Long-term therapy for chronic gout results in clinically important improvements in the health-related quality of life: short form-36 is responsive to change in chronic gout.
Short Form-36 (SF-36) is a validated outcome measure to assess health-related quality of life (HRQOL) in patients with gout. We assessed responsiveness to change of SF-36 in patients with gout. SF-36 was administered at baseline and at yearly intervals. We assessed the minimal clinically important differences (MCIDs) at the first and second year. We also assessed the responsiveness to change (effect size) and interpreted it based on Cohen's criteria. We modelled the improvement (defined as ≥MCID) in SF-36 scales and summary scores. Covariates included age, presence of tophi, comorbidities, baseline joint involvement, baseline serum urate, change in serum urate and the number of flares from baseline to 12 months. Of 99 subjects, 96 were male, mean age was 57.1 years, disease duration was 8.2 years and 40.4% had tophi. Ninety-two patients were treated with urate-lowering therapy (ULT) and daily colchicine, and seven were only on colchicine. Baseline mean serum urate level was 8.9 mg/dl and mean number of flares was 4.7 over last year. ULTs were associated with reduction in serum uric acid and number of flares (P < 0.001 for both) over 12 months. Therapy was associated with 22-70% of the patients achieving MCID in SF-36 scores at 12 months. Effect size estimates ranged from negligible to large (SF-36 mental component summary 0.08-bodily pain 1.09). Reduction in flares independently predicted improvements in three SF-36 physical scales (P = 0.001-0.06). Improvement in SF-36 scores was maintained at 2 years. In our real-life observational cohort, chronic urate lowering therapy and colchicine was associated with clinically meaningful improvements in HRQOL at 1 year and then maintained at 2 years. SF-36, especially physical domains and physical component summary, are responsive to change in gout.


Analysis of sensitivity and specificity of a new digital subtraction system: an in vitro study.
The purpose of this study was to compare a new digital subtraction system with conventional radiograph images for the detection of periapical and periodontal bone lesions. Periapical and periodontal bone lesions were simulated with cortical bone chips of varying sizes placed on a human dry mandible. Radiographic film images were acquired from varying projections and were subsequently digitized, registered, and subtracted. Four clinicians evaluated the subtracted images, and sensitivity and specificity were calculated. The mean sensitivity and specificity of the Diagnostic Subtraction Radiography system for detecting bone lesions of all sizes with varying projection geometry were 87.90% and 85.23%, respectively. The corresponding results for conventional radiograph images were 47.54% and 97.38%. The difference in sensitivity was statistically significant, whereas the difference in specificity was not. These results indicate that, even when radiographs are taken from disparate projection geometries, the Diagnostic Subtraction Radiography system is capable of excellent discrimination between healthy and disease states in this in vitro model.


Correlates of well-being among caregivers of long-term community-dwelling stroke survivors.
Although caregiving for stroke survivors is usually long-term, most studies on caregivers have generally involved only the first year following the event. We assessed and compared the long-term level of well-being measures among stroke survivors and their caregivers at more than 1 year following the stroke event and examined the associations between well-being, survivors' characteristics, and caregiver burden. We interviewed a convenience sample of 51 community-dwelling stroke survivors, at least 1 year after the last stroke event, and their primary caregivers. Disability of survivors was assessed using the Barthel index and the modified Rankin Scale; health-related quality of life by the SF-36 questionnaire; and depression and anxiety using the Hospital Anxiety Depression Scale. Caregivers filled the SF-36 questionnaire, Hospital Anxiety Depression Scale questionnaire, and the Zarit Burden Interview, which assesses caregiver burden. Caregivers reported low levels of health-related quality of life and high levels of burden, anxiety, and depression. Caregivers' anxiety level was higher than that of the survivors (7.7±5.1 vs. 5.8±4.5, respectively; P=0.02). Anxiety was the only characteristic of caregivers that was associated with overall caregiver burden. Our study suggests that there is a spillover effect of the disease on stroke patients' primary caregivers. Intervention programs for caregivers should focus on their mental state and address their specific needs.


Screening effect diverts the swimming directions from diaphototactic to positive phototactic in a disk-shaped green flagellate Mesostigma viride.
We found diaphototactic behavior (i.e. the cells swim perpendicularly with respect to the incident light) in a strain with colorless eyespot of a unicellular disk-shaped green flagellate Mesostigma viride. Lacking pigments completely in the eyespot, the screening effect in this strain was due only to the central part of the chloroplast whose cross section was thin. The diaphototaxis was most obvious when unilateral green stimulus light (520-580 nm) was given, whereas positive phototaxis appeared when given blue light (430-490 nm). The choice between diaphototaxis and (ordinary) phototaxis depended entirely on the transmission (%T) of the cell body against each wavelength of the stimulus: the green light penetrated well (%T > 90%), whereas the blue light was considerably shaded by the chloroplast (50% < %T < 70%). The fraction of positive phototactically behaving cells against each wavelength was in proportion to the front-to-back contrast value obtained at each individual wavelength. The fraction of diaphototaxis was inversely proportional to it. In addition, bilateral stimulus irradiations to wild-type cell with colored eyespot provided useful information about the principle of the diaphototactic steering.


Diagnosis and differentiation of bronchioloalveolar carcinoma from adenocarcinoma with bronchioloalveolar components with metabolic and anatomic characteristics using PET/CT.
(18)F-FDG PET has been reported to have reduced sensitivity in detecting bronchioloalveolar carcinoma (BAC) versus lung cancers with other histologies. However, there are CT characteristics that are suggestive of BAC, and potentially these could be useful to refine diagnostic criteria so PET/CT can be more accurate in the diagnosis of BAC. We correlated tumor size and density obtained with CT and glucose metabolism obtained with (18)F-FDG PET in patients with BAC and adenocarcinoma with BAC components (Adeno+BAC) to determine the roles of both the anatomic and the functional components of the PET/CT examination in diagnosing this disease. Also, the correlation between tumor size and (18)F-FDG uptake or Hounsfield unit (HU) value was determined in these 2 groups. This was a retrospective study on a consecutive series of 53 patients with 57 pathology-proven lesions (26 BAC, 31 Adeno+BAC) who underwent (18)F-FDG PET/CT scans. The standardized uptake value (SUV) and average HUs reported were obtained for the tumors. The tumor size, (18)F-FDG uptake, and HU values in both groups were compared. The correlation between metabolic (SUV) and CT (HU) characteristics for the lesions and tumor size was assessed using the Pearson correlation coefficient. A total of 26 lesions with pure BAC had a median SUVmax of 1.48 (range, 0.63-4.54). A total of 81% of patients with BAC (21/26 lesions) had SUVmax values of less than 2.5. Thirty-one lesions diagnosed as Adeno+BAC had a median SUVmax of 6.03 (range, 2.45-24) (P < 0.0001 vs. BAC). The mean SUVmax (1.77 +/- 0.99) of BAC was much lower than that of Adeno+BAC (6.55 +/- 4.33) (P < 0.0001). Maximum HU in BAC lesions (-111.96 +/- 123.92) was substantially lower than that in Adeno+BAC (82.03 +/- 33.77) lesions (P < 0.0001). The average maximum tumor dimension in the lung window was much smaller for BACs (17.63 +/- 5.5) than for Adeno+BACs (49.38 +/- 27.5) (P < 0.0001). A strong positive correlation between tumor size and HU was observed in the Adeno+BAC group (P = 0.0002). PET/CT can help differentiate between BAC and Adeno+BAC by using tumor size, CT density, and metabolic activity. Pure BAC exhibits smaller size, lower (18)F-FDG uptake, and lower tumor density than does Adeno+BAC. Many BACs have low SUVs (<2.0), but their low HU on CT aids in their proper identification.


Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram.
Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response. GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions. Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects. This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants.


Spatial-specific TGF-beta1 adenoviral expression determines morphogenetic phenotypes in embryonic mouse lung.
The precise spatial-temporal role that expression and activation of transforming growth factor (TGF)-beta plays in mammalian organ morphogenesis remains incompletely understood. Using replication deficient adenoviral vectors containing engineered TGF-beta1 cDNAs, we studied the spatial effects of locally over-expressing either latent or mutated, constitutively active TGF-beta1 protein during embryonic mouse lung branching morphogenesis in culture. Transfer of exogenous genes into lung epithelium was achieved by intra-tracheal micro-injection of recombinant adenovirus, while submerging lungs in virus resulted in gene transfer into the pleura and subjacent mesenchymal cells, as revealed by cytochemical staining for beta-galactosidase. Only lungs transfected with active, but not latent TGF-beta1 gene, showed elevated levels of active TGF-beta. Epithelial over-expression of active, but not latent TGF-beta1, via intra-tracheal micro-injection inhibited lung branching morphogenesis by 36 %. In contrast, lungs submerged with either active or latent TGF-beta1 recombinant virus did not demonstrate an inhibitory effect upon branching. Pulmonary gene regulation was assayed by competitive polymerase chain reaction coupled with reverse transcription. Direct respiratory tract micro-injection of adenovirus over-expressing active TGF-beta1 resulted in a dose-dependent inhibition of epithelial surfactant protein (SP)-C and SP-B mRNA levels by up to 76 % and 70 %, respectively, while in contrast, fibronectin and matrix Gla protein (MGP) mRNA levels remained stable. However, lungs that had been submerged in adenovirus expressing active TGF-beta1 demonstrated a concentration-dependent induction of both fibronectin and MGP mRNA levels up to 4.3- and 4.7-fold respectively in the presence of 1 x 10(11) pfu/ml active TGF-beta1 virus. On the other hand, lungs treated with adenovirus expressing latent TGF-beta1 either by micro-injection or submerging failed to demonstrate any regulatory effect either upon epithelial or mesenchymal gene expression. We conclude that adenovector-mediated over-expression of activated TGF-beta1 in specific spatial compartments results respectively in either inhibition of branching morphogenesis and epithelium-specific gene expression, or in induction of matrix gene expression without affecting morphogenesis or epithelium-specific gene expression, depending on the route of administration. Also, the lack of effect of latent TGF-beta1 over-expression strongly suggests that TGF-beta activation per se provides an important locus of fine regulation of the spatial effects of TGF-beta signaling during embryonic lung branching morphogenesis.


