FlexiQule (Boswellia extract) in the supplementary management of osteoarthritis: a supplement registry.
The aim of the present pilot, registry study was an assessment in a supplement study of FlexiQule (standardized Boswellia extract) capsules in the supplementary management of patients with symptomatic knee osteoarthritis (OA) also treated with the "standard management" (SM) in comparison with a group of patients only managed with SM. This 4-week study included patients with symptomatic knee arthrosis (X-ray). Registry subjects were able to perform a treadmill walking test and to understand questions from the WOMAC questionnaire. Exclusion criteria were conditions requiring drug treatment, Body Mass Index >25, metabolic disorders, surgery within three months prior to inclusion, oncological condition or inability to walk. Twenty-seven registry subjects using the supplement+SM and 28 using only SM completed the registry; at inclusion, the two groups were comparable including Karnofsky scale, WOMAC Score and the Treadmill Test. Of the subjects completing the registry 24 preferred to use the combination SM and the supplement. Safety evaluation: no problems - indicating the suspension of the supplementation ‑ were observed. Routine blood tests were normal at inclusion and did not significantly vary at 4 weeks. The Karnofski Scale at 4 weeks was improved in both groups: from 74.3;3.1 to 88.9;5.3 (P<0.05) in the Boswellia group in comparison with a variation from 75.3;5.2 to 79.4;3.3 (P<0.05) in the SM. The effects of the supplement were significantly higher (P<0.05). The WOMAC Score was decreased significantly more in the supplement+SM group in comparison with controls considering pain, stiffness and physical functions (P<0.05). Social/emotional functions improved better with the supplement (P<0.05). Both groups improved their walking distance at 4 weeks. The improvement was higher (P<0.05) in the Boswellia group. The need for other drugs or tests during the registry period was reduced more in the supplement group (P<0.05). The difference between SM and the supplementation associated to SM was significant) in favor of the supplementation with Boswellia for all target measurements evaluated in the registry at 4 weeks.


Chest radiograph in acute respiratory infections.
Chest radiography is widely used during the management of acute lower respiratory infections, but the benefits are unknown. To assess the effects of chest radiography on clinical outcome in acute lower respiratory infections. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1950 to January 2007) and EMBASE (January 1976 to February 2007). Randomised or quasi-randomised trials of chest radiography in acute respiratory infections. Both review authors independently applied the inclusion criteria, extracted data and assessed trial quality. We identified two trials. One, of 522 outpatient children (and performed by the review authors), found that 46% of both radiography and control participants had recovered by seven days (relative risk (RR) 1.01, 95% confidence interval (CI) 0.79 to 1.31). Thirty-three per cent of radiography participants and 32% of control participants made a subsequent hospital visit within four weeks (RR 1.02, 95% CI 0.79 to 1.30) and 3% of both radiography and control participants were subsequently admitted to hospital within four weeks (RR 1.02, 95% CI 0.41 to 2.52). The other trial involving 1502 adults attending an emergency department found no significant difference in length of illness, the single outcome prespecified for this review (mean of 16.9 days in radiograph group versus 17.0 days in control group, P > 0.05). There is no evidence that chest radiography improves outcome in outpatients with acute lower respiratory infection. The findings do not exclude a potential effect of radiography, but the potential benefit needs to be balanced against the hazards and expense of chest radiography. The findings apply to outpatients only.


Crystal engineering of a family of hybrid ultramicroporous materials based upon interpenetration and dichromate linkers.
A new family of 2-fold interpenetrated primitive cubic (pcu) networks of formula [M(L)2(Cr2O7)] n (M = Co2+, Ni2+, Cu2+ and Zn2+; L = 4,4'-azopyridine), DICRO-3-M-i, has been synthesised and their structures, permanent porosity and gas sorption properties were comprehensively characterised. Molecular simulations indicate that CO2 molecules occupy both of the two distinct ultramicropores that run through this isostructural series. The orientation of the Cr2O72- pillars is thought to contribute to high isosteric enthalpy of adsorption (Qst) towards CO2 and temperature programmed desorption experiments reveal that DICRO-3-Ni-i selectively adsorbs CO2 from gas mixtures that simulate flue gas. Performance in this context is among the highest for physisorbents measured to date and these materials are readily regenerated at 50 °C.


Mobile robots: motor challenges and materials solutions.
Bolted-down robots labor in our factories, performing the same task over and over again. Where are the robots that run and jump? Equaling human performance is very difficult for many reasons, including the basic challenge of demonstrating motors and transmissions that efficiently match the power per unit mass of muscle. In order to exceed animal agility, new actuators are needed. Materials that change dimension in response to applied voltage, so-called artificial muscle technologies, outperform muscle in most respects and so provide a promising means of improving robots. In the longer term, robots powered by atomically perfect fibers will outrun us all.


A Functional Link Between Bir1 and the Saccharomyces cerevisiae Ctf19 Kinetochore Complex Revealed Through Quantitative Fitness Analysis.
The chromosomal passenger complex (CPC) is a key regulator of eukaryotic cell division, consisting of the protein kinase Aurora B/Ipl1 in association with its activator (INCENP/Sli15) and two additional proteins (Survivin/Bir1 and Borealin/Nbl1). Here, we report a genome-wide genetic interaction screen in Saccharomyces cerevisiae using the bir1-17 mutant, identifying through quantitative fitness analysis deletion mutations that act as enhancers and suppressors. Gene knockouts affecting the Ctf19 kinetochore complex were identified as the strongest enhancers of bir1-17, while mutations affecting the large ribosomal subunit or the mRNA nonsense-mediated decay pathway caused strong phenotypic suppression. Thus, cells lacking a functional Ctf19 complex become highly dependent on Bir1 function and vice versa. The negative genetic interaction profiles of bir1-17 and the cohesin mutant mcd1-1 showed considerable overlap, underlining the strong functional connection between sister chromatid cohesion and chromosome biorientation. Loss of some Ctf19 components, such as Iml3 or Chl4, impacted differentially on bir1-17 compared with mutations affecting other CPC components: despite the synthetic lethality shown by either iml3∆ or chl4∆ in combination with bir1-17, neither gene knockout showed any genetic interaction with either ipl1-321 or sli15-3 Our data therefore imply a specific functional connection between the Ctf19 complex and Bir1 that is not shared with Ipl1.


