Measurement of Ocular Vestibular Evoked Myogenic Potentials: Nasion Reference Montage as an Alternative to the Clinical Standard Montage.
To compare two novel electrode montages for ocular, vestibular evoked myogenic potential using single-nasion reference electrodes with the clinical standard montage. Randomized crossover experiment. Tertiary referral center. Sixty healthy participants. Normal hearing and vestibular function were confirmed with an extensive test-battery. All ocular, vestibular evoked myogenic potential settings were measured with air-conducted tone bursts at 100-dB normal hearing level and a frequency of 500 Hz. Three electrode montages were measured in randomized order: the clinical standard montage ("S"), the nasion reference montage ("N"), and the nasion reference montage with a more lateral active electrode ("L"). Upgaze was standardized to 35 degrees. Detection rate, latency of N1 and P1, peak-to-peak amplitude of N1 and P1, signal-to-noise ratio (SNR), asymmetry ratio (AR), concordance of expert assessment, and reliability. All electrode montages showed detection rates greater than 90%. Latencies for "L" were shorter than for "S" and "N." Amplitudes and SNR for "S" and "N" were higher than for "L," whereas the values for "S" and "N" did not differ significantly. For AR, no significant differences between the montages were assessed. Concordance of experts ranged from 78% for "L" and 89.8% for "N." All montages provided excellent day-to-day reliability (intraclass correlation coefficient ≥0.9) for amplitudes and SNR. Montage N could be a useful alternative to the clinical standard montage: although results are roughly equivalent, montage N requires one less electrode to do so.


A Cross-Sectional Study of Variations in Reimbursement for Breast Reconstruction: Is A Healthcare Disparity On the Horizon?
Despite growing demand for breast reconstruction, financial disincentives to perform breast reconstruction in patients with government-sponsored insurance plans may lead to longer wait times and decreased access to care. We identify the variation in reimbursement for implant and autologous reconstruction as a step toward understanding these financial implications, to develop safeguards to minimize effects on access to care. Billing data were collected over a 10-year period for patients undergoing implant-based (19357) or free-flap (19364) breast reconstruction. Patients were placed into cohorts according to insurance type-Medicare, Medicaid, or private insurance, and these were directly compared. A total of 2691 women underwent breast reconstruction between 2003 and 2013; 71.2% had private insurance, 13.3% had Medicaid, and 14.49% had Medicare. For implant-based reconstructions, the average reimbursement of total charges was 16.3% for Medicaid, 28.3% for Medicare, and 67.2% for private insurance. For autologous reconstruction, average reimbursement was 12.37% for Medicaid, 22.9% for Medicare, and 35.35% for private insurance. Hourly reimbursement estimates for Medicaid patients undergoing autologous reconstruction were lowest. The highest hourly reimbursement estimate was for privately insured patients undergoing implant-based reconstruction. Over time, reimbursement for autologous reconstruction has declined significantly for all payor types, whereas implant-based reimbursement disparities are narrowing. We found that wide variations in reimbursement for breast reconstruction procedures exist and may preclude some surgeons from offering certain reconstructive options to a subset of patients. Understanding these discrepancies is a key first step in minimizing a potential care delivery disparity for this patient population.


Petri net modelling of biological networks.
Mathematical modelling is increasingly used to get insights into the functioning of complex biological networks. In this context, Petri nets (PNs) have recently emerged as a promising tool among the various methods employed for the modelling and analysis of molecular networks. PNs come with a series of extensions, which allow different abstraction levels, from purely qualitative to more complex quantitative models. Noteworthily, each of these models preserves the underlying graph, which depicts the interactions between the biological components. This article intends to present the basics of the approach and to foster the potential role PNs could play in the development of the computational systems biology.


Domain Adaptation and Feature Fusion for the Detection of Abnormalities in X-Ray Forearm Images.
The main challenge in adopting deep learning models is limited data for training, which can lead to poor generalization and a high risk of overfitting, particularly when detecting forearm abnormalities in X-ray images. Transfer learning from ImageNet is commonly used to address these issues. However, this technique is ineffective for grayscale medical imaging because of a mismatch between the learned features. To mitigate this issue, we propose a domain adaptation deep TL approach that involves training six pre-trained ImageNet models on a large number of X-ray images from various body parts, then fine-tuning the models on a target dataset of forearm X-ray images. Furthermore, the feature fusion technique combines the extracted features with deep neural models to train machine learning classifiers. Gradient-based class activation heat map (Grad CAM) was used to verify the accuracy of our results. This method allows us to see which parts of an image the model uses to make its classification decisions. The statically results and Grad CAM have shown that the proposed TL approach is able to alleviate the domain mismatch problem and is more accurate in their decision-making compared to models that were trained using the ImageNet TL technique, achieving an accuracy of 90.7%, an F1-score of 90.6%, and a Cohen's kappa of 81.3%. These results indicate that the proposed approach effectively improved the performance of the employed models individually and with the fusion technique. It helped to reduce the domain mismatch between the source of TL and the target task.


Parental hypercholesterolemia and family medical history as predictors of hypercholesterolemia in their children.
Parental hypercholesterolemia would be a better predictor of hypercholesterolemia than family medical history in children. To compare the strength of association and predictive values of parental hypercholesterolemia versus a positive family history in pediatric hypercholesterolemia. Material and methods. Cross-sectional, analytical study. Cholesterol levels were measured in children aged ≥ 6 and < 12 years and in their biological parents. A survey was administered to parents. The association was estimated using the odds ratio (OR), and its predictive value was determined. The relationship between hypercholesterolemia in parents and their children was studied with multilevel regression. A total of 332 children, 304 mothers, and 206 fathers were assessed. A cholesterol level ≥ 240 mg/dL in one or both parents and ≥ 200 mg/dL in children showed: OR= 6.40; 95 % confidence interval (CI)= 2.85-14.48; p < 0.0001; sensitivity= 69 %; specihcity= 74 %; positive predictive value (PPV)= 34 %; negative predictive value (NPV)= 93 %; positive likelihood ratio (LR+)= 2.69; negative likelihood ratio (LR-)= 0.42. Family medical history versus children with cholesterol level ≥ 200 showed: OR= 1.86; 95 % CI= 0.84-4.11; p= 0.1272; sensitivity= 69 %; specihcity= 46 %; PPV= 19 %; NPV= 89 %; LR+= 1.27; LR-= 0.68. Cholesterol was 2.9 and 2.5 mg/dL higher per every 10 mg/dL of increased cholesterol in mothers and fathers, respectively. Parental hypercholesterolemia was significantly associated with hypercholesterolemia in children and showed a higher predictive power than a positive family medical history.


Mutations in the alpha-synuclein gene in Parkinson's disease among Indians.
To investigate the prevalence of G88C, G209A and any other mutation(s) in exons 3 and 4 of the alpha-synuclein gene in Indian patients with Parkinson's disease (PD). A total of 169 PD patients comprising 18 familial, 3 juvenile, 48 early onset and 100 sporadic cases were included in this study. Genomic DNA was amplified by PCR using primers specific for Exons 3 and 4. Mutations at G88C and G209A were screened following restriction enzyme digestion of the PCR product. Direct PCR product sequencing of entire exons 3 and 4 was carried out for at least one proband each from the 10 familial cases. Neither G88C and G209A mutations nor any other mutation in exons 3 and 4 was found in the PD patients analysed. The G88C and G209A mutations do not seem to be the predominant genetic determinant of PD among Indians.


Directing crowd simulations using navigation fields.
We present a novel approach to direct and control virtual crowds using navigation fields. Our method guides one or more agents toward desired goals based on guidance fields. The system allows the user to specify these fields by either sketching paths directly in the scene via an intuitive authoring interface or by importing motion flow fields extracted from crowd video footage. We propose a novel formulation to blend input guidance fields to create singularity-free, goal-directed navigation fields. Our method can be easily combined with the most current local collision avoidance methods and we use two such methods as examples to highlight the potential of our approach. We illustrate its performance on several simulation scenarios.


Spatial Memory Performance Associated with Measures of Immune Function in Elderly Female Rhesus Macaques.
We recently reported that in aged female rhesus macaques, spatial learning and memory correlates with circadian sleep-wake measures and hippocampal muscarinic type 1 (M(1)) receptor binding. To investigate if spatial memory also correlates with measures of immune function, we now assessed the magnitude of the adaptive immune response to vaccination in the same old female rhesus macaques. Cognitively characterized animals were classified as good spatial performers (GSP) or poor spatial performers (PSP) based on performance in the Spatial Foodport maze. The GSP group had higher frequency of CD8, but not CD4, interferon-γ (IFN-γ) producing cells following vaccination compared to the PSP group, suggesting a stronger CD8 T cell response in the GSP group. In addition, the number of CD-8 IFN-γ positive cells correlated with measures of sleep quality. Interestingly, the PSP group had a significantly higher antibody titer compared to the GSP group, and antibody titer negatively correlated with day-time activity. Thus, in aged female rhesus macaques, superior cognitive performance is correlated with a more robust CD8 T cell response but a reduced antibody response to vaccination.


Application of the Novel Ventilation Mode FLow-Controlled EXpiration (FLEX): A Crossover Proof-of-Principle Study in Lung-Healthy Patients.
Traditionally, mechanical ventilation is achieved via active lung inflation during inspiration and passive lung emptying during expiration. By contrast, the novel FLEX (FLow-controlled EXpiration) ventilator mode actively decreases the rate of lung emptying. We investigated whether FLEX can be used during intraoperative mechanical ventilation of lung-healthy patients. In 30 adult patients scheduled for neurosurgical procedures, we studied respiratory system mechanics, regional ventilation, oxygenation, and hemodynamics during ventilation with and without FLEX at positive end-expiratory pressure (PEEP) of 5 and 7 cm H2O. The FLEX system was integrated into the expiratory limb and modified the expiratory flow profile by continuously changing expiratory resistance according to a computer-controlled algorithm. Mean airway pressure increased with PEEP by 1.9 cm H2O and with FLEX by 1 cm H2O (all P < .001). The expiratory peak flow was 42% lower with FLEX than without FLEX (P < .001). FLEX caused significant shifts in aeration from ventral to the dorsal lung regions. Respiratory mechanics, end-tidal carbon dioxide partial pressure, oxygenation, and hemodynamics were independent from FLEX and PEEP. We observed no critical incidents or FLEX malfunctions in any measurement that would have required an intervention or termination of the FLEX mode. FLEX can be used in lung-healthy patients who are mechanically ventilated during general anesthesia. FLEX improves the homogeneous distribution of ventilation in the lungs.