The impact of a package of behaviour change interventions on breastfeeding practices in East Java Province, Indonesia.
Suboptimal infant young child feeding practices are frequently reported globally, including in Indonesia. This analysis examined the impact of a package of behaviour change interventions on breastfeeding practices in Malang and Sidoarjo Districts, East Java Province, Indonesia. The BADUTA study (which in the Indonesian Language is an acronym for BAwah DUa TAhun, or children aged less than 2 years) was an impact evaluation using a cluster-randomized controlled trial with two parallel treatment arms. We conducted household surveys in 12 subdistricts from Malang and Sidoarjo. We collected information from 5175 mothers of children aged 0-23 months: 2435 mothers at baseline (February 2015) and 2740 mothers at endline (January to February 2017). This analysis used two indicators for fever and diarrhoea and seven breastfeeding indicators (early initiation of breastfeeding, prelacteal feeding, exclusive breastfeeding under 6 months, predominant breastfeeding, continued breastfeeding, age-appropriate breastfeeding and bottle-feeding). We used multilevel logistic regression analysis to assess the effect of the intervention. After 2 years of implementation of interventions, we observed an increased odds of exclusive breastfeeding under 6 months (adjusted odds ratio [aOR] = 1.85; 95% confidence interval [CI]: 1.35-2.53) and age-appropriate breastfeeding (aOR = 1.39; 95% CI: 1.07-1.79) in the intervention group than in the comparison group, at the endline survey. We found significantly lower odds for prelacteal feeding (aOR = 0.52; 95% CI: 0.41-0.65) in the intervention than in the comparison group. Our findings confirmed the benefits of integrated, multilayer behaviour change interventions to promote breastfeeding practices. Further research is required to develop effective interventions to reduce bottle use and improve other breastfeeding indicators that did not change with the BADUTA intervention.


Failure of delayed feedback deep brain stimulation for intermittent pathological synchronization in Parkinson's disease.
Suppression of excessively synchronous beta-band oscillatory activity in the brain is believed to suppress hypokinetic motor symptoms of Parkinson's disease. Recently, a lot of interest has been devoted to desynchronizing delayed feedback deep brain stimulation (DBS). This type of synchrony control was shown to destabilize the synchronized state in networks of simple model oscillators as well as in networks of coupled model neurons. However, the dynamics of the neural activity in Parkinson's disease exhibits complex intermittent synchronous patterns, far from the idealized synchronous dynamics used to study the delayed feedback stimulation. This study explores the action of delayed feedback stimulation on partially synchronized oscillatory dynamics, similar to what one observes experimentally in parkinsonian patients. We employ a computational model of the basal ganglia networks which reproduces experimentally observed fine temporal structure of the synchronous dynamics. When the parameters of our model are such that the synchrony is unphysiologically strong, the feedback exerts a desynchronizing action. However, when the network is tuned to reproduce the highly variable temporal patterns observed experimentally, the same kind of delayed feedback may actually increase the synchrony. As network parameters are changed from the range which produces complete synchrony to those favoring less synchronous dynamics, desynchronizing delayed feedback may gradually turn into synchronizing stimulation. This suggests that delayed feedback DBS in Parkinson's disease may boost rather than suppress synchronization and is unlikely to be clinically successful. The study also indicates that delayed feedback stimulation may not necessarily exhibit a desynchronization effect when acting on a physiologically realistic partially synchronous dynamics, and provides an example of how to estimate the stimulation effect.


Diffusion-facilitated direct determination of intrinsic parameters for rapid photoinduced bimolecular electron-transfer reactions in nonpolar solvents.
Bimolecular fluorescence-quenching reactions involving electron-transfer between electronically excited 5,10,15,20-tetraphenyl-21H,23H-porphine (TPP*) and 1,4-benzoquinone (BQ) or 1,4-naphthoquinone (NQ) were investigated using a set of alkane solvents that enabled the rapid reaction kinetics to be probed over a wide viscosity range, while minimizing changes in other relevant solvent parameters. Relative diffusion coefficients and reaction distances were recovered directly from analysis of fluorescence decay curves measured on a nanosecond time scale. The electron transfer from TPP* to BQ requires reactant contact, consistent with tightly associated exciplex formation in these nonpolar solvents. In contrast, electron transfer from TPP* to NQ displays a clear distance dependence, indicative of reaction via a much looser noncontact exciplex. This difference is attributed to the greater steric hindrance associated with contact between the TPP*/NQ pair. The diffusion coefficients recovered from fluorescence decay curve analysis are markedly smaller than the corresponding measured bulk relative diffusion coefficients. Classical hydrodynamics theory was found to provide a satisfactory resolution of this apparent discrepancy. The calculated hydrodynamic radii of TPP and NQ correlate very well with the van der Waals values. The hydrodynamic radius obtained for BQ is a factor of 6 times smaller than the van der Waals value, indicative of a possible tight cofacial geometry in the (TPP(+)/BQ(-))* exciplex. The present work demonstrates the utility of a straightforward methodology, based on widely available instrumentation and data analysis, that is broadly applicable for direct determination of kinetic parameter values for a wide variety of rapid bimolecular fluorescence quenching reactions in fluid solution.


Does investment in home visitors lead to better psychological health for HIV-affected families? Results from a quasi-experimental evaluation in South Africa.
Children and families affected by HIV are at considerable risk for psychological distress. Community-based home visiting is a common mechanism for providing basic counseling and other services to HIV-affected families. While programs emphasize home visitor training and compensation as means to promote high-quality service delivery, whether these efforts result in measurable gains in beneficiaries' well-being remains largely unanswered. This study employs a longitudinal quasi-experimental design to explore whether these kinds of investments yield concomitant gains in psychological outcomes among beneficiaries. Baseline and follow-up data were collected over a two-year period from children aged 10-17 at the time of program enrollment and their caregivers, with 80% retention. In this sample of 1487 children and 918 caregivers, the psychological health outcomes of those enrolled in programs with home visitors who receive intensive training, organizational support, and regular compensation (termed "paraprofessional") were compared to those enrolled in programs offering limited home visiting services from lay volunteers. Applying multilevel logistic regression, no measurable improvements were found among paraprofessional enrollees, and three outcomes were significantly worse at follow-up regardless of program model. Children's behavior problems became more prevalent even after adjusting for other factors, increasing from 29% to 35% in girls and from 28% to 43% in boys. Nearly one-quarter of girl and boys reported high levels of depression at follow-up, and this was a significant rise over time for boys. Rates of poor family functioning also significantly worsened over time, rising from 30% to 59%. About one-third of caregivers reported high levels of negative feelings at follow-up, with no improvements observed in the paraprofessional group. Results highlight that children's and caregivers' psychological outcomes may be relatively impervious to change even in paraprofessional home visiting models. Findings underscore the need for programs serving HIV-affected families to add focused evidence-based psychological interventions to supplement traditional home visiting.


Characterization of metal-substituted Klebsiella aerogenes urease.
Urease possesses a dinuclear Ni active site with the protein providing a bridging carbamylated lysine residue as well as an aspartyl and four histidyl ligands. The apoprotein can be activated in vitro by incubation with bicarbonate/CO2 and Ni(II); however, only approximately 15% forms active enzyme (Ni-CO2-ureaseA), with the remainder forming inactive carbamylated Ni-containing protein (Ni-CO2-ureaseB). In the absence of CO2, apoprotein plus Ni(II) forms a distinct inactive Ni-containing species (Ni-urease). The studies described here were carried out to better define the metal-binding sites for the inactive Ni-urease and Ni-CO2-ureaseB species, and to examine the properties of various forms of Co-, Mn-, and Cu-substituted ureases. Xray absorption spectroscopy (XAS) indicated that the two Ni atoms present in the Ni-urease metallocenter are coordinated by an average of two histidines and 3-4 N/O ligands, consistent with binding to the usual enzyme ligands with the lysine carbamate replaced by solvent. Neither XAS nor electronic spectroscopy provided evidence for thiolate ligation in the inactive Ni-containing species. By contrast, comparative studies of Co-CO2-urease and its C319A variant by electronic spectroscopy were consistent with a portion of the two Co being coordinated by Cys319. Whereas the inactive Co-CO2-urease possesses a single histidyl ligand per metal, the species formed using C319A apoprotein more nearly resembles the native metallocenter and exhibits low levels of activity. Activity is also associated with one of two species of Mn-CO2-urease. A crystal structure of the inactive Mn-CO2-urease species shows a metallocenter very similar in structure to that of native urease, but with a disordering of the Asp360 ligand and movement in the Mn-coordinated solvent molecules. Cu(II) was bound to many sites on the protein in addition to the usual metallocenter, but most of the adventitious metal was removed by treatment with EDTA. Cu-treated urease was irreversibly inactivated, even in the C319A variant, and was not further characterized. Metal speciation between Ni, Co, and Mn most affected the higher of two pKa values for urease activity, consistent with this pKa being associated with the metal-bound hydrolytic water molecule. Our results highlight the importance of precisely positioned protein ligands and solvent structure for urease activity.