[Between old and new targets: blood pressure control in hypertensive outpatients].
In developed countries, blood pressure (BP) control has increased over the past few decades and is now approaching 70% of patients. Herewith we report the results of a cross-sectional study carried out on hypertensive outpatients. In a cohort of 1,412 consecutive hypertensive outpatients (790 females, 622 males; mean age: 60.3±12.2 years) evaluated from January 2015 to December 2016, the following parameters were assessed: age, gender, body mass index (BMI), waist circumference (WC), smoking habits, BP in the sitting position, estimated glomerular filtration rate (eGFR), serum glucose, lipid profile, antihypertensive drugs prescribed. In agreement with the European guidelines, hypertension was defined as sitting BP ≥140/90 mmHg or use of antihypertensive drugs. Patients whose BP was <140/90 mmHg were considered as having achieved BP control. Furthermore, in compliance with the redefinition of hypertension suggested by the American College of Cardiology/American Heart Association (ACC/AHA), a second level of BP control (BP <130/80 mmHg) was evaluated. Overall, 75.7% of hypertensive patients achieved BP levels <140/90 mmHg, while 50.5% achieved BP levels <130/80 mmHg. In both contexts, compared with patients whose BP was not controlled, those achieving the BP targets were mainly younger and females with a lower prevalence of obesity, diabetes and chronic kidney disease. Furthermore, they also had a lower WC and a higher eGFR. Nearly 76% of patients achieved the BP target of <140/90 mmHg, a result which is higher than the 70% achieved in Europe, and 50.6% achieved that of <130/80 mmHg, a result which is slightly higher than the 47% recently reported in USA.


A systematic review on the impact of leg ulceration on patients' quality of life.
A systematic review was conducted to analyse journal articles that describe or measure the impact of leg ulceration on patients' quality of life (QoL) in order to improve the content of an educational programme that aims to enhance self-care agency in leg ulcer patients. Original articles published in English and German between 1990 and 2006 were included if the findings were analysed at the level of patients. Articles were excluded if (1) they investigated the impact of specific treatments or settings on QoL or (2) focused mainly on arterial ulcers or diabetic foot ulcers. Twenty-four original research articles met the inclusion criteria; 11 studies used a quantitative, 11 studies a qualitative, and 2 used a mixed method approach. The findings were collapsed into 5 core domains. Quantitative studies commonly investigated the parameters of pain, sleep, social isolation, and physical mobility. Patients had significantly more pain, more restrictions regarding social functioning, less vitality, and limitations with respect to emotional roles compared to the respective controls. Other problem areas identified were restrictions in work capacity, recreation, social interaction, psychological well-being, as well as problems caused by treatment regimes. Inconclusive results were obtained regarding pain intensity, physical restrictions, and gender effects. Numerous original studies neither undertook a differentiation of participants by ulcer aetiology nor did they analyse the results according to gender differences. As leg ulceration has an impact on QoL, national guidelines on the treatment of leg ulceration need to more specifically address these far-ranging effects identified in this review.


Dimensions of the local health care environment and use of care by uninsured children in rural and urban areas.
Despite concerted policy efforts, a sizeable percentage of children lack health insurance coverage. This article examines the impact of the health care safety net and health care market structure on the use of health care by uninsured children. We used the Medical Expenditure Panel Survey linked with data from multiple sources to analyze health care utilization among uninsured children. We ran analyses separately for children who lived in rural and urban areas and assessed the effects on utilization of the availability of safety net providers, safety net funding, supply of primary care physicians, health maintenance organization penetration, and the percentage of people who are uninsured, controlling for other factors that influence use. Fewer than half of uninsured children had office-based visits to health care providers during the year, 8% of rural and 10% of urban children visited the emergency department at least once, and just over half of children had medical expenditures or charges during the year. Among uninsured children in rural areas, living closer to a safety net provider and living in an area with a higher supply of primary care physicians were positively associated with higher use and medical expenditures. In urban areas, the supply of primary care physicians and the level of safety net funding were positively associated with uninsured children's medical expenditures, whereas the percentage of the population that was uninsured was negatively associated with use of the emergency department. Uninsured children had low levels of utilization over a range of different health care provider types and settings. The availability of safety net providers in the local area and the safety net's capacity to serve the uninsured influence access to care among children. Possible measures for ensuring access to health care among uninsured children include increasing the density of safety net providers in rural areas, enhancing funding for the safety net, and policies to increase primary care physician supply.


A systematic review of dermal fillers for age-related lines and wrinkles.
Dermal fillers are gaining popularity for rapid aesthetic improvement. Long-term efficacy and safety have not been well documented. The aim of this systematic review was to assess the safety and efficacy of injectable dermal fillers compared with other facial augmentation techniques for the management of age-related lines and wrinkles. Studies including patients receiving injectable semi-permanent or permanent dermal fillers for age-related lines and wrinkles were included in this review. Efficacy outcomes (including changes in skin thickness and patient satisfaction) and safety outcomes (including mortality, lumps and infections) were examined. Three randomized control trials and six case series were included. Permanent and semi-permanent dermal fillers improved subjective ratings of appearance and resulted in higher patient satisfaction than temporary fillers. Long-term efficacy appeared good in the few studies that reported it. Short-term safety appeared favourable. Lumps were reported in all but one study but received little follow-up. Long-term safety data were limited. The treatment of age-related lines and wrinkles with permanent and semi-permanent dermal fillers is more efficacious compared with temporary fillers in those studies that compared them. Case series evidence suggests that these fillers achieve their objective, which is to decrease the visible effects of age-related changes. These fillers appear at least as safe as temporary fillers in the short term in those studies that compared them. Long-term safety could not be determined.


Effects of anterior hypothalamic disconnection on the evolution of Goldblatt renal hypertension. A dual response.
The role of the central nervous system, in general, and of the hypothalamus, in particular, in the genesis of various forms of experimental hypertension has been the object of increased investigation. Lesions of the anteroventral area of the third ventricle (AV3V) in rats seem to block the development of various forms of hypertension. In the present experiments, AV3V was kept intact but its connections with the caudal neuroaxis were severed by means of a curved knife (2 mm radius), stereotaxically placed at the level of the arcuate nucleus. This disconnection, per se, induces polydipsia, and a reduction of the pressor effect of i.v.-infused angiotensin II. The interactions of simultaneously performed hypothalamic disconnection (HD) and Goldblatt one-kidney, one clip, (1K1C) or two-kidney, one clip (2K1C) hypertensions was studied. It was found that HD retards and attenuates the development of 1K1C hypertension but does not materially affect the evolution of the 2K1C model. Rats with established 1K1C or 2K1C hypertensions were not affected by HD, whereas rats with chronic HD (4 weeks) showed slight and slow developing hypertension in response to clipping. The possible significance of these results with respect to the neural connections of AV3V is discussed.


