Surveillance for certain health behaviors among states and selected local areas--Behavioral Risk Factor Surveillance System, United States, 2011.
Chronic conditions (e.g., heart diseases, cerebrovascular diseases, malignant neoplasms, and diabetes), infectious diseases (e.g., influenza and pneumonia), and unintentional injuries are the leading causes of morbidity and mortality in the United States. Adopting positive health behaviors (e.g., staying physically active, quitting tobacco use, always wearing seatbelts in automobiles) and accessing preventive health-care services (e.g., getting routine physical checkups, receiving recommended vaccinations on appropriate schedules, checking blood pressure and cholesterol and maintaining them at healthy levels) can reduce morbidity and mortality from chronic and infectious diseases. Monitoring the health-risk behaviors of a community's residents as well as their participation in and access to health-care services provides information critical to the development and maintenance of intervention programs as well as the implementation of strategies and health policies that address public health problems at the levels of state and territory, metropolitan and micropolitan statistical area (MMSA), and county. January-December 2011. The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing, state-based, random-digit-dialed telephone survey of noninstitutionalized adults aged ≥18 years residing in the United States. BRFSS collects data on health-risk behaviors, chronic diseases and conditions, access to health care, and use of preventive health services and practices related to the leading causes of death and disabilities in the United States. In 2011, BRFSS adopted a new weighting methodology (iterative proportional fitting, or raking) and for the first time included data from respondents who solely use cellular telephones (i.e., do not use landlines). This report presents results for the year 2011 for all 50 states, the District of Columbia, and participating U.S. territories including the Commonwealth of Puerto Rico and Guam, 198 MMSAs, and 224 counties. In 2011, the estimated prevalence of health-risk behaviors, chronic conditions, access to health care, and use of preventive health services substantially varied by state and territory, MMSA, and county. The following portion of this abstract summarizes selected results by some BRFSS measures. Each set of proportions refers to the range of estimated prevalence of the behaviors, diseases, or use of preventive health-care services as reported by survey respondents. Adults with good or better health: 65.5%-88.0% for states and territories, 72.0%-92.4% for MMSAs, and 74.3%-94.2% for counties. Adults aged <65 years with health-care coverage: 65.4%-92.3% for states and territories, 66.8%-94.7% for MMSAs, and 61.3%-95.6% for counties. Influenza vaccination received during the preceding 12 months among adults aged ≥65 years: 28.6%-70.2% for states and territories, 42.0% -80.0% for MMSAs, and 41.1%-78.2% for counties. Adults meeting the federal physical activity recommendations for both aerobic physical activity and muscle-strengthening activity: 8.5%-27.3% for states and territories, 7.3%-32.0% for MMSAs, and 11.0%-32.0% for counties. Current cigarette smokers: 11.8%-30.5% for states and territories, 8.4%-30.6% for MMSAs, and 8.1%-35.2% for counties. Binge drinking during the last month: 10.0%-25.0% for states and territories, 7.0%-32.5% for MMSAs, and 7.0%-32.5% for counties. Adults always wearing seatbelts while driving or riding in a car: 63.9%-94.1% for states and territories, 51.8%-96.9% for MMSAs, and 51.8%-97.0% for counties. Adults aged ≥18 who were obese: 20.7%-34.9% for states and territories, 15.1%-37.2% for MMSAs, and 15.1%-41.0% for counties. Adults with diagnosed diabetes: 6.7%-13.5% for states and territories, 3.9%-15.9% for MMSAs, and 3.5%-18.3% for counties. Adults with current asthma: 4.3%-12.1% for states and territories, 2.9%-14.1% for MMSAs, and 2.9%-15.6% for counties. Adults aged ≥45 years who have had coronary heart disease: 7.1%-16.2% for states and territories, 5.0%-19.4% for MMSAs, and 3.9%-18.5% for counties. Adults using special equipment because of any health problem: 5.1%-11.3% for states and territories, 3.9%-13.2% for MMSAs, and 2.4%-14.7% for counties. Because of the recent change in the BRFSS methodology, the results should not be compared with those from previous years. The findings in this report indicate that substantial variations exist in the reported health-risk behaviors, chronic diseases, disabilities, access to health-care services, and the use of preventive health services among U.S. adults at state and territory, MMSA, and county levels. The findings underscore the continued need for surveillance of health-risk behaviors, chronic conditions, and use of preventive health-care services as well as surveillance-informed programs designed to help improve health-related risk behaviors, levels of chronic disease and disability, and the access to and use of preventive services and health-care resources. State and local health departments and agencies can continue to use BRFSS data to identify populations at high risk for certain unhealthy behaviors and chronic conditions. Additionally, they can use the data to inform the design, implementation, direction, monitoring, and evaluation of public health programs, policies, and use of preventive services that can lead to a reduction in morbidity and mortality among U.S. residents.


Problematic internet use: an exploration of associations between cognition and COMT rs4818, rs4680 haplotypes.
Problematic internet users suffer from impairment in a variety of cognitive domains. Research suggests that COMT haplotypes exert differential effects on cognition. We sought to investigate differences in the genetic profiles of problematic internet users and whether those could shed light on potential cognitive differences. We recruited 206 non-treatment seeking participants with heightened impulsive traits and obtained cross-sectional demographic, clinical, and cognitive data as well as the genetic haplotypes of COMT rs4680 and rs4818. We identified 24 participants who presented with problematic internet use (PIU) and compared PIU and non-PIU participants using one-way analysis of variance (ANOVA) and chi square as appropriate. PIU was associated with worse performance on decision making, rapid visual processing, and spatial working memory tasks. Genetic variants were associated with altered cognitive performance, but rates of PIU did not statistically differ for particular haplotypes of COMT. This study indicates that PIU is characterized by deficits in decision making and working memory domains; it also provides evidence for elevated impulsive responses and impaired target detection on a sustained attention task, which is a novel area worth exploring further in future work. The effects observed in the genetic influences on cognition of PIU subjects imply that the genetic heritable components of PIU may not lie within the genetic loci influencing COMT function and cognitive performance; or that the genetic component in PIU involves many genetic polymorphisms each conferring only a small effect.


Determinants, and implications, of the shape and size of thylakoids and cristae.
Thylakoids are flattened sacs isolated from other membranes; cristae are attached to the rest of the inner mitochondrial membrane by the crista junction, but the crista lumen is separated from the intermembrane space. The shape of thylakoids and cristae involves membranes with small (5-30 nm) radii of curvature. While the mechanism of curvature is not entirely clear, it seems to be largely a function of Curt proteins in thylakoids and Mitochondrial Organising Site and Crista Organising Centre proteins and oligomeric FOF1 ATP synthase in cristae. A subordinate, or minimal, role is attributable to lipids with areas of their head group area greater (convex leaflet) or smaller (concave leaflet) than the area of the lipid tail; examples of the latter group are monogalactosyldiglyceride in thylakoids and cardiolipin in cristae. The volume per unit area on the lumen side of the membrane is less than that of the chloroplast stroma or cyanobacterial cytosol for thylakoids, and mitochondrial matrix for cristae. A low volume per unit area of thylakoids and cristae means a small lumen width that is the average of wider spaces between lipid parts of the membranes and the narrower gaps dominated by extra-membrane components of transmembrane proteins. These structural constraints have important implications for the movement of the electron carriers plastocyanin and cytochrome c6 (thylakoids) and cytochrome c (cristae) and hence the separation of the membrane-associated electron donors to, and electron acceptors from, these water-soluble electron carriers. The donor/acceptor pairs, are the cytochrome fb6Fenh complex and P700+ in thylakoids, and Complex III and Complex IV of cristae. The other energy flux parallel to the membranes is that of the proton motive force generated by redox-powered H+ pumps into the lumen to the proton motive force use in ATP synthesis by H+ flux from the lumen through the ATP synthase. For both the electron transport and proton motive force movement, concentration differences of reduced and oxidised electron carriers and protonated and deprotonated pH buffers are involved. The need for diffusion along a congested route of these energy transfer agents may limit the separation of sources and sinks parallel to the membranes of thylakoids and cristae.


Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons.
We previously identified a 90-kD (GP90), collagen-binding, membrane glycoprotein, termed extracellular matrix receptor III (ECMR III), that is homologous to the lymphocyte homing receptor and CD44 antigen (Gallatin, W. M., E. A. Wayner, P. A. Hoffman, T. St. John, E. C. Butcher, and W. G. Carter. 1989. Proc. Natl. Acad. Sci. USA. 86:4654-4658). CD44 is abundantly expressed in many epithelial tissues, and is localized predominantly to filopodia in cultured keratinocytes. Here we establish CD44 as a polymorphic family of related membrane proteoglycans and glycoproteins possessing extensive diversity in both glycosylation and core protein sequence. Human neonatal foreskin keratinocytes (HFKs) and QG56 lung squamous carcinoma cells express an alternatively spliced form of the CD44 core protein (termed CD44E) that contains an additional 132 amino acids in the carbohydrate attachment region of the extracellular domain. HFKs, HT1080 fibrosarcoma and QG56 cells, as well as many other human cells, contain varying ratios of GP90 and structurally related, higher molecular mass forms of CD44 that express the following characteristics: (a) each form reacted with anti-CD44 (mAbs) P1G12, P3H9, and P3H5. Each of these mAbs recognized a distinct, nonoverlapping epitope present on each CD44 form. (b) Differences in mass were due primarily to variation in carbohydrate moieties, including sulfated aspargine-linked glycopeptides (GP), chondroitin sulfate (CS), and heparan sulfate (HS) glycosaminoglycans, as well as O-linked mucin and polylactosamine structure(s). The major polymorphic forms were designated HT1080 GP90 and CS180, QG56 GP230, and HFK HS/CS250, based on dominant carbohydrate moieties and relative mass. (c) The polymorphic forms use CD44 and CD44E core proteins, each containing a unique set of potential attachment sites for O- and N-glycosides and glycosaminoglycans. (d) Immunofluorescence microscopy, differential extraction with Triton-X-114 detergent, and incorporation into liposomes indicated that all the forms were membrane bound glycoconjugates. These results define CD44 as a structurally diverse, but immunologically related, set of intrinsic membrane macromolecules, and suggests that these structurally varied forms might be expected to manifest multiple functions.


