Cross sectoral and scale-up impacts of greywater recycling technologies on catchment hydrological flows.
With the growth of urban areas and climate change, decisions need to be taken to improve water management. This paper reports an assessment of the impact of greywater recycling systems on catchment scale hydrological flows. A simulation model developed in InfoWorks CS (Wallingford Software Ltd) was used to evaluate how river flows, sewer flows, surface runoff and flooding events may be influenced when grey water recycling systems of different number and scale are implemented in a representative catchment. The simulations show the effectiveness of greywater recycling systems in reducing total wastewater volume and flood volume. However, no hydraulic impacts due to implementation of greywater was identified by the model.


Does furan affect the thymus in growing male rats?
Furan has been identified in foods such as heat-treated foods, including coffee, canned meat, hazelnuts, and infant foods and formulas. Children may be exposed to furan via either consumption of these foods or their derivatives. We evaluated the effects of furan on the thymus of weaning male rats in the present study. Five separate groups containing male rats were used: control, oil control, and three furan-treated groups. Furan was given orally to rats in the treatment groups at doses of 2, 4, and 8 mg/kg/day for 90 days. At the end of the experiment, thymus of the rats were examined morphologically, histopathologically, and immunohistochemically. We observed that absolute and relative weights of thymus were decreased significantly in rats treated with 4- and 8-mg/kg/day doses of furan. In histopathological examination, enlargement of interstitial connective tissue between the thymic lobules, lymphocyte depletion, and hemorrhage were observed. We detected an increase in apoptotic cell counts in thymus of the treatment groups. In addition, we found significant differences in the distribution of fibronectin and transforming growth factor-beta in the thymus of the treatment groups. In conclusion, we suggest that furan has affected the thymus in growing male rats.


Using the Early Childhood Environment Rating Scale-Revised in High Stakes Contexts: Does Evidence Warrant the Practice?
Increasingly, states establish different thresholds on the Early Childhood Environment Rating Scale-Revised (ECERS-R), and use these thresholds to inform high-stakes decisions. However, the validity of the ECERS-R for these purposes is not well established. The objective of this study is to identify thresholds on the ECERS-R that are associated with preschool-aged children's social and cognitive development. Applying non-parametric modeling to the nationally-representative Early Childhood Longitudinal Study Birth Cohort (ECLS-B) dataset, we found that once classrooms achieved a score of 3.4 on the overall ECERS-R composite score, there was a leveling-off effect, such that no additional improvements to children's social, cognitive, or language outcomes were observed. Additional analyses found that ECERS-R subscales that focused on teaching and caregiving processes, as opposed to the physical environment, did not show leveling-off effects. The findings suggest that the usefulness of the ECERS-R for discerning associations with children's outcome may be limited to certain score ranges or subscales.


Blood transfusion: implications of treating a Jehovah's Witness patient.
Jehovah's Witnesses believe that an individual's life is contained within blood, and that accepting transfusion of blood and blood products is sinful. The administration of blood to a Jehovah's Witness who has refused to accept transfusion may lead to criminal or civil proceedings. From an ethical viewpoint, if a rational adult who has been fully apprised of the consequences of not receiving this treatment persists in a refusal, the decision should be respected. Medical and nursing staff faced with such a problem should explore fully with the patient any transfusion alternatives that the patient might find acceptable, such as cell salvage, volume expanders, antifibrinolytics and pharmaceutical options, such as erythropoietin. This article examines the legal and consent issues around blood transfusion in Jehovah's Witness patients and their implications for medical and surgical management.


Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor.
Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC). We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)). Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312**) and MUS81a (P=0.0191*) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients. The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.


Early auditory processing in area V5/MT+ of the congenitally blind brain.
Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.


Sexual assault cases at a tertiary referral hospital in urban Ethiopia: One-year retrospective review.
Sexual assault is an important health and social problem affecting young girls. The aim of the study is therefore to do a one-year retrospective review of documents of alleged sexual assaults managed at Saint Paulo's Hospital Millennium Medical College (SPHMMC) to determine survivors' characteristics, circumstances of the assault, and treatment offered. This is a hospital-based one-year retrospective review of alleged sexual assault cases. The case records of survivors were retrieved, reviewed and information extracted analyzed using SPSS version 17. Characteristics of victims of the sexual assault, clinical presentation, and management provided were described by frequency and percentage distribution. A total of 170 cases of alleged sexual assault who received care during the study period were identified. Around 96% of the survivors were female while there were 6 male cases. The mean age of the victims was 13 yrs. with a range from 2 to 25 yrs. About 23.6% of the victims were less than 10 years. Half of the victims were assaulted by neighbors (45%) followed by strangers (36.5%). The interval between the incident and presentation to the hospital ranged from 2 hours to 93 days (2224 hours) with an average of 98 hours. Most (93.0%) had one or more physical examination findings at presentation. Serology tests for HIV, Hepatitis B, and Syphilis were done in 97.3%, 88.7%, and 84.5% cases respectively. Urine pregnancy tests were done in 62.5% of the cases. Prophylaxis against HIV and STI prophylaxis was provided to 42% and 45% respectively. Social support/counseling was provided to 61% of the victims and legal evidence (certificate) was provided to 45.5% of the cases. Although it is largely not reported by the victims, sexual assault is a grievous offense still happening constantly. Children and young girls remain the most vulnerable. There is inadequate forensic evidence collection, legal and medical care. There is also a delay in presentation to hospital by victims. Therefore, there is a need to have standardized protocols for comprehensive evaluation and care of the survivors. It is also imperative that a multidisciplinary approach like a one-stop clinic should be utilized to provide effective and efficient medical, social, psychological, and legal services. Finally, it is very necessary to increase public awareness and preventive interventions are required particularly to protect the vulnerable age group to enhance their safety.


Mfsd8 localizes to endocytic compartments and influences the secretion of Cln5 and cathepsin D in Dictyostelium.
The neuronal ceroid lipofuscinoses (NCLs) are a family of neurodegenerative diseases that affect people of all ages and ethnicities, yet many of the associated genes/proteins are not well characterized. Mutations in MFSD8 (major facilitator superfamily domain-containing 8) cause an infantile form of NCL referred to as CLN7 disease. In this study, we revealed the localization and binding partners of an ortholog of human MFSD8 (Mfsd8) in the social amoeba Dictyostelium discoideum. Putative lysosomal targeting motifs are conserved in Dictyostelium Mfsd8, as are several residues mutated in CLN7 disease patients. Mfsd8 tagged with GFP localizes to endocytic compartments, which includes acidic intracellular vesicles and late endosomes. We pulled-down GFP-Mfsd8 and used mass spectrometry to reveal the Mfsd8 interactome during Dictyostelium growth and starvation. Among the identified hits were the Dictyostelium ortholog of human cathepsin D (CtsD), as well as proteins linked to the functions of the CLN3 (Cln3) and CLN5 (Cln5) orthologs in Dictyostelium. To study the function of Mfsd8, we validated a publically available mfsd8- cell line (GWDI Project) and then used this knockout cell line to show that Mfsd8 influences the secretion of Cln5 and CtsD. This information is then integrated into an emerging model describing the molecular networking of NCL proteins in Dictyostelium. In total, this study identifies Dictyostelium as a new model system for studying CLN7 disease.


Identification of the sex pheromone of the tree infesting Cossid Moth Coryphodema tristis (Lepidoptera: Cossidae).
The cossid moth (Coryphodema tristis) has a broad range of native tree hosts in South Africa. The moth recently moved into non-native Eucalyptus plantations in South Africa, on which it now causes significant damage. Here we investigate the chemicals involved in pheromone communication between the sexes of this moth in order to better understand its ecology, and with a view to potentially develop management tools for it. In particular, we characterize female gland extracts and headspace samples through coupled gas chromatography electro-antennographic detection (GC-EAD) and two dimensional gas chromatography mass spectrometry (GCxGC-MS). Tentative identities of the potential pheromone compounds were confirmed by comparing both retention time and mass spectra with authentic standards. Two electrophysiologically active pheromone compounds, tetradecyl acetate (14:OAc) and Z9-tetradecenyl acetate (Z9-14:OAc) were identified from pheromone gland extracts, and an additional compound (Z9-14:OH) from headspace samples. We further determined dose response curves for the identified compounds and six other structurally similar compounds that are common to the order Cossidae. Male antennae showed superior sensitivity toward Z9-14:OAc, Z7-tetradecenyl acetate (Z7-14:OAc), E9-tetradecenyl acetate (E9-14:OAc), Z9-tetradecenol (Z9-14:OH) and Z9-tetradecenal (Z9-14:Ald) when compared to female antennae. While we could show electrophysiological responses to single pheromone compounds, behavioral attraction of males was dependent on the synergistic effect of at least two of these compounds. Signal specificity is shown to be gained through pheromone blends. A field trial showed that a significant number of males were caught only in traps baited with a combination of Z9-14:OAc (circa 95% of the ratio) and Z9-14:OH. Addition of 14:OAc to this mixture also improved the number of males caught, although not significantly. This study represents a major step towards developing a useful attractant to be used in management tools for C. tristis and contributes to the understanding of chemical communication and biology of this group of insects.


Genetic Testing for Hypertriglyceridemia in Academic Lipid Clinics: Implications for Precision Medicine-Brief Report.
Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown. We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight's Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride (<200 mg/dL), moderate (200-499 mg/dL), severe (500-999 mg/dL), or very severe (≥1000 mg/dL). PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 [P=0.02] after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone. The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies.