Characterising the inhibitory actions of ceramide upon insulin signaling in different skeletal muscle cell models: a mechanistic insight.
Ceramides are known to promote insulin resistance in a number of metabolically important tissues including skeletal muscle, the predominant site of insulin-stimulated glucose disposal. Depending on cell type, these lipid intermediates have been shown to inhibit protein kinase B (PKB/Akt), a key mediator of the metabolic actions of insulin, via two distinct pathways: one involving the action of atypical protein kinase C (aPKC) isoforms, and the second dependent on protein phosphatase-2A (PP2A). The main aim of this study was to explore the mechanisms by which ceramide inhibits PKB/Akt in three different skeletal muscle-derived cell culture models; rat L6 myotubes, mouse C2C12 myotubes and primary human skeletal muscle cells. Our findings indicate that the mechanism by which ceramide acts to repress PKB/Akt is related to the myocellular abundance of caveolin-enriched domains (CEM) present at the plasma membrane. Here, we show that ceramide-enriched-CEMs are markedly more abundant in L6 myotubes compared to C2C12 myotubes, consistent with their previously reported role in coordinating aPKC-directed repression of PKB/Akt in L6 muscle cells. In contrast, a PP2A-dependent pathway predominantly mediates ceramide-induced inhibition of PKB/Akt in C2C12 myotubes. In addition, we demonstrate for the first time that ceramide engages an aPKC-dependent pathway to suppress insulin-induced PKB/Akt activation in palmitate-treated cultured human muscle cells as well as in muscle cells from diabetic patients. Collectively, this work identifies key mechanistic differences, which may be linked to variations in plasma membrane composition, underlying the insulin-desensitising effects of ceramide in different skeletal muscle cell models that are extensively used in signal transduction and metabolic studies.


Multispecies probiotics promote perceived human health and wellbeing: insights into the value of retrospective studies on user experiences.
When taking a broader perspective on the societal impact of probiotics, engagement of end-users is important to discover unmet needs, define relevant health benefits and identify key considerations for successful implementation in daily practice. This study therefore takes a retrospective approach and analyses a database of user experiences to review the effects of four multispecies probiotic formulations. The user experiences were analysed in a dependent sample manner (without control group) and complement previous randomised controlled trials that have been performed with the formulations. The database consisted of 584 evaluable user experiences regarding the impact of probiotic supplementation on perceived quality of life (QoL), gastrointestinal (GIT) symptoms and reported stool consistency after two weeks of consumption. Two different scales were used (n=344 in a 5-point scale; n=240 in a 10-point scale), which are presented as separate analyses. In the combined population of the 5-point-scale questionnaire, a significant increase in perceived QoL and a significant reduction in perceived GIT symptoms was observed. Descriptive summaries also indicate that diarrhoea- and constipation-like stool patterns are reduced following supplementation. Moreover, half of participants indicated that probiotic supplementation had a positive effect on their unmet medical need, and 64% of users were likely to continue using the product. Similar results were observed in the 10-point scale questionnaire. Considering the clinical relevance of probiotic supplementation in specific target groups, subgroup analyses were performed on participants who consumed the products for diarrhoea, constipation, Inflammatory Bowel Disease, Irritable Bowel Syndrome, and antibiotic usage. Overall, findings support the potential of probiotics to advance perceived human health and support the daily wellbeing of users. This systematic analysis of user experiences thereby contributes to the external validity of studies evaluating clinical effects of probiotics and increases knowledge on their societal impact.


Clinical significance of Y chromosome loss in hematologic disease.
We have studied 215 male patients (aged 45-97 years) whose sole cytogenetic abnormality was clonal loss of the Y chromosome in metaphase cells from unstimulated cultures. The patients comprised a control group with no evidence of hematologic disease and four disease case groups: 1) myelodysplastic syndrome (MDS), refractory anemia, refractory anemia with excess blasts (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia; 2) acute myelogenous leukemia; 3) myeloproliferative disorder (MPD), chronic granulocytic leukemia, and polycythemia vera; and 4) B-cell lymphoma/leukemia. The frequency of cells with Y loss increased with age and was significantly greater in cases than in controls, but it was not correlated with survival or with prior therapy. The frequency of cases with a -Y clone was 6.3% of male karyotypes and represented 16.4% of all abnormal male cytogenetic reports. Much of the difference between cases and controls appears to be accounted for by a greater frequency of cases with > 75% Y loss. A value of 81% chromosome Y loss maximized the combined sensitivity (28%) and specificity (100%) for predicting disease status, but a 75% cutoff provided the best estimate of disease risk. Even in older males, if > 75% of metaphase cells are 45,X,-Y, they probably represent a disease-associated clonal population, and it is possible that the critical genetic change is not visible through the microscope. This observation is true for MDS, MPD, B-cell disease, and especially acute myelogenous leukemia. The prognostic association of Y chromosome loss for survival appears to be neutral or favorable. Genes Chromosomes Cancer 27:11-16, 2000.


Frequency of surveillance computed tomography in non-Hodgkin lymphoma and the risk of secondary primary malignancies: A nationwide population-based study.
With increasing usage of computed tomography (CT) for lymphoma patients receiving curative-intent treatment, development of secondary primary malignancy (SPM) related to radiation from CT scans becomes an emerging issue in these long-term survivors. We conducted a nationwide population-based study analyzing non-Hodgkin lymphoma (NHL) patients receiving curative-intent treatment between January 1997 and December 2010. Patients were divided into two populations by the medium number of CT performed. The cumulative incidence of SPM in these two groups was compared using the Kaplan-Meier method. Propensity score matching was applied to eliminate potential confounders. Group stratification and multivariate analyses calculated by Cox proportional hazard models using competing risk analyses adjusted for mortality were performed to identify independent predictors for SPM. Patients receiving >8 CT scans had a significantly greater risk for developing SPM (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.61-3.13; p < 0.001) than those with ≤8 scans and this difference remained significant even after correction with propensity score matching. Among the 180 SPM identified, those receiving more CT scans had significantly higher SPM incidence in cancers of the breast (HR 11.22), stomach (HR 5.22) and liver and biliary tract (HR 2.18) in comparison to those with less exposure. The risk of SPM was estimated to increase 3% per one more CT scan performed. Our study demonstrated that after curative-intent treatment, patients with NHL receiving more frequent surveillance CT scans would have an increased risk of SPM.


[Use of bifunctional reagents in the study of histones topography in chromatin].
The ability of bifunctional reagents--diimidoesters of sebacinic acid and tetranitromethane--to cross-link the histones in rat thymus chromatin was studied. The histone polymers formed were extracted with 0,8 N H2SO4 and analyzed by polyacrylamide gel electrophoresis. The results obtained suggest that in chromatin some histone fractions are localized in immediate proximity to each other. This phenomenon may probably account for the formation of chromatin structure and its functioning in the cell.


Elasticity of the coracohumeral ligament in patients with frozen shoulder following rotator interval injection: a case series.
Aim of the study: To evaluate changes in the elasticity of the coracohumeral ligament in patients with adhesive capsulitis of the shoulder treated with ultrasound-guided rotator interval injections. Methods: Shear wave elastography was used to evaluate elasticity of the coracohumeral ligament in symptomatic and asymptomatic shoulders in the shoulder-neutral position and 30° external rotation. A total of 24 shoulders were assessed. Symptomatic shoulders were treated with targeted steroid injection via the rotator interval and manipulation under local anaesthetic block. Follow-up assessment of the elasticity of the coracohumeral ligament was obtained at 10 weeks post-injection. Results: In all subjects, the coracohumeral ligament elastic modulus was larger at 30° external rotation than in the neutral position. In patients with adhesive capsulitis, the coracohumeral ligament thickness and elastic modulus was significantly greater in the symptomatic shoulder in the neutral position and 30° ER. Treated patients had an excellent response with improved Oxford Shoulder Score and reduced visual analogue scale pain scores. Median Oxford Shoulder Score was 13.5 pre-injection and 34 at 10 weeks post-injection. Median visual analogue scale pain scores measured 8.5 pre-injection, 3.5 at 1 day, 2 at 1 week, and 2.5 at 10 weeks. Improved Oxford Shoulder Score and visual analogue scale pain score was associated with a trend to normalisation of the elastic modus of the coracohumeral ligament. Conclusion: In patients with adhesive capsulitis of the shoulder, shear wave elastography demonstrated the coracohumeral ligament is stiffer in the symptomatic shoulder than in the unaffected shoulder. Treatment with the ultrasound-guided rotator interval injection is associated with improved Oxford Shoulder Score, reduced visual analogue scale pain scores, and reduced stiffness in the coracohumeral ligament.


SARS plague: duty of care or medical heroism?
Severe acute respiratory syndrome (SARS) is a new infectious disease that emerged in mid- November 2002 in Guangdong, southern China. The global pandemic began in late February 2003 in Hong Kong. By the time SARS was declared contained on 5 July 2003 by the World Health Organization (WHO), it had afflicted 8096 patients in 29 countries. No other disease had had such a phenomenal impact on healthcare workers (HCWs), who formed about 21% of SARS patients. In Vietnam, Canada and Singapore, HCWs accounted for 57%, 43% and 41% of SAR patients, respectively. At the beginning of the outbreak, there was practically no information on this disease, which did not even have a name until 16 March 2003, except that it was infectious and could result in potentially fatal respiratory failure. Indeed, HCWs had lost their lives to SARS. Understandably, some HCWs refused to look after SARS patients or even resigned. Initially, much negative publicity was given to such HCWs. It was a very trying time for HCWs as many were also ostracised by the society which they served. They were perceived to be a potential source of infection in the community because of their contact with SARS patients, whom they risked their lives looking after. Subsequently, as we learnt more about the disease and educated the public about the plight of the frontline HCWs, the public gave the frontline HCWs tremendous support and even honoured them as heroes. Being in the medical profession, caring for patients is one of our expected responsibilities. On the other hand, as public citizens, HCWs have the right to resign when they feel that their responsibility to their families should take priority over that to their patients. As a result of this scourge, each HCW learnt to decide if caring for patients is their chosen profession and vocation. Many chose to live up the Hippocratic oath.