The use of electrical source imaging in targeting lesional mesial temporal epilepsy for radiosurgical treatment.
Gamma knife radiosurgery (GK-RS) is a technique applied in selected cases of mesial-temporal epilepsy, although still limited to centres with adequate instrumentation and expertise. Here, we report a case of radio surgery targeted with the aid of electrical source imaging that localizes the cortical area generating the scalp epileptic discharges. The patient, a 39-year-old male, presented with a right mesio-temporal lesion; electrical source imaging localization partially overlapped with the lesional area but showed an important activation of the omolateral frontal area, concordant with the epileptic network. The patient underwent GK-RS, with good neurosurgical and clinical results. A radiosurgical ellipsoidal treatment volume area of 2 × 2 × 2 cm³, located over the right temporo-mesial region within a centre showing abnormal signal intensity, was considered. Seven months after treatment, the patient developed brain oedema that gradually resolved after one year. After three years of follow-up, the patient was seizure-free (Engel class I). Our very preliminary experience suggests that electrical source imaging appears to be a useful supporting tool for the definition of the radiosurgical treatment volume in selected patients with temporo-mesial lesional epilepsy.


Conversion of [15N]ammonia into urea and amino acids in humans and the effect of nutritional status.
Hepatic NH3 detoxification by ureagenesis requires an input of aspartate-N, originating either from amino acid-N or NH3-N. The relative importance of these two routes may depend on the nutritional state. To test this, four volunteers were given a liquid diet for 2 d and then on day 3 were either fed every 20 min or fasted. Doses of 15NH4Cl were taken orally every 20 min for 6 h (total 1.5 g) and blood was sampled hourly. Urea-N elimination under fasted conditions was only 0.75 of that for the fed state. Considering the increase in body urea pool during feeding, ureagenesis during fasting was probably closer to 0.6 of that during feeding. Since the [14N15N]urea enrichment was not different between the fed and fasted states, the proportion of the 15NH3 dose converted to urea during fasting was also 0.6 of that during the fed condition. No change in [14N15N]urea and [amide-15N]glutamine enrichment suggested that NH3 enrichment was also not affected by nutritional state. Enrichment of [15N15N]urea was approximately 0.05 that of [14N15N]urea which indicates that 15NH3 can also enter the aspartate route, the importance of which is yet unknown. Both [15N15N]urea and [amino-15N]glutamine enrichment in the fasted state were approximately 1.7 times that in the fed state, indicating increased labelling of precursors and/or increased NH3 flux through the aspartate route. Glutamate, valine, leucine and isoleucine showed comparable increases in enrichment during fasting. Arginine enrichment was unaltered by nutritional state, but was lower than [14N15N]urea, indicating incomplete equilibration with the arginine pool in periportal hepatocytes. The present study indicates that hepatic NH3 detoxification may use the aspartate route, gaining importance in the fasted state. The majority of urea was supplied with only one N atom from NH3, thus provision of the other may have consequences for alternative substrates, in particular amino acids.


Toxicity Evaluation of Quantum Dots (ZnS and CdS) Singly and Combined in Zebrafish (Danio rerio).
The exponential growth of nanotechnology has led to the production of large quantities of nanomaterials for numerous industrial, technological, agricultural, environmental, food and many other applications. However, this huge production has raised growing concerns about the adverse effects that the release of these nanomaterials may have on the environment and on living organisms. Regarding the effects of QDs on aquatic organisms, existing data is scarce and often contradictory. Thus, more information is needed to understand the mechanisms associated with the potential toxicity of these nanomaterials in the aquatic environment. The toxicity of QDs (ZnS and CdS) was evaluated in the freshwater fish Danio rerio. The fishes were exposed for seven days to different concentrations of QDs (10, 100 and 1000 µg/L) individually and combined. Oxidative stress enzymes (catalase, superoxide dismutase and glutathione S-transferase), lipid peroxidation, HSP70 and total ubiquitin were assessed. In general, results suggest low to moderate toxicity as shown by the increase in catalase activity and lipid peroxidation levels. The QDs (ZnS and CdS) appear to cause more adverse effects singly than when tested combined. However, LPO results suggest that exposure to CdS singly caused more oxidative stress in zebrafish than ZnS or when the two QDs were tested combined. Levels of Zn and Cd measured in fish tissues indicate that both elements were bioaccumulated by fish and the concentrations increased in tissues according to the concentrations tested. The increase in HSP70 measured in fish exposed to 100 µg ZnS-QDs/L may be associated with high levels of Zn determined in fish tissues. No significant changes were detected for total ubiquitin. More experiments should be performed to fully understand the effects of QDs exposure to aquatic biota.


Transposition of the oxacillin-hydrolyzing penicillinase gene.
We have found that the oxacillin-hydrolyzing penicillinase gene (oxa) encoded by plasmid RGN238 transposes to various plasmids in a recA background. We call this transposable element Tn2603. Tn2603 encodes the genes for streptomycin, sulfonamide, and mercury resistance in addition to the oxa gene. Tn2603 has a molecular size of 19.6 kilobase pairs and appears to be flanked by small inverted repeat sequences of about 200 base pairs long.


[Prevalence of drug use during pregnancy: a pharmacoepidemiological approach].
Few Brazilian papers on the use of medication in pregnancy have been found in the indexed medical literature. This paper describes the use of medication during pregnancy among women who gave birth in a teaching maternity hospital in the city of Campinas, Brazil. A retrospective study on the pattern of drug use during pregnancy was conducted among 1,000 mothers who were interviewed using a structured questionnaire after delivery, while they were still in hospital. The following parameters were registered: sociodemographic characteristics, obstetric and contraceptive history, data on prenatal care and medications used during pregnancy. Statistical analysis was performed using ANOVA and chi-square test at p = 0.05. Among the interviewed patients, 94.6% had taken at least one medication during pregnancy, and 46.1% had used medication in the first trimester. Of 3,778 medications reported, 88.8% had been prescribed by a doctor. The median of medications taken was 3 (ranging from 0 to 18). The six most used classes of medications were: analgesics, spasmolytics, gynecological antiinfectious agents, antianemics, antacids and systemic antibiotics. The five most used medications were: butyl scopolamine, ferrous sulfate, dipirone, nistatin and multivitamin tablets. Only 27.7% of the patients had been alerted to the risk of taking medication during pregnancy. Knowing the profile of medications used during pregnancy may help devising programs to provide information to the patients and continuing education to health care professionals.


Protocol for a cluster randomised controlled trial of an intervention to improve the mental health support and training available to secondary school teachers - the WISE (Wellbeing in Secondary Education) study.
Teachers are reported to be at increased risk of common mental health disorders compared to other occupations. Failure to support teachers adequately may lead to serious long-term mental disorders, poor performance at work (presenteeism), sickness absence and health-related exit from the profession. It also jeopardises student mental health, as distressed staff struggle to develop supportive relationships with students, and such relationships are protective against student depression. A number of school-based trials have attempted to improve student mental health, but these have mostly focused on classroom based approaches and have failed to establish effectiveness. Only a few studies have introduced training for teachers in supporting students, and none to date have included a focus on improving teacher mental health. This paper sets out the protocol (version 4.4 20/07/16) for a study aiming to address this gap. Cluster randomised controlled trial with secondary schools as the unit of randomisation. Intervention schools will receive: i) Mental Health First Aid (MHFA) training for a group of staff nominated by their colleagues, after which they will set up a confidential peer support service for colleagues ii) training in MHFA for schools and colleges for a further group of teachers, which will equip them to more effectively support student mental health iii) a short mental health awareness raising session and promotion of the peer support service for all teachers. Comparison schools will continue with usual practice. The primary outcome is teacher wellbeing measured using the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS). Secondary outcomes are teacher depression, absence and presenteeism, and student wellbeing, mental health difficulties, attendance and attainment. Measures will be taken at baseline, one year follow up (teachers only) and two year follow up. Economic and process evaluations will be embedded within the study. This study will establish the effectiveness and cost-effectiveness of an intervention that supports secondary school teachers' wellbeing and mental health, and improves their skills in supporting students. It will also provide information regarding intervention implementation and sustainability. International Standard Randomised Controlled Trial Number: ISRCTN95909211 registered 24/03/16.


Semi-quantitative assessment of right ventricular function in comparison to a 3D volumetric approach: a cardiovascular magnetic resonance study.
Right ventricular (RV) volume measurements with cardiovascular magnetic resonance (CMR) is considered the gold standard, but acquisition and analysis remain time-consuming. The aim of our study was therefore to investigate the accuracy and performance of a semi-quantitative assessment of RV function in CMR, compared to the standard quantitative approach. Seventy-five subjects with pulmonary hypertension (15), anterior myocardial infarction (15), inferior myocardial infarction (15), Brugada syndrome (15) and normal subjects (15) underwent cine CMR. RV end-systolic and end-diastolic volumes were determined to calculate RV ejection fraction (EF). Four-chamber cine images were used to measure tricuspid annular plane systolic excursion (TAPSE). RV fractional shortening (RVFS) was calculated by dividing TAPSE by the RV end-diastolic length. RV EF correlated significantly with TAPSE (r = 0.62, p < 0.01) and RVFS (r = 0.67, p < 0.01). Sensitivity to predict RV dysfunction was comparable between TAPSE and RVFS, with higher specificity for RVFS, but comparable areas under the ROC curve. Intra- and inter-observer variability of RV EF was better than TAPSE (3%/4% versus 7%/15%, respectively). For routine screening in clinical practice, TAPSE and RVFS seem reliable and easy methods to identify patients with RV dysfunction. The 3D volumetric approach is preferred to assess RV function for research purposes or to evaluate treatment response.