Inter-Relationship between Low-Dose Hyper-Radiosensitivity and Radiation-Induced Bystander Effects in the Human T98G Glioma and the Epithelial HaCaT Cell Line.
Over the past several years, investigations in both low-dose hyper-radiosensitivity and increased radioresistance have been a focus of radiation oncology and biology research, since both conditions occur primarily in tumor cell lines. There has been significant progress in elucidating their signaling pathways, however uncertainties exist when they are studied together with radiation-induced bystander effects. Therefore, the aim of this work was to further investigate this relationship using the T98G glioma and HaCaT cell lines. T98G glioma cells have demonstrated a strong transition from hyper-radiosensitivity to induced radioresistance, and HaCaT cells do not show low-dose hypersensitivity. Both cell lines were paired using a mix-and-match protocol, which involved growing nonirradiated cells in culture media from irradiated cells and covering all possible combinations between them. The end points analyzed were clonogenic cell survival and live calcium measurements through the cellular membrane. Our data demonstrated that T98G cells produced bystander signals that decreased the survival of both reporter T98G and HaCaT cells. The bystander effect occurred only when T98G cells were exposed to doses below 1 Gy, which was corroborated by the induction of calcium fluxes. However, when bystander signals originated from HaCaT cells, the survival fraction increased in reporter T98G cells while it decreased in HaCaT cells. Moreover, the corresponding calcium data showed no calcium fluxes in T98G cells, while HaCaT cells displayed a biphasic calcium profile. In conclusion, our findings indicate a possible link between low-dose hyper-radiosensitivity and bystander effects. This relationship varies depending on which cell line functions as the source of bystander signals. This further suggests that the bystander mechanisms are more complex than previously expected and caution should be taken when extrapolating bystander results across all cell lines and all radiation doses.


A secreted MMP is required for reepithelialization during wound healing.
Matrix metalloproteinases (MMPs) are extracellular proteases highly expressed at wound sites. However, the precise function of MMPs during reepithelialization in vivo has been elusive in mammalian models because of the high level of redundancy among the 24 mammalian MMPs. For this reason we used Drosophila melanogaster, whose genome encodes only two MMPs-one secreted type (Mmp1) and one membrane-anchored type (Mmp2)-to study the function and regulation of the secreted class of MMPs in vivo. In the absence of redundancy, we found that the Drosophila secreted MMP, Mmp1, is required in the epidermis to facilitate reepithelialization by remodeling the basement membrane, promoting cell elongation and actin cytoskeletal reorganization, and activating extracellular signal-regulated kinase signaling. In addition, we report that the jun N-terminal kinase (JNK) pathway upregulates Mmp1 expression after wounding, but that Mmp1 is expressed independent of the JNK pathway in unwounded epidermis. When the JNK pathway is ectopically activated to overexpress Mmp1, the rate of healing is accelerated in an Mmp1-dependent manner. A primary function of Mmp1, under the control of the JNK pathway, is to promote basement membrane repair, which in turn may permit cell migration and the restoration of a continuous tissue.


Single-dose levodopa administration and aging independently disrupt time production.
We tested the hypothesis that age-related time production deficits are dopamine-mediated. The experiment was conducted double-blind, and with random assignment of 32 healthy aged and 32 healthy young participants to either inert placebo or levodopa (200 mg) groups. The procedure included training participants to produce two target time intervals (6 and 17 sec) in separate blocks, drug/placebo administration, a 1-hr delay, and then delayed free-recall time production retesting without feedback. Participants also performed a speeded choice reaction time (RT) task, as a control for potential dopaminergic and aging effects on attention and psychomotor speed. Results indicate that during retesting, aged participants show duration-dependent timing errors that are larger than those shown by the young participants. Levodopa administration yielded lengthened time production of both target intervals. The aging and levodopa effects did not interact. Also, aging slowed RT and increased RT variability, but levodopa had no effect on the RT. These results suggest that at this dosage and under these specific conditions, timing is dopamine-mediated but the effect of aging on time production is not. Moreover, the levodopa timing effect cannot be attributed to the effects of dopaminergic function on psychomotor speed.


The formation and patterning of leaves: recent advances.
Leaves, the plant's major photosynthetic organs, form through the activity of groups of pluripotent cells, termed shoot apical meristems (SAMs), located at the growing tips of plants. Leaves develop with a dorso-ventral asymmetry, with the adaxial surface adjacent to the meristem and the abaxial surface developing at a distance from it. Molecular genetic studies have shown that the correct specification of adaxial/abaxial polarity requires communication between the incipient leaf and the meristem, and that the juxtaposition of adaxial/abaxial fates is necessary for lamina outgrowth (Waites and Hudson 1995; McConnell et al. 2001). Over the last few years, a number of factors that control cell fate specification in the apex have been identified. This review will focus on recent advances on distinct but overlapping aspects of leaf development, namely, the transition from meristem to leaf fate and the specification of abaxial/adaxial polarity and its possible role in leaf growth.


A longitudinal study of gait function and characteristics of gait disturbance in individuals with Alzheimer's disease.
Walking in daily life places high demands on the interplay between cognitive and motor functions. A well-functioning dual-tasking ability is thus essential for walking safely. The aims were to study longitudinal changes in gait function during single- and dual-tasking over a period of two years among people with initially mild AD (n=21). Data were collected on three occasions, twelve months apart. An optical motion capture system was used for three-dimensional gait analysis. Gait parameters were examined at comfortable gait speed during single-tasking, dual-tasking naming names, and naming animals. The dual-task cost for gait speed was pronounced at baseline (names 26%, animals 35%), and remained so during the study period. A significant (p<0.05) longitudinal decline in gait speed and step length during single- and dual-tasking was observed, whereas double support time, step width and step height showed inconsistent results. Systematic visual examination of the motion capture files revealed that dual-tasking frequently resulted in gait disturbances. Three main characteristics of such disturbances were identified: Temporal disturbance, Spatial disturbance and Instability in single stance. These aberrant gait performances may affect gait stability and increase the risk of falling. Furthermore, the observed gait disturbances can contribute to understanding and explaining previous reported gait variability among individuals with AD. However, the role that dual-task testing and aberrant dual-task gait performance play in the identification of individuals with early signs of cognitive impairment and in predicting fall risk in AD remains to be studied.