Effects of sex difference, gonadectomy, and estrogen on N-methyl-N-nitrosourea induced rat thyroid tumors.
The occurrence of thyroid tumors induced by N-methyl-N-nitrosourea (MNU) and low iodine diet in Long-Evans (LE) rats was studied with special reference to sex difference, effect of gonadectomy, and estradiol administration. Rats of experimental groups 1-6 were given i.v. injections of 40 mg of MNU/kg of body weight at 50 days of age and fed on low iodine diet from 28 days of age to the end of the experiment (30 weeks after MNU administration). They consisted of male, female, castrated male, ovariectomized female, and gonadectomized male and female rats given 2.5 mg estradiol pellets s.c. Rats of groups 7-10 served as the respective controls without MNU or low iodine diet. Levels of serum thyroid stimulating hormone and estrogen receptor of the thyroid lesions were also examined. It was noted that the incidence of thyroid carcinoma was higher in females than in males (P less than 0.01) and did not change by castration in males but decreased in ovariectomized rats (P less than 0.01). Administration of estradiol after gonadectomy significantly increased the incidence of thyroid carcinomas in castrated and ovariectomized rats. Increase of mean serum thyroid stimulating hormone levels and thyroid and pituitary weights was also predominant in females. Mean thyroid stimulating hormone levels of both sexes were decreased by gonadectomy. Mean thyroid and pituitary weights were inhibited from increasing not by castration but by ovariectomy. Estradiol supplemented after gonadectomy significantly increased all of these factors. Estrogen receptors were detected in transplanted thyroid tumors but not in euthyroid tissues. The results suggest that estradiol promoted the thyroid tumorigenesis through activation of thyrotrophs in pituitary or direct interaction of estradiol and estrogen receptors in the thyroid.


The radiological unknown primary of the head and neck: Recommendations for imaging strategies based on a systematic review.
To develop recommendations for the radiological investigation of clinically occult primary cancer in the head and neck. In accordance with PRISMA guidelines, a search was performed on Medline, Embase and Cochrane library databases to investigate the efficacy of ultrasound guided Fine Needle Aspiration (US FNAC), contrast enhanced CT (CECT), magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose PET-CT (18F-FDG PET-CT) in the investigation of head and neck squamous cell carcinoma from an unknown primary (HNSCCUP) presenting with a metastatic cervical lymph node (s). The Quality Assessment of Diagnostic Accuracy Studies Version 2 tool and SIGN 50 guidelines were used to assess the risk of bias and quality of the included studies. Adult patients presenting with metastatic cervical lymph nodes from a HNSCCUP. Utility of different imaging modalities (PET-CT, MRI, CE CT and US FNAC in the management of HNSCCUP). Twenty-eight studies met inclusion criteria; these were meta-analyses, systematic reviews, prospective and retrospective studies. The optimal imaging strategy involves utilisation of various imaging modalities. US FNAC can provide the initial diagnosis and HPV status of the occult primary tumour. CECT and MRI detect up to 44% of occult tumours and guide management. FDG PET-CT is the most sensitive imaging modality for the detection of CUP and should be performed prior to panendoscopy.


Methodology Used to Assess Acceptability of Oral Pediatric Medicines: A Systematic Literature Search and Narrative Review.
Regulatory guidelines require that any new medicine designed for a pediatric population must be demonstrated as being acceptable to that population. There is currently no guidance on how to conduct or report on acceptability testing. Our objective was to undertake a review of the methods used to assess the acceptability of medicines within a pediatric population and use this review to propose the most appropriate methodology. We used a defined search strategy to identify literature reports of acceptability assessments of medicines conducted within pediatric populations and extracted information about the tools used in these studies for comparison across studies. In total, 61 articles were included in the analysis. Palatability was the most common (54/61) attribute measured when evaluating acceptability. Simple scale methods were most commonly used, with visual analog scales (VAS) and hedonic scales used both separately and in combination in 34 of the 61 studies. Hedonic scales alone were used in 14 studies and VAS alone in just five studies. Other tools included Likert scales; forced choice or preference; surveys or questionnaires; observations of facial expressions during administration, ease of swallowing, or ability to swallow the dosage; prevalence of complaints or refusal to take the medicine; and time taken for a nurse to administer the medicine. The best scale in terms of validity, reliability, feasibility, and preference to use when assessing acceptability remains unclear. Further work is required to select the most appropriate method to justify whether a medicine is acceptable to a pediatric population.


Evaluation of a specific diagnostic marker for rheumatoid arthritis based on cyclic citrullinated peptide.
A specific peptide marker for diagnosing rheumatoid arthritis (RA) was found based on cyclic citrullinated peptide (CCP) using the following three steps: (1) analysis of the binding epitope of autoimmune antibodies using ϵ-aminocaproic acid-modified peptides; (2) RA diagnosis using sequence-modified peptides; and (3) evaluation of the peptides' diagnostic performance for RA diagnosis. Ninety-five serum samples were analyzed by ELISA and compared using MedCalc (version 15.2.1). Microplate binding ϵ-aminocaproic acid was added to the N- or C-terminal of the CCP sequence. The N-terminal anchoring peptide assay showed 15% higher specificity compared with the C-terminal anchoring peptide assay. Based on this result, the hydrophilic C-terminal sequence of CCP was substituted with a hydrophobic amino acid. Among the sequence-modified peptides, CCP11A (in which alanine was substituted for the 11th amino acid of CCP) assay showed the highest sensitivity (87%) and specificity (100%) for RA diagnosis. Thus, CCP11A was selected as a possible specific marker peptide for RA diagnosis and further analyzed. The results of this analysis indicated that CCP11A showed better specificity than the CCP assay in both healthy individuals (11% better) and OA cohort (20% better). From these results, CCP11A was evaluated as a specific marker for diagnosing RA with higher diagnostic performance.


Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities.
The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed. A COMPREHENSIVE LITERATURE SEARCH WAS PERFORMED UTILIZING PUBMED AND KEY WORDS: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics. Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications. In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery.


Determination of high-affinity oestrogen receptor sites in uterine supernatant preparations.
An assay method was developed for the determination of high-affinity oestradiol receptors in uterine supernatant preparations. When only high-affinity sites are present in such preparations, or when they predominate, the analysis of the equilibrium between oestradiol and receptor sites based on the Scatchard (1949) plot may be used to determine the dissociation constant of the equilibrium and the molar concentration of the high-affinity sites. When both high-affinity and low-affinity sites are present the Scatchard plot is no longer linear and cannot be used directly to determine high-affinity sites. Determination of the reverse velocity constants of the reaction between high-affinity (k(-1)) and low-affinity (k(-2)) receptor sites and [(3)H]oestradiol has shown that these constants differ by at least one order of magnitude. Advantage has been taken of this difference to introduce an additional step into the assay procedure that eliminates oestradiol bound to low-affinity sites and permits the determination of high-affinity sites in different species and under a variety of physiological conditions.


Breakdown of stria vascularis blood-labyrinth barrier in C3H/lpr autoimmune disease mice.
Sensorineural hearing loss related to autoimmune disease is a well-recognized condition, although the exact pathophysiologic mechanisms remain unclear. One current theory postulates immune complex-induced interference with blood-labyrinth barrier integrity in the stria vascularis. The C3H/lpr autoimmune mouse was chosen to study the permeability of capillaries in the stria vascularis because this mouse model has demonstrated abnormalities of the stria vascularis and shifts in the auditory brain stem response threshold during active disease. C3H/lpr mice with active disease were compared with younger mice without disease, as well as age-matched C3H/HeJ control mice. The mice were injected with the tracer ferritin and examined by transmission electron microscopy to evaluate the integrity of the capillary tight junctions in the stria vascularis. Four of five mice with active disease were noted to have extensive leakage of ferritin into the perivascular tissues. Neither the young, disease-free autoimmune mice nor the nonautoimmune control mice demonstrated vessel leakage. Thickening of the basement membrane was also noted in the diseased animals. The results imply that active disease leads to a breakdown in the blood-endolymph barrier, which could underlie the hearing loss accompanying autoimmune and other immune diseases.


Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits.
Herbal hepatotoxicity by the anxiolytic kava (Piper methysticum Forst. f.) emerged unexpectedly and was observed in a few patients worldwide. Liver injury occurred after the use of traditional aqueous kava extracts in the South Pacific region and of acetonic and ethanolic extracts in Western countries in rare cases, suggesting that the solvents used play no major causative role. In this review, we discuss actual pathogenetic issues of kava hepatotoxicity with special focus on developments regarding pipermethystine, flavokavain B, and mould hepatotoxins as possible culprits. There is abundant data of in vitro cytotoxicity including apoptosis by pipermethystine and flavokavain B added to the incubation media, yet evidence is lacking of in vivo hepatotoxicity in experimental animals under conditions similar to human kava use. Furthermore, in commercial Western kava extracts, pipermethystine was not detectable and flavokavain B was present as a natural compound in amounts much too low to cause experimental liver injury. There is concern, however, that due to high temperature and humidity in the South Pacific area, kava raw material might have been contaminated by mould hepatotoxins such as aflatoxins after harvest and during storage. Whether kava hepatotoxicity may be due to aflatoxicosis or other mould hepatotoxins, requires further studies.


