Ergonomics in the computer workstation.
Awareness of effects of long term use of computer and application of ergonomics in the computer workstation is important for preventing musculoskeletal disorders, eyestrain and psychosocial effects. To determine the awareness of physical and psychological effects of prolonged computer usage and application of ergonomicsin the workstation. One hundred and eighty one people were interviewed from tertiary educational institutions, telecommunications and media houses within Nairobi, Kenya. Descriptive cross sectional study. Majority (89.8%) of the respondents felt that prolonged computer use had an adverse effect on their health, with only 12.4% having received formal training on the same. Assessment of their workstations revealed the most applied ergonomic measure as feet placement on the floor: 100% (181) followed by correct monitor placement with 94.4% (171) fulfilling the requirements. The least applied ergonomic measures were non reflecting wall paint: 5% (9) and adjustable desk 9.9% (18). There is awareness among computer users on the effects of prolonged computer use but there is limited application of ergonomic measures.


Overweight in singletons compared to children with siblings: the IDEFICS study.
The aim of this study was to compare the prevalence of overweight in only children to those with siblings and to explore potential behavioral mediating factors. This study relies upon cross-sectional data collected at survey centers in eight European countries participating in Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS). The present analysis is based on measured anthropometry and parent or guardian-reported socio-demographic characteristics. Subjects include 12 720 children aged 2-9 years for whom number of siblings was known. Singletons were more likely (odds ratio 1.52, 95% confidence interval (CI):1.34-1.72) to be overweight than their peers with siblings when controlling for factors related to childhood overweight, including survey country, parental education, parental weight, maternal age, child's age, birth weight and gender. The three southernmost countries have over threefold risk of overweight, dominated by Italy, compared with the north-central countries, which is not explained by the prevalence of singleton children. The excess risk of overweight among children without siblings was robustly observed even when considering behavioral mediating factors (playtime, screen time per day, dietary propensities for sugar or fat, parental attitudes towards food rewards and television in the child's bedroom). Among singletons aged 6-9 years, the excess risk of overweight was 1.70 (95% CI: 1.44-2.01) compared with 1.32 (95% CI: 1.10-1.60) in younger singletons.


A cytosolic chaperone complex controls folding and degradation of type III CD38.
Cluster of differentiation 38 (CD38) is the best-studied enzyme catalyzing the synthesis of the Ca2+ messenger cyclic ADP-ribose. It is a single-pass transmembrane protein, but possesses dual orientations. We have documented the natural existence of type III CD38 in cells and shown that it is regulated by a cytosolic activator, calcium- and integrin-binding 1 (CIB1). However, how type III CD38 can be folded correctly in the reductive cytosol has not been addressed. Using the yeast two-hybrid technique with CD38's catalytic domain (sCD38) as bait, here we identified a chaperone, Hsp70-interacting protein (Hip), that specifically interacts with both the type III CD38 and sCD38. Immunoprecipitation coupled with MS identified a chaperone complex associated specifically with sCD38. Pharmacological and siRNA-mediated knockdown of Hsp90 chaperones decreased the expression levels of both sCD38 and type III CD38, suggesting that these chaperones facilitate their folding. Moreover, knockdown of Hsc70 or DNAJA2 increased the levels of both CD38 types, consistent with the roles of these proteins in mediating CD38 degradation. Notably, Hip knockdown decreased type III CD38 substantially, but only marginally affected sCD38, indicating that Hip was selective for the former. More remarkably, DNAJA1 knockdown decreased sCD38 but increased type III CD38 levels. Mechanistically, we show that Hsc70 mediates lysosomal degradation of type III CD38, requiring the lysosomal receptor Lamp2A and the C19-motif in the C terminus of CD38. Our results indicate that folding and degradation of type III CD38 is effectively controlled in cells, providing further strong support of its physiological relevance.


Fluoro-substituted N-nitrosamines. 4. Comparative genotoxic activities of N-nitrosodibutylamine and three fluorinated analogues in two bacterial systems.
N-Nitrosodibutylamine (NDBA) and three fluorinated analogues (N-nitroso (4,4,4-trifluorobutyl-amine, F3NDBA; N-nitrosobis (4,4,4-trifluorobutyl)amine, F6NDBA; and N-nitrosobis (2,2,3,3,4,4,4-heptafluorobutyl) amine, F14NDBA were comparatively investigated for biological activity in two bacterial systems. Opposite orders of magnitude were obtained for their potency in the two tests. For inducing his+ reversion in auxotrophic strains of Salmonella typhimurium the sequence was F3NDBA greater than F6NDBA greater than NDBA and for inducing lethal DNA damage in repair deficient strains of Escherichia coli WP2 it was NDBA greater than F6NDBA. F14NDBA was not active in either test system.


Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate.
Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood-brain barrier, increase GCase activity and reduce alpha-synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in healthy nonhuman primates. We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans.


Diuretics in the Management of Cardiorenal Syndrome.
The leading cause of death worldwide is cardiovascular disease. The heart and the kidneys are functionally interdependent, such that dysfunction in one organ may cause dysfunction in the other. By one estimate, more than 60% of patients with congestive heart failure develop chronic kidney disease. Volume overload and congestion are hallmarks of heart failure, and these findings are associated with severe symptoms and poor outcomes. Given the importance of congestion, diuretics remain a cornerstone of heart failure management. However, diuretic treatment remains largely empirical, with little evidence currently available to guide decisions. In this review, we discuss the pathophysiology of cardiorenal syndrome, the pharmacology of loop diuretics, mechanisms of diuretic resistance, and evidence-based treatment paradigms.


Investigation of a Multi-Anode Microchannel Plate PMT for Time-of-Flight PET.
We report on an investigation of a mulit-anode microchannel plate PMT for time-of-flight PET detector modules. The primary advantages of an MCP lie in its excellent timing properties (fast rise time and low transit time spread), compact size, and reasonably large active area, thus making it a good candidate for TOF applications. In addition, the anode can be segmented into an array of collection electrodes with fine pitch to attain good position sensitivity. In this paper, we investigate using the Photonis Planacon MCP-PMT with a pore size of 10 µm to construct a PET detector module, specifically for time-of-flight applications. We measure the single electron response by exciting the Planacon with pulsed laser diode. We also measure the performance of the Planacon as a PET detector by coupling a 4 mm × 4 mm × 10 mm LSO crystal to individual pixel to study its gain uniformity, energy resolution, and timing resolution. The rise time of the Planacon is 440 ps with pulse duration of about 1 ns. A transit time spread of 120 ps FWHM is achieved. The gain is fairly uniform across the central region of the Planacon, but drops off by as much as a factor of 2.5 around the edges. The energy resolution is fairly uniform across the Planacon with an average value of 18.6±0.7% FWHM. While the average timing resolution of 252±7 ps FWHM is achieved in the central region of the Planacon, it degrades to 280±9 ps FWHM for edge pixels and 316±15 ps FWHM for corner pixels. We compare the results with measurements performed with a fast timing conventional PMT (Hamamatsu R-9800). We find that the R9800, which has significantly higher PDE, has a better timing resolution than the Planacon. Furthermore, we perform detector simulations to calculate the improvement that can be achieved with a higher PDE Planacon. The calculation shows that the Planacon can achieve significantly better timing resolution if it can attain the same PDE as the R-9800, while only a 30% improvement is needed to yield a similar timing resolution as the R-9800.


[Do antihypertensive agents change the incidence of cardiovascular complications of hypertension?].
The main aim of the treatment of hypertension is to reduce the incidence and severity of its complications. Despite some bias affecting the major clinical trials of diuretics and/or beta blockers, the results of the meta-analysis taking them into account demonstrate the effectiveness of the prevention of cerebrovascular complications and the less effective prevention of coronary complications. Progress can be hoped for as a result of new therapeutic categories (converting enzyme inhibitors, calcium channel inhibitors ...) and to a greater extent from new treatment strategies, involving better identification of "genuinely high risk" subjects.


Schistosoma mansoni Polo-like kinase 1: A mitotic kinase with key functions in parasite reproduction.
Polo-like kinases (Plks) are conserved regulators of mitosis. In mammals, Plk1 is over-expressed in a wide range of tumour cells and constitutes a valuable target for anti-cancer therapy. This work presents the characterisation of the Plk1 homologue (SmPlk1) of Schistosoma mansoni, a trematode responsible for schistosomiasis, one of the most important parasitic diseases, second only to malaria. The intense levels of disease transmission and the severity of pathologies are the consequences of the exceptional reproductive activity of schistosomes, in which Plks may play a decisive role. Structural and functional analyses of SmPlk1 have demonstrated its homology with other Plk1 members and its conserved function in mitotic processes. Activation of SmPlk1 was shown to be dependent on phosphorylation of its conserved threonine residue (T(182)) and the ability of active SmPlk1 to induce mitosis was demonstrated in the Xenopus oocyte model. SmPlk1 transcripts were detected abundantly in parasite stages containing a high amount of germinal cells. A potential role of SmPlk1 in mitosis and/or meiosis in schistosomes was supported by the in situ detection of SmPlk1 transcripts in female vitelline cells and oocytes as well as in male spermatocytes. Several Plk inhibitors were shown to inhibit SmPlk1 activity in Xenopus oocytes, and BI 2536 (the first-in-class prototype Plk1 inhibitor) induced in vitro dramatic alterations in schistosome gonads, which affected oogenesis and spermatogenesis. These results indicate a major role for SmPlk1 in parasite reproduction and suggest its importance as a potential new target against schistosomiasis.


Do changes to supply chains and procurement processes yield cost savings and improve availability of pharmaceuticals, vaccines or health products? A systematic review of evidence from low-income and middle-income countries.
Improving health systems performance, especially in low-resource settings facing complex disease burdens, can improve population health. Specifically, the efficiency and effectiveness of supply chains and procurement processes for pharmaceuticals, vaccines and other health products has important implications for health system performance. Pharmaceuticals, vaccines and other health products make up a large share of total health expenditure in low-income and middle-income countries (LMICs), and they are critical for delivering health services. Therefore, programmes which achieve cost savings on these expenditures may help improve a health system's efficiency, whereas programmes that increase availability of health products may improve a health system's effectiveness. This systematic review investigates whether changes to supply chains and procurement processes can achieve cost savings and/or improve the availability of drugs in LMICs. Using the PRISMA guidelines for systematic reviews, we searched PubMed, Embase, CINAHL and the Health Economic Evaluation Database to identify. We identified 1264 articles, of which 38 were included in our study. We found evidence that centralised procurement and tendering can achieve direct cost savings, while supply chain management programmes can reduce drug stock outs and increase drug availability for populations. This research identifies a broad set of programmes which can improve the ways that health systems purchase and delivery health products. On the basis of this evidence, policymakers and programme managers should examine the root causes of inefficiencies in pharmaceutical supply chain and procurement processes in order to determine how best to improve health systems performance in their specific contexts.


