adoption of a narrative psychological perspective. The studies were examined on the basis of the notion of narrative they employ and the aspects of client narratives they focus on, and were grouped accordingly in the review. The majority of the studies reviewed assume a constructivist approach to narrative, adopt a representational view of language, focus primarily on client micro-narratives and relate to cognitive-constructivist and process-experiential psychotherapeutic approaches. A smaller group of studies assume a social constructionist approach to narrative and a functional view of language, focus on micro-narratives, highlight the interactional and wider social aspects of narrative and relate to postmodern trends in psychotherapy. The range of conceptualisations of narrative in the studies reviewed, from a representational psychological view to a constructionist social view, reflects tensions within narrative psychology itself. Moreover, two trends can be discerned in the field reviewed, narrative analysis of therapy, which draws from narrative theory and utilises the analytic approaches of narrative research to study psychotherapy, and analyses of narrative in therapy, which study client narratives using non-narrative qualitative methods. Finally, the paper highlights the need for integration of this diverse field of research and urges for the development of narrative studies of psychotherapy which employ a broader social understanding of narrative production and transformation.


Development and Validation of KASP-SNP Markers for QTL Underlying Resistance to Stripe Rust in Common Wheat Cultivar P10057.
Stripe rust (Puccinia striiformis f. sp. tritici) is among the most important diseases of wheat (Triticum aestivum L.) globally. Utilization of adult plant resistance (APR) constitutes a key tool for maintaining protection against this disease. The CIMMYT wheat cultivar P10057 displayed a high level of APR to stripe rust in germplasm evaluation in field environments. To clarify the genetic basis and identify quantitative trait loci (QTLs) involved in stripe rust resistance in P10057, three wheat populations were used: 150 F5:6 recombinant inbred lines (RILs) derived from the cross Mingxian 169 × P10057, and 161 and 140 F2:3 lines from Avocet S × P10057 and Zhengmai 9023 × P10057, respectively. These three populations were evaluated for infection type (IT) and disease severity (DS) in Shaanxi, Gansu, and Sichuan during the 2014-15 and 2015-16 cropping seasons. Genotyping was performed with Kompetitive Allelic Specific PCR (KASP) and simple sequence repeat (SSR) markers linked to the resistance loci. Using QTL analysis, two genomic regions associated with resistance were found on chromosome arms 2BS and 3BS, respectively. These two stable QTLs, designated Qyrlov.nwafu-2BS and Qyrlov.nwafu-3BS, were detected across all environments and explained average 22.6 to 31.6% and 21.3 to 32.3% of stripe rust severity phenotypic variation, respectively. Qyrlov.nwafu-2BS may be the resistance allele derived from CIMMYT germplasm and Qyrlov.nwafu-3BS likely corresponds to the locus Sr2/Lr27/Yr30/Pbc. The KASP markers IWA5377, IWA2674, and IWA5830 linked to QYrlov.nwafu-2BS and IWB57990 and IWB6491 linked to Qyrlov.nwafu-3BS were reliable for marker-assisted selection (MAS) in the Zhengmai 9023 × P10057 population. These QTLs with KASP markers are expected to contribute in developing wheat cultivars with improved stripe rust resistance.


Pre-radiation enhances the cytotoxicity of docetaxel in head and neck squamous cell carcinoma cells.
This study was designed to determine the effect of the treatment schedule on the interaction between docetaxel and irradiation. Human head and neck squamous cell carcinoma (HNSCC) cells with different p53 status, and HSC4 (p53 wild-type) and CAL27 (p53 mutant type) cells were treated with docetaxel and irradiation using three schedules: i) concurrent treatment, ii) docetaxel pretreatment and iii) pre-radiation. Docetaxel and radiation inhibited the proliferation of HSC4 and CAL27 cells in a dose-dependent manner. However, irradiation pretreatment was more effective than the other treatment regimens in all cells. Our data suggest that pre-radiation in HNSCC cells significantly enhances docetaxel cytotoxity by arresting S-phase, and this provides the most effective treatment sequence of docetaxel and radiation combination therapy. Therefore, radiation followed by docetaxel may be the most effective sequence for head and neck cancer therapy.


Development of a complex intervention for people with chronic pain after knee replacement: the STAR care pathway.
Approximately 20% of people who have total knee replacement experience chronic pain afterwards, but there is little evidence about effective interventions for managing this type of pain. This article describes the systematic development and refinement of a complex intervention for people with chronic pain after knee replacement. The intervention is a care pathway involving an assessment clinic and onward referral, with telephone follow-up as required. In the design of this multistage study, we chose to focus on ensuring that the intervention was deliverable, implementable and acceptable. In line with the UK Medical Research Council's recommendations for comprehensive development of complex interventions, multiple phases of work were undertaken. Following on from initial development work to design the intervention, the draft intervention content was refined through consensus questionnaires with 22 health professionals and discussion at meetings with 18 healthcare professionals. Testing of intervention delivery and acceptability to patients was undertaken by two health professionals delivering the assessment clinic to ten patients. Views about future implementation within the context of a randomised trial were evaluated through a questionnaire based on the Normalisation Measure Development (NoMAD) instrument with ten health professional stakeholders. Consensus work with health professionals ensured the components of the intervention were appropriate and informed a number of substantive changes to improve the intervention. Testing of intervention delivery identified a number of logistical issues that were then addressed in the development of a comprehensive intervention training manual. Engagement with stakeholders indicated that the intervention could be successfully implemented in a clinical setting for evaluation in a randomised trial. This work has informed the development and refinement of a complex intervention for people with chronic pain after knee replacement. The next stage is to evaluate the clinical and cost-effectiveness of the STAR care pathway in a multicentre randomised trial.


Inferior Mesenteric Artery Injury in Post-lumbar Microdiscectomy: A Case Report.
Iatrogenic vascular injury during lumbar microdiscectomy is a rather rare complication, but it can have fatal consequences. Here, we report a patient who underwent an L5-S1 microdiscectomy, which was complicated by inferior mesenteric artery injury. The patient presented in the recovery room with symptoms of hypotension and tachycardia after the operation which was successfully managed by endovascular embolization. The patient was positioned in a prone position, which may have contributed to the development of vascular injury. To prevent potential complications, we advised using the Jackson table rather than a standard surgical table and thoroughly inspecting the abdomen and pelvis prior to the operation.


Definition and application of performance specifications for measurement uncertainty of 23 common laboratory tests: linking theory to daily practice.
Laboratories should estimate and validate [using analytical performance specifications (APS)] the measurement uncertainty (MU) of performed tests. It is therefore essential to appropriately define APS for MU, but also to provide a perspective on suitability of the practical application of these APS. In this study, 23 commonly ordered measurands were allocated to the models defined during the 2014 EFLM Strategic Conference to derive APS for MU. Then, we checked if the performance of commercial measuring systems used in our laboratory may achieve them. Most measurands (serum alkaline phosphatase, aspartate aminotransferase, creatine kinase, γ-glutamyltransferase, lactate dehydrogenase, pancreatic amylase, total proteins, immunoglobulin G, A, M, magnesium, urate, and prostate-specific antigen, plasma homocysteine, and blood red and white cells) were allocated to the biological variation (BV) model and desirable APS were defined accordingly (2.65%, 4.75%, 7.25%, 4.45%, 2.60%, 3.15%, 1.30%, 2.20%, 2.50%, 2.95%, 1.44%, 4.16%, 3.40%, 3.52%, 1.55%, and 5.65%, respectively). Desirable APS for serum total cholesterol (3.00%) and urine albumin (9.00%) were derived using outcome-based model. Lacking outcome-based information, serum albumin, high-density lipoprotein cholesterol, triglycerides, and blood platelets were temporarily reallocated to BV model, the corresponding desirable APS being 1.25%, 2.84%, 9.90%, and 4.85%, respectively. A mix between the two previous models was employed for serum digoxin, with a 6.00% desirable APS. In daily practice by using our laboratory systems, 16 tests fulfilled desirable and five minimum APS, while two (serum albumin and plasma homocysteine) exceeded goals, needing improvements.


Functional connectivity between interoceptive brain regions is associated with distinct health-related domains: A population-based neuroimaging study.
Interoception is the sensation, perception, and integration of signals from within the body. It has been associated with a broad range of physiological and psychological processes. Further, interoceptive variables are related to specific regions and networks in the human brain. However, it is not clear whether or how these networks relate empirically to different domains of physiological and psychological health at the population level. We analysed a data set of 19,020 individuals (10,055 females, 8965 males; mean age: 63 years, age range: 45-81 years), who have participated in the UK Biobank Study, a very large-scale prospective epidemiological health study. Using canonical correlation analysis (CCA), allowing for the examination of associations between two sets of variables, we related the functional connectome of brain regions implicated in interoception to a selection of nonimaging health and lifestyle related phenotypes, exploring their relationship within modes of population co-variation. In one integrated and data driven analysis, we obtained four statistically significant modes. Modes could be categorised into domains of arousal and affect and cardiovascular health, respiratory health, body mass, and subjective health (all p < .0001) and were meaningfully associated with distinct neural circuits. Circuits represent specific neural "fingerprints" of functional domains and set the scope for future studies on the neurobiology of interoceptive involvement in different lifestyle and health-related phenotypes. Therefore, our research contributes to the conceptualisation of interoception and may lead to a better understanding of co-morbid conditions in the light of shared interoceptive structures.