Patterns and etiology of acute and chronic lung injury: insights from experimental evidence.
Adequate pulmonary function is pivotal for preterm infants. Besides being structurally immature, the preterm lung is susceptible to injury resulting from different prenatal conditions and postnatal insults. Lung injury might result in impaired postnatal lung development, contributing to chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD). This review focuses on lung injury mediated by and related to inflammatory changes in the lung. We give an overview on experimental models which have helped to elucidate mechanisms of pulmonary inflammation in prematurity. We describe experimental data linking acute and chronic chorioamnionitis with intrapulmonary inflammation, lung maturation and surfactant production in various animal models. In addition, experimental data has shown that fetal inflammatory response is modulated by the fetus himself. Experimental data has therefore helped to understand differential effects on lung function and lung maturation exerted by maternal administration of potentially anti-inflammatory substances like glucocorticosteroids (GCS). New approaches of modulation of pulmonary inflammation/injury caused by postnatal interventions during resuscitation and mechanical ventilation have been studied in animal models. Postnatal therapeutic interventions with widely used drugs like oxygen, steroids, surfactant, caffeine and vitamin A have been experimentally and mechanistically assessed regarding their effect on pulmonary inflammation and lung injury. Carefully designed experiments will help to elucidate the complex interaction between lung injury, lung inflammation, repair and altered lung development, and will help to establish a link between lung alterations originating in this early period of life and long-term adverse respiratory effects.


fMRI-driven DTT assessment of corticospinal tracts prior to cortex resection.
The role of diffusion tensor tractography (DTT) has become increasingly important in the preoperative mapping of brain white matter. Recently, functional magnetic resonance imaging (fMRI) driven DTT has provided the ability to evaluate the spatial relationship between the corticospinal tract (CST) and motor resection tumor boundaries. The main objective of this study was improvement of the preoperative assessment of the CST in patients with gliomas involving the motor cortical areas. Seventeen patients with gliomas involving motor cortical areas underwent 3 dimensions (3D) T1-weighted imaging for anatomical referencing, using both fMRI and diffusion tensor imaging (DTI). We used the fast-marching tractography (FMT) algorithm to define the 3D connectivity maps within the whole brain using seed points selected in the white matter adjacent to the location of fMRI activation. The target region of interest (ROI) was placed in the cerebral peduncle. Karnofsky performance status (KPS) scores were evaluated for each patient before and after surgery. The CST of a total seventeen patients were successfully tracked by choosing seed and target ROI on the path of the fibers. What is more, DTT can indicate preoperatively the possibility for total glioma removal or the maximum extent of surgical resection. The postoperative average KPS score for the seventeen patients enrolled increased by more than 10 points. Incorporation of fMRI driven DTT showed a maximum benefit in surgical treatment of gliomas. Our study of the assessment precision should enhance the accuracy of glioma operations with a resulting improvement in postoperative patient outcome.


Factors affecting willingness to provide buprenorphine treatment.
Buprenorphine is an effective long-term opioid agonist treatment. As the only pharmacological treatment for opioid dependence readily available in office-based settings, buprenorphine may facilitate a historic shift in addiction treatment from treatment facilities to general medical practices. Although many patients have benefited from the availability of buprenorphine in the United States, almost half of current prescribers are addiction specialists suggesting that buprenorphine treatment has not yet fully penetrated general practice settings. We examined factors affecting willingness to offer buprenorphine treatment among physicians with different levels of prescribing experience. Based on their prescribing practices, physicians were classified as experienced, novice, or as a nonprescriber and asked to assess the extent to which a list of factors impacted their prescription of buprenorphine. Several factors affected willingness to prescribe buprenorphine for all physicians: staff training; access to counseling and alternate treatment; visit time; buprenorphine availability; and pain medications concerns. Compared with other physicians, experienced prescribers were less concerned about induction logistics and access to expert consultation, clinical guidelines, and mental health services. They were more concerned with reimbursement. These data provide important insight into physician concerns about buprenorphine and have implications for practice, education, and policy change that may effectively support widespread adoption of buprenorphine.


Research on distribution network fault processing technology based on knowledge of graph.
Safety and reliability are the basis of the development of a distribution network. To analyze the risk transmission process in the distribution network and ensure the safe and reliable operation of the power system, this paper intends to use the knowledge graph method to realize the risk analysis of the distribution network information system. Firstly, the knowledge graph method is used to extract and integrate the risk knowledge of the multi-dimensional information collected by the distribution network. Secondly, the knowledge graph model of distribution network risk analysis is constructed, and the multi-dimensional distribution network fault handling and knowledge graph construction oriented to the feeder and platform area are designed. The distribution line parameters of the low-voltage distribution network model, neutral point grounding mode, and different fault types are analyzed, and the non-planned island is searched based on the knowledge graph adjacency matrix. Finally, combined with the simulation experiment, it is verified that the proposed method can effectively depict the information risk process of the distribution network. The structure of this paper starts from the multi-node complex distribution network, combined with a knowledge graph and deep learning method, which can solve the distribution network fault more quickly.


[Ethics in the authorship of scientific papers].
This article stresses the importance of ethical relations involved in intellectual production, particularly as regards quantity, quality, authorship and publication. It reaffirms the importance of ethics while managing workgroups, and the effective participation in the development of experimental projects.


Effects of a short-term interval training program on physical fitness in prepubertal children.
The aim of this study was to analyze the effects of a 7-week interval-training program on different aspects of physical fitness in children who were 8-11 years old. Forty-six boys and 54 girls (9.7 +/- 0.8 years) were divided into an experimental group and a control group. The 2 groups performed selected tests from the European physical fitness test battery before and after training. Training consisted of 2 specific 30-minute sessions per week of short high-intensity, intermittent-running aerobic exercises at velocities ranging from 100-130% of maximal aerobic speed. After training, the experimental group demonstrated a significant improvement in the standing broad jump (9.6%, p < 0.001, F = 12.9) and 20-meter shuttle run (5.4%, p < 0.001, F = 14.4), whereas for the control group, no significant changes were observed. It was concluded that a high-intensity, intermittent-running program improved children's aerobic performance and explosive strength.


Behçet's syndrome: recent advances to aid diagnosis.
Behçet's syndrome is a recurring inflammatory multiorgan disorder affecting the skin, mucosa, eyes, joints, stomach, and central nervous system. Behçet's syndrome epidemiology varies greatly among populations (0.64-420/100,000), and Behçet's syndrome has gained increasing international acclaim in the recent 50 years due to raising awareness of the syndrome, although it is rare in most population. In addition to the unclear etiology of the syndrome, the diagnosis of Behçet's syndrome is complicated by a vague clinical presentation, phenotypic heterogeneity and/or incomplete representation, and the lack of any specific laboratory, radiographic, or histological findings. There exists a dire need to elucidate factors that contribute to disease pathogenesis and/or are associated with clinical features of Behçet's syndrome and the classification of different forms of the syndrome. The identification of such molecular, cellular, and/or clinical factors are crucial for timely diagnosis and efficacious management of Behçet's syndrome. We discuss recent advances in the clinical diagnosis of Behçet's syndrome and related contributions of genetics, epigenetics, microbiome, inflammasomes, and autoantibodies to the improved diagnosis, management, and understanding of Behçet's syndrome.


Assessment of Sleep Quality and Quality of Life in Hypertensive Subjects at a Tertiary Care Hospital in Uttarakhand, India.
Hypertension is a leading risk factor for cardiovascular diseases with prevalence of 33% in urban and 25% in rural population in India. Studies have suggested that hypertension significantly affects the sleep quality and quality of life of subjects. Therefore, this study aimed to establish a correlation between sleep quality, quality of life, and hypertension in Uttarakhand. This observational cross-sectional study was carried out on hypertensive subjects at a tertiary care hospital in Uttarakhand following ethics approval. After taking consent from participants, blood pressure and anthropometric measurements were recorded. Then, their sleep quality and quality of life was assessed using Pittsburgh sleep quality index (PSQI) and WHO-QOL BREF questionnaire respectively. Statistical analysis was then carried out to correlate these parameters. 168 participants were recruited for this study, with 43.5% males and 56.5% females. It was found that 77.4% of these subjects were having poor sleep quality with the mean global PSQI score as 7.90 ± 3.713. These subjects assessed their Quality of life to be worst in physical domain (12.68 ± 3.13), followed by psychological, social relationship domain and environment domain. A significant association was found between sleep quality and different stages of hypertension (P value = 0.039) but quality of life and stages of hypertension have no significant association (P value > 0.05). Sleep quality, quality of life and blood pressure are correlated. So, clinicians should also focus on improving their patient's sleep quality and quality of life besides pharmacological treatment.


[Vaccines against human papillomavirus (HPV); between registration and implementation].
--Each year, 600-700 women in the Netherlands are diagnosed with cervical cancer. Over the last 10 years, an average of 250 women have died annually due to cervical cancer. --Gardasil, the first vaccine for Human papillomavirus (HPV), was recently approved in Europe for the prevention of cervical cancer. --The availability of a vaccine for HPV prompts the question whether it should be included in the Dutch National Immunisation Programme. --At the end of 2006, the Medicines Evaluation Board, the Health Council of the Netherlands and the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment organised a workshop for experts in the field to answer that question. --The HPV vaccine provides protection against HPV-16 and HPV-18, which cause approximately 70% of cervical cancers. --Because the efficacy of vaccination is only evident after many years, preserving good participation in the screening programme is essential. --The current screening could be improved by introducing an HPV test combined with self-sampling for women who do not participate in screening. --Vaccination is unarguably an important development. However, there are still several unanswered questions regarding vaccination and its actual protection, duration of protection, long-term safety and cost-effectiveness. --April 1st, 2008, the Health Council of the Netherlands had recommended including HPV vaccination in the National Immunisation Programme.


A role for heme oxygenase-1 in the antioxidant and antiapoptotic effects of erythropoietin: the start of a good news/bad news story?
Erythropoietin (EPO) is the major regulator of erythropoiesis. EPO's actions have been shown to be antiapoptotic and dependent on JAK2 signaling and Akt phosphorylation. These effects serve as link between EPO and heme oxygenase-1 (HO-1). HO-1 is an inducible enzyme with potent antioxidant and antiapoptotic activities which are regulated by Akt signaling. EPO's ability to alter cellular systems that involve apoptosis and oxidants suggests that EPO treatments are likely to have multiple and different effects which may start a good news/bad news story. Recombinant human EPO is the recognized treatment of choice to address anemia and to stimulate erythropoiesis in chronic renal failure patients, through its antiapoptotic action which likely involves HO-1. On the other hand, EPO treatment to address anemia in cancer patients, while providing significant improvements in cancer patients' quality of life, its effects on survival are equivocal, likely due to its linkage with HO-1. Two clinical trials of EPO in patients with solid tumors have, in fact, shown specific negative effects on survival. However, EPO's effect on tumor growth and survival is not uniformily pro growth and pro survival, as EPO may act synergistically with chemotherapy to induce apoptosis. Finally, compounds have been synthesized that do not trigger EPO receptor and thus may allow experimental distinction and, therefore, at least potentially affect at the clinical level the tissue-protective effects of EPO (e.g., antiapoptosis) without provoking its other potentially detrimental effects.