Biopsies from the Distal Radius after Implantation of Calcium Phosphate Cement.
Background: Calcium Phosphate (CaP) bone cement is gradually replaced by new bone when used as a gap-filler. Details of the re-modelling process are still unclear. Uncertainty is also present as to the possible release of cement particles during the resorption phase causing local soft tissue reactions. The objective of this study was to perform a comprehensive histological investigation of the injectable CaP bone cement used as a void filler in corrective radius osteotomies and adjacent tissue reactions. Methods: Fourteen patients, median age 56 years (18-72), 4 men/10 women, underwent removal of distal radius plates (11 dorsal/3 volar) due to tenosynovitis-like symptoms. Eleven study patients went through corrective osteotomies with CaP bone cement and three were control patients. Previous surgery in three controls consisted in (1) corrective osteotomy with bone graft (dorsal plate), and (2) plated distal radius fractures (1 dorsal/1 volar plate). Biopsies were taken of bone-cement-bone junctions (11), bone-bone graft-bone junctions (1), bone (2) and juxtaposing soft tissue (14). The interval from corrective CaP cement surgery to biopsy was median 1.1 (0.6-2.3) years. Results: Biopsies of bone-cement junctions showed the different stages of new bone formation from CaP to immature bone and later mature well-organised bone. The cement showed signs of osteoclast-mediated resorption. Cement particles, macrophages, multinucleated giant cells (MNGC) and plasma cells were observed in most soft tissue biopsies. MNGC with internalised particles were seen. Macrophages were found along and/or within tendon sheaths in all patients in both groups, but rarely containing cement particles. Conclusions: Gradual re-modelling of the cement into well-organised bone was observed confirming osteoclast-osteoblast coupling. There was no indication that cement particles were the cause of the tenosynovitis-like symptoms.


Simvastatin as an Adjunctive Therapy to Risperidone in Treatment of Autism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Providing novel treatments for autism has been a subject of long-standing research. Based on etiopathological findings, we aim at assessing potential therapeutic effects of statins, here simvastatin, on autism symptoms for the first time. In this randomized, double-blind, placebo-controlled, parallel-group 10-week clinical trial, 70 drug-free children aged 4 to 12 years old with diagnosis of autistic disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, who had an Aberrant Behavior Checklist-Community (ABC-C) scale irritability subscale score of ≥12, were equally randomized to receive either simvastatin (20-40 mg/day) or placebo as an adjunct to risperidone (1-2 mg/day) whereas administration of both drugs was started simultaneously from baseline. Patients with comorbid psychiatric disorders, active medical conditions, severe intellectual disability, seizure disorders, history of any treatments for autism in the past 6 months, or history of current anti-inflammatory drug consumption were excluded. Primary outcome was defined as the difference in mean change of the ABC-C scale irritability subscale score from baseline to the endpoint ( www.irct.ir ; IRCT201602041556N86). Significant differences in change of the ABC-C scale irritability (mean difference [95% confidence interval (CI)] = -3.45 [-5.37 to -1.54], p = 0.001; Cohen's d = 0.89) and hyperactivity/noncompliance (mean difference [95% CI] = -4.27 [-6.69 to -1.86], p = 0.001; Cohen's d = 0.87) subscales scores were detected between the two arms. No significant difference was detected in case of the other three subscales. This study provides preliminary evidence for potential therapeutic effects of simvastatin in the treatment of autism that warrants further investigations.


Serum interleukin‑17 levels predict inflammatory activity in patients with autoimmune hepatitis.
INTRODUCTION The etiology of autoimmune hepatitis (AIH) is unclear, with molecular mimicry between host and viral/drug antigens being the most plausible mechanism initiating the immune cascade that induces hepatocyte injury. Finding a serologic parameter that closely relates to the liver histology would be beneficial for monitoring AIH activity and optimizing treatment. OBJECTIVES We studied serum interleukin (IL)-17 levels and IL‑17 activators (IL‑6 and transforming growth factor β1 [TGF-β1]) in treatment-naive and immunosuppressed patients with AIH. We also analyzed the relationships between these cytokines and histological inflammation scores. PATIENTS AND METHODS A total of 44 patients with confirmed AIH were enrolled to the study (22 treatment-naive patients and 22 patients in clinical remission after at least 3 years of immunosuppression). Liver biopsies were performed, and the histological grading of inflammatory activity was performed by a single pathologist. The control group comprised 30 healthy age- and sex‑matched subjects. Serum IL‑17, IL‑6, and TGF‑β1 levels were measured by a quantitative sandwich enzyme immunoassay. RESULTS Serum IL‑17, IL‑6, and TGF‑β1 levels were higher in treatment-naive patients compared with controls (23.2 pg/ml vs 15.3 pg/ml, P = 0.0001; 5.20 pg/ml vs 1.42 pg/ml, P = 0.0001; and 40.5 ng/ml vs 30.1 ng/ml, P = 0.04; respectively). In treatment-naive patients, serum IL‑17 negatively correlated with hepatic inflammation (r = -0.63, P = 0.01). A reduced serum IL‑17 concentration correlated with an increased TGF‑β1 concentration in patients in clinical remission (r = -0.51, P = 0.03). CONCLUSIONS Serum IL‑17 levels may be a useful parameter for assessing disease activity in patients with AIH.


Serum acute phase proteins after orthotopic liver transplantation.
Acute phase proteins were measured in six patients before liver transplantation and for 72 h after orthotopic liver transplantation. The ability of the donor liver to mount an acute phase response was demonstrated, although the response was less than that seen in other groups of patients in whom this has been studied. Because of the reduced response to stress, the value of these measurements as indicators of liver function in this group of patients is limited.


Genome-wide analysis of natural and restored eastern oyster populations reveals local adaptation and positive impacts of planting frequency and broodstock number.
The release of captive-bred plants and animals has increased worldwide to augment declining species. However, insufficient attention has been given to understanding how neutral and adaptive genetic variation are partitioned within and among proximal natural populations, and the patterns and drivers of gene flow over small spatial scales, which can be important for restoration success. A seascape genomics approach was used to investigate population structure, local adaptation, and the extent to which environmental gradients influence genetic variation among natural and restored populations of Chesapeake Bay eastern oysters Crassostrea virginica. We also investigated the impact of hatchery practices on neutral genetic diversity of restored reefs and quantified the broader genetic impacts of large-scale hatchery-based bivalve restoration. Restored reefs showed similar levels of diversity as natural reefs, and striking relationships were found between planting frequency and broodstock numbers and genetic diversity metrics (effective population size and relatedness), suggesting that hatchery practices can have a major impact on diversity. Despite long-term restoration activities, haphazard historical translocations, and high dispersal potential of larvae that could homogenize allele frequencies among populations, moderate neutral population genetic structure was uncovered. Moreover, environmental factors, namely salinity, pH, and temperature, play a major role in the distribution of neutral and adaptive genetic variation. For marine invertebrates in heterogeneous seascapes, collecting broodstock from large populations experiencing similar environments to candidate sites may provide the most appropriate sources for restoration and ensure population resilience in the face of rapid environmental change. This is one of a few studies to demonstrate empirically that hatchery practices have a major impact on the retention of genetic diversity. Overall, these results contribute to the growing body of evidence for fine-scale genetic structure and local adaptation in broadcast-spawning marine species and provide novel information for the management of an important fisheries resource.


[An adult case of rhabdmyosarcoma of the urinary bladder].
A 37-year-old man was referred to our department for investigation of grosshematuria. Ultrasonography and computed tomography of the abdomen showed a mass in the urinary bladder. Emergency transurethral resection was performed for the control of bleeding. The histopathological diagnosis was rhabdomyosarcoma of the urinary bladder. Radical cystectomy and ileal neobladder substitution were performed. Taking into consideration the patient's request not to receive chemotherapy, postoperative chemotherapy was not instituted. For 18 months, the patient has been doing well, without any evidence of recurrence.


Polyol-enhanced dispersive liquid-liquid microextraction coupled with gas chromatography and nitrogen phosphorous detection for the determination of organophosphorus pesticides from aqueous samples, fruit juices, and vegetables.
Polyol-enhanced dispersive liquid-liquid microextraction has been proposed for the extraction and preconcentration of some organophosphorus pesticides from different samples. In the present study, a high volume of an aqueous phase containing a polyol (sorbitol) is prepared and then a disperser solvent along with an extraction solvent is rapidly injected into it. Sorbitol showed the best results and it was more effective on the extraction recoveries of the analytes than inorganic salts such as sodium chloride, potassium chloride, and sodium sulfate. Under the optimum extraction conditions, the method showed low limits of detection and quantification within the ranges of 12-56 and 44-162 pg/mL, respectively. Enrichment factors and extraction recoveries were in the ranges of 2799-3033 and 84-92%, respectively. The method precision was evaluated at a concentration of 10 ng/mL of each analyte, and relative standard deviations were found to be less than 5.9% for intraday (n = 6) and less than 7.8% for interday (n = 4). Finally, some aqueous samples were successfully analyzed using the proposed method and four analytes (diazinon, dimethoate, chlorpyrifos, and phosalone) were determined, some of them at ng/mL level.


