Prevalence of celiac disease and celiac-related antibody status in pediatric patients with type 1 diabetes in Jordan
Scientific findings regarding the prevalence of celiac disease (CD) in pediatric patients with type 1 diabetes (T1D) in the Arab world are scarce. We aimed to determine the prevalence of biopsy-proven celiac disease (BPCD) among pediatric patients with T1D from Jordan. We also assessed the possible predictors for developing CD in this cohort of patients and we compared T1D patients who developed BPCD with those who had positive CD serology but negative histology and/or fluctuating CD serology. Celiac serology and duodenal biopsy results from 2012 to 2017 were collected from patients with T1D. The outcome of positive celiac serology and the risk factors for CD in T1D patients were investigated. A total of 538 children of which 278 boys (51.7%) were included in the study. The prevalence of positive serology and the diagnosis of BPCD in this cohort of T1D patients were 16.6 and 9.1% respectively. Eighty percent of those with BPCD were asymptomatic and 47% were diagnosed with CD at onset of T1D. Spontaneous normalization of celiac serology occurred in 23.6% of those with positive serology. CD is prevalent in T1D pediatric patients from Jordan (9.1%). It is often asymptomatic and the majority of cases were diagnosed at onset or within 5 years of T1D diagnosis. Spontaneous normalization of CD serology occurred in some patients with T1D. Hence, a watchful follow-up is recommended in such patients.


Novel foods to treat food allergy and gastrointestinal infection.
The gastrointestinal tract communicates directly with the external environment. Necessary nutrients must be absorbed and commensal bacteria tolerated, and foreign proteins, antigens, and pathogens must be simultaneously excluded or destroyed. Immaturity or disruption of the mucosal immune defenses increases vulnerability to food allergy, intolerance, and infectious disease. Diseases resulting from ingested foreign proteins and organisms are increasing and cause morbidity and mortality worldwide. There is no specific treatment for food allergy other than avoidance. Vaccination for infectious disease is limited by the cost and logistics of distribution and administration, particularly in developing countries. Novel strategies are being explored to modulate the gut mucosal immune system by altering protein expression in food. Crops are being developed to remove deleterious allergens to prevent immunogenic exposure while preserving nutritional quality. Local food plants that express protein fragments of pathogens might provide an effective means to stimulate gut mucosal immunity while increasing vaccine accessibility.


Economic aspects of foot and mouth disease: perspectives of a free country, Australia.
Australia is a significant livestock producer and a major exporter of livestock, livestock products and livestock genetic material. An outbreak of foot and mouth disease (FMD) would have severe economic consequences on the economy. A recent study found that in an outbreak lasting six months, real gross domestic product in Australia would fall by an estimated 0.6% (AUS$3.5 billion), employment by 0.8%, and a depreciation of 3% would be recorded in the exchange rate in the first year. Much of this impact would be due to the loss of export markets. Given the significant consequences of an outbreak of FMD, Australia invests considerable resources in prevention and planning. These measures can be viewed at three levels, namely: pre-border, border and post-border. Australia recently further enhanced quarantine at the border to minimise the risk of entry of FMD. However, no matter how much is invested, there is no guarantee that FMD will not enter the country. Accordingly, it is important to ensure that comprehensive contingency plans are also in place. Recent outbreaks in previously free countries have shown that a large outbreak of FMD poses major problems for the animal health services of a country and a combined government and industry response is required.


The genetic and molecular basis for sunscreen biosynthesis in cyanobacteria.
Ultraviolet UV-A and UV-B radiation is harmful to living systems, causing damage to biological macromolecules. An important strategy for dealing with UV exposure is the biosynthesis of small-molecule sunscreens. Among such metabolites, the mycosporine and mycosporine-like amino acids (MAAs) are remarkable for their wide phylogenetic distribution and their unique chemical structures. Here, we report the identification of a MAA biosynthetic gene cluster in a cyanobacterium and the discovery of analogous pathways in other sequenced organisms. We have expressed the cluster in a heterologous bacterial host and characterized all four biosynthetic enzymes in vitro. In addition to clarifying the origin of the MAAs, these efforts have revealed two unprecedented enzymatic strategies for imine formation.


CD133 (Prominin) negative human neural stem cells are clonogenic and tripotent.
CD133 (Prominin) is widely used as a marker for the identification and isolation of neural precursor cells from normal brain or tumor tissue. However, the assumption that CD133 is expressed constitutively in neural precursor cells has not been examined. In this study, we demonstrate that CD133 and a second marker CD15 are expressed heterogeneously in uniformly undifferentiated human neural stem (NS) cell cultures. After fractionation by flow cytometry, clonogenic tripotent cells are found in populations negative or positive for either marker. We further show that CD133 is down-regulated at the mRNA level in cells lacking CD133 immunoreactivity. Cell cycle profiling reveals that CD133 negative cells largely reside in G1/G0, while CD133 positive cells are predominantly in S, G2, or M phase. A similar pattern is apparent in mouse NS cell lines. Compared to mouse NS cells, however, human NS cell cultures harbour an increased proportion of CD133 negative cells and display a longer doubling time. This may in part reflect a sub-population of slow- or non-cycling cells amongst human NS cells because we find that around 5% of cells do not take up BrdU over a 14-day labelling period. Non-proliferating NS cells remain undifferentiated and at least some of them are capable of re-entry into the cell cycle and subsequent continuous expansion. The finding that a significant fraction of clonogenic neural stem cells lack the established markers CD133 and CD15, and that some of these cells may be dormant or slow-cycling, has implications for approaches to identify and isolate neural stem cells and brain cancer stem cells. Our data also suggest the possibility that CD133 may be specifically down-regulated during G0/G1, and this should be considered when this marker is used to identify and isolate other tissue and cancer stem cells.


Improvement of Repeated-Sprint Ability and Horizontal-Jumping Performance in Elite Young Basketball Players With Low-Volume Repeated-Maximal-Power Training.
To examine the effects of a low-volume repeated-power-ability (RPA) training program on repeated-sprint and change-of- direction (COD) ability and functional jumping performance. Twenty-two male elite young basketball players (age 16.2 ± 1.2 y, height 190.0 ± 10.0 cm, body mass 82.9 ± 10.1 kg) were randomly assigned either to an RPA-training group (n = 11) or a control group (n = 11). RPA training consisted of leg-press exercise, twice a week for 6 wk, of 1 or 2 blocks of 5 sets × 5 repetitions with 20 s of passive recovery between sets and 3 min between blocks with the load that maximized power output. Before and after training, performance was assessed by a repeated-sprint-ability (RSA) test, a repeated-COD-ability test, a hop for distance, and a drop jump followed by tests of a double unilateral hop with the right and left legs. Within-group and between-groups differences showed substantial improvements in slowest (RSAs) and mean time (RSAm) on RSA; best, slowest and mean time on repeated-COD ability; and unilateral right and left hop in the RPA group in comparison with control. While best time on RSA showed no improvement in any group, there was a large relationship (r = .68, 90% CI .43;.84) between the relative decrement in RSAm and RSAs, suggesting better sprint maintenance with RPA training. The relative improvements in best and mean repeated-COD ability were very largely correlated (r = .89, 90% CI .77;.94). Six weeks of lowvolume (4-14 min/wk) RPA training improved several physical-fitness tests in basketball players.


Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation.
Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis. To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research. Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field. Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services. Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84-89% and specificity of 46-55%. Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling. Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain. Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis. This study is registered as PROSPERO CRD42017058688. The National Institute for Health Research Health Technology Assessment programme.


Using a nurse invented T-Bar device in a rehabilitation program improved the range of motion for rotator cuff repair patients.
This study investigates the effects on patient outcomes of using a T-bar in rehabilitation programs in shoulder arthroscopic surgical procedure patients. Orthopaedic nurses play an important role in facilitating restoration of patients' range of motion shoulder function. Conventionally, nurses instruct patients to use the unaffected arm to hold the surgical arm when performing range of motion. However, patients often have difficulty performing the entire range of motion efficiently in this manner. Therefore, nurses have invented a T-bar device to help patients perform range of motion in a rehabilitation program. A repeated-measure, quasi-experimental study. Sixty-eight participants were recruited from four orthopaedic wards of a medical center in Taipei, Taiwan. Of the patients meeting the inclusion criteria for the study, 33 were assigned to the experimental group and 35 to the comparison group. Both groups had the same shoulder rehabilitation program including identical activities, duration and frequency, except that the experimental group used the nurse invented T-bar device to facilitate range of motion while the comparison group used a conventional method. Data were collected when patients were admitted, five days and four weeks after the surgery. Outcome indicators were shoulder range of motion, muscle power and the American Shoulder and Elbow Society Shoulder Index. Statistical methods used for analysis included mean, standard deviation and repeated measures anova. All the participants completed the study. Results showed a significant improvement in shoulder abduction after surgery in experimental group versus the comparison group. No significant differences were found in other outcomes. The nurse invented T-bar device used in the rehabilitation program was effective in helping restore the abduction function of rotator cuff repair patients in our preliminary study. Using a T-bar in the rehabilitation program to improve range of motion may be considered for patients with shoulder surgery.


Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.
Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.


