Genetic characterization and expression in heterologous hosts of the 3-(3-hydroxyphenyl)propionate catabolic pathway of Escherichia coli K-12.
We report the complete nucleotide sequence of the gene cluster encoding the 3-(3-hydroxyphenyl)propionate (3-HPP) catabolic pathway of Escherichia coli K-12. Sequence analysis revealed the existence of eight genes that map at min 8 of the chromosome, between the lac and hemB regions. Six enzyme-encoding genes account for a flavin-type monooxygenase (mhpA), the extradiol dioxygenase (mhpB), and the meta-cleavage pathway (mhpCDFE). The order of these catabolic genes, with the sole exception of mhpF, parallels that of the enzymatic steps of the pathway. The mhpF gene may encode the terminal acetaldehyde dehydrogenase (acylating) not reported previously in the proposed pathway. Enzymes that catalyze the early reactions of the pathway, MhpA and MhpB, showed the lowest level of sequence similarity to analogous enzymes of other aromatic catabolic pathways. However, the genes mhpCDFE present the same organization and appear to be homologous to the Pseudomonas xyl, dmp, and nah meta-pathway genes, supporting the hypothesis of the modular evolution of catabolic pathways and becoming the first example of this type of catabolic module outside the genus Pseudomonas. Two bacterial interspersed mosaic elements were found downstream of the mhpABCDFE locus and flank a gene, orfT, which encodes a protein related to the superfamily of transmembrane facilitators that might be associated with transport. All of the genes of the 3-HPP cluster are transcribed in the same direction, with the sole exception of mhpR. Inducible expression of the mhp catabolic genes depends upon the presence, in the cis or trans position, of a functional mhpR gene, which suggests that the mhpR gene product is the activator of the 3-HPP biodegradative pathway. The primary structure of MhpR revealed significant similarities to that of members of the IclR subfamily of transcriptional regulators. A 3-HPP catabolic DNA cassette was engineered and shown to be functional not only in enteric bacteria (E. coli and Salmonella typhimurium) but also in Pseudomonas putida and Rhizobium meliloti, thus facilitating its potential application to improve the catabolic abilities of bacterial strains for degradation of aromatic compounds.


Plasma leptin levels in infants of diabetic mothers in fasting and satiety states.
Infants born to diabetic mothers have elevated cord blood leptin levels. The aim of this study was to investigate whether the situation persists at the 2nd postnatal day, taking the fasting and satiety states into account and the influence of fetal exposure to hyperinsulinemia, which are proven important contributing factors to plasma leptin levels. Twenty infants born to mothers with gestational diabetes (Group I) and 20 controls (Group II) were included in the study. Groups were similar for sex and anthropometric measurements. Group I had higher leptin concentrations compared to Group II in fasting and satiety states (p < 0.01). Fasting state leptin levels were significantly lower than seen in satiety in both groups (p < 0.01). There was a positive and significant correlation between leptin concentrations and body mass index of infants. Leptin concentrations were positively correlated with plasma insulin levels in Group I. These findings suggest that plasma leptin levels are high in both fasting and satiety states on the 2nd postnatal day in infants born to mothers with gestational diabetes. The possible mechanism underlying this condition is fetal exposure to hyperinsulinemia due to hyperglycemia. The uniqueness of this report are that fasting and satiety states were taken into account and that the data was collected from the samples taken on the 2nd postnatal day, thus reflecting the exact milieu of the infant excluding the effects of the mother and the placenta.


Neural underpinnings of music: the polyrhythmic brain.
Musical rhythm, consisting of apparently abstract intervals of accented temporal events, has the remarkable ability to move our minds and bodies. Why do certain rhythms make us want to tap our feet, bop our heads or even get up and dance? And how does the brain process rhythmically complex rhythms during our experiences of music? In this chapter, we describe some common forms of rhythmic complexity in music and propose that the theory of predictive coding can explain how rhythm and rhythmic complexity are processed in the brain. We also consider how this theory may reveal why we feel so compelled by rhythmic tension in music. First, musical-theoretical and neuroscientific frameworks of rhythm are presented, in which rhythm perception is conceptualized as an interaction between what is heard ('rhythm') and the brain's anticipatory structuring of music ('the meter'). Second, three different examples of tension between rhythm and meter in music are described: syncopation, polyrhythm and groove. Third, we present the theory of predictive coding of music, which posits a hierarchical organization of brain responses reflecting fundamental, survival-related mechanisms associated with predicting future events. According to this theory, perception and learning is manifested through the brain's Bayesian minimization of the error between the input to the brain and the brain's prior expectations. Fourth, empirical studies of neural and behavioral effects of syncopation, polyrhythm and groove will be reported, and we propose how these studies can be seen as special cases of the predictive coding theory. Finally, we argue that musical rhythm exploits the brain's general principles of anticipation and propose that pleasure from musical rhythm may be a result of such anticipatory mechanisms.


Survival Trends After Surgery for Acute Subdural Hematoma in Adults Over a 20-year Period.
We sought to determine 30-day survival trends and prognostic factors following surgery for acute subdural hematomas (ASDHs) in England and Wales over a 20-year period. ASDHs are still considered the most lethal type of traumatic brain injury. It remains unclear whether the adjusted odds of survival have improved significantly over time. Using the Trauma Audit and Research Network (TARN) database, we analyzed ASDH cases in the adult population (>16 yrs) treated surgically between 1994 and 2013. Two thousand four hundred ninety-eight eligible cases were identified. Univariable and multiple logistic regression analyses were performed, using multiple imputation for missing data. The cohort was 74% male with a median age of 48.9 years. Over half of patients were comatose at presentation (53%). Mechanism of injury was due to a fall (<2 m 34%, >2 m 24%), road traffic collision (25%), and other (17%). Thirty-six per cent of patients presented with polytrauma. Gross survival increased from 59% in 1994 to 1998 to 73% in 2009 to 2013. Under multivariable analysis, variables independently associated with survival were year of injury, Glasgow Coma Scale, Injury Severity Score, age, and pupil reactivity. The time interval from injury to craniotomy and direct admission to a neurosurgical unit were not found to be significant prognostic factors. A significant improvement in survival over the last 20 years was observed after controlling for multiple prognostic factors. Prospective trials and cohort studies are expected to elucidate the distribution of functional outcome in survivors.


Aesthetics of the Nasal Dorsum: Proportions, Light, and Shadow.
Due to its central location, the nose plays a prominent role in facial aesthetics. As tastes have shifted and techniques have advanced, the accepted "ideal" appearance and proportions of the nose have evolved over time. By assessing the aesthetics of the nasal dorsum through the use of lines and angles, one can more precisely elucidate a goal for the patient's postoperative nasal shape, which should, in turn, guide the surgeon to execute specific operative maneuvers needed to achieve that contour. In assessing the aesthetics of the nasal dorsum, practitioners calculate and observe aspects such as the paired dorsal aesthetic lines, the nasofrontal angle, and the nasofacial angle. There is also additional consideration given to nasal tip position as this must fit harmoniously with the shape of the dorsum. In contrast to the established aesthetic lines and angles, using nasal geometric polygons for the aesthetic evaluation and development of operative goals in rhinoplasty has recently been described in the literature. Constructed ideals, in the form of proportions, lines, and angles, should be used with caution, as there are many factors to consider in the aesthetic analysis of the nasal dorsum, including ethnic differences, and subjective and changing views of beauty.


Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo.
During platelet activation, phosphoinositide 3-kinases (PI3Ks) produce lipid second messengers participating in the regulation of functional responses. Here, we generated a megakaryocyte-restricted p110beta null mouse model and demonstrated a critical role of PI3Kbeta in platelet activation via an immunoreceptor tyrosine-based activation motif, the glyco-protein VI-Fc receptor gamma-chain complex, and its contribution in response to G-protein-coupled receptors. Interestingly, the production of phosphatidylinositol 3,4,5-trisphosphate and the activation of protein kinase B/Akt were strongly inhibited in p110beta null platelets stimulated either via immunoreceptor tyrosine-based activation motif or G-protein-coupled receptors. Functional studies showed an important delay in fibrin clot retraction and an almost complete inability of these platelets to adhere onto fibrinogen under flow condition, suggesting that PI3Kbeta is also acting downstream of alpha(IIb)beta(3). In vivo studies showed that these mice have a normal bleeding time and are not protected from acute pulmonary thromboembolism but are resistant to thrombosis after FeCl(3) injury of the carotid, suggesting that PI3Kbeta is a potential target for antithrombotic drugs.


Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam.
Observational evidence suggests that infection with helminths protects against allergic disease and allergen skin sensitization. It is postulated that such effects are mediated by helminth-induced cytokine responses, in particular IL-10. We tested this hypothesis in a rural area of central Vietnam where hookworm infection is endemic. One thousand five hundred and sixty-six schoolchildren aged 6-17 were randomly allocated to receive either anti-helminthic therapy or a placebo at 0, 3, 6, and 9 months. We compared changes in the prevalence of exercise-induced bronchoconstriction, allergen skin sensitization, flexural eczema on skin examination, questionnaire-reported allergic disease (wheeze and rhinitis symptoms), and immunological parameters (hookworm-induced IFN-gamma, IL-5, IL-10) between 0 and 12 months. One thousand four hundred and eighty-seven children (95% of these randomized) completed the study. The most common helminth infections were hookworm (65%) and Ascaris lumbricoides (7%). There was no effect of the therapy on the primary outcome, exercise-induced bronchoconstriction (within-participant mean percent fall in peak flow from baseline after anti-helminthic treatment 2.25 (SD 7.3) vs. placebo 2.19 (SD 7.8, P=0.9), or on the prevalence of questionnaire-reported wheeze [adjusted odds ratio (OR)=1.16, 95% confidence interval (CI) 0.35-3.82, P=0.8] and rhinitis (adjusted OR=1.39, 0.89-2.15, P=0.1), or flexural dermatitis on skin examination (adjusted OR=1.15, 0.39-3.45, P=0.8). However, anti-helminthic therapy was associated with a significantly higher allergen skin sensitization risk (adjusted OR=1.31, 1.02-1.67, P=0.03). This effect was particularly strong for children infected with A. lumbricoides at baseline (adjusted OR=4.90, 1.48-16.19, P=0.009). Allergen skin sensitization was inversely related to hookworm-specific IL-10 at baseline (adjusted OR=0.76, 0.59-0.99, P=0.04). No cytokine tested, including IL-10, changed significantly after the anti-helminthic therapy compared with the placebo. A significant reduction in worm burden over a 12-month period in helminth-infected children increases the risk of allergen skin sensitization but not of clinical allergic disease. The effect on skin sensitization could not be fully explained by any of the immunological parameters tested.


Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction.
Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress with increased cMyBP-C dephosphorylation, degradation, and the specific release of N'-fragments. Next, to define the proteolytic pattern of cMyBP-C post-MI, the left anterior descending coronary artery was ligated in adult male rats. Degradation of cMyBP-C was confirmed by a reduction in total cMyBP-C and the presence of degradation products in the infarct tissue. Phosphorylation levels of cMyBP-C were greatly reduced in ischemic areas of the MI heart compared to non-ischemic regions and sham control hearts. Post-MI plasma samples from these rats, as well as humans, were assayed for cMyBP-C and its fragments by sandwich ELISA and immunoprecipitation analyses. Results showed significantly elevated levels of cMyBP-C in the plasma of all post-MI samples. Overall, this study suggests that cMyBP-C is an easily releasable myofilament protein that is dephosphorylated, degraded and released into the circulation post-MI. The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease.


Do middle school students really have fixed images of elders?
The purpose of this study was to determine whether combinations of characteristics, abstracted from drawings of elders made by middle school students, grouped together to form cohesive perceptions, or stereotypes, of human aging. We abstracted 49 characteristics from drawings of elders made by 1,944 students at two middle schools in San Antonio, Texas, at the beginning of the 1998-1999 school year. Correlational and factor analyses were used to determine if there was an underlying structure or grouping to the characteristics. Logistic regression was used to determine the variables associated with the investigators' classification of the images as positive, neutral, or negative. The standardized alpha coefficient for the 49 variables was low (alpha = 0.37). The Spearman rho correlations between the variables were also low, with 90.2% of the 1,176 comparisons being < 0.10. Exploratory factor analyses did not provide a useful grouping of characteristics drawn by the students, including analyses stratified by gender and restricted to the most common 34 characteristics. Among the 49 characteristics that emerged from the drawings, 11, 4, and 11 traits were directly associated with classifying the drawings as positive, neutral, or negative, respectively. These analyses indicate that middle school students have not formed strong images regarding aging: No clear cohesive stereotypes of elders emerged from the images drawn by these children. Absence of stereotypic views implies that middle school students may not have a built-in bias toward older people and age-associated changes. This suggests that young adolescents are at a point where instruction including gerontological content can be used to effectively teach about aging and health promotion.


Reliability of CD4 quantitation in human immunodeficiency virus-positive children: implications for definition of immunologic response to highly active antiretroviral therapy.
Our objective was to develop data-based algorithms for definition of immunologic response to AIDS therapies in pediatric patients, taking account of T-cell subset measurement errors. The study design involved cross-protocol analysis of 2,148 enrollees in six completed Pediatric AIDS Clinical Trials Group trials. We used standard quantitation of T-cell subsets; linear modeling with mean-dependent measurement error variance was used to develop 95% tolerance limits for change in CD4%. For individuals with a CD4% of approximately 25%, the measurement error-based 95% tolerance interval ranges from 15% to 35%, whereas for individuals with a CD4% of approximately 5%, the tolerance interval ranges from 3% to 7%. When pairs of CD4% measures taken within a time interval of less than 30 days are averaged to estimate steady-state CD4%, tolerance interval width decreases by approximately 30%. A simple graphical tool that provides a data-based criterion for immunologic response over and above variation ascribable to T-cell measurement error is provided. Variability in CD4% due to measurement error is substantial, increases with level of CD4%, and complicates assessment of immunologic response to therapy. Replicates of CD4% measures could be used to improve precision of interpretation of CD4% measures.


Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study.
Patients with prostate cancer and their physicians need knowledge of treatment options and their potential complications, but limited data on complications are available in unselected population-based cohorts of patients. To measure changes in urinary and sexual function in men who have undergone radical prostatectomy for clinically localized prostate cancer. The Prostate Cancer Outcomes Study, a population-based longitudinal cohort study with up to 24 months of follow-up. Population-based cancer registries in 6 geographic regions of the United States. A total of 1291 black, white, and Hispanic men aged 39 to 79 years who were diagnosed as having primary prostate cancer between October 1, 1994, and October 31, 1995, and who underwent radical prostatectomy within 6 months of diagnosis for clinically localized disease. Distribution of and change in urinary and sexual function measures reported by patients at baseline and 6, 12, and 24 months after diagnosis. At 18 or more months following radical prostatectomy, 8.4% of men were incontinent and 59.9% were impotent. Among men who were potent before surgery, the proportion of men reporting impotence at 18 or more months after surgery varied according to whether the procedure was nerve sparing (65.6% of non-nerve-sparing, 58.6% of unilateral, and 56.0% of bilateral nerve-sparing). At 18 or more months after surgery, 41.9% reported that their sexual performance was a moderate-to-large problem. Both sexual and urinary function varied by age (39.0% of men aged <60 years vs 15.3 %-21.7% of older men were potent at > or =18 months [P<.001]; 13.8% of men aged 75-79 years vs 0.7%-3.6% of younger men experienced the highest level of incontinence at > or =18 months [P = .03]), and sexual function also varied by race (38.4% of black men reported firm erections at > or =18 months vs 25.9% of Hispanic and 21.3% of white men; P = .001). Our study suggests that radical prostatectomy is associated with significant erectile dysfunction and some decline in urinary function. These results may be particularly helpful to community-based physicians and their patients with prostate cancer who face difficult treatment decisions.


Air-water exchange of PAHs and OPAHs at a superfund mega-site.
Chemical fate is a concern at environmentally contaminated sites, but characterizing that fate can be difficult. Identifying and quantifying the movement of chemicals at the air-water interface are important steps in characterizing chemical fate. Superfund sites are often suspected sources of air pollution due to legacy sediment and water contamination. A quantitative assessment of polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAH (OPAHs) diffusive flux in a river system that contains a Superfund Mega-site, and passes through residential, urban and agricultural land, has not been reported before. Here, passive sampling devices (PSDs) were used to measure 60 polycyclic aromatic hydrocarbons (PAHs) and 22 oxygenated PAH (OPAHs) in air and water. From these concentrations the magnitude and direction of contaminant flux between these two compartments was calculated. The magnitude of PAH flux was greater at sites near or within the Superfund Mega-site than outside of the Superfund Mega-site. The largest net individual PAH deposition at a single site was naphthalene at a rate of -14,200 (±5780) (ng/m2)/day. The estimated one-year total flux of phenanthrene was -7.9×105 (ng/m2)/year. Human health risk associated with inhalation of vapor phase PAHs and dermal exposure to PAHs in water were assessed by calculating benzo[a]pyrene equivalent concentrations. Excess lifetime cancer risk estimates show potential increased risk associated with exposure to PAHs at sites within and in close proximity to the Superfund Mega-site. Specifically, estimated excess lifetime cancer risk associated with dermal exposure and inhalation of PAHs was above 1 in 1 million within the Superfund Mega-site. The predominant depositional flux profile observed in this study suggests that the river water in this Superfund site is largely a sink for airborne PAHs, rather than a source.


Cleavage and polyadenylation specificity factor 1 (CPSF1) regulates alternative splicing of interleukin 7 receptor (IL7R) exon 6.
Interleukin 7 receptor, IL7R, is expressed exclusively on cells of the lymphoid lineage, and its expression is crucial for the development and maintenance of T cells. Alternative splicing of IL7R exon 6 results in membrane-bound (exon 6 included) and soluble (exon 6 skipped) IL7R isoforms. Interestingly, the inclusion of exon 6 is affected by a single-nucleotide polymorphism associated with the risk of developing multiple sclerosis. Given the potential association of exon 6 inclusion with multiple sclerosis, we investigated the cis-acting elements and trans-acting factors that regulate exon 6 splicing. We identified multiple exonic and intronic cis-acting elements that impact inclusion of exon 6. Moreover, we utilized RNA affinity chromatography followed by mass spectrometry to identify trans-acting protein factors that bind exon 6 and regulate its splicing. These experiments identified cleavage and polyadenylation specificity factor 1 (CPSF1) among protein-binding candidates. A consensus polyadenylation signal AAUAAA is present in intron 6 of IL7R directly downstream from the 5' splice site. Mutations to this site and CPSF1 knockdown both resulted in an increase in exon 6 inclusion. We found no evidence that this site is used to produce cleaved and polyadenylated mRNAs, suggesting that CPSF1 interaction with intronic IL7R pre-mRNA interferes with spliceosome binding to the exon 6 5' splice site. Our results suggest that competing mRNA splicing and polyadenylation regulate exon 6 inclusion and consequently determine the ratios of soluble to membrane-bound IL7R. This may be relevant for both T cell ontogeny and function and development of multiple sclerosis.


Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP.
In genome-wide screening studies for de novo mutations underlying autism and intellectual disability, mutations in the ADNP gene are consistently reported among the most frequent. ADNP mutations have been identified in children with autism spectrum disorder comorbid with intellectual disability, distinctive facial features, and deficits in multiple organ systems. However, a comprehensive clinical description of the Helsmoortel-Van der Aa syndrome is lacking. We identified a worldwide cohort of 78 individuals with likely disruptive mutations in ADNP from January 2014 to October 2016 through systematic literature search, by contacting collaborators, and through direct interaction with parents. Clinicians filled in a structured questionnaire on genetic and clinical findings to enable correlations between genotype and phenotype. Clinical photographs and specialist reports were gathered. Parents were interviewed to complement the written questionnaires. We report on the detailed clinical characterization of a large cohort of individuals with an ADNP mutation and demonstrate a distinctive combination of clinical features, including mild to severe intellectual disability, autism, severe speech and motor delay, and common facial characteristics. Brain abnormalities, behavioral problems, sleep disturbance, epilepsy, hypotonia, visual problems, congenital heart defects, gastrointestinal problems, short stature, and hormonal deficiencies are common comorbidities. Strikingly, individuals with the recurrent p.Tyr719* mutation were more severely affected. This overview defines the full clinical spectrum of individuals with ADNP mutations, a specific autism subtype. We show that individuals with mutations in ADNP have many overlapping clinical features that are distinctive from those of other autism and/or intellectual disability syndromes. In addition, our data show preliminary evidence of a correlation between genotype and phenotype.


Development and evaluation of a multiplexed mass spectrometry based assay for measuring candidate peptide biomarkers in Alzheimer's Disease Neuroimaging Initiative (ADNI) CSF.
We describe the outcome of the Biomarkers Consortium CSF Proteomics Project (where CSF is cerebral spinal fluid), a public-private partnership of government, academia, nonprofit, and industry. The goal of this study was to evaluate a multiplexed MS-based approach for the qualification of candidate Alzheimer's disease (AD) biomarkers using CSF samples from the AD Neuroimaging Initiative. Reproducibility of sample processing, analytic variability, and ability to detect a variety of analytes of interest were thoroughly investigated. Multiple approaches to statistical analyses assessed whether panel analytes were associated with baseline pathology (mild cognitive impairment (MCI), AD) versus healthy controls or associated with progression for MCI patients, and included (i) univariate association analyses, (ii) univariate prediction models, (iii) exploratory multivariate analyses, and (iv) supervised multivariate analysis. A robust targeted MS-based approach for the qualification of candidate AD biomarkers was developed. The results identified several peptides with potential diagnostic or predictive utility, with the most significant differences observed for the following peptides for differentiating (including peptides from hemoglobin A, hemoglobin B, and superoxide dismutase) or predicting (including peptides from neuronal pentraxin-2, neurosecretory protein VGF (VGF), and secretogranin-2) progression versus nonprogression from MCI to AD. These data provide potential insights into the biology of CSF in AD and MCI progression and provide a novel tool for AD researchers and clinicians working to improve diagnostic accuracy, evaluation of treatment efficacy, and early diagnosis.


Tinnitus Management: Randomized Controlled Trial Comparing Extended-Wear Hearing Aids, Conventional Hearing Aids, and Combination Instruments.
Whereas hearing aids have long been considered effective for providing relief from tinnitus, controlled clinical studies evaluating this premise have been very limited. The purpose of this study was to systematically determine the relative efficacy of conventional receiver-in-the-canal hearing aids (HA), the same hearing aids with a sound generator (HA+SG), and extended-wear, deep fit hearing aids (EWHA), to provide relief from tinnitus through a randomized controlled trial. Each of these ear-level devices was a product of Phonak, LLC. Participants were randomized to HA, HA+SG, or EWHA and wore bilaterally fit devices for about 4 months. Fittings, adjustments, and follow-up appointments were conducted to comply with company guidelines and to ensure that all participants attended appointments on the same schedule. At 4-5 months, participants returned to complete final outcome measures, which concluded their study participation. Participants were 55 individuals (mean age: 63.1 years) with mild to moderately-severe hearing loss who: (a) did not currently use hearing aids; (b) reported tinnitus that was sufficiently bothersome to warrant intervention; and (c) were suitable candidates for each of the study devices. The primary outcome measure was the Tinnitus Functional Index (TFI). Secondary outcome measures included hearing-specific questionnaires and the Quick Speech in Noise test (QuickSIN). The goal of the analysis was to evaluate efficacy of the EWHA and HA+SG devices versus the HA standard device. There were 18 participants in each of the HA and EWHA groups and 19 in the HA+SG group. Gender, age, and baseline TFI severity were balanced across treatment groups. Nearly all participants had a reduction in tinnitus symptoms during the study. The average TFI change (improvement) from baseline was 21 points in the HA group, 31 points in the EWHA group, and 33 points in the HA+SG group. A "clinically significant" improvement in reaction to tinnitus (at least 13-point reduction in TFI score) was seen by 67% of HA, 82% of EWHA, and 79% of HA+SG participants. There were no statistically significant differences in the extent to which the devices reduced TFI scores. Likewise, the hearing-specific questionnaires and QuickSIN showed improvements following use of the hearing aids but these improvements did not differ across device groups. There is insufficient evidence to conclude that any of these devices offers greater relief from tinnitus than any other one tested. However, all devices appear to offer some improvement in the functional effects of tinnitus.


Experimental and theoretical investigation of a mesoporous K(x)WO3 material having superior mechanical strength.
Mesoporous materials with tailored properties hold great promise for energy harvesting and industrial applications. We have synthesized a novel tungsten bronze mesoporous material (K(x)WO3; x ∼ 0.07) having inverse FDU-12 type pore symmetry and a crystalline framework. In situ small angle X-ray scattering (SAXS) measurements of the mesoporous K(0.07)WO3 show persistence of a highly ordered meso-scale pore structure to high pressure conditions (∼18.5 GPa) and a material with remarkable mechanical strength despite having ∼35% porosity. Pressure dependent in situ SAXS measurements reveal a bulk modulus κ = 44 ± 4 GPa for the mesoporous K(x)WO3 which is comparable to the corresponding value for the bulk monoclinic WO3 (γ-WO3). Evidence from middle angle (MAXS) and wide angle X-ray scattering (WAXS), high-resolution transmission electron microscopy (HR-TEM) and Raman spectroscopy shows that the presence of potassium leads to the formation of a K-bearing orthorhombic tungsten bronze (OTB) phase within a monoclinic WO3 host structure. Our ab initio molecular dynamics calculations show that the formation of the OTB phase provides superior strength to the mesoporous K(0.07)WO3.


Risk factors for developing drug-related problems in patients with cardiovascular diseases attending Gondar University Hospital, Ethiopia.
Cardiovascular diseases (CVDs) are often accompanied with comoribidities and complications leading to taking multiple drugs and thus are more liable to be exposed to drug-related problems (DRPs). DRPs can occur at any stages of medication process from prescription to follow-up treatment. However, a few studies have assessed the specific risk factors for occurrence of at least one potential DRP per patient with CVDs in sub-Saharan African region. We aim to assess the risk factors for developing potential DRPs in patients with CVDs attending Gondar University Referral Hospital (GUH). This was a cross-sectional study. A structured systematic data review was designed focusing on patients with CVDs (both out and inpatients) with age >18 years of both genders attending GUH from April to June 2015. All DRPs were assessed using drugs.com and Medscape. The causes of DRPs were classified using Pharmaceutical Care Network Europe version 6.2. Risk factors that could cause DRPs were assessed using binary logistic regression showing odds ratio with 95% confidential interval. Statistical significance was set at P < 0.05. A total of 227 patients with CVDs were reviewed with a mean age of 52.0 ± 1.7 years. Majority were females (143, 63%), outpatients (133, 58.6%), and diagnosed with heart failure (71, 31.3%). Diuretics (199, 29.5%) were the most commonly prescribed drugs. A total of 265 DRPs were identified, 63.4% of patients have at least one DRP (1.17 ± 1.1). The most common DRPs were found to be an inappropriate selection of drug (36.1%) and dose (24.8%). The most identified risk factors causing DRPs were: Need of additional drug therapy and lack of therapeutic monitoring. The most identified risk factors for developing DRPs were the need of additional drug therapy and lack of therapeutic monitoring. There is a need for clinical pharmacist interventions to monitor and prevent the risk of developing DRPs and contribute to improve the clinical outcome in patients with CVDs.


Stem Cell Ophthalmology Treatment Study: bone marrow derived stem cells in the treatment of non-arteritic ischemic optic neuropathy (NAION).
Ten patients with bilateral visual loss due to sequential non-arteritic ischemic optic neuropathy (NAION) underwent autologous Bone Marrow Derived Stem Cell (BMSC) therapy within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical study utilizing autologous BMSC in the treatment of optic nerve and retinal diseases that meet inclusion criteria. The average age of the patients treated was 69.8 years. The average duration of visual loss in eyes treated was 9.8 years and ranged from 1 to 35 years. Affected eyes were treated with either retrobulbar, subtenons and intravenous BMSC or, following vitrectomy, intra-optic nerve, subtenons and intravenous BMSC. The primary outcome was visual acuity as measured by Snellen or converted to LogMAR. Following therapy in SCOTS, 80% of patients experienced improvement in Snellen binocular vision (P=0.029) with 20% remaining stable; 73.6% of eyes treated gained vision (P=0.019) and 15.9% remained stable in the post-operative period. There was an average of 3.53 Snellen lines of vision improvement per eye with an average 22.74% and maximum 83.3% improvement in LogMAR acuity per eye. The average LogMAR change in treated eyes was a gain of 0.364 (P=0.0089). Improvements typically manifested no later than 6 months post procedure. The use of BMSC in the Stem Cell Ophthalmology Treatment Study achieved meaningful visual improvements in a significant percentage of the NAION patients reported. Improvements typically manifested no later than 6 months post-procedure. Duration of visual loss did not appear to affect the ability of the eyes to respond to treatment. Possible mechanisms by which visual improvement occurred may include BMSC paracrine secretion of proteins and hormones, transfer of mitochondria, release of messenger RNA or other compounds via exosomes or microvesicles and neuronal transdifferentiation of the stem cells.