Liposome-entrapped plasmid DNA: characterisation studies.
Plasmid DNA pRc/CMV HBS (5.6 kb) (100 microg) encoding the S (small) region of hepatitis B surface antigen was incorporated by the dehydration-rehydration method into liposomes composed of 16 micromol egg phosphatidylcholine (PC), 8 micromol dioleoylphosphatidylcholine (DOPE) and 1, 2-diodeoyl-3-(trimethylammonium)propane (DOTAP) (cationic liposomes) or phosphatidylglycerol (anionic liposomes) in a variety of molar ratios. The method, entailing mixing of small unilamellar vesicles (SUV) with the DNA, followed by dehydration and rehydration, yielded incorporation values of 95-97 and 48-54% of the DNA used, respectively. Mixing of preformed cationic liposomes with 100 microg plasmid DNA also led to high complexation values of 73-97%. As expected, the association of DNA with preformed anionic liposomes was low (9%). Further work with cationic PC/DOPE/DOTAP liposomes attempted to establish differences in the nature of DNA association with the vesicles after complexation and the constructs generated by the process of dehydration/rehydration. Several lines of evidence obtained from studies on vesicle size and zeta-potential, fluorescent microscopy and gel electrophoresis in the presence of the anion sodium dodecyl sulphate (SDS) indicate that, under the conditions employed, interaction of DNA with preformed cationic SUV as above, or with cationic SUV made of DOPE and DOTAP (1:1 molar ratio; ESCORT Transfection Reagent), leads to the formation of large complexes with externally bound DNA. For instance, such DNA is accessible to and can be dissociated by competing anionic SDS molecules. However, dehydration of the DNA-SUV complexes and subsequent rehydration, generates submicron size liposomes incorporating most of the DNA in a fashion that prevents DNA displacement through anion competition. It is suggested that, in this case, DNA is entrapped within the aqueous compartments, in between bilayers, presumably bound to the cationic charges.


Insulin resistance, glycemic control and adiposity: key determinants of healthy lifespan.
Identification of genes and pathways that alter lifespan has allowed for new insights into factors that control the aging process as well as disease. While strong molecular links exist between aging and metabolism, we hypothesize that targeting the mechanisms involved in aging will also give rise to therapeutics that treat other devastating age-related diseases, such as neurodegeneration, cancer, inflammation and cardiovascular disease. Insulin sensitivity, glycemic control and adiposity are not only hallmarks of the major metabolic diseases, type 2 diabetes and obesity, but they also represent significant risk factors for the development of Alzheimer's Disease and cognitive impairment. Insulin/IGF-1 signaling is an important pathway regulating aging and disease in a variety of species, including mammals. Here we describe an important role for the gut-derived peptide ghrelin in upstream signaling through the insulin/IGF-1 pathway and exemplify modulation of ghrelin signaling as an approach to mechanistic treatment of multiple age-related diseases by virtue of its ability to regulate key metabolic functions.


Radiopacity of different shades of resin-based restorative materials compared to human and bovine teeth.
This study evaluated the radiopacity of different shades of resin-based restorative materials and compared the results to human and bovine dental hard tissues. Disk specimens 6 mm in diameter and 1 mm thick (N = 220, n = 10) were prepared from the following restorative materials: · eight shades of nanofilled composite (Aelite Aesthetic Enamel), · seven shades of nanohybrid composite (Grandio Universal), · six shades of photopolymerized polyacid modified compomer (Glasiosite), and · one shade of hybrid composite (X-tra fil U). Human canine dentin (n = 10), bovine enamel (n = 10), and an aluminum (Al) step wedge were used as references. The optical density values of each material were measured from radiographic images using a transmission densitometer. Al step wedge thickness and optical density values were plotted, and equivalent Al thickness (eq Al) values were determined for radiopacity measurements of each material. The data were analyzed using a non-parametric one-way ANOVA (Kruskal-Wallis), and multiple comparisons were made with a Student-Newman-Keuls post hoc test (a = 0.05). Different shades of resin-based restorative materials tested did not reveal statistically significant differences within each material group (p > 0.05). Radiopacity values of the resin-based restorative materials investigated varied depending on their types; however, within different shades of one material type, radiopacity values were comparable. Every shade of nanocomposite material other than Aelite Aesthetic Enamel Incisal LT Gray showed comparable radiopacity to human dentin. Other materials tested demonstrated higher radiopacity compared to human dentin and bovine enamel.


Task dependence of visual and category representations in prefrontal and inferior temporal cortices.
Visual categorization is an essential perceptual and cognitive process for assigning behavioral significance to incoming stimuli. Categorization depends on sensory processing of stimulus features as well as flexible cognitive processing for classifying stimuli according to the current behavioral context. Neurophysiological studies suggest that the prefrontal cortex (PFC) and the inferior temporal cortex (ITC) are involved in visual shape categorization. However, their precise roles in the perceptual and cognitive aspects of the categorization process are unclear, as the two areas have not been directly compared during changing task contexts. To address this, we examined the impact of task relevance on categorization-related activity in PFC and ITC by recording from both areas as monkeys alternated between a shape categorization and passive viewing tasks. As monkeys viewed the same stimuli in both tasks, the impact of task relevance on encoding in each area could be compared. While both areas showed task-dependent modulations of neuronal activity, the patterns of results differed markedly. PFC, but not ITC, neurons showed a modest increase in firing rates when stimuli were task relevant. PFC also showed significantly stronger category selectivity during the task compared with passive viewing, while task-dependent modulations of category selectivity in ITC were weak and occurred with a long latency. Finally, both areas showed an enhancement of stimulus selectivity during the task compared with passive viewing. Together, this suggests that the ITC and PFC show differing degrees of task-dependent flexibility and are preferentially involved in the perceptual and cognitive aspects of the categorization process, respectively.


Green tea catechin as a chemical chaperone in cancer prevention.
Green tea catechins have recently gained significant acceptance as a cancer preventive, and one of the important features of catechins is their interactions with various target molecules. We recently found a functional and structural similarity between catechins and chaperones: Stochastic conformational analysis in silico revealed numerous conformations of (-)-epigallocatechin gallate, (-)-epicatechin gallate and (-)-epigallocatechin, showing a unique flexibility and mobility of the catechin molecules and suggesting the significance of a galloyl group in conformational variation. Since these conformations result in interaction with various types of molecules, we think that green tea catechin induces cancer preventive activity mediated through a chaperone-like property.


Decreases in Suicide Deaths and Attempts Linked to the White Mountain Apache Suicide Surveillance and Prevention System, 2001-2012.
We evaluated the impact of a comprehensive, multitiered youth suicide prevention program among the White Mountain Apache of Arizona since its implementation in 2006. Using data from the tribally mandated Celebrating Life surveillance system, we compared the rates, numbers, and characteristics of suicide deaths and attempts from 2007 to 2012 with those from 2001 to 2006. The overall Apache suicide death rates dropped from 40.0 to 24.7 per 100 000 (38.3% decrease), and the rate among those aged 15 to 24 years dropped from 128.5 to 99.0 per 100 000 (23.0% decrease). The annual number of attempts also dropped from 75 (in 2007) to 35 individuals (in 2012). National rates remained relatively stable during this time, at 10 to 13 per 100 000. Although national rates remained stable or increased slightly, the overall Apache suicide death rates dropped following the suicide prevention program. The community surveillance system served a critical role in providing a foundation for prevention programming and evaluation.


Newer concepts in the medical management of patients with congestive heart failure.
Congestive heart failure (CHF) remains a major cause of morbidity and mortality in the United States, especially among the elderly. Although an underlying disturbance in cardiac function can be identified in most patients, manifestations of the disease are greatly influenced by other factors, particularly neurohumoral and peripheral adaptive responses which occur secondary to impaired cardiac function. The renin-angiotensin system (RAS) is integrally involved in the pathophysiology of CHF. Originally considered a humoral system, the RAS is now known to exist and operate within cardiac and vascular tissues. The importance of tissue-specific renin-angiotensin systems in CHF is presently under investigation. Most patients with symptomatic CHF benefit from the administration of an ACE inhibitor. Certain asymptomatic patients, such as those with severe left ventricular (LV) dysfunction and those who are at high risk for LV remodeling after anterior wall myocardial infarction, may also benefit from ACE inhibitor therapy. Diuretics and nitrates improve symptoms and often cardiac output in many patients with CHF. Although many new inotropic agents have been tested in CHF patients, none appear clinically superior to digitalis glycosides. The efficacy of digitalis glycosides in CHF may in part result from sympathoinhibitory properties such as the activation of baroreceptor mechanisms. Despite the fact that many CHF patients die from arrhythmias, treatment of asymptomatic ventricular arrhythmias in these patients is not recommended. Patients with symptomatic or sustained ventricular arrhythmias are best treated by a physician experienced in cardiac electrophysiology. Therapy with beta-blocking drugs for CHF patients is controversial. Anticoagulants are recommended for selected patients with CHF. Finally, exercise therapy may improve functional capacity in some patients with CHF through its effects on peripheral blood vessels and skeletal muscle tissues.


Modulation of RNA polymerase core functions by basal transcription factor TFB/TFIIB.
The archaeal basal transcriptional machinery consists of TBP (TATA-binding protein), TFB (transcription factor B; a homologue of eukaryotic TFIIB) and an RNA polymerase that is structurally very similar to eukaryotic RNA polymerase II. This constellation of factors is sufficient to assemble specifically on a TATA box-containing promoter and to initiate transcription at a specific start site. We have used this system to study the functional interaction between basal transcription factors and RNA polymerase, with special emphasis on the post-recruitment function of TFB. A bioinformatics analysis of the B-finger of archaeal TFB and eukaryotic TFIIB reveals that this structure undergoes rapid and apparently systematic evolution in archaeal and eukaryotic evolutionary domains. We provide a detailed analysis of these changes and discuss their possible functional implications.


Can older people remember medication reminders presented using synthetic speech?
Reminders are often part of interventions to help older people adhere to complicated medication regimes. Computer-generated (synthetic) speech is ideal for tailoring reminders to different medication regimes. Since synthetic speech may be less intelligible than human speech, in particular under difficult listening conditions, we assessed how well older people can recall synthetic speech reminders for medications. 44 participants aged 50-80 with no cognitive impairment recalled reminders for one or four medications after a short distraction. We varied background noise, speech quality, and message design. Reminders were presented using a human voice and two synthetic voices. Data were analyzed using generalized linear mixed models. Reminder recall was satisfactory if reminders were restricted to one familiar medication, regardless of the voice used. Repeating medication names supported recall of lists of medications. We conclude that spoken reminders should build on familiar information and be integrated with other adherence support measures.