Slow wave sleep deficits as a trait marker in patients with schizophrenia.
Among the sleep abnormalities found in schizophrenia, slow wave sleep deficits have been found to persist even after the resolution of active psychotic symptoms. Further, such abnormalities are observed in young healthy individuals at high risk of schizophrenia, which suggest that slow wave sleep deficits might be trait marker in schizophrenia. Sleep EEG was recorded in 20 right handed patients aged 18-45 years with ICD-10 DCR diagnosis of schizophrenia, 14 first degree relatives and 20 age and sex matched controls. Patients were rated on Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) for assessment of psychopathology. There was significant difference between the three groups in total sleep period (p<.01), total sleep time (p<.01), stage shifts (p<.05), stage 1 percentage of total sleep time (p<.05), stage 2 duration (p<.05), stage 3 latency (p<.05), stage 4 duration (p<.01) and stage 4 percentage of total sleep time (p<.01). There was significant positive correlation of REM percentage of total sleep time with BPRS total score (r(s) = .488, p = .029) and PANSS positive score (r(s) = .583, p = .007), whereas significant negative correlation of REM latency was found with BPRS total score (r(s) = -.640, p = .002) and PANSS positive score (r(s) = -.657, p = .002) in the patients. Slow wave sleep deficits are a possible trait marker in patients with schizophrenia, which needs replication in further studies.


Polyploidy and hybridization as main factors of speciation: complex reticulate evolution within the grass genus Helictochloa.
To study the origin and evolution of naturally occurring polyploids, we performed phylogenetic analyses of nuclear ribosomal DNA spacers combined with molecular cytogenetics in 55 accessions of 27 taxa of the oat genus Helictochloa. A complex pattern of reticulate evolution was revealed with many diploid species and extensive polyploidy up to 20x. Altogether 11 groups of internal transcribed spacer (ITS) sequences can be distinguished. Sequences from 1-3 different ITS lineages were detected in polyploids. Cytogenetic data allow reconstruction of 8 basic monoploid chromosome sets. Six of these genomes occur in different combinations in the polyploid species. Two genomes are only found in diploids. Our sequence and karyological data highlight the occurrence of autopolyploidy and allopolyploidy, provide new information about the evolutionary history of taxa, and allow a more accurate systematic treatment of the concerned species. The geographical distribution of the 11 ITS lineages distinguished is highly structured and points to an origin of the genus in western Asia, presumably in grasslands like steppes or mountain steppes and meadows. The evolutionary basal lineages are of Asian, Minor Asian and east Mediterranean distribution and are present also in North America. The western and central parts of the Mediterranean and northern Europe harbor the modern lineages.


Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes.
Transgenic mice expressing the oncogene SV40 T antigen (Tag) in the insulin-producing beta cells of the pancreas develop islet cell carcinomas. Expression of the oncogene beginning in adult life leads to autoimmunity and lymphocytic infiltration of premalignant lesions. Nevertheless, Tag-expressing solid tumors escape the immune surveillance and are devoid of infiltrating lymphocytes. Attempting to elicit a tumor inflammatory response, we have both expressed a potent costimulator in oncogene-expressing beta cells and increased the abundance of reactive T cells. Coexpression of the costimulator B7.1 and the Tag oncoprotein leads to destruction of normal and premalignant islets and severe diabetes. Nevertheless, Tag+ tumors eventually develop, evidencing significantly reduced B7.1 expression and no infiltration. Another approach, whereby the abundance of reactive T cells was increased in double transgenic mice expressing Tag and a Tag-specific, CD4+-restricted T-cell receptor, was similarly unable to elicit tumor infiltration and destruction. Thus, neither costimulatory tumor cells nor hyperactivated antitumor lymphocytes were sufficient to produce an effective tumor immune response. In contrast, adoptive transfer of lymphocytes activated ex vivo did result in modest tumor infiltration with a limited induction of high endothelial venules on tumor vasculature, provided that T cells were transferred into irradiated recipients. However, adoptive transfer of ex vivo activated lymphocytes did not produce the dramatic inflammation seen in premalignant lesions. Thus, in addition to the parameters of activation and abundance of antitumor lymphocytes, the tumor microenvironment is evidently a critical parameter that can suppress lymphocyte extravasation and/or function inside tumors, likely in part via distinctive properties of the tumor vasculature.


Dimensional caging of polyiodides.
Two series of iodide and polyiodide chain structures have been synthesized through the employment of secondary interactions between polycation, long-chain, hydrocarbon cations. These compounds represent examples of crystal engineering, employing a simple strategy of synthesis. The two series are related, and the capacity to incorporate polyiodide ions dependent on the length of the hydrocarbon chains is indicated.


International comparison of treatment and long-term outcomes for acute myocardial infarction in the elderly: Minneapolis/St. Paul, MN, USA and Goteborg, Sweden.
International studies provide an opportunity to compare treatment approaches and outcomes. The present study compares elderly hospitalized acute myocardial infarction (AMI) patients in Minneapolis/St. Paul, USA (MSP) and Göteborg, Sweden (GB). A population-based sample of hospitalized AMI (ICD-9 410) patients aged ≥75 in MSP and GB in 2001-02 was abstracted by trained nurses. Mortality was ascertained from medical records and death certificates. Demographics, cardiovascular procedures, and prescription medications were compared using sex-specific generalized linear models. Adjusted hazard ratios (HR) were calculated with Cox regression. In MSP 839 (387 men, 452 women) and in GB 564 (275 men, 289 women) patients were identified. Age was similar (men: MSP 83 ± 7, GB 82 ± 5; women: MSP 84 ± 6, GB 84 ± 6) yet MSP patients had more previous cardiovascular comorbidities and procedures (PCI/CABG). Guideline-based medication use was high in both locations. MSP patients were significantly more likely to undergo PCI (men: MSP 33%, GB 7%; women: MSP 30%, GB 7%). Survival at 7.5 years was 27.8% among MSP patients (men: 26.6%, women: 28.8%) and 17.2% among GB patients (men: 17.5%, women: 17.0%). After adjustment for baseline characteristics and guideline-based therapies, survival was higher among MSP men [HR: 0.66, 95% confidence interval (CI): 0.50-0.88] and women (HR: 0.49, 95% CI: 0.36-0.67) compared with GB. In MSP and GB, guideline-based therapy use was high. However, PCI use was markedly higher in MSP. Long-term survival was better among elderly men and women in MSP compared with GB possibly related to greater utilization of PCI.