Reliability, validity and administrative burden of the community reintegration of injured service members computer adaptive test (CRIS-CAT)".
The Computer Adaptive Test version of the Community Reintegration of Injured Service Members measure (CRIS-CAT) consists of three scales measuring Extent of, Perceived Limitations in, and Satisfaction with community integration. The CRIS-CAT was developed using item response theory methods. The purposes of this study were to assess the reliability, concurrent, known group and predictive validity and respondent burden of the CRIS-CAT.The CRIS-CAT was developed using item response theory methods. The purposes of this study were to assess the reliability, concurrent, known group and predictive validity and respondent burden of the CRIS-CAT. This was a three-part study that included a 1) a cross-sectional field study of 517 homeless, employed, and Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans; who completed all items in the CRIS item set, 2) a cohort study with one year follow-up study of 135 OEF/OIF Veterans, and 3) a 50-person study of CRIS-CAT administration. Conditional reliability of simulated CAT scores was calculated from the field study data, and concurrent validity and known group validity were examined using Pearson product correlations and ANOVAs. Data from the cohort were used to examine the ability of the CRIS-CAT to predict key one year outcomes. Data from the CRIS-CAT administration study were used to calculate ICC (2,1) minimum detectable change (MDC), and average number of items used during CAT administration. Reliability scores for all scales were above 0.75, but decreased at both ends of the score continuum. CRIS-CAT scores were correlated with concurrent validity indicators and differed significantly between the three Veteran groups (P < .001). The odds of having any Emergency Room visits were reduced for Veterans with better CRIS-CAT scores (Extent, Perceived Satisfaction respectively: OR = 0.94, 0.93, 0.95; P < .05). CRIS-CAT scores were predictive of SF-12 physical and mental health related quality of life scores at the 1 year follow-up. Scales had ICCs >0.9. MDCs were 5.9, 6.2, and 3.6, respectively for Extent, Perceived and Satisfaction subscales. Number of items (mn, SD) administered at Visit 1 were 14.6 (3.8) 10.9 (2.7) and 10.4 (1.7) respectively for Extent, Perceived and Satisfaction subscales. The CRIS-CAT demonstrated sound measurement properties including reliability, construct, known group and predictive validity, and it was administered with minimal respondent burden. These findings support the use of this measure in assessing community reintegration.


Knee Kinematics During Noncontact Anterior Cruciate Ligament Injury as Determined From Bone Bruise Location.
The motions causing noncontact anterior cruciate ligament (ACL) injury remain unclear. Tibiofemoral bone bruises are believed to be the result of joint impact near the time of ACL rupture. The locations and frequencies of these bone bruises have been reported, but there are limited data quantifying knee position and orientation near the time of injury based on these contusions. Knee position and orientation near the time of noncontact ACL injury include extension and anterior tibial translation. Descriptive laboratory study. Magnetic resonance images of 8 subjects with noncontact ACL injuries were acquired within 1 month of injury and were subsequently analyzed. All subjects exhibited bruises on both the femur and tibia in both medial and lateral compartments. The outer margins of bone and the bone bruise surfaces were outlined on each image to create a 3-dimensional model of each subject's knee in its position during magnetic resonance imaging (MRI position). Numerical optimization was used to maximize overlap of the bone bruises on the femur and tibia and to predict the position of injury. Flexion angle, valgus orientation, internal tibial rotation, and anterior tibial translation were measured in both the MRI position and the predicted position of injury. Differences in kinematics between the MRI position, which served as an unloaded reference, and the predicted position of injury were compared by use of paired t tests. Flexion angle was near full extension in both the MRI position and the predicted position of injury (8° vs 12°; P = .2). Statistically significant increases in valgus orientation (5°; P = .003), internal tibial rotation (15°; P = .003), and anterior tibial translation (22 mm; P < .001) were observed in the predicted position of injury relative to the MRI position. These results suggest that for the bone bruise pattern studied, landing on an extended knee is a high risk for ACL injury. Extension was accompanied by increased anterior tibial translation (22 mm), internal tibial rotation (15°), and valgus rotation (5°) in the predicted position of injury relative to the MRI position. This study provides novel data characterizing the motions associated with ACL injury, information critical to improving strategies aimed at injury prevention.


Frailty in Older Adults with Cardiovascular Disease: Cause, Effect or Both?
Cardiovascular disease (CVD) has been associated with an increased risk of frailty, but the direction of the association remains unclear. This study set out to examine the bidirectional longitudinal association between CVD and frailty over an extended period of time. Data are from 1432 older adults (aged 65-88yrs) of the Longitudinal Aging Study Amsterdam (LASA), who were followed for 17 years. At baseline and follow-up, CVD was assessed through self-report, medication use and medical records, and classified as angina pectoris, myocardial infarction, heart failure (HF), stroke, and peripheral artery disease. Throughout the study, frailty was assessed using Fried's frailty criteria. Cox regression models showed that patients with HF had an increased frailty risk (HR 2.7; 95%CI: 1.5-5.1) after a median follow-up of 8.4 yrs. This finding was independent of potential confounders (age, sex, several comorbidities). Examinations of the reverse association revealed that frail older adults were not at risk of incident CVD. Of all older adults with CVD, those with HF have an increased risk of frailty and frail older adults do not have an increased risk of CVD. Our findings emphasize the need for cardiac rehabilitation programs evaluating the effect of physical exercise programs in order to prevent frailty and therewith improve quality of life and independence of care in CVD patients.


The web-based ASSO-food frequency questionnaire for adolescents: relative and absolute reproducibility assessment.
A new food frequency questionnaire (FFQ) has been recently developed within the Italian Adolescents and Surveillance System for the Obesity prevention (ASSO) Project; it was found to be appropriate for ranking adolescents in food and nutrient levels of intake. The aim of this study was to assess the relative and absolute reproducibility of the ASSO-FFQ for 24 food groups, energy and 52 nutrients. A test-retest study was performed on two ASSO-FFQs administered one month apart of each other to 185 adolescents, aged 14-17 and attending secondary schools in Palermo (Italy). Wilcoxon test assessed differences in median daily intakes between the two FFQs. Agreement was evaluated by quintiles comparison and weighted kappa. Intraclass Correlation Coefficients (ICC) and Bland-Altman method assessed the relative and absolute reliability respectively. Significant difference (p < 0.05) in median intakes was found only for bread substitutes, savoury food, water, soft drinks, carbohydrates and sugar. The subjects classified into the same or adjacent quintiles for food groups ranged from 62% (white bread) to 91% (soft drinks); for energy and nutrients from 64% (polyunsaturated fatty acids) to 90% (ethanol). Mean values of weighted kappa were 0.47 and 0.48, respectively for food groups and nutrients. Fair to good ICC values (>0.40) were assessed for thirteen food groups, energy and forty-three nutrients. Limits of Agreement were narrow for almost all food groups and all nutrients. The ASSO-FFQ is a reliable instrument for estimating food groups, energy and nutrients intake in adolescents.


Comparison of fresh and aged lithium iron phosphate cathodes using a tailored electrochemical strain microscopy technique.
Electrochemical strain microscopy (ESM) is a powerful atomic force microscopy (AFM) mode for the investigation of ion dynamics and activities in energy storage materials. Here we compare the changes in commercial LiFePO4 cathodes due to ageing and its influence on the measured ESM signal. Additionally, the ESM signal dynamics are analysed to generate characteristic time constants of the diffusion process, induced by a dc-voltage pulse, which changes the ionic concentration in the material volume under the AFM tip. The ageing of the cathode is found to be governed by a decrease of the electrochemical activity and the loss of available lithium for cycling, which can be stored in the cathode.


Folate and vitamin B12 status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK.
Concerns about risks for older people with vitamin B12 deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12 and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n 2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12 status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15.8 (sd 14.7) nmol/l in 1995 to 31.1 (sd 26.2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12 status was unaffected by high v. low folate status (>30 nmol/l) (OR 1.50 (95 % CI 0.91, 2.46) v. 1.45 (95 % CI 1.19, 1.76)), respectively. The associations of cognitive impairment with low B12 status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2.46; 95 % CI 0.90, 6.71) v. (1.56; 95 % CI 1.30, 1.88)). There was no evidence of modification by high folate status of the associations of low B12 with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.


Regionalisation of the mouse embryonic ectoderm: allocation of prospective ectodermal tissues during gastrulation.
The regionalisation of cell fate in the embryonic ectoderm was studied by analyzing the distribution of graft-derived cells in the chimaeric embryo following grafting of wheat germ agglutinin--gold-labelled cells and culturing primitive-streak-stage mouse embryos. Embryonic ectoderm in the anterior region of the egg cylinder contributes to the neuroectoderm of the prosencephalon and mesencephalon. Cells in the distal lateral region give rise to the neuroectoderm of the rhombencephalon and the spinal cord. Embryonic ectoderm at the archenteron and adjacent to the middle region of the primitive streak contributes to the neuroepithelium of the spinal cord. The proximal-lateral ectoderm and the ectodermal cells adjacent to the posterior region of the primitive streak produce the surface ectoderm, the epidermal placodes and the cranial neural crest cells. Some labelled cells grafted to the anterior midline are found in the oral ectodermal lining, whereas cells from the archenteron are found in the notochord. With respect to mesodermal tissues, ectoderm at the archenteron and the distal-lateral region of the egg cylinder gives rise to rhombencephalic somitomeres, and the embryonic ectoderm adjacent to the primitive streak contributes to the somitic mesoderm and the lateral mesoderm. Based upon results of this and other grafting studies, a map of prospective ectodermal tissues in the embryonic ectoderm of the full-streak-stage mouse embryo is constructed.


