Temporal changes in resting heart rate and deaths from ischemic heart disease.
Resting heart rate (RHR) has long been recognized as an independent predictor of cardiovascular risk. However, whether temporal changes in RHR influence the risk of death from ischemic heart disease (IHD) in the general population is not known. To assess the association of long-term longitudinal changes in RHR with the risk of dying from IHD. A prospective cohort study of 13,499 men and 15,826 women without known cardiovascular disease in Norway. Resting heart rate was measured on 2 occasions around 10 years apart in the Nord-Trøndelag County Health Study. The second RHR measurement was obtained between August 1995 and June 1997, with subsequent mortality follow-up until December 31, 2008. A total of 60 participants were lost to follow-up, all due to emigration from Norway. Using Cox regression analyses, adjusted hazard ratios (AHRs) were estimated of death from IHD related to changes in RHR over time. In a corresponding analysis, death from all causes also was assessed. During a mean (SD) of 12 (2) years of follow-up, 3038 people died, and 388 deaths were caused by IHD. An increase in RHR was associated with increased risk of death from IHD. Compared with participants with a RHR of less than 70 beats/min at both measurements (8.2 deaths/10,000 person-years), the AHR was 1.9 (95% CI, 1.0-3.6) for participants with a RHR of less than 70 beats/min at the first measurement but greater than 85 beats/min at the second measurement (17.2 deaths/10,000 person-years). For participants with RHRs between 70 and 85 beats/min at the first measurement and greater than 85 beats/min at the second measurement (17.4 deaths/10,000 person-years), the AHR was 1.8 (95% CI, 1.2-2.8). The association of change in RHR with IHD mortality was not linear (P = .003 for quadratic trend), suggesting that a decrease in RHR showed no general mortality benefit. Excluding the first 3 years of follow-up did not substantially alter the findings. The associations for total mortality were similar but generally weaker than those observed for IHD mortality. Among men and women without known cardiovascular disease, an increase in RHR over a 10-year period was associated with increased risk of death from IHD and also for all-cause mortality.


Validity study of head and neck flexion-extension motion comparing measurements of a pendulum goniometer and roentgenograms.
Study completed in partial fulfillment of requirements for Master of Health Sciences Degree, Physical Therapy, Washington University, St. Louis, MO. Physical therapists measure head and neck flexion-extension with goniometers, assuming that such measures are an accurate appraisal of joint motion. The only universally accepted, reliable, and objective method of measuring joint motion, however, is by roentgenograms, which have potentially harmful effects and are too expensive to be used routinely for assessing changes in motion. A method is discussed for computing head-tilt on neck and neck flexion-extension motion from roentgenograms. Radiographic measures were compared to pendulum goniometer measures for total head and neck motion (i.e., head-tilt on neck plus neck motion in both the flexed and extended positions) showing good correlation (Pearson = 0.97) and good agreement [intraclass correlation (ICC) = 0.98] between measures. This study validated that the pendulum goniometer and roentgenograms obtain the same measures for head and neck motion in the sagittal plane. J Orthop Sports Phys Ther 1990;11(9):414-418.


Deep learning for MYC binding site recognition.
Motivation: The definition of the genome distribution of the Myc transcription factor is extremely important since it may help predict its transcriptional activity particularly in the context of cancer. Myc is among the most powerful oncogenes involved in the occurrence and development of more than 80% of different types of pediatric and adult cancers. Myc regulates thousands of genes which can be in part different, depending on the type of tissues and tumours. Myc distribution along the genome has been determined experimentally through chromatin immunoprecipitation This approach, although powerful, is very time consuming and cannot be routinely applied to tumours of individual patients. Thus, it becomes of paramount importance to develop in silico tools that can effectively and rapidly predict its distribution on a given cell genome. New advanced computational tools (DeeperBind) can then be successfully employed to determine the function of Myc in a specific tumour, and may help to devise new directions and approaches to experiments first and personalized and more effective therapeutic treatments for a single patient later on. Results: The use of DeeperBind with DeepRAM on Colab platform (Google) can effectively predict the binding sites for the MYC factor with an accuracy above 0.96 AUC, when trained with multiple cell lines. The analysis of the filters in DeeperBind trained models shows, besides the consensus sequence CACGTG classically associated to the MYC factor, also the other consensus sequences G/C box or TGGGA, respectively bound by the SP1 and MIZ-1 transcription factors, which are known to mediate the MYC repressive response. Overall, our findings suggest a stronger synergy between the machine learning tools as DeeperBind and biological experiments, which may reduce the time consuming experiments by providing a direction to guide them.


The economics of microgravity research.
In this introduction to the economics of microgravity research, DiFrancesco and Olson explore the existing landscape and begin to define the requirements for a robust, well-funded microgravity research environment. This work chronicles the history, the opportunities, and how the decisions made today will shape the future. The past 60 years have seen tremendous growth in the capabilities and resources available to conduct microgravity science. However, we are now at an inflection point for the future of humanity in space. A confluence of factors including the rise of commercialization, a shifting funding landscape, and a growing international presence in space exploration, and terrestrial research platforms are shaping the conditions for full-scale microgravity research programs. In this first discussion, the authors focus on the concepts of markets, tangible and intangible value, research pathways and their implications for investments in research projects, and the collateral platforms needed. The opportunities and implications for adopting new approaches to funding and market-making illuminate how decisions made today will affect the speed of advances the community will be able to achieve in the future.


A single run, rapid polarity switching method for determination of 30 pharmaceuticals and personal care products in waste water using Q-Exactive Orbitrap high resolution accurate mass spectrometry.
The analytical capability of the UPLC-Q Exactive™ Orbitrap MS was exploited for simultaneous determination of 30 acidic and basic PPCPs in a single run, using rapid polarity switching of the electrospray ionisation source. Full scan MS mode at resolution of 35,000 FWHM, Automatic gain control (AGC) target of 1E6 ions at injection time of 50 ms provided the optimum parameters for high sensitivity, together with sufficient data points per peak (≥15) for improved reproducibility. In addition to chromatographic retention times, method selectivity was achieved via applying high resolution accurate mass with low mass tolerance filter (<5 ppm) for identification of each target compound. Six-point linear calibration curves (R2 > 0.95) were established for all target analytes over a concentration range of 1-1500 ng/ml. Good results were obtained for method accuracy (% recovery = 76-104%), inter- and intra-day precision (relative standard deviation <15%) at 3 concentration levels. Instrumental detection and quantification limits ranged from (0.02-1.21 ng/ml) and (0.07-4.05 ng/ml), respectively. While optimised MS/MS analysis through parallel reaction monitoring (PRM) mode provided slightly higher sensitivity, Full scan MS mode allowed for higher mass resolution (selectivity), more data points per peak (reproducibility) and more importantly, the potential for post-acquisition screening of non-target compounds. Following solid phase extraction (SPE) of target analytes, the method was successfully applied to provide first data on PPCPs occurrence in effluent and surface water samples (n = 10) from Egypt. Moreover, screening for non-target compounds revealed the presence of bisphenol A, which was further confirmed via matching with an authentic standard. Overall, this study provides first insight into the high analytical capabilities of the Q-Exactive™ Orbitrap platform for both targeted/non-targeted analysis of PPCPs in environmental matrices.


Enhanced expression of cytokines and chemokines by blood monocytes to in vitro lipopolysaccharide stimulation are associated with hostility and severity of depressive symptoms in healthy women.
The current study investigated the relation of hostility and severity of depressive symptoms, separately and jointly, to the capacity of blood monocytes to secrete an array of cytokines when stimulated by bacterial lipopolysaccharide (LPS). Subjects were 44 healthy, non-smoking, premenopausal women (aged 23-49 years) not currently taking oral contraceptives. Data were collected during the follicular phase of the menstrual cycle. The Cook-Medley Hostility (Ho) scale and the Beck Depression Inventory (BDI) were used to assess hostility and severity of depressive symptoms, respectively. Dual-color flow cytometry was used to measure the total expression of interleukin (IL)-1alpha, IL-1beta, IL-8, tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1 and monocyte inflammatory protein (MIP)-1alpha in blood monocytes following 4 h in vitro LPS stimulation of whole blood. In analyses adjusting for age, body mass index (BMI), fasting cholesterol, alcohol use, race and 17beta-estradiol (E(2)), higher Ho scores were associated with greater LPS-stimulated expression of IL-1alpha (beta = 0.033, p = 0.02), IL-8 (beta = 0.046, p = 0.01) and IL-1beta (beta = 0.024, p = 0.06). Higher BDI scores were associated with greater expression of TNF-alpha (beta = 0.042, p = 0.02) and IL-8 (beta = 0.045, p = 0.04). The linear combination of Ho and BDI scores was significantly associated with IL-1beta (beta = 0.18, p = 0.057), IL-8 (beta = 0.36, p = 0.01), TNF-alpha (beta = 0.25, p = 0.03), and IL-1alpha (beta = 0.18, p < 0.07). Thus, in healthy women, these psychological risk factors, alone and in combination, induce a proinflammatory phenotype in circulating monocytes characterized by the up-regulation of proinflammatory cytokines, supporting the hypothesis that inflammation may be a key pathway whereby hostility and depressive symptoms contribute to atherosclerosis and subsequent coronary heart disease (CHD).


Six years genotype distribution of Human Papillomavirus in Calabria Region, Southern Italy: a retrospective study.
Although analysis of the Human papillomavirus (HPV) genotype spread in a particular area has a crucial impact on public health and prevention programmes, there is a lack of epidemiological data regarding HPV in the Calabria region of Italy. We therefore update information on HPV age/genotype distribution by retrospectively analysing a cohort of women, with and without cervical lesions, living in Calabria, who underwent HPV DNA testing; moreover, we also evaluated HPV age/genotype distribution in a subset of patients with cervical lesions. Cervical scrape specimens obtained from 9590 women (age range 20-75 years) from January 2010 to December 2015 were tested for HPV DNA. Viral types were genotyped by Linear Array HPV Genotyping® test (Roche, USA) at the Clinical Microbiology Operative Unit of six hospitals located in four provinces of the Calabria region. Cervical scrape specimens were also used to perform Pap smears for cytological analysis in a subset of 405 women; cytological classification of the samples was performed according to the Bethesda classification system. A total of 2974 women (31%) (C.I. 95% 30.09-31.94) were found to be HPV DNA positive for at least one (57.3%) or several (42.7%) HPV genotypes. Of single genotype HPV infections, 46.5% and 36.4 % were classed as high-risk (HR, Group 1) and low-risk (LR, Group 3) respectively, while 16.9% were classed as probably/possibly carcinogenic and 0.2% undetermined risk. Stratified by age, total HPV distribution, showed the highest prevalence within the range 30-39 years (37.2%), while single genotype infection distribution displayed a peak in women from the age range 20-29 years (37.5%). The most common high-risk HPV type was HPV 16 (19.1%), followed by HPV 31 (9.1%). We provide epidemiological data on HPV age/genotype distribution in women living in the Calabria region with or without cytological abnormalities, further to the enhancement of HPV screening/prevention programmes for the local population.