Lateral spread of neural excitation during microstimulation in intermediate gray layer of cat's superior colliculus.
1. Synaptically mediated spread of excitation has been studied during microstimulation in the intermediate gray layer of the superior colliculus of cats anesthetized with ketamine. Antidromic activation was used to identify those neurons sending axons to or through the contralateral pontine reticular formation. 2. Current thresholds were dependent on pulse duration, train length, and distance from the cell to the stimulus site. Stimulation with four cathodal pulses, 0.5 ms in duration, 30 microA in intensity, delivered at 400 Hz, excited cells of the intermediated gray up to 2-3 mm from the stimulus site. The results suggest that at least half the output cells in a region about 3 mm in diameter were driven by this stimulus. 3. The extent of spread in the unanesthetized midpontine-pretrigeminal cat was as great as, or greater than, that in animals anesthetized with ketamine. 4. Quick eye movements were evoked in ketamine-anesthetized cats by 100-ms trains of 0.5-ms pulses delivered at 400 Hz. Current thresholds for eye movements ranged from 15 to 90 microA, with most falling below 25 microA. 5. These results suggest that intracollicular microstimulation, with stimuli commonly used in studies of electrically evoked saccades, is accompanied by widespread synaptic activation of the intermediate gray layer. Since the metrics of electrically evoked saccades seem, nonetheless, to depend primarily on the location of the stimulating electrode, information about amplitude and direction must somehow be encoded in the distribution of neuronal discharge. 6. One possible form of such a distributed coding mechanism is discussed. This model assumes that the spatial densities of cells projecting to vertical and horizontal pulse generators of the saccadic system vary systematically beneath the retinotopic collicular map. Signals to the pulse generators change in magnitude as the collicular discharge zone occupies different positions in the connectional gradients and engages the specific output systems in varying proportion.


RAG-1 and RAG-2-dependent assembly of functional complexes with V(D)J recombination substrates in solution.
V(D)J recombination is initiated by RAG-1 and RAG-2, which introduce double-strand DNA breaks at recombination signal sequences (RSSs) of antigen receptor gene segments to produce signal ends, terminating in blunt, double-strand breaks, and coding ends, terminating in DNA hairpins. While the formation of RAG-RSS complexes has been documented, observations regarding the individual contributions of RAG-1 and RAG-2 to RSS recognition are in conflict. Here we describe an assay for formation and maintenance of functional RAG-RSS complexes in the course of the DNA cleavage reaction. Under conditions of in vitro cleavage, the RAG proteins sequester intact substrate DNA in a stable complex which is formed prior to strand scission. The cleavage reaction subsequently proceeds through nicking and hairpin formation without dissociation of substrate. Notably, the presence of both RAG-1 and RAG-2 is essential for formation of stable, functional complexes with substrate DNA under conditions of the sequestration assay. Two classes of substrate mutation are distinguished by their effects on RAG-mediated DNA cleavage in vitro. A mutation of the first class, residing within the RSS nonamer and associated with coordinate impairment of nicking and hairpin formation, greatly reduces the stability of RAG association with intact substrate DNA. In contrast, a mutation of the second class, lying within the RSS heptamer and associated with selective abolition of hairpin formation, has little or no effect on the half-life of the RAG-substrate complex.


Scholastic achievement at age 16 and risk of schizophrenia and other psychoses: a national cohort study.
There is abundant evidence that schizophrenia is associated with cognitive deficits in childhood. However, previous studies investigating school performance have been inconclusive. Furthermore, there are several biological and social factors that could confound the association. We investigated whether school performance at age 16 is associated with risk of adult schizophrenia and other psychoses in a large national cohort, while controlling for multiple confounders. Using a national sample of 907 011 individuals born in Sweden between 1973 and 1983, we used Cox regression to assess whether scholastic achievement at age 15-16 predicted hospital admission for psychosis between ages 17 and 31, adjusting for potential confounders. Poor school performance was associated with increased rates of schizophrenia [hazard ratio (HR) 3.9, 95% confidence interval (CI) 2.8-5.3], schizo-affective disorder (HR 4.2, 95% CI 1.9-9.1) and other psychoses (HR 3.0, 95% CI 2.3-4.0). Receiving the lowest (E) grade was significantly associated with risk for schizophrenia and other psychoses in every school subject. There was no evidence of confounding by migrant status, low birthweight, hypoxia, parental education level or socio-economic group. Poor school performance across all domains is strongly associated with risk for schizophrenia and other psychoses.


Lung Abscess and Recurrent Empyema After Infection With Mycoplasma hominis: A Case Report and Review of the Literature.
Mycoplasma hominis is a rarely identified cause of respiratory infection that can cause significant morbidity and mortality in immunocompromised patients. It is often missed due to the difficult detection of the organism with routine laboratory methods. We present the case of a 63-year-old male with a history of lymphoma who was transferred to our hospital with recurrent right-sided empyema and lung abscess in the right lower lobe. Advanced microbiological analysis finally revealed infection with M hominis. Despite appropriate antibiotic treatment, prolonged drainage as well as repeated surgery, which eventually resulted in right lower bilobectomy, were necessary for clinical improvement of our patient. Infection with M hominis may be more prevalent than previously indicated and can cause severe morbidity and mortality in thoracic surgery patients. Due to the diagnostic challenge, the appropriate antimicrobial treatment is often delayed. Inherent resistance to macrolides and inactivity of cell wall-active agents potentially complicate empiric antibiotic therapy. A review of the currently available literature enables a better understanding of the diagnostic difficulties and importance of this infection.


Systems pharmacology of arrhythmias.
Long QT syndrome (LQTS) is a congenital or drug-induced change in electrical activity of the heart that can lead to fatal arrhythmias. Mutations in 12 genes encoding ion channels and associated proteins are linked with congenital LQTS. With a computational systems biology approach, we found that gene products involved in LQTS formed a distinct functional neighborhood within the human interactome. Other diseases form similarly selective neighborhoods, and comparison of the LQTS neighborhood with other disease-centered neighborhoods suggested a molecular basis for associations between seemingly unrelated diseases that have increased risk of cardiac complications. By combining the LQTS neighborhood with published genome-wide association study data, we identified previously unknown single-nucleotide polymorphisms likely to affect the QT interval. We found that targets of U.S. Food and Drug Administration (FDA)-approved drugs that cause LQTS as an adverse event were enriched in the LQTS neighborhood. With the LQTS neighborhood as a classifier, we predicted drugs likely to have risks for QT effects and we validated these predictions with the FDA's Adverse Events Reporting System, illustrating how network analysis can enhance the detection of adverse drug effects associated with drugs in clinical use. Thus, the identification of disease-selective neighborhoods within the human interactome can be useful for predicting new gene variants involved in disease, explaining the complexity underlying adverse drug side effects, and predicting adverse event susceptibility for new drugs.


[Autonomy and health needs in the systematization of nursing assistance under the optics of the primary care].
Given recent changes in the organization of the primary health care in Brazil, it is necessary to reflect on the contributions of nursing care. This article aims to review the concepts of autonomy and health needs and its applications in different proposals for the systematization of the nursing care. It is a literature review on systematization of the nursing assistance, autonomy and health needs in databases LILACS and BDENF. The most relevant results indicate that autonomy incorporates aspects professional and patient's that are sustained by their respective categories. About needs we found that tracks biological needs and social needs, which intersect with the psychological to cover biopsychosocial needs. It was found that the application of the concepts was not present in classification systems of nursing. However, they were more related to International Classification of Nursing Practice (ICNP) and International Classification of Nursing Practice in Collective Heath (ICNPCH) projects.


[Pectoralis hand defects (Poland syndactylia)].
66 cases of pectoralis-hand defect are analyzed and the literature is reviewed. There is a high degree of variability of hand and arm malformations ranging from minor brachydactyly to peromelia. Genetic causes do not appear to be important for the majority of cases.


Effects of transcranial electrical stimulation of the right posterior parietal cortex on physical control responses.
The posterior parietal cortex plays an important role in postural stability by adapting to changes in input from the visual, vestibular, and proprioceptive systems. However, little is known regarding whether transcranial electrical stimulation of the posterior parietal cortex affects reactive postural responses. This study aimed to investigate changes in physical control responses to anodal and cathodal transcranial direct current stimulation and transcranial random noise stimulation of the right posterior parietal cortex using a simultaneous inertial measurement unit. The joint movements of the lower limb of 33 healthy volunteers were measured while standing on a soft-foam surface with eyes closed during various stimulation modalities. These modalities included anodal, cathodal transcranial direct current stimulation, and sham stimulation in Experiment 1, and transcranial random noise and sham stimulations in Experiment 2. The results showed that cathodal stimulation significantly decreased the joint angular velocity in the hip rotation, ankle inversion-eversion, and abduction-adduction directions compared to anodal or sham stimulation in Experiment 1. In contrast, there were no significant differences in physical control responses with transcranial random noise stimulation coeducation in Experiment 2. These findings suggest that transcranial electrical stimulation of the right posterior parietal cortex may modulate physical control responses; however, the effect depends on the stimulus modality.