High compliance with dietary recommendations in a cohort of meat eaters, fish eaters, vegetarians, and vegans: results from the European Prospective Investigation into Cancer and Nutrition-Oxford study.
The aim of this study was to investigate differences in dietary intakes between 30251 participants in the European Prospective Investigation into Cancer and Nutrition-Oxford study, comprising 18 244 meat eaters, 4 531 fish eaters, 6 673 vegetarians, and 803 vegans aged 30 to 90 years who completed semiquantitative food frequency questionnaires. We hypothesized that these groups characterized by varying degrees of animal product exclusion have significantly different intakes of many nutrients, with possible implications for dietary adequacy and compliance with population dietary goals. Nutrient intakes were estimated including fortification in foods, but excluding dietary supplements. Dietary supplementation practices were also evaluated. Highly significant differences were found in estimated nutrient intakes between meat eaters and vegans, with fish eaters and vegetarians usually having intermediate values. Meat eaters had the highest energy intakes, followed by fish eaters and vegetarians, whereas vegans had the lowest intakes. Vegans had the highest intakes of polyunsaturated fatty acids, dietary fiber, vitamins C and E, folate, magnesium, iron, and copper. Meat eaters had the highest intake of saturated fatty acids, protein, vitamin B2, vitamin B12, vitamin D, zinc, and iodine. Fish eaters had the highest intakes of calcium and selenium. There were no statistically significant differences in sodium and potassium intakes between dietary groups. With the exception of sodium intake, compliance with population dietary goals was high across diet groups. The results suggested a high prevalence of inadequacy for dietary vitamin B12 and iodine in vegans. The diet groups under study showed striking differences in dietary intakes, with possible implications for compliance with dietary recommendations, as well as cardiometabolic diseases risk.


Double accessory pathways in Wolff-Parkinson-White syndrome.
Intracardiac electrophysiological studies were performed in two patients with Wolff-Parkinson-White (WPW) syndrome. Atrial pacing at increasing rates or shorter coupling intervals produced inscription of the forward His bundle deflection at progressively longer intervals after the onset of ventricular depolarization. There was an associated increase in QRS duration without any change in the P-R (or St-V) interval. This response was consistent with a Kent bundle. Case 1 also had a short A-H interval which did not show the expected prolongation with stimulation at progressively faster rates. This suggested the presence of a James bundle in addition to the Kent bundle. In case 2 beats conducted exclusively through the atrioventricular (A-V) node had a short H-V interval but a delta wave was not inscribed. Absence of an initial slurring was attributed to the existence of an infra-His bundle bypass of the Mahaim type causing only slight pre-excitation, which was not of sufficient magnitude to be recorded by body surface leads. However, the existence of a congenitally short anterosuperior division of the left bundle could nt be excluded.


Identification of functional genic components of major fusarium head blight resistance quantitative trait loci in wheat cultivar Sumai 3.
Fusarium head blight (FHB) is a devastating disease worldwide, affecting wheat and other small grains. To identify key wheat genes involved in FHB pathogenesis, 406 FHB-related wheat expressed sequence tags functionally identified in Sumai 3 were investigated for their association with FHB-resistance quantitative trait loci (QTL) Fhb1 and Fhb_6BL in 2010 and 2011. A total of 47 candidate genes were identified by bulk analysis, near-isogenic screening and expression QTL mapping, and were finally mapped to their carrier chromosomes with Chinese Spring nulli-tetra deficiency lines. One gene, designated WFhb1_c1 (wheat Fhb1 candidate gene 1), was both functionally associated with and physically located within Fhb1 and was found to be weakly similar (E = 5e+0) to an Arabidopsis gene encoding pectin methyl esterase inhibitor. Two other genes, designated WFI_6BL1 and WFI_6BL2 (wheat-Fusarium interaction genes 6BL1 and 6BL2), were functionally associated with Fhb_6BL but physically mapped on chromosomes 7D and 5A, respectively. WFI_6BL1 was annotated as a 13- lipoxygenase gene and WFI_6BL2 might encode a PR-4-like protein. Our data suggested that i) Fhb1 seems to contribute to FHB resistance by reducing susceptibility in the first 60 h, ii) Fhb_6BL makes its contribution via the jasmonate-mediated pathways, and iii) wheat seems to activate its defense mechanism in the biotrophic phase of FHB pathogenesis.


Hirschsprung's disease: healthcare meets the needs.
The objective of this study was to examine the types of healthcare services used by children, adolescents, and adults with Hirschsprung Disease (HD) in relation to the severity of the initial defect (mild, severe), whether additional care was needed, the provision of information, transfer to adult care, and satisfaction with the care provided. Three hundred twenty (71%) HD patients, ages 6 to 54, completed a questionnaire that assessed the use of healthcare services, the need for more healthcare, the provision of information, the transfer to adult care and satisfaction with the provided care. In 6 months, 45% of the children, 14% of the adolescents, and 15% of the adults consulted a medical specialist. Compared with patients with a mild form of HD in the age range of 6 to 16 years, only the more severely afflicted adult patients visited medical professionals more often (10% vs 29%) (P < .05). Of the children, the adolescents, and the adults 23%, 8%, and 6% respectively consulted a nonmedical professional. Less than 15% of all patients whould have liked more treatment. In 6 months 51% of the children, 24% of the adolescents, and 21% of the adults received treatment information, of which respectively 14, 8, and 20% wished they had received more information. Three (12%) patients who needed adult care encountered problems with the transfer. Almost all patients were satisfied with the care provided. There is good access to medical healthcare services, especially for children. The only lacuna in the healthcare system we revealed was a lack of information, particularly for adult patients. Most parents and patients reported to be very satisfied with the provided care.


International and collaborative strategies to enhance genetic health in purebred dogs.
Health problems in pedigree dogs have recently been highlighted in the media worldwide and verified internationally by cynological organisations. Collaborative actions are now needed to deal with both existing and future issues. In this article, potential roles for various stakeholders are discussed and the value of national and international platforms for collaborations is stressed. Development of specific strategies for action must be based on criteria of significance, such as severity, prevalence and inheritance, as well as availability of effective preventive measures. Assessment of options should be founded on evidence from appropriate populations-at-risk and consider broader issues, such as demographics and human-animal interactions. Existing data, such as those from insurance statistics and health surveys, should be used as a reference until representative national/international population-level breed-specific data are available. Key issues and challenges, as well as possible strategies to address them, are discussed.


Internet use and depression among retired older adults in the United States: a longitudinal analysis.
The purpose of this study is to examine the association between Internet use among retired older adults in the United States and changes in a commonly used predictor of depression (the CES-D). Analyzing data from four waves (2002-2008) of the Health and Retirement Survey, we assess whether an available and commonly used index of a depression state was affected by prior values of the index and Internet use. The sample includes 3,075 respondents observed over 4 waves of data, yielding a total of 12,300 observations. We analyzed the effect on depression of Internet use and past depression in a full sample and a matched sample. We also conducted informal tests for confounders. Finally, we tested a basic mediation model to determine whether Internet use affected depression through its relationship with loneliness and social isolation. Across methods, we found a positive contribution of Internet use to mental well-being of retired older adults in the United States, where Internet use reduced the probability of a depression state by one third. We found no evidence of confounding. Some evidence of mediation was found. Our dynamic probit model indicates that for retired older adults in the United States, Internet use was found to reduce the probability of a depressed state by about 33%. Number of people in the household partially mediates this relationship, with the reduction in depression largest for people living alone. This provides some evidence that the mechanism linking Internet use to depression is the remediation of social isolation and loneliness. Encouraging older adults to use the Internet may help decrease isolation and depression.


Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties.
Out of the prominent global ailments, tuberculosis (TB) is still one of the leading causes of death worldwide due to infectious disease. Development of new drugs that shorten the current tuberculosis treatment time and have activity against drug resistant strains is of utmost importance. Towards these goals we have focused our efforts on developing novel anti-TB compounds with the general structure of 1-adamantyl-3-phenyl urea. This series is active against Mycobacteria and previous lead compounds were found to inhibit the membrane transporter MmpL3, the protein responsible for mycolic acid transport across the plasma membrane. However, these compounds suffered from poor in vitro pharmacokinetic (PK) profiles and they have a similar structure/SAR to inhibitors of human soluble epoxide hydrolase (sEH) enzymes. Therefore, in this study the further optimization of this compound class was driven by three factors: (1) to increase selectivity for anti-TB activity over human sEH activity, (2) to optimize PK profiles including solubility and (3) to maintain target inhibition. A new series of 1-adamantyl-3-heteroaryl ureas was designed and synthesized replacing the phenyl substituent of the original series with pyridines, pyrimidines, triazines, oxazoles, isoxazoles, oxadiazoles and pyrazoles. This study produced lead isoxazole, oxadiazole and pyrazole substituted adamantyl ureas with improved in vitro PK profiles, increased selectivity and good anti-TB potencies with sub μg/mL minimum inhibitory concentrations.