Interactions between response to inhaled prostaglandin E2 and chronic beta-adrenergic agonist treatment.
Cumulative inhalation dose-response curves for the response to prostaglandin E2 (PGE2) have been constructed in normal subjects and patients with mild, stable asthma. In normal subjects cumulative inhalation dose-response curves were also constructed for salbutamol. In normal subjects dose-related bronchodilatation occurred in response to both PGE2 and salbutamol, although both the within-subject and the between-subject variation was significantly greater with salbutamol. Most asthmatic subjects gave a biphasic response to PGE2 on at least one occasion, PGE2 being a bronchoconstrictor above a certain level of specific airways conductance (sGaw) and a bronchodilator below. Chronic treatment with inhaled salbutamol (400 micrograms four times a day) had no effect on the normal subjects' response to salbutamol but there was a significant shift of the PGE2 dose-response curve to the left, indicating increased bronchodilatation (p less than 0.02). Stabilisation of the asthmatics' dose-response curve in the direction of bronchodilatation also occurred and was more pronounced (p less than 0.005). In the normal subjects PGE2 may be concerned in the control of airway smooth-muscle tone and in limiting bronchoconstriction induced by mediators such as histamine, and chronic salbutamol treatment may be important in enhancing these effects of PGE2. 80 mg oral propranolol given one and a half hours before had no effect on PGE2-induced bronchodilatation; but the question whether chronic treatment with beta-blockers has any effect needs investigation.


Fetal fibronectin testing for reducing the risk of preterm birth.
Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where it is concentrated in this area between decidua and trophoblast. In normal conditions, FFN is found at very low levels in cervicovaginal secretions. Levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. In fact, FFN is one of the best predictors of preterm birth in all populations studied so far, and can help in selecting which women are at significant risk for preterm birth. This is an update of a review first published in 2008. To assess the effectiveness of management based on knowledge of FFN testing results for preventing preterm birth. For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (7 September 2018), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 September 2018), and reference lists of retrieved studies. Randomized controlled trials of pregnant women screened with FFN for risk of preterm birth. Studies included are based exclusively on knowledge of FFN results versus no such knowledge, and we have excluded studies including women with only positive or only negative FFN results. Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach. We identified 16 trials, of which six were eligible for inclusion. The six included studies randomized 546 women with singleton gestations and threatened preterm labor (PTL) at 23 0/7 to 34 6/7 weeks. A total of 277 women were randomized to knowledge and 269 to no knowledge of FFN. No trials were identified on asymptomatic women or multiple gestations.The risk of bias of included studies was mixed. For selected important outcomes, preterm birth before 37, 34, and 32 weeks, and maternal hospitalization, we graded the quality of the evidence and created a 'Summary of findings' table. For these outcomes, the evidence was graded as mainly low quality due to the imprecision of effect estimates.Management based on knowledge of FFN results may reduce preterm birth before 37 weeks (21.6%) versus controls without such knowledge (29.2%) (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.52 to 1.01; 4 trials; 357 women; low-quality evidence). However, management based on knowledge of FFN results may make little or no difference to preterm birth before 34 (RR 1.09, 95% CI 0.54 to 2.18; 4 trials; 357 women; low-quality evidence) or maternal hospitalization (RR 1.06, 95% CI 0.79 to 1.43; 5 trials; 441 women; low-quality evidence). The evidence for preterm birth before 32 weeks is uncertain because the quality was found to be very low (average RR 0.79, 95% CI 0.16 to 3.96; 4 trials; 357 women; very low-quality evidence).For all other outcomes, for which there were available data (preterm birth less than 28 weeks; gestational age at delivery (weeks); birthweight less than 2500 g; perinatal death; tocolysis; steroids for fetal lung maturity; time to evaluate; respiratory distress syndrome; neonatal intensive care unit (NICU) admission; and NICU days), knowledge of FFN results may make little or no difference to the outcomes. The evidence from this review suggests that management based on knowledge of FFN results may reduce preterm birth before 37 weeks. However, our confidence in this result is limited as the evidence was found to be of low quality. Effects on other substantive outcomes are uncertain due to serious concerns in study design, inconsistency, and imprecision of effect estimates. No trials were identified on asymptomatic women, or multiple gestations.Future studies are needed that include specific populations (e.g. singleton gestations with symptoms of preterm labor), a study group managed with a protocol based on the FFN results, and that report not only maternal but also important perinatal outcomes. Cost-effectiveness analyses are also needed.


Brain macro- and microscopic damage in patients with paediatric MS.
To characterise, using conventional and diffusion tensor (DT) MRI, the nature and distribution of lesions and the extent of damage in the brain normal-appearing white matter (NAWM) and grey matter (GM) from a relatively large population of paediatric multiple sclerosis (MS) patients. Brain conventional and DT MRI scans were acquired from 48 patients with paediatric MS (10 clinically isolated syndromes (CIS), 38 relapsing remitting (RR) MS), 30 adult CIS, 27 adult RRMS, 15 paediatric healthy controls (HC) and 18 adult HC. T2-lesion probability maps and DT MRI of lesions, NAWM and GM were compared among controls and MS groups. T2-visible lesion volumes did not differ among patient groups, but T2 lesions were more frequently located in the posterior periventricular regions in adult RRMS patients than in adult CIS and paediatric RRMS patients. Adult RRMS patients had a significantly higher lesion average mean diffusivity than paediatric RRMS patients. No DT MRI changes in the NA tissues were found in paediatric and adult CIS patients. DT MRI abnormalities were limited to the NAWM in paediatric RRMS patients, while they involved the NAWM and GM in adult RRMS patients. The extent of NAWM involvement was similar between adult and paediatric RRMS patients and was significantly correlated with T2-visible lesion burden. A less severe intrinsic lesion damage, a less frequent lesion occurrence in the posterior periventricular WM and the sparing of GM may help to explain the favourable short-/medium-term disease outcome of paediatric MS.


Being Conscious of Water Intake Positively Associated with Sufficient Non-Alcohol Drink Intake Regardless of Seasons and Reasons in Healthy Japanese; the KOBE Study: A Cross Sectional Study.
The present study sought to clarify if being conscious of water intake (CWI) is associated with sufficient non-alcohol drink (NAD) intake. We used data of healthy participants without diabetes, aged 40-74 years, in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. The association between being CWI and NAD intake was evaluated by multivariate linear regression analyses after adjusting for age, sex, surveyed months (seasons), alcohol drinking, health-awareness life habits, socioeconomic factors, serum osmolarity, estimated daily salt intake, and reasons for NAD intake. Among 988 (698 women and 290 men) participants eligible for the present analyses, 644 participants (65.2%) were CWI and 344 participants (34.8%) were not CWI (non-CWI). The most popular reason for being CWI was to avoid heat stroke in summer and to prevent ischemic cerebral stroke in winter. The CWI group took more NAD, especially decaffeinated beverages, than the non-CWI group (1846.7 ± 675.1 mL/day vs. 1478.0 ± 636.3 ml/day, p < 0.001). There was a significant association between being CWI and NAD intake in multivariate linear regression analyses ever after adjusting for the relevant variables (β = 318.1, p < 0.001). These findings demonstrated CWI, regardless of the reasons and the seasons, was associated with high NAD intake in Japanese healthy population.


GPo1 alkB gene expression for improvement of the degradation of diesel oil by a bacterial consortium.
To facilitate the biodegradation of diesel oil, an oil biodegradation bacterial consortium was constructed. The alkane hydroxylase (alkB) gene of Pseudomonas putida GPo1 was constructed in a pCom8 expression vector, and the pCom8-GPo1 alkB plasmid was transformed into Escherichia coli DH5α. The AlkB protein was expressed by diesel oil induction and detected through SDS-polyacrylamide gel electrophoresis. The culture of the recombinant (pCom8-GPo1 alkB/E. coli DH5α) with the oil biodegradation bacterial consortium increased the degradation ratio of diesel oil at 24 h from 31% to 50%, and the facilitation rates were increased as the proportion of pCom8-GPo1 alkB/E. coli DH5α to the consortium increased. The results suggested that the expression of the GPo1 gene in E. coli DH5α could enhance the function of diesel oil degradation by the bacterial consortium.


Two DNA-bound E2 dimers are required for strong transcriptional activation and for cooperation with cellular factors in most cells.
The E2 transcriptional activator encoded by papillomaviruses binds as a dimer to the palindromic sequence ACCGNNNNCGGT present in several copies in the viral genomes. We show that strong activation requires that a minimum of two E2 binding sites are actually occupied by the protein. Studies with constructs bearing two E2 sites separated by variable lengths of DNA showed that there is no stereospecific constraint for E2 homosynergy. The capacity of E2 to cooperate with cellular factors interacting with the promoter/enhancer sequences of the genomes of human papilloma virus types 16, 18, or 33 was further investigated. In epithelial cells, one E2 dimer could not cooperate with the AP1 complex, the glucocorticoid receptor, or the NF1/K factor, whereas several E2 dimers could. These results lead to the notion of the "functional E2 tetramer" as the unit for strong transcriptional activation by E2 and for cooperativity with other cellular factors in this process. Finally, our results suggest that activators such as E2 or the glucocorticoid receptor may interact with partially different targets in the transcriptional machinery.