Basic and applied research on multiple aminoglycoside antibiotic resistance of actinomycetes: an old-timer's recollection.
A list of our research achievements on multiple aminoglycoside antibiotic (AG) resistance in AG-producing actinomycetes is outlined. In 1979, the author discovered a novel AG (istamycin)-producing Streptomyces tenjimariensis SS-939 by screening actinomycetes with kanamycin (KM)-resistance and plasmid profiles. This discovery directed our biochemical and genetic approaches to multiple AG resistance (AGR) of AG producers. In this article, the following discoveries will be outlined: (1) AGR profiles correlating with the productivity of AGs in AG-producers, (2) Wide distribution of multiple AG resistance in AG-nonproducing actinomycetes, (3) Involvement of ribosomal resistance and AG-acetylating enzymes as underlying AGR factors, (4) Activation by single nucleotide substitution of a silent gene coding for aminoglycoside 3-N-acetyltransferase, AAC(3), in S. griseus, (5) Discovery of a novel antibiotic indolizomycin through protoplast fusion treatment between S. tenjimariensis and S. griseus strains with different AGR phenotypes, and (6) Double stage-acting activity of arbekacin (ABK; an anti-MRSA semisynthetic AG) discovered by acetylation of ABK with cloned AACs; that is both ABK and its acetylated derivatives showed remarkable antibiotic activities.


DOES DYSLEXIA DEVELOP FROM LEFT-EYE DOMINANCE?
The purpose of this theoretical analysis and synthesis is to indicate how left-eye sighting dominance may lead to reading failure through dysfunctional right hemisphere letter encoding. Differing compensatory strategies are postulated to lead to outcomes that include the development of the phonologically impaired and phonologically proficient subtypes of dyslexia as well as specific spelling disability. Evidence is presented indicating that these disorders might be prevented by delaying the introduction of letter writing until the age of 8 years. Early childhood speech categorization in children genetically at-risk of developing dyslexia is also considered from this perspective. Convergent support for this premature writing hypothesis is provided by a comparison with the development of the left-hand inverted writing posture.


Impact of cabbage pectin-protein complex on microbial β-glucuronidase activity.
We previously demonstrated that pectin-protein complex (PPC) isolated from white cabbage adsorbs the β-glucuronidase (βG) enzyme of E. coli. Concurrently, we discovered a significant increase in βG activity in the presence of PPC. The aim of this study is to identify the structural components of PPC that are responsible for βG adsorption and activation. PPC was isolated from white cabbage using a saline solution containing hydrochloric acid (pH 1.5) at 37 °C for 4 h. PPC proteins were precipitated by aqueous 10% (m/v) trichloroacetic acid to yield the pectin-protein fractions PPC1 and PPC2. PPC was digested using 1,4-α-d-galacturonase, yielding the PPC6 fraction. Partial acid hydrolysis of PPC revealed the galacturonan fraction, PPC3, to be the core of the macromolecule. The purified PPC4 and PPC5 fractions were isolated from PPC by ion-exchange chromatography on DEAE-cellulose. βG activity and its adsorption in the PPC fractions were studied in vitro. Crystalline cellulose was used as a control. This study found that the PPC3 fraction (the galacturonan core) does not adsorb βG and does not affect its activity. The adsorption of βG in the PPC samples is inversely proportional to the degree of methyl esterification of its carbohydrate component. The PPC4 and PPC5 fractions adsorb the highest proportion of βG (51.2% and 54%, respectively). The stimulation of βG enzyme activity is directly proportional to the protein content of the PPC sample. The PPC and PPC1 samples have the greatest ability to increase βG activity (57.6% and 52.1%, respectively).


Fragmentation and Coverage Variation in Viral Metagenome Assemblies, and Their Effect in Diversity Calculations.
Metagenomic libraries consist of DNA fragments from diverse species, with varying genome size and abundance. High-throughput sequencing platforms produce large volumes of reads from these libraries, which may be assembled into contigs, ideally resembling the original larger genomic sequences. The uneven species distribution, along with the stochasticity in sample processing and sequencing bias, impacts the success of accurate sequence assembly. Several assemblers enable the processing of viral metagenomic data de novo, generally using overlap layout consensus or de Bruijn graph approaches for contig assembly. The success of viral genomic reconstruction in these datasets is limited by the degree of fragmentation of each genome in the sample, which is dependent on the sequencing effort and the genome length. Depending on ecological, biological, or procedural biases, some fragments have a higher prevalence, or coverage, in the assembly. However, assemblers must face challenges, such as the formation of chimerical structures and intra-species variability. Diversity calculation relies on the classification of the sequences that comprise a metagenomic dataset. Whenever the corresponding genomic and taxonomic information is available, contigs matching the same species can be classified accordingly and the coverage of its genome can be calculated for that species. This may be used to compare populations by estimating abundance and assessing species distribution from this data. Nevertheless, the coverage does not take into account the degree of fragmentation, or else genome completeness, and is not necessarily representative of actual species distribution in the samples. Furthermore, undetermined sequences are abundant in viral metagenomic datasets, resulting in several independent contigs that cannot be assigned by homology or genomic information. These may only be classified as different operational taxonomic units (OTUs), sometimes remaining inadvisably unrelated. Thus, calculations using contigs as different OTUs ultimately overestimate diversity when compared to diversity calculated from species coverage. In order to compare the effect of coverage and fragmentation, we generated three sets of simulated Illumina paired-end reads with different sequencing depths. We compared different assemblies performed with RayMeta, CLC Assembly Cell, MEGAHIT, SPAdes, Meta-IDBA, SOAPdenovo, Velvet, Metavelvet, and MIRA with the best attainable assemblies for each dataset (formed by arranging data using known genome coordinates) by calculating different assembly statistics. A new fragmentation score was included to estimate the degree of genome fragmentation of each taxon and adjust the coverage accordingly. The abundance in the metagenome was compared by bootstrapping the assembly data and hierarchically clustering them with the best possible assembly. Additionally, richness and diversity indexes were calculated for all the resulting assemblies and were assessed under two distributions: contigs as independent OTUs and sequences classified by species. Finally, we search for the strongest correlations between the diversity indexes and the different assembly statistics. Although fragmentation was dependent of genome coverage, it was not as heavily influenced by the assembler. The sequencing depth was the predominant attractor that influenced the success of the assemblies. The coverage increased notoriously in larger datasets, whereas fragmentation values remained lower and unsaturated. While still far from obtaining the ideal assemblies, the RayMeta, SPAdes, and the CLC assemblers managed to build the most accurate contigs with larger datasets while Meta-IDBA showed a good performance with the medium-sized dataset, even after the adjusted coverage was calculated. Their resulting assemblies showed the highest coverage scores and the lowest fragmentation values. Alpha diversity calculated from contigs as OTUs resulted in significantly higher values for all assemblies when compared with actual species distribution, showing an overestimation due to the increased predicted abundance. Conversely, using PHACCS resulted in lower values for all assemblers. Different association methods (random-forest, generalized linear models, and the Spearman correlation index) support the number of contigs, the coverage, and fragmentation as the assembly parameters that most affect the estimation of the alpha diversity. Coverage calculations may provide an insight into relative completeness of a genome but they overlook missing fragments or overly separated sequences in a genome. The assembly of a highly fragmented genomes with high coverage may still lead to the clustering of different OTUs that are actually different fragments of a genome. Thus, it proves useful to penalize coverage with a fragmentation score. Using contigs for calculating alpha diversity result in overestimation but it is usually the only approach available. Still, it is enough for sample comparison. The best approach may be determined by choosing the assembler that better fits the sequencing depth and adjusting the parameters for longer accurate contigs whenever possible whereas diversity may be calculated considering taxonomical and genomic information if available.


Tobacco smoking among students in an urban area in Northern Italy.
Tobacco smoking, which usually begins in teenage, is one of the most important lifestyle risk factors for chronic diseases and a major public health problem worldwide. The aims of the study were to determine the prevalence of tobacco smoking and the mean age of initiation among adolescents in Genoa (Italy) and to identify some socio-demographic predictors that could be associated with the onset of smoking. 2,301 randomly selected students (14-19 years old) in Genoa completed an ad hoc questionnaire. The Kaplan-Meier method was used to evaluate the instantaneous risk of experimenting with smoking. A multivariate logistic regression model was used to determine whether current or previous smoking status was associated with socio-demographic characteristics. 59.5% of respondents had tried smoking, while 35.6% defined themselves as current smokers. No difference in current smoking prevalence emerged between males and females (35.2% and 35.9%, respectively, p = 0.83). The mean age on initiation was 13.5 years for males and 13.9 years for females. The instantaneous probability of trying smoking changed with age, reaching a maximum at 14 years. Subjects who tried smoking before this age were more inclined to continue smoking. The probability of being a current smoker was significantly higher among students from unmarried-parent families and those attending vocational and technical secondary schools. There is a great need for the activation of new health promotion interventions and enforcement of those already existing, in order to raise awareness of the damage caused by smoking among adolescents, especially those belonging to high-risk groups.


Short-term exercise training augments sympathetic vasoconstrictor responsiveness and endothelium-dependent vasodilation in resting skeletal muscle.
We tested the hypotheses that 4 wk of exercise training would diminish the magnitude of vasoconstriction in response to sympathetic nerve stimulation and augment endothelium-dependent vasodilation (EDD) in resting skeletal muscle in a training intensity-dependent manner. Sprague-Dawley rats were randomly assigned to sedentary time-control (S), mild- (M; 20 m/min, 5% grade), or heavy-intensity (H; 40 m/min, 5% grade) treadmill exercise groups. Animals trained 5 days/wk for 4 wk with training volume matched between groups. Rats were anesthetized and instrumented for study 24 h after the last training session. Arterial pressure and femoral artery blood flow were measured, and femoral vascular conductance (FVC) was calculated. Lumbar sympathetic chain stimulation was delivered continuously at 2 Hz and in patterns at 20 and 40 Hz. EDD was assessed by the vascular response to intra-arterial bolus injections of ACh. The response (% change FVC) to sympathetic stimulation increased (P < 0.05) in a training intensity-dependent manner at 2 Hz (S: -20.2 ± 9.8%, M: -34.0 ± 6.7%, and H: -44.9 ± 2.0%), 20 Hz (S: -22.0 ± 10.6%, M: -31.2 ± 8.4%, and H: -42.8 ± 5.9%), and 40 Hz (S: H -24.5 ± 8.5%, M: -35.1 ± 8.9%, H: -44.9 ± 6.5%). The magnitude of EDD also increased in a training intensity-dependent manner (P < 0.05). These data demonstrate that short-term exercise training augments the magnitude of vasoconstriction in response to sympathetic stimulation and EDD in resting skeletal muscle in a training intensity-dependent manner.