New pressure-induced polymorphic transitions of anhydrous magnesium sulfate.
The effects of pressure on the crystal structure of the three known polymorphs of magnesium sulfate (α-MgSO4, β-MgSO4, and γ-MgSO4) have been theoretically studied by means of density-functional theory calculations up to 45 GPa. We determined that under ambient conditions γ-MgSO4 is an unstable polymorph, which decomposes into MgO + SO3, and that the response of the other two polymorphs to hydrostatic pressure is non-isotropic. Additionally, we found that at all pressures β-MgSO4 has a larger enthalpy than α-MgSO4. This indicates that β-MgSO4 is thermodynamically unstable versus α-MgSO4 and predicts the occurrence of a β-α phase transition under moderate compression. Our calculations also predict the existence under pressure of additional phase transitions to two new polymorphs of MgSO4, which we named δ-MgSO4 and ε-MgSO4. The α-δ transition is predicted to occur at 17.5 GPa, and the δ-ε transition at 35 GPa, pressures that nowadays can be experimentally easily achieved. All the predicted structural transformations are characterized as first-order transitions. This suggests that they can be non-reversible, and therefore the new polymorphs could be recovered as metastable polymorphs under ambient conditions. The crystal structure of the two new polymorphs is reported. In them, the coordination number of sulfur is four as in the previously known polymorphs, but the coordination number of magnesium is eight instead of six. In this article we will report the axial and bond compressibility for the four polymorphs of MgSO4. The pressure-volume equation of state of each phase is also given, which is described by a third-order Birch-Murnaghan equation. The values obtained for the bulk modulus are 62 GPa, 57 GPa, 102 GPa, and 119 GPa for α-MgSO4, β-MgSO4, δ-MgSO4, and ε-MgSO4, respectively. Finally, the electronic band structure of these four polymorphs of MgSO4 has been calculated for the first time. The obtained results will be presented and discussed.


Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control.
GCN4 encodes a transcriptional activator of amino acid-biosynthetic genes in Saccharomyces cerevisiae that is regulated at the translational level by upstream open reading frames (uORFs) in its mRNA leader. uORF4 (counting from the 5' end) is sufficient to repress GCN4 under nonstarvation conditions; uORF1 is required to overcome the inhibitory effect of uORF4 and stimulate GCN4 translation in amino acid-starved cells. Insertions of sequences with the potential to form secondary structure around uORF4 abolish derepression, indicating that ribosomes reach GCN4 by traversing uORF4 sequences rather than by binding internally to the GCN4 start site. By showing that wild-type regulation occurred even when uORF4 was elongated to overlap GCN4 by 130 nucleotides, we provide strong evidence that those ribosomes which translate GCN4 do so by ignoring the uORF4 AUG start codon. This conclusion is in accord with the fact that translation of a uORF4-lacZ fusion was lower in a derepressed gcd1 mutant than in a nonderepressible gcn2 strain. We also show that increasing the distance between uORF1 and uORF4 to the wild-type spacing that separates uORF1 from GCN4 specifically impaired the ability of uORF1 to derepress GCN4 translation. As expected, this alteration led to increased uORF4-lacZ translation in gcd1 cells. Our results suggest that under starvation conditions, a substantial fraction of ribosomes that translate uORF1 fail to reassemble the factors needed for reinitiation by the time they scan to uORF4, but become competent to reinitiate after scanning the additional sequences to GCN4. Under nonstarvation conditions, ribosomes would recover more rapidly from uORF1 translation, causing them all to reinitiate at uORF4 rather than at GCN4.


Anthropogenic and naturally produced brominated substances in Baltic herring (Clupea harengus membras) from two sites in the Baltic Sea.
In the eutrophicated Baltic Sea, several naturally produced hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been found in marine biota. OH-PBDEs are toxic to adult and developing zebrafish and shown to be potent disruptors of oxidative phosphorylation (OXPHOS). Disturbed OXPHOS can result in altered energy metabolism and weight loss. In herring, the concentration of OH-PBDEs (i.e. 2'-OH-BDE68 and 6-OH-BDE47) has increased during the period 1980-2010 in the Baltic Proper. Over the same time period, the condition and fat content in Baltic herring have decreased. Given the toxicity and increasing trends of OH-PBDEs in Baltic herring it is important to further assess the exposure to OH-PBDEs in Baltic herring. In this study, the concentrations of OH-PBDEs and related brominated substances i.e. polybrominated phenols (PBPs), polybrominated anisoles (PBAs), methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and polybrominated diphenyl ethers (PBDEs) were measured in herring sampled in the northern Baltic Proper (Askö, n = 12) and the southern Bothnian Sea (Ängskärsklubb, n = 12). The geometric mean (GM) concentrations (ng/g l.w.) at Askö and Ängskärsklubb were; Σ2PBPs: 4.3 and 9.6, Σ(2)PBAs: 34 and 20, Σ(6)OH-PBDEs: 9.4 and 10, Σ(7)MeO-PBDEs: 42 and 150, Σ(6)PBDEs: 54 and 27, respectively. 6-OH-BDE47 dominated the OH-PBDE profile and comprised 87% (Askö) and 91% (Ängskärsklubb) of the ΣOH-PBDEs. At Ängskärsklubb the mean concentration of ΣMeO-PBDEs (150 ng/g l.w.) was 15 times higher than ΣOH-PBDEs. As other fish species are known to metabolically transform MeO-PBDEs to OH-PBDEs, high levels of MeO-PBDEs can be of concern as a precursor for more toxic OH-PBDEs in herring and their roe.


Lateralization of the human mirror neuron system.
A cortical network consisting of the inferior frontal, rostral inferior parietal, and posterior superior temporal cortices has been implicated in representing actions in the primate brain and is critical to imitation in humans. This neural circuitry may be an evolutionary precursor of neural systems associated with language. However, language is predominantly lateralized to the left hemisphere, whereas the degree of lateralization of the imitation circuitry in humans is unclear. We conducted a functional magnetic resonance imaging study of imitation of finger movements with lateralized stimuli and responses. During imitation, activity in the inferior frontal and rostral inferior parietal cortex, although fairly bilateral, was stronger in the hemisphere ipsilateral to the visual stimulus and response hand. This ipsilateral pattern is at variance with the typical contralateral activity of primary visual and motor areas. Reliably increased signal in the right superior temporal sulcus (STS) was observed for both left-sided and right-sided imitation tasks, although subthreshold activity was also observed in the left STS. Overall, the data indicate that visual and motor components of the human mirror system are not left-lateralized. The left hemisphere superiority for language, then, must be have been favored by other types of language precursors, perhaps auditory or multimodal action representations.


Equality for (almost) all: Egalitarian advocacy predicts lower endorsement of sexism and racism, but not ageism.
Past research has assumed that social egalitarians reject group-based hierarchies and advocate for equal treatment of all groups. However, contrary to popular belief, we argue that egalitarian advocacy predicts greater likelihood to support "Succession"-based ageism, which prescribes that older adults step aside to free up coveted opportunities (e.g., by retiring). Although facing their own forms of discrimination, older individuals are perceived as blocking younger people, and other unrepresented groups, from opportunities-that in turn, motivates egalitarian advocates to actively discriminate against older adults. In 9 separate studies (N = 3,277), we demonstrate that egalitarian advocates endorse less prejudice toward, and show more support for, women and racial minorities, but harbor more prejudice toward (Studies 1 and 2), and show less advocacy for (Studies 3-6), older individuals. We demonstrate downstream consequences of this effect, such as support for, and resource allocation to, diversity initiatives (Studies 3-6). Further, we isolate perceived opportunity blocking as a critical mediator, demonstrating that egalitarian advocates believe that older individuals actively obstruct more deserving groups from receiving necessary resources and support to get ahead (Studies 4-6). Finally, we explore the intersectional nature of this effect (Study 7). Together this research suggests that when it comes to egalitarianism, equality for all may only mean equality for some. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Pulmonary Air Embolism: An Infrequent Complication in the Radiology Suite.
BACKGROUND Air embolism can occur in a number of medical-surgical situations. Venous air embolism is frequently lethal when a substantial amount enters the venous circulation rapidly and can lead to significant morbidity if crossover to the systemic arterial circulation occurs. The diagnosis of massive air embolism is usually made on clinical grounds by the development of abrupt hemodynamic compromise. The true incidence, morbidity, and mortality of this event is unknown given the difficulties in diagnosis. CASE REPORT An inadvertent antecubital venous injection of 150 mL of air using a contrast power injector during a computed tomography (CT) is reported. Immediate imaging (CT) showed a significant amount of air in the right atrium and right ventricular cavity, and air mixed with contrast in the main pulmonary artery and proximal divisions of the pulmonary circulation. Patient condition deteriorated requiring mechanical ventilation for 48 hours. Condition improved over the next few days and patient was successfully extubated and discharged home. CONCLUSIONS Air embolism is a rare complication, the potential for this to be life threatening makes prevention and early detection of this condition essential. This condition should be suspected when patients experience sudden onset respiratory distress and/or experience a neurological event in the setting of a known risk factor. Treatment options include Durant's maneuver; left-lateral decubitus, head-down positioning; to decrease air entry into the right ventricle outflow tract, hyperbaric therapy, 100% O2 and supportive care.


Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study.
Published guidelines recommend spirometry to accurately diagnose chronic obstructive pulmonary disease (COPD). However, even spirometry-based COPD prevalence estimates can vary widely. We compared properties of several spirometry-based COPD definitions using data from the international Burden of Obstructive Lung Disease (BOLD)study. 14 sites recruited population-based samples of adults aged > or =40 yrs. Procedures included standardised questionnaires and post-bronchodilator spirometry. 10,001 individuals provided usable data. Use of the lower limit of normal (LLN) forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) ratio reduced the age-related increases in COPD prevalence that are seen among healthy never-smokers when using the fixed ratio criterion (FEV(1)/FVC <0.7) recommended by the Global Initiative for Chronic Obstructive Lung Disease. The added requirement of an FEV(1) either <80% predicted or below the LLN further reduced age-related increases and also led to the least site-to-site variability in prevalence estimates after adjusting for potential confounders. Use of the FEV(1)/FEV(6) ratio in place of the FEV(1)/FVC yielded similar prevalence estimates. Use of the FEV(1)/FVC<LLN criterion instead of the FEV(1)/FVC <0.7 should minimise known age biases and better reflect clinically significant irreversible airflow limitation. Our study also supports the use of the FEV(1)/FEV(6) as a practical substitute for the FEV(1)/FVC.