Rapid, Culture-Free Detection of Staphylococcus aureus Bacteremia.
S. aureus bacteremia (SAB) is a common condition with high rates of morbidity and mortality. Current methods used to diagnose SAB take at least a day, and often longer. Patients with suspected bacteremia must therefore be empirically treated, often unnecessarily, while assay results are pending. In this proof-of-concept study, we describe an inexpensive assay that detects SAB via the detection of micrococcal nuclease (an enzyme secreted by S. aureus) in patient plasma samples in less than three hours. In total, 17 patient plasma samples from culture-confirmed S. aureus bacteremic individuals were tested. 16 of these yielded greater nuclease assay signals than samples from uninfected controls or individuals with non-S. aureus bacteremia. These results suggest that a nuclease-detecting assay may enable the rapid and inexpensive diagnosis of SAB, which is expected to substantially reduce the mortality and morbidity that result from this condition.


Bayesian inference of accurate population sizes and FRET efficiencies from single diffusing biomolecules.
It is of significant biophysical interest to obtain accurate intramolecular distance information and population sizes from single-molecule Förster resonance energy transfer (smFRET) data obtained from biomolecules in solution. Experimental methods of increasing cost and complexity are being developed to improve the accuracy and precision of data collection. However, the analysis of smFRET data sets currently relies on simplistic, and often arbitrary methods, for the selection and denoising of fluorescent bursts. Although these methods are satisfactory for the analysis of simple, low-noise systems with intermediate FRET efficiencies, they display systematic inaccuracies when applied to more complex systems. We have developed an inference method for the analysis of smFRET data from solution studies based on rigorous model-based Bayesian techniques. We implement a Monte Carlo Markov chain (MCMC) based algorithm that simultaneously estimates population sizes and intramolecular distance information directly from a raw smFRET data set, with no intermediate event selection and denoising steps. Here, we present both our parametric model of the smFRET process and the algorithm developed for data analysis. We test the algorithm using a combination of simulated data sets and data from dual-labeled DNA molecules. We demonstrate that our model-based method systematically outperforms threshold-based techniques in accurately inferring both population sizes and intramolecular distances.


Metagenomic analysis of medicinal Cannabis samples; pathogenic bacteria, toxigenic fungi, and beneficial microbes grow in culture-based yeast and mold tests.
Background: The presence of bacteria and fungi in medicinal or recreational Cannabis poses a potential threat to consumers if those microbes include pathogenic or toxigenic species. This study evaluated two widely used culture-based platforms for total yeast and mold (TYM) testing marketed by 3M Corporation and Biomérieux, in comparison with a quantitative PCR (qPCR) approach marketed by Medicinal Genomics Corporation. Methods: A set of 15 medicinal Cannabis samples were analyzed using 3M and Biomérieux culture-based platforms and by qPCR to quantify microbial DNA. All samples were then subjected to next-generation sequencing and metagenomics analysis to enumerate the bacteria and fungi present before and after growth on culture-based media. Results: Several pathogenic or toxigenic bacterial and fungal species were identified in proportions of >5% of classified reads on the samples, including Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Ralstonia pickettii, Salmonella enterica, Stenotrophomonas maltophilia, Aspergillus ostianus, Aspergillus sydowii, Penicillium citrinum and Penicillium steckii. Samples subjected to culture showed substantial shifts in the number and diversity of species present, including the failure of Aspergillus species to grow well on either platform. Substantial growth of Clostridium botulinum and other bacteria were frequently observed on one or both of the culture-based TYM platforms. The presence of plant growth promoting (beneficial) fungal species further influenced the differential growth of species in the microbiome of each sample. Conclusions: These findings have important implications for the Cannabis and food safety testing industries.


Two corticotectal areas facilitate multisensory orientation behavior.
It had previously been shown that influences from two cortical areas, the anterior ectosylvian sulcus (AES) and the rostral lateral suprasylvian sulcus (rLS), play critical roles in rendering superior colliculus (SC) neurons capable of synthesizing their cross-modal inputs. The present studies examined the consequences of selectively eliminating these cortical influences on SC-mediated orientation responses to cross-modal stimuli. Cats were trained to orient to a low-intensity modality-specific cue (visual) in the presence or absence of a neutral cue from another modality (auditory). The visual target could appear at various locations within 45 degrees of the midline, and the stimulus effectiveness was varied to yield an average of correct orientation responses of approximately 45%. Response enhancement and depression were observed when the auditory cue was coupled with the target stimulus: A substantially enhanced probability in correct responses was evident when the cross-modal stimuli were spatially coincident, and a substantially decreased response probability was obtained when the stimuli were spatially disparate. Cryogenic blockade of either AES or rLS disrupted these behavioral effects, thereby eliminating the enhanced performance in response to spatially coincident cross-modal cues and degrading the depressed performance in response to spatially disparate cross-modal cues. These disruptive effects on targets contralateral to the deactivated cortex were restricted to multisensory interactive processes. Orientation to modality-specific targets was unchanged. Furthermore, the pattern of orientation errors was unaffected by cortical deactivation. These data bear striking similarities to the effects of AES and rLS deactivation on multisensory integration at the level of individual SC neurons. Presumably, eliminating the critical influences from AES or rLS cortex disrupts SC multisensory synthesis that, in turn, disables SC-mediated multisensory orientation behaviors.


The effects of weather on daily mood: a multilevel approach.
The present study examines the effects of six weather parameters (temperature, wind power, sunlight, precipitation, air pressure, and photoperiod) on mood (positive affect, negative affect, and tiredness). Data were gathered from an online diary study (N = 1,233), linked to weather station data, and analyzed by means of multilevel analysis. Multivariate and univariate analyses enabled distinction between unique and shared effects. The results revealed main effects of temperature, wind power, and sunlight on negative affect. Sunlight had a main effect on tiredness and mediated the effects of precipitation and air pressure on tiredness. In terms of explained variance, however, the average effect of weather on mood was only small, though significant random variation was found across individuals, especially regarding the effect of photoperiod. However, these individual differences in weather sensitivity could not be explained by the Five Factor Model personality traits, gender, or age.


Kolliphor surfactants affect solubilization and bioavailability of fenofibrate. Studies of in vitro digestion and absorption in rats.
Selection of excipients for drug formulations requires both intellectual and experimental considerations as many of the used excipients are affected by physiological factors, e.g., they may be digested by pancreatic enzymes in the gastrointestinal tract. In the present paper we have looked systematically into the differences between Kolliphor ELP, EL, and RH40 and how they affect the bioavailability of fenofibrate, through pharmacokinetic studies in rats and in vitro lipolysis studies. The study design was made as simple as possible to avoid confounding factors, for which reason the tested formulations only comprised an aqueous micellar solution of the model drug (fenofibrate) in varying concentrations (2-25% (w/v)) of the three tested surfactants. Increased concentrations of Kolliphor ELP and EL led to increased fenofibrate AUC0-24h values. For the Kolliphor RH40 formulations, an apparent fenofibrate absorption optimum was seen at 15% (w/v) surfactant, displaying both the highest AUC0-24h and Cmax. The reduced absorption of fenofibrate from the formulation containing the highest level of surfactant (25% w/v) was thought to be caused by some degree of trapping within Kolliphor RH40 micelles. In vitro, Kolliphor ELP and EL were found to be more prone to digestion than Kolliphor RH40, though not affecting the in vivo results. The highest fenofibrate bioavailability was attained from formulations with high Kolliphor ELP/EL levels (25% (w/v)), indicating that these surfactants are the better choice for solubilizing fenofibrate in order to increase the absorption upon oral administration. Due to drug dependent effects of the different types of Kolliphor, more studies are recommended in order to understand which type of Kolliphor is best suited for a given drug.


Identifying patients with bacterial infections using a combination of C-reactive protein, procalcitonin, TRAIL, and IP-10 in the emergency department: a prospective observational cohort study.
The aim was to effectively reduce the unnecessary use of broad spectrum antibiotics in the emergency department (ED), patients with bacterial infections need to be identified accurately. We investigated the diagnostic value of a combination of biomarkers for bacterial infections, C-reactive protein (CRP), and procalcitonin (PCT), together with biomarkers for viral infections, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and interferon-gamma-induced protein-10 (IP-10), in identifying suspected and confirmed bacterial infections in a general ED population with fever. This is a sub-study in the HiTEMP cohort. Patients with fever were included during ED triage, and blood samples were obtained. Using both diagnostics and expert panel analysis, all patients were classified as having either suspected or confirmed bacterial infections, or non-bacterial disease. Using multivariable logistic regression analysis, three biomarker models were analysed: model 1, CRP, TRAIL, IP-10; model 2, PCT, TRAIL, IP-10; and model 3, CRP, PCT, TRAIL, IP-10. A total of 315 patients were included, of whom 228 patients had a suspected or confirmed bacterial infection. The areas under the curve for the combined models were the following: model 1, 0.730 (95% CI 0.665-0.795); model 2, 0.748 (95% CI 0.685-0.811); and model 3, 0.767(95% CI 0.704-0.829). These findings show that a combination of CRP, PCT, TRAIL and IP-10 can identify bacterial infections with higher accuracy than single biomarkers and combinations of a single bacterial biomarkers combined with TRAIL and IP-10.