Steam sterilisation's energy and water footprint.
Objective The aim of the present study was to quantify hospital steam steriliser resource consumption to provide baseline environmental data and identify possible efficiency gains. We sought to find the amount of steriliser electricity and water used for active cycles and for idling (standby), and the relationship between the electricity and water consumption and the mass and type of items sterilised. Methods We logged a hospital steam steriliser's electricity and water meters every 5min for up to 1 year. We obtained details of all active cycles (standard 134°C and accessory or 'test' cycles), recording item masses and types. Relationships were investigated for both the weight and type of items sterilised with electricity and water consumption. Results Over 304 days there were 2173 active cycles, including 1343 standard 134°C cycles that had an average load mass of 21.2kg, with 32% of cycles <15kg. Electricity used for active cycles was 32652kWh (60% of total), whereas the water used was 1243495L (79%). Standby used 21457kWh (40%) electricity and 329200L (21%) water. Total electricity and water consumption per mass sterilised was 1.9kWhkg-1 and 58Lkg-1, respectively. The linear regression model predicting electricity use was: kWh=15.7+ 0.14×mass (in kg; R2=0.58, P<0.01). Models for water and item type were poor. Electricity and water use fell from 3kWhkg-1 and 200Lkg-1, respectively, for 5-kg loads to 0.5kWhkg-1 and 20Lkg-1, respectively, for 40-kg loads. Conclusions Considerable electricity and water use occurred during standby, load mass was only moderately predictive of electricity consumption and light loads were common yet inefficient. The findings of the present study are a baseline for steam sterilisation's environmental footprint and identify areas to improve efficiencies. What is known about the topic? There is increasing interest in the environmental effects of healthcare. Life cycle assessment ('cradle to grave') provides a scientific method of analysing environmental effects. Although data of the effects of steam sterilisation are integral to the life cycles of reusable items and procedures using such items, there are few data available. Further, there is scant information regarding the efficiency of the long-term in-hospital use of sterilisers. What does this paper add? We quantified, for the first time, long-term electricity and water use of a hospital steam steriliser. We provide useful input data for future life cycle assessments of all reusable, steam-sterilised equipment. Further, we identified opportunities for improved steriliser efficiencies, including rotating off idle sterilisers and reducing the number of light steriliser loads. Finally, others could use our methods to examine steam sterilisers and many other energy-intensive items of hospital equipment. What are the implications for practitioners? We provide useful input data for all researchers examining the environmental footprint of reusable hospital equipment and procedures using such equipment. As a result of the present study, staff in the hospital sterile supply department have reduced steam steriliser electricity and water use considerably without impeding sterilisation throughput (and reduced time inefficiencies). Many other hospitals could benefit from similar methods to improve steam steriliser and other hospital equipment efficiencies.


Duplicate coverage and demand for health care. The case of Catalonia.
An individual has duplicate coverage when he enjoys a compulsory medical public insurance, and in addition he has purchased a private one. This paper studies the implications of duplicate coverage on both demand for visits to specialists and on the selection process of the private insurance market. Econometric models, estimated by the generalized method of moments, accommodate both the endogeneity of insurance choice decision and the non-negativity of the variable number of visits. The choice of instrumental variables is motivated within a theoretical model of demand for health care. The results shows that endogeneity is important for the subsample of heads of household, but not for the subsample of non-heads of household. For the subsample of non-heads of household, a positive effect of duplicate coverage on the number of visits to specialists is found. Health related variables, education and income are also important. Results are consistent with the idea that heads of household that buy private insurance are the ones with poor unobservable health conditions. It is argued that this last result is related to the existence of a compulsory public insurance.


Salinity tolerance in halophytes.
Halophytes, plants that survive to reproduce in environments where the salt concentration is around 200 mm NaCl or more, constitute about 1% of the world's flora. Some halophytes show optimal growth in saline conditions; others grow optimally in the absence of salt. However, the tolerance of all halophytes to salinity relies on controlled uptake and compartmentalization of Na+, K+ and Cl- and the synthesis of organic 'compatible' solutes, even where salt glands are operative. Although there is evidence that different species may utilize different transporters in their accumulation of Na+, in general little is known of the proteins and regulatory networks involved. Consequently, it is not yet possible to assign molecular mechanisms to apparent differences in rates of Na+ and Cl- uptake, in root-to-shoot transport (xylem loading and retrieval), or in net selectivity for K+ over Na+. At the cellular level, H+-ATPases in the plasma membrane and tonoplast, as well as the tonoplast H+-PPiase, provide the trans-membrane proton motive force used by various secondary transporters. The widespread occurrence, taxonomically, of halophytes and the general paucity of information on the molecular regulation of tolerance mechanisms persuade us that research should be concentrated on a number of 'model' species that are representative of the various mechanisms that might be involved in tolerance.


The chromatin structure of Saccharomyces cerevisiae autonomously replicating sequences changes during the cell division cycle.
The chromatin structures of two well-characterized autonomously replicating sequence (ARS) elements were examined at their chromosomal sites during the cell division cycle in Saccharomyces cerevisiae. The H4 ARS is located near one of the duplicate nonallelic histone H4 genes, while ARS1 is present near the TRP1 gene. Cells blocked in G1 either by alpha-factor arrest or by nitrogen starvation had two DNase I-hypersensitive sites of about equal intensity in the ARS element. This pattern of DNase I-hypersensitive sites was altered in synchronous cultures allowed to proceed into S phase. In addition to a general increase in DNase I sensitivity around the core consensus sequence, the DNase I-hypersensitive site closest to the core consensus became more nuclease sensitive than the distal site. This change in chromatin structure was restricted to the ARS region and depended on replication since cdc7 cells blocked near the time of replication initiation did not undergo the transition. Subsequent release of arrested cdc7 cells restored entry into S phase and was accompanied by the characteristic change in ARS chromatin structure.


Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity.
To evaluate the reliability and validity of a semistructured measure of obsessive-compulsive symptom severity in children and adolescents with obsessive-compulsive disorder (OCD). Sixty-five children with OCD (25 girls and 40 boys, aged 8 to 17 years) were assessed with the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Interrater agreement was assessed by four raters in a subsample (n = 24). Discriminant and convergent validity were assessed by comparing CY-BOCS scores to self-ratings of depression, anxiety, and obsessive-compulsive symptoms. Internal consistency was high, measuring .87 for the 10 items. The intraclass correlations for the CY-BOCS Total, Obsession, and Compulsion scores were .84, .91, and .68, suggesting good to excellent interrater agreement for subscale and total scores. The CY-BOCS Total score showed a significantly higher correlation with a self-report of obsessive-compulsive symptoms (r = .62 for the Leyton survey) compared with the Children's Depression Inventory (r = .34) and the Children's Manifest Anxiety Scale (r = .37) (p = .02 and .05, respectively). The CY-BOCS yields reliable and valid subscale and total scores for obsessive-compulsive symptom severity in children and adolescents with OCD. Reliability and validity appear to be influenced by age of the child and the hazards associated with integrating data from parental and patient sources.


Center-surround antagonistic organization in small-field luminosity horizontal cells of turtle retina.
1. The spatial properties of the small-field luminosity horizontal cell (L2-HC) were investigated in the retina of the turtle by using circular or annular light stimuli of varying dimensions. 2. The amplitude of the hyperpolarizing response induced by dim light spots decreased when the diameter of the spot was increased beyond about 1,000 micrometer. 3. With bright-light stimuli the peak amplitude of the light responses increased monotonically when increasing the illuminated area, but a delayed antagonistic effect appeared with spots of more than 1,000-micrometer diameter. 4. Depolarizing responses were observed if the periphery of the receptive field was stimulated with annuli of light in the presence of central background illumination. 5. The interaction of the inputs converging on the L2-HC from the peripheral and central regions of the receptive field was found to be nonlinear. The same peripheral stimulation could result either in an enhancement or in a depression of the central response according to the intensity of the central illumination. 6. By comparing the receptive-field properties of the L2-HC and the red cones a model is proposed that explains the antagonistic surround mechanism of the L2-HC on the basis of the antagonistic peripheral mechanism in cones. '


The HDAC inhibitor valproate induces a bivalent status of the CD20 promoter in CLL patients suggesting distinct epigenetic regulation of CD20 expression in CLL in vivo.
Treatment with anti-CD20 antibodies is only moderately efficient in chronic lymphocytic leukemia (CLL), a feature which has been explained by the inherently low CD20 expression in CLL. It has been shown that CD20 is epigenetically regulated and that histone deacetylase inhibitors (HDACis) can increase CD20 expression in vitro in CLL. To assess whether HDACis can upregulate CD20 also in vivo in CLL, the HDACi valproate was given to three del13q/NOTCH1wt CLL patients and CD20 levels were analysed (the PREVAIL study). Valproate treatment resulted in expected global activating histone modifications suggesting HDAC inhibitory effects. However, although valproate induced expression of CD20 mRNA and protein in the del13q/NOTCH1wt I83-E95 CLL cell line, no such effects were observed in the patients studied. In contrast to the cell line, in patients valproate treatment resulted in transient recruitment of the transcriptional repressor EZH2 to the CD20 promoter, correlating to an increase of the repressive histone mark H3K27me3. This suggests that valproate-mediated induction of CD20 may be hampered by EZH2 mediated H3K27me3 in vivo in CLL. Moreover, valproate treatment resulted in induction of EZH2 and global H3K27me3 in patient cells, suggesting transcriptionally repressive effects of valproate in CLL. Our results suggest new in vivo mechanisms of HDACis which may have implications on the design of future clinical trials in B-cell malignancies.