The impact of height on the risk of atrial fibrillation: the Cardiovascular Health Study.
Atrial fibrillation (AF) is the most common sustained arrhythmia. Increased body size has been associated with AF, but the relationship is not well understood. In this study, we examined the effect of increased height on the risk of AF and explore potential mediators and implications for clinical practice. We examined data from 5860 individuals taking part in the Cardiovascular Health Study, a cohort study of older US adults followed for a median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age-stratified Cox proportional hazards and risk models were used, with focus on the effect of height on both prevalent and incident AF. Among 684 (22.6%) and 568 (27.1%) incident cases in women and men, respectively, greater height was significantly associated with AF risk [hazard ratio (HR)(women) per 10 cm 1.32, confidence interval (CI) 1.16-1.50, P < 0.0001; HR(men) per 10 cm 1.26, CI 1.11-1.44, P < 0.0001]. The association was such that the incremental risk from sex was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32-1.65, without height, and HR 0.94, CI 0.85-1.20, with height included). Inclusion of height in the Framingham model for incident AF improved discrimination. In sequential models, however, we found minimal attenuation of the risk estimates for AF with adjustment for left ventricular (LV) mass and left atrial (LA) dimension. The associations of LA and LV size measurements with AF risk were weakened when indexed to height. Independent from sex, increased height is significantly associated with the risk of AF.


Ultrafiltered milk reduces bitterness in reduced-fat Cheddar cheese made with an exopolysaccharide-producing culture.
The objectives were to reduce bitterness in reduced-fat Cheddar cheese made with an exopolysaccharide (EPS)-producing culture and study relationships among ultra-filtration (UF), residual chymosin activity (RCA), and cheese bitterness. In previous studies, EPS-producing cultures improved the textural, melting, and viscoelastic properties of reduced-fat Cheddar cheese. However, the EPS-positive cheese developed bitterness after 2 to 3 mo of ripening due to increased RCA. We hypothesized that the reduced amount of chymosin needed to coagulate UF milk might result in reduced RCA and bitterness in cheese. Reduced-fat Cheddar cheeses were manufactured with EPS-producing and nonproducing cultures using skim milk or UF milk (1.2x) adjusted to a casein:fat ratio of 1.35. The EPS-producing culture increased moisture and RCA in reduced-fat Cheddar cheese. Lower RCA was found in cheese made from UF milk compared with that in cheese made from control milk. Ultrafiltration at a low concentration rate (1.2x) produced EPS-positive, reduced-fat cheese with similar RCA to that in the EPS-negative cheese. Slower proteolysis was observed in UF cheeses compared with non-UF cheeses. Panelists reported that UF EPS-positive cheese was less bitter than EPS-positive cheese made from control milk. This study showed that UF at a low concentration factor (1.2x) could successfully reduce bitterness in cheese containing a high moisture level. Because this technology reduced the RCA level (per g of protein) to a level similar to that in the control cheeses, the contribution of chymosin to cheese proteolysis would be similar in both cheeses.


Do bimanual coordination, tool use, and body posture contribute equally to hand preferences in bonobos?
Approximately 90% of the human population is right-handed. The emergence of this hand preference in humans is thought to be linked to the ability to execute complex tasks and habitual bipedalism. In order to test these hypotheses, the present study explored, for the first time, hand preference in relation to both body posture (seated and bipedal) and task complexity (bimanual coordination and two tool use tasks of different complexity) in bonobos (Pan paniscus). Few studies have explored the effects of both posture and task complexity on handedness, and investigations with bonobos are scarce, particularly studies on tool use. Our study aims to overcome such a gap by addressing two main questions: 1) Does a bipedal posture increase the strength of hand preference and/or create a directional bias to the use of the right hand? 2) Independent of body posture, does task complexity increase the strength of the hand preference and/or create a directional bias to the use of the right hand? Our results show that independent of body posture, the more complex the task, the more lateralization occurred. Moreover, subjects tended to be right-handed for tasks involving tool use. However, posture had no significant effect on hand preference in the tasks tested here. Therefore, for a given task, bonobos were not more lateralized in a bipedal posture than in a seated one. Task complexity might thus have contributed more than bipedal posture to the emergence of human lateralization and the preponderance of right-handedness, although a larger sample size and more data are needed to be conclusive.


Soil microorganisms as controllers of atmospheric trace gases (H2, CO, CH4, OCS, N2O, and NO).
Production and consumption processes in soils contribute to the global cycles of many trace gases (CH4, CO, OCS, H2, N2O, and NO) that are relevant for atmospheric chemistry and climate. Soil microbial processes contribute substantially to the budgets of atmospheric trace gases. The flux of trace gases between soil and atmosphere is usually the result of simultaneously operating production and consumption processes in soil: The relevant processes are not yet proven with absolute certainty, but the following are likely for trace gas consumption: H2 oxidation by abiontic soil enzymes; CO cooxidation by the ammonium monooxygenase of nitrifying bacteria; CH4 oxidation by unknown methanotrophic bacteria that utilize CH4 for growth; OCS hydrolysis by bacteria containing carbonic anhydrase; N2O reduction to N2 by denitrifying bacteria; NO consumption by either reduction to N2O in denitrifiers or oxidation to nitrate in heterotrophic bacteria. Wetland soils, in contrast to upland soils are generally anoxic and thus support the production of trace gases (H2, CO, CH4, N2O, and NO) by anaerobic bacteria such as fermenters, methanogens, acetogens, sulfate reducers, and denitrifiers. Methane is the dominant gaseous product of anaerobic degradation of organic matter and is released into the atmosphere, whereas the other trace gases are only intermediates, which are mostly cycled within the anoxic habitat. A significant percentage of the produced methane is oxidized by methanotrophic bacteria at anoxic-oxic interfaces such as the soil surface and the root surface of aquatic plants that serve as conduits for O2 transport into and CH4 transport out of the wetland soils. The dominant production processes in upland soils are different from those in wetland soils and include H2 production by biological N2 fixation, CO production by chemical decomposition of soil organic matter, and NO and N2O production by nitrification and denitrification. The processes responsible for CH4 production in upland soils are completely unclear, as are the OCS production processes in general. A problem for future research is the attribution of trace gas metabolic processes not only to functional groups of microorganisms but also to particular taxa. Thus, it is completely unclear how important microbial diversity is for the control of trace gas flux at the ecosystem level. However, different microbial communities may be part of the reason for differences in trace gas metabolism, e.g., effects of nitrogen fertilizers on CH4 uptake by soil; decrease of CH4 production with decreasing temperature; or different rates and modes of NO and N2O production in different soils and under different conditions.