The hepatic sinusoid in aging and cirrhosis: effects on hepatic substrate disposition and drug clearance.
The fenestrated sinusoidal endothelium ('liver sieve') and space of Disse in the healthy liver do not impede the transfer of most substrates, including drugs and oxygen, from the sinusoidal lumen to the hepatocyte. Plasma components transfer freely in both directions through the endothelial fenestrations and into the space of Disse. The endothelium is attenuated, there is no basement membrane and there is minimum collagen in the space of Disse, thus minimising any barriers to substrate diffusion. Both cirrhosis and aging are associated with marked structural changes in the sinusoidal endothelium and space of Disse that are likely to influence bulk plasma transfer into the space of Disse, and diffusion through the endothelium and space of Disse. These changes, termed capillarisation and pseudocapillarisation in cirrhosis and aging, respectively, impede the transfer of various substrates. Capillarisation is associated with exclusion of albumin, protein-bound drugs and macromolecules from the space of Disse, and the progressive transformation of flow-limited to barrier-limited distribution of some substrates. There is evidence that the sinusoidal changes in cirrhosis and aging contribute to hepatocyte hypoxia, thus providing a mechanism for the apparent differential reduction of oxygen-dependent phase I metabolic pathways in these conditions. Structural change and subsequent dysfunction of the liver sieve warrant consideration as a significant factor in the impairment of overall substrate handling and hepatic drug metabolism in cirrhosis and aging.


Learning New Sensorimotor Contingencies: Effects of Long-Term Use of Sensory Augmentation on the Brain and Conscious Perception.
Theories of embodied cognition propose that perception is shaped by sensory stimuli and by the actions of the organism. Following sensorimotor contingency theory, the mastery of lawful relations between own behavior and resulting changes in sensory signals, called sensorimotor contingencies, is constitutive of conscious perception. Sensorimotor contingency theory predicts that, after training, knowledge relating to new sensorimotor contingencies develops, leading to changes in the activation of sensorimotor systems, and concomitant changes in perception. In the present study, we spell out this hypothesis in detail and investigate whether it is possible to learn new sensorimotor contingencies by sensory augmentation. Specifically, we designed an fMRI compatible sensory augmentation device, the feelSpace belt, which gives orientation information about the direction of magnetic north via vibrotactile stimulation on the waist of participants. In a longitudinal study, participants trained with this belt for seven weeks in natural environment. Our EEG results indicate that training with the belt leads to changes in sleep architecture early in the training phase, compatible with the consolidation of procedural learning as well as increased sensorimotor processing and motor programming. The fMRI results suggest that training entails activity in sensory as well as higher motor centers and brain areas known to be involved in navigation. These neural changes are accompanied with changes in how space and the belt signal are perceived, as well as with increased trust in navigational ability. Thus, our data on physiological processes and subjective experiences are compatible with the hypothesis that new sensorimotor contingencies can be acquired using sensory augmentation.


Platelet-rich plasma: a milieu of bioactive factors.
Platelet concentrates such as platelet-rich plasma (PRP) have gained popularity in sports medicine and orthopaedics to promote accelerated physiologic healing and return to function. Each PRP product varies depending on patient factors and the system used to generate it. Blood from some patients may fail to make PRP, and most clinicians use PRP without performing cell counts on either the blood or the preparation to confirm that the solution is truly PRP. Components in this milieu have bioactive functions that affect musculoskeletal tissue regeneration and healing. Platelets are activated by collagen or other molecules and release growth factors from alpha granules. Additional substances are released from dense bodies and lysosomes. Soluble proteins also present in PRP function in hemostasis, whereas others serve as biomarkers of musculoskeletal injury. Electrolytes and soluble plasma hormones are required for cellular signaling and regulation. Leukocytes and erythrocytes are present in PRP and function in inflammation, immunity, and additional cellular signaling pathways. This article supports the emerging paradigm that more than just platelets are playing a role in clinical responses to PRP. Depending on the specific constituents of a PRP preparation, the clinical use can theoretically be matched to the pathology being treated in an effort to improve clinical efficacy.


Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care.
Older patients with newly diagnosed acute myeloid leukemia (AML) in the phase 3 AZA-AML-001 study were evaluated at entry for cytogenetic abnormalities, and a subgroup of patients was assessed for gene mutations. Patients received azacitidine 75 mg/m2/day x7 days (n = 240) or conventional care regimens (CCR; n = 245): intensive chemotherapy, low-dose cytarabine, or best supportive care only. Overall survival (OS) was assessed for patients with common (occurring in ≥10% of patients) cytogenetic abnormalities and karyotypes, and for patients with recurring gene mutations. There was a significant OS improvement with azacitidine vs CCR for patients with European LeukemiaNet-defined Adverse karyotype (HR 0.71 [95%CI 0.51-0.99]; P = 0.046). Azacitidine-treated patients with -5/5q-, -7/7q-, or 17p abnormalities, or with monosomal or complex karyotypes, had a 31-46% reduced risk of death vs CCR. The most frequent gene mutations were DNMT3A (27%), TET2 (25%), IDH2 (23% [R140, 15%; R172, 8%]), and TP53 (21%). Compared with wild-type, OS was significantly reduced among CCR-treated patients with TP53 or NRAS mutations and azacitidine-treated patients with FLT3 or TET2 mutations. Azacitidine may be a preferred treatment for older patients with AML with Adverse-risk cytogenetics, particularly those with chromosome 5, 7, and/or 17 abnormalities and complex or monosomal karyotypes. The influence of gene mutations in azacitidine-treated patients warrants further study.


Permissive regulation: A critical review of the regulatory history of buprenorphine formulations in Canada.
Suboxone (buprenorphine-naloxone) is an opioid product approved in the US and Canada for the treatment of opioid use disorder. The drug is considered an important response to the opioid overdose epidemic with consistent calls for wider prescribing and deregulation. The history of Suboxone regulation in Canada has not been critically examined. Part of the rationale for doing so stems from the US regulatory experience, with documented irregularities, or what some have called abuses, that support profit-making by Suboxone's manufacturers. This regulatory analysis allows us to determine how opportunities to address health crises through drug innovation are managed at a federal level. We used public drug and patent registries to critically examine Suboxone's Canadian history. First, we investigated Suboxone's entry into the Canadian market to understand how it achieved market exclusivity. Second, we examined Health Canada's risk mitigation process to address extramedical use and diversion to understand the intersection of regulation and brand promotion. Insights from these two analyses were then extended to the recent approval of two related buprenorphine-containing products and their specific pathways to Canadian market exclusivity. We identified inconsistencies in Suboxone's regulatory history that suggest Health Canada's functions of health protection and promotion were compromised in favour of an "innovations" agenda that supports profit-making. Despite six years of market exclusivity in Canada, there was no evidence suggesting Suboxone achieved formal exclusivity (i.e., through patent or data protection). Health Canada's process to address safety concerns of Suboxone were compromised by reliance on the manufacturer to carry out post-market education, allowing the manufacturer to create and market a branded "education" program for its product. Similar inconsistencies have afforded market exclusivity for two related products despite marginal innovation. These analyses reveal a case of permissive regulation, where principles of health protection are compromised by economic imperatives. Such a regulatory approach has the potential to adversely impact public health due to unnecessarily high costs for medicines deemed essential to stem a major health crisis. Alternative pharmaceutical policies are urgently needed to safely and efficiently expand treatment access for opioid use disorder.


Rapid antigen diagnostic testing for the diagnosis of group A beta-haemolytic streptococci pharyngitis.
It is difficult to make a diagnosis of group A beta-haemolytic streptococci (GABHS) pharyngitis solely on clinical findings. The McIssac scoring system has been recommended as a reliable clinical tool for diagnosis. The rapid antigen detection test (RADT) has been shown to considerably increase the number of patients who are appropriately treated for streptococcal pharyngitis, compared with the use of traditional throat cultures. It also reduces the time to start treatment. We evaluated the diagnostic utility of RADT in comparison with throat swab culture. Using the McIssac scoring system, RADT and throat swab cultures in those with a McIssac score of 3 or more, we evaluated 165 children (aged 2-15 years) with a clinical diagnosis of pharyngitis. GABHS pharyngitis was confirmed in 41 (24.8%) by throat swab culture and RADT was positive in 39(23.6%). Only in 2 (4.9%) children, RADT was negative but throat swab was positive. The sensitivity of RADT was 89.7% and specificity was 98.4% with a positive predictive value of 94.6%, negative predictive value of 96.9% and diagnostic accuracy of 96.4%. RADT performed was observed to have high sensitivity and sensitivity for the diagnosis of GABHS pharyngitis in contrast to an earlier report from India. Our observations suggest that using RADT as a point-of-care test is reliable and cost-effective and needs to be propagated in Indian settings where facilities for throat swab culture are not routinely available and also because clinical diagnosis based on scoring systems are comparatively less reliable.


Assay of pyrogens by interleukin-6 release from monocytic cell lines.
A novel in-vitro system has been developed for the detection and quantification of pyrogen in pharmaceutical products. The measured variable was evoked secretion of the pyrogenic cytokine interleukin-6 from MONO MAC 6 monocytic cells incubated with the product. The interleukin-6 was detected using a specific and sensitive ELISA developed for this purpose. The test system detected pyrogenic contamination in 3 batches of therapeutic human serum albumin which had caused adverse reactions in recipients. The contamination was not detected in conventional tests: the rabbit pyrogen test and the limulus amoebocyte lysate test.