Analysis of a urinary biomarker panel for obstructive nephropathy and clinical outcomes.
To follow up renal function changes in patients with obstructive nephropathy and to evaluate the predictive value of biomarker panel in renal prognosis. A total of 108 patients with obstructive nephropathy were enrolled in the study; 90 patients completed the follow-up. At multiple time points before and after obstruction resolution, urinary samples were prospectively collected in patients with obstructive nephropathy; the levels of urinary kidney injury molecule-1 (uKIM-1), liver-type fatty acid-binding protein (uL-FABP), and neutrophil gelatinase associated lipocalin (uNGAL) were determined by enzyme-linked immunosorbent assay (ELISA). After 1 year of follow-up, the predictive values of biomarker panel for determining the prognosis of obstructive nephropathy were evaluated. uKIM-1 (r = 0.823), uL-FABP (r = 0.670), and uNGAL (r = 0.720) levels were positively correlated with the serum creatinine level (all P<0.01). The levels of uKIM-1, uL-FABP, and uNGAL were higher in the renal function deterioration group than in the renal function stable group. Cox regression analysis revealed that the 72-h postoperative uKIM-1 level and the preoperative and 72-h postoperative uL-FABP levels were all risk factors for renal function deterioration (all P<0.01). The area under the curve of Receiver Operating Characteristic(ROC-AUCs) of 72-h postoperative uKIM-1, preoperative uL-FABP, and 72-h postoperative uL-FABP were 0.786, 0.911, and 0.875, respectively. When the combined preoperative uKIM-1, uL-FABP, and uNGAL levels or combined 72-h postoperative uKIM-1, uL-FABP, and uNGAL levels were considered, the accuracy of prediction for renal prognosis was markedly increased, with an ROC-AUC of 0.967 or 0.964, respectively. Kaplan-Meier survival curve analysis demonstrated that a 72-h postoperative uKIM-1>96.69 pg/mg creatinine (Cr), a preoperative uL-FABP>154.62 ng/mg Cr, and a 72-h postoperative uL-FABP>99.86 ng/mg Cr were all positively correlated with poor prognosis (all P<0.01). Biomarker panel may be used as a marker for early screening of patients with obstructive nephropathy and for determining poor prognosis.


An educational tool for photodynamic therapy of Barrett esophagus with high-grade dysplasia: from screening through follow-up.
Photodynamic therapy using a centering balloon was recently approved by the Food and Drug Administration for ablation of Barrett esophagus with high-grade dysplasia. This article is an educational tool for the photodynamic therapy team, addressing four important steps involved with photodynamic therapy: screening for potential patients, patient education, treatment using the centering balloon, and follow-up after treatment. Each step ensures proper care for the patient requiring photodynamic therapy.


An improved method to prepare hyaluronic acid and type II collagen composite matrices.
An improved method to prepare hyaluronic acid (HyA) and type II collagen composite matrices was developed. HyA and type II collagen formed polyion complex (PIC) in aqueous solution due to their opposite electrostatic charges. Therefore, optimal conditions at which PIC was not formed between HyA and type II collagen were determined in order to directly crosslink using a water-soluble carbodiimide [WSC; 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride]. HyA-collagen composite matrices were successfully obtained using WSC in the presence of 0.4M NaCl, which was found the optimal concentration to suppress PIC formation. Fourier transformed infrared spectra of the obtained matrices showed ester bond formation, indicating that the crosslinking reaction between HyA molecules, HyA and collagen molecules, and collagen molecules proceeded. The swelling ratio of a HyA-collagen composite matrix depended on the WSC concentration and HyA content. From scanning electron microscopy observations, the lyophilized matrices possess multi pore structures. The HyA-collagen composite matrices using this improved method will be useful in the preparation of cartilage regenerative scaffolds, and this methodology may be applied to other polyanion-polycation combinations as well.


[Anterior retropharyngeal debridement combined with posterior atlantoaxial fusion for atlantoaxial Tuberculosis].
To evaluate the clinical efficacy of anterior debridement combined with posterior atlantoaxial fusion for atlantoaxial Tuberculosis. From February 2005 to February 2013, 7 patients, 3 males and 4 females, with atlantoaxial Tuberculosis underwent anterior debridement combined with posterior atlantoaxial fusion in Department of Orthopedics Zhengzhou University People's Hospital were selected.In the preoperative and final follow-up, Japanese Orthopaedic Association score (JOA), neck disability index (NDI) and Frankel Classification were used to evaluate neurological function and calculate improvement rate.At final follow-up, clinical efficacy was evaluated by Odom's grade.Situation of internal fixation, fusion of upper cervical were assessed by X-ray, CT scan and MRI scan. Bony fusion were achieved in 7 cases after operation in 12 months. Tuberculosis were reached clinical cure between 17 and 21 months. At follow The JOA score increased from (11.1±0.7) preoperatively to (15.3±0.5) in final follow-up(P<0.05), and the NDI decreased from (34.0±4.6) preoperatively to (10.1±1.3) in final follow-up (P<0.05). At last follow-up, according to Odom's standard, excellent were obtained in 5 cases, good 1 cases and ordinary 1 case. Frankel Classification of all cases improved from D class to E. The treatment of anterior retropharyngeal debridement combine with atlantoaxial fusion, and local anti-tuberculosis drug using intraoperative, not only could obtain reliable clinical efficacy, completly removal of lesions, but also obtain strong stability, which plays an important role in the treatment of atlantoaxial Tuberculosis.


Impact of genotype on endocrinal complications in β-thalassemia patients.
In β-thalassemia, certain mutations cause a complete absence of β-globin chain synthesis, termed β0-thalassemia, while others may allow certain β-globin production and are termed β+- or β++-thalassemia. The homozygous state results in severe anemia, which requires regular blood transfusion. By contrast, frequent blood transfusion can in turn lead to iron overload, which may result in several endocrinal complications. The present study aimed to investigate the impact of genotype on the development of endocrine complications in β-thalassemia patients. A cross-sectional study was conducted on 100 thalassemia patients >10 years. A data abstraction form was designed to capture the appropriate information from the individual medical records, including full clinical, laboratory, transfusion and chelation data. The genotype of the patients was identified by the DNA sequencing technique. Growth retardation and hypogonadism were the most prominent endocrinal complications (70 and 67%, respectively) followed by hypothyroidism, diabetes mellitus and hypoparathyrodism (8, 8 and 7%, respectively). The most common mutations identified were IVS-1-110, IVS-1-1 and IVS-1-6 (63, 47 and 41%, respectively). Patients with the β0β0 genotype had a significantly higher prevalence of growth retardation, hypogonadism, hypothyroidism and hypoparathyrodism compared to those with the β0β+ and β+β+ genotypes (P<0.001, P<0.001, P<0.001 and P=0.037, respectively). Patients with the homozygous IVS-11-745 mutation had a significantly higher prevalence of diabetes (P=0.001). The underlying genetic defect in thalassemia patients is a contributing factor for the development of endocrinal complications, as patients with the more severe defects have a greater rate of iron loading through higher red cell consumption.


Comparative metagenomics: natural populations of induced prophages demonstrate highly unique, lower diversity viral sequences.
To understand the similarities and differences between a free living viral population and its co-occurring temperate population, metagenomes of each type were prepared from the same seawater sample from Tampa Bay, FL. Libraries were prepared from extracted DNA of the ambient viruses and induced prophages from the co-occurring, viral-reduced microbial assemblage. Duplicate libraries were also prepared using the same DNA amplified by multiple displacement amplification. A non-viral-reduced, induced, amplified viral dataset from the same site in 2005 was reanalysed for temporal comparison. The induced viral metagenome was higher in identifiable virus sequences and differed from the other three datasets based on principal component, rarefaction, trinucleotide composition and contig spectrum analyses. This study indicated that induced prophages are unique and have lower overall community diversity than ambient viral populations from the same site. Both of the amplified contemporary metagenomes were enriched in single-stranded DNA (ssDNA) viral sequences. Six and 16 complete, circular ssDNA viral genomes were assembled from the amplified induced and ambient libraries, respectively, mostly similar to circoviruses. The amplified ambient metagenome contained genomes similar to an RNA-DNA hybrid virus recently identified in a hot spring and to an ssDNA virus infecting the diatom Chaetoceros.


Basic Principles in the Management of Acute Burn Injuries in Adults.
This review outlines an overview of up-to-date, stage-appropriate treatment methods for burn injuries as practiced at the National Burn Center of the University Hospital Zurich. It intends to provide practitioners with recommendations for the management of acute minor to severe burn injuries based on scientific evidence as well as the long-term experience of the Burn Center. The focus is on a practical guideline and various options including novel, innovative conceptual approaches.


Biodegradation of nitro-explosives.
Environmental contamination by nitro compounds is associated principally with the explosives industry. However, global production and use of explosives is unavoidable. The presently widely used nitro-explosives are TNT (Trinitrotoluene), RDX (Royal Demolition Explosive) and HMX (High Melting Explosive). Nevertheless, the problems of these nitro-explosives are almost parallel due to their similarities of production processes, abundance of nitro-explosives and resembling chemical structures. The nitro-explosives per se as well as their environmental transformation products are toxic, showing symptoms as methaemoglobinaemia, kidney trouble, jaundice etc. Hence their removal/degradation from soil/water is essential. Aerobic and anaerobic degradation of TNT and RDX have been reported, while for HMX anaerobic or anoxic degradation have been described in many studies. A multisystem involvement using plants in remediation is gaining importance. Thus the information about degradation of nitro-explosives is available in jigsaw pieces which needs to be arranged and lacunae filled to get concrete degradative schemes so that environmental pollution from nitro-explosives can be dealt with more successfully at a macroscale. An overview of the reports on nitro-explosives degradation, future outlook and studies done by us are presented in this review.


Hemodynamic and vascular effects of ventricular sourcing by stent-based ventricle to coronary artery bypass in patients with multivessel disease undergoing coronary artery bypass surgery.
The hemodynamic and vascular effects of ventricular sourcing by a stent-based (VSTENT, Percardia) left ventricle-to-coronary artery bypass were studied in a patient subgroup of the European multicenter ADVANTAGE study (ADjunctive treatment with the VCAB/VSTENT myocardial implANT system in coronary Artery bypass Graft patiEnts). Twelve patients who underwent VSTENT implantation in addition to coronary artery bypass surgery were studied up to 12 months after the procedure. The VSTENT was implanted distal to a hemodynamically relevant coronary artery stenosis. Coronary flow velocity was assessed at rest and during dobutamine stress. Intraoperative VSTENT implantation was successful in 11 of 12 patients. Early postoperative angiograms showed patent VSTENT in 8 of 11 patients, with predominantly systolic flow distal to the VSTENT. Coronary flow velocity reserve induced by dobutamine stress was 1.7+/-0.1 (P=0.006). VSTENT patency at 2- to 6-month follow-up was present in 5 of 11 patients, with concomitant VSTENT stenosis in 4 of those 5. In all patients, coronary flow velocity increased 3- to 4-fold proximal to the VSTENT, which was associated with a moderate degree of arterial remodeling. Except for target vessel reintervention (n=5), no other major adverse events were observed in 11 of 12 patients. One patient died on the second postoperative day, though the cause was probably not related to the VSTENT implantation. VSTENT implantation seems to be safe in the mid-term follow-up and leads to a predominantly systolic coronary flow pattern in the vessel supplied by the VSTENT, with a flow reserve similar or close to that seen with conventional bypass. VSTENT patency rate, however, was unacceptably low at 3- to 6-month follow-up and needs to be improved.