Synthesis and photophysical properties of linear gold(I) complexes based on a CCC carbene.
The reaction between allenylpyridine (L1) and (Me2S)AuCl resulted in the quantitative formation of the (Indolizy)gold chloride complex 1 (Indolizy = indolizin-2-ylidene). The reaction of 1 with carbazole in the presence of KOtBu affords the corresponding (Indolizy)Au(Cz) complex 2. Both compounds show high air- and temperature stability. The crystal structure of 2 confirmed the linear co-planar geometry. Complex 1 shows an intense low energy absorption of mixed character in the UV-vis spectrum, ascribed to intraligand and (M + Hal)L charge transfer processes, and exhibits bright yellow phosphorescence with an excited state lifetime of 62.8 μs in the crystal and a luminescence quantum yield up to 65%. On the other hand, the carbazolate complex 2 in a polystyrene matrix shows bright red delayed fluorescence at 617 nm with a sub-microsecond excited state lifetime and a quantum yield of 21.6%.


Selective effects of low-dose dopamine D1 and D2 receptor antagonists on rat information processing.
It is well established that the dopaminergic system influences simple reaction time (RT) performance. However, the role of this system in more complex information processing remains to be clarified. The present study was aimed at addressing this issue. To this end, we used an inferential method that relies on choice RT procedures and allows one to identify information processing stages in both humans and rats. Long-Evans rats responded to lateral visual cues (left or right). Two task factors, signal intensity and foreperiod duration, were manipulated. Low doses of two pharmacological agents, SCH 23390 (a D1 receptor antagonist; 0.015 and 0.025 micromol/kg) and eticlopride (a D2 receptor antagonist; 0.01 and 0.02 micromol/kg), were administrated systemically. Both drugs increased choice RT: eticlopride interacted with signal intensity on RT, showing that D2 receptors mediate at least the sensory stage of stimulus preprocessing. In addition, eticlopride interacted with signal intensity on omission rate, thereby suggesting an involvement of D2 receptors in attentional processes; and SCH 23390 interacted with foreperiod duration on RT, indicating that D1 receptors specifically mediate the response adjustment stage. The effect of this drug on RT rests entirely in its interaction with foreperiod duration, allowing us to conclude that this D1 antagonist affects the response adjustment stage while sparing all other processing stages.


Direct Cell-Cell Contact with Chondrocytes Is a Key Mechanism in Multipotent Mesenchymal Stromal Cell-Mediated Chondrogenesis.
Using a combination of articular chondrocytes (ACs) and mesenchymal stromal cells (MSCs) has shown to be a viable option for a single-stage cell-based treatment of focal cartilage defects. However, there is still considerable debate whether MSCs differentiate or have a chondroinductive role through trophic factors. In addition, it remains unclear whether direct cell-cell contact is necessary for chondrogenesis. Therefore, the aim of this study was to investigate whether direct or indirect cell-cell contact between ACs and MSCs is essential for increased cartilage production in different cellular environments and elucidate the mechanisms behind these cellular interactions. Human ACs and MSCs were cultured in a 10:90 ratio in alginate beads, fibrin scaffolds, and pellets. Cells were mixed in direct cocultures, separated by a Transwell filter (indirect cocultures), or cultured with conditioned medium. Short tandem repeat analysis revealed that the percentages of ACs increased during culture, while those of MSCs decreased, with the biggest change in fibrin glue scaffolds. For alginate, where the lack of cell-cell contact could be confirmed by histological analysis, no difference was found in matrix production between direct and indirect cocultures. For fibrin scaffolds and pellet cultures, an increased glycosaminoglycan production and type II collagen deposition were found in direct cocultures compared with indirect cocultures and conditioned medium. Positive connexin 43 staining and transfer of cytosolic calcein indicated communication through gap junctions in direct cocultures. Taken together, these results suggest that MSCs stimulate cartilage formation when placed in close proximity to chondrocytes and that direct cell-cell contact and communication through gap junctions are essential in this chondroinductive interplay.


Ureteral Rupture Caused by a Suprapubic Catheter in a Male Patient With Spinal Cord Injury: A Case Report.
Spinal cord injury (SCI) may lead to urinary system disturbances. Patients with SCI usually have neurogenic bladder, and treatment optionss for this condition include clean intermittent catheterization and a permanent indwelling urethral or suprapubic catheter. Complications of catheterization include urinary tract infection, calculi, urinary tract injury, bladder contraction, bladder spasm, renal dysfunction, bladder cancer, and so forth. To the best of our knowledge, ureteral rupture is an unusual complication of catheterization, and ureteral rupture has been rarely reported in SCI patients. Therefore, here we report a case of ureteral rupture caused by a suprapubic catheter used for the treatment of neurogenic bladder with vesicoureteral reflux in a male patient with SCI. Due to SCI with neurogenic bladder, ureteral size can be reduced and the suprapubic catheter tip can easily migrate to the distal ureteral orifice. Thus, careful attention is required when a catheter is inserted into the bladder in patients with SCI.


A pilot study for testing a low-cost 3D design with an inertial sensor for the quantitative assessment of finger tapping in patients with Parkinson's Disease.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders worldwide. Current identification and monitoring of its motor symptoms depends on the clinical expertise. Repetitive finger tapping is one of the most common clinical maneuvers to assess for bradykinesia. Despite the increasing use of technology aids to quantitatively characterize the motor symptoms of PD, there is still a relative lack of clinical evidence to support their widespread use, particularly in low-resource settings. In this pilot study, we used a low-cost design prototype coupled with an inertial sensor is coupled to quantify the frequency of the finger tapping movements in four participants with PD. Repetitive finger tapping was performed using both hands before and after taking levodopa as part of their clinical treatment. The proposed 3D design allowed repetitive movements to be performed without issues. The maximum frequency of finger tapping was in the range of 0.1 to 4.3 Hz. Levodopa was associated with variable changes in the maximum frequency of finger tapping. This pilot study shows the feasibility for low-cost technology to quantitatively characterize repetitive movements in people living with PD.Clinical relevance- In this pilot study, a low-cost inertial sensor coupled to a design prototype was feasible to characterize the frequency of repetitive finger tapping movements in four participants with PD. This method could be used to quantitatively identify and monitor bradykinesia in people living with PD.


In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.
The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.


[Avian CELO adenovirus as a possible contaminant in cell cultures of Japanese quail embryos].
Avian adenovirus CELO was found to replicate poorly in Japanese quail embryos (JQE) and cell cultures of them. The infectious process in these systems was latent. The antigen of adenovirus CELO in JQE cell culture was detectable by the fluorescent antibody method (FAM) within the first 24-72 hours after inoculation as fluorescent cytoplasmic granules. Subsequently, fluorescence of nuclei and macrophage cytoplasm was observed. The results indicate that JQE and their cell cultures are not contaminated with avian adenovirus CELO despite regular circulation of this agent among avian populations. The advantages of FAM (rapidity and clearness) for identification of adenovirus as substrates contaminant as compared with other biological methods have been demonstrated.


Obtaining spruce hemicelluloses of desired molar mass by using pressurized hot water extraction.
There is growing interest in utilizing galactoglucomannan, the main hemicellulose in softwoods, for various applications such as cosmetics, pharmaceuticals, textiles, alimentary, and health products, as well as for the production of fuels. For fuel production and for using the rare sugars as platform chemicals, the hemicelluloses need to be hydrolyzed to sugar monomers, and for this purpose, low-molecular-mass extracts are favorable. However, for the other applications high molecular masses are required, which presents an even greater challenge for extraction. The ability to optimize the extraction process according to the needs of further processing, by using solely water as the solvent, is a key issue in the environmentally friendly utilization of this versatile raw material. The goal of this work is to study how the average molar mass of hemicelluloses extracted from spruce sapwood can be influenced by altering the experimental conditions. The main parameters influencing the extraction and hydrolysis of the hemicelluloses, namely, extraction time, temperature, pH, and chip size, were studied. The results show that it is feasible to develop an extraction process for harvesting spruce hemicelluloses, also of large molar masses, for industrial applications by using pressurized hot water extraction.


Ultrafast Dynamics of Encapsulated Molecules Reveals New Insight on the Photoisomerization Mechanism for Azobenzenes.
Spatial confinement can have a profound impact on the dynamics of chemical reactions, especially for isomerization reactions that involve large-amplitude structural rearrangement of a molecule. This work uses ultrafast spectroscopy to probe the effects of confinement on trans → cis photoisomerization following ππ* excitation of 4-propyl stilbene and 4-propyl azobenzene encapsulated in a supramolecular host-guest complex. Transient absorption spectroscopy of the encapsulated azobenzene derivative reveals the formation of two distinct excited-state species with spectral signatures resembling the cis and trans isomers. Formation of the cis species indicates a direct excited-state isomerization channel that is not observed in cyclohexane solution. Comparison with the stilbene analogue suggests that this "hot" excited-state isomerization pathway for encapsulated azobenzene involves primarily in-plane inversion, whereas a 10-fold increase of the excited-state lifetime for the trans isomer suggests that crowding in the capsule hinders isomerization from the relaxed S1 geometry of the trans isomer. This work provides new mechanistic insight on the relative roles of inversion and rotation in the ultrafast photoisomerization of azobenzene derivatives.


Differential Behavior of Fibroblasts and Epithelial Cells on Structured Implant Abutment Materials: A Comparison of Materials and Surface Topographies.
The aim of this study was to compare the proliferation and attachment behavior of fibroblasts and epithelial cells on differently structured abutment materials. Three different surface topographies were prepared on zirconia and titanium alloy specimens and defined as follows: machined (as delivered without further surface modification), smooth (polished), and rough (sandblasted). Energy-dispersive X-ray spectroscopy, topographical analysis, and water contact angle measurements were used to analyze the surface properties. Fibroblasts (HGF1) and epithelial cells (HNEpC) grown on the specimens were investigated 24 hours and 72 hours after seeding and counted using fluorescence imaging. To investigate adhesion, the abundance and arrangement of the focal adhesion protein vinculin were evaluated by immunocytochemistry. Similar surface topographies were created on both materials. Fibroblasts exhibited significant higher proliferation rates on comparable surface topographies of zirconia compared with the titanium alloy. The proliferation of fibroblasts and epithelial cells was optimal on different substrate/topography combinations. Cell spreading was generally higher on polished and machined surfaces than on sandblasted surfaces. Rough surfaces provided favorable properties in terms of cellular adhesion of fibroblasts but not of epithelial cells. Our data support complex soft tissue cell-substrate interactions: the fibroblast and epithelial cell response is influenced by both the material and surface topography.