Detection of Mg2+-dependent, coaxial stacking rearrangements in a bulged three-way DNA junction by single-molecule FRET.
Three-way helical junctions (3WJs) arise in genetic processing, and they have architectural and functional roles in structured nucleic acids. An internal bulge at the junction core allows the helical domains to become oriented into two possible, coaxially stacked conformers. Here, the helical stacking arrangements for a series of bulged, DNA 3WJs were examined using ensemble fluorescence resonance energy transfer (FRET) and single-molecule FRET (smFRET) approaches. The 3WJs varied according to the GC content and sequence of the junction core as well as the pyrimidine content of the internal bulge. Mg2+ titration experiments by ensemble FRET show that both stacking conformations have similar Mg2+ requirements for folding. Strikingly, smFRET experiments reveal that a specific junction sequence can populate both conformers and that this junction undergoes continual interconversion between the two stacked conformers. These findings will support the development of folding principles for the rational design of functional DNA nanostructures.


Diauxic shift-dependent relocalization of decapping activators Dhh1 and Pat1 to polysomal complexes.
Dhh1 and Pat1 in yeast are mRNA decapping activators/translational repressors thought to play key roles in the transition of mRNAs from translation to degradation. However, little is known about the physical and functional relationships between these proteins and the translation machinery. We describe a previously unknown type of diauxic shift-dependent modulation of the intracellular locations of Dhh1 and Pat1. Like the formation of P bodies, this phenomenon changes the spatial relationship between components involved in translation and mRNA degradation. We report significant spatial separation of Dhh1 and Pat1 from ribosomes in exponentially growing cells. Moreover, biochemical analyses reveal that these proteins are excluded from polysomal complexes in exponentially growing cells, indicating that they may not be associated with active states of the translation machinery. In contrast, under diauxic growth shift conditions, Dhh1 and Pat1 are found to co-localize with polysomal complexes. This work suggests that Dhh1 and Pat1 functions are modulated by a re-localization mechanism that involves eIF4A. Pull-down experiments reveal that the intracellular binding partners of Dhh1 and Pat1 change as cells undergo the diauxic growth shift. This reveals a new dimension to the relationship between translation activity and interactions between mRNA, the translation machinery and decapping activator proteins.


Medical students' perception of dyad practice.
Training in pairs (dyad practice) has been shown to improve efficiency of clinical skills training compared with single practice but little is known about students' perception of dyad practice. The aim of this study was to explore the reactions and attitudes of medical students who were instructed to work in pairs during clinical skills training. A follow-up pilot survey consisting of four open-ended questions was administered to 24 fourth-year medical students, who completed four hours of dyad practice in managing patient encounters. The responses were analyzed using thematic analysis. The students felt dyad practice improved their self-efficacy through social interaction with peers, provided useful insight through observation, and contributed with shared memory of what to do, when they forgot essential steps of the physical examination of the patient. However, some students were concerned about decreased hands-on practice and many students preferred to continue practising alone after completing the initial training. Dyad practice is well received by students during initial skills training and is associated with several benefits to learning through peer observation, feedback and cognitive support. Whether dyad training is suited for more advanced learners is a subject for future research.


Type I interferons protect neonates from acute inflammation through interleukin 10-producing B cells.
Newborns and infants are highly susceptible to viral and bacterial infections, but the underlying mechanism remains poorly understood. We show that neonatal B cells effectively control the production of proinflammatory cytokines by both neonatal plasmacytoid and conventional dendritic cells, in an interleukin (IL) 10-dependent manner, after Toll-like receptor (TLR) 9 triggering. This antiinflammatory property of neonatal B cells may extend to other TLR agonists (Pam3CSK4, lipopolysaccharide, and R848) and viruses. In the absence of B cells or of CD5(+) B cell subsets, neonatal mice developed stronger inflammatory responses and became lethally susceptible to CpG challenge after galactosamine sensitization, whereas wild-type (WT) mice were resistant. Paradoxically, interferon (IFN)-alpha/beta enhanced the inflammatory response to CpG challenge in adult mice, whereas they helped to control neonatal acute inflammation by stimulating the secretion of IL-10 by neonatal B cells. Finally, WT neonatal B cells rescued IL-10(-/-) neonates from a lethal CpG challenge, whereas IFN-alpha/beta receptor-deficient B cells did not. Our results show that type I IFNs support a negative regulatory role of neonatal B cells on TLR-mediated inflammation, with important implications for neonatal inflammation and infection.


Functional and physical interactions between formyl-peptide-receptors and scavenger receptor MARCO and their involvement in amyloid beta 1-42-induced signal transduction in glial cells.
Recent studies suggest that the chemotactic G protein-coupled receptor formyl-peptide-receptor-like-1 (FPRL1) or the scavenger receptor MARCO (macrophage receptor with collagenous structure) plays an essential role in the inflammatory response of host defense mechanisms and neurodegenerative disorders such as Alzheimer's disease. We therefore analyzed the involvement of FPRL1 and MARCO in amyloid beta1-42 (Abeta1-42)-induced signalling by extracellular-signal regulated kinases 1/2 (ERK1/2) phosphorylation and cAMP level measurement in glial cells (astrocytes and microglia) and in transfected HEK293 cells. Receptors were inhibited by small interference RNA and the consequences in Abeta1-42- and MARCO agonist fucoidan-induced signal transduction were determined. Receptor deactivation by antagonists or small interference RNA verified the importance of FPRL1 for Abeta1-42-mediated signal transduction by ERK1/2 phosphorylation and cAMP level measurement in glial cells. Furthermore, for the first time, we have demonstrated a functional interaction between FPRL1 and scavenger receptors in fucoidan-mediated signalling by ERK1/2 phosphorylation and cAMP level measurement. In addition, co-immunoprecipitation data and fluorescence microscopy measurements revealed a physical interaction between FPR, FPRL1 and MARCO. These results suggest that FPRL1 plays a pivotal role for Abeta1-42-induced signal transduction in glial cells and the interaction with MARCO could explain the broad ligand spectrum of formyl peptide receptors.


Cardiac T-Tubule Microanatomy and Function.
Unique to striated muscle cells, transverse tubules (t-tubules) are membrane organelles that consist of sarcolemma penetrating into the myocyte interior, forming a highly branched and interconnected network. Mature t-tubule networks are found in mammalian ventricular cardiomyocytes, with the transverse components of t-tubules occurring near sarcomeric z-discs. Cardiac t-tubules contain membrane microdomains enriched with ion channels and signaling molecules. The microdomains serve as key signaling hubs in regulation of cardiomyocyte function. Dyad microdomains formed at the junctional contact between t-tubule membrane and neighboring sarcoplasmic reticulum are critical in calcium signaling and excitation-contraction coupling necessary for beat-to-beat heart contraction. In this review, we provide an overview of the current knowledge in gross morphology and structure, membrane and protein composition, and function of the cardiac t-tubule network. We also review in detail current knowledge on the formation of functional membrane subdomains within t-tubules, with a particular focus on the cardiac dyad microdomain. Lastly, we discuss the dynamic nature of t-tubules including membrane turnover, trafficking of transmembrane proteins, and the life cycles of membrane subdomains such as the cardiac BIN1-microdomain, as well as t-tubule remodeling and alteration in diseased hearts. Understanding cardiac t-tubule biology in normal and failing hearts is providing novel diagnostic and therapeutic opportunities to better treat patients with failing hearts.


A cross-sectional study of demographic, environmental and parental barriers to active school travel among children in the United States.
Promoting daily routine physical activities, such as active travel to school, may have important health implications. Practitioners and policy makers must understand the variety of factors that influence whether or not a child uses active school travel. Several reviews have identified both inhibitors and promoters of active school travel, but few studies have combined these putative characteristics in one analysis. The purpose of this study is to examine associations between elementary school children's active school travel and variables hypothesized as correlates (demographics, physical environment, perceived barriers and norms). The current project uses the dataset from the National Evaluation of Walk to School (WTS) Project, which includes data from 4th and 5th grade children and their parents from 18 schools across the US. Measures included monthly child report of mode of school travel during the previous week (n = 10,809) and perceived barriers and social norms around active school travel by parents (n = 1,007) and children (n = 1,219). Generalized linear mixed models (GLMM) with log-link functions were used to assess bivariate and multivariate associations between hypothesized correlates and frequency of active school travel, assuming random school effect and controlling for the distance to school. The final model showed that the most relevant significant predictors of active school travel were parent's perceived barriers, specifically child resistance (Estimate = -0.438, p < 0.0001) and safety and weather (Estimate = -0.0245, p < 0.001), as well as the school's percentage of Hispanic students (Estimate = 0.0059, p < 0.001), after adjusting for distance and including time within school cluster as a random effect. Parental concerns may be impacting children's use of active school travel, and therefore, future interventions to promote active school travel should more actively engage parents and address these concerns. Programs like the Walk to School program, which are organized by the schools and can engage community resources such as public safety officials, could help overcome many of these perceived barriers to active transport.