Crystal structure of human DAAM1 formin homology 2 domain.
Reorganization of the actin filament is an essential process for cell motility, cell-cell attachment and intracellular transport. Formin proteins promote nucleation and elongation of the actin filament, and thus are key regulators for this process. The formin homology 2 (FH2) domain forms a head-to-tail ring-shaped dimer, and processively moves towards the barbed end. Dishevelled-associated activator of morphogenesis (DAAM) is a Rho-regulated formin implicated in neuronal development. Here, we present the crystal structure of human DAAM1 FH2 dimer at 2.8 A resolution. This is the first dimeric structure of the mammalian formin. The core structure of human DAAM1 is similar to those of mouse mDia1 and yeast Bni1p, whereas the orientations of the FH2 dimeric rings are different between human DAAM1 and yeast Bni1p, despite their similar dimer interactions. This difference supports the previous prediction that the dimer architecture of the formin is highly flexible in the actin-free state. The results of the actin assembly assays using the DAAM1 mutants demonstrated that the length of the linker connecting the N-terminal domain and the core region is crucial for the activity.


Interfacial rheometry of polymer at a water-oil interface by intra-pair magnetophoresis.
We describe an interfacial rheometry technique based on pairs of micrometer-sized magnetic particles at a fluid-fluid interface. The particles are repeatedly attracted and repelled by well-controlled magnetic dipole-dipole forces, so-called interfacial rheometry by intra-pair magnetophoresis (IPM). From the forces (∼pN), displacements (∼μm) and velocities (∼μm s(-1)) of the particles we are able to quantify the interfacial drag coefficient of particles within a few seconds and over very long timescales. The use of local dipole-dipole forces makes the system insensitive to fluid flow and suited for simultaneously recording many particles in parallel over a long period of time. We apply IPM to study the time-dependent adsorption of an oil-soluble amino-modified silicone polymer at a water-oil interface using carboxylated magnetic particles. At low polymer concentration the carboxylated particles remain on the water side of the water-oil interface, while at high polymer concentrations the particles transit into the oil phase. Both conditions show a drag coefficient that does not depend on time. However, at intermediate polymer concentrations data show an increase of the interfacial drag coefficient as a function of time, with an increase over more than three orders of magnitude (10(-7) to 10(-4) N s m(-1)), pointing to a strong polymer-polymer interaction at the interface. The time-dependence of the interfacial drag appears to be highly sensitive to the polymer concentration and to the ionic strength of the aqueous phase. We foresee that IPM will be a very convenient technique to study fluid-fluid interfaces for a broad range of materials systems.


Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients.
Underutilization of anticoagulant prophylaxis may be due to lack of evidence that prophylaxis prevents clinically important outcomes in hospitalized medical patients at risk for venous thromboembolism. To assess the effects of anticoagulant prophylaxis in reducing clinically important outcomes in hospitalized medical patients. MEDLINE, EMBASE, and Cochrane databases were searched to September 2006 without language restrictions. Randomized trials comparing anticoagulant prophylaxis with no treatment in hospitalized medical patients. Any symptomatic pulmonary embolism (PE), fatal PE, symptomatic deep venous thrombosis, all-cause mortality, and major bleeding. Pooled relative risks and associated 95% CIs were calculated. For treatment effects that were statistically significant, the authors determined the absolute risk reduction and the number needed to treat for benefit (NNT(B)) to prevent an outcome. 9 studies (n = 19 958) were included. During anticoagulant prophylaxis, patients had significant reductions in any PE (relative risk, 0.43 [CI, 0.26 to 0.71]; absolute risk reduction, 0.29%; NNT(B), 345) and fatal PE (relative risk, 0.38 [CI, 0.21 to 0.69]; absolute risk reduction, 0.25%; NNT(B), 400), a nonsignificant reduction in symptomatic deep venous thrombosis (relative risk, 0.47 [CI, 0.22 to 1.00]), and a nonsignificant increase in major bleeding (relative risk, 1.32 [CI, 0.73 to 2.37]). Anticoagulant prophylaxis had no effect on all-cause mortality (relative risk, 0.97 [CI, 0.79 to 1.19]). 2 of 9 included studies were not double-blind. Anticoagulant prophylaxis is effective in preventing symptomatic venous thromboembolism during anticoagulant prophylaxis in at-risk hospitalized medical patients. Additional research is needed to determine the risk for venous thromboembolism in these patients after prophylaxis has been stopped.


Non-invasive prenatal testing (NIPT) by low coverage genomic sequencing: Detection limits of screened chromosomal microdeletions.
To study the detection limits of chromosomal microaberrations in non-invasive prenatal testing with aim for five target microdeletion syndromes, including DiGeorge, Prader-Willi/Angelman, 1p36, Cri-Du-Chat, and Wolf-Hirschhorn syndromes. We used known cases of pathogenic deletions from ISCA database to specifically define regions critical for the target syndromes. Our approach to detect microdeletions, from whole genome sequencing data, is based on sample normalization and read counting for individual bins. We performed both an in-silico study using artificially created data sets and a laboratory test on mixed DNA samples, with known microdeletions, to assess the sensitivity of prediction for varying fetal fractions, deletion lengths, and sequencing read counts. The in-silico study showed sensitivity of 79.3% for 10% fetal fraction with 20M read count, which further increased to 98.4% if we searched only for deletions longer than 3Mb. The test on laboratory-prepared mixed samples was in agreement with in-silico results, while we were able to correctly detect 24 out of 29 control samples. Our results suggest that it is possible to incorporate microaberration detection into basic NIPT as part of the offered screening/diagnostics procedure, however, accuracy and reliability depends on several specific factors.