Safety of botulinum toxin for dysphagia in oculopharyngeal muscular dystrophy.
Despite multiple studies reporting marked benefit of botulinum toxin (BTX) for treatment of cricopharyngeal dysphagia, little is known about its safety for this indication. We examined the safety of cricopharyngeal BTX for dysphagia in oculopharyngeal muscular dystrophy (OPMD). We reviewed records of patients with OPMD who received cricopharyngeal BTX. Twenty-four patients underwent 66 procedures. Overall adverse event frequency was 44%. The most common adverse events were dysphonia (24%) and worsened dysphagia (14%). Logistic regression demonstrated that dose was a significant predictor of worsened dysphagia (P = 0.036) and of the composite event of dysphonia or worsened dysphagia (P = 0.009). There was a nonsignificant trend for dose as a predictor of dysphonia (P = 0.073). 59% of procedures were associated with symptomatic improvement. While BTX appears to be beneficial for treatment of dysphagia in OPMD, caution is warranted when injecting the cricopharyngeus muscle due to dose-related risk of dysphonia or worsened dysphagia.


The novel Legionella pneumophila type II secretion substrate NttC contributes to infection of amoebae Hartmannella vermiformis and Willaertia magna.
The type II protein secretion (T2S) system of Legionella pneumophila secretes over 25 proteins, including novel proteins that have no similarity to proteins of known function. T2S is also critical for the ability of L. pneumophila to grow within its natural amoebal hosts, including Acanthamoeba castellanii, Hartmannella vermiformis and Naegleria lovaniensis. Thus, T2S has an important role in the natural history of legionnaires' disease. Our previous work demonstrated that the novel T2S substrate NttA promotes intracellular infection of A. castellanii, whereas the secreted RNase SrnA, acyltransferase PlaC, and metalloprotease ProA all promote infection of H. vermiformis and N. lovaniensis. In this study, we determined that another novel T2S substrate that is specific to Legionella, designated NttC, is unique in being required for intracellular infection of H. vermiformis but not for infection of N. lovaniensis or A. castellanii. Expanding our repertoire of amoebal hosts, we determined that Willaertia magna is susceptible to infection by L. pneumophila strains 130b, Philadelphia-1 and Paris. Furthermore, T2S and, more specifically, NttA, NttC and PlaC were required for infection of W. magna. Taken together, these data demonstrate that the T2S system of L. pneumophila is critical for infection of at least four types of aquatic amoebae and that the importance of the individual T2S substrates varies in a host cell-specific fashion. Finally, it is now clear that novel T2S-dependent proteins that are specific to the genus Legionella are particularly important for L. pneumophila infection of key, environmental hosts.


Clinically apparent adverse reactions to intra-wound vancomycin powder in early onset scoliosis are rare.
Spine surgeons have increasingly used intraoperative application of topical vancomycin powder (TVP) to prevent surgical site infections (SSIs). The goals of this study were to define the rate of pharmacological adverse reaction to TVP in young patients undergoing posterior spinal surgery and to summarise institutional variation in TVP dosing. This retrospective observational study included ten spine centres in the United States and one in Europe. Patients with early onset scoliosis who underwent posterior spine surgery were eligible for inclusion. Age, weight, TVP dose and surgery type were recorded. Surgeries where patient age was > 12 years were excluded. Pharmacological adverse reactions were defined as clinical instances of Red Man Syndrome, rash, nephrotoxicity, proteinuria, hepatotoxicity or ototoxicity. The rate of pharmacological adverse reaction to TVP was calculated. Dosing practices were summarised. Patient age was in the range of seven months to 12 years (median ten years). Of 1398 observations, there was one possible pharmacological adverse reaction. This was in a ten-year-old, 20.4-kg female patient with neuromuscular sco-liosis undergoing growing rod implantation. She was dosed with 1500 mg of TVP and immediately developed a transient rash without systemic symptoms. This abated over minutes without any medical intervention. There were no other adverse reactions in the sample. The population rate of pharmacological adverse reaction was 0.072% (95% confidence interval 0 to 0.4). Significant variability in dosing practices existed between centres. Pharmacological adverse reactions to TVP are rare. Future work may establish evidence-based guidelines for TVP dosing based on patient weight and other variables.


Is there a need for professional regulation for primary care mental health workers?
Primary care mental health (PCMH) workers need not have a professional qualification. The development of the role of these workers highlights the influence of a number of factors that provide a framework that offers assurance of the protection of the public and the promotion of quality of care. Factors such as legislation, codes of practice, stringent recruitment procedures, clinical supervision, employing evidence-based practice, and training all play an equal part in determining safe and good practice. Together, these factors formulate standards of practice which limit the need for professional regulation. The training of PCMH workers is guided by a national curriculum and other requirements. Practice of these workers is governed by various legislative frameworks and guidance. The requirement for clinical supervision for PCMH workers is a crucial element in promoting safe and effective care. In addition, stringent recruitment procedures ensure unsuitable candidates are not selected for the positions. This paper argues that professional regulation is not needed as there are other systems with similar significance that promote quality of care and can offer protection to the public.


Association of Apolipoproteins B and A-1 With Markers of Vascular Health or Cardiovascular Events.
Apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) are markers of lipoprotein metabolism. Although their relationship to cardiovascular disease has been well documented, little is known regarding their correlation to measures of vascular structure and function. This study was conducted to investigate the relationship between apoA-1, apoB, and measures of vascular function, as well their relationship to adverse cardiovascular events. Moreover, we evaluated whether apoB or the apoB/apoA-1 ratio was more closely related to vascular markers than was low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C). One thousand five hundred twenty-two healthy middle-aged men of the Firefighters and Their Endothelium (FATE) cohort were assessed for risk factors and flow-mediated dilatation (FMD), hyperemic velocity (VTI), and carotid intima-media thickness (CIMT). Participants were then followed for 7.2 ± 1.7 years. ApoA-1 and apoB levels were measured at baseline. ApoA-1 was not correlated with VTI, FMD, or CIMT, whereas apoB was significantly related to VTI and CIMT. Multiple regression analyses confirmed apoB as being related to both VTI (β = -0.083; P = 0.001) and CIMT (β = 0.055; P = 0.022) in models adjusted for age; blood pressure; high-density lipoprotein C (HDL-C), triglyceride and insulin levels; waist circumference; and C-reactive protein levels. In substituted models, LDL-C (β = -0.092; P < 0.001) and non-HDL-C (β = -0.089; P = 0.001) levels appeared to have the same degree of association as apoB for VTI but were not associated with CIMT. ApoB was found to be associated with cardiovascular events (hazard ratio, 1.349; 95% confidence interval, 1.073-1.695; P = 0.010). ApoB had an independent but weak relationship with indices of microvascular health. Nevertheless, it was associated with occurrence rates of adverse cardiovascular events.


Synthesis and In Vitro Photodynamic Activity of Cationic Boron Dipyrromethene-Based Photosensitizers against Methicillin-Resistant Staphylococcus aureus.
A series of cationic boron dipyrromethene (BODIPY) derivatives were synthesized and characterized with various spectroscopic methods. Having the ability to generate singlet oxygen upon irradiation, these compounds could potentially serve as photosensitizers for antimicrobial photodynamic therapy. Of the five BODIPYs being examined, the dicationic aza-BODIPY analogue (compound 5) demonstrated the highest potency against a broad spectrum of clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), including four ATCC-type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two strains carrying specific antibiotic resistance mechanisms [-AAC(6')-APH(2") and RN4220/pUL5054], and ten non-duplicate clinical strains from hospital- and community-associated MRSAs of the important clonal types ST239, ST30, and ST59, which have previously been documented to be prevalent in Hong Kong and its neighboring countries. The in vitro anti-MRSA activity of compound 5 was achieved upon irradiation with near-infrared light (>610 nm) with minimal bactericidal concentrations (MBCs) ranging from 12.5 to 25 µM against the whole panel of MRSAs, except the hospital-associated MRSAs for which the MBCs were in the range of 50-100 µM. Compound 5 was significantly (p < 0.05) more potent than methylene blue, which is a clinically approved photosensitizer, indicating that it is a promising antimicrobial agent that is worthy of further investigation.


A Secure Base from which to Cooperate: Security, Child and Parent Willing Stance, and Adaptive and Maladaptive Outcomes in two Longitudinal Studies.
Early secure attachment plays a key role in socialization by inaugurating a long-term mutual positive, collaborative interpersonal orientation within the parent-child dyad. We report findings from Family Study (community mothers, fathers, and children, from age 2 to 12, N = 102, 51 girls) and Play Study (exclusively low-income mothers and children, from age 3.5 to 7, N = 186, 90 girls). We examined links among observed secure attachment at toddler age, child and parent receptive, willing stance to each other, observed in parent-child contexts at early school age, and developmental outcomes. The developmental outcomes included parent-rated child antisocial behavior problems and observed positive mutuality with regard to conflict issues at age 12 in Family Study, and mother-rated child antisocial behavior problems and observed child regard for rules and moral self at age 7 in Play Study. In mother-child relationships, the child's willing stance mediated indirect effects of child security on positive mutuality in Family Study and on all outcomes in Play Study. In father-child relationships, both the child's and the parent's willing stance mediated indirect effects of child security on both outcomes. Early security initiates an adaptive developmental cascade by enlisting the child and the parent as active, willingly receptive and cooperative agents in the socialization process. Implications for children's parenting interventions are noted.