Zinc and other trace elements in liver cirrhosis.
Alterations in trace element concentrations may be observed in patients with chronic liver disease. Notably, selenium and zinc levels are reduced both in serum and in liver tissue of cirrhotic patients. Low selenium levels have been involved in the pathogenesis of liver damage as this element is important in controlling the levels of toxic oxygen radicals in the cells. Zinc deficiency has been involved in the pathogenesis of a number of clinical findings in chronic liver disease. These include the possible role of zinc deficiency in the pathogenesis of hepatic encephalopathy, by inducing alterations in urea metabolism. In CC14 cirrhotic rats oral zinc supplementation reduces ammonia levels and increases OCT activity in the liver. Oral zinc supplementation has been also proposed in the treatment of cirrhotic patients with chronic hepatic encephalopathy, the results however are not yet conclusive.


Biofilm formation and susceptibility to gentamicin and colistin of extremely drug-resistant KPC-producing Klebsiella pneumoniae.
KPC-producing Klebsiella pneumoniae (KPC-Kpn) is a worldwide challenging pathogen, yet its biofilm-forming potential is not defined. We characterized biofilm formation of this pathogen and determined biofilm susceptibility to gentamicin and colistin. Forty-six KPC-Kpn clinical isolates were studied [sequence type (ST) 258, n = 28; and other STs, n = 18]. Biofilm biomass was determined using the standard assay measured by OD590 (where OD stands for optical density) and visualized using confocal microscopy. Antibiotic effect on biofilm formation was evaluated and susceptibility within biofilm was determined by the minimal biofilm elimination concentration (MBEC) method. KPC-Kpn isolates produced biofilm in the range of 0.02-0.3 OD590, where ST258 isolates produced less biofilm compared with other STs (median OD590 0.07 versus 0.15, respectively; P < 0.05). Biofilm biovolumes were in the range of 354 ± 323 to 27,461.4 ± 11,886.7 μm(3). In the planktonic state, ST258 isolates were less resistant to gentamicin compared with other STs (resistance rates: 14% versus 66%, respectively; P < 0.05). Gentamicin-resistant isolates (MIC ≥ 32 mg/L) showed a dramatic increase in resistance within the biofilm (up to 234-fold), whereas gentamicin-susceptible isolates (MIC <32 mg/L) retained their susceptibility. The elevated gentamicin resistance was not due to overexpression of the aminoglycoside resistance gene aac(3)-II in the biofilm state. Resistance to colistin in biofilm increased as well, but was less prominent (P < 0.05). Biofilm biomass did not affect the MBECs of gentamicin and colistin, regardless of the genetic lineage. KPC-Kpn and particularly ST258 do not form massive biofilms. Nevertheless, susceptibility to gentamicin of this endemic lineage is retained in its biofilm state, supporting the use of this antibiotic in the clinical scenario.


Optimal gating strategy for determining CD4+ recent thymic emigrants in human immunodeficiency virus-1 infected patients.
Alterations of the frequencies of recent thymic emigrants (RTEs) in blood have been demonstrated to be associated with human immunodeficiency virus-1 (HIV-1) disease progression and immune reconstitution following antiretroviral therapy. Flow cytometry is a technology that offers many advantages over T-cell receptor excision circles (TRECs) quantification to determine the RTE subset in blood. However, the gating strategies for identifying RTEs by flow cytometry have not been evaluated and compared in much detail. In the present study, we compared the frequencies and the senescence levels of RTEs in 54 HIV-1 seronegative controls (HC) and 70 HIV-1 seropositive (HIV-1+) subjects using two different gating strategies by flow cytometry. Our analysis indicated that the CD4+ RTE population determined by the expressing pattern CD45RO-CD31+ contained the terminal effector memory T-cell population after HIV-1 infection, which could significantly affect the further phenotypic and functional studies. Our data demonstrate the necessity of including an additional marker such as CCR7 to distinguish better CD4+RTE subset in HIV-1+ subjects.


Prospective comparative study of efficacy and toxicity of netilmicin and amikacin.
Eighty patients were treated with either amikacin or netilmicin in a prospective randomized study of serious gram-negative bacillary infections, including 11 due to gentamicin-resistant pathogens. Thirty-six treated with netilmicin and 35 treated with amikacin were evaluable for efficacy or toxicity, or both. The overall groups differed significantly only in age. There were no significant differences in efficacy of the two drugs. There were no statistically significant differences at the 95% level between the netilmicin group and the amikacin group with respect to nephrotoxic reactions (38 versus 28%, respectively) or ototoxic reactions (9 versus 25%, respectively). Further comparative trials of netilmicin and other aminoglycosides appear warranted before it is widely used.


Extensively drug-resistant bacteria are an independent predictive factor of mortality in 130 patients with spontaneous bacterial peritonitis or spontaneous bacteremia.
To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis. We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm(3). In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed. Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011). XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.


Phrasal prosody constrains word segmentation in French 16-month-olds.
Infants who are in the process of acquiring their mother tongue have to find a way of segmenting the continuous speech stream into word-sized units. We present an experiment showing that French 16-month-olds are able to exploit phonological phrase boundaries in order to constrain lexical access. Using the conditioned head-turning technique, we showed that infants trained to turn their head for a bisyllabic word responded more often to sentences that contained this word, than to sentences that contained both syllables of this word separated by a phonological phrase boundary. We compare these results with similar results obtained with English-speaking infants, and discuss their implication for lexical and syntactic acquisition.


[Prognostication and treatment of fronto-spheno-ethmoiditis in patients with post-traumatic deformities of the upper and middle parts of the face].
Different types of frontosphenoethmoiditis in patients with posttraumatic deformities of the upper and middle facial regions including deformation of the naso-orbito-ethmoidal, naso-fronto-orbito-ethmoidal and sphenoidal complexes are described. Mechanisms of development of posttraumatic sinusitis are considered regarding type of the trauma. Clinical symptoms and diagnosis, problems of reconstructive interventions, variants of treatment policy are discussed.


Establishment of the human reflex tear two-dimensional polyacrylamide gel electrophoresis reference map: new proteins of potential diagnostic value.
To understand the changes in protein expression associated with various physiological states as well as the development of pathological eye disease, we have begun to map the protein components of normal human reflex tears. An analytical reference map of normal human reflex tears was created using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) with pH 3.5-10 immobilized pH gradients (IPGs). Micropreparatively loaded gels were transferred to polyvinylidene difluoride (PVDF) and analysed by a combination of N-terminal sequence tagging and amino acid compositional analysis. Thirty spots were sequence tagged, resulting in identification of six different proteins (lipocalin, lysozyme, lactotransferrin, zinc-alpha-2 glycoprotein, cystatin S, cystatin SN) that matched to entries in the SWISS-PROT database. A group of N-terminally blocked proteins was clearly identified from SWISS-PROT by amino acid analysis, isoelectric point (pI) and molecular weight (Mr). A number of highly expressed protein components remain unidentified despite being subjected to amino acid analysis and Edman sequencing. A majority of the abundant proteins showed varying degrees of charge heterogeneity attributed to post-translational processing such as glycosylation and N-terminal truncation. We have identified a previously undescribed protein that we have named lacryglobin. This protein displays strong homology with mammaglobin, a protein overexpressed in breast cancer. The discovery of this homologue in tears offers the potential for disease diagnosis by screening tear fluid proteins.


Comparison of hinged and contoured rods for occipitocervical arthrodesis in adults: A clinical study.
A rigid construct that employs an occipital plate and upper cervical screws and rods is the current standard treatment for craniovertebral junction (CVJ) instability. A rod is contoured to accommodate the occipitocervical angle. Fatigue failure has been associated these acute bends. Hinged rod systems have been developed to obviate intraoperative rod contouring. The aim of this study is to determine the safety and efficacy of the hinged rod system in occipitocervical fusion. This study retrospectively evaluated 39 patients who underwent occipitocervical arthrodesis. Twenty patients were treated with hinged rods versus 19 with contoured rods. Clinical and radiographic data were compared and analyzed. Preoperative and postoperative Nurick and Frankel scores were similar between both groups. The use of allograft, autograft or bone morphogenetic protein was similar in both groups. The average number of levels fused was 4.1 (±2.4) and 3.4 (±2) for hinged and contoured rods, respectively. The operative time, estimated blood loss, and length of stay were similar between both groups. The occiput to C2 angle was similarly maintained in both groups and all patients demonstrated no movement across the CVJ on flexion-extension X-rays during their last follow-up. The average follow-up for the hinged and contoured rod groups was 12.2 months and 15.9 months, respectively. Hinged rods provide a safe and effective alternative to contoured rods during occipitocervical arthrodesis.


Characterization of glucose transport in an insulin-secreting cell line.
The rat insulinoma-derived RINm5F cell line retains many differentiated functions of islet beta-cells. However, it fails to recognize glucose as an insulin secretagogue in the physiological concentration range. With this cell line, glucose-transport kinetics were investigated, by using a double-label technique with the non-metabolizable glucose analogue 3-O-methylglucose (OMG). RINm5F cells possess a passive glucose-transport system with high capacity and low affinity. Equilibration across the plasma membrane of extracellular OMG concentrations up to at least 20 mM is achieved within 2 min at 37 degrees C. The half-saturation of OMG uptake occurs at 32 mM. At lower temperatures OMG uptake is markedly retarded, with a temperature coefficient (Q10) of 2.9. As indicated by efflux measurements, transport is symmetrical. Cytochalasin B at micromolar concentrations and phlorrhizin in millimolar concentrations are potent inhibitors of OMG uptake. Neutralization of the secreted insulin with antibodies does not alter OMG uptake kinetics. The glucose metabolism of RINm5F cells is much exaggerated compared with that of islet beta-cells. Nonetheless, when measured in parallel to uptake, transport exceeds by far the rate of metabolism at glucose concentrations above 3 mM. Measurements of intracellular D-glucose reveal a lower intracellular glucose concentration relative to the extracellular in RINm5F cells. This seems to be due to abnormalities in the subsequent steps of glucose metabolism, rather than to abnormalities in hexose uptake. The loss of glucose-induced insulin release in RINm5F cells cannot be explained by alterations in hexose transport.


Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells.
In the past decade, considerable progress has been made in the understanding of the biology of rodent oligodendrocyte precursor cells and their role in the generation of oligodendrocytes in the developing and adult rodent CNS. Much less is known about human oligodendrocyte lineage cells and about the reasons for the failure of the regeneration of the oligodendrocyte population during chronic stages of multiple sclerosis (MS). In particular, the fate of the oligodendrocyte precursor population in MS has remained elusive. The present study examined the possibility that oligodendrocyte regeneration ultimately fails because of the local destruction of both oligodendrocytes and their precursor cells. Analysis of chronic stage MS tissue suggested that this is not the case, because all chronic MS lesions studied contained significant numbers of oligodendrocyte precursor cells, identified as process-bearing cells that bound the O4 antibody but not antibodies to GalC and GFAP. The oligodendrocyte precursor cells appeared, however, to be relatively quiescent, because none expressed the nuclear proliferation antigen recognized by the Ki-67 antibody, and because most lesions lacked myelinating oligodendrocytes in their centers. Thus, it appears that the regeneration of the oligodendrocyte population fails during chronic stages of MS because of the inability of oligodendrocyte precursor cells to proliferate and differentiate rather than because of the local destruction of all oligodendrocyte lineage cells. The identification of ways of stimulating the endogenous oligodendrocyte precursor population to expand and generate remyelinating cells may represent an alternative to transplantation of oligodendrocyte lineage cells to promote myelin repair in MS.


Deficiency of the NR4A orphan nuclear receptor NOR1 decreases monocyte adhesion and atherosclerosis.
The orphan nuclear receptor NOR1 is a member of the evolutionary highly conserved and ligand-independent NR4A subfamily of the nuclear hormone receptor superfamily. Members of this subfamily have been characterized as early response genes regulating essential biological processes including inflammation and proliferation; however, the role of NOR1 in atherosclerosis remains unknown. The goal of the present study was to determine the causal contribution of NOR1 to atherosclerosis development and to identify the mechanism by which this nuclear receptor participates in the disease process. In the present study, we demonstrate expression of NOR1 in endothelial cells of human atherosclerotic lesions. In response to inflammatory stimuli, NOR1 expression is rapidly induced in endothelial cells through a nuclear factor kappaB-dependent transactivation of the NOR1 promoter. Overexpression of NOR1 in human endothelial cells increased the expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule-1, whereas NOR1 deficiency altered adhesion molecule expression in response to inflammatory stimuli. Transient transfection experiments and chromatin immunoprecipitation assays revealed that NOR1 induces VCAM-1 promoter activity by binding to a canonical response element for NR4A receptors in the VCAM-1 promoter. Further functional studies confirmed that NOR1 mediates monocyte adhesion by inducing VCAM-1 and intercellular adhesion molecule-1 expression in endothelial cells. Finally, we demonstrate that NOR1 deficiency reduces hypercholesterolemia-induced atherosclerosis formation in apoE(-/-) mice by decreasing the macrophage content of the lesion. In concert, these studies identify a novel pathway underlying monocyte adhesion and establish that NOR1 serves a previously unrecognized atherogenic role in mice by positively regulating monocyte recruitment to the vascular wall.


Lung adenocarcinoma patients of young age have lower EGFR mutation rate and poorer efficacy of EGFR tyrosine kinase inhibitors.
Patients aged ≤50 years are rarely diagnosed with nonsmall cell lung cancer. We conducted a retrospective cohort study to understand the mutation status of EGFR and the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in young Asian patients with lung adenocarcinoma. We collected tumour specimens and malignant pleural effusions from lung adenocarcinoma patients from June 2005 to April 2014, recorded their clinical demographic data, and analysed EGFR mutations by reverse transcriptase PCR. EGFR mutation data were collected from 1039 lung adenocarcinoma patients, including 161 patients aged ≤50 years and 878 patients aged >50 years. Fewer patients aged ≤50 years had EGFR mutations than older patients (p=0.043), but they showed a higher rate of uncommon EGFR mutations (p=0.035). A total of 524 patients with EGFR mutations received EGFR-TKI treatment, including 81 patients aged ≤50 years. Younger patients had a lower response rate than older patients (p=0.038) and had the shortest progression-free survival compared with other predefined age categories (p=0.033). Multivariate analysis of overall survival revealed age ≤50 years as a poor prognostic factor. In conclusion, fewer Asian patients aged ≤50 years had EGFR mutations, but the EGFR mutation types were more uncommon. Age ≤50 years is associated with poorer efficacy of EGFR-TKI treatment.


Nutrient composition, digestible and metabolizable energy content, and prediction of energy for animal protein byproducts in finishing pig diets.
An industry survey and animal experiment were conducted to evaluate compositional variability and DE and ME content of animal protein byproducts and to generate equations to predict DE and ME content based on chemical analysis. For the 220 samples collected, the greatest concentration of CP was observed in blood meal (BM) and the least in meat and bone meal (MBM) and the greatest concentration of ether extract was in meat meal and the least in BM, with ash content greatest in MBM and least in BM, with Ca and P levels being 36.1 and 16.3% of the ash content, respectively. For the balance experiment, a corn-soybean meal basal diet was used with test diets formulated by mixing 80% of the basal diet with 20% of the animal protein byproduct, except for BM, which was included at 10 and 20% of the test diets. Ten groups of 24 gilts (92.5 ± 7.4 kg final BW) were randomly assigned to the test or basal diet within each group, resulting in 16 replications per animal protein byproduct or basal diet, except for BM determinations (20 replications). Gilts were placed in metabolism crates and offered 2.4 kg daily of their assigned diet for 13 d, with total collection of feces and urine during the last 4 d. Gross energy in the diets, feces, and urine was used to calculate the DE and ME content of each ingredient by the difference procedure, using DE and ME of the basal diet as a covariate among groups of pigs. The DE content of the animal protein byproducts ranged from 5,367 to 2,567 kcal DE/kg DM, and ME ranged from 4,783 to 2,340 kcal ME/kg DM. Using all animal protein byproducts, the best-fit equations were as follows: DE (kcal/kg DM) = -2,468 + (1.26 × GE, kcal/kg DM), with of 0.84, SE = 390, and < 0.01, and ME (kcal/kg DM) = -2,331 + (1.15 × GE, kcal/kg DM), with of 0.86, SE = 327, and < 0.01. The apparent total tract digestibility (ATTD) of Ca and P were also determined using the difference procedure, with the average ATTD of Ca and P for the animal protein byproducts, excluding BM and feather meal, being 27.1 and 39.1%, respectively. These data indicate that DE and ME substantially varied among the animal protein byproducts and sources and that a variety of nutritional components can be used to accurately predict DE and ME for finishing pigs. In addition, it appears that high dietary inclusion rates of animal protein byproducts may result in low ATTD estimates of Ca and P, which may be due to excessive concentrations of total Ca and P affecting digestibility.


Immunohistochemical analysis of B-cell lymphoma -2 in pleomorphic adenoma and mucoepidermoid carcinoma.
Salivary gland tumors form a major area in the field of oral pathology. B-cell lymphoma -2 (Bcl-2) is an anti-apoptotic gene with up-regulation in various neoplasms. The aim of the present case-control study was to comparatively investigate the expression of Bcl-2 protein in pleomorphic adenoma (PA) and mucoepidermoid carcinoma (MEC) and assess its potential diagnostic role in differentiating these tumors. A total of 28 cases (18 specimens of PA [control] and 10 blocks of MEC [case]) were selected for analysis by streptavidin-biotin peroxidase method with antibody against Bcl-2. The percentage of positive cells was calculated from a minimum of 1000 neoplastic cells and H-score was identified (% positive cells × intensity of staining). Data were analyzed using two-way ANOVA, t-test, Spearman, Chi-square and Fisher tests (α = 0.05). bcl-2 expression was shown in 13 cases (71%) of PA and 3 cases (30%) of MEC. In addition, four cases of PA showed strong staining. There was a significant difference between the expression intensity of Bcl-2 in the two tumors (P = 0.048) according to ANOVA. No correlation was observed between Bcl-2 expression with the size and location of tumors (P > 0.05). Bcl-2 expression might be used for differentiating these tumors. Bcl-2 protein was overexpressed in PA compared with MEC. Hence, it seems that unlike what was observed in PA, Bcl-2 probably does not participate in the pathogenesis of MEC.


Genetic Variants and Hamstring Injury in Soccer: An Association and Validation Study.
This study aimed to investigate the association of candidate single nucleotide polymorphisms (SNP) with noncontact hamstring muscle injuries in elite soccer players and to create and validate a model to assess the risk of hamstring injury. A total of 107 elite male outfield players were prospectively followed for six seasons. Players were genotyped for 37 SNP previously investigated in relation to musculoskeletal injuries. The association of SNP, previous injury, age, level of play, position, and anthropometric data with 129 hamstring injuries (413 observations) was investigated in the discovery phase (2010-2015), and a multivariable Cox frailty model was created using forward selection. The model's discriminative ability was tested in the validation phase (2015-2016, 31 injuries, 98 observations) using Harrell's C index. Five SNP were found to be significantly associated with hamstring injury in a multivariable model: matrix metalloproteinase 3 rs679620 (A vs G, hazard ratio [HR] = 2.06, 95% confidence interval [CI] = 1.51-2.81), tenascin C rs2104772 (A vs T, HR = 1.65, 95% CI = 1.17-2.32), interleukin 6 rs1800795 (GG vs GC + CC, HR = 1.68, 95% CI = 1.11-2.53), nitric oxide synthase 3 rs1799983 (G vs T, HR = 1.35, 95% CI = 1.01-1.79), and hypoxia-inducible factor-1α rs11549465 (CC vs CT, HR = 2.08, 95% CI = 1.00-4.29). Age also entered the model (≥24 vs <24 yr, HR = 2.10, 95% CI = 1.29-3.42). The model showed acceptable discrimination in the discovery phase (C index = 0.74), but not in the validation phase (C index = 0.52). Genetic variants appear to be involved in the etiology of hamstring injuries but were not found to have predictive value by themselves. Further research, increasing the number of genetic variants and including environmental factors in complex multifactorial risk models, is necessary.