Women's HIV disclosure to the dentist: Does frequent contact matter?
Research has shown inconsistent patterns of patients' HIV serostatus disclosure to their dentists. Common barriers to disclosure have included confidentiality concerns, fear of treatment refusal, and discrimination. This study evaluated the prevalence of HIV serostatus disclosure to the dentist, whether the frequency of dental care utilization is associated with disclosure, and reasons for nondisclosure among women living with HIV. We administered a cross-sectional oral health survey to 1,526 women living with HIV in the Women's Interagency HIV Study including questions regarding HIV serostatus disclosure to dentists. Logistic regression models were used to analyze the association between dental care utilization (at least annually versus less than annually) and HIV serostatus disclosure to dentists. Overall, 83 percent of women reported that they disclosed their HIV serostatus to their dentist. The most common reasons for nondisclosure were: a) the dentist did not ask, b) believing that the dentist did not need to know, and c) not having a consistent dentist. In the multivariable logistic regression model, at least annual dental care utilization, compared to less than annual, led to a 59 percent reduction in the odds of HIV nondisclosure to the dentist. Study findings highlight that dentists who see their patients infrequently should consider methods for overcoming barriers to HIV nondisclosure and the possibility that their patient's HIV serostatus is undisclosed. Educating women living with HIV about how disclosure to dentists is a critical component of their dental assessment and treatment, and how preventive dental treatment can improve overall health outcomes, is important.


Structure-activity relationships for the formation of secondary radicals and inhibition of keratinocyte proliferation by 9-anthrones.
The biological properties of tumor-promoting and antipsoriatic 9-anthrones have been hypothesized to be mediated by free radical products such as the corresponding 9-anthron-10-yl radicals or by O2-, OH, and other persistent secondary radicals that are formed in the skin after topical treatment with 9-anthrones. To gain additional insights into the possible role of reactive oxygen or secondary radicals in mediating the biological effects of 9-anthrones, we have used EPR spectroscopy to investigate the formation of these species by a series of 9-anthrones or 9-anthrone dimers with known tumor-promoting and antipsoriatic activities. The effect of the 9-anthrones on keratinocyte proliferation in vitro was also investigated. 5,5-Dimethyl-1-pyrroline N-oxide was used as a spin trap to detect reactive oxygen-centered radicals in aqueous buffer/dimethylsulfoxide solutions. Super-radicals in aqueous buffer/dimethylsulfoxide solutions. Superoxide was trapped during the autoxidation of most of the 9-anthrones. For 9-anthrones that generated no detectable superoxide, evidence of anthronyl-peroxyl radical formation was found instead. In the presence of Fe3+ complexed to EDTA, but not diethylenetriaminepentaacetic acid, the hydroxyl radical was produced by all of the 9-anthrones. 9-Anthrone dimers produced oxygen-centered radicals only weakly or not at all. Direct EPR was used to detect 9-anthrone-derived secondary radicals in keratinocyte suspensions or in dimethysulfoxide solutions. These radicals were similar to those previously reported to occur in skin after topical treatment with the antipsoriatic drug anthralin (1,8-dihydroxy-9-anthrone). In contrast to the ubiquitous ability of the 9-anthrones to generate reactive oxygen radicals, only the hydroxy-substituted 9-anthrones or their dimers possessed significant secondary radical-forming ability. The ability of the 9-anthrones or dimers to form secondary radicals in keratinocytes was found to correlate with their in vitro inhibition of keratinocyte proliferation. The data suggest the possible importance of reactive dimeric intermediates in mediating the biological effects of the 9-anthrones.


Amantadine hydrochloride treatment in heredodegenerative ataxias: a double blind study.
A group of 27 patients with Friedreich's ataxia and another group of 30 patients with olivopontocerebellar atrophies were each randomly divided into two subgroups, one receiving placebo and the other amantadine hydrochloride (AH; 200 mg daily) for three to four months. The effect of double blind treatment was evaluated by simple visual and auditory reaction time (RT) and movement time (MT) for both right and left hands. The subgroup with olivopontocerebellar atrophies receiving AH showed significant improvement on seven out of eight variables studied by analysis of covariance. In patients with Friedreich's ataxia, improvement was definitely less. Treatment remained contraindicated for those with cardiomyopathies or drug intolerance. The rationale of AH use in heredodegenerative ataxias can be explained by its replacement effect (dopamine release) and by direct involvement of N-methyl-D-aspartate (NMDA) in glutamate mediated neurotoxicity in cerebellar granular cells; memantine, an AH analogue, is a potent blocker of NMDA receptors.


Caveolin-1 exists and may function in cardiomyocytes.
Whether ventricular cardiac myocytes of mouse contain caveolin-1 is disputed. It has been claimed to be exclusively in nearby endothelial cell profiles. Recently, matrix metalloproteinase-2 (MMP-2) was reported to be present in mouse ventricular cardiac myocytes, colocalized with caveolin-1, and caveolin-1 knockout was found to cause the loss of MMP-2 from mouse ventricular cardiac myocytes and affect their functioning. To resolve this dispute, we labeled cardiac myocytes with caveolin-1 and endothelial cells with caveolin-2. Caveolin-2 is agreed to be present exclusively in endothelial cells. The results showed that mouse ventricular myocytes were labeled with caveolin-1 antibodies independently of any caveolin-2 labeling, and endothelial cells were labeled with both caveolin-1 and caveolin-2 antibodies. This confirms that caveolin-1 is present in mouse ventricular cardiac myocytes as well as endothelial cells. Previous evidence confirms that loss of caveolin-1 affects the function of mouse ventricular cardiac myocytes and suggests that MMP-2 may be involved.


Cultural influences behind cholera transmission in the Far North Region, Republic of Cameroon: a field experience and implications for operational level planning of interventions.
In recent years, the Far North Region of Cameroon has experienced serious and recurrent cholera outbreaks. Yet, understanding of cultural influences on outbreaks and spread remain poorly understood. This qualitative study explored cultural influences on cholera exposure in this region. Interviews and group discussions were conducted in two phases. Phase I involved key informants and phase II included focus group and household discussions. Thematic techniques including word repetition, key-indigenous-terms, and key-words-in-context were used for qualitative data analysis. Key informants attributed cholera etiology to dirt and spread through water (caneri) and food (group eating or faire-un-rond) while group discussions attributed it to a reprimand from god and transmission through the air. Participants suggested that funerals, weddings, open defecation, and mountaintop burial might influence cholera exposure and facilitate its spread. Hospital avoidance and non-adherence with cholera treatment regimens were linked to favorable beliefs about traditional medicine (rural-urban mentality confrontation). Furthermore, a multiplicity of ethnic languages, mistrust of message sources, culture of dependency and sentimental animal husbandry were barriers to the reception of public health messages. Many participants had limited scientific knowledge about cholera etiology and transmission. The cultural practice of mountain burial seemed to explain the high cholera attack rate in the mountainous terrain compared to the floodplains. Cultural factors are likely to play important roles in the exposure to and spread of cholera. Understanding cultural context, individual and community perceptions of risk and disease may help public health agencies in response to outbreak prevention and control.


An interactive integrative approach to translating knowledge and building a "learning organization" in health services management.
This paper proposes a basic approach to ensuring that knowledge from research studies is translated for use in health services management with a view towards building a "learning organization". (A learning organization is one in which the environment is structured in such a way as to facilitate learning as well as the sharing of knowledge among members or employees.) This paper highlights various dimensions that determine the complexity of knowledge translation, using the problem-solving cycle as the backbone for gaining a better understanding of how different types of knowledge interact in health services management. It is essential to use an integrated and interactive approach to ensure that knowledge from research is translated in a way that allows a learning organization to be built and that knowledge is not used merely to influence a single decision in isolation from the overall services and management of an organization.


ATRX Contributes to MeCP2-Mediated Pericentric Heterochromatin Organization during Neural Differentiation.
Methyl-CpG binding protein 2 (MeCP2) is a multi-function factor involved in locus-specific transcriptional modulation and the regulation of genome architecture, e.g., pericentric heterochromatin (PCH) organization. MECP2 mutations are responsible for Rett syndrome (RTT), a devastating postnatal neurodevelopmental disorder, the pathogenetic mechanisms of which are still unknown. MeCP2, together with Alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX), accumulates at chromocenters, which are repressive PCH domains. As with MECP2, mutations in ATRX cause ATR-X syndrome which is associated with severe intellectual disability. We exploited two murine embryonic stem cell lines, in which the expression of MeCP2 or ATRX is abolished. Through immunostaining, chromatin immunoprecipitation and western blot, we show that MeCP2 and ATRX are reciprocally dependent both for their expression and targeting to chromocenters. Moreover, ATRX plays a role in the accumulation of members of the heterochromatin protein 1 (HP1) family at PCH and, as MeCP2, modulates their expression. Furthermore, ATRX and HP1 targeting to chromocenters depends on an RNA component. 3D-DNA fluorescence in situ hybridization (FISH) highlighted, for the first time, a contribution of ATRX in MeCP2-mediated chromocenter clustering during neural differentiation. Overall, we provide a detailed dissection of the functional interplay between MeCP2 and ATRX in higher-order PCH organization in neurons. Our findings suggest molecular defects common to RTT and ATR-X syndrome, including an alteration in PCH.


[Successful Biocompatible Treatment of Diaphragmatic Hernia in a Rat Model].
Treatment of major congenital diaphragmatic hernia (CDH) is a challenging task in paediatric surgery. Gore-Tex® is now commonly used to treat CDH, but it carries the risk of recurrences, infections and other complications. The aim of our study was to analyse to what extent Lyoplant® - an acellular, avascular biocompatible collagen mesh - is suitable for CDH in the rat model. A median laparotomy was performed in young Wistar Furth rats with a body weight of 155 - 205 g. A defect was created by excising a 1.0 × 1.0 cm muscular segment of the left diaphragm, which was closed by implanting a PTFE mesh (n = 5), or a Lyoplant mesh (n = 6). For control purposes (sham group, n = 2), the defect was closed directly. Each rat was examined frequently for the duration of 12 weeks. After this period, the abdomen was reopened, examined for adhesions and the left diaphragm was explanted for histological examination. All operated Wistar Furth rats exhibited a physiological body weight gain after the procedure. During the above period, no recurrence of CDH could be found, either radiologically or clinically. In all animals (PTFE vs. Lyoplant vs. sham group), strong adhesions of the left liver lobe to the implanted material were found. In contrast to the PTFE mesh, constant tissue remodeling and continuous neovascularisation were found in the Lyoplant group. Our results show that Lyoplant can successfully be used for the biocompatible therapy of CDH in the rat model. The extent to which it can also be used to treat congenital diaphragmatic defects must be demonstrated by further experimental and clinical studies.