Immunoelectron microscopy of influenza A virus neuraminidase glycoprotein topography.
Using immunoelectron microscopy, the distribution of influenza A virus neuraminidase (NA) glycoproteins was examined, after performing immunoreactions to virions on the grid. With polyclonal antibody, the immunolabels of the glycoproteins were found to be homogeneously distributed, whereas with monoclonal antibody they were found to be distributed in clusters. After destruction of haemagglutinin (HA) but not of NA activity with a high concentration of trypsin, the remaining visible spikes were evenly distributed. This finding was consistent with the absence of immunolabelling with anti-HA antibody, and the homogeneous pattern of immunolabels with anti-NA polyclonal antibody, but not with the clustered labelling with the anti-NA monoclonal antibody. Thus, the immunolabelling image with anti-NA polyclonal antibody was considered to reflect the true one.


[Comparative study of the effects of antibodies to S-100 protein and ouabain on neurons of Helix pomatia].
Ouabain, used in 5.10(-4) M concentration, elicits 12 +/- 5 mV (15 experiments) depolarization of membrane of snail Helix neurons. In 80% of experiments depolarization is not accompanied by changes in membrane conductance, in 20% of experiments the decrease of the membrane conductance is observed. Application of the antibodies to S-100 protein (their concentration in the micropipette being 0.05 mg/ml) induces similar effects. The effects of ouabain and antibodies to S-100 protein are not additive and the main difference in their action lies in the ability of the cell to recover the resting potential of the membrane in the solution containing ouabain.


An interactionist perspective on the socioeconomic context of human development.
This article addresses the relationship between socioeconomic status (SES), family processes, and human development. The topic is framed as part of the general issue of health disparities, which involves the oft-observed positive relationship between SES and the cognitive, social, emotional, and physical well-being of adults and children. A review of recent research and theory identifies three general theoretical approaches that provide possible explanations for the association between SES and individual development: the social causation, social selection, and interactionist perspectives. Empirical evidence demonstrates support for the social causation view that SES affects families and the development of children in terms of both family stress processes (the family stress model) and family investments in children (the family investment model). However, there also is empirical support for the social selection argument that individual characteristics lead to differences in SES. Especially important, recent research is consistent with an interactionist approach, which proposes a dynamic relationship between SES and developmental change over time. Drawing on the combined set of research findings, the article concludes with the description of an interactionist model that serves as a heuristic for future studies of the links among SES, parenting behaviors, and child development.


67 kDa calcimedin, a new Ca2+-binding protein.
A set of four proteins, termed calcimedins, are isolatable from smooth, cardiac and skeletal muscle by using a fluphenazine-Sepharose affinity column. The calcimedins show apparent Mr values of 67,000, 35,000, 33,000 and 30,000 by SDS/polyacrylamide-gel electrophoresis. The 67,000-Mr calcimedin (67 kDa calcimedin) has now been purified to homogeneity by using DEAE-cellulose chromatography followed by Ca2+-dependent binding to phenyl-Sepharose. The amino acid analysis of the 67 kDa calcimedin shows this protein does not contain trimethyl-lysine but does contain 2 mol of tryptophan/mol of protein. The 67 kDa calcimedin shows positive ellipticity in the near-u.v. range with c.d. Ca2+-binding studies indicate one high-affinity Ca2+-binding site with Kd 0.4 microM. The data show that the 67 kDa calcimedin is distinct from other Ca2+-binding proteins described to date.


AJCC melanoma staging update: impact on dermatopathology practice and patient management.
Changes in the 2010 American Joint Commission on Cancer melanoma staging guidelines include the evaluation of primary tumor mitotic index (mitogenicity) and the recognized prognostic significance of a single melanoma cell in a sentinel lymph node. These revised criteria have important practice implications for dermatopathologists as well as for dermatologists, oncologists and surgeons who treat patients with cutaneous melanoma.


Formation and properties of dimeric recombinant horseradish peroxidase in a system of reversed micelles.
Wild-type recombinant horseradish peroxidase purified and refolded from Escherichia coli inclusion bodies has been studied in the system of bis(2-ethylhexyl)sulphosuccinate sodium salt (Aerosol OT)-reversed micelles in octane. In contrast with native horseradish peroxidase the wild-type recombinant enzyme forms dimeric structures as judged by sedimentation analysis. Peroxidase substrates affect the equilibrium between monomeric and dimeric enzyme forms. The dependence of the catalytic activity of recombinant peroxidase on the degree of hydration of the surfactant exhibits two maxima with pyrogallol, o-phenylene- diamine, guaiacol and o-dianisidine, with different ratios of activities for the first and second maxima. The differences in activities of monomeric and dimeric forms of the recombinant horseradish peroxidase provide evidence for active-site screening in dimeric forms. This has been used to model a dimeric structure of recombinant horseradish peroxidase with the screened entrance to the active site. In the model structure obtained, three of eight glycosylation sites were screened. This might explain the absence of dimeric structures in native enzyme peroxidase. The system of reversed micelles provides, for the first time, evidence for the formation of dimeric structures by recombinant plant peroxidase with an altered substrate specificity compared with the native enzyme. Thus one can assume that haem-containing peroxidases in general are able to form dimeric structures.


The changing fate of a secretory glycoprotein in developing maize endosperm.
Zeins are the major storage proteins in maize (Zea mays) endosperm, and their accumulation in zein bodies derived from the endoplasmic reticulum is well characterized. In contrast, relatively little is known about post-Golgi compartments or the trafficking of vacuolar proteins in maize endosperm, specifically the presence of globulins in structures resembling protein storage vacuoles that appear in early to mid-stage seed development. We investigated this pathway by expressing and analyzing a recombinant reporter glycoprotein during endosperm maturation, using a combination of microscopy and sensitive glycopeptide analysis. Specific N-glycan acceptor sites on the protein were followed through the stages of grain development, revealing a shift from predominantly paucimannosidic vacuolar glycoforms to predominantly trimmed glycan structures lacking fucose. This was accompanied by a change in the main subcellular localization of the protein from large protein storage vacuole-like post-Golgi organelles to the endoplasmic reticulum and zein bodies. The endogenous storage proteins corn alpha-globulin and corn legumin-1 showed a similar spatiotemporal profile both in transgenic plants expressing the reporter glycoprotein and in wild-type plants. This indicates that the shift of the intracellular trafficking route, as observed with our reporter glycoprotein, may be a common strategy in maize seed development.


DHA-rich fish oil lowers heart rate during submaximal exercise in elite Australian Rules footballers.
Omega-3 fatty acids (n-3) can improve cardiovascular (CV) function. This study examined the effects of n-3 on endurance performance, recovery and CV risk factors in elite Australian Rules football players. 25 players were randomised, double-blind, to 6 g/day of docosahexaenoic acid (DHA)-rich fish oil (FO; n=12) or sunflower oil (SO; n=13) during 5 weeks of training. At baseline erythrocyte n-3 content, resting blood pressure (BP), fasting serum triglycerides (TG) and heart rate (HR) during treadmill running at 10 km/h were assessed. Two treadmill runs (T1 and T2) to exhaustion, separated by 5 min, were then performed at the average speed for a recent 2200 m time-trial. After 5 weeks, erythrocyte n-3 increased (FO 3.8+/-0.6%, SO 0.6+/-0.3%; P<0.001) while TG (FO -0.32+/-0.09 mmol l(-1), SO 0.08+/-0.05 mmol l(-1); P<0.001), diastolic BP (FO 1.3+/-1.3 mmHg, SO 6.8+/-1.7 mmHg; P=0.04) and HR during submaximal exercise (FO -7.8+/-2.3 beats min(-1), SO -1.9+/-1.9 beats min(-1); P=0.03) decreased in FO compared with SO. Time to exhaustion (TTE) during T1 increased by Week 5 (FO 10.2+/-2.2%, SO 17.3+/-4.3%; P<0.001 for time). Recovery (TTE for T2 as % T1) decreased in both groups (FO, -3.4+/-4.5%, SO -8.8+/-3.9%; P=0.05 for time). We conclude that 5 weeks of supplementation with FO improved CV function and reduced CV risk factors, but did not improve endurance performance or recovery in elite Australian Rules footballers.


Fronto-striatal alterations correlate with apathy severity in behavioral variant frontotemporal dementia.
Structural and functional changes in cortical and subcortical regions have been reported in behavioral variant frontotemporal dementia (bvFTD), however, a multimodal approach may provide deeper insights into the neural correlates of neuropsychiatric symptoms. In this multicenter study, we measured cortical thickness (CTh) and subcortical volumes to identify structural abnormalities in 37 bvFTD patients, and 37 age- and sex-matched healthy controls. For seed regions with significant structural changes, whole-brain functional connectivity (FC) was examined in a sub-cohort of N = 22 bvFTD and N = 22 matched control subjects to detect complementary alterations in brain network organization. To explore the functional significance of the observed structural and functional deviations, correlations with clinical and neuropsychological outcomes were tested where available. Significantly decreased CTh was observed in the bvFTD group in caudal middle frontal gyrus, left pars opercularis, bilateral superior frontal and bilateral middle temporal gyrus along with subcortical volume reductions in bilateral basal ganglia, thalamus, hippocampus, and amygdala. Resting-state functional magnetic resonance imaging showed decreased FC in bvFTD between: dorsal striatum and left caudal middle frontal gyrus; putamen and fronto-parietal regions; pallidum and cerebellum. Conversely, bvFTD showed increased FC between: left middle temporal gyrus and paracingulate gyrus; caudate nucleus and insula; amygdala and parahippocampal gyrus. Additionally, cortical thickness in caudal, lateral and superior frontal regions as well as caudate nucleus volume correlated negatively with apathy severity scores of the Neuropsychiatry Inventory Questionnaire. In conclusion, multimodal structural and functional imaging indicates that fronto-striatal regions have a considerable influence on the severity of apathy in bvFTD.


Rapid orienting toward face-like stimuli with gaze-relevant contrast information.
Human faces under natural illumination, and human eyes in their unique morphology, include specific contrast polarity relations that face-detection mechanisms could capitalise on. Newborns have been shown to preferentially orient to simple face-like patterns only when they contain face- or gaze-relevant contrast. We investigated whether human adults show similar preferential orienting towards schematic face-like stimuli, and whether this effect depends on the contrast polarity of the stimuli. In two experiments we demonstrate that upright schematic face-like patterns elicit faster eye movements in adult humans than inverted ones, and that this occurs only if they contain face- or gaze-relevant contrast information in the whole stimulus or in the eye region only. These results suggest that primitive mechanisms underlying the orienting bias towards faces and eyes influence and modulate social cognition not just in infants but in adults as well.