The controlled-environment chamber: a new mouse model of dry eye.
To develop a controlled-environment chamber (CEC) for mice and verify the effects of a low-humidity setting on ocular surface signs in normal mice. Eight- to 12-week-old BALB/c mice were used in a controlled-environment chamber (CEC) where relative humidity (RH), temperature (T), and airflow (AF) are regulated and monitored. Mice were placed into the CEC and exposed to specific environmentally controlled conditions (RH = 18.5% +/- 5.1%, AF = 15 L/min, T = 21-23 degrees C) for 3, 7, 14, and 28 days. Control mice were kept in a normal environment (RH = 50%-80%, no AF, T = 21-23 degrees C) for the same duration. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (score, 0-15), and goblet cell density in the superior and inferior conjunctiva were measured by a masked observer. No statistically significant differences between the groups were found at baseline. Decreased tear secretion and increased corneal fluorescein staining were significantly present on day 3, 7, 14, and 28 in animals kept in the CEC. Goblet cell density was significantly decreased in the superior conjunctiva on day 7, and on day 3, 7, and 14 in the inferior conjunctiva in the CEC-kept mice compared with control animals. This study indicates that exposure of normal mice to a low-humidity environment in a CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs.


Theoretical study of the reaction of vitamin B6 with 1O2.
Singlet oxygen is known to cause oxidative stress in cells, leading to severe damage (e.g., lipid peroxidation, membrane degradation, mutagenic alterations to DNA, protein misfunctionality). Recently, pyridoxine has been discovered to be capable of quenching singlet oxygen, however, the mechanism of this reaction remains essentially unknown. In this work, we have investigated four sets of reactions: 1) 1,3-addition to a double bond connected to a hydrogen-carrying group, resulting in the formation of allylic hydroperoxides; 2) [pi2+pi2] 1,2-cycloaddition to an isolated double bond, resulting in the formation of 1,2-peroxides; 3) 1,4-cycloaddition to a system containing at least two conjugated double bonds, resulting in the formation of the so-called 1,4-peroxides; 4) 1,4-addition to phenols and naphthols with the formation of hydroperoxide ketones. Thermodynamically, reaction 4 and the 6(9), 3(8), and 5(8) cases of reaction 1 are the most exergonic ones, with energies ranging from -16 to -18 kcal mol(-1). Furthermore, reaction 4 shows the lowest barrier through the reaction path, and is predicted to be the preferred mechanism for the pyridoxine + singlet-oxygen reaction, which is in agreement with previous experimental results.


The economic burden of endoscopic treatment for anastomotic leaks following oncological Ivor Lewis esophagectomy.
Complications after surgery for esophageal cancer are associated with significant resource utilization. The aim of this study was to analyze the economic burden of two frequently used endoscopic treatments for anastomotic leak management after esophageal surgery: Treatment with a Self-expanding Metal Stent (SEMS) and Endoscopic Vacuum Therapy (EVT). Between January 2012 and December 2016, we identified 60 German-Diagnosis Related Group (G-DRG) cases of patients who received a SEMS and / or EVT for esophageal anastomotic leaks. Direct costs per case were analyzed according to the Institute for Remuneration System in Hospitals (InEK) cost-accounting approach by comparing DRG payments on the case level, including all extra fees per DRG catalogue. In total, 60 DRG cases were identified. Of these, 15 patients were excluded because they received a combination of SEMS and EVT. Another 6 cases could not be included due to incomplete DRG data. Finally, N = 39 DRG cases were analyzed from a profit-center perspective. A further analysis of the most frequent DRG code -G03- including InEK cost accounting, revealed almost twice the deficit for the EVT group (N = 13 cases, € - 9.282 per average case) compared to that for the SEMS group (N = 9 cases, € - 5.156 per average case). Endoscopic treatments with SEMS and EVT for anastomotic leaks following oncological Ivor Lewis esophagectomies are not cost-efficient for German hospitals. Due to longer hospitalization and insufficient reimbursements, EVT is twice as costly as SEMS treatment. An adequate DRG cost compensation is needed for SEMS and EVT.


Dynamic imaging in living cells: windows into local signaling.
Highly localized changes in intracellular calcium concentration [Ca2+]i play a critical role in regulating numerous cellular functions, ranging from muscle contraction to neurotransmitter and hormone secretion to gene transcription. Fluorescent Ca2+ indicators have been invaluable tools in elucidating the role of localized changes in [Ca2+]i in regulating ion channels and other key proteins in various signaling pathways. Other techniques used to investigate localized changes in [Ca2+]i include approaches based on fluorescence resonance energy transfer, and electrophysiological measurements of ionic flux through Ca2+-sensitive channels. This Perspective discusses research using fluorescent Ca2+ indicators to study excitation-contraction coupling in cardiac myocytes, presenting both key findings and limitations of this approach. Complementary approaches useful in studying localized changes in Ca2+ and other second messengers (such as cyclic adenosine monophosphate) are also discussed.


Mutations affecting development of the notochord in zebrafish.
The notochord is critical for the normal development of vertebrate embryos. It serves both as the major skeletal element of the embryo and as a signaling source for the establishment of pattern within the neurectoderm, the paraxial mesoderm and other tissues. In a large-scale systematic screen of mutations affecting embryogenesis in zebrafish we identified 65 mutations that fall into 29 complementation groups, each leading to a defect in the formation and/or maintenance of the notochord. These mutations produce phenotypic abnormalities at numerous stages of notochord development, thereby establishing a phenotypic pathway, which in turn suggests a genetic pathway for the development of the notochord. Perturbations within adjacent tissues in mutant embryos further indicate the importance of notochord-derived signals for patterning within the embryo and suggest that these mutations will yield additional insight into the cues that regulate these patterning processes.