Muscle cell differentiation in ascidian embryos analysed with a tissue-specific monoclonal antibody.
Utilizing a muscle-specific monoclonal antibody (Mu-2) as a probe, we analysed developmental mechanisms involved in muscle cell differentiation in ascidian embryos. The antigen recognized by Mu-2 was a single polypeptide with a relative molecular mass of about 220 X 10(3). It first appeared at the early tailbud stage and continued to be expressed until the swimming larva stage. There were distinct and separate puromycin and actinomycin D sensitivity periods during the occurrence of the antigen, suggesting the new synthesis of the polypeptide by developing muscle cells. Embryos that had been permanently arrested with aphidicolin in the early cleavage stages up to the 32-cell stage did not express the antigen. DNA replications may be required for the antigen expression. Embryos that had been arrested with cytochalasin B in the 8-cell and later stages developed the antigen, and the number and position of the arrested blastomeres exhibiting the differentiation marker almost corresponded to those of the B4.1-line muscle lineage. Furthermore, in quarter embryos developed from each blastomere pair isolated from the 8-cell embryo, all the B4.1 as well as a part of b4.2 partial embryos expressed the antigen, while the a4.2 and A4.1 partial embryos did not show the antigen expression. These results may provide further support for the existence of cytoplasmic determinants for muscle cell differentiation in this mosaic egg.


Alternating layer addition approach to CdSe/CdS core/shell quantum dots with near-unity quantum yield and high on-time fractions.
We report single-particle photoluminescence (PL) intermittency (blinking) with high on-time fractions in colloidal CdSe quantum dots (QD) with conformal CdS shells of 1.4 nm thickness, equivalent to approximately 4 CdS monolayers. All QDs observed displayed on-time fractions > 60% with the majority > 80%. The high-on-time-fraction blinking is accompanied by fluorescence quantum yields (QY) close to unity (up to 98% in an absolute QY measurement) when dispersed in organic solvents and a monoexponential ensemble photoluminescence (PL) decay lifetime. The CdS shell is formed in high synthetic yield using a modified selective ion layer adsorption and reaction (SILAR) technique that employs a silylated sulfur precursor. The CdS shell provides sufficient chemical and electronic passivation of the QD excited state to permit water solubilization with greater than 60% QY via ligand exchange with an imidazole-bearing hydrophilic polymer.


Extracellular Ca2+ increases cytosolic free Ca2+ in freshly isolated rat odontoblasts.
Recent evidence suggests that extracellular Ca2+ may modulate cell function in mineralized tissue. To determine whether dentinogenic cells, in particular, are sensitive to extracellular Ca2+, fura-2 microfluorometry was used to monitor intracellular calcium levels in odontoblasts freshly isolated from rat incisor. In response to applications of 0.5-4.0 mM extracellular calcium (CaCl2), most odontoblasts (84%; 107/128) showed an increase in intracellular calcium. For the majority of these cells (70%; 75/107), the typical response was biphasic; there was an initial, transient increase in intracellular calcium which reached peak levels within 30-50 s and decayed rapidly, followed by a slower (> 300 s) recovery toward basal levels. In general, the response of these cells to calcium was repeatable and the mean calcium concentration for the half-maximal response was approximately 1.3 mM. This effect could be partially blocked by either 200 microM lanthanum, a nonspecific blocker of Ca2+ channels, or 20 microM dantrolene, a potent inhibitor of Ca2+ release from internal stores. Used in combination, lanthanum, and dantrolene nearly abolished the calcium response completely. In addition, this response was sensitive to the dihydropyridine-sensitive calcium channel blocking agent nicardipine (60 microM), indicating a role for voltage-gated calcium channels during these events. These results show that odontoblasts respond to external calcium through mechanisms involving both influx of external calcium as well as release of calcium from internal stores and suggest a role for extracellular calcium in regulating the function of these cells.


Experience with an external quality assessment programme for point-of-care-testing (POCT) devices for the determination of blood glucose.
This article describes the preparation and internal and external evaluation of materials, critical issues in the external quality assessment (EQA) of point-of-care testing (POCT) devices for measuring blood glucose. A comparison was made between different materials, both of natural and synthetic origin and with and without stabilisers. The aims were to produce a material which was compatible with as many POCT-devices as possible and so reduce the number of materials sent out in each campaign as well as to optimise the precision and comparability of results between methods and devices. Although the use of near natural material--sterile-filtered plasma spiked with glucose--survived internal testing, this material proved to be unsuitable for EQA surveys. The study resulted in the reduction of materials for each survey to stabilised whole blood for one device, stabilised plasma for two devices and a synthetic material based on a polyethylene glycol matrix for all other devices. Samples were sent as pairs six times annually. The POCT-devices tested measured precisely but inaccurately in the synthetic material, when compared with the reference method (gas-chromatography coupled with isotope-dilution mass-spectrometry; GC-IDMS), so that the devices could only be evaluated for precision. The construction of ratios between the concentrations measured on the two samples distributed allowed an indirect assessment of accuracy. The need for surveillance of POCT devices is stressed in this publication, which combines theory and practice in setting up and running an EQA programme for blood glucose.


The evolution of the ribonucleotide reductases: much ado about oxygen.
Ribonucleotide reduction is the only known biological means for de novo production of deoxyribonucleotides, the building blocks of DNA. These are produced from ribonucleotides, the building blocks of RNA, and the direction of this reaction has been taken to support the idea that, in evolution, RNA preceded DNA as genetic material. However, an understanding of the evolutionary relationships among the three modern-day classes of ribonucleotide reductase and how the first reductase arose early in evolution is still far off. We propose that the diversification of this class of enzymes is inherently tied to microbial colonization of aerobic and anaerobic niches. The work is of broader interest, as it also sheds light on the process of adaptation to oxygenic environments consequent to the evolution of atmospheric oxygen.


[Cryptosporidiosis in the Andean region of Colombia: seroprevalence and recognition of antigens].
The objective of this study was to investigate, for the first time, the seroprevalence of cryptosporidiosis among urban and rural inhabitants in several departments of the Andean region of Colombia. The antigen recognition of Cryptosporidium parvum was also studied with sera. Between June 1996 and October 1998 1,778 serum samples were collected from people selected through convenience sampling. The detection of anti-C. parvum antibodies (IgM, IgA, and IgG) was carried out with enzyme-linked immunosorbent assay, and antigen recognition was done with immunoblotting. A prevalence of 83.3% was found, and the antibody percentages were 72.2% for IgM, 27.7% for IgA, and 27.6% for IgG. Higher seropositivity percentages were found among women, persons less than 30 years old, and residents of rural areas. IgM seroprevalence decreased with age, while IgG and IgA seroprevalences increased with age. These three immunoglobulin isotypes most frequently recognized the antigens from 51 to 69 kDa, which can be considered immunodominant. Of note was the immunoreactivity of IgM and IgA to protein fractions from 12 to 14 kDa and from 42 to 48 kDa, respectively, which could indicate exposure to the parasite. These results indicate that cryptosporidiosis is endemic in the Andean region of Colombia, and that it is possible to attribute many cases of diarrheal syndrome to C. parvum.


Contractile inactivation in frog skeletal muscle fibers. The effects of low calcium, tetracaine, dantrolene, D-600, and nifedipine.
Short muscle fibers (approximately 1.5 mm) of Rana pipiens were voltage-clamped with a two-microelectrode technique at a holding potential of -100 mV. Using conditioning depolarizing ramps, with slopes greater than 0.2 mV/s, partially inactivated responses are obtained at threshold values between -55 and -35 mV. With slopes equal to or slower than 0.1 mV/s, one inactivates contraction without ever activating it. When the membrane potential is brought slowly to values more positive than about -40 mV, test pulses, applied on top of the ramps, bringing the membrane potential to values up to +100 mV, are ineffective in eliciting contractile responses, which indicates complete inactivation. After inactivation, contractile threshold is shifted by perhaps 10 mV, to about -40 mV. The sensitivity of fibers to depolarizing ramps is increased by D-600 (50 microM), dantrolene (50 microM), tetracaine (100 microM), and low calcium (10(-8) M). In the presence of these agents, complete inactivation was obtained using ramp slopes of 1, 0.8, 0.4, and 0.2 mV/s, respectively. Nifedipine was less effective. With D-600, once inactivation had been induced, no repriming occurred after repolarization to -100 mV, and partial recovery occurred after washing out the drug. With low calcium, tetracaine, and nifedipine, the tension-voltage relationship was not affected, whereas the steady state inactivation curve (obtained in repriming experiments) was shifted by 10-25 mV toward more negative potentials. With D-600, the activation curve was not modified, whereas the inactivation curve could not be obtained, because of repriming failure. With dantrolene, the inactivation curve was not affected, whereas the activation curve was shifted toward less negative potentials and peak tension diminished, depending on the pulse duration. The results indicate that it is possible to induce complete inactivation without activation, and to differentiate activation and inactivation parameters pharmacologically, which suggests that the two are separate processes.


Characterization and Pathogenicity of Lasiodiplodia theobromae Causing Black Root Rot and Identification of Novel Sources of Resistance in Mulberry Collections.
Black root rot (BRR) caused by Lasiodiplodia theobromae is an alarming disease of mulberry that causes tremendous economic losses to sericulture farmers in India and China. Successful control of this disease can be attained by screening germplasm and identifying resistant sources. Seventy four diseased root samples were collected from farmer's fields belonging to four major mulberry growing states of South India. Based on morpho-cultural and scanning electron microscopy studies, 57 fungal isolates were characterized and identified as L. theobromae. Phylogenetic analysis of concatenated internal transcribed spacer and β-tubulin sequences revealed variation of the representative 20 isolates of L. theobromae. Following the root dip method of inoculation, pathogenicity studies on susceptible mulberry genotypes (Victory-1 and Thailand male) recognized the virulent isolate MRR-142. Accordingly, MRR-142 isolate was used to evaluate resistance on a set of 45 diverse mulberry accessions. In the repeated experiments, the mulberry accession ME-0168 which is an Indonesian origin belonging to Morus latifolia was found to be highly resistant consistently against BRR. Eight accessions (G2, ME-0006, ME-0011, ME-0093, MI-0006, MI-0291, MI-0489, and MI-0501) were found to be resistant. These promising resistant resources may be exploited in mulberry breeding for developing BRR resistant varieties and to develop mapping populations which successively helps in the identification of molecular markers associated with BRR.