Development of embryonic and larval cells containing serotonin, catecholamines, and FMRFamide-related peptides in the gastropod mollusc Phestilla sibogae.
The present immunocytochemical study provides one of the first detailed descriptions of the development of cells containing a variety of neurotransmitters during much of the larval life of a nudibranch gastropod. Throughout much of early development, serotonergic cells were located only in the apical organ; as larvae approached metamorphosis, serotonergic cells were also detected in the cerebropleural and pedal ganglia. Cells exhibiting tyrosine hydroxylase immunoreactivity (indicative of catecholamine synthesis) were first located near the mouth but by late embryonic stages were also located in the apical organ and near the velum and eyes. By late larval stages, numerous catecholaminergic cells were found in the foot, with concentrations in the propodium. Finally, the first cells exhibiting FMRFamide immunoreactivity were detected posterior to the neuropil of the cerebropleural ganglia in the early embryo. Fibers that presumably originated from these cells subsequently invaded the cerebral and pedal ganglia and the apical organ. By early larval stages, a second pair of peptidergic neurons was located near the first pair, and additional peptidergic neurons were located in the apical organ and peripheral positions in the foot and medial and dorsal to the eyes. In addition to providing a unique phyletic perspective to our understanding of gastropod neural development, the present study also sets the stage for future studies into changes in the nervous system as this gastropod undergoes metamorphosis.


The experiences of people with borderline personality disorder admitted to acute psychiatric inpatient wards: a meta-synthesis.
Background: Acute psychiatric inpatient care is recommended for people with borderline personality disorder (BPD) to manage a crisis. Qualitative research exploring service user experience is valuable for the development of evidence-based treatment guidelines. Aim: To conduct a meta-synthesis of qualitative research exploring the experiences of people with BPD on acute psychiatric inpatient wards. Methods: Literatures searches of five electronic databases. Data were analysed using a three-stage theme identification process. Results: Eight primary studies and three first-hand accounts met the inclusion criteria. Four overarching themes were found to explain the data: contact with staff and fellow inpatients; staff attitudes and knowledge; admission as a refuge; and the admission and discharge journey. Conclusions: Similar experiences of acute psychiatric inpatient care were reported by people with BPD across the studies. Opportunities to be listened to and to talk to staff and fellow inpatients, time-out from daily life and feelings of safety and control were perceived as positive elements of inpatient care. Negative experiences were attributed to: a lack of contact with staff, negative staff attitudes, staff's lack of knowledge about BPD, coercive involuntary admission and poor discharge planning.


Skin toxicity during breast irradiation: pathophysiology and management.
Radiotherapy is a critical component in the treatment of breast cancer, a disease that is estimated to have affected 203,500 US women in 2002. According to the data from some series, an estimated 90% of patients treated with radiotherapy for breast cancer will develop a degree of radiation-induced dermatitis. This review describes the indications and techniques of radiotherapy for breast cancer. The pathophysiology, clinical presentation, and contributing factors of radiation-related skin injury are discussed. A review of recent clinical research addressing skin toxicity is provided.


Short- and long-term effects of very low- and low-calorie ketogenic diets on metabolism and cardiometabolic risk factors: a narrative review.
Worldwide obesity and cardiovascular diseases have encouraged the adoption of new and efficient dietary strategies. Among various proposed diets, ketogenic diets, both the very-low-calorie ketogenic diet (VLCKD) and the low-calorie ketogenic diet (LCKD), have been suggested in recent years as an effective nutritional approach for obesity management. The VLCKD and the LCKD are characterized by a low carbohydrate content (<50 g/day), 1-1.5 g of protein/kg of ideal body weight, less than 20-30 g of lipids, and a daily intake of about 800 calories for VLCKD and about 1200-1400 calories for LCKD. The purpose of our narrative review is to offer an overview of the most impactful studies in the scientific literature regarding VLCKD and LCKD to discuss their short- and long-term effects (less than 12 months and more than 12 months respectively) on weight loss, metabolic and cardiovascular aspects. Articles we focused on were cohort studies, case-control studies, cross-sectional studies, randomized controlled trials, and meta-analyses. Results indicate that VLCKD and LCKD could be helpful to ameliorate metabolic and cardiovascular risk factors such as weight loss, glucose, and cholesterol levels, both in the short and long term. Further research in this area may include more randomized controlled trials to gather more data.


Low-reflective wire-grid polarizers with absorptive interference overlayers.
Wire-grid (WG) polarizers with low reflectivity for visible light have been successfully developed. We theoretically consider the optical properties of simple sandwich structures of absorptive layer/transparent layer (gap layer)/high-reflective mirrors and found that it is possible to develop an antireflection (AR) coating owing to the interference along with the absorption in the absorptive layer. A wide variety of materials can be used for AR coatings by tuning the thicknesses of both the absorptive and the gap layers. This AR concept has been applied to reduce the reflectance of WG polarizers of Al. FeSi(2) as an absorptive layer has been deposited by the glancing angle deposition technique immediately on the top of Al wires covered with a thin SiO(2) layer as a gap layer. For the optimum combination of the thicknesses of FeSi(2) and SiO(2), the reflectance becomes lower than a few per cent, independent of the polarization, whereas the transmission polarization properties remain good. Because low-reflective (LR) WG polarizers are completely composed of inorganic materials, they are useful for applications requiring high-temperature durability such as liquid crystal projection displays.


Effects of inorganic acids and divalent hydrated metal cations (Mg(2+), Ca(2+), Co(2+), Ni(2+)) on γ-AlOOH sol-gel process.
In-depth understanding of the sol-gel process plays an essential role in guiding the preparation of new materials. Herein, the effects of different inorganic acids (HCl, HNO3 and H2SO4) and divalent hydrated metal cations (Mg(2+), Ca(2+), Co(2+), Ni(2+)) on γ-AlOOH sol-gel process were studied based on experiments and density functional theory (DFT) calculations. In these experiments, the sol originating from the γ-AlOOH suspension was formed only with the addition of HCl and HNO3, but not with H2SO4. Furthermore, the DFT calculations showed that the strong adsorption of HSO4(-) on the surface of the γ-AlOOH particles, and the hydrogen in HSO4(-) pointing towards the solvent lead to an unstable configuration of electric double layer (EDL). In the experiment, the gelation time sequence of γ-AlOOH sol obtained by adding metal ions changed when the ionic strength was equal to or greater than 0.198 mol kg(-1). The DFT calculations demonstrated that the adsorption energy of hydrated metal ions on the γ-AlOOH surface can actually make a difference in the sol-gel process.


An In vitro Study of Bio-Control and Plant Growth Promotion Potential of Salicaceae Endophytes.
Microbial communities in the endosphere of Salicaceae plants, poplar (Populus trichocarpa) and willow (Salix sitchensis), have been demonstrated to be important for plant growth promotion, protection from biotic and abiotic stresses, and degradation of toxic compounds. Our study aimed to investigate bio-control activities of Salicaceae endophytes against various soil borne plant pathogens including Rhizoctonia solani AG-8, Fusarium culmorum, Gaeumannomyces graminis var. tritici, and Pythium ultimum. Additionally, different plant growth promoting traits such as biological nitrogen fixation (BNF), indole-3-acetic acid (IAA) biosynthesis, phosphate solubilization, and siderophore production were assessed in all bio-control positive strains. Burkholderia, Rahnella, Pseudomonas, and Curtobacterium were major endophyte genera that showed bio-control activities in the in-vitro assays. The bio-control activities of Burkholderia strains were stronger across all tested plant pathogens as compared to other stains. Genomes of sequenced Burkholderia strains WP40 and WP42 were surveyed to identify the putative genes involved in the bio-control activities. The ocf and hcnABC gene clusters responsible for biosynthesis of the anti-fungal metabolites, occidiofungin and hydrogen cyanide, are present in the genomes of WP40 and WP42. Nearly all endophyte strains showing the bio-control activities produced IAA, solubilized tricalcium phosphate, and synthesized siderophores in the culture medium. Moreover, some strains reduced acetylene into ethylene in the acetylene reduction assay, a common assay used for BNF. Salicaceae endophytes could be useful for bio-control of various plant pathogens, and plant growth promotion possibly through the mechanisms of BNF, IAA production, and nutrient acquisition.


Dietary habits contributing to breast cancer risk among Iranian women.
The aim of this study was to investigate demographic features, dietary habits, and some possible risk factors for being susceptible to breast cancer in Iranian women. A study of dietary habits and breast cancer was conducted among 53 Iranian women with histological confirmed disease and 40 matched controls. A dietary habits questionnaire was used to evaluate the pattern of selected food intakes. The risk of cancer was analyzed after adjustment for confounding factors. Age, weight, body mass index (BMI), waist circumference, educational status, parity, lactation, marital status, menopause, history of estrogen therapy, and family history of breast disease or cancer were assessed among participants. Special attention was given to the relationship between consumption of high fat meat, milk, yogurt and cheese as well use of frying oils for frying foods, use of olive/liquid oils for cooking, removing fat from meat and poultry, removing chicken skin and not use of mayonnaise as salad dressing and the risk of breast cancer. Moreover, salad, vegetable and fruit consumption, and eating outdoors owere investigated. Our results revealed significant lower education and higher BMI and waist circumference levels in patients with breast cancer. There was significantly increased breast cancer risk in overweight women in comparison with normal weight (OR=2.91, 95%CI 1.24 to 6.82). High intake of fat dairy products including milk and cheese was found to be a statistically significant factor for increasing breast cancer risk in models adjusting for age, BMI and education. Use of olive/liquid oils for cooking and avoidance of mayonnaise as salad dressing are related to lower risk of breast cancer. The frequency of vegetable and fruit consumption was significantly lower in patients with breast cancer compared to healthy women. Dietary habits might be risk factors for breast cancer among Iranian women. Adoption of a prudent diet could be an appropriate strategy for preventing breast cancer.