Bias in interpretation of ambiguous scenarios in eating disorders.
Eating disorders appear to be associated with biased information processing, particularly in judgments involving the self. This study investigated three possible biases. Patients with anorexia nervosa, patients with bulimia nervosa and female controls completed questionnaires designed to assess interpretation of ambiguous scenarios with either a negative or positive outcome. When events had a negative outcome the patients responded spontaneously to open-ended questions with a weight and shape interpretation. Later, in a forced-choice format, they selected the weight and shape interpretation in preference to interpretations not connected to weight and shape. In both open-ended and forced-choice format this bias was specific to judgments involving the self. When events had a positive outcome the bias was reversed and, in the two formats, it was found only in judgments involving others. In both cases, i.e. for negative self-referent events and for positive other-referent events, patients predicted that weight and shape explanations were more likely. Both groups of patients estimated that negative outcomes involving the self would be more costly. The patients with bulimia nervosa also estimated that positive outcomes involving the self would be more beneficial. Theoretical explanations and clinical implications are discussed.


Early prenatal diagnosis of the fragile site at Xq27.3 associated with Martin-Bell syndrome.
Early prenatal diagnosis of the fragile X was attempted in 44 pregnancies, including one twin pregnancy at risk of Martin-Bell (MB) syndrome. The sex ratio was 24M:21F. The fragile site was reproducibly demonstrated in cultured chorionic villus (CV) cells in eight male and five female fetuses. Six of the male and three of the female fetuses were terminated. Simultaneous RFLP analysis provided confirmative data with flanking DNA markers in 3 of 13 analysed cases. Recombination and/or non-informativeness at available distal and/or proximal loci were found in nine cases. In one male fetus, discordance between the haplotype and cytogenetics (fragile-X-negative) suggested the presence of a normal male transmitter, a double meiotic cross-over within the region, or a false-negative cytogenetic diagnosis. However, discordance between prenatal and post-termination/postnatal cytogenetic findings was not observed in this series. The use of excess thymidine for induction of the fragile X in cultured CV cells provided in the majority of cases a safe and rapid method for cytogenetic diagnosis, with options for early induced termination in fragile-X-positive pregnancies, for simultaneous RFLP analysis, and for subsequent second-trimester analysis of fetal blood in complicated cases.


The vascular wall as a source of stem cells.
We have characterized the emerging hematopoietic system in the human embryo and fetus. Two embryonic organs, the yolk sac and aorta, support the primary emergence of hematopoietic stem cells (HSCs), but only the latter contributes lymphomyeloid stem cells for definitive, adult-type hematopoiesis. A common feature of intra- and extraembryonic hematopoiesis is that in both locations hematopoietic cells emerge in close vicinity to vascular endothelial cells. We have provided evidence that a population of angiohematopoietic mesodermal stem cells, marked by the expression of flk-1 and the novel BB9/ACE antigen, migrate from the paraaortic splanchnopleura into the ventral part of the aorta, where they give rise to hemogenic endothelial cells and, in turn, hematopoietic cells. HSCs also appear to develop from endothelium in the embryonic liver and fetal bone marrow, albeit at a much lower frequency. This would imply that the organism does not function during its whole life on a stock of hematopoietic stem cells established in the early embryo, as is usually accepted. We next examined whether the vessel wall can contribute stem cells for other cell lineages, primarily in the model of adult skeletal muscle regeneration. By immunohistochemistry and flow cytometry, we documented the existence in skeletal muscle, besides genuine endothelial and myogenic cells, of a subset of satellite cells that coexpress endothelial cell markers. This suggested the existence of a continuum of differentiation from vascular cells to endothelial cells that was confirmed in long-term culture. The regenerating capacity of these cells expressing both myogenic and endothelial markers is being investigated in skeletal and cardiac muscle, and the results are being compared with those generated by satellite cells. Altogether, these results point to a generalized progenitor potential of a subset of endothelial, or endothelium-like, cells in blood vessel walls, in pre- and postnatal life.


Na+/H+ antiport and buffering capacity in human polymorphonuclear and mononuclear leucocytes.
1. Na+/H+ antiport activity was measured in peripheral blood polymorphonuclear and mononuclear cells of 12 healthy subjects by using an intracellular pH clamp technique to determine the external Na(+)-dependent H+ efflux rate in cells loaded with a pH-sensitive fluorescent dye, bis(carboxyethyl)carboxyfluorescein. The change in external Na+ concentrations for all pH measurements was similar in both cell types. 2. A significant difference between the two types of cells was found, the polymorphonuclear leucocytes having a higher Na+/H+ antiport activity than the lymphocytes. Cellular intrinsic buffering capacity measured in the absence of HCO3- was also higher in the polymorphonuclear cells than in the lymphocytes. 3. These differences may be associated with a difference in the role of the Na+/H+ exchanger in these two types of cells, although in vivo the presence of HCO3-/Cl- exchangers may also contribute to intracellular pH homoeostasis.


Light adaptation in motion direction judgments.
We examined the time course of light adaptation in the visual motion system. Subjects judged the direction of a two-frame apparent-motion display, with the two frames separated by a 50-ms interstimulus interval of the same mean luminance. The phase of the first frame was randomly determined on each trial. The grating presented in the second frame was phase shifted either leftward or rightward by pi/2 with respect to the grating in the first frame. At some variable point during the first frame, the mean luminance of the pattern increased or decreased by 1-3 log units. Mean luminance levels varied from scotopic or low mesopic to photopic levels. We found that the perceived direction of motion depended jointly on the luminance level of the first frame grating and the time at which the shift in average luminance occurs. When the average luminance increases from scotopic or mesopic to photopic levels at least 0.5 s before the offset of the first frame, motion in the 3pi/2 direction is perceived. When average luminance decreases to low mesopic or scotopic levels, motion in the pi/2 direction is perceived if the change occurs 1.0 s or more before first frame offset, depending on the size of the luminance step. Thus light adaptation in the visual motion system is essentially complete within 1 s. This suggests a rapid change in the shape (biphasic or monophasic) of the temporal impulse response functions that feed into a first-order motion mechanism.


Modified Smith predictor based cascade control of unstable time delay processes.
An improved cascade control structure with a modified Smith predictor is proposed for controlling open-loop unstable time delay processes. The proposed structure has three controllers of which one is meant for servo response and the other two are for regulatory responses. An analytical design method is derived for the two disturbance rejection controllers by proposing the desired closed-loop complementary sensitivity functions. These two closed-loop controllers are considered in the form of proportional-integral-derivative (PID) controller cascaded with a second order lead/lag filter. The direct synthesis method is used to design the setpoint tracking controller. By virtue of the enhanced structure, the proposed control scheme decouples the servo response from the regulatory response in case of nominal systems i.e., the setpoint tracking controller and the disturbance rejection controller can be tuned independently. Internal stability of the proposed cascade structure is analyzed. Kharitonov's theorem is used for the robustness analysis. The disturbance rejection capability of the proposed scheme is superior as compared to existing methods. Examples are also included to illustrate the simplicity and usefulness of the proposed method.


Heart failure therapy in patients with coronary artery disease.
Heart failure and coronary artery disease share many risk factors. Coronary artery disease often pre-dates the development of heart failure with reduced ejection fraction. A diagnosis of heart failure should be considered in any patient with a history of coronary artery disease who presents with breathlessness, ankle oedema or fatigue. Several therapies, such as renin-angiotensin antagonists and B blockers, have been proven to improve survival in patients with heart failure with reduced ejection fraction but evidence for effectiveness in heart failure with preserved ejection fraction is lacking. The management of heart failure and coronary artery disease overlaps considerably but can also be conflicting. Optimal risk factor management is key to preventing progression to heart failure in patients with coronary artery disease.


Minimal invasive treatment of ureteropelvic junction obstruction in low volume pelvis: A comparative study of endopyelotomy and laparoscopic nondismembered pyeloplasty.
To evaluate the role of nondismembered laparoscopic pyeloplasty and percutaneous endopyelotomy for ureteropelvic junction obstruction (UPJO) with low volume renal pelvis. Retrospective acquired data of 34 patients of laparoscopic nondismembered pyeloplasty was compared with 26 patients of UPJO with pelvic volume less than 50 ml undergoing antegrade endopyelotomy and analyzed for clinical parameters, operative outcomes and success of procedures. All patients were followed up clinically and with diuretic renogram at regular intervals. Mean age, renal pelvic volume and preoperative glomerular filtration rate (GFR) was 25 years, 43.6 ml and 42.5 ml/min, respectively in endopyelotomy group and 21 years, 34.4 ml and 39.9 ml/min, respectively in laparoscopic pyeloplasty group. Mean operative time, postoperative analgesic requirement and mean hospital stay was 100min, 250 mg and 4 days, respectively in endopyelotomy group and 210 min, 300 mg and 4 days, respectively in laparoscopic pyeloplasty group. Only operative time was significantly different between two groups (P < 0.05). Mean follow-up was 36 and 39 months and success rates were 91.2% and 88.8% in laparoscopy and endopyelotomy group, respectively (P < 0.05). No significant complication was seen in endopyelotomy group while two patients had hematuria (one requiring blood transfusion) and three had increased drain output for more than 3 days in laparoscopy group. Percutaneous endopyelotomy is associated with significantly less operative time and postoperative complication rate and provides equivalent success in comparison to nondismembered laparoscopic pyeloplasty in patients with UPJO and low volume pelvis. It can be a preferred minimally invasive treatment modality for such patients.


Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.
Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of physiologically based pharmacokinetic (PBPK) modeling related publications and regulatory submissions have risen dramatically in recent years. However, the extent of use of PBPK modeling by researchers, and the public availability of models has not been systematically evaluated. This review evaluates PBPK-related publications to 1) identify the common applications of PBPK modeling; 2) determine ways in which models are developed; 3) establish how model quality is assessed; and 4) provide a list of publically available PBPK models for sensitive P450 and transporter substrates as well as selective inhibitors and inducers. PubMed searches were conducted using the terms "PBPK" and "physiologically based pharmacokinetic model" to collect published models. Only papers on PBPK modeling of pharmaceutical agents in humans published in English between 2008 and May 2015 were reviewed. A total of 366 PBPK-related articles met the search criteria, with the number of articles published per year rising steadily. Published models were most commonly used for drug-drug interaction predictions (28%), followed by interindividual variability and general clinical pharmacokinetic predictions (23%), formulation or absorption modeling (12%), and predicting age-related changes in pharmacokinetics and disposition (10%). In total, 106 models of sensitive substrates, inhibitors, and inducers were identified. An in-depth analysis of the model development and verification revealed a lack of consistency in model development and quality assessment practices, demonstrating a need for development of best-practice guidelines.


Analysis of Specialist and Patient Perspectives on Strategies to Improve Cardiovascular Disease Prevention Among Persons With Psoriatic Disease.
Patients with psoriatic disease are at increased risk of cardiovascular disease (CVD), which is a leading cause of mortality in this population. However, many of these patients do not have an active relationship with a primary care physician, and there may be a role for specialist-led care in prevention of CVD. To explore clinician and patient perspectives regarding strategies to improve CVD prevention via specialist-led care. Using electronically collected surveys, a best-worst scaling experimental survey study was conducted among dermatologists through the National Psoriasis Foundation as well as the American Academy of Dermatology from October 27, 2020, to April 1, 2021, to rank the strategies according to their potential to improve CVD prevention among patients with psoriatic disease. Participants were asked about the feasibility of specialist-led screening through an electronically delivered survey from the National Psoriasis Foundation conducted between February 1 and April 21, 2021. Patients with psoriatic disease were asked about whether they would like the specialist to screen for CVD risk factors. In addition, patients reported their likelihood to engage in CVD risk screening and management behaviors in scenarios in which either the primary care physician or specialist was making the recommendations. For the clinician surveys, the primary outcome was the ratio scaled preference score (range, 0-100; higher is more preferred), as well as whether they think calculating a 10-year CVD risk score and prescribing statins seems feasible. For the patient surveys, the primary outcome was the likelihood to check cholesterol level, incorporate diet and exercise, or use statin therapy depending on whether recommended by the specialist or primary care physician, whether they would like their specialist to educate them about CVD risk, and whether they would find it convenient to have their cholesterol level checked by their specialist. Among 183 dermatologists (102 [55.7%] women; mean [SD] age not collected), clinical decision support (preference score, 22.3; 95% CI, 20.7-24.0), patient education (preference score, 14.1; 95% CI, 12.5-15.7), and clinician education (preference score, 15.8; 95% CI, 14.3-17.3) were ranked as strategies likely to improve CVD prevention in patients with psoriatic disease. In addition, 69.3% (95% CI, 62.2%-76.0%) of dermatologists agreed or strongly agreed that checking lipid levels was feasible. Among 160 patients with psoriasis and 162 patients with psoriatic arthritis (226 [70.2%] women; mean [SD] age, 54 [13.3] years), patients reported they were as likely to engage in cardiovascular risk screening and management behaviors whether recommended by their primary care physician or their specialist. In addition, 60.0% (95% CI, 52.0%-67.7%) of patients with psoriasis and 75.3% (95% CI, 67.9%-81.7%) of those with psoriatic arthritis agreed that it would be convenient for them to have their cholesterol checked by their dermatologist/rheumatologist. In this survey study, dermatologists and patients with psoriatic disease expressed positive perspectives about engaging in a specialist-led model of care to improve CVD prevention. Dermatologists appear to view several strategies as having potential to improve cardiovascular risk prevention.


Structural and biochemical characterization of the cytochrome P450 CypX (CYP134A1) from Bacillus subtilis: a cyclo-L-leucyl-L-leucyl dipeptide oxidase.
Cytochrome P450 CypX (CYP134A1), isolated from Bacillus subtilis, has previously been implicated in the three-step oxidative transformation of the diketopiperazine cyclo-l-leucyl-l-leucyl into pulcherriminic acid, a precursor of the extracellular iron chelate pulcherrimin. In this study, we present the first experimental data relating to CYP134A1, where we show that CYP134A1 binds cyclo-l-leucyl-l-leucyl with an affinity of 24.5 +/- 0.5 muM. Structurally related diketopiperazines sharing similar alkyl side chains to cyclo-l-leucyl-l-leucyl also bind to CYP134A1 with comparable affinity. CYP134A1 is capable of catalyzing the in vitro oxidation of diketopiperazine substrates when supported with several alternate electron transfer partner systems. Products containing one additional oxygen atom and which are intermediate products of the expected pulcherriminic acid were identified by GCMS. The oxidation of related diketopiperazines reveals that different oxidative pathways exist for CYP134A1-catalyzed diketopiperazine oxidation. The crystal structure of CYP134A1 has been determined to 2.7 A resolution in the absence of substrate and in the presence of bound phenylimidazole ligands to 3.1 and 3.2 A resolution. The active site is dominated by hydrophobic residues and contains an unusual proline residue in place of the normally conserved alcohol residue that typically plays an important role in oxygen activation. The B-B(2) substrate recognition loop, which forms part of the active site, shows considerable flexibility and was found in both open and closed conformations in different structures. These results represent the first insights into the structural and biochemical basis underlying the multistep oxidation catalyzed by CYP134A1.


Metabolic characteristics of aorta from spontaneously hypertensive and renal and deoxycorticosterone acetate-salt hypertensive rats.
The purpose of this study was to determine if any changes occurred in the basal and stimulated rates of oxygen consumption and lactate production of thoracic aortas from spontaneously hypertensive rats (SHR) and renal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats, and, if so, whether these changes were similar in these three models of hypertension. Rings of thoracic aorta were placed in an isothermic (37 degrees C) muscle bath, and isometric tension development, oxygen consumption, and lactate production were measured. The results indicated that under basal conditions oxygen consumption, but not lactate production, was higher in aortas from all three hypertensive models; the elevation above control was greatest in the renal model (95%) and smallest in SHR (34%). On stimulation with 60 mM KCl, a significant increase in oxygen consumption above basal value occurred in all aorta samples (p less than 0.05); however, lactate production was increased above basal only in aortas from hypertensive animals. Only in aortas from renal and DOCA-salt models was the rate of oxygen consumption during stimulation significantly greater than that of their normotensive controls (p less than 0.05). Developed active stress in response to KCl was the same in all groups, and when the change in lactate production or oxygen consumption was expressed relative to the amount of active stress developed, no differences were observed. These results suggest that, 1) compared to values in aortas from normotensive animals, only the basal rate of oxygen consumption is higher; 2) this higher level of basal metabolic activity is not associated with an alteration in the metabolic cost of force development.(ABSTRACT TRUNCATED AT 250 WORDS)


Can static foot posture measurements predict regional plantar surface area?
The intent of this study was to determine if the use of a single or combination of static foot posture measurements can be used to predict rearfoot, midfoot, and forefoot plantar surface area in individuals with pronated or normal foot types. Twelve foot measurements were collected on 52 individuals (mean age 25.8 years) with the change in midfoot width used to place subjects in a pronated or normal foot mobility group. Dynamic plantar contact area was collected during walking with a pressure sensor platform. The 12 measures were entered into a stepwise regression analysis to determine the optimal set of measures associated with regional plantar surface area. A two variable model was found to describe the relationship between the foot measurements and forefoot plantar contact area (r(2)=0.79, p<0.0001). A four variable model was found to describe the relationship between the foot measurements and midfoot plantar contact area (r(2)=0.85, p<0.0001) in those individuals with a 1.26cm or greater change in midfoot width. The results indicate that clinicians can use a combination of simple, reliable and time efficient foot measures to explain 79% and 85% of the plantar surface area in the forefoot and midfoot, respectively.


De Novo Synthesis of DNA-Like Molecules by Polynucleotide Phosphorylase In Vitro
In the presence of Mg2+ ions, polynucleotide phosphorylase (PNPase, EC 188.8.131.52) is known to synthesize RNA-like polymers using ribonucleoside-5'-diphosphate (NDP) substrates but to be unable to utilize deoxyribonucleoside substrates. Our experiments show that when MgCl2 is replaced by FeCl3, PNPase becomes able to synthesize deoxyheteropolymers using deoxyribonucleoside-5'-diphosphates (dNDPs). The deoxyheteropolymer formed from the four dNDPs is degraded by pancreatic DNase, but not by RNase, and is readily used as a template by DNA-dependent DNA polymerase. Synthesis of this DNA-like polymer is accomplished de novo without the help of any primer or preexisting template. What is more, dA/dG and dC/dT ratios of polymers synthesized by different bacterial PNPases closely match ratios found in DNA of the bacterial species the enzyme came from.


Contractile effect of radish and betel nut extracts on rabbit gallbladder.
Raphanus sativus (abbreviated in this paper as Rs.Cr) and Areca catechu (Ac.Cr), commonly known as radish and betel nut respectively, are traditionally used in South Asia for different gastrointestinal, gallbladder, and hepatic diseases. There has not been any study to see how they modulate gallbladder contractility. We selected isolated rabbit gallbladder tissue preparations, mounted them in tissue baths containing Krebs-Henseleit solution at 37°C, and then recorded the changes in baseline tone of the tissues upon administration of Rs.Cr and Ac.Cr. Both the extracts exhibited concentration-dependent stimulant effect on the baseline tone of gallbladder tissues, similar to carbachol, a muscarinic receptor agonist. The stimulant effect of the extract, as well as that of carbachol, was completely blocked in the presence of atropine, a muscarinic antagonist, indicating similarity in the mechanism of action of the extracts with carbachol. The result shows potential of these extracts to contract the gallbladder and to subsequently increase bile secretion, but this remains to be investigated in detail. This study justifies the traditional use of radish and betel nut in different gastrointestinal disorders.