Attitudes, Behaviors, and Risks of Sun Protection to Prevent Skin Cancer Amongst Children, Adolescents, and Adults.
Skin cancer is the most common cancer diagnosis worldwide. Many factors are involved in the development of skin cancers, but ultraviolet (UV) light exposure is the most modifiable. Our lifetime cumulative UV exposure may be a result of poor sun protection practices in childhood and adolescence. Modifying the attitudes and behaviors of children can be done in the classroom, at recreational activities, and at home. A review of the literature was conducted using Embase and PubMed to examine the relationship between attitudes and behaviors as they relate to sun protection strategies. Well-developed, standardized sun protection educational programs are needed to instruct children and adolescents. Individualized counseling from physicians or online programs is needed to help parents increase sun-safe standards for their children. Many young women utilize indoor tanning beds frequently, but many instructional programs increased their tanning bed usage. Time should be allotted at schools, sports practices, camps, and other outdoor activities for sunscreen reapplication. Many parents and children report the media is their primary source of information about sun safety. Media outlets may positively change attitudes and behaviors when reporting about sun safety. Parents and children need individualized programs or counseling to reduce ultraviolet (UV) exposure and increase sun protection. At-risk populations need tailored instruction, but few strategies have worked to decrease UV exposure.


Anomalous gray matter structural networks in recent onset post-traumatic stress disorder.
Alterations of the topological organization of abnormal regions or network-level structural aberrations are still poorly understood for post-traumatic stress disorder (PTSD). Herein, we investigated brain structural networks in recent-onset PTSD patients, all affected by the coalmine-flood disaster. Cortical networks were studied in recent onset PTSD patients (n = 15) and matched healthy controls (n = 25). Cortical networks were constructed by thresholding correlation matrices of 150 regions and quantified using graph theoretical approaches. Contributions of high-degree nodes, and regional and global network measures, including degree and betweenness, were studied. Compared with healthy controls, PTSD patients showed altered quantitative values in global network properties, characterized by shorter path length and higher clustering. Moreover, PTSD patients exhibited decreased connectivity in the right lingual gyrus, parahippocampal gyrus, left supramarginal gyrus, parahippocampal gyrus, bilateral superior and inferior frontal gyrus, superior frontal gyrus, and posterior cingulate gyrus. Nodal centrality decreased predominantly in the occipital regions (lingual gyrus) and default-mode regions, while increased correlations and centralities were observed in the medial temporal lobe and posterior cingulate cortex. PTSD-related networks exhibited a less efficient organization and regional connectivity. According to these findings, we conclude that regional connections involving fear-processing and re-experiential-processing cortex may play a role in maintaining or adapting to PTSD pathology.


Inhibition of histone deacetylases induces formation of multipolar spindles and subsequent p53-dependent apoptosis in nasopharyngeal carcinoma cells.
Histone deacetylases (HDACs) play crucial roles in the initiation and progression of cancer, offering a promising target for cancer therapy. HDACs inhibitor MGCD0103 (MGCD) exhibits effective anti-tumor activity by blocking proliferation and inducing cell death in malignant cells. However, the molecular mechanisms of HDACs inhibition induces cell death have not been well elucidated. In this study, we showed that MGCD effectively restored histone acetylation, suppressed cell growth and induced apoptosis in two-dimensional (2D) and three-dimensional (3D) cultured CNE1 and CNE2 nasopharyngeal carcinoma (NPC) cells. Importantly, MGCD arrested cell cycle at mitosis (M) phase with formation of multipolar spindles, which was associated with activated p53-mediated postmitotic checkpoint pathway to induce apoptotic cell death. Moreover, MGCD-induced apoptosis was decreased by inhibition of p53 using short interfering RNA (siRNA), suggesting that p53 was required for MGCD-induced cell apoptosis. Consistently, MGCD in combination with Nutlin-3, a MDM2 inhibitor showed synergistic effect on inducing apoptosis in 2D and 3D cultured CNE2 cells. Collectively, our data revealed that MGCD induced p53-dependent cell apoptosis following formation of multipolar spindles in NPC cells, suggesting the therapeutic potential of combinations of HDACs and MDM2 inhibitors for NPC treatment.


[Induction of alpha-fetoprotein synthesis in nonproliferating hepatocytes].
The localization of alpha-fetoprotein (alpha-FP) and the proliferative activity of hepatocytes were studied after an insignificant liver damage. On the 3rd--6th day after the operation alpha-FP was detectable in hepatocytes localized on the boundary with the zone of damage. The most intensely stained cells were found adjacent to some vessels lying near this zone. The overwhelming majority of alpha-FP-containing hepatocytes did not incorporate 3H-thymidine. The data obtained allow a conclusion that the synthesis of alpha-FP is not related to cell proliferation.


Antioxidant activity of polyphenolic compounds isolated from ethyl-acetate fraction of Acacia hydaspica R. Parker.
Acacia hydaspica belongs to family leguminosae possess antioxidant, anti-inflammatory and anticancer activities. During our search for antioxidant compounds from A. hydaspica, we carried out bioassay guided fractionation and obtained antioxidant compounds with free radical scavenging activity. The polyphenol compounds in the plant extract of A. hydaspica were isolated by combination of different chromatographic techniques involving vacuum liquid chromatography and medium pressure liquid chromatography. The structural heterogeneity of isolated compounds was characterized by high pressure liquid chromatography, MS-ESI and NMR spectroscopic analyses. The antioxidant potential of isolated compounds has been investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging potential, hydroxyl radical scavenging potential, ferric reducing/antioxidant power (FRAP) model systems and total antioxidant capacity measurement. The isolated compounds show the predominance of signals representative of 7-O-galloyl catechins, catechins and methyl gallate. Flash chromatographic separation gives 750 mg of 7-O galloyl catechin, 400 mg of catechin and 150 mg of methyl gallate from 4 g loaded fraction on ISCO. Results revealed that C1 was the most potent compound against DPPH (EC50 1.60 ± 0.035 µM), nitric oxide radical (EC50 6 ± 0.346 µM), showed highest antioxidant index (1.710 ± 0.04) and FRAP [649.5 ± 1.5 µM Fe(II)/g] potency at 12.5 µM dose compared to C2, C3 and standard reference, whereas C3 showed lower EC50 values (4.33 ± 0.618 µM) in OH radical scavenging assay. Present research reports for the first time the antioxidant activity of polyphenolic compounds of A. hydaspica. Result showed good resolution and separation from other constituents of extract and method was found to be simple and precise. The isolation of catechin from this new species could provide a varied opportunity to obtain large quantities of catechin and catechin isomers beside from green tea. Free radical scavenging properties of isolated catechin isomers from A. hydaspica merit further investigations for consumption of this plant in oxidative stress related disorders.


Mechanism of action of efinaconazole, a novel triazole antifungal agent.
The mechanism of action of efinaconazole, a new triazole antifungal, was investigated with Trichophyton mentagrophytes and Candida albicans. Efinaconazole dose-dependently decreased ergosterol production and accumulated 4,4-dimethylsterols and 4α-methylsterols at concentrations below its MICs. Efinaconazole induced morphological and ultrastructural changes in T. mentagrophytes hyphae that became more prominent with increasing drug concentrations. In conclusion, the primary mechanism of action of efinaconazole is blockage of ergosterol biosynthesis, presumably through sterol 14α-demethylase inhibition, leading to secondary degenerative changes.


Generating MnO2 nanoparticles using simulated amorphization and recrystallization.
Models of MnO2 nanoparticles, with full atomistic detail, have been generated using a simulated amorphization and recrystallization strategy. In particular, a 25,000-atom "cube" of MnO2 was amorphized (tension-induced) under molecular dynamics (MD). Long-duration MD, applied to this system, results in the sudden evolution of a small crystalline region of pyrolusite-structured MnO2, which acts as a nucleating "seed" and facilitates the recrystallization of all the surrounding (amorphous) MnO2. The resulting MnO2 nanoparticle is about 8 nm in diameter, conforms to the pyrolusite structure (isostructural with rutile TiO2, comprising 1 x 1 octahedra) is heavily twinned and comprises a wealth of isolated and clustered point defects such as cation vacancies. In addition, we suggest the presence of ramsdellite (2 x 1 octahedra) intergrowths. Molecular graphical snapshots of the crystallization process are presented.


Pharmacy Student Anxiety and Success With Objective Structured Clinical Examinations.
Objective. To evaluate whether a relationship exists between the degree of student state-anxiety and pass rates on moderate-to-high stakes objective structured clinical examinations (OSCE). Methods. Third-professional year (P3) students were assessed using the Speilberger State-Trait Anxiety Index (STAI) three weeks prior to their first moderate-to-high stakes OSCEs. Students' OSCE station pass rates, individual station analytical scores, and the overall pass rate for the class were compared with student responses on STAI surveys to measure their association. Results. Seventy-three students (100%) provided consent to participate in the research; 64 (87%) sufficiently completed the STAI survey. Degree of student state-anxiety or train-anxiety was not associated with any of the outcomes assessed in this study. Overall pass rate, individual station pass rates, and station analytical checklist scores were not inversely correlated with state- or trait-anxiety scores. Conclusions. Efforts to assist students in OSCE performance should focus on means other than reducing associated anxiety. Future research in this area should focus on what interventions beyond instruction could be put in place to help students be more successful during OSCEs.