CeO2 /Bi2 WO6 Heterostructured Microsphere with Excellent Visible-light-driven Photocatalytic Performance for Degradation of Tetracycline Hydrochloride.
CeO2 /Bi2 WO6 heterostructured microsphere with excellent and stable photocatalytic activity for degradation tetracyclines was successfully synthesized via a facile solvothermal route. The photocatalytic experiments indicated that CeO2 /Bi2 WO6 heterostructured microspheres exhibited enhanced photocatalytic activity compared to pure Bi2 WO6 in both the degradation of tetracycline hydrochloride (TCH) and rhodamine B (RhB) under visible-light irradiation. The 1CeO2 /2Bi2 WO6 exhibited the best photocatalytic activity for degradation of TCH, reaching 91% after 60 min reaction. The results suggested that the particular morphological conformation of the microspheres resulted in smaller size and more uniform morphology so as to increase the specific surface area. Meanwhile, the heterojunction was formed by coupling CeO2 and Bi2 WO6 in the as-prepared microspheres, so that the separation efficiency of photogenerated electrons and holes was dramatically improved and the lifetimes of charge carriers were prolonged. Hence, introduction of CeO2 could significantly enhance the photocatalytic activity of CeO2 /Bi2 WO6 heterostructured microspheres and facilitate the degradation of TCH. This work provided not only a principle method to synthesize CeO2 /Bi2 WO6 with the excellent photocatalytic performance for actual produce, but also a excellent property of the photocatalyst for potential application in photocatalytic treatment of tetracyclines wastewater from pharmaceutical factory.


Mfa4, an Accessory Protein of Mfa1 Fimbriae, Modulates Fimbrial Biogenesis, Cell Auto-Aggregation, and Biofilm Formation in Porphyromonas gingivalis.
Porphyromonas gingivalis, a gram-negative obligate anaerobic bacterium, is considered to be a key pathogen in periodontal disease. The bacterium expresses Mfa1 fimbriae, which are composed of polymers of Mfa1. The minor accessory components Mfa3, Mfa4, and Mfa5 are incorporated into these fimbriae. In this study, we characterized Mfa4 using genetically modified strains. Deficiency in the mfa4 gene decreased, but did not eliminate, expression of Mfa1 fimbriae. However, Mfa3 and Mfa5 were not incorporated because of defects in posttranslational processing and leakage into the culture supernatant, respectively. Furthermore, the mfa4-deficient mutant had an increased tendency to auto-aggregate and form biofilms, reminiscent of a mutant completely lacking Mfa1. Notably, complementation of mfa4 restored expression of structurally intact and functional Mfa1 fimbriae. Taken together, these results indicate that the accessory proteins Mfa3, Mfa4, and Mfa5 are necessary for assembly of Mfa1 fimbriae and regulation of auto-aggregation and biofilm formation of P. gingivalis. In addition, we found that Mfa3 and Mfa4 are processed to maturity by the same RgpA/B protease that processes Mfa1 subunits prior to polymerization.


Social support in chat sessions for adolescents and young adults living with a family member with mental illness.
Children from families with a mental illness are at risk of developing negative health outcomes. Online interventions are a new way to offer support to these children. The present study utilized a website that had been developed to support Dutch youth who had a family member with a mental illness. The objective was to analyse monitored and unmonitored chatroom conversations among these young people, and specifically to compare supportive messages and self-disclosures of experiences. We electronically imported session transcripts of 34 chatroom conversations into the qualitative analysis software Atlas.ti. A content analysis was performed on 4252 messages from 22 female participants. A correlational analysis was then conducted to identify significant associations between sent and received supportive statements and disclosing statements. We found supporting comments in approximately 34% of the conversations and disclosures of problems in the home in approximately 15-18% of the messages. Participants made approximately twice as many disclosing statements and approximately half as many supportive statements in the monitored sessions compared to the unmonitored sessions. The number of disclosures that were sent was positively correlated with the amount of social support that was received. The number of disclosures sent was negatively correlated with the amount of social support that was sent, but only in the unmonitored sessions. Considering the greater reach of Internet interventions, online chatroom sessions might be provided as complementary to, or as an alternative to, face-to-face groups for supporting youth with a family member who has a mental illness.


Estimating the number of people who inject drugs: a proposal to provide figures nationwide and its application to France.
This article provides an original method of estimating the prevalence of injecting drug users (IDU) in France. In order to overcome legal restrictions hampering data linkage, the method relies on a single-source capture-recapture framework and makes use of individual data collected by a standardized survey conducted within treatment centres. Taking the hierarchical structure of data collection into consideration, a multilevel Zelterman regression model was used. In 2014, last year IDU were thought to be 103 800 (85 300; 130 000), prevalence of 2.6‰ (2.1; 3.2), and last month IDU 86 000 (69 200; 110 400), prevalence of 2.2‰ (1.7; 2.7). Estimates have been broken down by gender, revealing a 3 to 1 ratio of male-to-female; and age, showing young adults less prone to regular use of injection. It is thought that one IDU out of three was seen in treatment centres in 2014. The number of last month IDU has remained stable when compared with the last available figures calculated in 2006. Nowadays IDU include heroin, buprenorphine, polydrug and stimulant users. This greater diversity ought to be taken into account by prevention policies, and underlines the need for perennial monitoring of IDU.


A study on cellular reactions and fibrogenic effects of mineral dusts.
In vivo cytotoxicity including cellular metabolic activity, lysozyme content and total protein content in rat bronchoalveolar lavage, capacity of interleukin-1 released from rat pulmonary cells and fibrogenic effects evaluated from rat lung dry weight, collagen content of the whole lung and pathological grading induced by mineral dust were assayed. The results showed that: (1) The relationship among in vivo cytotoxicity, interleukin-1 release, fibrogenic effects on the lung induced by mineral dusts correlated well with the free SiO2 content in mineral dusts in most (but not all) cases; (2) The biological harmful effects of mixed dusts were not simply the additive effect of single dust. In the group of WO3-SiO2 mixture, the fibrogenicity was mainly due to SiO2, tungsten trioxide (WO3) showed neither fibrogenic effect, nor significant potentiality to enhance SiO2 fibrogenicity, while in the group of SnO2-SiO2, SnO2 was suppressive to the effect of SiO2, although the contents of SiO2 in the two mixed dusts were similar.


A 2-year follow-up of primary molars, pulpotomized with a gentle technique and capped with calcium hydroxide.
The prognosis for pulpotomy of primary molars with calcium hydroxide as wound dressing was evaluated clinically and radiographically. Thirty-three primary mandibular molars were amputated under the following conditions: (1) chronic coronal pulpitis, (2) the amputation was done with diamond instruments and a high-speed machine under aseptic conditions, and (3) application of calcium hydroxide in contact with the wound surface. After 1 year the treatment was regarded as successful for 22 of the teeth (67%); 11 teeth showed internal dentin resorption. After 2 years the frequency of success, allowing for drop-out, was 59%. Internal dentin resorption was seen in 14 root canals; in 10 of them within the first 6 months. A histologic study of nine root pulps with internal dentin resorption revealed an extra-pulpal blood clot on the wound surface in five.


Fluorescent Dye Labeling of Erythrocytes and Leukocytes for Studying the Flow Dynamics in Mouse Retinal Circulation.
The retinal and choroidal blood flow dynamics may provide insight into the pathophysiology and sequelae of various ocular diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration (AMD) and other ocular inflammatory conditions. It may also help to monitor the therapeutic responses in the eye. The proper labeling of the blood cells, coupled with live-cell imaging of the labeled cells, allows for the investigation of the flow dynamics in the retinal and choroidal circulation. Here, we describe the standardized protocols of 1.5% indocyanine green (ICG) and 1% sodium fluorescein labeling of mice erythrocytes and leukocytes, respectively. Scanning laser ophthalmoscopy (SLO) was applied to visualize the labeled cells in the retinal circulation of C57BL/6J mice (wild type). Both methods demonstrated distinct fluorescently labeled cells in the mouse retinal circulation. These labeling methods can have wider applications in various ocular disease models.


An open-label study of naltrexone in the treatment of kleptomania.
The present study was designed to test the short-term efficacy and safety of naltrexone in the treatment of kleptomania. 10 subjects (7 women, 3 men) who fulfilled DSM-IV criteria for kleptomania and were free from other Axis I diagnoses by the Structured Clinical Interview for DSM-IV screening participated in a 12-week naltrexone open-label trial. Kleptomania symptom change was assessed with the Clinical Global Impressions scale (both severity and improvement measures), Sheehan Disability Scale (SDS), Global Assessment of Functioning (GAF), and Kleptomania Symptom Assessment Scale. Side effects were monitored weekly, and liver function tests were administered every 2 weeks. Naltrexone reduced urges to steal and stealing behavior. Subjects showed significant improvement (p < .005) over the 11-week treatment period in all measures compared with measures taken at baseline. Seven subjects (70.0%) were very much improved and 2 (20.0%) were much improved at study end. Subjects also reported overall significant improvement in social and occupational functioning as determined by both the GAF and the SDS (p < .000). Men responded to naltrexone as well as women. The mean naltrexone dose required for effective symptom control was 145 mg/day. Nausea was common during the first week of treatment. Five subjects (50.0%) reported previous trials of medication and cognitive-behavioral therapy without any effect on kleptomania symptoms. The present findings provide evidence that naltrexone may be effective in the treatment of kleptomania. The present report is preliminary. Further studies are needed to confirm these findings.


Estimation of errors introduced by confocal imaging into the data on segmentation gene expression in Drosophila.
Currently the confocal scanning microscopy of fluorescently tagged molecules is extensively employed to acquire quantitative data on gene expression at cellular resolution. Following this approach, we generated a large dataset on the expression of segmentation genes in the Drosophila blastoderm, that is widely used in systems biology studies. As data accuracy is of critical importance for the success of studies in this field, we took a shot to evaluate possible errors introduced in the data by acquisition and processing methods. This article deals with errors introduced by confocal microscope. In confocal imaging, the inevitable photon noise is commonly reduced by the averaging of multiple frames. The averaging may introduce errors into the data, if single frames are clipped by microscope hardware. A method based on censoring technique is used to estimate and correct this type of errors. Additional source of errors is the quantification of blurred images. To estimate and correct these errors, the Richardson-Lucy deconvolution method was modified to provide the higher accuracy of data read off from blurred images of the Drosophila blastoderm. We have found that the sizes of errors introduced by confocal imaging make up approximately 5-7% of the mean intensity values and do not disguise the dynamic behavior and characteristic features of gene expression patterns. We also defined a range of microscope parameters for the acquisition of sufficiently accurate data. http://urchin.spbcas.ru/downloads/step/step.htm


Eminence-based medicine versus evidence-based medicine: is anterior cruciate ligament reconstruction optimally performed with the double-bundle technique?
The anterior cruciate ligament (ACL) comprises 2 distinct bands or bundles-the anteromedial bundle, which is tighter in flexion, and the posterolateral bundle, which is tighter in extension. Traditional ACL reconstruction uses 1 graft. A new technique, known as the double-bundle technique, uses 2 tendon grafts to more closely approximate normal anatomy. Because the medical literature does not provide a definitive answer as to which reconstruction method is better, we surveyed 500 experts in sports medicine in a previous study to determine whether they agreed with the statement "ACL reconstruction is optimally performed with the double-bundle technique." Respondents were inclined to answer "This statement is probably false." Our article interprets the expert responses by reviewing the basic and clinical sciences implicit in the question and reviewing the literature regarding outcomes. We found that double-bundle ACL reconstruction is theoretically appealing, but evidence proving that it improves clinical outcomes is unavailable. High-quality studies are under way on the topic, which may provide a definitive answer. However, until such data are available, the expert consensus from our survey was that the double-bundle technique is not necessarily the optimal approach.