Differences in the salivary effects of wild-caught versus colonized Phlebotomus papatasi (Diptera: Psychodidae) on the development of zoonotic cutaneous leishmaniasis in BALB/c mice.
Preimmunization of mice with salivary gland homogenate (SGH) of long-term colonized (F29) female Phlebotomus papatasi Scopoli (Diptera: Psychodidae) induced protection against Leishmania major Yakimoff & Schokhor (Kinetoplastida: Trypanosomatidae) co-inoculated with the same type of SGH. In contrast, preimmunization of mice with SGH of wild-caught female P. papatasi did not confer protection against L. major co-inoculated with the same type of SGH. Similarly, SGH from recently colonized (F1) female P. papatasi did not protect mice against L. major. These results suggest that when developing a sand fly saliva-based vaccine, the natural vector populations should be considered.


Risk of thromboembolic complications after intracerebral hemorrhage according to ethnicity.
Incidence of thromboembolic (TE) disease varies with race and ethnicity yet little is known about whether these differences also apply to the poststroke period. We review the literature and compare published data with observations from two recent global trials on intracerebral hemorrhage (ICH). A systematic review of the literature in EMBASE/Medline identified relevant articles. Published data were compared to the TE events--myocardial infarction (MI), cerebral infarction (CI), deep venous thrombosis (DVT), and pulmonary embolism (PE)--observed among placebo patients in two trials investigating the efficacy and safety of recombinant factor VIIa (rFVIIa) (Novo Nordisk A/S, Denmark) in the treatment of spontaneous ICH. The relative risk of TE complications after ICH was estimated for blacks/African Americans and Asians after adjustment for relevant risk factors. Only four relevant studies on TE disease after stroke were identified with data limited to poststroke MI and CI in a mixture of ischemic stroke and ICH patient populations. In the literature, blacks/African Americans appear to have a lower incidence rate of cardiac and cerebro-vascular complications after stroke, and Asians have a higher incidence rate of recurrent strokes, compared with Caucasians. In the two global trials, the overall poststroke incidence rates of MI, CI, DVT, and PE at 3 months after ICH onset were 2.3%, 2.0%, 3.7%, and 1.1%, respectively. After adjustment for differences in baseline risk factors, blacks/African Americans had a significantly higher risk of developing DVT compared with Caucasians (OR=5.64, P=0.0334), while Asians had a strong trend toward a higher risk of DVT (odds ratio=3.22, P=0.0932). The adjusted relative risk of PE, CI, and MI was not significantly different across ethnicities. This is the first study to specifically examine the risk of TE complications in the post-ICH period according to ethnicity. In a limited ICH population, we observed a significantly higher risk of DVT in blacks/African Americans compared with Caucasians after adjustment for differences in risk factors. We observed nonsignificant trends toward differences in the relative risk of MI, CI, or PE across ethnicities.


Oleuropein prevents the development of experimental autoimmune myocarditis in rats.
Oleuropein (OLE) is a natural secoiridoid that is derived from Olea europaea. OLE possesses cardioprotective effects in experimental models of hypertension, myocardial infarction, atherosclerosis and hyperlipidaemia. In the present study, the effects of OLE on experimental autoimmune myocarditis (EAM) were evaluated. EAM in rats were induced by subcutaneous injections of porcine cardiac myosin. Cardiac function parameters, myocardial pathology, myocardial inflammatory cell infiltration and nuclear factor kappa-B (NF-κB) expression were measured. Our data showed that the postmyocarditis rats exhibited increased left ventricular end systolic diameters, left ventricular end diastolic diameters, left ventricular end-diastolic pressures (LVEDP), and decreased ejection fractions. However, OLE significantly suppressed these changes in EAM rats. Histological analysis revealed that myosin induced miliary foci of discolouration on endocardial surfaces and extensive myocardial injuries with inflammatory cell infiltration were significantly improved by OLE therapy. A definitive positive correlation between the histological scores and LVEDP was observed. Moreover, OLE inhibited CD4+, CD8+ cells and macrophage infiltration in myocardium and decreased the serum production of tumour necrosis factor-a (TNF-a), interleukin-1β (IL-1β) and IL-6 in EAM rats. Expectedly, the myocardial levels of NF-κB p65, p-IκBa, IKKa were significantly attenuated by OLE, indicating the inhibitory effects of OLE on the NF-κB pathway. Furthermore, OLE decreased the myocardial expressions of phosphorylated-p38 MAPK, phosphorylated-ERK, and did not change the levels of p38 MAPK and ERK in EAM rats. Collectively, our results suggest that OLE effectively prevents the development of myocarditis, at least in part, by inhibiting the MAPKs and NF-κB mediated inflammatory responses.


Characterization of specific V1a vasopressin-binding sites on a rat mammary-tumour-cell line.
WRK 1, a cloned cell line derived from a rat mammary tumour, carries specific vasopressin-binding sites. Specific binding of 2-tyrosine-3H-labelled [8-lysine]vasopressin ([3H]vasopressin) was time-dependent, saturable and reversible. Scatchard-plot analysis of hormone binding indicated the presence of a single class of receptors with an equilibrium dissociation constant of 12.7 +/- 0.2 nM. The maximal binding capacity was 75 +/- 6 fmol/10(6) cells, which corresponds to approx. 45,000 sites per cell. Oxytocin and a highly potent oxytocin analogue were able to inhibit completely [3H]vasopressin binding, but, in this respect, they were far less potent than vasopressin. This clearly demonstrates the vasopressinergic nature of this receptor. Pharmacological studies using a series of 14 vasopressin or oxytocin analogues indicated that the ligand selectivity of the vasopressin receptor found on WRK 1 cells resembles that of the rat hepatocyte. This signifies that this vasopressin receptor is of the V1a subtype. This conclusion was confirmed by the observation that vasopressin did not influence the production of intracellular cyclic AMP in WRK 1 cells.


Infection of Chick Chorioallantoic Membrane (CAM) as a Model for the Pathogenesis of Cryptococcus gattii.
The use of embryonated egg as an alternative in the study of the pathogenesis of fungi is evolving. Although murine models are the "gold standard," embryonated egg models are also used to screen determinants of virulence among fungi species. This study was aimed at determining the virulence potential of Cryptococcus gattii strains R265, R272, and EJB18, and Malassezia sympodialis using chorioallantoic membrane (CAM) of embryonated egg. At a concentration of 107 cfu/ml, C. gattii R272 was more virulent than R265 in the egg model, while EJB18 had low virulence. The CAM model supported the growth of Malassezia sympodialis strain and induced the formation of hyphae. The formation of lesions by the organism and its re-isolation from CAM suggest that the model can be used for evaluating the virulence of C. gattii. Histopathology of CAM from both strains also revealed massive disruption of CAM. This study suggests that embryonated egg is a useful alternative tool to pre-screen Cryptococcus gattii strains to select strains for subsequent testing in murine models and could also be a potential medium for studying the hyphal growth in Malassezia species.


Nanomechanical biomarkers of single circulating tumor cells for detection of castration resistant prostate cancer.
Emerging evidence shows that nanomechanical phenotypes of circulating tumor cells (CTC) could become potential biomarkers for metastatic castration resistant prostate cancer (mCRPC). To determine the nanomechanical phenotypes of CTCs we applied atomic force microscopy (AFM) employing the PeakForce quantitative nanomechanical (QNM) imaging. We assessed biophysical parameters (elasticity, deformation, and adhesion) of 130 CTCs isolated from blood samples from five castration sensitive (CS) and 12 castration resistant prostate cancer (CRPCa) patients. We found that CTCs from CRPCa patients are three times softer, three times more deformable, and seven times more adhesive than counterparts from CSPCa patients. Both nonsupervised hierarchical clustering and principle component analysis show that three combined nanomechanical parameters could constitute a valuable set to distinguish between CSPCa and CRPCa. [corrected] Our study indicates that nanomechanical phenotypes of CTCs may serve as novel and effective biomarkers for mCRPC.


Effect of vitamin D3 supplementation on HIV-infected adults: a systematic reviewVitamin Dӡ Supplementation on HIV-Infected Adults: A Systematic Review.
Introduction: much evidence confirms that vitamin D may be associated with an improvement in CD4 cell counts in HIV-infected individuals, where antiretroviral therapy (ART) is used and associated with decreased 25(OH)D levels. Objective: to carry out a systematic review on the effect of vitamin D supplementation on HIV-infected adult patients. Methods: the research was conducted in the databases Science Direct, PubMed, BVS, Scielo Cochrane and Periods, from February to April 2018, with publication limit from 2000 to 2018, without restriction of gender, ethnicity and involving individuals with age older than 18 years. To evaluate the quality of the studies, we used the protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Jadad scale. Results: the search initially resulted in 198 articles. After the selection process 5 articles were identified as eligible, where they highlight that vitamin D supplementation may be an associated and effective intervention to reduce hypovitaminosis. ART reduces vitamin D3 levels and changes its metabolism, being associated with the risk of mortality. However, adequate levels of 25(OH)D are positively associated with the number of CD4 + cells and the reduction of infection levels. Conclusion: vitamin D supplementation promotes immune recovery. However, the cases analysed were few, insufficient to fully confirm the benefits and recommend supplementation. Therefore, intervention studies are needed to elucidate the role of vitamin D in human protection against HIV infections.


Characterization of mutations contributing to sulfathiazole resistance in Escherichia coli.
A sulfathiazole-resistant dihydropteroate synthase (DHPS) present in two different laboratory strains of Escherichia coli repeatedly selected for sulfathiazole resistance was mapped to folP by P1 transduction. The folP mutation in each of the strains was shown to be identical by nucleotide sequence analysis. A single C-->T transition resulted in a Pro-->Ser substitution at amino acid position 64. Replacement of the mutant folP alleles with wild-type folP significantly reduced the level of resistance to sulfathiazole but did not abolish it, indicating the presence of an additional mutation(s) that contributes to sulfathiazole resistance in the two strains. Transfer of the mutant folP allele to a wild-type background resulted in a strain with only a low level of resistance to sulfathiazole, suggesting that the presence of the resistant DHPS was not in itself sufficient to account for the overall sulfathiazole resistance in these strains of E. coli. Additional characterization of an amplified secondary resistance determinant, sur, present in one of the strains, identified it as the previously identified bicyclomycin resistance determinant bcr, a member of a family of membrane-bound multidrug resistance antiporters. An additional mutation contributing to sulfathiazole resistance, sux, has also been identified and has been shown to affect the histidine response to adenine sensitivity displayed by these purU strains.