Critically important antibiotics: criteria and approaches for measuring and reducing their use in food animal agriculture.
Globally, increasing acquired antimicrobial resistance among pathogenic bacteria presents an urgent challenge to human and animal health. As a result, significant efforts, such as the One Health Initiative, are underway to curtail and optimize the use of critically important antimicrobials for human medicine in all applications, including food animal production. This review discusses the rationale behind multiple and competing "critically important antimicrobial" lists and their contexts as created by international, regional, and national organizations; identifies discrepancies among these lists; and describes issues surrounding risk management recommendations that have been made by regulatory organizations on the use of antibiotics in food animal production. A more harmonized approach to defining criticality in its various contexts (e.g., for human versus animal health, enteric diseases versus other systemic infections, and direct versus indirect selection of resistance) is needed in order to identify shared contextual features, aid in their translation into risk management, and identify the best ways to maintain the health of food animals, all while keeping in mind the wider risks of antimicrobial resistance, environmental impacts, and animal welfare considerations.


Broadening consent--and diluting ethics?
Biobank research is potentially fruitful. It is argued that broad consent is acceptable for future research on biological material because a) the benefit is high, b) it pays respect to people's autonomy, c) it is consistent with current practices and d) because the risk is low. Furthermore, broad consent should be allowed if information is handled safely, people can withdraw and expanded research should be approved by an ethics review board. However, these arguments are flawed and the criteria for broad consent are either too restrictive to allow any research or fail to address important challenges with biobank research. Broad consent for biobank research can hide substantial ethical challenges and threaten trust in research. This does not mean that biobank research should be abandoned or that people cannot authorise future research on donated biological material.


Spatially resolved calcium dynamics of mammalian Purkinje cells in cerebellar slice.
Microfluorometric imaging was used to study the correlation of intracellular calcium concentration with voltage-dependent electrical activity in guinea pig cerebellar Purkinje cells. The spatiotemporal dynamics of intracellular calcium concentration are demonstrated during spontaneous and evoked activity. The results are in agreement with hypotheses of dendritic segregation of calcium conductances suggested by electrophysiological experiments. These in vitro slice fluorescence imaging methods are applicable to a wide range of problems in central nervous system biochemical and electrophysiological functions.


Oyster sperm bindin is a combinatorial fucose lectin with remarkable intra-species diversity.
Sperm of the oyster, Crassostrea gigas, have ring-shaped acrosomes that, after exocytosis, bind the sperm to the egg vitelline layer. Isolated acrosomal rings contain proteins of various sizes: 35-, 48-, 63-, 75- and 88-kDa. These proteins, called bindins, have identical 24-residue signal peptides and conserved 97-residue N-terminal sequences, and they differ in mass because of the presence of between 1 and 5 tandemly repeated 134-residue fucose-binding lectin (F-lectin) domains. Southern blots suggest that oyster bindin is a single copy gene, but F-lectin repeat number and sequence are variable within and between individuals. Eight residues in the F-lectin fucose-binding groove are subject to positive diversifying selection, indicating a history of adaptive evolution at the lectin's active site. There is one intron in the middle of each F-lectin repeat, and recombination in this intron creates many combinations of repeat halves. Alternative splicing creates many additional size and sequence variants of the repeat array. Males contain full-length bindin cDNAs of all 5 possible sizes, but only one or two protein mass forms exist in each individual. Sequence analysis indicates that recombination and alternate splicing create hundreds, possibly thousands, of different bindin sequences in C. gigas. The extreme within-species sequence variation in the F-lectin sequence of oyster bindin is a novel finding; most male gamete-recognition proteins are much less variable. In experimental conditions oyster eggs have poor polyspermy blocks, and bindin diversity could be an evolutionary response by sperm to match egg receptors that have diversified to avoid being fertilized by multiple sperm.


A Meta-Analysis: Acoustic Measurement of Roughness and Breathiness.
Over the last 5 decades, many acoustic measures have been created to measure roughness and breathiness. The aim of this study is to present a meta-analysis of correlation coefficients (r) between auditory-perceptual judgment of roughness and breathiness and various acoustic measures in both sustained vowels and continuous speech. Scientific literature reporting perceptual-acoustic correlations on roughness and breathiness were sought in 28 databases. Weighted average correlation coefficients (rw) were calculated when multiple r-values were available for a specific acoustic marker. An rw ≥ .60 was the threshold for an acoustic measure to be considered acceptable. From 103 studies of roughness and 107 studies of breathiness that were investigated, only 33 studies and 34 studies, respectively, met the inclusion criteria of the meta-analysis on sustained vowels. Eighty-six acoustic measures were identified for roughness and 85 acoustic measures for breathiness on sustained vowels, in which 43 and 39 measures, respectively, yielded multiple r-values. Finally, only 14 measures for roughness and 12 measures for breathiness produced rw ≥ .60. On continuous speech, 4 measures for roughness and 21 measures for breathiness were identified, yielding 3 and 6 measures, respectively, with multiple r-values in which only 1 and 2, respectively, had rw ≥ .60. This meta-analysis showed that only a few acoustic parameters were determined as the best estimators for roughness and breathiness.


Consistent patterns of expression of HLA class I free heavy chains in healthy individuals and raised expression in spondyloarthropathy patients point to physiological and pathological roles.
Major histocompatibility complex class I (MHC-I) proteins exist at the cell surface in antigen presenting forms and as beta2m-independent free heavy chains (FHCs). FHCs have been implicated in spondyloarthritis, but little is known about their expression in healthy individuals. We studied FHC expression on various human cell types, comparing spondyloarthropathy patients with healthy and rheumatoid arthritis (RA) patient controls. MHC-I expression was analysed by flow cytometry. FHC levels were normalized for overall MHC-I to generate a relative expression level. Relative FHC levels were analysed for peripheral blood and trophoblast samples from healthy volunteers, RA and spondyloarthropathy patients. Macrophages and dendritic cells were cultured in vitro to analyse changes following activation. Peripheral blood leucocytes from patients with ankylosing spondylitis (AS) and RA were treated with inflammatory stimuli and subsequent alterations in their relative FHC levels were analysed. We found consistent patterns of differential relative FHC expression across lymphocyte subpopulations and particularly high expression on extravillous trophoblast. FHCs were present at higher levels in a reactive arthritis (ReA) population than in healthy controls and RA patients; differences not merely due to the presence of Human Leucocyte Antigen (HLA) B27. Treatment of leucocytes from arthritic patients with bacterial lipopolysaccharide resulted in significant up-regulation of FHC compared with an HLA B27+ control population. Our findings define normal levels and tissue expression of FHCs, and support the hypothesis that disregulation of heavy chain expression may play a pathogenic role in spondyloarthropathy.


Dropouts in a long-term follow-up study involving voluntary counseling and HIV testing: experience from a cohort of police officers in Dar Es Salaam, Tanzania.
Results of most population-based studies primarily are derived from people who responded positively and thereby continued to participate in such studies. It is, however, equally important to know the characteristics of study subjects who drop out to learn the reasons that kept them from continuing to participate in the study, especially because they had initially agreed to participate in such a study. In studies with long-term follow-up, reasons for nonresponse may provide invaluable information that may be gathered through continued contact with study subjects who have withdrawn from the study. To determine characteristics of study participants who withdrew from an ongoing study of police officers, which involved counseling and HIV testing, and to determine reasons for their discontinued participation. Demographic characteristics of a cohort of police officers who had been participating in a study to determine their suitability for HIV vaccine trials were analyzed. Characteristics of those who did not return for the second survey of appointments for HIV testing were compared with those who continued their participation. A randomly selected sample of 132 police officers who did not participate in the second survey of HIV testing were asked why they did not return. Answers were obtained from 84 people who had discontinued their participation. Of eligible police officers, 2087 (72.1%) responded to the call for follow-up appointments, whereas 807 (27.9%) did not return. Those who did not return to participate in the second survey had significantly higher rates of HIV seropositivity (17.2%) than those who did return (13.5%) (p <.05). The rate of return in unmarried participants was worse (p <.05) than the rate among married participants. Rates of sexual contacts with partners other than their spouses and levels of alcohol consumption did not differ between the two groups. Reasons for dropping out of the study included fear of knowing results of HIV testing in 54.6%, lack of time to continue in 34.5%, and fears about job security in 3.6%. Fears of finding out that one might be seropositive need to be answered at recruitment, and practical arrangements must be made to facilitate further follow-up. A bias for lower incidence might be introduced in vaccine trials if participants thought to be at highest risk for HIV infection discontinue participation.


Boronic acids for sensing and other applications - a mini-review of papers published in 2013.
Boronic acids are increasingly utilised in diverse areas of research. Including the interactions of boronic acids with diols and strong Lewis bases as fluoride or cyanide anions, which leads to their utility in various sensing applications. The sensing applications can be homogeneous assays or heterogeneous detection. Detection can be at the interface of the sensing material or within the bulk sample. Furthermore, the key interaction of boronic acids with diols allows utilisation in various areas ranging from biological labelling, protein manipulation and modification, separation and the development of therapeutics. All the above uses and applications are covered by this mini-review of papers published during 2013.


Loss of REEP4 causes paralysis of the Xenopus embryo.
Members of the REEP (Receptor expression enhancing protein) family contain a TB2/DP1, HVA22 domain that is involved in intracellular trafficking and secretion. Consistent with the presence of this domain, REEP1 and REEP3 enhance the expression of odorant and taste receptors in mammals, while mutation of these genes causes defects in neural development. REEP4 was identified in the course of a functional antisense morpholino oligonucleotide screen searching for genes involved in the early development of Xenopus tropicalis: although over-expression of the gene causes no phenotype, embryos lacking REEP4 develop a slightly kinked body axis and are paralysed. At tailbud stages of development, REEP4 is expressed in the somites and neural tube. The paralysis observed in embryos lacking REEP4 might therefore be caused by defects in the nervous system or in muscle. To address this point, we examined the expression of various neural and muscle markers and found that although all are expressed normally at early stages of development, many are down regulated by the tailbud stage. This suggests that REEP4 plays a role in the maintenance of both the nervous system and the musculature.