Differences in Short-Term Sport-Specific Functional Recovery After Primary ACL Reconstruction in the Adolescent Athlete.
Although anterior cruciate ligament (ACL) injury rates have been studied extensively, it is unclear whether levels of functional and psychological readiness for return-to-sport after primary ACL reconstruction (ACLR) differ based on an athlete's primary sport. Youth athletes in different primary sports will demonstrate differences in short-term functional recovery, as well as patient-reported psychological and functional recovery after primary ACLR. Retrospective cohort study of consecutive patients treated for ACL injury in pediatric sports medicine clinics. Level 3. Patients included underwent primary ACLR between December 1, 2015 and December 31, 2019 and reported sports participation at the time of injury. Demographic data, sports participation, surgical data, functional testing scores (Y-Balance Test [YBT]), functional and psychological patient-reported outcome measures (PROMs), and timing of return-to-play clearance were reviewed. YBT scores were the primary metric for clearance. Four groups were studied: soccer, football, basketball, and other. A total of 220 male and 223 female athletes were included; 65.28% of soccer players were female and 100% of football players were male (P < 0.01). At initial postoperative YBT testing (6-9 months), soccer players had higher operative (P < 0.01) and nonoperative (P < 0.01) leg composite scores when compared with basketball players. No significant differences were found between sports in functional or psychological PROMs at presurgical baseline or 6 months postoperatively. When compared with football, soccer players completed functional clearance in a shorter time from surgery (P = 0.02). Multivariate analysis showed level of competition as a significant independent variable for clearance in female athletes. After primary ACLR, athletes, especially female athletes, demonstrated short-term sport-specific differences in YBT scores. Soccer players attained clearance sooner than football players. Level of competition influenced YBT composite scores in all athletes and time to clearance in female athletes. Sport-specific differences in reinjury should be investigated to determine whether changes in return-to-play evaluation should be implemented.


Second-order many-body perturbation expansions of vibrational Dyson self-energies.
Second-order many-body perturbation theories for anharmonic vibrational frequencies and zero-point energies of molecules are formulated, implemented, and tested. They solve the vibrational Dyson equation self-consistently by taking into account the frequency dependence of the Dyson self-energy in the diagonal approximation, which is expanded in a diagrammatic perturbation series up to second order. Three reference wave functions, all of which are diagrammatically size consistent, are considered: the harmonic approximation and diagrammatic vibrational self-consistent field (XVSCF) methods with and without the first-order Dyson geometry correction, i.e., XVSCF[n] and XVSCF(n), where n refers to the truncation rank of the Taylor-series potential energy surface. The corresponding second-order perturbation theories, XVH2(n), XVMP2[n], and XVMP2(n), are shown to be rigorously diagrammatically size consistent for both total energies and transition frequencies, yield accurate results (typically within a few cm(-1) at n = 4 for water and formaldehyde) for both quantities even in the presence of Fermi resonance, and have access to fundamentals, overtones, and combinations as well as their relative intensities as residues of the vibrational Green's functions. They are implemented into simple algorithms that require only force constants and frequencies of the reference methods (with no basis sets, quadrature, or matrix diagonalization at any stage of the calculation). The rules for enumerating and algebraically interpreting energy and self-energy diagrams are elucidated in detail.


Electrochemically Active Thin Carbon Films with Enhanced Adhesion to Silicon Substrates.
Thin carbon films deposited on technologically relevant substrates, such as silicon wafers, can be easily implemented in miniaturized electrochemical devices and used for sensing applications. However, a major issue in most carbon films is the weak film/substrate adhesion that shortens the working device lifetime. This paper describes the facile preparation of robust thin carbon films on silicon substrates by one-pot sol-gel synthesis. The improved adherence of these carbon films is based on the incorporation of silica through the controlled synthesis of a resorcinol/formaldehyde gel modified with aminopropyltriethoxysilane. The films demonstrate excellent adhesion to the silicon substrate, good homogeneity, excellent electrical conductivity and superior electrochemical performance. Moreover, this approach opens the door to the fabrication of carbon thin-film electrodes by photolithographic techniques.


High resolution modeling of agricultural nitrogen to identify private wells susceptible to nitrate contamination.
Given the lack of data on private wells, public health and water quality specialists must explore alternative datasets for understanding associated exposures and health risks. Characterizing agricultural nitrogen inputs would be valuable for identifying areas where well water safety may be compromised. This study incorporated existing methods for estimating nutrient loading at the county level with datasets derived from a state permitting program for confined animal feeding operations and agricultural enterprise budget worksheets to produce a high resolution agricultural nitrogen raster map. This map was combined with data on soil leachability and new well locations. An algorithm was developed to calculate nitrogen loading and leachability within 1,000 meters of each well. Wells with a nonzero nitrogen total linked to soils with high leachability were categorized and displayed on maps communicating well susceptibility across the state of Oregon. Results suggest that 4% of recently drilled wells may be susceptible to nitrate contamination, while areas identified for mitigation are too restrictive to include all susceptible wells. Predicted increases in population density and the steady addition of approximately 3,800 new wells annually may lead to a large number of residents, especially those in rural areas, experiencing long-term exposures to nitrate in drinking water.


Coupled aggregation of mitochondrial single-strand DNA-binding protein tagged with Eos fluorescent protein visualizes synchronized activity of mitochondrial nucleoids.
Oligomer aggregation of green-to-red photoconvertible fluorescent protein Eos (EosFP) is a natural feature of the wild‑type variant. The aim of the present study was to follow up mitochondrial nucleoid behavior under natural conditions of living cells transfected with mitochondrial single‑strand DNA‑binding protein (mtSSB) conjugated with EosFP. HEPG2 and SH‑SY5Y cells were subjected to lentiviral transfection and subsequently immunostained with anti‑DNA, anti‑transcription factor A, mitochondrial (TFAM) or anti‑translocase of the inner membrane 23 antibodies. Fluorescent microscopy, conventional confocal microscopy, superresolution biplane fluorescence photo-activation localization microscopy and direct stochastic optical reconstruction microscopy were used for imaging. In the two cell types, apparent couples of equally‑sized mtSSB‑EosFP‑visualized dots were observed. During the time course of the ongoing transfection procedure, however, a small limited number of large aggregates of mtSSB‑EosFP‑tagged protein started to form in the cells, which exhibited a great co‑localization with the noted coupled positions. Antibody staining and 3D immunocytochemistry confirmed that nucleoid components such as TFAM and DNA were co‑localized with these aggregates. Furthermore, the observed reduction of the mtDNA copy number in mtSSB‑EosFP‑transfected cells suggested a possible impairment of nucleoid function. In conclusion, the present study demonstrated that coupled nucleoids are synchronized by mtSSB‑EosFP overexpression and visualized through their equal binding capacity to mtSSB‑EosFP‑tagged protein. This observation suggested parallel replication and transcription activity of nucleoid couples native from a parental one. Preserved coupling in late stages of artificial EosFP‑mediated aggregation of tagged proteins suggested a rational manner of mitochondrial branching that may be cell-type specifically dependent on hierarchical nucleoid replication.


The role of the P2X₇ receptor in infectious diseases.
ATP is an extracellular signal for the immune system, particularly during an inflammatory response. It is sensed by the P2X₇ receptor, the expression of which is upregulated by pro-inflammatory cytokines. Activation of the P2X₇ receptor opens a cation-specific channel that alters the ionic environment of the cell, activating several pathways, including (i) the inflammasome, leading to production of IL-1β and IL-18; (ii) the stress-activated protein kinase pathway, resulting in apoptosis; (iii) the mitogen-activated protein kinase pathway, leading to generation of reactive oxygen and nitrogen intermediates; and (iv) phospholipase D, stimulating phagosome-lysosome fusion. The P2X₇ receptor can initiate host mechanisms to remove pathogens, most particularly those that parasitise macrophages. At the same time, the P2X₇ receptor may be subverted by pathogens to modulate host responses. Moreover, recent genetic studies have demonstrated significant associations between susceptibility or resistance to parasites and bacteria, and loss-of-function or gain-of-function polymorphisms in the P2X₇ receptor, underscoring its importance in infectious disease.


Resolution of Cannabinoid Hyperemesis Syndrome with Benzodiazepines: A Case Series.
Cannabinoid hyperemesis syndrome (CHS) is under-recognized by clinicians. It is characterized by nausea, severe abdominal pain, and cyclical vomiting in the context of chronic cannabis use. Oral benzodiazepine is a proposed treatment for CHS. It decreases activation of Cannabinoid Type 1 Receptor (CB1) in the frontal cortex, has a sedative and hypnotic effect and reduces the anticipation of nausea and vomiting. These effects on the central nervous system (CNS) might explain its beneficial antiemetic effect for this syndrome. To increase the index of suspicion for CHS, a unique syndrome that requires a unique treatment with benzodiazepines and not antiemetics. We describe a series of four patients with documented cannabis use, who were admitted to an internal medicine department of Meir Medical Center due to symptoms consistent with abdominal pain, nausea, and vomiting. They were initially treated with conventional antiemetics and proton pump inhibitors without response. Intensive investigations were conducted to exclude common and sometimes urgent gastrointestinal or CNS syndromes. After excluding urgent gastrointestinal and CNS origins for the vomiting, we suspected CHS. All four patients experienced similar symptoms and failure of conventional treatment with antiemetics and proton pump inhibitors. They experienced relief after administration of benzodiazepines. A high index of suspicion for CHS allows for rapid, appropriate treatment with benzodiazepines, which in turn may lead to cessation of the debilitating symptoms caused by this syndrome.