[Uremic pruritus].
Uremic pruritus is a common and sometimes severe complication of chronic renal failure. Itch affects 50-90% of patients undergoing peritoneal dialysis or hemodialysis and 25% of patients with preterminal chronic renal failure. The mechanism underlying uremic pruritus is poorly understood; possibilities include histamin, proteases, interleukin-2 and TNF- produced by skin mast-cells, substance P, neuropathy and neurological changes, high level of Ca, P, PTH, Al, Mg, divalent ion abnormalities, hypervitaminosis A, inflammation, or some combination of these. Therapeutic measures include regular efficient dialysis, transplantation, topical measures as an emollients, topical steroids, systemic measures as diet, opioids and physical treatment with phototherapy, acupuncture etc. Treatment results are highly variable and more research is needed to understand the patophysiology of this condition and to establish more reliable treatments. Most effective treatments in this moment are efficient dialysis, dietary restrictions, phosphate-binding therapy and phototherapy.


In patients treated with peritoneal dialysis, icodextrin improves erythropoietin-resistant anemia through blockade of asialo receptors on hepatocytes.
Although erythropoietin (EPO) derivatives improve anemic status in most end-stage renal disease patients, some EPO-resistant patients remain. Asialo-type EPO is as effective as is native EPO in vitro, but in vivo, it is quickly trapped by the hepatic asialo receptors. Alkaline phosphatase (ALP) also binds to the asialo receptor for degradation. We compared hematologic indices in 27 stable PD patients 1-3 months before and after the start of icodextrin solution. In selected patients, we also performed imaging with 99m-technetium-labeled galactosyl serum albumin (GSA) for asialo receptors. Resistance to EPO was defined as a hematocrit below 30% concurrent with EPO administration of more than 18,000 IU monthly. In 19 patients without EPO resistance started on icodextrin, the average hematocrit level did not change (-1.2%), and the average ALP activity increased 36%. But in 8 patients with EPO resistance, the average hematocrit level increased by 12% (p = 0.03 as compared with baseline), and ALP activity increased by 79% (p = 0.02 as compared to non EPO resistant cases) after icodextrin introduction. In the patients with marked elevation of ALP activity, GSA scintigraphy showed inhibition of tracer binding. These results indicate that improvement in EPO-resistant anemia and greater ALP activity with icodextrin administration are mediated through blockade of the asialo receptors on hepatocytes.


Constructing a Foundational Platform Driven by Japan's K Supercomputer for Next-Generation Drug Design.
The cost of pharmaceutical R&D has risen enormously, both worldwide and in Japan. However, Japan faces a particularly difficult situation in that its population is aging rapidly, and the cost of pharmaceutical R&D affects not only the industry but the entire medical system as well. To attempt to reduce costs, the newly launched K supercomputer is available for big data drug discovery and structural simulation-based drug discovery. We have implemented both primary (direct) and secondary (infrastructure, data processing) methods for the two types of drug discovery, custom tailored to maximally use the 88 128 compute nodes/CPUs of K, and evaluated the implementations. We present two types of results. In the first, we executed the virtual screening of nearly 19 billion compound-protein interactions, and calculated the accuracy of predictions against publicly available experimental data. In the second investigation, we implemented a very computationally intensive binding free energy algorithm, and found that comparison of our binding free energies was considerably accurate when validated against another type of publicly available experimental data. The common feature of both result types is the scale at which computations were executed. The frameworks presented in this article provide prospectives and applications that, while tuned to the computing resources available in Japan, are equally applicable to any equivalent large-scale infrastructure provided elsewhere.


Leukotriene production by fresh human bone marrow cells: evidence of altered lipoxygenase activity in chronic myelocytic leukemia.
The metabolism of arachidonic acid through the lipoxygenase pathway was studied in suspensions of fresh human bone marrow cells from eight patients with chronic myelocytic leukemia (CML) and 10 normal controls. After the cells were incubated with the calcium ionophore A23187 and arachidonic acid, a technique including reverse- and straight-phase high-pressure liquid chromatography (HPLC) was employed to isolate and detect different lipoxygenase-mediated compounds. The detected compounds included leukotriene B4 (LTB4), with its two major nonenzymatic isomers 6-trans-LTB4 and 12-epi-6-trans-LTB4 5S,12S-DHETE, and the monohydroxy eicosatetraenoic acids 5-HETE, 12-HETE, and 15-HETE. The pattern of lipoxygenase-mediated products from the bone marrows was similar to that previously described from human peripheral blood. Of eight bone marrow samples from CML patients, five expressed values above 600 ng LTB4/10(8) nucleated cells, as compared to only one out of 10 controls. In contrast, the CML patients produced significantly lower amounts of both the double-dioxygenation product 5S,12S-DHETE (56.8 +/- 16.0 ng [mean +/- SE] versus 146.1 +/- 31.3 ng; p less than 0.05) and the monohydroxy acid 12-HETE (965 +/- 351 ng versus 4390 +/- 1801 ng; p less than 0.05), indicating a 12-lipoxygenase deficiency. The present results show that leukotrienes are formed by human bone marrow cells and further suggest the existence of altered lipoxygenase activity in CML.


Donor Characteristics and Recipient Outcomes After Heart Transplantation in Adult Congenital Heart Disease.
Background Patients with adult congenital heart disease (ACHD) experience long waitlist times for heart transplantation (HTx) while a large proportion of donor hearts are refused. The goal of this study was to inform optimal donor selection for patients with ACHD listed for HTx by examining the impact of donor characteristics on post-HTx outcomes. Methods and Results Using the Scientific Registry of Transplant Recipients, we conducted a retrospective analysis of patients aged ≥18 years listed for HTx in the United States between 2000 and 2016. We compared waitlist times between patients with ACHD and patients with noncongenital heart disease and constructed multivariate hazard models to identify donor characteristics associated with increased waitlist time. We then compared post-HTx survival between patients with ACHD and patients with noncongenital heart disease and constructed multivariate hazard models to identify donor characteristics associated with mortality. There were very few differences in donor characteristics between HTx recipients with ACHD and those with noncongenital heart disease. Status 1A-listed patients with ACHD experienced longer waitlist times compared with patients with noncongenital heart disease. Increased wait times were associated with some donor characteristics. Post-HTx outcomes varied over time, with patients with ACHD having inferior early mortality (0 to 30 days), similar intermediate mortality (31 days to 4 years), and superior late mortality (>4 years). We identified no donor characteristics associated with mortality to justify the observed differences in donor selection or waitlist time. Conclusions HTx candidates with ACHD wait longer for transplant but do not require unique donor selection criteria. HTx teams should consider liberalizing donor criteria and focusing only on evidence-based selection to improve waitlist outcomes and reduce the recipient-donor disparity.


Personalisation and embodiment in e-Learning for health professionals: A randomised controlled trial.
Mayer's theory of multimedia learning proposes that personalisation and embodiment (P/E) can improve outcomes in e-Learning. The authors hypothesised that an e-Learning module enhanced by P/E principles would lead to higher knowledge, perceived P/E and motivation among health care professionals, compared with an unenhanced module. The authors conducted a randomised trial comparing two versions of a 30-minute multimedia e-Learning module addressing the antibiotic management of pneumonia. The unenhanced format used slides with voiceover (human voice but no visible speaker), formal language and no specific P/E strategies. The enhanced format additionally implemented P/E strategies including conversational style, polite language, visible author, social congruence, human-like presence and professional presence by subtly changing the script and substituting several short videos of subject matter experts. Participants included pharmacists, physicians and advanced practice providers from three academic and several community hospitals. Outcomes included knowledge, perceived P/E (assessed by the Congruence Personalisation Questionnaire, CPQ), motivation (assessed via the Instructional Materials Motivation Survey [IMMS] and Motivated Strategies for Learning Questionnaire [MSLQ]) and course satisfaction. There were 406 participants including 225 pharmacists, 109 physicians and 72 advanced practice providers. Post-module knowledge was slightly higher for the enhanced versus the unenhanced format, but the difference did not reach statistical significance (adjusted mean difference, 0.04 of 10 possible, [95% CI -0.26, 0.34], p = 0.78; Cohen d 0.02). Participant perceptions of P/E (measured via CPQ) were significantly greater for the enhanced format (difference 0.46 of 5 possible [0.35, 0.56], p < 0.001; Cohen d 0.85), as were motivational features of the e-Learning course (measured via IMMS) (difference 0.14 of 5 possible [0.02, 0.26], p = 0.02; Cohen d 0.24). Participants' overall motivational orientation (measured via MSLQ) and course satisfaction were not significantly different between the two formats (p > 0.05). Application of P/E principles to an e-Learning module led to greater perceived P/E and motivational features but did not influence knowledge.


Non Hodgkin's lymphoma presenting with chest pain.
Non-Hodgkin's Lymphoma is a heterogeneous group of lymphoproliferative malignancies which can have differing patterns of behavior and clinical presentation. Unlike Hodgkin's disease, Non-Hodgkin's Lymphoma is much less predictable and has a far greater predilection for disseminating to extranodal sites. We offer a case of a 50 year old Caucasian male who presented with chest pain, and was ultimately diagnosed with follicular lymphoma by means of liver biopsy, in conjunction with immunohistochemistry. This malignancy grew at a rapid rate and over came our patient in a short period of time. The combination of a large tumor burden and cardiac infiltration made resuscitation extremely difficult when it became necessary, and this also made a positive outcome unlikely. It is rare for an immunocompetent patient to present with cardiac lymphoma without any previous signs and symptoms. Due to the rarity and the vague clinical presentation there must be a high degree of suspicion in order to diagnose cardiac lymphoma. As evidenced by this case time is of the essence to increase the likelyhood of survival in these patients.


Cortisone and corticotropin in allergic disease.
Cortisone and corticotropin (ACTH) in adequate doses usually promptly relieve allergic rhinitis, bronchial asthma, atopic eczema, urticaria, drug reactions and poison oak and ivy dermatitis. However, as the symptoms recur upon discontinuance of the hormones, and longcontinued use entails certain hazards, it is necessary to determine the underlying allergic cause of the symptoms and to institute measures to overcome it. However, when adequate antiallergic treatment does not control symptoms, the continued use of small doses of these steroids or of larger doses for weeks or months in severe or intractable cases is justified. In the few cases in which prolonged use of these hormones is necessary, the patient ought to be told of the possible complications, of the expense of laboratory studies that must be carried out, and of the cost of the hormones.