Use of a Teledentistry-based Program for Screening of Early Childhood Caries in a School Setting.
Aim The aim of this study was to assess the reliability and feasibility of using teledentistry for the screening and diagnosis of dental caries in children between the age groups of three to six years. Design This study included a total of 318 school-going children whose caries scores were calculated by visual method and using digital photographs generated by an intraoral camera by two examiners: examiner 1 and examiner 2 (E1 and E2). Intra-examiner and inter-examiner variability were determined. Reliability was compared across the three groups. Results Intra-examiner and inter-examiner variability when compared revealed no significant difference. A Cronbach's alpha of 0.983 was generated, which shows high reliability. Conclusions Effective screening for early childhood caries (ECC) in young children was possible with digital images generated in a school setting, thus paving the way for the application of teledentistry as effective means for the diagnosis of dental caries.


Passing return to sports tests after ACL reconstruction is associated with greater likelihood for return to sport but fail to identify second injury risk.
A limited number of patients return to sport (RTS) after an anterior cruciate ligament reconstruction (ACLR) and patients who RTS have a relatively high risk for second ACL injury. The purpose of the current study was to compare the results of a test battery between patients who returned to the pre-injury level of sport (RTS group) and patients who did not (NO-RTS group). It was hypothesized that the RTS group showed better test results. Sixty-four patients (age 27.8 ± 8.8 years) were included. The results of a multicomponent test battery (jump-landing task assessed with the Landing Error Scoring System (LESS), three hop tests, isokinetic strength test for quadriceps and hamstring) were compared between groups with a 2 × 2 ANOVA. The RTS group showed a significantly lower LESS score (p = 0.010), significantly higher absolute scores on hop tests with both legs (injured leg: single leg hop test p = 0.013, triple leg hop test p = 0.024, side hop test p = 0.021; non-injured leg: single leg hop test p = 0.011, triple leg hop test p = 0.023, side hop test p = 0.032) and significantly greater hamstring strength in the injured leg (p = 0.009 at 60°/s, p = 0.012 at 180°/s and p = 0.013 at 300°/s). No differences in test results were identified between patients who sustained a second ACL injury and patients who did not. Patients after ACLR with better jump-landing patterns, hop performance and greater hamstring strength have greater likelihood for RTS. However, our findings show that RTS criteria fail to identify patients who are at risk for a second ACL injury.


AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats.
Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ, N-methyl-D-aspartate receptor, and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve. Meanwhile, ozone significantly suppressed CCI-induced activation of spinal microglia. More importantly, the anti-nociceptive effect of ozone depended on the activation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), which was proved by the fact that the phosphorylated AMPK level increased during the ozone therapy and AMPK antagonist abolished the effect of ozone in vivo and in vitro. In addition, direct injection of AMPK agonist could replicate the anti-nociceptive effect of ozone in CCI rats. In conclusion, our observations indicate that peri-sciatic nerve injection of ozone activates AMPK to attenuate CCI-induced neuropathic pain.


Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline.
Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario's Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken. Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline. Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer. Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)-based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without "high-risk" features should not receive adjuvant chemotherapy. For patients with "high-risk" features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer.


The Effects of Proprioceptive Neuromuscular Facilitation Stretching on Post-Exercise Delayed Onset Muscle Soreness in Young Adults.
Until recently, the scientific community believed that post-exercise stretching could reduce delayed onset muscle soreness (DOMS), but recent reviews of studies on the topic have concluded that pre- or post-exercise static stretching has no effect on mitigating DOMS. However, the effect of proprioceptive neuromuscular facilitation (PNF) post-exercise stretching on preventing DOMS has not been adequately studied. The purpose of this study was to determine the effect of post-exercise PNF stretching on DOMS. Young adult participants (N=57) were randomly assigned to a PNF stretching group (n=19), a static stretching group (n=20), and to a no-stretching control group (n=18). All participants completed exercise designed to induce DOMS prior to post-exercise experimental stretching protocols. Participants rated their soreness level on a pain scale 24 and 48 hours post-exercise. A 3 × 2 mixed ANOVA showed there was an effect for time (p<.01). Post hoc testing revealed that DOMS pain significantly decreased (p<.05) from 24 to 48 hours post-exercise for the PNF and control groups, but not for the static stretching group. Other analyses revealed a significant correlation (r=.61, p<.01) between the pre- and post-exercise stretch scores and the 48 hour post-exercise pain score for the PNF group. Consistent with the results of previous research on post-exercise static stretching, these results indicate that post-exercise PNF stretching also does not prevent DOMS. However, the correlation analysis suggests it is possible the pre-stretch muscle contractions of the post-exercise PNF protocol may have placed a load on an already damaged muscle causing more DOMS for some participants.


Exploring the function of protein kinases in schistosomes: perspectives from the laboratory and from comparative genomics.
Eukaryotic protein kinases are well conserved through evolution. The genome of Schistosoma mansoni, which causes intestinal schistosomiasis, encodes over 250 putative protein kinases with all of the main eukaryotic groups represented. However, unraveling functional roles for these kinases is a considerable endeavor, particularly as protein kinases regulate multiple and sometimes overlapping cell and tissue functions in organisms. In this article, elucidating protein kinase signal transduction and function in schistosomes is considered from the perspective of the state-of-the-art methodologies used and comparative organismal biology, with a focus on current advances and future directions. Using the free-living nematode Caenorhabditis elegans as a comparator we predict roles for various schistosome protein kinases in processes vital for host invasion and successful parasitism such as sensory behavior, growth and development. It is anticipated that the characterization of schistosome protein kinases in the context of parasite function will catalyze cutting edge research into host-parasite interactions and will reveal new targets for developing drug interventions against human schistosomiasis.


Pursuing equity: contact with primary care and specialist clinicians by demographics, insurance, and health status.
Long-term shifts in specialty choice and health workforce policy have raised concern about the future of primary care in the United States. The objective of this study was to examine current use of primary and specialty care across the US population for policy-relevant subgroups, such as disadvantaged populations and persons with chronic illness. Data from the Medical Expenditure Panel Survey from 2004 were analyzed using a probability sample patients or other participants from the noninstitutionalized US population in 2004 (N = 34,403). The main and secondary outcome measures were the estimates of the proportion of Americans who accessed different types of primary care and specialty physicians and midlevel practitioners, as well as the fraction of ambulatory visits accounted for by the different clinician types. Data were disaggregated by income, health insurance status, race/ethnicity, rural or urban residence, and presence of 5 common chronic diseases. Family physicians were the most common clinician type accessed by adults, seniors, and reproductive-age women, and they were second to pediatricians for children. Disadvantaged adults with 3 markers of disadvantage (poverty, disadvantaged minority, uninsured) received 45.6% (95% CI, 40.4%-50.7%) of their ambulatory visits from family physicians vs 30.5% (95% CI, 30.0%-32.1%) for adults with no markers. For children with 3 vs 0 markers of disadvantage, the proportion of visits from family physicians roughly doubled from 16.5% (95% CI, 14.4%-18.6%) to 30.1% (95% CI, 18.8%-41.2%). Family physicians constitute the only clinician group that does not show income disparities in access. Multivariate analyses show that patterns of access to family physicians and nurse-practitioners are more equitable than for other clinician types. Primary care clinicians, especially family physicians, deliver a disproportionate share of ambulatory care to disadvantaged populations. A diminished primary care workforce will leave considerable gaps in US health care equity. Health care workforce policy should reflect this important population-level function of primary care.


Identification of quinone-binding and heme-ligating residues of the smallest membrane-anchoring subunit (QPs3) of bovine heart mitochondrial succinate:ubiquinone reductase.
The smallest membrane-anchoring subunit (QPs3) of bovine heart succinate:ubiquinone reductase was overexpressed in Escherichia coli JM109 as a glutathione S-transferase fusion protein using the expression vector pGEX2T/QPs3. The yield of soluble active recombinant glutathione S-transferase-QPs3 fusion protein was isopropyl-1-thio-beta-D-galactopyranoside concentration-, induction growth time-, temperature-, and medium-dependent. Maximum yield of soluble recombinant fusion protein was obtained from cells harvested 3.5 h post-isopropyl-1-thio-beta-D-galactopyranoside (0.4 mM)-induction growth at 25 degrees C in 2.0% tryptone, 0.5% yeast extract, 10 mM NaCl, 2.5 mM KCl, 10 mM MgCl2, 20 mM glucose (SOC medium) containing 440 mM sorbitol and 2.5 mM betaine. QPs3 was released from the fusion protein by proteolytic cleavage with thrombin. Isolated recombinant QPs3 shows one protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis that corresponds to subunit V of mitochondrial succinate:ubiquinone reductase. Although purified recombinant QPs3 is dispersed in 0.01% dodecylmaltoside, it is in a highly aggregated form, with an apparent molecular mass of more than 1 million. The recombinant QPs3 binds ubiquinone, causing a spectral blue shift. Upon titration of the recombinant protein with ubiquinone, a saturation behavior is observed, suggesting that the binding is specific and that recombinant QPs3 may be in the functionally active state. Two amino acid residues, serine 33 and tyrosine 37, in the putative ubiquinone binding domain of QPs3 are involved in ubiquinone binding because the S33A- or Y37A-substituted recombinant QPs3s do not cause the spectral blue shift of ubiquinone. Although recombinant QPs3 contains little cytochrome b560 heme, the spectral characteristics of cytochrome b560 are reconstituted upon addition of hemin chloride. Reconstituted cytochrome b560 in recombinant QPs3 shows a EPR signal at g = 2.92. Histidine residues at positions 46 and 60 are responsible for heme ligation because the H46N- or H60N-substituted QPs3 fail to restore cytochrome b560 upon addition of hemin chloride.