Thyrotropin receptor/thyroglobulin messenger ribonucleic acid in peripheral blood and fine-needle aspiration cytology: diagnostic synergy for detecting thyroid cancer.
RT-PCR for thyroglobulin (Tg) and TSH receptor (TSHR) mRNA has been used to detect circulating thyroid cancer cells. Little is known, however, regarding the preoperative sensitivity of this test to detect cancer. Seventy-two patients with thyroid disease (36 with malignancy and 36 with benign disease) were evaluated preoperatively. TSHR and Tg mRNA transcripts were detected by RT-PCR assays, previously determined to be specific for cancer cells. There was 100% concordance between TSHR and Tg mRNA RT-PCR results. Of 36 cancer patients, 11 had recurrent disease, and all were positive by RT-PCR. Among 25 patients with no prior thyroid surgery, 18 tested positive preoperatively (sensitivity 72%). Seven of 36 patients with benign disease tested positive (specificity 80%). The overall preoperative diagnostic accuracy was 77%. Preoperative fine-needle aspiration (FNA) biopsy was performed on 46 of 61 patients with no prior thyroid surgery. FNA was diagnostic in 28 (61%) patients. Preoperative cytology was adequate but not diagnostic in 18 (39%) patients. RT-PCR correctly classified 14 of these 18 patients with indeterminate FNA, and the test detected three of four cancer patients as positive (75% sensitive) and 11 of 14 patients (78% specific) with benign disease as negative. The combined diagnostic performance characteristics for RT-PCR and FNA cytology were sensitivity = 95%, specificity = 83%, and diagnostic accuracy = 89%, with positive and negative predictive values of 84 and 95%, respectively. Our results suggest that the molecular detection of circulating thyroid cancer cells by RT-PCR for TSHR/Tg mRNA complements FNA cytology in the preoperative differentiation of benign from malignant thyroid disease and their combined use may save unnecessary surgeries.


Global flows of critical metals necessary for low-carbon technologies: the case of neodymium, cobalt, and platinum.
This study, encompassing 231 countries and regions, quantifies the global transfer of three critical metals (neodymium, cobalt, and platinum) considered vital for low-carbon technologies by means of material flow analysis (MFA), using trade data (BACI) and the metal contents of trade commodities, resolving the optimization problem to ensure the material balance of the metals within each country and region. The study shows that in 2005 international trade led to global flows of 18.6 kt of neodymium, 154 kt of cobalt, and 402 t of platinum and identifies the main commodities and top 50 bilateral trade links embodying these metals. To explore the issue of consumption efficiency, the flows were characterized according to the technological level of each country or region and divided into three types: green ("efficient use"), yellow ("moderately efficient use"), and red ("inefficient use"). On this basis, the shares of green, yellow, and red flows in the aggregate global flow of Nd were found to be 1.2%, 98%, and 1.2%, respectively. For Co, the respective figures are 53%, 28%, and 19%, and for Pt 15%, 84%, and 0.87%. Furthermore, a simple indicator focusing on the composition of the three colored flows for each commodity was developed to identify trade commodities that should be prioritized for urgent technical improvement to reduce wasteful use of the metals. Based on the indicator, we discuss logical, strategic identification of the responsibilities and roles of the countries involved in the global flows.


The SR-B1 Receptor as a Potential Target for Treating Glioblastoma.
The goal of these studies was to provide proof of concept for a novel targeted therapy for Glioblastoma Multiforme (GBM). Methods. These studies involve the evaluation of reconstituted high density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for the drug, mammalian Target of Rapamycin (mTOR) inhibitor Everolimus (EVR) to GBM cells. Cytotoxicity studies and assessment of downstream effects, including apoptosis, migration, and cell cycle events, were probed, in relation to the expression of scavenger receptor B type 1 (SR-B1) by GBM cells. Findings from cytotoxicity studies indicate that the rHDL/EVR formulation was 185 times more potent than free EVR against high SR-B1 expressing cell line (LN 229). Cell cycle analysis revealed that rHDL/EVR treated LN229 cells had a 5.8 times higher apoptotic cell population than those treated with EVR. The sensitivity of GBM cells to EVR treatment was strongly correlated with SR-B1 expression. These studies present strong proof of concept regarding the efficacy of delivering EVR and likely other agents, via a biocompatible transport system, targeted to the SR-B1 receptor that is upregulated in most cancers, including GBM. Targeting the SR-B1 receptor could thus lead to effective personalized therapy of GBM.


Theoretical insights on methylbenzene side-chain growth in ZSM-5 zeolites for methanol-to-olefin conversion.
The key step in the conversion of methane to polyolefins is the catalytic conversion of methanol to light olefins. The most recent formulations of a reaction mechanism for this process are based on the idea of a complex hydrocarbon-pool network, in which certain organic species in the zeolite pores are methylated and from which light olefins are eliminated. Two major mechanisms have been proposed to date-the paring mechanism and the side-chain mechanism-recently joined by a third, the alkene mechanism. Recently we succeeded in simulating a full catalytic cycle for the first of these in ZSM-5, with inclusion of the zeolite framework and contents. In this paper, we will investigate crucial reaction steps of the second proposal (the side-chain route) using both small and large zeolite cluster models of ZSM-5. The deprotonation step, which forms an exocyclic double bond, depends crucially on the number and positioning of the other methyl groups but also on steric effects that are typical for the zeolite lattice. Because of steric considerations, we find exocyclic bond formation in the ortho position to the geminal methyl group to be more favourable than exocyclic bond formation in the para position. The side-chain growth proceeds relatively easily but the major bottleneck is identified as subsequent de-alkylation to produce ethene. These results suggest that the current formulation of the side-chain route in ZSM-5 may actually be a deactivating route to coke precursors rather than an active ethene-producing hydrocarbon-pool route. Other routes may be operating in alternative zeotype materials like the silico-aluminophosphate SAPO-34.


Chemical and biological methods for probing the structure and functions of polysialic acids.
Owing to its poly-anionic charge and large hydrodynamic volume, polysialic acid (polySia) attached to neural cell adhesion molecule regulates axon-axon and axon-substratum interactions and signalling, particularly, in the development of the central nervous system (CNS). Expression of polySia is spatiotemporally regulated by the action of two polysialyl transferases, namely ST8SiaII and ST8SiaIV. PolySia expression peaks during late embryonic and early post-natal period and maintained at a steady state in adulthood in neurogenic niche of the brain. Aberrant polySia expression is associated with neurological disorders and brain tumours. Investigations on the structure and functions, over the past four decades, have shed light on the physiology of polySia. This review focuses on the biological, biochemical, and chemical tools available for polySia engineering. Genetic knockouts, endo-neuraminidases that cleave polySia, antibodies, exogenous expression, and neuroblastoma cells have provided deep insights into the ability of polySia to guide migration of neuronal precursors in neonatal brain development, neuronal clustering, axonal pathway guidance, and axonal targeting. Advent of metabolic sialic acid engineering using ManNAc analogues has enabled reversible and dose-dependent modulation polySia in vitro and ex vivo. In vivo, ManNAc analogues readily engineer the sialoglycans in peripheral tissues, but show no effect in the brain. A recently developed carbohydrate-neuroactive hybrid strategy enables a non-invasive access to the brain in living animals across the blood-brain barrier. A combination of recent advances in CNS drugs and imaging with ManNAc analogues for polySia modulation would pave novel avenues for understanding intricacies of brain development and tackling the challenges of neurological disorders.


Metabolism of tea flavonoids in the gastrointestinal tract.
There is considerable interest in the bioavailability of flavan-3-ols such as tea catechins and their bioactivity in vivo. Although flavanols such as catechin and epicatechin have long been characterized as powerful antioxidants in vitro, evidence suggests that these compounds undergo significant metabolism and conjugation during absorption in the small intestine and in the colon. In the small intestine these modifications lead primarily to the formation of glucuronide conjugates that are more polar than the parent flavanol and are marked for renal excretion. Other phase II processes lead to the production of O-methylated forms that have reduced antioxidant potential via the methylation of the B-ring catechol. Significant modification of flavanols also occurs in the colon where the resident microflora degrade them to smaller phenolic acids, some of which may be absorbed. Cell, animal and human studies have confirmed such metabolism by the detection of flavanol metabolites in the circulation and tissues. This review will highlight the major sites of flavanol metabolism in the gastrointestinal tract and the processes that give rise to potential bioactive forms of flavan-3-ols in vivo.