A multivariate logistic model (MLM) for analyzing binary family data.
We consider modeling the familial correlation between 2 related individuals using a multiple logistic regressive model. It is shown that there is a discrepancy in the marginal probability of the second individual. We investigate the conditions under which this discrepancy can be minimized and show how it can have a direct effect on handling missing values and ascertainment. We derive a functional relationship between the parameters in the model that eliminates this discrepancy, hence solving the problems that can arise in the handling of missing values and ascertainment. Because this methodology fails when there are more than 2 related individuals, we present a new model based on a multivariate logistic distribution. Residual familial correlations can be directly related to the parameters of this model. The likelihood for family data under this model is independent of the order in which the family members enter the calculation. The marginal probabilities can be easily computed.


Inhibitory Effect of Camptothecin against Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae RS-2.
Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial brown stripe, by measuring cell growth, DNA damage, cell membrane integrity, the expression of secretion systems, and topoisomerase-related genes, as well as the secretion of effector protein Hcp. Results indicated that CPT solutions at 0.05, 0.25, and 0.50 mg/mL inhibited the growth of strain RS-2 in vitro, while the inhibitory efficiency increased with an increase in CPT concentration, pH, and incubation time. Furthermore, CPT treatment affected bacterial growth and replication by causing membrane damage, which was evidenced by transmission electron microscopic observation and live/dead cell staining. In addition, quantitative real-time PCR analysis indicated that CPT treatment caused differential expression of eight secretion system-related genes and one topoisomerase-related gene, while the up-regulated expression of hcp could be justified by the increased secretion of Hcp based on the ELISA test. Overall, this study indicated that CPT has the potential to control the bacterial brown stripe pathogen of rice.


A Blockchain-Assisted Intelligent Transportation System Promoting Data Services with Privacy Protection.
Being able to obtain various environmental and driving data from vehicles is becoming more and more important for current and future intelligent transportation systems (ITSs) to operate efficiently and economically. However, the limitations of privacy protection and security of the current ITSs are hindering users and vehicles from providing data. In this paper, we propose a new ITS architecture by using blockchain technology solving the privacy protection and security problems, and promoting users and vehicles to provide data to ITSs. The proposed architecture uses blockchain as a trust infrastructure to protect users' privacy and provide trustworthy services to users. It is also compatible with the legacy ITS infrastructure and services. In addition, the hierarchical organization of chains enables the scalability of the system, and the use of smart contracts provides a flexible way for introducing new services in the ITS. The proposed architecture is demonstrated by a proof of concept implementation based on Ethereum. The test results show that the proposed architecture is feasible.


Lead potentiates cytokine- and glutamate-mediated increases in permeability of the blood-brain barrier.
We have measured the transendothelial electrical resistance across the blood-brain barrier (BBB) with a microelectrode technique and determined the effects of subcutaneous injections (five injections over ten days) of lipopolysaccharide (LPS, 100 ng/g), recombinant mouse interleukin-6 (IL-6, 5 ng/g), and/or inorganic lead (lead, 2.5 5 micrograms/g) on the ion permeability of arterioles in the temporoparietal cortex of anaesthetized mice between 10 and 40 days of age. In controls the electrical resistance increased with age. It was decreased in animals treated with IL-6, but unaffected by lead at the different ages studied. In IL-6 treated mice, repeated neonatal exposure to lead (five injections between 2 and 10 days after birth) caused a delay in the increase in arteriole resistance with age. LPS injections caused a 36% increase in ion permeability of the BBB in twenty-day-old mice, and lead potentiated this effect of LPS. Intra-arterial injections of glutamate did not alter vascular resistance, but topical applications of glutamate on the cerebrum caused a reversible decrease in the resistance in mice not treated with lead, and an irreversible decrease in mice treated with lead. Injections of glutamate in the lumen of arterial vessels in the parietal and temporoparietal brain areas of mice pretreated with lead and LPS, plus a topical application of glutamate, caused depolarization of neurons in the temporoparietal cortex. These results suggest that disruption of the BBB can allow serum glutamate to penetrate the brain, causing further disruption of the BBB, and that lead irreversibly potentiates this cascade of harmful events.


Systematic application of two-dimensional 1H nuclear-magnetic-resonance techniques for studies of proteins. 2. Combined use of correlated spectroscopy and nuclear Overhauser spectroscopy for sequential assignments of backbone resonances and elucidation of polypeptide secondary structures.
This paper describes a new nuclear magnetic resonance approach for the determination of secondary structure in globular proteins. To illustrate the practical application of the new procedure, two-dimensional correlated spectroscopy and two-dimensional nuclear Overhauser enhancement spectroscopy were used to obtain individual assignments for all the backbone protons of the beta-sheet secondary structures in the basic pancreatic trypsin inhibitor. First, combined connectivity diagrams of these two methods recorded in both 2H2O solution and H2O solution of the inhibitor were employed to obtain sequential, individual resonance assignments for the separate strands in the beta sheet. Second, a 2D nuclear Overhauser enhancement spectrum recorded with a long mixing time was used to determine how the separate, extended polypeptide strands are linked by hydrogen bonds in the sheet structures. By combination of these results with the identifications of the amino acid side-chain resonances described in the preceding paper, the beta-sheet structures can, without reference to data on the spatial structure obtained with other techniques, be localized in the amino acid sequence. This investigation confirms results on limited regions of the beta sheet in the inhibitor obtained previously with one-dimensional nuclear magnetic resonance experiments and demonstrates that the entire beta-sheet structure seen in single crystals of the inhibitor is preserved in aqueous solution.


A case report of acute febril neutrophilic dermatosis (Sweet's syndrome) and Crohn's disease.
A case of Crohn's disease complicated by Sweet's syndrome is presented. The main ultrastructural findings were the multiplication of basal lamina surrounding the venulea, interendothelial gaps and in perivascular locations mixed infiltrates of neutrophiles and erythrocytes. The changes indicate that the initial site of the reaction was the walls of the dermal vessels.


Potential role of imaging in assessing harmful effects on spermatogenesis in adult testes with varicocele.
Varicocele is characterized by an abnormal dilatation and retrograde blood flow in the spermatic veins. Varicocele is the leading correctable cause of male infertility. Although it is highly prevalent in infertile men, it is also observed in individuals with normal fertility. Determining which men are negatively affected by varicocele would enable clinicians to better select those men who will benefit from treatment. To assess the functional status of the testes in men with varicocele, color Doppler sonographic parameters were evaluated. Testicular arterial blood flow was significantly reduced in men with varicocele, reflecting an impairment of spermatogenesis. An improvement in the testicular blood supply was found after varicocelectomy on spectral Doppler analysis. Testicular contrast harmonic imaging and elastography might improve our knowledge about the influence of varicocele on intratesticular microcirculation and tissue stiffness, respectively, providing possible information on the early damage of testicular structure by varicocele. Magnetic resonance imaging (MRI), with measurement of apparent diffusion coefficient has been used to assess the degree of testicular dysfunction and to evaluate the effectiveness of varicocele repair. Large prospective studies are needed to validate the possible role of functional sonography and MRI in the assessment of early defects of spermatogenesis in testes with varicocele.


Induction of the suicide HSV-TK gene by activation of the Egr-1 promoter with radioisotopes.
In investigating new methods for the treatment of pancreatic cancer, we have explored the possibility of using a combination of radiation and gene therapies. We demonstrate herein that the early growth response gene 1 promoter (Egr-1) is sufficient to confer selective expression of the luciferase gene (Luc) in a human pancreatic tumor cell line (AsPc-1) when exposed to ionizing radiation. The Egr-1 promoter directed the radioinducible expression of luciferase, and yielded higher levels of Luc activity than that in nonirradiated lines. The radioisotopes Tc-99m, I-131, and Ga-67-citrate were selected as Egr-1 activators for their potential to accumulate in tumors. We studied Ga-67-citrate, a radioisotope employed in tumor scintigraphy, for its suitability for selective gene induction. The plasmid vector pEgr-1-Luc was transfected into AsPc-1 cells and then exposed to radioisotopes. Luciferase activity increased by 100-300 times over control. We also inserted the herpes thymidine kinase gene (TK) downstream of Egr-1 and transfected this construct into AsPc-1 cells. Ga-67-citrate and ganciclovir were added to the cells and cell survival was assessed by MTT assay. The growth of AsPc-1 cells transfected with the pEgr-TK construct was suppressed 2 days after exposure of the cells to Ga-67-citrate. The results indicate that Ga-67-citrate may be useful in combining radiation and gene therapies.


Automated approach to detecting behavioral states using EEG-DABS.
Electrocorticographic (ECoG) signals represent cortical electrical dipoles generated by synchronous local field potentials that result from simultaneous firing of neurons at distinct frequencies (brain waves). Since different brain waves correlate to different behavioral states, ECoG signals presents a novel strategy to detect complex behaviors. We developed a program, EEG Detection Analysis for Behavioral States (EEG-DABS) that advances Fast Fourier Transforms through ECoG signals time series, separating it into (user defined) frequency bands and normalizes them to reduce variability. EEG-DABS determines events if segments of an experimental ECoG record have significantly different power bands than a selected control pattern of EEG. Events are identified at every epoch and frequency band and then are displayed as output graphs by the program. Certain patterns of events correspond to specific behaviors. Once a predetermined pattern was selected for a behavioral state, EEG-DABS correctly identified the desired behavioral event. The selection of frequency band combinations for detection of the behavior affects accuracy of the method. All instances of certain behaviors, such as freezing, were correctly identified from the event patterns generated with EEG-DABS. Detecting behaviors is typically achieved by visually discerning unique animal phenotypes, a process that is time consuming, unreliable, and subjective. EEG-DABS removes variability by using defined parameters of EEG/ECoG for a desired behavior over chronic recordings. EEG-DABS presents a simple and automated approach to quantify different behavioral states from ECoG signals.