High-frequency hearing of dental personnel.
234 dentists and dental nurses were examined with a normal and a high-frequency audiometer in high standard clinical conditions. Their ordinary and high-frequency hearing as compared with the controls showed no significant differences. Thus, exposure to high-frequency noise from high-speed drills and other modern dental instrumentation does not appear to be harmful to one's hearing and does not necessitate audiologic screening procedures for dental personnel.


Jannaschia donghaensis sp. nov., isolated from seawater of the East Sea, Korea.
A Gram-negative, non-motile and rod-, oval- or coccoid-shaped strain, DSW-17(T), was isolated from seawater of the East Sea, Korea, and subjected to a polyphasic taxonomic study. Strain DSW-17(T) grew optimally at pH 7.0-8.0 and 25 degrees C. It contained Q-10 as the predominant ubiquinone and C(18 : 1)omega7c as the major fatty acid. Major polar lipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and an unidentified glycolipid. The DNA G+C content was 65.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain DSW-17(T) was phylogenetically most closely affiliated to the genus Jannaschia. Strain DSW-17(T) exhibited 16S rRNA gene sequence similarity values of 96.5 % with the type strains of three recognized species of the genus Jannaschia. DNA-DNA relatedness data and differential phenotypic properties, together with the phylogenetic distinctiveness, demonstrated that strain DSW-17(T) is distinguishable from the recognized species of the genus Jannaschia. On the basis of phenotypic, phylogenetic and genetic data, strain DSW-17(T) was classified in the genus Jannaschia as a member of a novel species, for which the name Jannaschia donghaensis sp. nov. is proposed. The type strain is DSW-17(T) (=KCTC 12862(T)=JCM 14563(T)).


Minocycline blocks bilirubin neurotoxicity and prevents hyperbilirubinemia-induced cerebellar hypoplasia in the Gunn rat.
Encephalopathy induced by hyperbilirubinemia in infants has been described in the medical literature for over a century but neither the cellular nor molecular mechanisms underlying bilirubin neurotoxicity are well understood. In this study, we have demonstrated that minocycline potently protects primary cultured rat cerebellar granule neurons against bilirubin neurotoxicity (IC50 approximately 2 microm) and almost completely blocks cerebellar hypoplasia and the profound loss of Purkinje and granule neurons observed in homozygous Gunn rats, a genetic model of hyperbilirubinemia-induced neurotoxicity. Minocycline-treated newborn Gunn rats had nearly equivalent numbers of viable Purkinje and granule neurons in the cerebellum as did control animals. Moreover, minocycline inhibits the bilirubin-induced phosphorylation of p38 mitogen-activated protein kinase both in vivo as well as in vitro. Taken together our data demonstrate that minocycline is able to greatly reduce bilirubin-induced neurotoxicity and suggest that minocycline's neuroprotective effects may be due in part to an inhibition of p38 mitogen-activated protein kinase activity. Our findings may lead to novel approaches for treating bilirubin-induced encephalopathy.


B cell modulation strategies in autoimmunity: the SLE example.
The paradigm that T cells are the prime effectors of autoimmune diseases has been recently challenged by growing evidence that B-lymphocytes play a role in the development, re-activation and persistence of autoimmune disorders. B-cells of different subsets may play different roles in autoimmune pathologies due to their ability to secrete antibodies, produce cytokines, present antigen and form ectopic germinal centers. Thus, a given therapeutic approach or drug may have distinct outcomes depending on which specific B cell subset is targeted. Immunosuppressive therapies such as azathioprine (AZA), cyclophosphamide (CyC) or methotrexate (MTX) are conventionally used in autoimmune diseases with the aim of reducing disease activity and improving the patient's general health conditions. These treatments do not target a specific cellular type or subset and have substantial side effects, such as impairment of liver function and fertility. Moreover, autoimmune patients may be refractory to immunosuppressive therapy. In these cases finding an effective treatment becomes a challenge. The fast evolution in antibody technology is leading to the production of a wide array of humanized monoclonal antibodies, targeting specific cell types or pathways, initiating a new era in the treatment of autoimmune disorders. In addition, the recent discovery that toll like receptors (TLRs) activation can fire up autoimmunity in humans and maintain disease gives the grounds for the development of new drugs targeting the TLR/MyD88 pathway. In contrast to conventional immune-suppression, the availability of drugs interfering with B-cell specific pathogenetic pathways gives the possibility to choose therapies tailored to each disease and, possibly, to each patient.


Traumatic brain injury in horses: 34 cases (1994-2004).
To investigate the clinical, clinicopathologic, and diagnostic characteristics; treatment; and outcome associated with acute traumatic brain injury (TBI) in horses and assess risk factors for nonsurvival in TBI-affected horses. Retrospective case series. 34 horses with TBI. Procedures-Medical records of horses that had sustained trauma to the head and developed neurologic signs were reviewed. Data that included signalment, clinicopathologic findings, diagnosis, treatment, and outcome were analyzed. Clinicopathologic variables among horses in survivor and nonsurvivor groups were compared, and risk factors for nonsurvival were determined. Median age of affected horses was 12 months. Findings of conventional survey radiography of the head alone failed to identify all horses with fractures of the calvarium. Horses with basilar bone fractures were 7.5 times as likely not to survive as horses without this type of fracture. Depending on clinical signs, horses received supportive care, osmotic or diuretic treatments, antimicrobials, anti-inflammatory drugs, analgesics, or anticonvulsants. Twenty-one (62%) horses survived to discharge from the hospital. In the nonsurvivor group, mean PCV was significantly higher, compared with the value in the survivor group (40% vs 33%). Risk factors associated with nonsurvival included recumbency of more than 4 hours' duration after initial evaluation (odds ratio, 18) and fracture of the basilar bone (odds ratio, 7.5). Results suggest that prognosis for survival in horses with acute TBI may be more favorable than previously reported. Among horses with TBI, persistent recumbency and fractures involving the basilar bones were associated with a poor prognosis.


Matrix Gla protein (MGP) promoter polymorphic variants and its serum level in stenosis of coronary artery.
Although the role of matrix Gla protein (MGP) is not completely known but, its expression within subendothelial macrophages and vascular smooth muscle cells is suggested to be involved in vascular calcification. In this study, we investigated the associations between the serum MGP levels and the MGP promoter high minor allele frequency (MAF) variants with the development of stenosis in coronary arteries. Moreover, we evaluated the allele changes within predicted transcription factor elements with bioinformatics tools. 182 subjects were recruited from who underwent coronary angiography. The MGP promoter rs1800801, rs1800802 and rs1800799 genotypes and haplotypes were detected by ARMS-RFLP PCR techniques. The serum MGP concentration was measured using ELISA method. Jaspar profiles were used for scoring the polymorphic variations within the transcription factor elements. The genotype and two-allelic haplotype distributions were not significant between the patient and control groups (P > 0.05). The serum MGP levels had not significant differences between the genotypes (P > 0.1) and haplotypes (P > 0.4). Based on the prediction studies, we did not observe significant differences between the polymorphic scores in the predicted elements (P > 0.05). We concluded that the genotype and haplotype distributions of the MGP promoter high-MAF polymorphisms, as confirmed in the prediction studies and the serum MGP level are not significantly associated with the coronary artery disease. Based on the study results, the MGP protein did not play an important role in the development of stenosis of coronary arteries.


Systemic exposure to bacterial amyloid curli alters the gut mucosal immune response and the microbiome, exacerbating Salmonella-induced arthritis.
The Salmonella biofilm-associated amyloid protein, curli, is a dominant instigator of systemic inflammation and autoimmune responses following Salmonella infection. Systemic curli injections or infection of mice with Salmonella Typhimurium induce the major features of reactive arthritis, an autoimmune disorder associated with Salmonella infection in humans. In this study, we investigated the link between inflammation and microbiota in exacerbating autoimmunity. We studied C57BL/6 mice from two sources, Taconic Farms and Jackson Labs. Mice from Taconic Farms have been reported to have higher basal levels of the inflammatory cytokine IL - 17 than do mice from Jackson Labs due to the differences in their microbiota. When we systemically injected mice with purified curli, we observed a significant increase in diversity in the microbiota of Jackson Labs mice but not in that of the Taconic mice. In Jackson Labs, mice, the most striking effect was the expansion of Prevotellaceae. Furthermore, there were increases in the relative abundance of the family Akkermansiaceae and decreases in families Clostridiaceae and Muribaculaceae in Jackson Labs mice. Curli treatment led to significantly aggravated immune responses in the Taconic mice compared to Jackson Labs counterparts. Expression and production of IL - 1β, a cytokine known to promote IL - 17 production, as well as expression of Tnfa increased in the gut mucosa of Taconic mice in the first 24 hours after curli injections, which correlated with significant increases in the number of neutrophils and macrophages in the mesenteric lymph nodes. A significant increase in the expression of Ccl3 in colon and cecum of Taconic mice injected with curli was detected. Taconic mice injected with curli also had elevated levels of inflammation in their knees. Overall, our data suggest that autoimmune responses to bacterial ligands, such as curli, are amplified in individuals with a microbiome that promote inflammation.