Effects of blue light on the circadian system and eye physiology.
Light-emitting diodes (LEDs) have been used to provide illumination in industrial and commercial environments. LEDs are also used in TVs, computers, smart phones, and tablets. Although the light emitted by most LEDs appears white, LEDs have peak emission in the blue light range (400-490 nm). The accumulating experimental evidence has indicated that exposure to blue light can affect many physiologic functions, and it can be used to treat circadian and sleep dysfunctions. However, blue light can also induce photoreceptor damage. Thus, it is important to consider the spectral output of LED-based light sources to minimize the danger that may be associated with blue light exposure. In this review, we summarize the current knowledge of the effects of blue light on the regulation of physiologic functions and the possible effects of blue light exposure on ocular health.


Repurposing Drugs in Oncology (ReDO)-Propranolol as an anti-cancer agent.
Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers.


Declining Prevalence of Disease Vectors Under Climate Change.
More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales.


U.K. Controlled trial of intrapleural streptokinase for pleural infection.
Intrapleural fibrinolytic agents are used in the drainage of infected pleural-fluid collections. This use is based on small trials that did not have the statistical power to evaluate accurately important clinical outcomes, including safety. We conducted a trial to clarify the therapeutic role of intrapleural streptokinase. In this double-blind trial, 454 patients with pleural infection (defined by the presence of purulent pleural fluid or pleural fluid with a pH below 7.2 with signs of infection or by proven bacterial invasion of the pleural space) were randomly assigned to receive either intrapleural streptokinase (250,000 IU twice daily for three days) or placebo. Patients received antibiotics and underwent chest-tube drainage, surgery, and other treatment as part of routine care. The number of patients in the two groups who had died or needed surgical drainage at three months was compared (the primary end point); secondary end points were the rates of death and of surgery (analyzed separately), the radiographic outcome, and the length of the hospital stay. The groups were well matched at baseline. Among the 427 patients who received streptokinase or placebo, there was no significant difference between the groups in the proportion of patients who died or needed surgery (with streptokinase: 64 of 206 patients [31 percent]; with placebo: 60 of 221 [27 percent]; relative risk, 1.14 [95 percent confidence interval, 0.85 to 1.54; P=0.43), a result that excluded a clinically significant benefit of streptokinase. There was no benefit to streptokinase in terms of mortality, rate of surgery, radiographic outcomes, or length of the hospital stay. Serious adverse events (chest pain, fever, or allergy) were more common with streptokinase (7 percent, vs. 3 percent with placebo; relative risk, 2.49 [95 percent confidence interval, 0.98 to 6.36]; P=0.08). The intrapleural administration of streptokinase does not improve mortality, the rate of surgery, or the length of the hospital stay among patients with pleural infection.


Critical Factors to Practicing Medical Acupuncture in Family Medicine: Patient and Physician Perspectives.
Although an increasing number of physicians are completing medical acupuncture training, only half of those physicians are able to successfully incorporate acupuncture into practice. We conducted a qualitative study to identify the factors and barriers that can enhance and impede physicians' delivery of and patients' engagement in medical acupuncture within the family medicine clinic. We conducted interviews with 15 family physicians and 17 patients in a US family medicine clinic that has integrated medical acupuncture into its practice. Audio recordings were transcribed and analyzed by 2 members of the study team in ATLAS.ti, using the constant comparative method. We identified 3 physician themes of factors/barriers that impact delivery/engagement: 1) patients' aversion to needles, 2) time challenges, and 3) access to resources. We identified 3 additional themes from patient interviews: 1) appointment access; 2) wanting noninvasive, no side effects alternative; and 3) openness to anything. The factors and barriers reported by physicians/patients help illustrate conditions needed to enhance physicians' ability to provide acupuncture and patients' willingness to engage and sustain it. Participants' experiences help to illustrate strategic approaches to managing these barriers-strategies that can be used by other individuals/institutions to enhance care delivery and patient engagement.


120 Years of U.S. Residential Housing Stock and Floor Space.
Residential buildings are a key driver of energy consumption and also impact transportation and land-use. Energy consumption in the residential sector accounts for one-fifth of total U.S. energy consumption and energy-related CO2 emissions, with floor space a major driver of building energy demands. In this work a consistent, vintage-disaggregated, annual long-term series of U.S. housing stock and residential floor space for 1891-2010 is presented. An attempt was made to minimize the effects of the incompleteness and inconsistencies present in the national housing survey data. Over the 1891-2010 period, floor space increased almost tenfold, from approximately 24,700 to 235,150 million square feet, corresponding to a doubling of floor space per capita from approximately 400 to 800 square feet. While population increased five times over the period, a 50% decrease in household size contributed towards a tenfold increase in the number of housing units and floor space, while average floor space per unit remains surprisingly constant, as a result of housing retirement dynamics. In the last 30 years, however, these trends appear to be changing, as household size shows signs of leveling off, or even increasing again, while average floor space per unit has been increasing. GDP and total floor space show a remarkably constant growth trend over the period and total residential sector primary energy consumption and floor space show a similar growth trend over the last 60 years, decoupling only within the last decade.


Acute effects of oral olanzapine treatment on the expression of fatty acid and cholesterol metabolism-related gene in rats.
Second-generation antipsychotic drugs (SGAs) have a high risk for serious metabolic side-effects including dyslipidemia. This study aimed to investigate the acute effects of oral olanzapine treatment on the expression of genes for fatty acid and cholesterol biosynthesis in rats. Female Sprague-Dawley rats were treated orally with olanzapine (1mg/kg, equivalent to a human clinical dose of 10mg) via self-administration aimed to measure pharmacokinetics. Based on the pharmacokinetic analysis, the acute effects of olanzapine on sterol regulatory element binding protein (SREBP)-related fatty acid/cholesterol metabolism genes were investigated in the liver and perirenal white adipose tissue (WAT) by Real-time quantitative PCR. A pharmacokinetic analysis demonstrated that the maximum concentration of olanzapine in plasma (Cmax) occurred at 6h with a peak concentration of 276.5ng/ml after a single oral treatment and with a plasma elimination half-life of 3.5h after peak. The mRNA expression of SREBP-2 and target genes for cholesterol synthesis and transport was increased 1.9 8.8 fold compared with the control at 6h after olanzapine administration but returned to basal level at 12h post-treatment, while the increased mRNA expression of SREBP-1c and its targeted fatty acid-related genes appeared at both 6h and 12h post-treatment. The present study provided evidence that olanzapine at a clinically-relevant dose caused abnormal expression of genes involved in lipid metabolism in the liver and WAT. These results suggest that olanzapine may cause dyslipidemia side-effects through direct effects on lipid biosynthesis and efflux genes associated with SREBP-stimulated transcriptional changes.


Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer.
Docetaxel is highly active in the second-line treatment of patients with metastatic or unresectable locally advanced nonsmall-cell lung cancer (NSCLC). As there is a need for first-line chemotherapy that is more effective than standard platinum-based chemotherapy, this study was undertaken to evaluate the efficacy and tolerability of a docetaxel/cisplatin combination as first-line chemotherapy in advanced NSCLC. Newly diagnosed, chemotherapy-naive patients with histologically confirmed NSCLC (measurable stage IIIB/IV NSCLC; Karnofsky performance status, 70-100; adequate bone marrow, renal, hepatic, and cardiac function) were eligible for the study. Docetaxel 75 mg/m2 was administered IV over 1 h, followed immediately by cisplatin 75 mg/m2, given IV over 30 min, with cycles repeated every 3 weeks, for up to six or nine cycles. Thirty-nine patients were enrolled and treated. Their median age was 59 years (range, 32-71 years) and median performance status, 90 (range, 70-100). Histologically, 23 patients (59%) had adenocarcinoma, 12 (30.8%) had squamous cell carcinoma, and 16 patients (41%) had stage IV disease. Thirty-seven patients were eligible for inclusion. In the 39 patients evaluable for safety, significant grade 3/4 toxicities included neutropenia (82%), nausea (10.3%), fatigue (10.3%), and diarrhea (7.7%). Of the 33 patients evaluable for response, 16 patients (48.5%) achieved a partial response and 7 showed progressive disease. Median overall survival time in all eligible patients was 10.5 months. Docetaxel/cisplatin produced promising response rates that compare favorably with those of current standard platinum combinations, with manageable toxicity. Further investigations of this first-line combination in NSCLC are warranted.


Tissue Engineering at the Blood-Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development.
Tissue engineered vascular grafts (TEVGs) are beginning to achieve clinical success and hold promise as a source of grafting material when donor grafts are unsuitable or unavailable. Significant technological advances have generated small-diameter TEVGs that are mechanically stable and promote functional remodeling by regenerating host cells. However, developing a biocompatible blood-contacting surface remains a major challenge. The TEVG luminal surface must avoid negative inflammatory responses and thrombogenesis immediately upon implantation and promote endothelialization. The surface has therefore become a primary focus for research and development efforts. The current state of TEVGs is herein reviewed with an emphasis on the blood-contacting surface. General vascular physiology and developmental challenges and strategies are briefly described, followed by an overview of the materials currently employed in TEVGs. The use of biodegradable materials and stem cells requires careful control of graft composition, degradation behavior, and cell recruitment ability to ensure that a physiologically relevant vessel structure is ultimately achieved. The establishment of a stable monolayer of endothelial cells and the quiescence of smooth muscle cells are critical to the maintenance of patency. Several strategies to modify blood-contacting surfaces to resist thrombosis and control cellular recruitment are reviewed, including coatings of biomimetic peptides and heparin.