Correlation of CD4 cell count with gingival bleeding index in HIV positive individuals.
To correlate CD4 cell count with gingival bleeding index in HIV positive individuals. Fifty-one serologically confirmed HIV positive individuals were included in the study. Plaque index and bleeding index was recorded by a single examiner. CD4 cell count was obtained within 30 days from the day of examination. CD4 cell counts and gingival bleeding index was correlated using Spearman's correlation test. p < 0.01 was considered as statistically significant. Mean plaque score, mean gingival bleeding index score and mean CD4 cell count was 1.40, 0.96 and 249.86 cells/mm3 respectively. It was noticed that gingival bleeding was enhanced in individuals with increased immunosuppression. However, no significant positive correlation was seen between mean CD4 cell count and gingival bleeding (p = 0.14). Though CD4 cells are an important indicator for clinical aggravation of HIV infection, periodontal disease as measured by bleeding index is not directly associated to the cell count.


Studies on fluid dynamics of the flow field and gas transfer in orbitally shaken tubes.
Orbitally shaken cylindrical bioreactors [OrbShake bioreactors (OSRs)] without an impeller or sparger are increasingly being used for the suspension cultivation of mammalian cells. Among small volume OSRs, 50-mL tubes with a ventilated cap (OSR50), originally derived from standard laboratory centrifuge tubes with a conical bottom, have found many applications including high-throughput screening for the optimization of cell cultivation conditions. To better understand the fluid dynamics and gas transfer rates at the liquid surface in OSR50, we established a three-dimensional simulation model of the unsteady liquid forms (waves) in this vessel. The studies verified that the operating conditions have a large effect on the interfacial surface. The volumetric mass transfer coefficient (kL a) was determined experimentally and from simulations under various working conditions. We also determined the liquid-phase mass transfer coefficient (kL ) and the specific interfacial area (a) under different conditions to demonstrate that the value of a affected the gas transfer rate more than did the value of kL . High oxygen transfer rates, sufficient for supporting the high-density culture of mammalian cells, were found. Finally, the average axial velocity of the liquid was identified to be an important parameter for maintaining cells in suspension. Overall these studies provide valuable insights into the preferable operating conditions for the OSR50, such as those needed for cell cultures requiring high oxygen levels. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:192-200, 2017.


The phorbol ester TPA inhibits cyclic AMP phosphodiesterase activity in intact hepatocytes.
Treatment of intact hepatocytes with the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) potentiated the ability of glucagon to increase intracellular cyclic AMP concentrations. This effect was dose-dependent upon TPA, exhibiting an EC50 of 0.39 ng/ml and such activation was observed at both saturating and sub-saturating concentrations of glucagon. However, this stimulatory effect of TPA was completely abolished by the presence of the cyclic AMP phosphodiesterase inhibitor 1-isobutyl-3-methylxanthine, when TPA now inhibited the glucagon-stimulated increase in intracellular cyclic AMP concentrations. It is suggested that, as well as inhibiting glucagon-stimulated adenylate cyclase activity, TPA also inhibits cyclic AMP phosphodiesterase activity in intact hepatocytes. Treatment of either hepatocyte homogenates or purified cyclic AMP phosphodiesterase with TPA failed to show any direct inhibitory effect of TPA on activity showing that TPA did not exert any direct inhibitory action on phosphodiesterase activity. However, homogenates made from hepatocytes that had been pre-treated with TPA did show a reduced cyclic AMP phosphodiesterase activity. It is suggested that TPA might inhibit cyclic AMP phosphodiesterase activity through phosphorylation by C-kinase.


Transient elastography: a valid alternative to biopsy in patients with chronic liver disease.
Transient elastography is a novel and non-invasive technique for the evaluation of fibrosis in chronic liver disease. Few studies that exist value the efficacy of transient elastography, mainly in hepatitis C virus-infected patients. To evaluate the effectiveness, objectivity, reproducibility and safety of this technique. We included 103 consecutive patients who underwent a liver biopsy in the last 48 months with a wide spectrum of chronic liver diseases. Median stiffness value (expressed as kilopascals - kPa) was kept as representative of the liver elastic modulus. All biopsy specimens were analysed by the same pathologist according to the METAVIR scoring system. Median value of stiffness in patients with mild or moderate fibrosis (FI and FII), and severe fibrosis or cirrhosis (FIII and FIV) was of 7, 4 +/- 5 and 16, 4 +/- 10 kPa, respectively, with a significant difference between them (P < 0.05). The areas under the receiver operating characteristic curves showed the optimal liver stiffness cut-off values for each group. We found a positive correlation between the liver stiffness found by transient elastography and fibrosis stage on biopsy in all patients, independently of the liver disease aetiology. Transient elastography is an easy, quick to perform and safe non-invasive procedure, reliable for assessing liver fibrosis.


A live oral recombinant Salmonella enterica serovar typhimurium vaccine expressing Clostridium perfringens antigens confers protection against necrotic enteritis in broiler chickens.
Necrotic enteritis (NE) in broiler chickens is caused by Clostridium perfringens, and there is currently no effective vaccine for NE. We previously showed that in broiler chickens protection against NE can be achieved through intramuscular immunization with alpha toxin (AT) and hypothetical protein (HP), and we subsequently identified B-cell epitopes in HP. In the present study, we identified B-cell epitopes in AT recognized by chickens immune to NE. The gene fragments encoding immunodominant epitopes of AT as well as those of HP were codon optimized for Salmonella and cloned into pYA3493, and the resultant plasmid constructs were introduced into an attenuated Salmonella enterica serovar Typhimurium chi9352 vaccine vehicle. The expression of these Clostridium perfringens proteins, alpha toxoid (ATd) and truncated HP (HPt), was confirmed by immunoblotting. The protection of broiler chickens against experimentally induced NE was assessed at both the moderate and the severe levels of challenge. Birds immunized orally with Salmonella expressing ATd were significantly protected against moderate NE, and there was a nonsignificant trend for protection against severe challenge, whereas HPt-immunized birds were significantly protected against both severities of challenge. Immunized birds developed serum IgY and mucosal IgA and IgY antibody responses against Clostridium and Salmonella antigens. In conclusion, this study identified, for the first time, the B-cell epitopes in AT from an NE isolate recognized by chickens and showed the partial protective ability of codon-optimized ATd and HPt against NE in broiler chickens when they were delivered orally by using a Salmonella vaccine vehicle.


Evaluating and regulating lead in synthetic turf.
In 2007, a synthetic turf recreational field in Newark, New Jersey, was closed because lead was found in synthetic turf fibers and in surface dust at concentrations exceeding hazard criteria. Consequently, public health professionals across the country began testing synthetic turf to determine whether it represented a lead hazard. Currently, no standardized methods exist to test for lead in synthetic turf or to assess lead hazards. Our objectives were to increase awareness of potential lead exposure from synthetic turf by presenting data showing elevated lead in fibers and turf-derived dust; identify risk assessment uncertainties; recommend that federal and/or state agencies determine appropriate methodologies for assessing lead in synthetic turf; and recommend an interim standardized approach for sampling, interpreting results, and taking health-protective actions. Data collected from recreational fields and child care centers indicate lead in synthetic turf fibers and dust at concentrations exceeding the Consumer Product Safety Improvement Act of 2008 statutory lead limit of 300 mg/kg for consumer products intended for use by children, and the U.S. Environmental Protection Agency's lead-dust hazard standard of 40 µg/ft² for floors. Synthetic turf can deteriorate to form dust containing lead at levels that may pose a risk to children. Given elevated lead levels in turf and dust on recreational fields and in child care settings, it is imperative that a consistent, nationwide approach for sampling, assessment, and action be developed. In the absence of a standardized approach, we offer an interim approach to assess potential lead hazards when evaluating synthetic turf.


Quasi-phase matched second-harmonic generation through thermal poling in femtosecond laser-written glass waveguides.
Quasi-phase matched second-harmonic generation at 532 nm is demonstrated in a channel waveguide that is written in bulk fused silica using a femtosecond laser. The second-order nonlinear grating is fabricated using uniform thermal poling followed by periodic erasure inside an e-beam deposition system caused, by what we believe to be, x-rays. A SHG conversion efficiency of 2 x10(-5) %/W-cm(2) was obtained for a 1 cm long device, corresponding to an effective nonlinear coefficient of 0.0075 pm/V.


Effectiveness of face-to-face versus telephone support in increasing physical activity and mental health among university employees.
Follow-up support increases the effectiveness of physical activity interventions. This study evaluates the effectiveness of 2 support modes on physical activity and mental health. University employees were randomly assigned to a coaching program with 4 face-to-face (N = 33) or telephone-based (N = 33) support contacts. Both programs included an initial face-to-face intake session and an informational brochure. Physical activity, trait anxiety, self-efficacy, and social support were measured by self-report before and after the interventions that lasted 3 months. Both groups increased leisure-time physical activity, self-efficacy, and social support and decreased sitting time and trait anxiety. The only significant time by group interaction was found for active transportation. More specifically, participants in the face-to-face group reported a significant increase in their active transportation from pretest to posttest, whereas participants in the telephone group reported no significant change. Both face-to-face support and telephone support proved to be effective in increasing the physical activity level and mental health of university employees.


Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone.
The three mammalian Runt homology domain transcription factors (Runx1, Runx2, Runx3) support biological control by functioning as master regulatory genes for the differentiation of distinct tissues. Runx proteins also function as cell context-dependent tumor suppressors or oncogenes. Abnormalities in Runx mediated gene expression are linked to cell transformation and tumor progression. Runx2 is expressed in mesenchymal linage cells committed to the osteoblast phenotype and is essential for bone formation. This skeletal transcription factor is aberrantly expressed at high levels in breast and prostate tumors and cells that aggressively metastasize to the bone environment. In cancer cells, Runx2 activates expression of bone matrix and adhesion proteins, matrix metalloproteinases and angiogenic factors that have long been associated with metastasis. In addition, Runx2 mediates the responses of cells to signaling pathways hyperactive in tumors, including BMP/TGFbeta and other growth factor signals. Runx2 forms co-regulatory complexes with Smads and other co-activator and co-repressor proteins that are organized in subnuclear domains to regulate gene transcription. These activities of Runx2 contribute to tumor growth in bone and the accompanying osteolytic disease, established by interfering with Runx2 functions in metastatic breast cancer cells. Inhibition of Runx2 in MDA-MB-231 cells transplanted to bone decreased tumorigenesis and prevented osteolysis. This review evaluates evidence that Runx2 regulates early metastatic events in breast and prostate cancers, tumor growth, and osteolytic bone disease. Consideration is given to the potential for inhibition of this transcription factor as a therapeutic strategy upstream of the regulatory events contributing to the complexity of metastasis to bone.


An experimental investigation into the transmission of antivax attitudes using a fictional health controversy.
Although vaccines are an invaluable weapon in combatting diseases, they are often surrounded by controversy. Vaccine controversies usually arise with the claims of some parents or doctors who link vaccines to harmful outcomes. These controversies often negatively affect vaccination coverage. This experiment simulated a vaccine controversy to understand which content features of vaccination-related information are well transmitted and how this transmission affects vaccine intention. All participants (N = 64) read two conflicting views (pro- and anti-) about a fictional vaccine ('dipherpox vaccine'). These conflicting views were held by a parent and a doctor, whose views varied across conditions. This information was transmitted along linear chains of four participants who recalled it and the product of their recall was passed to the next participant within their chain. They also responded whether they would vaccinate or not. The experience-based view held by the parent was better transmitted than the medical-based view held by the doctor, while the pro-vaccine and anti-vaccine views were similarly transmitted. Despite all the participants having neutral or positive attitudes towards vaccines in general, 39.1% of them decided not to vaccinate. Nevertheless, vaccination attitude was the strongest predictor of vaccination intention. The less positive participants' attitudes were towards vaccines in general, the less likely they were to vaccinate against dipherpox after exposure to the controversy. The results suggest that vaccination campaigns may be made more effective by including personal experiences of the negative consequences of non-vaccination.


Predictive factors and outcomes in endoscopic sinus surgery for chronic rhinosinusitis.
To assess objective and quality of life (QOL) outcomes before and after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS) and to determine preoperative factors that predict surgical outcome in these patients. One hundred nineteen adult patients with CRS and a mean follow-up of 1.4 +/- 0.35 years were evaluated prospectively including the following patient factors: prior sinus surgery, polyps, asthma, acetylsalicylic acid intolerance (ASA), smoking, allergy, depression, and sex. Computed tomography (CT), endoscopy, and QOL assessment was performed. Predictive value of patient factors was determined based on change in endoscopy and QOL scores after ESS. Objective outcomes: preoperative CT scores were significantly worse in patients with polyps, asthma, and ASA, whereas CT score was unaffected by prior sinus surgery, smoking, allergy, depression, and sex. Patients with CRS demonstrated significant improvement on nasal endoscopy after ESS, but preoperative, postoperative, and change in scores were affected by certain patient factors. Endoscopy scores were significantly worse in patients with prior sinus surgery, polyps, asthma, and ASA, but these patients also experienced the greatest improvement in endoscopy scores. Smokers and patients with depression had the least change in endoscopy scores. QOL outcomes: patients with CRS experienced improvement in QOL after ESS. Pre- and postoperative QOL was positively affected by polyps and adversely affected by ASA, depression, and female sex, but these groups still experienced significant improvement in QOL scores. Pre- and postoperative QOL was unaffected by prior sinus surgery, asthma, smoking, and allergies, and all of these groups experienced significant improvement in QOL scores. Factors predictive of outcome: ASA and depression were predictive of worse outcome. Preoperative CT scores approached significance as being predictive of outcome. Surgical management of CRS was associated with significant improvement on objective and QOL measures; however, specific patient factors, in particular ASA and depression, predict poorer outcome. Preoperative CT may be a predictor of endoscopic and QOL outcome and deserves further study.


Preventive effect of ferulic acid on bone loss in ovariectomized rats.
An extract from corn germ induced a positive response in the pigeon crop sack test, used for the detection of prolactin-like substances. One of the substances extracted was identified as ferulic acid, which was reported to affect serum gonadotropin levels in ovariectomized male rats. To evaluate the effects of ferulic acid on bone loss, ovariectomized female rats of the Sprague-Dawley strain at age 35 weeks were given ferulic acid and/or 17a-ethynylestradiol daily for 8 weeks, and serum hormone levels and tibial bone mineral density were measured. In metaphysis of the tibia, which was abundant in cancellous bone and more reflective of BMD than whole tibia, the BMD was markedly reduced by ovariectomy and enhanced by the treatment with estrogen or ferulic acid in the ovariectomized rats. The treatment slightly increased the serum levels of estrogen and progesterone and alkaline phosphatase activity, which was reduced by estrogentreatment, i.e. the mechanism of bone formation by ferulic acid was suggested to be different from that by estrogens. These results indicate that ferulic acid promotes bone remodeling, leading to a predominantly osteoblastic phase, besides bone resorption by osteoclasts.


Trachoma survey methods: a literature review.
Reliable population-based prevalence data are essential for planning, monitoring and evaluating trachoma control programmes and understanding the scale of the problem, yet they are not currently available for 22 out of 56 trachoma-endemic countries. Three survey methods have been advocated for trachoma: cluster random sampling (CRS); trachoma rapid assessment (TRA); and acceptance sampling trachoma rapid assessment (ASTRA). Our review highlights the benefits of CRS being simple, efficient, repeatable and giving population-based prevalence estimates of all signs of trachoma. There are limitations to TRA, which include: non-representative sampling; does not estimate prevalence; and lacks consistency and accuracy. ASTRA advocates small sample sizes but it is relatively complex, may result in imprecise prevalence estimates and does not estimate cicatricial signs of trachoma. We conclude that CRS should therefore remain the 'gold' standard for trachoma surveys. However, among the CRS surveys reviewed, we also found several methodological deficiencies of sample-size calculations, standardization of trachoma graders, reporting of confidence intervals of prevalence estimates, variability of age groups for presentation of age-specific prevalence, and lack of estimation of district prevalence estimates. Properly conducted surveys will be crucial if the objective of global elimination of blinding trachoma is to be charted and realized. Harmonization of survey methods will enhance the conduct and comparability of trachoma surveys needed for reliable mapping of prevalence within endemic countries. Consistent with WHO recommendations, we advocate for continued use of CRS as the survey design of choice for trachoma control programmes and propose ways of improving future surveys based on this method.


Local stakeholders' acceptance of model-generated data used as a communication tool in water management: The Rönneå Study.
The objective of this study was to increase the knowledge of local stakeholders' acceptance of model-generated data when used as a communication tool in water quality management. The Rönneå catchment in the southwest of Sweden was chosen as the study area. The results indicate the model-generated data served as a uniting factor. Simultaneously, the stakeholders were concerned with presented data, the main problems being sources of pollution, which were not accounted for, lack of trustworthiness when measuring pollution, and the uncertainty of the impact of natural variation and delayed effects. Four clusters of factors were identified as influencing stakeholders' acceptance of the model-generated data: confidence in its practical applications, confidence in the people involved in or providing material for the dialog (such as experts, decision-makers, and media), the social characteristics of the participants (such as age and profession), and the way of communicating the data (such as tone of communication, group composition, duration, and geographical scope of the dialog). The perception of the fairness of the practical application of given model-generated data was also an important factor for acceptance.


Spectral method and high-order finite differences for the nonlinear cable equation.
We use high-order approximation schemes for the space derivatives in the nonlinear cable equation and investigate the behavior of numerical solution errors by using exact solutions, where available, and grid convergence. The space derivatives are numerically approximated by means of differentiation matrices. Nonlinearity in the equation arises from the Hodgkin-Huxley dynamics of the gating variables for ion channels. We have investigated in particular the effects of synaptic current distribution and compared the accuracy of the spectral solutions with that of finite differencing. A flexible form for the injected current is used that can be adjusted smoothly from a very broad to a narrow peak, which furthermore leads, for the passive cable, to a simple, exact solution. We have used three distinct approaches to assess the numerical solutions: comparison with exact solutions in an unbranched passive cable, the convergence of solutions with progressive refinement of the grid in an active cable, and the simulation of spike initiation in a biophysically realistic single-neuron model. The spectral method provides good numerical solutions for passive cables comparable in accuracy to those from the second-order finite difference method and far greater accuracy in the case of a simulated system driven by inputs that are smoothly distributed in space. It provides faster convergence in active cables and in a realistic neuron model due to better approximation of propagating spikes.