Filterability of subpopulations of leukocytes: effect of pentoxifylline.
Human leukocytes were separated by density into two fractions, one containing predominantly granulocytes (FI) and the other, lymphocytes and monocytes (FII). The filterability of these fractions and their mixture was determined from the pressure measured during constant flow through 5-microns Nuclepore filters. The pressure-time curve of FI indicates the behavior of a relatively homogeneous cell population. The FII pressure-time curve can be analyzed to distinguish the effect of the more numerous and more filterable lymphocytes from that of the sparser but less filterable monocytes. Pressure generated by mixed leukocytes, which had been treated with 1 and 10 mmol/L of pentoxifylline (PTX) or its metabolite I, was substantially less than untreated control; at 10 mmol/L, the pressure was reduced to about 50% of control. PTX appears to affect the filterability of monocytes and polymorphonuclear leukocytes but not lymphocytes. Scanning electron microscopy showed an inhibition of protopod formation in the treated granulocytes. The degree of cell adhesion to the filter, as measured by the number of cells remaining on the outflow side of the filter, was similar in all groups (FI and FII, treated and untreated). The results indicate that the variations in filterability between the leukocyte subpopulations and the improvement by PTX treatment reflect differences in the cells' ability to deform under the test conditions.


Inhibitory effect of AQP1 silencing on adhesion and angiogenesis in ectopic endometrial cells of mice with endometriosis through activating the Wnt signaling pathway.
The development mechanism of endometriosis remains unknown. Water channel aquaporin-1 (AQP1) enhances water flux across cell membranes, which is highly expressed and associated with cell migration, metastasis and angiogenesis in some human cancers. In this study, the role of the Wnt signaling pathway mediated by AQP1 in endometriosis was investigated, in a bid to provide new therapeutic targets for endometriosis. Microarray expression profiles were screened to acquired differentially expressed genes related to endometriosis. Mouse models with endometriosis were established and grouped. The level of endometriosis was evaluated by measurement of the volume of ectopic region. The expression of AQP1, pathway-related factors (Wnt1 and Wnt4), adhesion molecules (VCAM-1 and ICAM-1), invasive factors (MMP-2, MMP-9, TIMP-1 and TIMP-2), angiogenic factors (VEGF-A, VEGFR1 and VEGFR2) and apoptotic factors (Caspase-3, Caspase-9, Bax and BcL-2) was measured by RT-qPCR and western blot analysis. Furthermore, the role of AQP1 in adhesion, invasion, angiogenesis, and apoptosis of ectopic endometrial cells was determined by transfection of si-AQP1 plasmid. AQP1 was robustly expressed in endometriosis. AQP1 gene silencing alleviated the progression of endometriosis by activating the Wnt signaling pathway in mice with endometriosis. Specifically, silencing of AQP1 gene inhibited ectopic endometrial cell adhesion and invasion abilities, suppressed angiogenesis while promoted apoptosis. Collectively, the present study highlights the role of AQP1 in the regulation of the Wnt signaling pathway in endometriosis mouse models, suggesting that AQP1 could represent a new target aimed at improving the survival of patients with endometriosis.


Use of Rapid Enzyme-Linked Immunosorbent Assays for Serological Screening of Melioidosis in Myanmar.
Burkholderia pseudomallei, the etiologic agent of melioidosis, is an important but under-recognized cause of disease in the tropics. Although first described over a century ago as a septicemic illness associated with morphine addicts in Rangoon, Burma, there is little information regarding the incidence of melioidosis in present-day Myanmar. To address this issue, we used two recently developed and validated serological assays to detect B. pseudomallei-specific antibodies in 124 serum samples obtained from febrile patients in the delta region of Myanmar. Using cutoff values derived from culture-confirmed melioidosis cases in neighboring Thailand, 3.2% of the samples exhibited reactivity profiles consistent with active B. pseudomallei infections. Collectively, these findings indicate that melioidosis likely represents a significant cause of morbidity and mortality in Myanmar and support the need for further studies to assess the true burden of disease in this country.


Redetermined structure, inter-molecular inter-actions and absolute configuration of royleanone.
The structure of the title diterpenoid, C(20)H(28)O(3), {systematic name: (4bS,8aS)-3-hy-droxy-2-isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octa-hydro-phenanthrene-1,4-dione} is confirmed [Eugster et al. (1993 ▶). Private communication (refcode HACGUN). CCDC, Union Road, Cambridge] and its packing is now described. Its absolute structure was established by refinement against data collected with Cu radiation: the two stereogenic centres both have S configurations. One cyclo-hexane ring adopts a chair conformation whereas the other cyclo-hexane ring is in a half-chair conformation and the benzoquinone ring is slightly twisted. An intra-molecular O-H⋯O hydrogen bond generates an S(5) ring motif. In the crystal, mol-ecules are linked into chains along [010] by O-H⋯O hydrogen bonds and weak C-H⋯O inter-actions. The packing also features C⋯O [3.131 (3) Å] short contacts.


Bioinformatic analysis suggests potential mechanisms underlying parasitoid venom evolution and function.
Hymenopteran parasitoid wasps are a diverse collection of species that infect arthropod hosts and use factors found in their venoms to manipulate host immune responses, physiology, and behaviour. Whole parasitoid venoms have been profiled using proteomic approaches, and here we present a bioinformatic characterization of the venom protein content from Ganaspis sp. 1, a parasitoid that infects flies of the genus Drosophila. We find evidence that diverse evolutionary processes including multifunctionalization, co-option, gene duplication, and horizontal gene transfer may be acting in concert to drive venom gene evolution in Ganaspis sp.1. One major role of parasitoid wasp venom is host immune evasion. We previously demonstrated that Ganaspis sp. 1 venom inhibits immune cell activation in infected Drosophila melanogaster hosts, and our current analysis has uncovered additional predicted virulence functions. Overall, this analysis represents an important step towards understanding the composition and activity of parasitoid wasp venoms.


A simple electrochemical approach to fabricate functionalized MWCNT-nanogold decorated PEDOT nanohybrid for simultaneous quantification of uric acid, xanthine and hypoxanthine.
Medical diagnostics and detection of food spoilage require estimation of hypoxanthine (HX), xanthine (XN), and uric acid (UA). A selective sensing platform has been proposed for simultaneous detection of all these species. Functionalized multi-walled carbon nanotube (fMWCNT) stabilized nanogold decorated PEDOT:TOS polymeric nanocomposite (Au-PEDOT-fMWCNT) was synthesized through rapid one-step electropolymerization to enhance conductivity and active surface area by several folds. Electrochemical activities of the proposed sensing platform were analyzed by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS). Analyses through SEM, FESEM and TEM were performed to explore the surface morphology and elemental analysis of the polymeric nanohybrid was investigated by XPS, Raman, FTIR, XRD spectroscopy. Electro-catalysis of UA, XN and HX occurred at low oxidation potentials i.e. 0.082, 0.463 and 0.808 V, respectively in the optimized conditions. The uniquely designed simple, interference free Au-PEDOT-fMWCNT/GCE sensor exhibited high selectivity, good reproducibility, reusability (∼180 times) and stability (∼3 month) with excellent sensitivity of 1.73, 14.31 and 3.82 μA μM-1 cm-2 for UA, XN and HX, respectively. The sensor exhibited linear ranges of detection as 0.1-800, 0.05-175 and 0.1-150 μM with detection limits of 199.3, 24.1 and 90.5 nM for quantification of UA, XN and HX respectively. The performance of the proposed sensor was validated by addition of UA, XN and HX in human serum, urine and fish samples by comparing to those using HPLC. The results indicated good applicability of the proposed sensor for simultaneous detection of UA, XN, HX in real biological fluids.


A photochemical layer-by-layer solution process for preparing organic semiconducting thin films having the right material at the right place.
The synergistic action of properly integrated semiconducting materials can bring about sophisticated electronic processes and functions. However, it is often a great challenge to achieve optimal performance in organic devices because of the limited control over the distribution of different materials in active layers. Here, we employ a unique photoreaction-based layer-by-layer solution process for preparing ternary organic photovoltaic layers. This process is applicable to a variety of compounds from wide-band-gap small molecules to narrow-band-gap π-extended systems, and enables the preparation of multicomponent organic semiconducting thin films having the right compound at the right place. The resulting ternary photovoltaic devices afford high internal quantum efficiencies, leading to an approximately two times higher power-conversion efficiency as compared to the corresponding binary bulk-heterojunction system. This work opens up new possibilities in designing materials and active layers for solution-processed organic electronic devices.


Arel: Investigating [Eu(H2O)9]3+ Photophysics and Creating a Method to Bypass Luminescence Quantum Yield Determinations.
Lanthanide luminescence has been treated separate from molecular photophysics, although the underlying phenomena are the same. As the optical transitions observed in the trivalent lanthanide ions are forbidden, they do belong to the group that molecular photophysics has yet to conquer, yet the experimental descriptors remain valid. Herein, the luminescence quantum yields (ϕlum), luminescence lifetimes (τobs), oscillator strengths (f), and the rates of nonradiative (knr) and radiative (kr ≡ A) deactivation of [Eu(H2O)9]3+ were determined. Further, it was shown that instead of a full photophysical characterization, it is possible to relate changes in transition probabilities to the relative parameter Arel, which does not require reference data. While Arel does not afford comparisons between experiments, it resolves emission intensity changes due to emitter properties from intensity changes due to environmental effects and differences in the number of photons absorbed. When working with fluorescence this may seem trivial; when working with lanthanide luminescence it is not.