ZNF91 deletion in human embryonic stem cells leads to ectopic activation of SVA retrotransposons and up-regulation of KRAB zinc finger gene clusters.
Transposable element (TE) invasions have shaped vertebrate genomes over the course of evolution. They have contributed an extra layer of species-specific gene regulation by providing novel transcription factor binding sites. In humans, SINE-VNTR-Alu (SVA) elements are one of three still active TE families; approximately 2800 SVA insertions exist in the human genome, half of which are human-specific. TEs are often silenced by KRAB zinc finger (KZNF) proteins recruiting corepressor proteins that establish a repressive chromatin state. A number of KZNFs have been reported to bind SVAs, but their individual contribution to repressing SVAs and their roles in suppressing SVA-mediated gene-regulatory effects remains elusive. We analyzed the genome-wide binding profile for ZNF91 in human cells and found that ZNF91 interacts with the VNTR region of SVAs. Through CRISPR-Cas9-mediated deletion of ZNF91 in human embryonic stem cells, we established that loss of ZNF91 results in increased transcriptional activity of SVAs. In contrast, SVA activation was not observed upon genetic deletion of the ZNF611 gene encoding another strong SVA interactor. Epigenetic profiling confirmed the loss of SVA repression in the absence of ZNF91 and revealed that mainly evolutionary young SVAs gain gene activation-associated epigenetic modifications. Genes close to activated SVAs showed a mild up-regulation, indicating SVAs adopt properties of cis-regulatory elements in the absence of repression. Notably, genome-wide derepression of SVAs elicited the communal up-regulation of KZNFs that reside in KZNF clusters. This phenomenon may provide new insights into the potential mechanisms used by the host genome to sense and counteract TE invasions.


[Mathematical simulation support to the dosimetric monitoring on the Russian segment of the International Space Station].
To ensure radiation safety of cosmonauts, it is necessary not only to predict, but also to reconstruct absorbed dose dynamics with the knowledge of how long cosmonauts stay in specific space vehicle compartments with different shielding properties and lacking equipment for dosimetric monitoring. In this situation, calculating is one and only way to make a correct estimate of radiation exposure of cosmonaut's organism as a whole (tissue-average dose) and of separate systems and organs. The paper addresses the issues of mathematical simulation of epy radiation environment of standard dosimetric instruments in the Russian segments of the International Space Station (ISS RS). Results of comparing the simulation and experimental data for the complement of dosimeters including ionization chamber-based radiometer R-16, DB8 dosimeters composed of semiconductor detectors, and Pille dosimeters composed of thermoluminescent detectors evidence that the current methods of simulation in support of the ISS RS radiation monitoring provide a sufficiently good agreement between the calculated and experimental data.


Functional cooperation of metabotropic adenosine and glutamate receptors regulates postsynaptic plasticity in the cerebellum.
G-protein-coupled receptors (GPCRs) may form heteromeric complexes and cooperatively mediate cellular responses. Although heteromeric GPCR complexes are suggested to occur in many neurons, their contribution to neuronal function remains unclear. We address this question using two GPCRs expressed in cerebellar Purkinje cells: adenosine A1 receptor (A1R), which regulates neurotransmitter release and neuronal excitability in central neurons, and type-1 metabotropic glutamate receptor (mGluR1), which mediates cerebellar long-term depression, a form of synaptic plasticity crucial for cerebellar motor learning. We examined interaction between these GPCRs by immunocytochemical, biochemical, and Förster resonance energy transfer analyses in cultured mouse Purkinje cells and heterologous expression cells. These analyses revealed that the GPCRs closely colocalized and formed heteromeric complexes on the cell surfaces. Furthermore, our electrophysiological analysis showed that CSF levels (40-400 nm) of adenosine or synthetic A1R agonists with comparable potencies blocked mGluR1-mediated long-term depression of the postsynaptic glutamate-responsiveness (glu-LTD) of cultured Purkinje cells. A similar dose of the A1R agonist decreased the ligand affinity of mGluR1 and did not affect depolarization-induced Ca(2+) influx, which is an essential factor in inducing glu-LTD. The A1R agonist did not affect glu-LTD mimicked by direct activation of protein kinase C. These results suggest that A1R blocked glu-LTD by decreasing the ligand sensitivity of mGluR1, but not the coupling efficacy from mGluR1 to the intracellular signaling cascades. These findings provide a new insight into neuronal GPCR signaling and demonstrate a novel regulatory mechanism of synaptic plasticity.


Ginkgo biloba extract reverses CCl4-induced liver fibrosis in rats.
To study the reversing effect of Ginkgo biloba extract (GbE) on established liver fibrosis in rats. Following confirmation of CCl(4)-induced liver fibrosis, GbE or saline was administrated to the rats for 4 weeks. The remaining rats received neither CCl(4) nor GbE as normal control. The four groups were compared in terms of serum enzymes, tissue damage, expression of alphaSMA and tissue inhibitor-1 of metalloproteinase (TIMP-1) and metalloproteinase-1 (MMP-1). Compared with saline-treated group, liver fibrosis rats treated with GbE had decreased serum total bilirubin (P<0.01) and aminotransferase levels (P<0.01) and increased levels of serum albumin (P<0.01). Microscopic studies revealed that the livers of rats receiving GbE showed alleviation in fibrosis (P<0.05) as well as expression of alphaSMA (P<0.01). The liver collagen and reticulum contents were lower in rats treated with GbE than saline-treated group (P<0.01). RT-PCR revealed that the level of TIMP-1 decreased while the level of MMP-1 increased in GbE group. Administration of GbE improved CCl(4)-induced liver fibrosis. It is possibly attributed to its effect of inhibiting the expression of TIMP-1 and promoting the apoptosis of hepatic stellate cells.


Sulfate-dependant microbially induced corrosion of mild steel in the deep sea: a 10-year microbiome study.
Metal corrosion in seawater has been extensively studied in surface and shallow waters. However, infrastructure is increasingly being installed in deep-sea environments, where extremes of temperature, salinity, and high hydrostatic pressure increase the costs and logistical challenges associated with monitoring corrosion. Moreover, there is currently only a rudimentary understanding of the role of microbially induced corrosion, which has rarely been studied in the deep-sea. We report here an integrative study of the biofilms growing on the surface of corroding mooring chain links that had been deployed for 10 years at ~2 km depth and developed a model of microbially induced corrosion based on flux-balance analysis. We used optical emission spectrometry to analyze the chemical composition of the mooring chain and energy-dispersive X-ray spectrometry coupled with scanning electron microscopy to identify corrosion products and ultrastructural features. The taxonomic structure of the microbiome was determined using shotgun metagenomics and was confirmed by 16S amplicon analysis and quantitative PCR of the dsrB gene. The functional capacity was further analyzed by generating binned, genomic assemblies and performing flux-balance analysis on the metabolism of the dominant taxa. The surface of the chain links showed intensive and localized corrosion with structural features typical of microbially induced corrosion. The microbiome on the links differed considerably from that of the surrounding sediment, suggesting selection for specific metal-corroding biofilms dominated by sulfur-cycling bacteria. The core metabolism of the microbiome was reconstructed to generate a mechanistic model that combines biotic and abiotic corrosion. Based on this metabolic model, we propose that sulfate reduction and sulfur disproportionation might play key roles in deep-sea corrosion. The corrosion rate observed was higher than what could be expected from abiotic corrosion mechanisms under these environmental conditions. High corrosion rate and the form of corrosion (deep pitting) suggest that the corrosion of the chain links was driven by both abiotic and biotic processes. We posit that the corrosion is driven by deep-sea sulfur-cycling microorganisms which may gain energy by accelerating the reaction between metallic iron and elemental sulfur. The results of this field study provide important new insights on the ecophysiology of the corrosion process in the deep sea.


The miR-96 and RARγ signaling axis governs androgen signaling and prostate cancer progression.
Expression levels of retinoic acid receptor gamma (NR1B3/RARG, encodes RARγ) are commonly reduced in prostate cancer (PCa). Therefore, we sought to establish the cellular and gene regulatory consequences of reduced RARγ expression, and determine RARγ regulatory mechanisms. RARG shRNA approaches in non-malignant (RWPE-1 and HPr1-AR) and malignant (LNCaP) prostate models revealed that reducing RARγ levels, rather than adding exogenous retinoid ligand, had the greatest impact on prostate cell viability and gene expression. ChIP-Seq defined the RARγ cistrome, which was significantly enriched at active enhancers associated with AR binding sites. Reflecting a significant genomic role for RARγ to regulate androgen signaling, RARγ knockdown in HPr1-AR cells significantly regulated the magnitude of the AR transcriptome. RARγ downregulation was explained by increased miR-96 in PCa cell and mouse models, and TCGA PCa cohorts. Biochemical approaches confirmed that miR-96 directly regulated RARγ expression and function. Capture of the miR-96 targetome by biotin-miR-96 identified that RARγ and a number of RARγ interacting co-factors including TACC1 were all targeted by miR-96, and expression of these genes were prominently altered, positively and negatively, in the TCGA-PRAD cohort. Differential gene expression analyses between tumors in the TCGA-PRAD cohort with lower quartile expression levels of RARG and TACC1 and upper quartile miR-96, compared to the reverse, identified a gene network including several RARγ target genes (e.g., SOX15) that significantly associated with worse disease-free survival (hazard ratio 2.23, 95% CI 1.58 to 2.88, p = 0.015). In summary, miR-96 targets a RARγ network to govern AR signaling, PCa progression and disease outcome.


Epidermal growth factors enhances viral transformation of granulosa cells.
Kirsten sarcoma virus produced a low incidence of transient morphological transformation in primary cultures of rat ovarian granulosa cells. In the presence of epidermal growth factor, the incidence of transient transformation increased severalfold and two continuous cell lines were established. Epidermal growth factor, a naturally occurring polypeptide hormone, appears to act here as a tumor promoter in the retrovirus-induced transformation of a mesodermally derived epithelium.