Methylation-Mediated Silencing of RBP7 Promotes Breast Cancer Progression through PPAR and PI3K/AKT Pathway.
Retinoid-binding protein7 (RBP7) is a member of the cellular retinol-binding protein (CRBP) family, which is involved in the pathogenesis of breast cancer. The study aims to illustrate the prognostic value and the potential regulatory mechanisms of RBP7 expression in breast cancer. Bioinformatics analysis with the TCGA and CPTAC databases revealed that the mRNA and protein expression levels of RBP7 in normal were higher compared to breast cancer tissues. Survival analysis displayed that the lower expression of RBP7, the worse the prognosis in ER-positive (ER+) breast cancer patients. Genomic analysis showed that low expression of RBP7 correlates with its promoter hypermethylation in breast cancer. Functional enrichment analysis demonstrated that downregulation of RBP7 expression may exert its biological influence on breast cancer through the PPAR pathway and the PI3K/AKT pathway. In summary, we identified RBP7 as a novel biomarker that is helpful for the prognosis of ER+ breast cancer patients. Promoter methylation of RBP7 is involved in its gene silencing in breast cancer, thus regulating the occurrence and development of ER+ breast cancer through the PPAR and PI3K/AKT pathways.


Enhanced weak-signal sensitivity in two-photon microscopy by adaptive illumination.
We describe a technique to enhance both the weak-signal relative sensitivity and the dynamic range of a laser scanning optical microscope. The technique is based on maintaining a fixed detection power by fast feedback control of the illumination power, thereby transferring high measurement resolution to weak signals while virtually eliminating the possibility of image saturation. We analyze and demonstrate the benefits of adaptive illumination in two-photon fluorescence microscopy.


Neurotrophic factor receptors in epiretinal membranes after human diabetic retinopathy.
Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to determine whether neurotrophic factor receptors (tyrosine kinase receptors trkA, trkB, and trkC; low-affinity neurotrophin [NT] receptor p75 [p75(NTR)]; glial cell line-derived neurotrophic factor receptor-alpha1 [GFR alpha 1] and GFR alpha 2; and Ret) are involved in the formation of ERMs after PDR. ERM samples were obtained by vitrectomy from 19 subjects with PDR aged 57 +/- 8 years with 17 +/- 8 years of diabetes and 15 subjects with idiopathic ERM. They were processed for RT-PCR analysis. In addition, 11 ERM samples from PDR patients aged 47 +/- 18 years with 13 +/- 4 years of diabetes were processed for immunohistochemical analysis. Expressions of trkA, trkB, trkC, p75(NTR), and Ret mRNAs were similar in both groups. In contrast, GFR alpha 2 expression levels were significantly higher (17 of 19 vs. 2 of 15 subjects in idiopathic ERM, P < 0.0001) in PDR subjects. Accordingly, immunohistochemical analysis revealed expression of GFR alpha 2 protein in all of the 11 ERMs derived from PDR patients, and that region was double-labeled with glial cell-specific markers. On the other hand, GFR alpha 1 expression was lower (8 of 19 vs. 12 of 15 subjects with idiopathic ERM, P = 0.0258) in PDR subjects. These results suggest a possibility that glial cell line-derived neurotrophic factor receptor (GDNF) subtypes are differently involved in the formation of ERMs.


Conformational changes induced in plasmodium actin polymer by Ca2+ in the presence of muscle native tropomysin.
The flexible polymer of plasmodium actin (Mg-polymer) combines with muscle native tropomyosin up to a weight ratio of actin: tropomyosin:troponin = 6:1:1. Mg-polymer which combined with muscle native tropomyosin undergoes a conformational change when the Ca2+ concentration of the solution is decreased by adding 0.5 mM ethylene glycol bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA): the viscosity of the solution increases by 50% and its ATPase activity decreases to about 20% of the original value, which suggests that the structure of Mg-polymer becomes more rigid. This change is reversible with respect to the Ca2+ concentration in the solution. The threshold concentration of Ca2+ for the conformational change is about 10(-6) M. The possible role of this transformation in vivo is discussed.


Serum half-life of intravenously injected intestinal and hepatic alkaline phosphatase isoenzymes in the cat.
The serum half-life of feline intestinal alkaline phosphatase (ALP) in the cat was 2 minutes, and that of feline hepatic ALP, 5.8 hours. The feline hepatic ALP could not be identified in the urine of the cats, nor was the clearance rate affected by bilateral nephrectomy. These data indicated the shor serum half-life of hepatic ALP was not a reusult of renal excretion. Since canine hepatic ALP cleared from feline blood at the same rate as the feline hepatic ALP, possibly the discrepancy in hepatic ALP half-life between the species was related to the cats' ability to clear the blood of the enzyme.


Role of complement receptor type 2 and endogenous complement in the humoral immune response to conjugates of complement C3d and pneumococcal serotype 14 capsular polysaccharide.
Conjugation of the complement fragment C3d to both T-cell-dependent (TD) protein and T-cell-independent type 2 (TI-2) polysaccharide antigens enhances the humoral immune response in mice immunized with either type of antigen. However, the ability of C3d-protein conjugates to enhance the antibody response in mice deficient in complement receptor types 1 and 2 (CR1 and CR2) has raised questions about the role of C3d-CR2 interactions in the adjuvant effect of C3d. In this study, we examined the role of CR2 binding and endogenous complement activation in the antibody response to conjugates of C3d and serotype 14 pneumococcal capsular polysaccharide (PPS14). To block binding of PPS14-C3d conjugates to CR2, mice were immunized with a mixture of vaccine and (CR2)2-immunoglobulin G1 (IgG1). Mice receiving (CR2)2-IgG1 at the time of primary immunization had a marked reduction in the primary anti-PPS14 antibody response but an enhanced secondary anti-PPS14 response, suggesting that C3d-CR2 interactions are required for the primary response but can have negative effects on the memory response. Further, compared with mice receiving PPS14-C3d having a high C3d/PPS14 ratio, mice immunized with PPS14-C3d with low C3d/PPS14 ratios had an enhanced secondary antibody response. Treatment of mice with cobra venom factor to deplete complement had insignificant effects on the antibody response to PPS14-C3d. Experiments with CBA/N xid mice confirmed that PPS14-C3d conjugates retain the characteristics of TI-2 rather than TD antigens. Thus, the adjuvant effect of C3d conjugated to PPS14 requires C3d-CR2 interactions, does not require activation of endogenous complement, and is not mediated by TD carrier effects.


Palm cooling does not improve running performance.
The aim of this study was to test the efficacy of the BEX Runner palm cooling device during a combination of exercise and environmental heat stress. Twelve subjects completed two randomly ordered time-to-exhaustion runs at 75% VO2max, 30 °C, and 50% relative humidity with and without palm cooling. Time to exhaustion runs started once the warm-up had elicited a core temperature of 37.5 °C. Heart rate, Rating of Perceived Exertion, Feeling Scale, and core temperature were recorded at 2-min intervals during each run. Time to exhaustion was longer in control than treatment (46.7±31.1 vs. 41.3±26.3 min, respectively, p<0.05); however, when warm-up time was included in analysis, there was no difference between trials for total exercise time (52.5±24.2 vs. 54.5±31.4 min, respectively). The rate-of-rise of core temperature was not different between control and treatment (0.047 vs. 0.048 °C · min-1, respectively). The use of the BEX Runner palm cooling device during a run in hot conditions did not eliminate or even attenuate the rise in core temperature. Exercise time in hot conditions did not increase with the use of the palm cooling device and time to exhaustion was reduced.


The role of mental disorder in attacks on European politicians 1990-2004.
The only systematic studies of attacks on public figures come from the USA. These studies de-emphasize the role of mental illness and suggest threats are of no predictive value. This study re-examines these questions through a study of attacks on European politicians. All non-terrorist attacks on elected politicians in Western Europe between 1990 and 2004 were analysed. Twenty-four attacks were identified, including five involving fatalities, and eight serious injuries. Ten attackers were psychotic, four drunk, nine politically motivated and one unclassifiable. Eleven attackers evidenced warning behaviours. The mentally disordered, most of whom gave warnings, were responsible for most of the fatal and seriously injurious attacks. A greater awareness of the link between delusional fixations on public figures and subsequent attacks could aid prevention. Equally importantly, recognition would encourage earlier intervention in people who, irrespective of whether they eventually attack, have delusional preoccupations which ruin their lives.


Longitudinal falls data in Parkinson's disease: feasibility of fall diaries and effect of attrition.
Identifying causes of falls for people with Parkinson's disease has met with limited success. Prospective falls measurement using the "gold standard" approach is challenging. This paper examines the process and outcomes associated with longitudinal falls reporting in this population. Participants were recruited from ICICLE-GAIT (a collaborative study with ICICLE-PD; an incident cohort study). Monthly falls diaries were examined over 48 months for accuracy of data and rate of attrition. To further inform analysis, characteristics of participants with 36-month completed diaries were compared with those who did not complete diaries. One hundred and twenty-one participants were included at baseline. By 12 months, falls diary data had reduced to 107 participants; to 81 participants by 36 months; and to 59 participants by 48 months. Key reasons for diary attrition were withdrawal from ICICLE-gait (n = 16) (13.2%), and noncompliance (n = 11) (9.1%). The only significant difference between the completed and non-completed diary groups was age at 36 months, with older participants being more likely to send in diaries. Prospective falls data is feasible to collect over the long term. Attrition rates are high; however, participants retained in the study are overall representative of the total falls diary cohort. Implications for Rehabilitation Understanding falls evolution in Parkinson's disease through consistent, personalized monitoring of falls events is critical to inform effective management. Our study shows that it is feasible to collect longitudinal falls data using "gold standard" methodology, although significant resources are required for implementation. We anticipate that our study methodology is broadly applicable to any at-risk falls cohort including older adults and diverse neurological conditions. Researchers and clinicians collating prospective falls data must ensure that participants understand what constitutes a fall, as per the World Health Organization definition. A second key point is to ensure prompt recording of any fall event.