Expression of APG-2 protein, a member of the heat shock protein 110 family, in developing rat brain.
APG-2 protein is a member of the heat shock protein 110 family, and it is thought to play an important role in the maintenance of neuronal functions under physiological and stress conditions. However, neither the tissue-distribution of APG-2 protein nor developmental change of its expression has been studied at the protein level. Therefore, we generated an antiserum against APG-2 protein and studied expression of this protein in rat brain and other tissues by use of the Western blot method. The results showed a high expression of APG-2 protein in various regions of the central nervous system (cerebral cortex, hippocampus, striatum, midbrain, hypothalamus, cerebellum, medulla pons, and spinal cord) throughout the entire postnatal stage. Similarly, a high level of APG-2 protein was detected in the whole brain of rat embryos and in adult rat tissues such as liver, lung, spleen, and kidney. In contrast, its expression in heart was high at postnatal days 1 and 3, but thereafter drastically decreased to a low level. Furthermore, APG-2 protein was detected in neuronal primary cultures prepared from rat cerebral cortex, and its level did not change notably during neuronal differentiation. These results show that APG-2 protein is constitutively expressed in various tissues and also in neuronal cells throughout the entire embryonic and postnatal period. suggesting that it might play an important role in these tissues under non-stress conditions.


Zonisamide in the management of epilepsy in the elderly.
Zonisamide (ZNS), a second-generation antiepileptic drug, indicated as add-on treatment of focal epilepsy, has been recently approved as monotherapy for the treatment of partial seizures in adults affected by newly diagnosed epilepsy in Europe. Evidence on the efficacy and tolerability of antiepileptic drugs in the elderly is still lacking as these patients are frequently excluded from clinical trials. Here, a comprehensive overview of available data regarding the use of ZNS in the treatment of epilepsy in elderly people is provided. In a pooled analysis conducted in patients aged ≥65 years, no new/unexpected safety findings have emerged. Few data from uncontrolled investigations suggest that ZNS may be effective and well tolerated when administered as monotherapy or adjunctive antiepileptic treatment in the elderly. However, evidence from these observational studies is less than satisfactory, and randomized controlled trials focused on these patients are still needed.


ANTIGENIC VARIANTS OF EASTERN EQUINE ENCEPHALITIS VIRUS.
A study by hemagglutination-inhibition test showed that 19 strains of eastern equine encephalitis virus grouped themselves in two main types, which have been designated North American and South American. The former consists of ten strains from the eastern half of the United States, from Massachusetts to Florida; Jamaica, the Dominican Republic, and, subject to confirmation, Thailand. The South American type comprises nine strains from Panama, Trinidad, British Guiana, Brazil, and Argentina. The strains were isolated from different natural hosts over a period of 30 years.


The intragastric host-mediated assay for the assessment of the formation of direct mutagens in vivo.
The intragastric host-mediated assay (h.m.a.) was devised and carried out with a view to assessing the formation of direct mutagens in the gastrointestinal tract of mammals. The h.m.a. consists in the injection of nitrosable compounds, NaNO2 and cells of the yeast S. pombe, by gavage into the animals' stomachs and in the recovery of the target cells from the faeces for mutation-induction analysis. Methylurea was chosen as a model nitrosable compound, and the effects of nitrosation modulators such as ascorbic acid and thiocyanate were studied. Cimetidine, a drug nitrosable in vitro, was tested with the system. Positive results were obtained only at very large doses and in artificially produced low pH. The new host-mediated assay seems to be efficient in revealing the formation, in vivo, of direct, short-living mutagens.


Postoperative wound infections following cardiac surgery: significance of contaminated cases performed in the preceding 48 hours.
Postoperative wound infections following open heart cardiac surgery increased markedly after hospital relocation (7 of 77 v 4 of 320; p = .0007). Of the multiple identified risk factors, significant patient and procedural association included prolonged operative time of infected patients (384 minutes +/- 115 SD v 318 +/- 67, p = .025) and operation in a room used within the previous 48 hours for a contaminated case (4/7 infected v 10/67 not infected; p = .023). Several defects were discovered in the air handling system. After appropriate changes, the infection rate decreased in the next 12 months (1 of 109; p less than .02). Other concurrent surgical wound infection rates remained unchanged suggesting that defective air handling may have impacted only on the open heart cardiac surgery patients. Preceding contaminated surgery and prolonged operative time were associated with postoperative wound infections in cardiac surgery.


[The development consultation for children in whom the physician suspects a developmental disorder: early experiences in Maastricht].
The so-called development consultation of the Heuvelland health care organization in Maastricht was organized with a view to early detection of developmental disorders in young children (< or = 6 years), thereby minimizing dysfunctioning. Health centre physicians, general practitioners and school doctors can refer children aged 0-6 years to this combined consultation hour of a paediatrician, a children's neurologist, a children's physiotherapist and in some cases, an educationalist and a speech therapist. After the starting-up phase, the number of referred children was three to six per month. The referring physician is usually present at the joint consultation after the examinations. At this meeting it is attempted to arrive at a diagnosis or at least to draw up a treatment plan. After the meeting, the child's parents or guardians are informed of the team's findings. The first group of 60 children included 9 with a cerebral paresis and 18 with retarded motor development and speech retardation; 8 children were referred for exclusion of neurological/cerebral abnormalities.


Gastrointestinal microphysiological systems.
Gastrointestinal diseases are a significant health care and economic burden. Prevention and treatment of these diseases have been limited by the available human biologic models. Microphysiological systems comprise organ-specific human cultures that recapitulate many structural, biological, and functional properties of the organ in smaller scale including aspects of flow, shear stress and chemical gradients. The development of intestinal microphysiological system platforms represents a critical component in improving our understanding, prevention, and treatment of gastrointestinal diseases. This minireview discusses: shortcomings of classical cell culture models of the gastrointestinal tract; human intestinal enteroids as a new model and their advantages compared to cell lines; why intestinal microphysiological systems are needed; potential functional uses of intestinal microphysiological systems in areas of drug development and modeling acute and chronic diseases; and current challenges in the development of intestinal microphysiological systems. Impact statement The development of a gastrointestinal MPS has the potential to facilitate the understanding of GI physiology. An ultimate goal is the integration of the intestinal MPS with other organ MPS. The development and characterization of nontransformed human intestinal cultures for use in MPS have progressed significantly since the inception of the MPS program in 2012, and these cultures are a key component of advancing MPS. Continued efforts are needed to optimize MPS to comprehensively and accurately recapitulate the complexity of the intestinal epithelium within intestinal tissue. These systems will need to include peristalsis, flow, and oxygen gradients, with incorporation of vascular, immune, and nerve cells. Regional cellular organization of crypt and villus areas will also be necessary to better model complete intestinal structure.


Basal energy expenditure measured by indirect calorimetry in patients with squamous cell carcinoma of the esophagus.
Determination of Basal Energy Expenditure (BEE) is essential for planning nutritional therapy in patients with esophageal cancer. The objective of this study was to determine BEE through indirect calorimetry (IC) in patients with squamous cell carcinoma of the esophagus (SCC). Cross-sectional study involving 30 patients admitted with a diagnosis of SCC who underwent IC before starting cancer therapy. The BEE was evaluated using IC and also estimated by means of the Harris-Benedict Equation (HBE). Nutritional assessment was conducted using anthropometric parameters (body mass index, arm circumference, triceps skinfold thickness, arm muscle circumference, and weight loss), biochemical parameters (albumin, transferrin and C-reactive protein) and tetrapolar bioimpedance to assess body composition (fat free mass). Additionally, lung capacity was measured and clinical staging of the cancer established by the TNM method. The mean of the BEE for IC and Harris-Benedict Equation were 1421.8 ± 348.2 kcal/day and 1310.6 ± 215.1 kcal/day, respectively. No association was found between BEE measured by IC and clinical staging (p=0.255) or the Tiffeneau Index (p=0.946). There were no significant associations between BEE measured by IC and altered dosages of transferrin, albumin and C-reactive protein (p=0.364, 0.309 and 0.780 respectively). The factors most associated with BEE were BMI and fat free mass. The BEE of patients with SCC was underestimated when using the HBE, and the result overestimated when incorporating an injury factor with the HBE. Therefore, despite the practical difficulties of implementing IC, its use should be considered.


Activation of peripheral blood mononuclear cells and extracellular matrix and inflammatory gene profile in acute myocardial infarction.
Inflammation and ECM (extracellular matrix) remodelling play important roles in LV (left ventricular) remodelling following acute MI (myocardial infarction). Previous studies show elevated plasma MMP (matrix metalloproteinase) levels in patients with acute MI, but their sources are not clear. The recruitment of mononuclear cells into the infarcted myocardium is critical for inflammatory responses, but their exact roles in LV remodelling have not been fully investigated, as it is difficult to isolate and study the function of regional inflammatory cells. To address these questions, we isolated PBMCs (peripheral blood mononuclear cells) from blood samples of patients with acute MI or stable angina, or healthy controls (n=14, 8 and 12 respectively). PBMCs were cultured for 24 h and the MMP9 level in the culture medium was measured by gelatin zymography, and MMP9 gene expression was measured by real-time PCR. Two superarrays (ECM and adhesion molecules, and common cytokines; 84 genes included in each array) were employed to screen gene expression profiles by PBMCs in five patients with acute MI and five controls. We found that MMP9 expression by PBMCs at both the mRNA and protein levels was increased 2-fold (both P<0.05) in patients with acute MI compared with the two control groups. Notably, MMP2 was not expressed by PBMCs. Superarray screening revealed that PBMCs not only expressed MMPs, TIMPs (tissue inhibitors of metalloproteinases) and matrix proteins, but also served as an important source of cell adhesion molecules, inflammatory cytokines and growth factors. A total of 42 genes were differentially expressed in patients with acute MI compared with controls. Expression of selected genes was confirmed by real-time PCR. In conclusion, PBMCs constitute a key cellular source for elevated plasma MMP9, but not for MMP2. PBMCs also contribute to systemic and regional inflammation and matrix remodelling in acute MI.