Class B alkaline stabilization to achieve pathogen inactivation.
Liming is a cost-effective treatment currently employed in many Class B biosolids production plants in the United States. A bench scale model of lime stabilization was designed to evaluate the persistence of viral, bacterial and parasitic pathogens. The survival of fecal coliforms, Salmonella, adenovirus type 5, rotavirus Wa, bacteriophage MS-2, Cryptosporidium parvum oocysts, Giardia lamblia cysts, and Ascaris lumbricoides ova was evaluated under lime stabilization conditions in a water matrix. Fecal coliforms and Salmonella were undetectable following 2 hours of lime stabilization, demonstrating a 7-log reduction. Adenovirus, MS-2 and rotavirus were below detectable levels following 2 h of liming, demonstrating a 4-log reduction. G. lamblia cysts were also inactivated. A. lumbricoides ova remained viable following 72 hours of liming as did C. parvum oocysts. While this study confirmed that Ascaris ova are resistant to liming, their scarcity in sludge and low recovery efficiencies limit their use as indicator. The persistence of C. parvum oocysts after exposure to lime, suggests that this parasite would be a better choice as indicator for evaluating biosolids intended for land application. The studies done with adenovirus Type 5, rotavirus Wa and male specific bacteriophage provided preliminary data demonstrating similar inactivation rates. Monitoring anthropogenic viruses is a time consuming, labor intensive and expensive process. If further studies could demonstrate that phage could be used as an indicator of other enteric viruses, enhanced monitoring could result in greater acceptance of land application of biosolids while demonstrating no increased public health threat.


Evaluation of the role of risk perception in stakeholder engagement to prevent lead exposure in an urban setting.
Stakeholder engagement is a vital sustainable remediation practice for obtaining useful feedback and identifying societal needs. Evaluating and integrating risk perception of stakeholders into remediation and outreach efforts allows for greater insight, increases the likelihood of success and ultimately, benefits the community by protecting its members from environmental hazards. In this study, we identified risk perception factors that influenced residents' level of concern for mitigating their exposure to elevated concentrations of lead in household paint and historic fill material. Risk perception factors were assessed by an in-person survey conducted in public green spaces. The analysis of survey participants' responses indicated that their perception of risk to exposed lead was mostly influenced by the presence of hazardous materials in close proximity to their residence, the ability to address pollution, and awareness, interest, and individual accountability in mitigating environmental risks. Responses also revealed that residents considered risk of lead and soil pollution as less menacing than the presence of more immediate and perceptible risks posed by factors such as air and water pollution. In addition, the community seemed to exhibit "optimism bias" and did not identify itself at high risk to susceptible and immediate hazards, including lead exposure. This lack of concern over lead exposure created a significant obstacle to community participation in state-led education and outreach programs. By integrating risk perception analysis and increasing stakeholder engagement, we can bring more attention to this issue, educate the public about the threat of lead pollution, and efficiently use financial resources to implement a more sustainable solution.


Fan-in issues in a holographic grating interconnect system.
Coherent holographic grating interconnect systems exhibit deleterious interference effects when multiple optical beams are fanned into a single beam with the use of multiplexed gratings. Elimination of such effects is possible with the use of arrays of incoherent sources for readout, temporal sequencing, random phase modulation of the readout beams, or allocated volume configurations. The merits and drawbacks of each alternative are analyzed.


Isolation and characterization of sesquiterpenes from Arecophila saccharicola YMJ96022401 with NO production inhibitory activity.
Sesquiterpenes, arecoic acids A-F and arecolactone, were isolated from the ethyl acetate extracts of the fermented broth of Arecophila saccharicola YMJ96022401 along with two known analogues 1,7α,10α-trihydroxyeremophil-11(13)-en-12,8-olide and 1,10α,13-trihydroxyeremophil-7(11)-en-12,8-olide. Their structures were elucidated on the basis of spectroscopic data analyses. The inhibitory effects of all of these compounds on nitric oxide (NO) production in lipopolysaccharide (LPS, 200 μg/mL)-activated murine macrophage RAW264.7 cells were also evaluated. Among these compounds, 1,7α,10α-trihydroxyeremophil-11(13)-en-12,8-olide significantly inhibited NO production without any cytotoxicity, and its average maximum inhibition (E(max)) at 100 μM and median inhibitory concentration (IC₅₀) were 85.7%±0.8% and 16.5±1.0 μM, respectively. Arecolactone was the most potent, with the E(max) at 12.5 μM and IC₅₀ being 94.7%±0.8% and 1.32±0.1 μM, respectively, but displayed cytotoxicity at considerable higher concentrations than 25 μM. Analyses of Western blotting indicated that arecolactone (0.8-12.5 μM) inhibited induction of inducible NO synthase (iNOS) by LPS, which involved suppression of NF-κB activation and the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH₂-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) in activated RAW 264.7 cells. In addition, arecolactone concentration-dependently prevented the vascular hyporeactivity to phenylephrine induced by LPS (300 ng/mL) through iNOS pathway in isolated rat thoracic aortic rings. These results indicated that both of these naturally occurring iNOS inhibitors may provide a rationale for the potential anti-inflammatory effect of A. saccharicola YMJ96022401.


Tumor necrosis factor -α, interleukin-10, intercellular and vascular adhesion molecules are possible biomarkers of disease severity in complicated Plasmodium vivax isolates from Pakistan.
Cytokine-mediated endothelial activation pathway is a known mechanism of pathogenesis employed by Plasmodium falciparum to induce severe disease symptoms in human host. Though considered benign, complicated cases of Plasmodium vivax are being reported worldwide and from Pakistan. It has been hypothesized that P.vivax utilizes similar mechanism of pathogenesis, as that of P.falciparum for manifestations of severe malaria. Therefore, the main objective of this study was to characterize the role of cytokines and endothelial activation markers in complicated Plasmodium vivax isolates from Pakistan. A case control study using plasma samples from well-characterized groups suffering from P.vivax infection including uncomplicated cases (n=100), complicated cases (n=82) and healthy controls (n=100) were investigated. Base line levels of Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Intercellular adhesion molecule-1 (ICAM-1), Vascular adhesion molecule-1(VCAM-1) and E-selectin were measured by ELISA. Correlation of cytokines and endothelial activation markers was done using Spearman's correlation analysis. Furthermore, significance of these biomarkers as indicators of disease severity was also analyzed. The results showed that TNF-α, IL-10, ICAM-1and VCAM-1 were 3-fold, 3.7 fold and 2 fold increased between uncomplicated and complicated cases. Comparison of healthy controls with uncomplicated cases showed no significant difference in TNF-α concentrations while IL-6, IL-10, ICAM-1, VCAM-1 and E-selectin were found to be elevated respectively. In addition, significant positive correlation was observed between TNF-α and IL-10/ ICAM-1, IL-6 and IL-10, ICAM-1 and VCAM-1.A Receiver operating curve (ROC) was generated which showed that TNF-α, IL-10, ICAM-1 and VCAM-1 were the best individual predictors of complicated P.vivax malaria. The results suggest that though endothelial adhesion molecules are inducible by pro-inflammatory cytokine TNF-α, however, cytokine-mediated endothelial activation pathway is not clearly demonstrated as a mechanism of pathogenesis in complicated P.vivax malaria cases from Pakistan.


Using previous models to bias structural learning in the hierarchical BOA.
Estimation of distribution algorithms (EDAs) are stochastic optimization techniques that explore the space of potential solutions by building and sampling explicit probabilistic models of promising candidate solutions. While the primary goal of applying EDAs is to discover the global optimum or at least its accurate approximation, besides this, any EDA provides us with a sequence of probabilistic models, which in most cases hold a great deal of information about the problem. Although using problem-specific knowledge has been shown to significantly improve performance of EDAs and other evolutionary algorithms, this readily available source of problem-specific information has been practically ignored by the EDA community. This paper takes the first step toward the use of probabilistic models obtained by EDAs to speed up the solution of similar problems in the future. More specifically, we propose two approaches to biasing model building in the hierarchical Bayesian optimization algorithm (hBOA) based on knowledge automatically learned from previous hBOA runs on similar problems. We show that the proposed methods lead to substantial speedups and argue that the methods should work well in other applications that require solving a large number of problems with similar structure.


Transcriptional responses of intestinal epithelial cells to infection with Vibrio cholerae.
Vibrio cholerae is a noninvasive enteric bacterium that causes the severe diarrheal disease cholera. Candidate cholera vaccines have been engineered by deleting genes encoding known virulence factors in V. cholerae; however, many of these attenuated strains were still reactogenic in human volunteers. In this study, DNA arrays were utilized to monitor the transcriptional responses of human intestinal epithelial cells (T84) to eight strains of V. cholerae, including attenuated, toxigenic, and environmental isolates. cDNA probes generated from host RNA samples were hybridized against low- and high-density gene arrays. V. cholerae induced the transcription of a variety of host genes and repressed the expression of a lower number of genes. Expression patterns were confirmed for certain genes by reverse transcriptase PCR and enzyme-linked immunosorbent assays. A core subset of genes was found to be differentially regulated in all experiments. These genes included genes involved in innate mucosal immunity, intracellular signaling, and cellular proliferation. Reactogenic vaccine strains induced greater expression of genes for certain proinflammatory cytokines than nonreactogenic strains. Wild-type and attenuated derivatives induced and repressed many genes in common, although there were differences in the transcription profiles. These results indicate that the types of host genes modulated by attenuated V. cholerae, and the extent of their induction, may mediate the symptoms seen with reactogenic cholera vaccine strains.


Disruption of the Man-6-P targeting pathway in mice impairs osteoclast secretory lysosome biogenesis.
Osteoclasts are specialized cells that secrete lysosomal acid hydrolases at the site of bone resorption, a process critical for skeletal formation and remodeling. However, the cellular mechanism underlying this secretion and the organization of the endo-lysosomal system of osteoclasts have remained unclear. We report that osteoclasts differentiated in vitro from murine bone marrow macrophages contain two types of lysosomes. The major species is a secretory lysosome containing cathepsin K and tartrate-resistant acid phosphatase (TRAP), two hydrolases critical for bone resorption. These secretory lysosomes are shown to fuse with the plasma membrane, allowing the regulated release of acid hydrolases at the site of bone resorption. The other type of lysosome contains cathepsin D, but little cathepsin K or TRAP. Osteoclasts from Gnptab(-/-) (gene encoding GlcNAc-1-phosphotransferase α, β-subunits) mice, which lack a functional mannose 6-phosphate (Man-6-P) targeting pathway, show increased secretion of cathepsin K and TRAP and impaired secretory lysosome formation. However, cathepsin D targeting was intact, showing that osteoclasts have a Man-6-P-independent pathway for selected acid hydrolases.