Military Occupations Most Affected by Head/Sensory Injuries and the Potential Job Impact of Those Injuries.
Identifying Department of Defense (DoD) occupations affected by injuries to the head and sensory systems. We explored the Defense Medical Epidemiology Database to identify occupations with the highest incidence of injured personnel, then ranked how frequently they occurred in a top 10 list for each of four injury categories (head/brain, visual, auditory, vestibular) encompassing 25 injury codes. Across all four categories, the most affected occupations were identified, among which we chose three Army combat-related military occupational specialties (MOSs) for detailed study. We identified skills needed to perform these MOSs and explored whether MOS-critical deficits could be expected following the injuries. Some DoD occupations are more likely to suffer from these injuries, including Infantry, Combat Operations Control, Artillery/Gunnery, Motor Vehicle Operator, Combat Engineering, and Armor/Amphibious. Within these DoD occupations, we explored three Army combatant MOSs: Infantry (11B), Cavalry Scout (19D), and Artillery (13B), confirming that these jobs are likely to be disrupted by injuries within the four categories. Head and sensory injuries disproportionately affect certain military occupations. Relatively few injuries disrupt combat-related abilities that are job critical (e.g., firearms operation) and job specific (e.g., Artillery gunnery problems); these should be the focus of efforts to improve rehabilitation and RTD outcomes.


Chromatin-modifying enzymes as modulators of nuclear size during lineage differentiation.
The mechanism of nuclear size determination and alteration during normal lineage development and cancer pathologies which is not fully understood. As recently reported, chromatin modification can change nuclear morphology. Therefore, we screened a range of pharmacological chemical compounds that impact the activity of chromatin-modifying enzymes, in order to get a clue of the specific types of chromatin-modifying enzymes that remarkably effect nuclear size and shape. We found that interrupted activity of chromatin-modifying enzymes is associated with nuclear shape abnormalities. Furthermore, the activity of chromatin-modifying enzymes perturbs cell fate determination in cellular maintenance and lineage commitment. Our results indicated that chromatin-modifying enzyme regulates cell fate decision during lineage differentiation and is associate with nuclear size alteration.


Fibrous dysplasia of the clivus and sphenoid sinus.
Fibrous dysplasia is a primary disease of bone that may lead to bony distortion, expansion, and weakness. Craniofacial involvement is an important entity for physicians to be aware of because of the potential for impingement on neurovascular structures, intracranial extension, and cosmetic deformity. We report two cases of craniofacial fibrous dysplasia and discuss the clinical presentation, radiographic and histologic findings, and the management of affected patients.


A Case of Mayer-Rokitansky-Küster-Hauser Syndrome with a Fused Pancake-shaped Pelvic Kidney.
Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome is a female reproductive system disorder. It is characterized by a defect in the Müllerian ducts development, and it causes the absence of the uterus in variable degrees in upper vaginal hypoplasia. In addition, it is often associated with the unilateral renal dysplasia. Müllerian agenesis affects 1 in 4500 newborn girls and is considered as a sporadic anomaly. Women with MRKH Syndrome have a normal female chromosome pattern 46, XX with normal ovarian function. The presence of bilateral kidney agenesis with a pelvic pancake-shaped kidney is a rare condition, and a few cases have been reported in medical journals. This case study focuses on a case of MRKH Syndrome with bilateral renal agenesis and a pancake-shaped kidney.


Ciguatera poisoning.
Ciguatera is a form of poisoning that occurs after eating tropical and subtropical ciguatoxic fish. The ciguatoxins are a family of heat stable, lipid soluble cyclic polyether compounds that bind to and open voltage-sensitive Na(+) channels at resting membrane potential, resulting in neural hyperexcitability, as well as swelling of the nodes of Ranvier. The authors describe a 45-year-old man who developed acute gastrointestinal symptoms in Antigua soon after eating red snapper and grouper, potentially "ciguatoxic fish". This was followed by neurological symptoms 24-48 hours later, including temperature reversal (paradoxical dysaesthesia), intense pruritus and increased nociception as a result of a small fibre peripheral neuropathy. The patient's symptoms and small fibre neuropathy improved over a period of 10 months.


Testis-specific linker histone H1t is multiply phosphorylated during spermatogenesis. Identification of phosphorylation sites.
During normal spermatogenesis, the testis-specific linker histone H1t appears at pachytene stage becomes phosphorylated in early spermatids and disappears in late spermatids. Using reversed-phase and hydrophilic interaction liquid chromatography, H1t from rat and mouse testes was isolated, subjected to enzymatic digestion, and analyzed by mass spectrometry. We observed different phosphorylated states of H1t (mono-, di-, and triphosphorylated) as well as the unphosphorylated protein. Tandem mass spectrometry and immobilized metal ion affinity chromatography experiments with MS/MS/MS and multistage activation were utilized to identify five phosphorylation sites on H1t from rats. Phosphorylation occurs on both serine and threonine residues, whereas only two of these sites were located on peptides containing the CDK consensus motif (S/T)PXZ. Rat H1t phosphorylation starts first by phosphorylation of the nonconsensus motif SPKS in the COOH-terminal domain, namely at Ser-140 and to a smaller degree at a further nonconsensus motif at Ser-186. This is followed by phosphorylation of Ser-177 and Thr-155, both located in CDK consensus motifs. A single phosphorylation site at Ser-8 in the NH2-terminal tail was also found. Mouse H1t lacks Ser-186 and is phosphorylated at up to four sites. In contrast to somatic linker histones, no strict order of increasing phosphorylation could be detected in H1t. Thus, it appears that not the order of up-phosphorylation but the number of the phosphate groups is necessary for regulated chromatin decondensation, thus facilitating the substitution of H1t by transition proteins and protamines.


Severe obstructive sleep apnea alleviated by oral appliance in a three-year-old boy.
This clinical report describes a 3.5-year-old boy suffering from chronic daytime fatigue, accumulated snoring and dramatically appearing apnea during sleep. Oxycardiorespirography revealed a breathing pattern similar to repetitive obstructive apnea and an oxygen saturation periodically dropping to 80%. During tidal breathing, fiberoptic bronchoscopy showed aspiration of the aryepiglottic folds and the epiglottis during inspiration. Adenotonsillar hypertrophy was excluded. Due to the acknowledged side effects from various surgical approaches and nasal continuous positive airway pressure, a removable, functional Fraenkel II oral appliance was applied during sleep. Clinical assessment demonstrated resolution of the main respiratory symptoms, and oxycardiorespirography revealed a fundamental reduction in periodic obstructive apnea and desaturation. In conclusion, we consider the use of an oral functional appliance for severe obstructive sleep apnea in children to be a valuable alternative to other treatment methods.


Prospective randomized trial of emergency portacaval shunt and emergency medical therapy in unselected cirrhotic patients with bleeding varices.
A prospective randomized trial was conducted in unselected, consecutive patients with bleeding esophageal varices resulting from cirrhosis comparing (1) emergency portacaval shunt performed within 8 hr of initial contact (21 patients) with (2) emergency medical therapy (intravenous vasopressin and esophageal balloon tamponade) followed in 9 to 30 days by elective portacaval shunt in survivors (22 patients). All patients underwent the same diagnostic workup within 3 to 6 hr of initial contact, and received identical supportive therapy initially. All patients were followed up for at least 10 yr. The protocol contained no escape or cross-over provisions. There were no statistically significant differences between the two treatment groups in the incidence of any of the clinical variables, results of laboratory tests or degree of portal hypertension. Child's risk classes in the shunt group were A-2 patients, B-8 patients and C-11 patients, whereas in the medical group they were A-10 patients, B-5 patients, and C-7 patients, a significant difference (p < 0.01) that might have favored emergency medical treatment. Bleeding was controlled initially and permanently by emergency shunt in every patient, but by medical therapy in only 45% (p < 0.001). Mean requirement for blood transfusion was 7.1 +/- 2.6 units in the shunt group and 21.4 +/- 2.6 units in the medical group (p < 0.001). Eighty-one percent of the patients in the shunt group were discharged alive compared with 45% in the medical group (p = 0.027). Five- and 10-yr observed survival rates were 67% and 57%, respectively, after emergency shunt compared with 18% and 18%, respectively, after the combination of emergency medical therapy and elective shunt (p < 0.01). These survival rates produced by emergency shunt performed within 8 hr of initial contact confirm the effectiveness of this procedure observed in our previous unrandomized studies.


Highly selective colorimetric bacteria sensing based on protein-capped nanoparticles.
A rapid and cost-effective colorimetric sensor has been developed for the detection of bacteria (Bacillus subtilis was selected as an example). The sensor was designed to rely on lysozyme-capped AuNPs with the advantages of effective amplification and high specificity. In the sensing system, lysozyme was able to bind strongly to Bacillus subtilis, which effectively induced a color change of the solution from light purple to purplish red. The lowest concentration of Bacillus subtilis detectable by the naked eye was 4.5 × 10(3) colony-forming units (CFU) mL(-1). Similar results were discernable from UV-Vis absorption measurements. A good specificity was observed through a statistical analysis method using the SPSS software (version 17.0). This simple colorimetric sensor may therefore be a rapid and specific method for a bacterial detection assay in complex samples.


Enterovirus D68 infection upregulates SOCS3 expression to inhibit JAK-STAT3 signaling and antagonize the innate interferon response of the host.
Enterovirus D68 (EV-D68) can cause respiratory diseases and acute flaccid paralysis, posing a great threat to public health. Interferons are cytokines secreted by host cells that have broad-spectrum antiviral effects, inducing the expression of hundreds of interferon-stimulated genes (ISGs). EV-D68 activates ISG expression early in infection, but at a later stage, the virus suppresses ISG expression, a strategy evolved by EV-D68 to antagonize interferons. Here, we explore a host protein, suppressor of cytokine signaling 3 (SOCS3), is upregulated during EV-D68 infection and antagonizes the antiviral effects of type I interferon. We subsequently demonstrate that the structural protein of EV-D68 upregulated the expression of RFX7, a transcriptional regulator of SOCS3, leading to the upregulation of SOCS3 expression. Further exploration revealed that SOCS3 plays its role by inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). The expression of SOCS3 inhibited the expression of ISG, thereby inhibiting the antiviral effect of type I interferon and promoting EV-D68 transcription, protein production, and viral titer. Notably, a truncated SOCS3, generated by deleting the kinase inhibitory region (KIR) domain, failed to promote replication and translation of EV-D68. Based on the above studies, we designed a short peptide named SOCS3 inhibitor, which can specifically bind and inhibit the KIR structural domain of SOCS3, significantly reducing the RNA and protein levels of EV-D68. In summary, our results demonstrated a novel mechanism by which EV-D68 inhibits ISG transcription and antagonizes the antiviral responses of host type I interferon.