Response of common bean (Phaseolus vulgaris L.) to nitrogen, phosphorus and rhizobia inoculation across variable soils in Zimbabwe.
Common bean is an important crop with potential to curb malnutrition in poor Sub-Saharan African populations. Yields of common bean (Phaseolus vulgaris L.) are, however poor, limited by low soil phosphorus (P), nitrogen (N) and poor biological N2-fixation. On-farm experiments were carried out to study the effect of N, P and rhizobia inoculation on common bean yield and yield components during the 2014/2015 and 2015/2016 cropping seasons in Eastern Zimbabwe. Experiments were conducted on five farmers' fields located in two agroecologies; three fields were considered to be degraded with soil organic carbon (SOC) < 4 g kg-1 and available P < 6 mg kg-1, while the two non-degraded sites had SOC > 7 g kg-1 and available P > 15 mg kg-1. Two common bean varieties (Gloria and NUA45) were tested in a split-plot arranged in randomized complete block design. The main plot factor was the combination of N (0 and 40 kg ha-1) and P (0 and 20 kg ha-1), and the sub-plot factors were variety (Gloria and NUA 45) and inoculation with Rhizobium tropici strain CIAT899 (+/- inoculum). At planting, both N and P were applied at 20 kg ha-1, with an additional 20 kg ha-1 N top dressing applied at flowering. Analysis of variance indicated common bean did not respond to rhizobia inoculation (P > 0.05) whilst P significantly increased the number of nodules and active nodules per plant (P < 0.001), and grain yield. Application of 40 kg ha-1 N significantly increased the number of pods per plant, number of seeds per pod, and grain yields. A significant NP interaction was only observed on grain yield for non-degraded soils. Co-application of N and P in non-degraded sites increased grain yields from 0.27 to 1.48 Mg ha-1during the first season and from 0.37 to 2.09 Mg ha-1during the second season. On degraded sites, NP application resulted in uninspiring grain yield gains of 0.09 to 0.19 Mg ha-1 during the first season, and from 0.16 to 0.28 Mg ha-1 in the second season. In general, effects of N or P were not significantly different, suggesting that farmers could invest in either of these nutrients for increased common bean grain yields. Strategically, P investments would be more logical as residual P effects to rotational cereals improve overall cropping system performance. The response of common bean to inoculation in Zimbabwe still needs to be widely investigated for these and other varieties.


Deep and superficial abdominal muscle activation during trunk stabilization exercises with and without instruction to hollow.
The deepest muscle of the human ventro-lateral abdominal wall, the Transversus Abdominis (TrA), has been ascribed a specific role in spine stabilization, which has motivated special core stability exercises and hollowing instruction to specifically involve this muscle. The purpose here was to evaluate the levels of activation of the TrA and the superficial Rectus Abdominis (RA) muscles during five common stabilization exercises performed in supine, bridging and four-point kneeling positions, with and without instruction to hollow, i.e. to continuously pull the lower part of the abdomen towards the spine. Nine habitually active women participated and muscle activity was recorded bilaterally from TrA and RA with intramuscular fine-wire electrodes introduced under the guidance of ultrasound. Results showed that subjects were able to selectively increase the activation of the TrA, isolated from the RA, with the specific instruction to hollow and that side differences in the amplitude of TrA activity, related to the asymmetry of the exercises, remained even after the instruction to hollow. The exercises investigated caused levels of TrA activation from 4 to 43% of that during maximal effort and can thus be used clinically to grade the load on the TrA when designing programs aiming at training that muscle.


Relationship between control and the intermediate term outcome of anorexia nervosa in Hong Kong.
To examine the relationship between control and the intermediate term outcome of Chinese patients with anorexia nervosa. 88 patients who fulfilled the DSM-III-R criteria for typical (fat phobic, n=63) and atypical (non-fat phobic, n=25) anorexia nervosa were contacted 9 years after the onset of illness. They completed the Morgan-Russell Outcome Assessment Schedule, Shapiro Control Inventory, and Eating Disorder Inventory-I. 62.2%, 32.4% and 5.4% of patients had good, intermediate, and poor outcome. Outcome was positively correlated with the overall general and specific sense of control, positive sense of control, and negatively with negative sense of control. Patients with good outcome exhibited the least negative modes of control and had the least desire for control. Typical and atypical patients showed similar but not identical control profiles. Healthier control was associated with better outcome of anorexia nervosa but their causal relationship was far from clear because of the cross-sectional nature of the present study. The Shapiro Control Inventory is a potentially useful instrument for studying control in eating disorders.


Enhanced survival of bone-marrow-derived pluripotent stem cells in an animal model of auditory neuropathy.
The loss of spiral ganglion neurons (SGNs) is one of the major causes of profound sensorineural hearing loss (SNHL). Stem cell replacement therapy, which is still in its infancy, has the potential to treat or cure those who suffer from an array of illnesses and degenerative neurologic disorders, including sensorineural deafness (SNHL). Little is known about the potentials of mesenchymal stem cells (MSCs) and their ability to take on properties of SGNs. The two main purposes of this study were to evaluate the survival of mouse MSCs transplanted into normal and ouabain-treated gerbil cochleae and to determine the migratory patterns of MSCs with two differing injection methods. Thirty-two Mongolian gerbils, 3 to 4 months old, were used as recipients, and four 6-week-old TgN(ACTbEGFP) mice that ubiquitously express green fluorescent protein (GFP) were used as donors. The animals were deafened by ouabain, which damaged SGNs while leaving hair cell systems intact. After 4 weeks of recovery, the animals received an intraperilymphatic transplantation of 1.0x10(6) GFP-positive undifferentiated MSCs via two different injection methods: scala tympani injection and modiolar injection. Seven days after the transplantation, the survival of MSCs was evaluated by microscopic examination of frozen sections cut through the cochleae of the recipient animals. The number of profiles was counted on the five most central modiolar sections. One-way analyses of variance (ANOVA) were used to determine any significantdifferences among mean profile counts across the experimental conditions. Our findings indicated that undifferentiated MSCs were able to survive in the modiolus both in the control and the ouabain-treated cochleae. The average number of profiles found in the modiolus was greater in the ouabain-treated cochleae than in the control cochleae. This difference was statistically significant (P<.01) as determined using a one-way ANOVA and an ad hoc Tukey-Kramer's test. With the scala tympani injection, there were no profiles found in the modiolus either in the control or ouabain-treated cochleae. This finding may indicate that donor MSCs need to be directly injected into the modiolus to replace injured SGNs. Finally, there was no evidence of hyperacute rejection in any of the gerbils despite the use of xenotransplantation. These findings may have important clinical implications as a means of delivering MSCs in the cochlea for stem-cell replacement therapy. Survival of transplanted MSCs into the modiolus of the cochlea may result in regeneration of damaged SGNs.


Data-dependent kernel machines for microarray data classification.
One important application of gene expression analysis is to classify tissue samples according to their gene expression levels. Gene expression data are typically characterized by high dimensionality and small sample size, which makes the classification task quite challenging. In this paper, we present a data-dependent kernel for microarray data classification. This kernel function is engineered so that the class separability of the training data is maximized. A bootstrapping-based resampling scheme is introduced to reduce the possible training bias. The effectiveness of this adaptive kernel for microarray data classification is illustrated with a k-Nearest Neighbor (KNN) classifier. Our experimental study shows that the data-dependent kernel leads to a significant improvement in the accuracy of KNN classifiers. Furthermore, this kernel-based KNN scheme has been demonstrated to be competitive to, if not better than, more sophisticated classifiers such as Support Vector Machines (SVMs) and the Uncorrelated Linear Discriminant Analysis (ULDA) for classifying gene expression data.


Supported liquid extraction combined with liquid chromatography tandem mass spectrometry for the quantitative analysis of a TLR7 agonist imiquimod LFX453 in plasma at low picograms per milliliter: Method validation and its application to a pharmacokinetic study in minipig.
Sample preparation is essential for low-level compound determination. In the present work, supported liquid extraction (SLE) was used as sample preparation for the low-level determination of a new TLR7 agonist imiquimod compound, LFX453. Samples were extracted on ISOLUTE® SLE 96-well plates using tert-butyl-methyl ether followed by evaporation and dry residue reconstitution with 150 μl of a mixture of 0.1% formic acid in acetonitrile-water (50/50, v/v). Samples were eluted using a flow rate of 0.750 ml/min on a C18 column (50 × 2.1 mm, 2.7 μm) with a mobile phase consisting of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B). Tandem mass spectrometry was used to analyze the samples in positive mode. The method run time was 6.5 min, and the low limit of quantification was 1.00 pg/ml with 0.100 ml of minipig plasma. Intra-run and inter-run precision and accuracy were within the acceptance criteria at four concentration levels over a concentration ranging from 1.00 to 200 pg/ml. There was no matrix effect and recovery, three freeze-thaw cycles and incurred samples reanalysis were validated. The method was successfully applied for measuring LFX453 in minipig plasma after application on minipig skin.


Patient characteristics and procedural and safety outcomes of percutaneous transesophageal gastro-tubing: A nationwide database study in Japan.
Percutaneous transesophageal gastro-tubing (PTEG) is an alternative interventional procedure in cases where gastrostomy is not feasible. However, the safety and complication rates of PTEG have not yet been evaluated. We aimed to describe the characteristics of patients who underwent PTEG and investigate complications using a nationwide Japanese inpatient database. In this retrospective cohort study, we used the Diagnosis Procedure Combination database in Japan to identify patients who underwent PTEG from April 2012 to March 2020. The outcomes were the occurrence of complications, invasive treatment within 7 days after PTEG, and tube replacement within 14 days after PTEG. We statistically compared patient background, complication rates, and outcomes using PTEG indications. A total of 3,684 patients underwent PTEG, which was performed in 1,455 patients for decompression and 2,193 patients for feeding. The patients' mean age was 73.1 years, and 62.1% were men. More patients in the decompression group had cancer than those in the feeding group. The overall number of complications was 47 cases (1.3%). The most common treatment administered after PTEG was red blood cell transfusion (3.9%), followed by early tube replacement (3.3%). As invasive treatments for PTEG complications, percutaneous drainage and transcatheter arterial embolization were required in 4 and 1 cases, respectively, and no cases required surgery. We performed a descriptive study on PTEG using a nationwide database in Japan. This study also showed a low complication rate after PTEG in the real world. Our findings provide practical information on the safety of PTEG in Japan.