Incorporating HIV prevention into the medical care of persons living with HIV. Recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.
Reducing transmission of human immunodeficiency virus (HIV) in the United States requires new strategies, including emphasis on prevention of transmission by HIV-infected persons. Through ongoing attention to prevention, risky sexual and needle-sharing behaviors among persons with HIV infection can be reduced and transmission of HIV infection prevented. Medical care providers can substantially affect HIV transmission by screening their HIV-infected patients for risk behaviors; communicating prevention messages; discussing sexual and drug-use behavior; positively reinforcing changes to safer behavior; referring patients for services such as substance abuse treatment; facilitating partner notification, counseling, and testing; and identifying and treating other sexually transmitted diseases (STDs). To help incorporate HIV prevention into the medical care of HIV-infected persons, CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America developed these recommendations. The recommendations are general and apply to incorporating HIV prevention into the medical care of all HIV-infected adolescents and adults, regardless of age, sex, or race/ethnicity. They are intended for all persons who provide medical care to HIV-infected persons (e.g., physicians, nurse practitioners, nurses, physician assistants); they might also be useful to those who deliver prevention messages (e.g., case managers, social workers, health educators). The recommendations were developed by using an evidence-based approach. For each recommendation, the strength of the recommendation, the quality of available evidence supporting the recommendation, and the outcome for which the recommendation is rated are provided. The recommendations are categorized into three major components: screening for HIV transmission risk behaviors and STDs, providing brief behavioral risk-reduction interventions in the office setting and referring selected patients for additional prevention interventions and other related services, and facilitating notification and counseling of sex and needle-sharing partners of infected persons.


Genetics of susceptibility to plasmacytoma induction. I. BALB/cAnN (C), C57BL/6N (B6), C57BL/Ka (BK), (C times B6)F1, (C times BK)F1, and C times B recombinant-inbred strains.
Plasmacytomas were found in 58% of 373 BALB/cAnN (C) mice given three 0.5-ml doses of mineral oil (Bayol F or light mineral oil) or 2,6,10,14-tetramethylpentadecane (pristane) ip. The incidence of plasmacytomas in C57BL/6N (B6), C57BL/Ka (BK), (C times B6)F1 and (C times BK)F1 was 6.4, 0, 11.5, and 16.5%, respectively. The plasmacytomas occurred in old B6 mice, in contrast to their early appearance in strain C mice. The incidence of plasmacytomas in mineral oil-treated or pristane-treated C times B recombinant-inbred (Rl) strain mice was 28.3% in C times BD, 17.5% IN C times BE, 36.5% IN C times BG, 0% in C times BH, 2.9% in C times Bl, 48% in C times BJ, and 4.3% in C times BK. C times BD, C times BG, and C times BJ strains were considered susceptible to plascytoma induction by mineral oil or pristane; C times BE had a low susceptibility, and C times BH, C times Bl, and C times BK were resistant. The results suggested that there were only a few gene difference between C and B6 or BK that determined susceptibility or resistance to plasmacytoma induction, and that B6 and BK have at least one dominant resistance gene. The distribution pattern of susceptibility and resistance in the C times B Rl strains suggested the presence of a resistance gene on chromosome 9, linkage group II.


Performance enhancements and muscular adaptations of a 16-week recreational football intervention for untrained women.
The present study investigated the performance effects and physiological adaptations over 16 weeks of recreational football training and continuous running for healthy untrained premenopausal women in comparison with an inactive control group [Football group (FG): n=21; running group (RG): n=18; CO: n=14]. Two weekly 1-h training sessions were performed in FG and RG. After 4 and 16 weeks of training VO(2max) was elevated (P<0.05) by 7% and 15%, respectively, in FG, and by 6% and 10%, respectively, in RG. After 16 weeks, Yo-Yo intermittent endurance level 2 performance was 33% and 19% better (P<0.05) for FG and 29% and 21% better (P<0.05) for RG than after 4 and 0 weeks, respectively. Peak sprinting speed was 12% higher (21.0 +/- 0.6 vs 18.8 +/- 0.7 km/h; P<0.05) for FG after the training period, whereas no difference was observed for RG. After 4 weeks citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD) activity was 9% and 8%, respectively, higher (P<0.05) than before training in FG with no further changes during the last 12 weeks. In RG, CS increased (P<0.05) by 12% after 4 weeks and no significant increase was observed for HAD. In FG, the number of capillaries per fiber was 18% higher (P<0.05) after 16 weeks (2.44 +/- 0.15 vs 2.07 +/- 0.05 cap/fiber), with no significant difference for RG. No differences were observed between 0 and 16 weeks for CO. In conclusion, recreational women's football leads to significant increases in VO(2max), performance and muscular adaptations throughout a 16-week training period. Thus, football can be used as an activity to elevate the physical capacity of untrained women.


The Role of Cognition, Personality, and Trust in Fraud Victimization in Older Adults.
Older adults are more at risk to become a victim of consumer fraud than any other type of crime (Carcach et al., 2001) but the research on the psychological profiles of senior fraud victims is lacking. To bridge this significant gap, we surveyed 151 (120 female, 111 Caucasian) community-dwelling older adults in Southern Ontario between 60 and 90 years of age about their experiences with fraud. Participants had not been diagnosed with cognitive impairment or a neurological disorder by their doctor and looked after their own finances. We assessed their self-reported cognitive abilities using the MASQ, personality on the 60-item HEXACO Personality Inventory, and trust tendencies using a scale from the World Values Survey. There were no demographic differences between victims and non-victims. We found that victims exhibit lower levels of cognitive ability, lower honesty-humility, and lower conscientiousness than non-victims. Victims and non-victims did not differ in reported levels of interpersonal trust. Subsequent regression analyses showed that cognition is an important component in victimization over and above other social factors. The present findings suggest that fraud prevention programs should focus on improving adults' overall cognitive functioning. Further investigation is needed to understand how age-related cognitive changes affect vulnerability to fraud and which cognitive processes are most important for preventing fraud victimization.


Correlation of Cognitive Reappraisal and the Microstructural Properties of the Forceps Minor: A Deductive Exploratory Diffusion Tensor Imaging Study.
Cognitive reappraisal (CR) is a mechanism for emotion regulation, and the prefrontal cortex (PFC) plays a central role in the regulation of emotions. We tested the hypothesis of an association between CR function and microstructural properties of forceps minor (a commissural bundle within the PFC) in healthy subjects (HS). We analyzed a population of 65 young HS of a public dataset. The diffusion tensor imaging (DTI) sequence of every subject was analyzed to extract the derived shape (diameter and volume) and DTI metrics in terms of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of the forceps minor. The CR subscale of the German version of the Emotion Regulation Questionnaire (ERQ) was used for CR assessment. The Shapiro-Wilk test was applied to test the assumption of normality in all these parameters, adopting a statistical threshold at p < 0.05. Whenever appropriate a non-parametric two-tailed partial correlation analysis was applied to test for correlations between the CR ERQ score and the derived shape and DTI metrics, including age and sex as confounders, adopting a statistical threshold at p < 0.05. The non-parametric two-tailed partial correlation analysis revealed a mildly significant correlation with FA (ρ = 0.303; p = 0.016), a weakly significant negative correlation with MD (ρ = - 0.269; p = 0.033), and a mildly significant negative correlation with RD (ρ = - 0.305; p = 0.015). These findings suggest a correlation between DTI microstructural properties of forceps minor and CR.


Role of dual energy X-ray absorptiometry in monitoring fracture healing in a rat femoral fracture model.
To dynamically monitor the bone mineral density (BMD) and the histomorphological changes during fracture healing in a rat femoral fracture model and to explore the role of dual energy X-ray absorptiometry (DEXA) in evaluating bone fracture healing. Sixty three-month-old female Sprague Dawley rats were used to establish right femoral fracture models. The BMD of the callus of the fractured right femur were scanned by DEXA at 2, 4, 6, 8, 10 and 12 weeks after operation, respectively. A light microscope was used to evaluate the callus of each rat at the same time. The corresponding segment of the left femur was taken as a control. The BMD at the fractured site increased significantly during the process of fracture healing, which shows an obvious healing trend. The callus BMDs were 29.5%, 48.3%, 85.3%, and 105.2% of the BMD of the control limb at 2, 4, 6 and 8 weeks after fracture, respectively. There was a significantly difference between the groups. A compatibility on time was found between the BMD and the histomorphological characteristics at the fractured site during the process of fracture healing. The fracture healing was almost completed at 8 weeks after fracture as assessed by its histomorphological characteristics when the callus BMD reached to 105.2% of the BMD of the control limb. The BMD of the distal metaphysis decreased until 12 weeks after fracture. DEXA can evaluate the mineralization of the callus during the fracture healing process accurately and quantitatively and is more sensitive than plain radiography in detecting impaired bone unions, which indicates that it may play an important role in monitoring fracture healing.


Soluble carbon nanotubes and their applications.
Carbon nanotubes (CNTs) have been the forefront of nanoscience and nanotechnology due to their unique electrical and mechanical properties and specific functions. However, due to their poor solubility in solvents, the applications using the materials have been limited. Therefore, strategic approaches toward the solubilization of CNTs are important in wide fields including chemistry, physics, biochemistry, biology, pharmaceuticals, and medical sciences. In this article, we summarize: (i) the strategic approaches toward the solubilization of CNTs using chemical and physical modifications, (ii) nanocomposites of CNTs and biological molecules including DNA, (iii) formation of CNTs with topological structures, (iv) separation of metallic and semiconducting nanotubes, (v) the preparations of films and fibers of CNTs and hybrid materials of CNTs and organic and inorganic molecules.