Evaluation of a national physical activity intervention for children: VERB campaign, 2002-2004.
Amid concern for the consequences of physical inactivity among children, the Centers for Disease Control and Prevention started a campaign using commercial marketing methods to promote physical activity to children. Longitudinal study using a telephone survey to assess physical activity behaviors and attitudes at baseline and for 2 years of follow-up. Relationships of campaign awareness to behavioral and psychosocial effects were analyzed with use of propensity scoring. Nationally representative cohort of 2257 parent-child dyads. Marketing campaign (VERB) directed to all U.S. children aged 9 to 13 years. Components included general market and ethnic-specific advertisements on television and radio, in print, and through promotions in communities, schools, and on the Internet. Advertising ran nationally at consistent levels from June 2002 through June 2004. Psychosocial measures and self-reports of free-time and organized physical activity during nonschool hours in the week before the interview and on the day before the interview. After 2 years, a dose-response effect was detected in the study population. The more children who reported seeing VERB messages, the more physical activity they reported and the more positive their attitudes were about the benefits of being physically active. Children aware of VERB reported engaging in significantly more physical activity than children unaware of VERB. These results were considerably stronger than the effects after Year 1, which were only for physical activity among subpopulations. The VERB campaign continued to positively influence children's attitudes about physical activity and their physical activity behaviors and expanded the effects to more children. With adequate and sustained investment, health marketing shows promise to affect the attitudes and behavior of children.


Updating ACSM's Recommendations for Exercise Preparticipation Health Screening.
The purpose of the American College of Sports Medicine's (ACSM) exercise preparticipation health screening process is to identify individuals who may be at elevated risk for exercise-related sudden cardiac death and/or acute myocardial infarction. Recent studies have suggested that using the current ACSM exercise preparticipation health screening guidelines can result in excessive physician referrals, possibly creating a barrier to exercise participation. In addition, there is considerable evidence that exercise is safe for most people and has many associated health and fitness benefits; exercise-related cardiovascular events are often preceded by warning signs/symptoms; and the cardiovascular risks associated with exercise lessen as individuals become more physically active/fit. Consequently, a scientific roundtable was convened by the ACSM in June 2014 to evaluate the current exercise preparticipation health screening recommendations. The roundtable proposed a new evidence-informed model for exercise preparticipation health screening on the basis of three factors: 1) the individual's current level of physical activity, 2) presence of signs or symptoms and/or known cardiovascular, metabolic, or renal disease, and 3) desired exercise intensity, as these variables have been identified as risk modulators of exercise-related cardiovascular events. Identifying cardiovascular disease risk factors remains an important objective of overall disease prevention and management, but risk factor profiling is no longer included in the exercise preparticipation health screening process. The new ACSM exercise preparticipation health screening recommendations reduce possible unnecessary barriers to adopting and maintaining a regular exercise program, a lifestyle of habitual physical activity, or both, and thereby emphasize the important public health message that regular physical activity is important for all individuals.


Practice variation in anti-epileptic drug use for neonatal hypoxic-ischemic encephalopathy among regional NICUs.
While intercenter variation (ICV) in anti-epileptic drug (AED) use in neonates with seizures has been previously reported, variation in AED practices across regional NICUs has not been specifically and systematically evaluated. This is important as these centers typically have multidisciplinary neonatal neurocritical care teams and protocolized approaches to treating conditions such as hypoxic ischemic encephalopathy (HIE), a population at high risk for neonatal seizures. To identify opportunities for quality improvement (QI), we evaluated ICV in AED utilization for neonates with HIE treated with therapeutic hypothermia (TH) across regional NICUs in the US. Children's Hospital Neonatal Database and Pediatric Health Information Systems data were linked for 1658 neonates ≥36 weeks' gestation, > 1800 g birthweight, with HIE treated with TH, from 20 NICUs, between 2010 and 2016. ICV in AED use was evaluated using a mixed-effect regression model. Rates of AED exposure, duration, prescription at discharge and standardized AED costs per patient were calculated as different measures of utilization. Ninety-five percent (range: 83-100%) of patients with electrographic seizures, and 26% (0-81%) without electrographic seizures, received AEDs. Phenobarbital was most frequently used (97.6%), followed by levetiracetam (16.9%), phenytoin/fosphenytoin (15.6%) and others (2.4%; oxcarbazepine, topiramate and valproate). There was significant ICV in all measures of AED utilization. Median cost of AEDs per patient was $89.90 (IQR $24.52,$258.58). Amongst Children's Hospitals, there is marked ICV in AED utilization for neonatal HIE. Variation was particularly notable for HIE patients without electrographic seizures, indicating that this population may be an appropriate target for QI processes to harmonize neuromonitoring and AED practices across centers.


Dorsal and ventral stream contributions to form-from-motion perception in a patient with form-from motion deficit: a case report.
The main model of visual processing in primates proposes an anatomo-functional distinction between the dorsal stream, specialized in spatio-temporal information, and the ventral stream, processing essentially form information. However, these two pathways also communicate to share much visual information. These dorso-ventral interactions have been studied using form-from-motion (FfM) stimuli, revealing that FfM perception first activates dorsal regions (e.g., MT+/V5), followed by successive activations of ventral regions (e.g., LOC). However, relatively little is known about the implications of focal brain damage of visual areas on these dorso-ventral interactions. In the present case report, we investigated the dynamics of dorsal and ventral activations related to FfM perception (using topographical ERP analysis and electrical source imaging) in a patient suffering from a deficit in FfM perception due to right extrastriate brain damage in the ventral stream. Despite the patient's FfM impairment, both successful (observed for the highest level of FfM signal) and absent/failed FfM perception evoked the same temporal sequence of three processing states observed previously in healthy subjects. During the first period, brain source localization revealed cortical activations along the dorsal stream, currently associated with preserved elementary motion processing. During the latter two periods, the patterns of activity differed from normal subjects: activations were observed in the ventral stream (as reported for normal subjects), but also in the dorsal pathway, with the strongest and most sustained activity localized in the parieto-occipital regions. On the other hand, absent/failed FfM perception was characterized by weaker brain activity, restricted to the more lateral regions. This study shows that in the present case report, successful FfM perception, while following the same temporal sequence of processing steps as in normal subjects, evoked different patterns of brain activity. By revealing a brain circuit involving the most rostral part of the dorsal pathway, this study provides further support for neuro-imaging studies and brain lesion investigations that have suggested the existence of different brain circuits associated with different profiles of interaction between the dorsal and the ventral streams.


Molecular characterization of invasive Neisseria meningitidis strains isolated in Chile during 2010-2011.
With the upcoming licensure of Outer Membrane Protein-based vaccines against meningococcal disease, data on disease incidence and molecular characteristic of circulating N. meningitidis strains in Latin American countries is needed. Chile is, to date, one of the few countries in the region that has performed this type of work in a comprehensive collection of disease-associated strains from two consecutive years, 2010-2011. A total of 119 N. meningitidis strains isolated from patients with invasive disease in Chile in 2010-2011 were characterized by the National Reference Laboratory. Serogroup determination, MLST and porA typing were performed. Serogroup B was predominant in both study years, but W135 experienced a noticeable increase in 2011 compared to 2010. ST-11 complex, ST-41/44 complex ST-32 complex were the most prevalent among the isolates, and were strongly associated with serogroups W135 (ST-11 Complex) and B (ST-41/44 and ST-32 complexes). Likewise, the major porA types detected were strongly associated with these three clonal complexes: P1.5,2 was found exclusively among W135:ST-11 isolates, whereas P1.7, 2-3 was only detected in C:ST-11. ST-41/44 isolates mainly had P1.10-8, and ST-32 complex were associated with a P1.18-8 porA. Our data show disease-associated N. meningitidis circulating in Chile are similar to those found in other parts of the world. The increase on W135:ST-11 isolates observed in 2011 foretold the unusual epidemiological situation experienced in the country in 2012, and MLST data show that this strain is indistinguishable from the one linked to the global Hajj 2000-related outbreak that occurred in 2001. Finally, this work demonstrates the importance of maintaining a strong national surveillance program integrating clinical, epidemiological and laboratory data and incorporating gold standard diagnostic and characterization techniques that allow the data to be compared all over the world.


Hormonal and nutritional drivers of intrauterine growth.
Size at birth is critical in determining life expectancy with both small and large neonates at risk of shortened life spans. This review examines the hormonal and nutritional drivers of intrauterine growth with emphasis on the role of foetal hormones as nutritional signals in utero. Nutrients drive intrauterine growth by providing substrate for tissue accretion, whereas hormones regulate nutrient distribution between foetal oxidative metabolism and mass accumulation. The main hormonal drivers of intrauterine growth are insulin, insulin-like growth factors and thyroid hormones. Together with leptin and cortisol, these hormones control cellular nutrient uptake and the balance between accretion and differentiation in regulating tissue growth. They also act indirectly via the placenta to alter the materno-foetal supply of nutrients and oxygen. By responding to nutrient and oxygen availability, foetal hormones optimize the survival and growth of the foetus with respect to its genetic potential, particularly during adverse conditions. However, changes in the intrauterine growth of individual tissues may alter their function permanently. In both normal and compromised pregnancies, intrauterine growth is determined by multiple hormonal and nutritional drivers which interact to produce a specific pattern of intrauterine development with potential lifelong consequences for health.