Synthesis, Structure, and SAR of Tetrahydropyran-Based LpxC Inhibitors.
In the search for novel Gram-negative agents, we performed a comprehensive search of the AstraZeneca collection and identified a tetrahydropyran-based matrix metalloprotease (MMP) inhibitor that demonstrated nanomolar inhibition of UDP-3-O-(acyl)-N-acetylglucosamine deacetylase (LpxC). Crystallographic studies in Aquifex aeolicus LpxC indicated the tetrahydropyran engaged in the same hydrogen bonds and van der Waals interactions as other known inhibitors. Systematic optimization of three locales on the scaffold provided compounds with improved Gram-negative activity. However, the optimization of LpxC activity was not accompanied by reduced inhibition of MMPs. Comparison of the crystal structure of the native product, UDP-3-O-(acyl)-glucosamine, in Aquifex aeolicus to the structure of a tetrahydropyran-based inhibitor indicates pathways for future optimization.


Quantitative study of yeast growth in the presence of added ethanol and methanol using a calorimetric approach.
Using a calorimeter with 24 sample units the heat evolved during incubation of yeast cultures at 30 degrees C was detected in the form of growth thermograms. Ethanol and methanol added to the culture medium produced changes in the growth thermograms that could be analyzed to calculate the 50% inhibitory concentration (Ki) and minimum inhibitory concentration (MIC). Correlation of the heat evolution curves with the number of cells and the turbidity of the culture was found to be very good. It was found that addition of ethanol and methanol up to 7.65% had clear effects of inhibition on growth of all yeast strains studied, reducing the growth rate constant and delaying growth. However, the amounts of ethanol produced from the nutrients available in the culture vial was only little affected by the initial addition of up to 7.65% (v/v) of ethanol or methanol in the medium.


Postoperative recurrence of hepatocellular carcinoma.
Sixty-nine patients with hepatocellular carcinoma underwent curative hepatic resections as primary cases from 1981 to 1986. Seven patients died in the hospital after operation. The other 62 patients left the hospital and were closely followed for 25 to 78 months. Recurrence of carcinoma became obvious in 41 (66%) of 62 patients. The clinical and pathologic features of these 41 patients were not significantly different from those of the other patients. Recurrent tumors were found in the residual liver in 38 patients (93%), in the bone in 2 (5%), and in the lung in 1 (2%). Recurrence was diagnosed within 1 year, between 1 and 2 years, and more than 2 years after the operation in 22 (56%), 10 (26%), and 7 (18%) patients, respectively. It was difficult to determine the exact time of recurrence in two patients. There was a significant negative correlation between the size of primary tumor and time until recurrence; the larger the primary tumor, the shorter the time until recurrence. Among the 29 patients who underwent local excisions for their primary tumors, 19 recurrences were observed. Eighteen were found in the residual liver, in the same segment as the primary tumor, or in one near it. Larger hepatic resection for primary tumors is thus advocated to prevent recurrence.


Visuomotor priming of action preparation and motor programming is similar in visually guided and memory-guided actions.
The present study examined whether the planning and execution of a reach-to-grasp movement is susceptible to visuomotor priming, and whether the strength of the priming effect depends on the availability of visual feedback. Participants grasped a target object as quickly as possible with either a whole-hand grip or a precision grip upon hearing an auditory stimulus. Prior to the auditory cue, a prime stimulus was presented. The prime stimulus depicted an object that was either congruent, incongruent, or ambiguous with respect to the required grasp, or it showed no object at all. In addition, participants performed the grasping task in one of three vision conditions: participants' vision was either occluded during both the motor programming and online-control phase (no-vision), participants had vision only during the motor programming phase (partial-vision), or they had vision available throughout task performance (full-vision). Results revealed the presence of two discrete priming effects. First, we found a facilitative effect of congruent compared to incongruent prime-grip combinations that influenced reaction times and kinematic parameters. Second, we found that movements were initiated slower during the no prime compared to all other conditions. However, this effect did not affect movement kinematics. Importantly, the size of both effects was similar regardless of vision. Together, these results suggest that visuomotor priming effects exhibit a similar influence on memory-guided and visually guided actions, indicating the same underlying object representations for those actions, and thus further challenging the real-time view of motor programming. Furthermore, the two different priming effects suggest the presence of functionally distinct, yet related modules or processes related to action preparation and motor programming, and hint towards possible ventrodorsal interactions.


Shortened CRISPR-Cas9 arrays enable multiplexed gene targeting in bacteria from a smaller DNA footprint.
CRISPR technologies comprising a Cas nuclease and a guide RNA (gRNA) can utilize multiple gRNAs to enact multi-site editing or regulation in the same cell. Nature devised a highly compact means of encoding gRNAs in the form of CRISPR arrays composed of conserved repeats separated by targeting spacers. However, the capacity to acquire new spacers keeps the arrays longer than necessary for CRISPR technologies. Here, we show that CRISPR arrays utilized by the Cas9 nuclease can be shortened without compromising and sometimes even enhancing targeting activity. Using multiplexed gene repression in E. coli, we found that each region could be systematically shortened to varying degrees before severely compromising targeting activity. Surprisingly, shortening some spacers yielded enhanced targeting activity, which was linked to folding of the transcribed array prior to processing. Overall, shortened CRISPR-Cas9 arrays can facilitate multiplexed editing and gene regulation from a smaller DNA footprint across many bacterial applications of CRISPR technologies.


Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression.
Gastric cancer (GC) is still a serious health problem and remains the second most common type of fatal cancer worldwide. Comprehensive gene expression analyses may be useful to identify genes associated with invasion/metastasis in GC. Among them, array-based hybridization and serial analysis of gene expression (SAGE) are currently the most common approaches. Over the past 3 years, several large-scale gene expression studies with array-based hybridization and SAGE have been performed and several genes have been identified. This review describes genes associated with invasion/metastasis in GC which have been identified by array-based hybridization and SAGE. We compared the expression levels of the genes identified by array-based hybridization with our SAGE data. In addition, expression of the candidate genes obtained by SAGE was further investigated by quantitative RT-PCR of 40 GC samples. MIA and GW112 were overexpressed in 10 (25%) and 22 (55%) of 40 GC samples, and the overexpression of these two genes was associated with tumor stage, respectively. We also discuss the significance of HMGB1/amphoterin in invasion and metastasis of GC.


Tracing coffee tabletop traces.
Crystallization processes under different conditions are of fundamental interest in chemistry, pharmacy, and medicine. Therefore, we have studied the formation of micro- and nanosized crystals using water-caffeine (1,3,7-trimethyl-1 H-purine-2,6(3 H,7 H)-dione) solutions under ambient conditions as a relevant model system. When droplets of an aqueous caffeine solution evaporate and eventually dry on surfaces (glass, polystyrene, and polyester), stable "coffee tabletop" rings with a perimeter of typically 3 mm are formed after 20 to 50 min. Using a micro focus X-ray beam available at the BESSY muSpot-beamline, the fine structure of different caffeine needles can be distinguished. Unexpectedly, both crystal modifications (alpha- and beta-caffeine) are present, but locally separated in these rings. Furthermore, AFM studies reveal the presence of even smaller particles on a nanometer length scale. To eliminate influences of surface irregularities from the crystallization process, acoustic levitation of liquid samples was employed. Such levitated droplets are trapped in a stable position and only surrounded by air. The solvent in an ultrasonically levitated drop evaporates completely, and the resulting crystallization of caffeine was followed in situ by synchrotron X-ray diffraction. In this case, the diffraction pattern is in accordance with pure alpha-caffeine and does not indicate the formation of the room temperature polymorph beta-caffeine. Hence, our investigations open new vistas that may lead to a controlled formation of cocrystals and novel polymorphs of micro- and nanocrystalline materials, which are of relevance for fundamental studies as well as for pharmaceutical and medical applications.


Novel self-association fibronectin sites.
In this study, we report a strong interaction between two contiguous proteolytic fragments of fibronectin, each having a mass of about 16 kDa. This interaction was stable in 4 M NaCl and 4 M urea and dissociation of the two fragments required buffers containing 0.5% sodium dodecyl sulphate. After purification, these peptides maintained their ability to interact when mixed. One fragment was made up of type III repeat 4 and part of 5, the other by repeat 6 and part of 5. Such strong interaction between two fibronectin regions may play a role in fibronectin conformation as well as during fibronectin fibril formation.


Haemotherapy with Fibrinogen for Perioperative Bleeding Prevention-A View on Arterial Thrombogenesis and Myocardial Infarction in the Rat In Vivo.
Major blood loss during cardiac surgery is associated with increased morbidity and mortality. Clinical pilot studies indicated that preoperative fibrinogen supplementation reduces postoperative blood loss without increasing thrombotic complications. However, an increase in fibrinogen concentration might rather aggravate pre-existing thrombosis than increase the incidence of thrombotic events. Therefore, we investigated, in the present study, whether fibrinogen supplementation influences (1) arterial thrombus formation, (2) the extent of myocardial infarction and (3) the cardioprotective effect of ischaemic preconditioning. Arterial thrombogenesis of the femoral artery was induced by topic FeCl3 treatment in anaesthetised Wistar rats after pretreatment with 60 mg/kg (Fiblow), 120 mg/kg (Fibhigh) or vehicle (Con). Vessel blood flow was monitored, and time to vessel occlusion was analysed as a marker for arterial thrombogenesis. In addition, regional myocardial I/R injury was induced by temporary left coronary artery occlusion in rats pretreated with or without fibrinogen supplementation. In additional groups, ischaemic preconditioning (IPC) was induced by 3 cycles of 5 min of ischaemia/reperfusion. In all groups, myocardial infarct size was determined by triphenyltetrazoliumchlorid staining. Arterial thrombogenesis was not affected by fibrinogen pretreatment. No differences in time until vessel occlusion between Con, Fiblow and Fibhigh groups were observed. In addition, fibrinogen supplementation in low and high concentrations had no effect on infarct size after regional myocardial ischaemia and reperfusion (Fiblow: 66 ± 10%, Fibhigh: 62 ± 9%; each ns vs. Con). IPC reduced infarct size from 62 ± 14% to 34 ± 12% (p < 0.05 vs. Con). Furthermore, both fibrinogen concentrations did not affect cardioprotection by ischaemic preconditioning (Fiblow + IPC: 34 ± 11%, Fibhigh + IPC: 31 ± 13%; each ns vs. IPC). Haemotherapy with fibrinogen did not affect arterial thrombogenesis, myocardial infarction and the cardioprotective effect of ischaemic preconditioning.


Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks.
How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG) properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI) of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa) were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are "progressive and earlier" or "abrupt but delayed" account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious state. This theoretical approach also offers a principled explanation of how the brain reconstitutes consciousness and cognitive functions after physiologic (sleep), pharmacologic (anesthesia), and pathologic (coma) perturbations.


Atomic-scale structure of dislocations revealed by scanning tunneling microscopy and molecular dynamics.
The intersection between dislocations and a Ag(111) surface has been studied using an interplay of scanning tunneling microscopy (STM) and molecular dynamics. Whereas the STM provides atomically resolved information about the surface structure and Burgers vectors of the dislocations, the simulations can be used to determine dislocation structure and orientation in the near-surface region. In a similar way, the subsurface structure of other extended defects can be studied. The simulations show dislocations to reorient the partials in the surface region leading to an increased splitting width at the surface, in agreement with the STM observations. Implications for surface-induced cross slip are discussed.


Developmental regulation of metabotropic glutamate receptor 5b protein in rodent brain.
The metabotropic glutamate receptor type 5 (mGlu5) is expressed in two splice variants, mGlu5a and mGlu5b, which differ in that mGlu5b has a 33-amino acid insert in the intracellular C-terminal domain. This receptor subtype is highly regulated, with higher levels found in developing animals, but the contributions of the individual splice variants to the receptor population at any time are unknown. An antibody that specifically reacts with the insert was developed and used to measure the regional and developmental distribution of mGlu5b in the mouse and rat brain. In contrast to total mGlu5 receptor protein, most brain regions exhibit a less than two-fold alteration between post-natal day 7 and adult levels of mGlu5b. In the adult cortex, there is a three-fold increase of mGlu5b protein relative to at post-natal day 7. Estimates of mGlu5a protein indicate that most of the developmental alteration in total mGlu5 is due to changes in expression of this variant. Comparison of mGlu5b protein and mRNA levels indicates that greatly different post-transcriptional regulation occurs across brain regions. These results indicate that mGlu5 expression is precisely and complexly controlled at the level of transcription and that different functions of mGlu5 during different developmental periods and in distinct regions are likely mediated by different splice variants.


Back pain caused by a pseudo-tumorous vertebral collapse: atypical presentation of primary vertebral hydatidosis.
Hydatidosis, also known as echinococcosis, is a rare but serious parasitic disease in endemic areas. Primary spinal location is extremely rare. This case report describes a rare instance of hydatid cyst that caused severe and progressive low-back pain and neurologic dysfunction. Spine MRI showed a unique vertebral collapse of Th12 body with multicystic lesions filling the spinal canal. In addition, hydatidosis serodiagnostic test was positive at 1/725. Treatment depended on the actual surgical removal of the cysts. Surgery consisted in excision and extirpation of the cysts, associated with decompressive laminectomy. The diagnosis was confirmed on the basis of histological results. No coincidental hydatid visceral involvement was found. Antihelminthic drugs (Albendazole) were promptly given before surgery for a long period. The outcome was satisfactorily marked by total regression of the motor deficit and sphincter disorders.


Partially matched bone marrow transplantation in patients with myelodysplastic syndromes.
Six patients with a myelodysplastic syndrome (MDS) were treated with bone marrow transplantation (BMT) using partially-matched related (3) or unrelated (3) donors. Patients' ages ranged from 7 to 31 years (median, 10 years). Bone marrow karyotype abnormalities were present in five patients included four with monosomy 7 and one with trisomy 8. One patient was in complete remission before transplant; the remaining five had excess of blasts or were undergoing leukemic transformation. Donor, and recipient were mismatched at the DR locus (2), A locus (2), B locus (1), or A and B loci (1). Conditioning included busulfan, cytarabine, cyclophosphamide, methylprednisolone, and total body irradiation. Cyclosporine was started on day -1. Marrows were T-cell depleted using a monoclonal antibody (MoAb) (CD3) and normal rabbit serum. Four patients engrafted routinely. One patient died of aspergillosis before engraftment (day 12) and one patient failed to engraft on first attempt, but engrafted following additional preparation. Median time to neutrophils greater than 500/microL and platelets greater than 25,000/microL were 16 and 19 days, respectively. Acute graft-v-host disease (GVHD) was less than or equal to grade II in all patients. One patient died with recurrent disease (day 257). One patient died at day 515 of pancreatitis and respiratory failure. Three patients are alive and disease-free at 240, 395, and 560 days post-BMT including two patients with unrelated donors. Partially matched T-depleted bone marrow from related or unrelated donors may be effective, and possibly curative therapy for patients with MDS who lack a histocompatibility locus antigen (HLA)-identical sibling donor.


Extra-Short 4-mm Implants Splinted to 10-mm Implants in the Posterior Maxilla: 3-year Results.
To evaluate the 3-year success and survival rates of fixed prostheses supported by 4-mm extra-short implants splinted to 10-mm implants in patients with shortened maxillary arches and low maxillary sinus floors. A total of 11 patients with reduced alveolar bone heights due to low maxillary sinus floors received two or three titanium-zirconium tissue-level implants: one or two extra-short (4 mm) implants, and one implant 10 mm in length. After 6 months, prosthetic rehabilitation with splinted crowns connecting the 4- and 10-mm implants was performed. Follow-up visits and maintenance protocols were implemented every 4 to 6 months. The 11 patients were treated with 11 10-mm implants and 17 4-mm implants. One extra-short implant failed and was removed before loading, and its planned design was modified from three splinted crowns to a bridge between the 10- and 4-mm implants. After 36 months, all (11/11) prosthetic rehabilitations connecting the 10-mm (11/11) and 4-mm (16/16) implants were functional. At the 10-mm implant sites, the median (interquartile range [IQR]) probing depth and marginal bone loss measured 2.9 mm (2.3 to 3.2) and 1.3 mm (1.0 to 1.5), respectively. At the 4-mm implant sites, the median (IQR) probing depth and marginal bone loss measured 2.9 mm (2.4 to 3.1) and 0.3 mm (0.1 to 0.5), respectively. Prosthetic rehabilitation with splinted crowns connecting 4-mm and 10-mm implants showed promising outcomes in shortened maxillary dental arches after 3 years. Additional studies are needed to further validate these findings.


Simulating Timescale Dynamics of Network Traffic Using Homogeneous Modeling.
Simulating and understanding traffic dynamics in large networks are difficult and challenging due to the complexity of such networks and the limitations inherent in simulation modeling. Typically, simulation models used to study traffic dynamics include substantial detail representing protocol mechanisms across several layers of functionality. Such models must be restricted in space and time in order to be computationally tractable. We propose an alternative simulation approach that uses homogeneous modeling with an increased level of abstraction, in order to explore networks at larger space-time scales than otherwise feasible and to develop intuition and insight about the space-time dynamics of large networks. To illustrate the utility of our approach, we examine some current understandings of the timescale dynamics of network traffic, and we discuss some speculative results obtained with homogeneous modeling. Using a wavelet-based technique, we show correlation structures, and changes in correlation structures, of network traffic under variations in traffic sources, transport mechanisms, and network structure. Our simulation results justify further investigation of our approach, which might benefit from cross-verifications against more detailed simulation models.


Effects of intravenous benzo[a]pyrene dose administration on levels of exposure biomarkers, DNA adducts, and gene expression in rats.
The effects of benzo[a]pyrene (BaP) administration on biomarkers of exposure and early effects were studied in male Sprague-Dawley rats intravenously injected with doses of 0.4, 4, 10, or 40 μmol BaP/kg . Blood, tissues, and excreta were collected 8 and 24 h posttreatment. BaP and several of its metabolites were simultaneously measured in blood, tissues and excreta by ultra-high-performance liquid chromatography (UHPLC)/fluorescence. DNA adducts of BaP diol epoxide (BaPDE) in lungs were quantified using an ultrasensitive immunoassay with chemiluminescence detection. Expression of selected genes in lungs of treated rats (lung RNA) compared to control rats was also assessed by quantitative real-time polymerase chain reaction. There was a dose-dependent increase in blood, tissue, and excreted levels of BaP metabolites. At 8 and 24 h postinjection, BaP and hydroxyBaP were found in higher concentrations in blood and tissues compared to other analytes. However, diolBaP were excreted in greater amounts in urine and apparently more rapidly than hydroxyBaP. Mean percentages (± SD) of injected dose excreted in urine as 4,5-diolBaP during the 0-8 h and 0-24 h period posttreatment were 0.16 ± 0.027% and 0.14 ± 0.083%, respectively. Corresponding values for 3-OHBaP were 0.0045 ± 0.0009% and 0.026 ± 0.014%. BaP-diones were not detectable in blood, tissues, and excreta; 7,8-diolBaP and BaPtetrol were found to be minor metabolites. There was also a dose-dependent increase in DNA adduct formation in lung. Analysis of gene expression further showed a modulation of Cyp1a1, Cyp1b1, Nqo1, Nrf2, Fos, and Ahr expression at 10- and 40-μmol/kg doses, but not at the lower doses. This study provided a better assessment of the influence of absorbed BaP doses on biological levels of diolBaP and OHBaP exposure biomarkers and association of the latter with early biological alterations, such as DNA adducts and gene expression.