Modified microkeratome-assisted posterior lamellar keratoplasty using a tissue adhesive.
To compare graft stability and astigmatic change using suture vs tissue adhesive in an experimental model of microkeratome-assisted posterior lamellar keratoplasty. A 300-microm-thick partial flap keratectomy was performed in human donor corneoscleral rims using an artificial anterior chamber and a manual microkeratome. The flap stopped at the left central opening border, providing a wide hinge to add stability. After flap reflection, a 6.25-mm trephination was performed to obtain a disc of posterior stroma, Descemet membrane, and endothelium. The disc was positioned in a sutureless fashion, and the flap secured with either 5 interrupted sutures or a chondroitin-sulfate-aldehyde-based adhesive. Increasing intrachamber pressures were created to detect graft stability. Videokeratographic data were recorded to evaluate astigmatic change. The mean (SD) astigmatic change was 3.08 (0.84) diopters (D) in the sutured group and 1.13 (0.55) D in the glued group (P = .008). Mean (SD) resisted pressures were 95.68 (27.38) mm Hg and 82.45 (18.40) mm Hg in the sutured and glued groups, respectively (P = .97). This modified technique of microkeratome-assisted posterior lamellar keratoplasty showed excellent graft stability in both groups. Flaps sealed with the novel tissue adhesive had reduced astigmatic changes in our experimental model. Sutureless microkeratome-assisted posterior lamellar keratoplasty using tissue adhesive may become a new alternative in the surgical treatment of corneal endothelial disorders.


Chirality-dependent transport in double-walled carbon nanotube assemblies: the role of inner tubes.
A fundamental understanding of the electrical properties of carbon nanotubes is vital when fabricating high-performance polymeric composites as well as transparent conductive films. Herein, the chirality-dependent transport mechanisms in peapod- and chemical vapor deposition-grown double-walled carbon nanotubes (DWNTs) films are discussed by identifying the chiralities of the inner and the outer tubes using fast Fourier transform image processing, as well as optical studies (e.g., Raman, UV, and photoluminescence spectroscopies). The observed conduction mechanisms are strongly dependent on the total fraction of the metallic inner and outer tubes within the DWNT samples. Furthermore, the contribution of the inner tubes to the electronic transport properties of DWNT films is confirmed by photochemically deactivating the outer tubes in both types of DWNT samples.


The effects of MAOA genotype, childhood trauma, and sex on trait and state-dependent aggression.
Monoamine oxidase A (MAOA) genotypic variation has been associated with variation in aggression, especially in interaction with childhood trauma or other early adverse events. Male carriers of the low-expressing variant (MAOA-L) with childhood trauma or other early adverse events seem to be more aggressive, whereas female carriers with the high-expressing variant (MAOA-H) with childhood trauma or other early adverse events may be more aggressive. We further investigated the effects of MAOA genotype and its interaction with sex and childhood trauma or other early adverse events on aggression in a young adult sample. We hypothesized that the association between genotype, childhood trauma, and aggression would be different for men and women. We also explored whether this association is different for dispositional (trait) aggression versus aggression in the context of dysphoric mood. In all, 432 Western European students (332 women, 100 men; mean age 20.2) were genotyped for the MAOA gene. They completed measures of childhood trauma, state and trait measures of aggression-related behaviors (STAXI), and cognitive reactivity to sad mood (LEIDS-R), including aggression reactivity. Women with the MAOA-H had higher aggression reactivity scores than women with the MAOA-L. This effect was not observed in men, although the nonsignificant findings in men may be a result of low power. Effects on the STAXI were not observed, nor were there gene by environment interactions on any of the aggression measures. A protective effect of the low-expression variant in women on aggression reactivity is consistent with previous observations in adolescent girls. In females, the MAOA-H may predispose to aggression-related problems during sad mood.


Influence of socioeconomic status on the relationship between locus of control and oral health.
The objectives of this study were to assess the relationship between Locus of Control (LoC) and oral health among a group of rural adolescent school children and to examine the influence of socioeconomic status (SES) on the association between health, LoC and oral health status. A total of 318 children 15 years of age from a public and private school formed the study population. The children were administered following the Indian translation of the 18-item Multidimensional Health Locus of Control scale, and subsequently examined for caries and oral hygiene. T tests and correlation analyses showed a significant relationship between higher 'Internal' Locus of Control and dental caries. A hierarchical multiple regression analysis was performed to assess the effect of socioeconomic status on LoC and oral health using three interaction models which showed a statistically significant interaction between 'Internal' LoC and socioeconomic status on caries. Socioeconomic stratum-specific estimates of the relationship between the LoC and caries revealed a positive association between Internal LoC and caries in the middle socioeconomic group. The results demonstrated the relationship between Locus of Control and oral health, and the role of socioeconomic status having a strong bearing on this relationship.


Development and Characterization of PEDOT:PSS/Alginate Soft Microelectrodes for Application in Neuroprosthetics.
Reducing the mechanical mismatch between the stiffness of a neural implant and the softness of the neural tissue is still an open challenge in neuroprosthetics. The emergence of conductive hydrogels in the last few years has considerably widened the spectrum of possibilities to tackle this issue. Nevertheless, despite the advancements in this field, further improvements in the fabrication of conductive hydrogel-based electrodes are still required. In this work, we report the fabrication of a conductive hydrogel-based microelectrode array for neural recording using a hybrid material composed of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), and alginate. The mechanical properties of the conductive hydrogel have been investigated using imaging techniques, while the electrode arrays have been electrochemically characterized at each fabrication step, and successfully validated both in vitro and in vivo. The presence of the conductive hydrogel, selectively electrodeposited onto the platinum microelectrodes, allowed achieving superior electrochemical characteristics, leading to a lower electrical noise during recordings. These findings represent an advancement in the design of soft conductive electrodes for neuroprosthetic applications.


Exposure assessment of high molecular weight sensitisers: contribution to occupational epidemiology and disease prevention.
An important group of sensitising agents are so called high molecular weight sensitisers--proteins or glycoproteins with molecular weights in the 5-70 kDa range that can provoke a specific IgE response in workers exposed to these agents. Exposure to high molecular weight sensitisers could only be evaluated indirectly in the recent past. Few measurement techniques existed that made it possible to measure the allergens directly. As a result, few studies focused on establishing exposure-response relations, and exposure standards have not been established for high molecular weight sensitisers, or those that have are of doubtful scientific basis. Recent use of immunoassays changed this perspective dramatically. Antibodies used in the assays can originate from human serum (sensitized workers), serum from sensitised animals (rabbits producing polyclonal antibodies), or animal derived cell cultures producing monoclonal antibodies. Although few comparative studies exist, the available evidence suggests that although the correlation of allergen concentrations obtained with different assays is good, large systematic differences occur. The use of conversion factors to make data from previously performed allergen measurements comparable or exchangeable is limited and thorough standardization of assays is preferred. Validation and comparison of different assays by comparisons between laboratories seem important issues that have not received the attention needed. Epidemiological studies in several industries that used immunoassay for the exposure characterisation have shown that risk of sensitisation increases with increasing exposure to allergens. Several studies have also shown that clear differences in potency seem to exist. Sensitisation to rat urinary allergens and fungal alpha-amylase occurred in the pg/m3 and ng/m3 range. The main research questions of the near future have to focus on the prevention of occupational sensitisation. Standard setting seems possible for some allergenson the basis of the available scientific evidence for the existence of exposure response relations. However, assays for characterising exposure to allergens have to be rigorously standardised before they can be used under field conditions.


Characterization of a novel self-associating Mr 40,000 platelet glycoprotein.
A novel platelet glycoprotein has been purified and characterized. This glycoprotein, designated Pltgp40, is an acidic sialylated 40,000-dalton protein that bears both O-linked and N-linked oligosaccharides. Treatment of Pltgp40 with neuraminidase resulted in a 5,000-dalton reduction in its Mr and a 1.5 Unit alkaline shift in the isoelectric point, indicating the presence of a large number of sialic acid residues. A similar size reduction and change in pl were observed after treatment of Pltgp40 with O-glycanase showing that sialic acids are present on O-linked oligosaccharides. Digestion of Pltgp40 with N-glycanase reduced the Mr to approximately 20,000 daltons but did not affect the isoelectric point, suggesting that Pltgp40 contains six to seven nonsialylated N-linked carbohydrate chains. High Mr proteins were observed in affinity purified Pltgp40 and were identified as detergent-stable protein oligomers consisting of multiple 40,000-dalton monomers. Immunodepletion and direct binding studies indicated that Pltgp40 was not equivalent to Ig Fc receptor type II, another 40,000-dalton glycoprotein expressed on platelets. However, Pltgp40 copurified with Fc receptor type II when platelet extracts were loaded onto human IgG affinity columns, raising the possibility that Pltgp40 may associate with Fc receptors or Fc receptor-lg complexes. Amino acid sequence analysis of the N-terminus of Pltgp40 was performed and confirmed that Pltgp40 is a novel platelet glycoprotein. Epitopes on Pltgp40 appear to be widely expressed because monoclonal antibodies against Pltgp40 also reacted with a variety of myeloid, lymphoid, and epithelial cells. Pltgp40 was detected on activated but not resting platelets, indicating that Pltgp40 is a platelet activation marker.