Strategic differentiation and integration of genomic-level heritabilities facilitate individual differences in preparedness and plasticity of human life history.
Life history (LH) strategies refer to the pattern of allocations of bioenergetic and material resources into different domains of fitness. While LH is known to have moderate to high population-level heritability in humans, both at the level of the high-order factor (Super-K) and the lower-order factors (K, Covitality, and the General Factor of Personality), several important questions remain unexplored. Here, we apply the Continuous Parameter Estimation Model to measure individual genomic-level heritabilities (termed transmissibilities). These transmissibility values were computed for the latent hierarchical structure and developmental dynamics of LH strategy, and demonstrate; (1) moderate to high heritability of factor loadings of Super-K on its lower-order factors, evidencing biological preparedness, genetic accommodation, and the gene-culture coevolution of biased epigenetic rules of development; (2) moderate to high heritability of the magnitudes of the effect of the higher-order factors upon their loadings on their constituent factors, evidencing genetic constraints upon phenotypic plasticity; and (3) that heritability of the LH factors, their factor loadings, and the magnitudes of the correlations among factors, are weaker among individuals with slower LH speeds. The results were obtained from an American sample of 316 monozygotic (MZ) and 274 dizygotic (DZ) twin dyads and a Swedish sample of 863 MZ and 475 DZ twin dyads, and indicate that inter-individual variation in transmissibility is a function of individual socioecological selection pressures. Our novel technique, opens new avenues for analyzing complex interactions among heritable traits inaccessible to standard structural equation methods.


Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis.
To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. The transcriptome of lens epithelia and fiber cells was obtained from C57BL/6 LEGSKO (lens GSH-synthesis knockout) and buthionine sulfoximine (BSO)-treated LEGSKO mice and compared to C57BL/6 wild-type mice using RNA-Seq. Transcriptomic data were confirmed by qPCR and Western blot/ELISA on a subset of genes. RNA-Seq results were in excellent agreement with qPCR (correlation coefficients 0.87-0.94 and P < 5E-6 for a subset of 36 mRNAs). Of 24,415 transcripts mapped to the mouse genome, 441 genes showed significantly modulated expression. Pathway analysis indicated major changes in epithelial-mesenchymal transition (EMT) signaling, visual cycle, small molecule biochemistry, and lipid metabolism. GSH-deficient lenses showed upregulation of detoxification genes, including Aldh1a1, Aldh3a1 (aldehyde dehydrogenases), Mt1, Mt2 (metallothioneins), Ces1g (carboxylesterase), and Slc14a1 (urea transporter UT-B). Genes in canonical EMT pathways, including Wnt10a, showed upregulation in lens epithelia samples. Severely GSH-deficient lens epithelia showed downregulation of vision-related genes (including crystallins). The BSO-treated LEGSKO lens epithelia transcriptome has significant correlation (r = 0.63, P < 0.005) to that of lens epithelia undergoing EMT. Protein expression data correlated with transcriptomic data and confirmed EMT signaling activation. These results show that GSH-deficiency in the lens leads to expression of detoxifying genes and activation of EMT signaling, in addition to changes in transport systems and lipid homeostasis. These data provide insight into the adaptation and consequences of GSH-deficiency in the lens and suggest that GSH plays an important role in lenticular EMT pathology.


Climate change, aeroallergens, natural particulates, and human health in Australia: state of the science and policy.
The objective of this article is to systematically review and assess what is known about the impacts of climate change on aeroallergens and other naturally derived particulates, and the associated human health impacts, and to examine responses to these in Australia, focusing on adaptation. Prior research was searched using several general and discipline-specific research databases. The review concludes that whereas there is little original research on the impacts of climate change on aeroallergens and other naturally derived particulates in Australia, or the human health consequences of these, research from overseas suggests that these impacts may be adverse and of considerable magnitude. More research is required to assess the impacts of climate change on these airborne particles and associated diseases in Australia and other parts of the Asia-Pacific. There are important policy implications of this review. There is a need for enhanced monitoring of the atmospheric environment and associated health conditions in Australia. Education about climate change and human health in general, and air quality and related diseases specifically, is required for the community, health professionals, and others. Improvements are needed in the preparedness of infrastructure, such as health care facilities and early warning systems, particularly for aeroallergens, and all of these adaptive policy responses require further research.


Maternal residential proximity to chlorinated solvent emissions and birth defects in offspring: a case-control study.
Some studies have noted an association between maternal occupational exposures to chlorinated solvents and birth defects in offspring, but data are lacking on the potential impact of industrial air emissions of these solvents on birth defects. With data from the Texas Birth Defects Registry for births occurring in 1996-2008, we examined the relation between maternal residential proximity to industrial air releases of chlorinated solvents and birth defects in offspring of 60,613 case-mothers and 244,927 control-mothers. Maternal residential exposures to solvent emissions were estimated with metrics that took into account residential distances to industrial sources and annual amounts of chemicals released. Logistic regression was used to generate odds ratios and 95% confidence intervals for the associations between residential proximity to emissions of 14 chlorinated solvents and selected birth defects, including neural tube, oral cleft, limb deficiency, and congenital heart defects. All risk estimates were adjusted for year of delivery and maternal age, education, race/ethnicity, and public health region of residence. Relative to exposure risk values of 0, neural tube defects were associated with maternal residential exposures (exposure risk values >0) to several types of chlorinated solvents, most notably carbon tetrachloride (adjusted odds ratio [aOR] 1.42, 95% confidence interval [CI] 1.09, 1.86); chloroform (aOR 1.40, 95% CI 1.04, 1.87); ethyl chloride (aOR 1.39, 95% CI 1.08, 1.79); 1,1,2-trichloroethane (aOR 1.56, 95% CI 1.11, 2.18); and 1,2,3-trichloropropane (aOR 1.49, 95% CI 1.08, 2.06). Significant associations were also noted between a few chlorinated solvents and oral cleft, limb deficiency, and congenital heart defects. We observed stronger associations between some emissions and neural tube, oral cleft, and heart defects in offspring of mothers 35 years or older, such as spina bifida with carbon tetrachloride (aOR 2.49, 95% CI 1.09, 5.72), cleft palate with 1,2-dichloroethane (aOR 1.93, 95% 1.05, 3.54), cleft lip with or without cleft palate with ethyl chloride (aOR 1.81, 95% CI 1.06, 3.07), and obstructive heart defects with trichloroethylene (aOR 1.43, 95% CI 1.08, 1.88). These findings suggest that maternal residential proximity to industrial emissions of chlorinated solvents might be associated with selected birth defects in offspring, especially among older mothers.


Care stress in caregivers of disabled stroke patients: a cross-sectional survey.
A cross-sectional survey was performed on the family membersof disabled stroke survivors, those who are both the patient's medical authorizer and caregiver,to identify the sources of the caring stress and inform appropriate interventions. A total of 242 family members of stroke patients, who were treated in a tertiary geriatric hospital in Haikou, the capital city of Hainan Province, were enrolled in the current study by using convenience sampling. Questionnaire forms were used to investigate care stress caused by family members' current care activitiesand analyze its causes. The care stress of the family members was moderately positively correlated with financial pressure (r=0.476, P<0.01). Family members' educational background, financial pressure, the times of hospitalizations, the dependency of stroke patients, and the degree of family members' participation in treatment decisionmaking during the patient's hospital stay were the primary sources of the caring stress (P<0.05 or P<0.01). A substantial proportion of family members are under high stress when caring for disabled stroke patients. Strategies including knowledge training, empowerment, home-based rehabilitation, and information and emotional support may effectively relieve the caring stress, to improve the family support of patients, improve the quality of life of both patients and caregivers, and enhance the rehabilitation effectiveness.


Effects of polymorphic variation on the mechanism of Endoplasmic Reticulum Aminopeptidase 1.
Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) generates antigenic peptides for loading onto Major Histocompatibility Class I molecules (MHCI) and can regulate adaptive immune responses. During the last few years, many genetic studies have revealed strong associations between coding Single Nucleotide Polymorphisms (SNPs) in ERAP1 and common human diseases ranging from viral infections to cancer and autoimmunity. Functional studies have established that these SNPs affect enzyme activity resulting to changes in antigenic peptide processing, presentation by MHCI and cellular cytotoxic responses. These disease-associated polymorphisms are, however, located away from the enzyme's active site and are interspersed to different structural domains. As a result, the mechanism by which these SNPs can affect function remains largely elusive. ERAP1 utilizes a complex catalytic mechanism that involves a large conformational change between inactive and active forms and has the unique property to trim larger peptides more efficiently than smaller ones. We analyzed two of the most consistently discovered disease-associated polymorphisms, namely K528R and Q730E, for their effect on the ability of the enzyme to select substrates based on length and to undergo conformational changes. By utilizing enzymatic and computational analysis we propose that disease-associated SNPs can affect ERAP1 function by influencing: (i) substrate length selection and (ii) the conformational distribution of the protein ensemble. Our results provide novel insight on the mechanisms by which polymorphic variation distal from the active site of ERAP1 can translate to changes in function and contribute to immune system variability in humans.


Using experimental design to define boundary manikins.
When evaluating human-machine interaction it is central to consider anthropometric diversity to ensure intended accommodation levels. A well-known method is the use of boundary cases where manikins with extreme but likely measurement combinations are derived by mathematical treatment of anthropometric data. The supposition by that method is that the use of these manikins will facilitate accommodation of the expected part of the total, less extreme, population. In literature sources there are differences in how many and in what way these manikins should be defined. A similar field to the boundary case method is the use of experimental design in where relationships between affecting factors of a process is studied by a systematic approach. This paper examines the possibilities to adopt methodology used in experimental design to define a group of manikins. Different experimental designs were adopted to be used together with a confidence region and its axes. The result from the study shows that it is possible to adapt the methodology of experimental design when creating groups of manikins. The size of these groups of manikins depends heavily on the number of key measurements but also on the type of chosen experimental design.