Structure of posttraumatic stress disorder symptoms and psychosocial functioning in Veterans of Operations Enduring Freedom and Iraqi Freedom.
Posttraumatic stress disorder (PTSD) is one of the most prevalent psychiatric conditions in Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF-OIF), but little is known about the structure of PTSD symptoms, and associations between PTSD symptom clusters and psychosocial functioning in this population. A total of 272 OEF-OIF Veterans in Connecticut completed a mail survey containing measures of psychopathology, resilience, and psychosocial functioning. Confirmatory factor analyses revealed that the 4-factor dysphoria model, which is comprised of separate re-experiencing, avoidance, dysphoria, and hyperarousal symptom clusters, provided the best representation of PTSD symptom structure in this sample. Dysphoria symptoms were independently associated with a broad range of psychosocial measures, even after controlling for age, combat exposure, and other PTSD symptom clusters. Re-experiencing symptoms were associated with alcohol use problems, and avoidance symptoms were associated with increased psychosocial difficulties and decreased perceptions of postdeployment social support. These results suggest that dysphoria symptoms were strongly related to a broad range of psychosocial measures in this sample of OEF-OIF Veterans. Dysphoria symptoms may deserve special attention in the assessment and treatment of symptomatic OEF-OIF Veterans.


Evaluation of the hepatic artery in potential donors for living donor liver transplantation by computed tomography angiography using multidetector-row computed tomography: comparison of volume rendering and maximum intensity projection techniques.
To compare the volume rendering (VR) and maximum intensity projection (MIP) computed tomography angiography (CTA) techniques using multidetector-row CT for hepatic artery evaluation of potential donors for living donor liver transplantation (LDLT). Over a 9-month period, CTA using multidetector-row CT and conventional angiography was performed in 62 consecutive potential donors for LDLT. Acquisition of arterial phase scans was initiated within 5 seconds after reaching enhancement of the descending aorta up to 70 HU as measured by a bolus-tracking technique (collimation = 1.25 mm, table speed = 7.5 mm, reconstruction interval = 0.625 mm). Postprocessing was performed on a commercially available workstation. Computed tomography angiography images of the hepatic artery were made using the VR and MIP techniques. A total of 10 to 30 images of various planes were generated to reveal the origins and branching patterns of hepatic arteries. With a 2-week interval, two reviewers separately evaluated CTA using VR and MIP techniques, specifically evaluating anatomic variations and hepatic arterial conspicuity. The results of conventional angiography were considered to represent the gold standard. The difference in postprocessing time between the two techniques was statistically analyzed by the Student t test, and the differences in arterial conspicuity and in the identified number of the hepatic artery to segment IV of the liver were analyzed by the chi2 test. Two CT examinations (3%) were technically inadequate for generating CTA because of respiratory motion artifact. The average times for postprocessing of VR and MIP images were 8.1 +/- 3.8 minutes and 5.0 +/- 0.7 minutes, respectively. Variations of hepatic arterial anatomy were present in 19 patients (32%) on conventional angiography. In 8 patients (13%), there was discrepancy in the variations of hepatic arterial anatomy between the two techniques: MIP was correct in 7 patients, and VR was correct in 1 patient. The dominant artery supplying segment IV was identified in 51 patients (85%) with MIP and in 39 patients (65%) with VR. There was no significant difference in conspicuity of the hepatic arteries using either the MIP or VR technique. In CTA techniques using multidetector-row CT, MIP is superior to VR for the hepatic arterial evaluation of potential LDLT donors in terms of depicting anatomic variations and postprocessing time.


Sulfobacillus disulfidooxidans sp. nov., a new acidophilic, disulfide-oxidizing, gram-positive, spore-forming bacterium.
An acidophilic, disulfide-oxidizing, mesophilic, aerobic bacterium was isolated from wastewater sludge. The new organism is a gram-positive sporulated rod. It can use elemental sulfur and pyrite as sole energy sources and grows on organic substrates such as glutamate and glucose. It also grows on the following organic sulfur substrates: oxidized and reduced glutathione, cysteine, cystine, and dithio(bis)benzothiazole and clearly shows a preference for disulfide bond-containing substrates. The optimal pH of growth is between 1.5 and 2.5, depending on the substrate used, and the growth temperature range varies from 4 to 40 degrees C, with an optimal value at 35 degrees C. The G + C chromosomal DNA content was measured at 53 +/- 1 mol%. Phylogenetic analysis of 16S genes coding for rRNA sequences places the new isolate in the genus Sulfobacillus. In addition, unique phenotypic and physiologic characteristics and DNA homology values assign the isolate to a new species in the genus. Therefore, this new isolate has been named Sulfobacillus disulfidooxidans and has been assigned ATCC number 51911.


Frigoribacterium salinisoli sp. nov., isolated from saline soil, transfer of Frigoribacterium mesophilum to Parafrigoribacterium gen. nov. as Parafrigoribacterium mesophilum comb. nov.
A Gram-stain-positive, short-rod, aerobic bacterium, designated as strain LAM9155T, was isolated from saline soil sample collected from Lingxian County, Shandong Province, PR China. The strain grew optimally at 25-30 °C, pH 7.0 and 0.5 % (w/v) NaCl. The 16S rRNA gene sequence analysis revealed that strain LAM9155T belonged to the genus Frigoribacterium and was closely related to Frigoribacteriumendophyticum EGI 6500707T (99.4 %), Frigoribacteriumfaeni 801T (98.6 %) and Frigoribacteriummesophilum MSL-08T (96.2 %). The DNA-DNA hybridization values between strain LAM9155T and F. endophyticum JCM 30093T and between strain LAM9155T and F. faeni DSM 10309T were 40.2±2.1 and 32.8±1.6 %, respectively. The major fatty acids of LAM9155T were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The cell-wall analysis showed the B-type peptidoglycan containing alanine, glutamate, glycine, serine and lysine and that the cell wall contained the sugars galactose and ribose. The genomic DNA G+C content of strain LAM9155T was 68.2 mol%. The predominant menaquinone was MK-9. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, one unknown glycolipid and four unknown lipids. Based on the DNA-DNA hybridization and phenotypic, phylogenetic and chemotaxonomic properties, strain LAM9155T could be distinguished from the recognized species of the genus Frigoribacterium and was suggested to represent a novel species, for which the name Frigoribacterium salinisoli sp. nov. is proposed. The type strain is LAM9155T (=ACCC 19902T=JCM 30848T). Moreover, the transfer of F. mesophilum Dastager et al. 2008 to Parafrigoribacterium gen. nov. as Parafrigoribacterium mesophilum comb. nov. (type strain MSL-08T=DSM 19442T=KCTC 19311T) is also proposed.


Renal Glomerular Mitochondria Function in Salt-Sensitive Hypertension.
Salt-sensitive (SS) hypertension is accompanied with an early onset of proteinuria, which results from the loss of glomerular podocytes. Here, we hypothesized that glomerular damage in the SS hypertension occurs in part due to mitochondria dysfunction, and we used a unique model of freshly isolated glomeruli to test this hypothesis. In order to mimic SS hypertension, we used Dahl SS rats, an established animal model. Animals were fed a 0.4% NaCl (normal salt, NS) diet or challenged with a high salt (HS) 4% NaCl diet for 21 days to induce an increase in blood pressure (BP). Similar to previous studies, we found that HS diet caused renal hypertrophy, increased BP, glomerulosclerosis, and renal lesions such as fibrosis and protein casts. We did not observe changes in mitochondrial biogenesis in the renal cortex or isolated glomeruli fractions. However, Seahorse assay performed on freshly isolated glomeruli revealed that basal mitochondrial respiration, maximal respiration, and spare respiratory capacity were lower in the HS compared to the NS group. Using confocal imaging and staining for mitochondrial H2O2 using mitoPY1, we detected an intensified response to an acute H2O2 application in the podocytes of the glomeruli isolated from the HS diet fed group. TEM analysis showed that glomerular mitochondria from the HS diet fed group have structural abnormalities (swelling, enlargement, less defined cristae). Therefore, we report that glomerular mitochondria in SS hypertension are functionally and structurally defective, and this impairment could eventually lead to loss of podocytes and proteinuria. Thus, the glomerular-mitochondria axis can be targeted in novel treatment strategies for hypertensive glomerulosclerosis.


Conducting polymer electrodes for electroencephalography.
Conducting polymer electrodes are developed on a flexible substrate for electroencephalography applications. These electrodes yield higher quality recordings than dry electrodes made from metal. Their performance is equivalent to commercial gel-assisted electrodes, paving the way for non-invasive, long-term monitoring of the human brain.


Assessing the planning and implementation strategies for the ICD-10-CM/PCS coding transition in Alabama hospitals.
Health information management (HIM) professionals play a significant role in transitioning from ICD-9-CM to ICD-10-CM/PCS. ICD-10-CM/PCS coding will impact many operational aspects of healthcare facilities, such as physicians' documentation in health records, coders' process for review of clinical information, the billing process, and the payers' reimbursement to the healthcare facilities. This article examines the level of readiness and planning for ICD-10-CM/PCS implementation among hospitals in Alabama, identifies training methods/approaches to be used by the hospitals, and discusses the challenges to the ICD-10-CM/PCS coding transition. A 16-question survey was distributed to 116 Alabama hospital HIM directors in December 2011 with follow-up through February 2012. Fifty-three percent of respondent hospitals began the planning process in 2011, and most facilities were halfway or less than halfway to completion of specific implementation tasks. Hospital coders will be or are being trained using in-house training, through seminars/webinars, or by consultants. The impact of ICD-10-CM/PCS implementation can be minimized by training coders in advance, hiring new coders, and adjusting coders' productivity measures. Three major challenges to the transition were identified: the need to interact with physicians and other providers more often to obtain information needed to code in ICD-10-CM/PCS systems, education and training of coders and other ICD-10-CM/PCS users, and dependence on vendors for major technology upgrades for ICD-10-CM/PCS systems. Survey results provide beneficial information for HIM professionals and other users of coded data to assist in establishing sound practice standards for ICD-10-CM/PCS coding implementation. Adequate planning and preparation will be essential to the successful implementation of ICD-10-CM/PCS.