Differential expression of selected histone modifier genes in human solid cancers.
Post-translational modification of histones resulting in chromatin remodelling plays a key role in the regulation of gene expression. Here we report characteristic patterns of expression of 12 members of 3 classes of chromatin modifier genes in 6 different cancer types: histone acetyltransferases (HATs)- EP300, CREBBP, and PCAF; histone deacetylases (HDACs)- HDAC1, HDAC2, HDAC4, HDAC5, HDAC7A, and SIRT1; and histone methyltransferases (HMTs)- SUV39H1and SUV39H2. Expression of each gene in 225 samples (135 primary tumours, 47 cancer cell lines, and 43 normal tissues) was analysedby QRT-PCR, normalized with 8 housekeeping genes, and given as a ratio by comparison with a universal reference RNA. This involved a total of 13,000 PCR assays allowing for rigorous analysis by fitting a linear regression model to the data. Mutation analysis of HDAC1, HDAC2, SUV39H1, and SUV39H2 revealed only two out of 181 cancer samples (both cell lines) with significant coding-sequence alterations. Supervised analysis and Independent Component Analysis showed that expression of many of these genes was able to discriminate tumour samples from their normal counterparts. Clustering based on the normalized expression ratios of the 12 genes also showed that most samples were grouped according to tissue type. Using a linear discriminant classifier and internal cross-validation revealed that with as few as 5 of the 12 genes, SIRT1, CREBBP, HDAC7A, HDAC5 and PCAF, most samples were correctly assigned. The expression patterns of HATs, HDACs, and HMTs suggest these genes are important in neoplastic transformation and have characteristic patterns of expression depending on tissue of origin, with implications for potential clinical application.


Branched-chain amino acids and central fatigue.
An account of the tryptophan (Trp)-5-hydroxytryptamine (5-HT)-central fatigue theory is provided and an explanation of how oral administration of BCAAs can decrease fatigue on the basis of this theory is given. The rate-limiting step in the synthesis of 5-HT is the transport of Trp across the blood-brain barrier. This transport is influenced by the fraction of Trp available for transport into the brain and the concentration of the other large neutral amino acids, including the BCAAs, which are transported via the same carrier system. During endurance exercise, there is an uptake of Trp by the brain, suggesting that this may increase the synthesis and release of 5-HT in the brain. Oral intake of BCAAs may reduce this uptake and also brain 5-HT synthesis and release, thereby delaying fatigue. Other hypotheses for the effect of BCAAs on central fatigue are included.


Two centuries of masting data for European beech and Norway spruce across the European continent.
Tree masting is one of the most intensively studied ecological processes. It affects nutrient fluxes of trees, regeneration dynamics in forests, animal population densities, and ultimately influences ecosystem services. Despite a large volume of research focused on masting, its evolutionary ecology, spatial and temporal variability, and environmental drivers are still matter of debate. Understanding the proximate and ultimate causes of masting at broad spatial and temporal scales will enable us to predict tree reproductive strategies and their response to changing environment. Here we provide broad spatial (distribution range-wide) and temporal (century) masting data for the two main masting tree species in Europe, European beech (Fagus sylvatica L.) and Norway spruce (Picea abies (L.) H. Karst.). We collected masting data from a total of 359 sources through an extensive literature review and from unpublished surveys. The data set has a total of 1,747 series and 18,348 yearly observations from 28 countries and covering a time span of years 1677-2016 and 1791-2016 for beech and spruce, respectively. For each record, the following information is available: identification code; species; year of observation; proxy of masting (flower, pollen, fruit, seed, dendrochronological reconstructions); statistical data type (ordinal, continuous); data value; unit of measurement (only in case of continuous data); geographical location (country, Nomenclature of Units for Territorial Statistics NUTS-1 level, municipality, coordinates); first and last record year and related length; type of data source (field survey, peer reviewed scientific literature, gray literature, personal observation); source identification code; date when data were added to the database; comments. To provide a ready-to-use masting index we harmonized ordinal data into five classes. Furthermore, we computed an additional field where continuous series with length >4 yr where converted into a five classes ordinal index. To our knowledge, this is the most comprehensive published database on species-specific masting behavior. It is useful to study spatial and temporal patterns of masting and its proximate and ultimate causes, to refine studies based on tree-ring chronologies, to understand dynamics of animal species and pests vectored by these animals affecting human health, and it may serve as calibration-validation data for dynamic forest models.


An improved technique to enable 2-dimensional shoe sole impression evidence to be photographically recorded "to scale".
An improved technique to photographically record 2-Dimensional shoe sole impressions "to scale" is described. This technique was developed as a result of continual attacks in court in relation to the question of precise SCALE. Staff at our laboratory are routinely required to examine shoe sole impressions evidence that has been collected by our Scenes of Crime Officers. The Scenes of Crime Officers have been instructed in the appropriate photographic techniques which should be used to record 2-Dimensional shoe sole impressions, however, for one reason or another, including inexperience, this technique is not rigidly adhered to. We have seventy-five (75) Scenes of Crime Officers throughout Queensland, and nearly all of the shoe sole interpretation work is done in the Brisbane Headquarters. It is the case that the Scenes of Crime Officers record the scene and other photographers record the Test Impression. There are three problems that affect the quality of the scale photographs submitted. 1. The camera is not directly over the center of the subject. 2. The camera is not exactly parallel to the subject. 3. The designs of the camera lens. These problems are highlighted when barristers compare the scale photos of the test impressions made in the laboratory, with the scale photos of the scene impressions. Barristers actually measure the distance between features and usually a discrepancy (albeit slight) is found. The GRID allows us to demonstrate to Lay persons and Lawyers the interrelationship of identification features, by reference to a particular GRID.


Association between healthcare water systems and Pseudomonas aeruginosa infections: a rapid systematic review.
Pseudomonas aeruginosa is an opportunistic pathogen with a particular propensity to cause disease in the immunocompromised. Water systems have been reported to contribute to P. aeruginosa transmission in healthcare settings. To systematically assess the evidence that healthcare water systems are associated with P. aeruginosa infection; to review aspects of design that can increase their potential to act as a reservoir; and to compare the efficacy of strategies for eradicating contamination and preventing infection. A rapid review methodology with a three-step search strategy was used to identify published studies. Scientific advisors were used to identify unpublished studies. Twenty-five relevant studies were included. There was plausible evidence of transmission of P. aeruginosa from water systems to patients and vice versa, although no direct evidence to explain the exact mode of transfer. Two studies provided plausible evidence for effective interventions: point-of-use filters and increasing chlorine disinfection. Non-touch taps and aspects of water system design were identified as probable risk factors for P. aeruginosa biofilm formation and subsequent transmission to patients. Poor hand hygiene or compliance with contact precautions were identified as potential contributory factors; plausible evidence to confirm this was not available. Water systems can act as a source of P. aeruginosa infection in healthcare settings, although the route of transmission is unclear. Contamination appears to be confined to the distal ends of a water system and can persist for prolonged periods. Further studies are required to establish effective methods of preventing transmission and eradicating P. aeruginosa from plumbing systems.


[Binding of 1-0-alkyl-2-0-acetyl-sn-glycero-3-phosphocholine (thrombocyte activating factor) by plasma components. Exchange of the thrombocyte activating factor between lipoproteins and thrombocytes].
The binding of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a platelet activating factor (PAF), to plasma components was studied. Gel filtration and lipoprotein fractionation revealed the presence in the plasma of PAF-binding fractions corresponding to plasma albumin as well as of low and high density lipoproteins. Incubation of PAF-containing lipoproteins with rabbit platelets resulted in a transfer of PAF to the platelets. PAF bound to plasma albumin is less exchangeable than PAF bound to lipoproteins. The PAF-transferring efficiency of high density lipoproteins (HDL) and of low density lipoproteins (LDL) correlates with the amounts of HDL- and LDL-receptors on the platelet surface. It may thus be assumed that PAF released by various cells interacts with lipoproteins which further transport the bound PAF to target cells carrying lipoprotein receptors.


Knowledge and use of evidence-based practice by allied health and health science professionals in the United Kingdom.
Clinical effectiveness (CE) and evidence-based practice (EBP) are the cornerstone of modern-day health care. Although many studies have explored attitudes and perceived knowledge of individual professions, few have compared these factors between professional groups, especially in the allied health professions (AHP) and health science services (HSS). We report a study comparing the knowledge and practice of 14 different professional groups from the AHP and HSS in terms of EBP and CE. The aim was to highlight any differences between the 14 professional groups along with the needs of the groups. A postal questionnaire survey was completed by a random sample of 1,000 members of AHP and HSS across the United Kingdom. There were significant differences between professional groups with, in general, professionals from the HSS groups rating their knowledge and application of CE and EBP as lower than members of the AHP. Differences were also noted between individual professional groups. For example, podiatrists, radiographers, and orthoptists reported having less knowledge of CE and EBP than physiotherapists, occupational therapists, dietitians, speech and language therapists, and psychologists. Barriers to implementing EBP were similar for all groups, with lack of both time and money cited as the main issues. A number of differences between professions were recorded that highlight the difference in educational and policy approach required for greater uptake of EBP.


[Racial, sociodemographic, and prenatal and childbirth care inequalities in Brazil, 1999-2001].
To analyze social inequalities and inequalities in access to and utilization of health care services according to skin color in a representative sample of postpartum women receiving hospital childbirth care. A cross-sectional study was carried out in a sample of 9,633 postpartum women, of whom 5,002 were white (51.9%), 2,796 mulatto (29.0%), and 1,835 black skin color (19.0%), seen in public maternity hospitals, hospitals contracted out by the Unified National Health System, and private hospitals in the period 1999-2001. Data were collected from medical records and through interviews with the mothers in the immediate postpartum period using standardized questionnaires. Statistical analyses were performed using chi(2) tests to assess homogeneity of proportions and Student's t-test for comparison of measures. The analysis was stratified by maternal schooling. A persistent unfavorable situation was seen for mulatto and black women as compared to white women. Mulatto and black women had the highest rates of adolescent mothers, low schooling, unpaid occupation, and not having a partner. History of physical violence, smoking, attempts to interrupt pregnancy, and visits to several hospitals before being admitted were more frequent among black women, followed by mulatto and then white women of low schooling. High schooling group of women showed better indicators but the same pattern was seen. This variability is also seen in the opposite direction in terms of the level of satisfaction with prenatal and childbirth care. It was distinguished two forms of discrimination, by educational level and skin color, in care delivered by health services to postpartum women in Rio de Janeiro.