Controversies in complex percutaneous coronary intervention: radial versus femoral.
Evolution in the technology used in the cardiac catheterization laboratory has permitted a migration from the femoral to radial artery access for many interventional procedures while concurrently improving outcomes. As a disruptive technology, transradial access has been associated with several controversies including a dichotomous relationship with femoral access. Areas covered: Several different patient subsets along with perceived technical challenges in interventional cardiology are reviewed with regard to the issue of access site. Evolving technological improvements germane to transradial techniques are also discussed as garnered from the literature of recent clinical trials and reports. Expert commentary: Radial techniques have been enhanced by newer technology and the spread of knowledge. Fusion of radial techniques with those of the femoral approach is evolving into a unifying concept of using the access that is most appropriate for the patient. No one access technique can cover all clinical subsets of patients. There is a need for complimentary access skillsets for even the most advanced cardiovascular technology used in the cardiac catheterization laboratory if the patients' outcomes are to be idealized.


[Functional anatomy of the pelvic floor].
The pelvic floor is the support of the pelvic viscera. The levator ani muscle (LA) with its two bundles (pubo- and iliococcygeus) is the major component of this pelvic floor. LA is formed essentially by type I fibers (slow twitch, with high oxidative capability and presence of slow myosin) as in postural muscles. The aerobic metabolism makes LA fragile to excentric contraction and to mitochondrial dysfunction. The innervation of the pelvic floor comes from the 2nd, 3rd, 4th anterior sacral roots; denervation affects pelvic dynamism. Perineum includes the musculofascial structures under the LA: ventrally the striated sphincter of urethra and the ischiocavernosus and bulbospongiosus, caudally the fatty tissue filling the ischioanal fossa. Pelvic fascia covers the muscles ; it presents reinforcements : the uterosacral and cardinal ligaments, the arcus tendineus fascia pelvis (ATFP) and the arcus tendineus levator ani (ATLA). The pelvis statics is supported by the combined action of all this anatomical structures anteriorly forming the perineal "hammock," medially the uterosacral and cardinal ligaments, posteriorly the rectovaginal fascia and the perineal body. The angles formed by the pelvic viscera with their evacuation ducts participate to the pelvic statics. During the pelvic dynamics the modification of these angles expresses the action of the musculofascial structures.


[Sleep disorders in psychiatry and their treatment].
Sleep disturbances are frequent and multifaceted and have serious consequences. They play an important role within psychiatric symptoms and disorders. On the one hand they may appear as a symptom of a disorder, which may also be a diagnostic criterion, as for example in affective disorders, on the other hand they may be independent disorders or last but not least sequelae of psychiatric disorders or their pharmacological therapy, as with antidepressants or neuroleptics, which may cause or deteriorate nocturnal movement disorders. They may aggravate psychiatric disorders, perpetuate them or predict a disease onset, like in depressive or manic episodes. Also in organic sleep disorders, such as sleep-related breathing disorders or nocturnal movement disorders, increased anxiety or depression scores may be observed. Patients suffering from sleep disorders do not only experience impaired well-being, but also show deteriorations in cognition and performance, have a higher risk of accidents, are generally more prone to health problems, have a higher sickness absence rate, seek medical help more often and thus are also an important socioeconomic factor. This is why sleep disorders should be taken seriously and treated adequately.


Therapeutic radiation for lymphoma: risk of malignant mesothelioma.
Ionizing radiation has been used since the 1950s to treat a variety of cancers. Cancer patients who are treated with radiotherapy have shown increased risks for a variety of second malignancies, including mesothelioma, in several recent reports. The only existing study of Hodgkin lymphoma (HL) and subsequent mesothelioma had a short observation period. The authors used Surveillance, Epidemiology, and End Results data over a 30-year period to identify patients with HL and non-Hodgkin lymphoma (NHL) who also were diagnosed with mesothelioma. Standardized incidence ratios (SIR) and absolute excess risks were calculated by sex and treatment modality for both types of lymphoma. Twenty-six patients were identified who had mesothelioma as second primaries based on 21,881 diagnoses of HL and 101,001 diagnoses of NHL. There was a statistically significant increase in mesothelioma (4 diagnoses; SIR, 6.59; 95% confidence interval [95% CI], 1.79-16.87) among men with HL who received radiation, but no women survivors were identified who had a diagnosis of mesothelioma. For NHL survivors, there was a nonsignificant excess of mesothelioma among men (SIR, 1.91; 95% CI, 0.77-3.93) and women (SIR, 3.75; 95% CI, 0.77-10.95) who had received radiation treatment. There were no increases among patients who were unirradiated. Mesothelioma rates for patients who had received radiotherapy were increased for survivors of HL and NHL. No increases were observed among the unirradiated. These findings and the existing body of supporting studies confirmed that radiotherapy is a cause of mesothelioma.


Effect of verb network strengthening treatment in moderate-to-severe aphasia.
This Phase II treatment study examined the effect of Verb Network Strengthening Treatment (VNeST) on individuals with moderate-to-severe aphasia. Research questions addressed (a) pre- to posttreatment changes and pretreatment to treatment phase changes on probe sentences containing trained verbs (e.g., "The carpenter is measuring the stairs") and semantically related untrained verbs (e.g., "The nurse is weighing the baby"); (b) lexical retrieval changes in single-word naming, sentence, and discourse measures; (c) functional communication by way of proxy and participant report; and (d) error evolution. A multiple-baseline approach across participants was used. Effect sizes were calculated for pre- and posttreatment and maintenance probe responses. A C statistic was used to determine changes from the baseline to treatment phases. One participant exhibited improvement on all generalization measures, whereas the other participant exhibited more limited generalization. Both participants showed improvement on the functional communication measure. As predicted, the participants did not show the same extent of improvement that was observed in participants with more moderate aphasia (Edmonds, Nadeu, & Kiran, 2009). Nonetheless, the findings suggest that VNeST may be appropriate for persons with moderate-to-severe aphasia, especially with a small adaptation to the treatment protocol that will be retained for future iterations of VNeST.


Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients.
Myalgic encephalomyelitis chronic fatigue syndrome (ME/CFS) is a common debilitating disorder associated with an intense fatigue, a reduced physical activity, and an impaired quality of life. There are no established biological markerof the syndrome. The etiology is unknown and its pathogenesis appears to be multifactorial. Various stressors, including intense physical activity, severe infection, and emotional stress are reported in the medical history of ME/CFS patients which raises the question whether any physiological and biological abnormalities usually found in these patients could be indicative of the etiology and/or the quality-of-life impairment. Thirty-six patients and 11 age-matched healthy controls were recruited. The following variables that appear to address common symptoms of ME/CFS were studied here: (1) muscle fatigue during exercise has been investigated by monitoring the compound muscle action potential (M-wave); (2) the excessive oxidative stress response to exercise was measured via two plasma markers (thiobarbituric acid reactive substances: TBARS; reduced ascorbic-acid: RAA); (3) a potential inflammatory component was addressed via expression of CD26 on peripheral blood mononuclear cells; (4) quality-of-life impairment was assessed using the London Handicap Scale (LHS) and the Medical Outcome Study Short Form-36 (SF-36). The medical history of each patient, including the presence of stressors such as intense sports practice, severe acute infection and/or severe emotional stress was documented. We observed that: (1) there were striking differences between cases and controls with regard to three biological variables: post-exercise M-wave, TBARS variations and CD26-expression at rest; (2) each of these three variables correlated with the other two; (3) abnormalities in the biomarkers associated with health-related quality of life: the LHS score was negatively correlated with the exercise-induced TBARS increase and positively correlated with CD26-expression while the pain component of SF-36 was negatively correlated with CD26-expression; (4) the TBARS increase and the M-wave decrease were the highest, and the CD26-expression level the lowest in patients who had been submitted to infectious stressors. In ME/CFS patients, severe alterations of the muscle excitability, the redox status, as well as the CD26-expression level are correlated with a marked impairment of the quality-of-life. They are particularly significant when infectious stressors are reported in the medical history.


Generation and Imaging of Magnetoacoustic Waves over Millimeter Distances.
Using hybrid piezoelectric-magnetic systems we have generated large amplitude magnetization waves mediated by magnetoelasticity with up to 25 degrees variation in the magnetization orientation. We present direct imaging and quantification of both standing and propagating acoustomagnetic waves with different wavelengths, over large distances up to several millimeters in a nickel thin film.


Cell cycle-regulated multi-site phosphorylation of Neurogenin 2 coordinates cell cycling with differentiation during neurogenesis.
During development of the central nervous system, the transition from progenitor maintenance to differentiation is directly triggered by a lengthening of the cell cycle that occurs as development progresses. However, the mechanistic basis of this regulation is unknown. The proneural transcription factor Neurogenin 2 (Ngn2) acts as a master regulator of neuronal differentiation. Here, we demonstrate that Ngn2 is phosphorylated on multiple serine-proline sites in response to rising cyclin-dependent kinase (cdk) levels. This multi-site phosphorylation results in quantitative inhibition of the ability of Ngn2 to induce neurogenesis in vivo and in vitro. Mechanistically, multi-site phosphorylation inhibits binding of Ngn2 to E box DNA, and inhibition of DNA binding depends on the number of phosphorylation sites available, quantitatively controlling promoter occupancy in a rheostat-like manner. Neuronal differentiation driven by a mutant of Ngn2 that cannot be phosphorylated by cdks is no longer inhibited by elevated cdk kinase levels. Additionally, phosphomutant Ngn2-driven neuronal differentiation shows a reduced requirement for the presence of cdk inhibitors. From these results, we propose a model whereby multi-site cdk-dependent phosphorylation of Ngn2 interprets cdk levels to control neuronal differentiation in response to cell cycle lengthening during development.


Prediction for the Risk of Multiple Chronic Conditions Among Working Population in the United States With Machine Learning Models.
Objective: Chronic diseases have become the most prevalent and costly health conditions in the healthcare industry, deteriorating the quality of life, adversely affecting the work productivity, and costing astounding medical resources. However, few studies have been conducted on the predictive analysis of multiple chronic conditions (MCC) based on the working population. Results: Seven machine learning algorithms are used to support the decision making of healthcare practitioner on the risk of MCC. The models were developed and validated using checkup data from 451,425 working population collected by the healthcare providers. Our result shows that all proposed models achieved satisfactory performance, with the AUC values ranging from 0.826 to 0.850. Among the seven predictive models, the gradient boosting tree model outperformed other models, achieving an AUC of 0.850. Conclusions: Our risk prediction model shows great promise in automating real-time diagnosis, supporting healthcare practitioners to target high-risk individuals efficiently, and helping healthcare practitioners tailor proactive strategies to prevent the onset or delay the progression of the chronic diseases.