Gastric cytoprotection and honey intake in albino rats.
Beneficial effect of honey has been widely reported particularly on wound healings, gastrointestinal disorders and as antibacterial agent. However, there is paucity of report on its cytoprotective effect on the gastric mucosa despite its common usage worldwide including Nigeria. This study was therefore carried out to evaluate the effect of this widely consumed substance on gastric mucosa using animal model and also to explore possible mechanism of its action on the gastric mucosa .Twenty male adult albino rats of Wistar strain, weighing between 210-220g were used in the experiment. They were randomly assigned into two groups, the control group and the honey-fed (test) group, each containing ten rats. The Control group was fed on normal rat feed and water while the test group was fed on normal rat feed with honey added to its drinking water (1ml of honey for every initial 10ml of water for each rat daily) for twenty two weeks. After twenty two weeks the rats were weighed after being starved overnight. They were anaesthetized with urethane (0.6ml/100g body weight). Gastric ulceration was induced using 1.5ml acid-alcohol prepared from equivolume of 0.1NHCl and 70% methanol introduced into the stomach via a portex cannula tied and left in place following an incision made on the antral-pyloric junction of the stomach. The acid-alcohol was allowed to stay for 1hr. After 1hr, laparatomy was performed and the stomach isolated, cut open along the greater curvature, rinsed with normal saline and fastened in place with pins on a dissecting board for ulcer examination and scores. The result obtained showed mean ulcer scores of 14.5+/-0.70 for the control group and 1.6+/-0.11 for the test group. The result showed that honey significantly reduced ulcer scores as well as caused scanty haemorrhage in the test group compared with increased ulcer scores and multiple haemorrhage in the control group. It is therefore concluded that honey intake offered cytoprotection on the gastric mucosa of albino rats.


Reliability and Validity of the Turkish Version of the ABILHAND-Kids Survey in Children with Cerebral Palsy.
The aim of the present study is to develop a Turkish version of the ABILHAND-Kids Survey, which evaluates upper extremity function in children with cerebral palsy (CP), and to carry out a validity and reliability study of the survey for Turkish CP patients. Between November 2016 and March 2017, a total of 109 pediatric CP patients (62 males, 47 females; mean age 9.3±2.9 years; range, 6 to 15 years) followed in our outpatient clinic were included. The demographic characteristics and type of CP of the patients were recorded. A functional evaluation was made using the ABILHAND-Kids and Manual Ability Classification System (MACS) surveys. The reliability of the surveys was tested based on internal consistency (Cronbach's α) and test-retest (intraclass correlation coefficient [ICC]) methods. The validity of the approach was evaluated using converted scores from an ABILHAND-Kids Rasch analysis and a correlation of the MACS levels. The ICC value for the test/retest reliability was 0.98 and internal consistency was 0.94. A strong negative correlation was found between the Turkish version of the ABILHAND-Kids and MACS surveys (r=-0.849; p<0.001). A Rasch analysis indicated good item fit, unidimensionality, and model fit. The Turkish version of the ABILHAND-Kids survey is a reliable and valid scale for the assessment of manual ability in Turkish children with CP.


Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).
Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). Particulate matter air pollution contributes to lung cancer incidence in Europe. European Community's Seventh Framework Programme.


Gastroesophageal reflux in pregnancy: a systematic review on the benefit of raft forming agents.
The prevalence of gastroesophageal reflux disease (GERD) symptoms in pregnancy is very high, up to 80%, with a maximum peak during the third trimester. Together with lifestyle modifications, antacids and antisecretive agents, such as proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2RAs), are commonly prescribed in non-pregnant, adult population. In certain Countries these drugs are not allowed in or are allowed only during the late stages of pregnancy. Alginate-based formulations have been used for the symptomatic treatment of heartburn for decades, as they usually contain sodium or potassium bicarbonate. In the presence of gastric acid, a foamy raft is created above the gastric contents. The alginate raft moves into the esophagus in place or ahead of acidic gastric contents during reflux episodes physically preventing reflux of gastric contents into the esophagus. Alginate-based formulations are allowed with no restrictions also in pregnancy: their safety profile make them a very valid option taking into account the risk/benefit ratio for both parturient and unborn baby. This systematic review paper aims to explore the use of medications for treating GERD in pregnancy, including alginate raft-forming-agents, highlighting the benefits for both the mother and the fetus. Electronic search in databases was conducted on databases such as Medline, PubMed, Ovid retrieving data concerning the reflux treatments in pregnancy, with a special focus on alginate raft forming antireflux agents. From the literature on alginate use in pregnancy, no particular risks have been shown to date for both parturient and unborn baby when alginate had been administered during all the pregnancy trimesters. The physical mode of action ensures the maximum esophageal protection by the neutral foam floating in the stomach, maintaining physiological pH values at stomach level, without interfering with the digestive processes. The symptoms' healing has been markedly improved during the weeks of observation; the symptoms monitored in all studies were: heartburn, regurgitation, pain (chest). After four weeks of treatment little or no change was observed in maternal mean sodium or potassium concentrations. No sodium restriction diet has been adopted. No edema of lower limbs or weight gain occurred. No adverse reactions related to the testing drug had been reported and all the authors concluded that alginate was safe for the unborn baby. Nowadays pharmacological treatments for GER are available as OTC drugs, including antacids, antisecretive agents, PPIs and H2RAs, and as medical devices, such as alginate raft forming antireflux agents (i.e.: Reflubloc™, Novartis NCH Italy). On this last product, considering the specific indication in pregnancy and the safety profile, without restrictions of administration during the whole pregnancy period, furthermore the physical mode of action, it gives the gynecologists a very important option in treating GER in pregnancy, taking care of both pregnant and fetus. Raft-forming-antireflux agents are safe and effective in GER treatment during pregnancy.


Role of no reflow and microvascular obstruction in the prognostic stratification of STEMI patients.
Effective reperfusion of ischemic myocardium is the final aim of both pharmacological and mechanical reperfusive strategies in patients with ST-segment elevation myocardial infarction. More effective reperfusion is related to better prognosis. In contrast, ineffective reperfusion (no reflow) has been showed to be related to an increased rate of adverse events in the flow-up. Several techniques can be used to assess the effectiveness of reperfusion, and the evolved over the last decades according to the treatment methods but also to technological advancements. ST-segment resolution represented the only way to assess reperfusion in the era of pharmacological treatment. Later, angiographic assessment became the gold standard to assess reperfusion after primary percutaneous coronary intervention. In the last years, cardiac magnetic resonance showed improved accuracy and prognostic stratification ability compared with angiography. However, in clinical practice, coronary angiographic still remains the more widely used assessment technique for no reflow.


[Prevalence of signs/symptoms suggestive of latex sensitization in health care workers.].
In the literature, the references on adverse reactions to latex products have been significantly increasing for the last few years. However, it lacks Brazilian data regarding the prevalence of latex-related sensitization in health care workers. The objective of this study was to evaluate the prevalence of signs and symptoms suggestive of latex-related sensitization in health care workers. Upon approval by the Ethics Committee it were selected a population of subjects from the Institution's departmental workforce: the Surgical Center Cleaning, Accounting and Nursing personnel and the physicians working at the Surgery, Gynecology, Obstetrics, Anesthesiology, Intensive Care Unit and Medical Clinics. After the informed consent has been obtained, the subjects were submitted to a questionnaire on: age, gender, professional category; type and length of time in contact with latex products; type of gloves; signs/symptoms suggestive of latex-related sensitization (LS) in and out of the hospital environment; signs/symptoms suggestive of atopy and food allergy. A total of 326 questionnaires were evaluated (193 women and 133 men, aged between 30 and 73 years old). Out of this total, 75% of interviewees had up to 10-year length of service in their professions. The prevalence of signs/symptoms suggestive of sensitization to latex in the hospital environment, between the group of employees working in the Accounting Sector (therefore not exposed to latex in the workplace) and the remaining employees (exposed to latex products in their working environment) was significantly different (p<0.001). Also, the percentage of signs/symptoms suggestive of LS in the hospital environment was higher in subjects showing higher average time of use of gloves per day. The present study demonstrated higher prevalence of signs/symptoms suggestive of LS among those workers exposed to latex products in the hospital environment and with higher contact time with any type of gloves. Therefore, it is clear the need to proceed with this research, for laboratorial confirmation of the latex-related sensitization, as well as that a proposal be submitted to the Institution towards the adoption of preventive measures regarding latex-related sensitization issue. Also, a consensus must exist to the fact that the health care workers comprise a population in risk for allergy to latex products.


Cancer stem cells: are they responsible for treatment failure?
Overcoming resistance to standard anticancer treatments represents a significant challenge. The interest regarding cancer stem cells, a cellular population that has the ability to self-renew and to propagate the tumor, was prompted by experimental evidence delineating the molecular mechanisms that are selectively activated in this cellular subset in order to survive chemotherapy. This has also stimulated combination strategies aimed at rendering cancer stem cells vulnerable to anticancer agents. Moreover, cancer stem cells offer a unique opportunity for modeling human cancers in mice, thus emerging as a powerful tool for testing novel drugs and combinations in a simulation of human disease. These novel animal models may lay the foundation for a new generation of clinical trials aimed at anticipating the benefit to patients of anticancer therapies.