Role of cyclic nucleotides in relaxation of fetal lamb ductus arteriosus.
Although prostaglandin E1 is used to dilate the constricted ductus arteriosus in infants with cyanotic heart disease, the mechanism is unknown. To test the hypothesis that the cyclic nucleotides adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) play a role in relaxation, isolated rings of the ductus arteriosus of fetal lambs were studied. Tension of isometric contraction was measured by force displacement transducers. After contraction with oxygen, a control group was compared with rings in which the stimulus for relaxation was either nitrogen gas, prostaglandin E1 (PGE1), nitroglycerin (NTG), or nitroprusside (NPS). During relaxation, tissue was frozen at 30 seconds and at 1, 2, and 5 minutes and analyzed for cAMP and cGMP. PGE1 (10(-6) mol/L) decreased tension by 33% compared with 70% for nitrogen gas, 81% for NTG (10(-5) mol/L), and 92% for NPS (10(-5) mol/L). The maximal relaxation induced by PGE1 was associated with an 11-fold increase in cAMP; PGE1 had no significant effect on cGMP tissue levels. Nitrogen gas, NTG, and NPS produced similar increases in cAMP, and eight-, 25-, and nine-fold increases in cGMP, respectively. These results suggest that the patency of the ductus arteriosus is dependent on activation of both guanylate cyclase and adenylate cyclase and that the nitrovasodilators may be clinically useful in maintaining patency of the ductus arteriosus.


History of antibiotics: from fluoroquinolones to daptomycin (Part 2).
In the Modern Era, physicians attested to the reciprocal influence among a technologically advanced society, rapid scientific progresses in medicine, and the need for new antimicrobials. The results of these changes were not only seen in the prolongation of life expectancy but also by the emergence of new pathogens. We first observed the advent of Gram-negative bacteria as a major source of nosocomial infections. The treatment of these microorganisms was complicated by the appearance and spread of drug resistance. We first focused on the development of two major classes of antimicrobials still currently used for the treatment of Gram-negative bacteria, such as fluoroquinolones and carbapenemes. Subsequently, we directed our attention to the growth of the incidence of infections due to Methicillin-Resistant Staphylococcus aureus (MRSA). Although the first MRSA was already isolated in 1961, the treatment of this new pathogen has been based on the efficacy of vancomycin for more than four decades. Only in the last 15 yr, we assisted in the development of new antimicrobial agents such as linezolid and daptomycin.


Renal implications of arterial hypertension.
Renal vascular damage caused by arterial hypertension participates in alterations of the systemic vascular function and structure. Nephrosclerosis seems to run in parallel with the systemic atherosclerosis that accounts for the increased cardiovascular morbidity and mortality seen in hypertensive patients. Parameters indicating the existence of an alteration in renal function (increased serum creatinine, proteinuria and microalbuminuria) are independent predictors for an increased cardiovascular morbidity and mortality. Hence, parameters of renal function must be considered in any stratification of cardiovascular risk in hypertensive patients.


Open-loop and closed-loop control of posture: Stabilogram-diffusion analysis of center-of-pressure trajectories among people with stroke.
Many people with stroke (PwS) demonstrate reduced balance and increased postural sway afterwards, which may ultimately lead to falls and injury. In this study, we aimed to better understand postural sway behavior and the mechanisms of balance control by examining balance in upright standing among PwS using methods from statistical mechanics i.e., the Stabilogram diffusion analysis (SDA). Center-of-pressure displacements while standing still were measured in 25 PwS and 11 healthy subjects. The traditional postural sway parameters were measured, and the SDA was used to characterize balance control in eyes-open and eyes-closed conditions. We found that PwS demonstrated significantly greater postural sway in the mediolateral and anterior-posterior directions and significantly higher SDA short-term diffusion coefficients and critical displacement in both eyes-open and eyes-closed conditions. There was also a significant group-by-condition interaction, whereas PwS demonstrated more sway in the eyes-closed condition. The SDA analysis revealed unstable behavior during short-term intervals, interpreted as larger distance of sway until closed-loop control took place. This significant group-by-condition interaction suggests that PwS have a significantly greater reliance on visual input compared with healthy subjects.


Effects of alternative cropping systems on globe artichoke qualitative traits.
Traditionally, globe artichoke cultivation in the Mediterranean basin is based on monoculture and on use of high amounts of nitrogen fertiliser. This raises issues regarding its compatibility with sustainable agriculture. We studied the effect of one typical conventional (CONV) and two alternative cropping systems [globe artichoke in sequence with French bean (NCV1), or in biannual rotation (NCV2) with cauliflower and with a leguminous cover crop in inter-row spaces] on yield, polyphenol and mineral content of globe artichoke heads over two consecutive growing seasons. NCV2 showed statistical differences in terms of fresh product yield with respect to the monoculture systems. In addition, the dihydroxycinnamic acids and dicaffeoylquinic acids of non-conventional samples were one-fold significantly higher than the conventional one. All the samples reported good mineral content, although NCV2 achieved a higher Fe content than conventional throughout the two seasons. After two and three dates of sampling, the CONV samples showed the highest levels of K content. In our study, an acceptable commercial yield and quality of 'Spinoso sardo' were achieved by shifting the common conventional agronomic management to more sustainable ones, by means of an accurate choice of cover crop species and rotations introduced in the systems. © 2017 Society of Chemical Industry.


Ginsenoside Rb3 strengthens the hypoglycemic effect through AMPK for inhibition of hepatic gluconeogenesis.
Ginsenoside Rb3 is one of the major active components in protopanaxdiol type ginsenosides, and has demonstrated anti-diabetic activity. However, the mechanism of this action has yet to be elucidated. The present study investigated the effects of ginsenoside Rb3 on the AMP-activated protein kinase (AMPK) gluconeogenesis pathway. The present study involved the use of HepG2 cells and western blot analysis to systematically evaluate the effect of ginsenoside Rb3 on AMPK signaling proteins and key factors of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, forkhead transcription factor 1 (FOXO1) and hepatic nuclear receptor 4α (HNF4α)]. The results indicated that 25 µM ginsenoside Rb3 significantly activated AMPK activity, increased the ratio of p-AMPK/total-AMPK, and had synergistic effects with the activator of AICAR on the activation of AMPK. Further analysis indicated that the expression of the transcription factor FOXO1 and HNF4α protein, two important factors in the pathway of HepG2 cell gluconeogenesis, was significantly suppressed by ginsenoside Rb3. PEPCK and G6Pase were subsequently inhibited, which led to the suppression of gluconeogenesis. These effects were partially blocked by the AMPK inhibitor, Compound C, which indicated that the inhibition effects of ginsenoside Rb3 on hepatic gluconeogenesis were predominantly due to the activation of the AMPK signaling pathway. These data suggested that ginsenoside Rb3 can suppress hepatic gluconeogenesis, at least partially through stimulation of AMPK activity.


Changes in consistency of occlusal contact in myofascial pain-dysfunction (MPD) syndrome.
The sound patterns produced by tooth contact were recorded in 24 subjects with myofascial pain-dysfunction (MPD) syndrome prior to and following treatment using an Occlusograph. Recordings also were obtained on 12 control subjects. Evaluation of the sound patterns showed a close correlation between the improvement in symptoms of MPD syndrome following treatment and the consistency of repeated occlusal contacts. The consistency following successful treatment of the subjects with MPD syndrome was equivalent to that of the control subjects.


Twenty-year follow-up of a familial case of PTH1R-associated primary failure of tooth eruption.
Nonsyndromic primary failure of eruption (PFE) is a rare autosomal dominant disorder of dental eruption with no obvious dental or soft tissue interference. The purposes of this study were to genetically and clinically characterize a family with many members affected by PFE and to describe the natural evolution of the disorder. Three generations of a family with 18 members, 10 of them clinically affected by PFE, were evaluated periodically during 20 years of clinical follow-up. PFE was observed in varying degrees of severity in both sexes. Clinical presentation became more severe in adulthood. One patient had spontaneous reeruption of 2 posterior teeth. Cervical root resorptions were observed in 3 members. Genetic analysis showed a deleterious heterozygous mutation in intron 9 of the PTH1R gene (c.639-2A>G) and diagnosed an additional affected member. The long-term follow-up of PFE cases in this family permitted the following observations: (1) the onset occurred from the preemergence to the postemergence phases, (2) PFE appeared to be closely related to ankylosis, (3) affected teeth maintained the eruptive potential even in adulthood, (4) the earlier the onset the more severe the open bite, and (5) cervical root resorptions occurred in 3 affected members.


Role of hypercholesterolemia in accelerated transplant coronary vasculopathy: results of surgical therapy with partial ileal bypass in rabbits undergoing heterotopic heart transplantation.
We tested the hypothesis that plasma cholesterol lowering action of partial ileal bypass (PIB) is beneficial in mitigating accelerated transplantation coronary vasculopathy. Forty-one New Zealand white rabbits were randomized to receive a normal (n = 21) or 1% cholesterol diet (n = 20). They underwent heterotopic heart transplantation with sham-PIB (n = 19) or PIB (n = 22) and immunosuppression with cyclosporine A (CyA). CyA increased plasma cholesterol of rabbits receiving a normal diet. This effect was mitigated by PIB (101 +/- 50 mg/dl CyA vs baseline 24 +/- 8, p < 0.001; vs 54 +/- 25 mg/dl with PIB, p < 0.05). In cholesterol-fed rabbits, PIB decreased plasma cholesterol levels (520 +/- 236 mg/dl PIB vs baseline 720 +/- 359, p < 0.05; vs 1502 +/- 253 mg/dl with sham PIB, p < 0.00001). Coronary arteries (CA) of 21 5-week survivors were evaluated by light microscopy and digital morphometry. No rejection was noted. Histologic study revealed vasculopathy in 3% of 705 native and 18% of 654 transplant CA (p < 0.05). Graft vasculopathy (GV) was present in 25% of 365 CA of sham-PIB and 10% of 289 CA of PIB rabbits (p = 0.07). In cholesterol-fed rabbits, GV was characterized by fatty proliferative lesions in 75% of 91 pathologic CA of sham and 21% of 28 pathologic CA of PIB rabbits (p < 0.05). Graft intimal hyperplasia was not correlated with cholesterol intake or PIB and was present in 18 of 119 pathologic CA. GV was characterized by fatty intimal proliferation, fibrous intimal hyperplasia, and a "mixed type." Fibrous intimal hyperplasia developed in native and transplanted hearts, and CyA seemed to promote this state. Hypercholesterolemia promoted fatty proliferative lesions, worsening GV. PIB significantly decreased total cholesterol and retarded fatty proliferation of CA of native and transplanted hearts but did not prevent intimal hyperplastic vasculopathy. Therapy of hypercholesterolemia is recommended to at least mitigate the fatty intimal proliferation of GV.