Random plasma glucose values measured in community dental practices: findings from the dental practice-based research network.
This study aimed to examine feasibility of testing and frequency of abnormal plasma glucose among dental patients in The Dental Practice-Based Research Network. Eligible dental patients were > or = 19 years old and had at least 1 American Diabetes Association-defined risk factor for diabetes mellitus or an existing diagnosis of diabetes or pre-diabetes. Random (fasting not required) plasma glucose was measured in standardized fashion using a commercial glucometer. Readings <70 or >300 mg/dl triggered re-testing. Patients with glucose > or = 126 mg/dl were referred for medical follow-up. Of 498 subjects in 28 dental practices, 491 (98%) consented and 418 (85.1%) qualified for testing. Fifty-one patients (12.2%) had diabetes; 24 (5.7%) had pre-diabetes. Glucose ranged from 50 to 465 mg/dl. One-hundred-twenty-nine subjects (31%) had readings outside the normal range; of these, 28 (6.7%) had readings < 80 mg/dl and 101 (24.2%) had readings > or = 126 mg/dl; in 9 patients (7 with diabetes), glucose was > 200 mg/dl. A significant proportion of patients tested had abnormal blood glucose. Routine glucose testing in dental practice of populations at risk or diagnosed with diabetes may be beneficial and community dental practices hold promise as settings for diabetes and pre-diabetes screening and monitoring. Results suggest that implementation of glucose measurement in dental practice may provide important clinical and health information for both patients and practitioners.


Assessment of hindfoot deformity by three-dimensional MRI in infant club foot.
In 12 infants aged under 16 months with unilateral club foot we used MRI in association with multiplanar reconstruction to calculate the volume and principal axes of inertia of the bone and cartilaginous structures of the hindfoot. The volume of these structures in the club foot is about 20% smaller than that in the normal foot. The reduction in volume of the ossification centre of the talus (40%) is greater than that of the calcaneus (20%). The long axes of both the ossification centre and the cartilaginous anlage of the calcaneus are identical in normal and club feet. The long axis of the osseous nucleus of the talus of normal and club feet is medially rotated relative to the cartilaginous anlage, but the angle is greater in club feet (10 degrees v 14 degrees). The cartilaginous structure of the calcaneus is significantly medially rotated in club feet (15 degrees) relative to the bimalleolar axis. The cartilaginous anlage of the talus is medially rotated in both normal and club feet, but with a smaller angle for club feet (28 degrees v 38 degrees). This objective technique of measurement of the deformity may be of value preoperatively.


2014 Oman Heart Association protocol for the management of acute atrial fibrillation.
Although atrial fibrillation (AF) is the most common cardiac arrhythmia, there is variation in practice with regard to the management of acute AF among the hospitals and even within the same hospital in Oman. This variation likely reflects a lack of high-quality evidence. Standard guidelines and textbooks do not offer clear evidence-based direction for physicians to guide the management of acute AF. Particularly controversial is the issue of using rhythm control or rate control. This stimulated Oman Heart Association (OHA) to issue a simplified protocol for the management of acute AF to be applied by the entire cardiac caregivers all over the country. The priorities for acute management of AF include stabilizing the patient's hemodynamic status, symptom control, treatment of the underlying and precipitating cause, and more importantly protecting the brain.


Suicide in circumpolar regions: an introduction and overview.
This extended editorial introduces the Special Issue on Suicide and Resilience in Circumpolar Regions, the results of the knowledge synthesis project by an international research team funded by the Canadian Institutes of Health Research and endorsed by the Arctic Council. It focuses on the extent and magnitude of the problem of suicidal behaviours and thoughts from a circumpolar perspective - the variation across Arctic States and their northern regions, the excess risk among some indigenous groups and their demographic characteristics. Much remains to be learned about the design and implementation of youth-focused intervention programmes, especially in a circumpolar comparative framework.


Degradation of myosin light chain in isolated rat hearts subjected to ischemia-reperfusion injury: a new intracellular target for matrix metalloproteinase-2.
Matrix metalloproteinase-2 (MMP-2) contributes to cardiac dysfunction resulting from ischemia-reperfusion (I/R) injury. MMP-2 not only remodels the extracellular matrix but also acts intracellularly in I/R by degrading troponin I. Whether other intracellular targets exist for MMP-2 during I/R is unknown. Isolated rat hearts were subjected to 20 minutes of ischemia and 30 minutes of reperfusion. The impaired recovery of mechanical function of the heart was attenuated by the MMP inhibitors o-phenanthroline or doxycycline. Quantitative 2D electrophoresis of homogenates of aerobically perfused hearts (control) or those subjected to I/R injury (in the presence or absence of MMP inhibitors) showed 3 low-molecular-weight proteins with levels that were significantly increased upon I/R injury and normalized to control levels by MMP inhibitors. Mass spectrometry analysis identified all 3 proteins as fragments of myosin light chain 1, which possesses theoretical cleavage recognition sequences for MMP-2 and is rapidly degraded by it in vitro. The association of MMP-2 with the thick myofilament in fractions prepared from I/R hearts was observed with immunogold electron microscopy, gelatin zymography for MMP-2 activity, and immunoprecipitation. MMP-2 was found to cleave myosin light chain 1 between tyrosine 189 and glutamine 190 at the C terminus. Our results demonstrate that myosin light chain 1 is another novel substrate for MMP-2 in the cardiomyocyte and that its degradation may contribute to contractile dysfunction resulting from I/R injury to the heart.


Incorporating a hole-transport material into the emissive layer of solid-state light-emitting electrochemical cells to improve device performance.
Solid-state light-emitting electrochemical cells (LECs) based on ionic transition metal complexes (iTMCs) have several advantages such as high efficiency, low operation voltage and simple device structure. To improve the device efficiency of iTMC-based LECs for practical applications, improving the carrier balance to achieve a centered recombination zone would be an important issue. In this work, incorporating a hole-transport material (HTM) into the emissive layer of iTMC-based LECs is shown to improve device performance. When mixed with an HTM (12%), the LECs based on a Ru complex exhibit 1.9× and 1.5× enhancement in peak light output and peak external quantum efficiency (EQE) as compared to neat-film devices. Furthermore, over 2× enhancement in stabilized EQE can be achieved in LECs mixed with an HTM. It is attributed to that a more centered recombination zone in LECs mixed with an HTM is beneficial in reducing exciton quenching in the recombination zone approaching extended doped layers. Estimating the temporal evolution of the recombination zone in the LECs mixed with an HTM by employing the microcavity effect is demonstrated to confirm the physical origin for improved device performance. These results reveal that incorporating of an HTM in the emissive layer of LECs based on an iTMC is a feasible way to improve carrier balance and thus enhance light output and device efficiency.


Changes in HIV testing rates among patients with tuberculosis in a large multiethnic city in the UK.
Screening for HIV in patients with tuberculosis (TB) is essential, as HIV/TB co-infection has an adverse prognosis. We compared HIV testing practices in 2005 and 2008/09 in the Birmingham and Solihull region of the UK and evaluated the trends before and after the implementation of the British HIV Association (BHIVA) HIV testing guidelines (2008). A total of 371 TB patients in 2005 and 407 in 2008/09 were included. Demographics across both cohorts were similar. HIV testing increased from 14% in 2005 to 43% in 2008/09. Patients aged ≥55 years and Asian patients were less likely to be tested in 2005 and those aged ≥35 years in 2008/09. An increased rate of HIV testing was seen in all patient categories in 2008/09 compared with 2005. The odds of being tested was high in black African patients (compared with white ethnicity) in both years and increased among black Africans and African Caribbeans between both time points, albeit with wide confidence intervals (CIs). No significant difference in HIV testing was found in 2008/09 before and after the publication of the BHIVA guidelines. This study underlines the importance of continued efforts to minimize the significant gaps in HIV testing rates in TB services.


The SOD like activity of copper:carnosine, copper:anserine and copper:homocarnosine complexes.
Carnosine, anserine and homocarnosine are natural compounds which are present in high concentrations (2-20 mM) in skeletal muscles and brain of many vertebrates. We have demonstrated in a previous work that these compounds can act as antioxidants, a result of their ability to scavenge peroxyl radicals, singlet oxygen and hydroxyl radicals. Carnosine and its analogues have been shown to be efficient chelating agents for copper and other transition metals. Since human skeletal muscle contains one-third of the total copper in the body (20-47 mmol/kg) and the concentration of carnosine in this tissue is relatively high, the complex of carnosine:copper may be of biological importance. We have studied the ability of the copper:carnosine (and other carnosine derivatives) complexes to act as superoxide dismutase. The results indicate that the complex of copper:carnosine can dismute superoxide radicals released by neutrophils treated with PMA in an analogous mechanism to other amino acids and copper complexes. Copper:anserine failed to dismute superoxide radicals and copper:homocarnosine complex was efficient when the cells were treated with PMA or with histone-opsonized streptococci and cytochalasine B. The possible role of these compounds to act as physiological antioxidants that possess superoxide dismutase activity is discussed.


Use of the vascular closure staple clip applier for microvascular anastomosis in free-flap surgery.
We report our initial experience using the vascular closure staple clip applier (a nonpenetrating titanium clip applied in an interrupted, everting fashion) for microvascular anastomosis in free-flap surgery. In total, 153 anastomoses were performed in 87 free flaps (174 potential anastomoses) using the vascular closure stapler between October of 1997 and June of 1999. In 66 flaps, both the arterial and venous anastomosis were performed with the clip applier, whereas in 21 flaps only the venous anastomosis was performed using the clips. A total of 146 anastomoses were performed in an end-to-end fashion, and seven were performed end-to-side. Of the 87 flaps there were 53 TRAM flaps, seven bilateral TRAM, five latissimus dorsi, four gastrocnemius, three rectus abdominis, two radial forearm fibula, and four Rubens fat-pad flaps. Seventy flaps were used for breast reconstruction, seven flaps for lower limb reconstruction, four flaps for head and neck reconstruction, and six flaps for chest wall/trunk reconstruction. There were no postoperative anastomotic complications of bleeding, thrombosis, or need for revision (100 percent patency rate), with a significantly reduced time for completion of anastomoses. The clip applier is a safe, reliable method for performing microvascular anastomoses, allowing reduced operating time and possible cost savings in free-flap surgery.