Biological and biochemical consequences of global deletion of exon 3 from the ER alpha gene.
To address issues resulting from α estrogen receptor-knockout (αERKO) residual N-terminal truncated estrogen receptor α, and to allow tissue-selective deletion of ERα, we generated loxP-flanked exon 3 mice. Initial characterization of global sox2 cre-derived exon 3-deleted Ex3αERKO mice indicated no ERα protein in uterine tissue and recapitulation of previously described female phenotypes, confirming successful ablation of ERα. Body weights of Ex3αERKO female mice were 1.4-fold higher than wild-tupe (WT) females and comparable to WT males. Microarray indicated the Ex3αERKO uterus is free of residual estrogen responses. RT-PCR showed Nr4a1 is increased 41-fold by estrogen in WT and 7.4-fold in αERKO, and not increased in Ex3αERKO. Nr4a1, Cdkn1a, and c-fos transcripts were evaluated in WT and Ex3αERKO mice following estrogen, IGF1, or EGF injections. All 3 were increased by all treatments in WT. None were increased by estrogen in Ex3αERKO. Nr4a1 increased 24.5- and 14.7-fold, Cdkn1a increased 14.2- and 12.3-fold, and c-fos increased 20.9-fold and 16.2-fold after IGF1 and EGF treatments, respectively, in the Ex3αERKO mice, confirming that growth factor regulation is independent of ERα. Our Ex3α ERα model will be useful in studies of complete or selective ablation of ERα in target tissues.


Barriers and Facilitators of Engaging Community Health Workers in Non-Communicable Disease (NCD) Prevention and Control in China: A Systematic Review (2006⁻2016).
Background: Non-communicable diseases (NCDs) have become a dominant disease burden in China. Although China has a prevention-centered NCD strategy, the implementation effect in the community has been subjected to manpower and financial difficulties. Engaging community health workers (CHWs) in community-based interventions may be a cost-effective approach to relieve the resource shortage and improve health. This review aimed to synthesize evidence on types of NCD-related care that was provided by CHWs in China, and to identify relevant barriers and facilitators. Methods: A literature search was conducted in Medline, PubMed, ProQuest, and Google Scholar databases for English-written, peer-reviewed articles published from 1996 to 2016 that reported findings from NCD-related interventions delivered by CHWs in China. Each article was extracted independently by two researchers. Results: Twenty distinct studies met the inclusion criteria. The two most common types of CHW-led NCD-related care were diabetes and hypertension management (n = 7) and mental health care (n = 7). Thirteen studies discussed the barriers and 16 studies reported facilitators. The most common barriers included lack of support (n = 6), lack of resources (n = 4), and heavy reliance on technology (n = 4). The common facilitators included an integrated health system (n = 9), community and patient trust (n = 5), high quality training (n = 5), and CHWs' capacity (n = 5). Fourteen studies mentioned training content, while only eight described detailed procedures and duration. Conclusions: This review suggests that trained and supervised Chinese CHWs had the capacity to provide grassroots NCDs preventive interventions. In order to increase the generalizability and sustainability of such programs, studies with robust designs are needed to explore the effectiveness of CHW-led programs, and the intervention strategies to improve the practice of CHWs in various settings.


Distinctive Patterns of Flavonoid Biosynthesis in Roots and Nodules of Datisca glomerata and Medicago spp. Revealed by Metabolomic and Gene Expression Profiles.
Plants within the Nitrogen-fixing Clade (NFC) of Angiosperms form root nodule symbioses with nitrogen-fixing bacteria. Actinorhizal plants (in Cucurbitales, Fagales, Rosales) form symbioses with the actinobacteria Frankia while legumes (Fabales) form symbioses with proteobacterial rhizobia. Flavonoids, secondary metabolites of the phenylpropanoid pathway, have been shown to play major roles in legume root nodule symbioses: as signal molecules that in turn trigger rhizobial nodulation initiation signals and acting as polar auxin transport inhibitors, enabling a key step in nodule organogenesis. To explore a potentially broader role for flavonoids in root nodule symbioses across the NFC, we combined metabolomic and transcriptomic analyses of roots and nodules of the actinorhizal host Datisca glomerata and legumes of the genus Medicago. Patterns of biosynthetic pathways were inferred from flavonoid metabolite profiles and phenylpropanoid gene expression patterns in the two hosts to identify similarities and differences. Similar classes of flavonoids were represented in both hosts, and an increase in flavonoids generally in the nodules was observed, with differences in flavonoids prominent in each host. While both hosts produced derivatives of naringenin, the metabolite profile in D. glomerata indicated an emphasis on the pinocembrin biosynthetic pathway, and an abundance of flavonols with potential roles in symbiosis. Additionally, the gene expression profile indicated a decrease in expression in the lignin/monolignol pathway. In Medicago sativa, by contrast, isoflavonoids were highly abundant featuring more diverse and derived isoflavonoids than D. glomerata. Gene expression patterns supported these differences in metabolic pathways, especially evident in a difference in expression of cinnamic acid 4-hydroxylase (C4H), which was expressed at substantially lower levels in D. glomerata than in a Medicago truncatula transcriptome where it was highly expressed. C4H is a major rate-limiting step in phenylpropanoid biosynthesis that separates the pinocembrin pathway from the lignin/monolignol and naringenin-based flavonoid branches. Shikimate O-hydroxycinnamoyltransferase, the link between flavonoid biosynthesis and the lignin/monolignol pathway, was also expressed at much lower levels in D. glomerata than in M. truncatula. Our results indicate (a) a likely major role for flavonoids in actinorhizal nodules, and (b) differences in metabolic flux in flavonoid and phenylpropanoid biosynthesis between the different hosts in symbiosis.


5-alk(en)ylresorcinols as the major active components in wheat bran inhibit human colon cancer cell growth.
We and others have found that wheat bran oil is the active constituent in wheat bran for colon cancer prevention. However, the active components in wheat bran oil are still unknown. Using human colon cancer cells (HCT-116 and HT-29) as the guiding assays, we further purified the active components from wheat bran using column chromatography. In this study, we identified that a fraction containing 5-n-alk(en)ylresorcinols had the strongest inhibitory effect on the proliferation of human HCT-116 and HT-29 colon cancer cells. Further purification led to the identification of 14 5-alk(en)ylresorcinols. Among them, 7, (10'Z,13'Z,16'Z)-5-(nonadeca-10',13',16'-trienyl)resorcinol, is a novel compound and 5, 6, 9, 10, and 13 were purified as individual compounds for the first time. The identification and structural elucidation of these compounds were based on 1D and 2D NMR and tandem mass spectral analyses. All these compounds (1-14) except 10 were evaluated for growth inhibition of human colon cancer cell lines (HCT-116 and HT-29). Our results indicate that increasing the length of the side chain will diminish the inhibitory activity, and the existence of a double bond and a carbonyl group will strengthen such an activity.


The Effectiveness of Hypnosis Intervention in Alleviating Postpartum Psychological Symptoms.
Psychological symptoms, particularly postpartum depression, may impair women's well-being after childbirth. Mind-body treatments such as hypnosis are available to help prepare women to maintain or improve their well-being postpartum. The aims of the present study are to determine the effectiveness of a hypnosis intervention in alleviating psychological symptoms (stress, anxiety, and depression) and the symptoms of postpartum depression. A quasi-experimental design was utilized in this study. The experimental group participants (n = 28) received a hypnosis intervention at weeks 16, 20, 28, and 36 of their pregnancies. Participants in the control group (n = 28) received routine prenatal care. The final data collection, occurring at two months postpartum, included 16 women from the experimental group and 11 women from the control group. The Depression Anxiety Stress Scale-21 (DASS-21) was used to measure psychological symptoms, and postpartum depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS). The results at two months postpartum showed that the experimental group had significantly lower postpartum anxiety than the control group (M = 2.88 versus M = 38.36, p = .023). Similarly, the experimental group had significantly lower postpartum depressive symptoms than the control group (M = 1.25 versus M = 6.73, p < .002). Group differences in postpartum stress symptoms were not significant (p = .363). Finally, the results indicated that the experimental group experienced reduced postpartum depression when compared to the control group (M = 5.69 versus M = 10.64, p < .001). Thus, hypnosis conducted during pregnancy may promote improvements in psychological well-being postpartum.


Anti-neurotrophic effects from autoantibodies in adult diabetes having primary open angle glaucoma or dementia.
To test for anti-endothelial and anti-neurotrophic effects from autoantibodies in subsets of diabetes having open-angle glaucoma, dementia, or control subjects. Protein-A eluates from plasma of 20 diabetic subjects having glaucoma or suspects and 34 age-matched controls were tested for effects on neurite outgrowth in rat pheochromocytoma PC12 cells or endothelial cell survival. The mechanism of the diabetic glaucoma autoantibodies' neurite-inhibitory effect was investigated in co-incubations with the selective Rho kinase inhibitor Y27632 or the sulfated proteoglycan synthesis inhibitor sodium chlorate. Stored protein-A eluates from certain diabetic glaucoma or dementia subjects which contained long-lasting, highly stable cell inhibitory substances were characterized using mass spectrometry and amino acid sequencing. Diabetic primary open angle glaucoma (POAG) or suspects (n = 20) or diabetic dementia (n = 3) autoantibodies caused significantly greater mean inhibition of neurite outgrowth in PC12 cells (p < 0.0001) compared to autoantibodies in control diabetic (n = 24) or non-diabetic (n = 10) subjects without glaucoma (p < 0.01). Neurite inhibition by the diabetic glaucoma autoantibodies was completely abolished by 10 μM concentrations of Y27632 (n = 4). It was substantially reduced by 30 mM concentrations of sodium chlorate (n = 4). Peak, long-lasting activity survived storage ×5 years at 0-4°C and was associated with a restricted subtype of Ig kappa light chain. Diabetic glaucoma or dementia autoantibodies (n = 5) caused contraction and process retraction in quiescent cerebral cortical astrocytes effects which were blocked by 5 μM concentrations of Y27632. These data suggest that autoantibodies in subsets of adult diabetes having POAG (glaucoma suspects) and/or dementia inhibit neurite outgrowth and promote a reactive astrocyte morphology by a mechanism which may involve activation of the RhoA/p160 ROCK signaling pathway.