Measurement Issues: Review of four patient reported outcome measures: SDQ, RCADS, C/ORS and GBO - their strengths and limitations for clinical use and service evaluation.
There is an international drive for routine use of Patient Reported Outcome Measures (PROMs) across all health services including in relation to Child and Adolescent Mental Health Services (CAMHS). A number of reviews have summarized the validity and reliability of well-being and mental health measures for children but there are fewer attempts to consider utility for routine use. This review considers four child self-report measures: the Strengths and Difficulties Questionnaire (SDQ), the Revised Child Anxiety and Depression Scale (RCADS), (Child) Outcomes Rating Scale (C/ORS) and Goals Based Outcomes (GBOs). It explores the strengths and limitations of each and considers how they can be used to support both clinical practice and service evaluation. There is evidence for the clinical utility of RCADS, C/ORS and GBOs, although the utility of the SDQ as a feedback measure remains unclear. For service evaluation, the SDQ has the greatest evidence for norms making it useful for comparison and there is evidence that the RCADS may be the most sensitive to change of the measures reviewed; C/ORS has issues around ceiling effect, data error and data manipulation. More research is required around GBOs before their use for service evaluation can be determined. In summary, these different measures may be viewed as complementary tools and determining the best way to make use of them severally and individually in clinical and community settings is a current focus for child mental health practitioners.


Association of LOX gene G473A polymorphism with the occurrence of allergic rhinitis and efficacy of montelukast sodium in children.
Allergic rhinitis (AR) is very common in adolescents, and current treatment options are complex and unsatisfactory. The objective of this study was to analyze the association of lysyl oxidase (LOX) gene G473A polymorphism with susceptibility to AR in children. In addition, we analyzed the therapeutic effect of montelukast sodium on AR. Forty-five children with AR (research group, 8.16±2.88 years old) and 51 healthy children (control group, 8.22±3.87 years old) during the same period were selected. The LOX gene G473A polymorphism was detected with polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The effect of G473A polymorphism in the occurrence of AR was assessed by logistic regression analysis. In addition, the levels of C-reactive protein (CRP), Interleukin (IL-6), and IL-8 were measured to observe the relationship between G473A polymorphism and inflammatory factors. Finally, montelukast sodium was given to children with AR to investigate the effect of G473A polymorphism on clinical outcomes. The number of G473A polymorphisms in the research group was not significantly different from the control group for GA-type (P = 0.521). However, the number of GG-type polymorphisms was less while the number of type AA was more than the control group (P = 0.044 and 0.046). Children carrying the AA gene had an approximately 4-fold increased risk of AR, while those carrying the GG gene had a decreased risk (P < 0.001). Moreover, children carrying the GG gene had lower levels of CRP, IL-6, and IL-8 and better clinical outcomes, while those carrying the AA gene had higher levels of inflammatory factors and worse outcomes (P<0.05). LOX gene G473A polymorphism is closely associated with AR pathogenesis and may have an important research value in antagonizing the therapeutic effect of montelukast sodium.


Orphanin FQ/nociceptin blocks cocaine-induced behavioral sensitization in rats.
Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, shows similarities to dynorphin A (1-17) in structure and functions. Dynorphin and other kappa opioid receptor agonists have been shown to block cocaine sensitization. The present study was designed to examine the ability of OFQ/N to block cocaine-induced behavioral sensitization. Rats were habituated to testing chambers for 1 h, injected with artificial cerebrospinal fluid (aCSF) or OFQ/N (15 nmol) followed by saline or cocaine (20 mg/kg) and locomotor activity was measured for a further 1 h. Rats were treated similarly for the next 2 days except the dose of OFQ/N was doubled on each subsequent day. Rats were then challenged with cocaine (7.5 mg/kg) in the absence of OFQ/N on day 8. The specificity of OFQ/N's action was examined in the presence of J-113397 (30 nmol), an ORL-1 receptor antagonist. The ability of OFQ/N to block the context-independent component of cocaine sensitization was also tested wherein rats were treated in their home cages on days 1-3. Finally, the effect of intra-VTA OFQ/N administration on cocaine sensitization was examined. Sensitization did not develop in rats repeatedly treated with OFQ/N, via either route of administration, prior to cocaine administration on days 1-3. The inhibitory effect of OFQ/N was not dependent on context and was blocked by pretreatment with J-113397. Our results indicate that OFQ/N blocks cocaine-induced behavioral sensitization through activation of the ORL-1 receptor and that the VTA may be one of the substrates for this action of OFQ/N.


PPCS: A Progressive Popularity-Aware Caching Scheme for Edge-Based Cache Redundancy Avoidance in Information-Centric Networks.
This article proposes a novel chunk-based caching scheme known as the Progressive Popularity-Aware Caching Scheme (PPCS) to improve content availability and eliminate the cache redundancy issue of Information-Centric Networking (ICN). Particularly, the proposal considers both entire-object caching and partial-progressive caching for popular and non-popular content objects, respectively. In the case that the content is not popular enough, PPCS first caches initial chunks of the content at the edge node and then progressively continues caching subsequent chunks at upstream Content Nodes (CNs) along the delivery path over time, according to the content popularity and each CN position. Therefore, PPCS efficiently avoids wasting cache space for storing on-path content duplicates and improves cache diversity by allowing no more than one replica of a specified content to be cached. To enable a complete ICN caching solution for communication networks, we also propose an autonomous replacement policy to optimize the cache utilization by maximizing the utility of each CN from caching content items. By simulation, we show that PPCS, utilizing edge-computing for the joint optimization of caching decision and replacement policies, considerably outperforms relevant existing ICN caching strategies in terms of latency (number of hops), cache redundancy, and content availability (hit rate), especially when the CN's cache size is small.


eVOC: a controlled vocabulary for unifying gene expression data.
Expression data contribute significantly to the biological value of the sequenced human genome, providing extensive information about gene structure and the pattern of gene expression. ESTs, together with SAGE libraries and microarray experiment information, provide a broad and rich view of the transcriptome. However, it is difficult to perform large-scale expression mining of the data generated by these diverse experimental approaches. Not only is the data stored in disparate locations, but there is frequent ambiguity in the meaning of terms used to describe the source of the material used in the experiment. Untangling semantic differences between the data provided by different resources is therefore largely reliant on the domain knowledge of a human expert. We present here eVOC, a system which associates labelled target cDNAs for microarray experiments, or cDNA libraries and their associated transcripts with controlled terms in a set of hierarchical vocabularies. eVOC consists of four orthogonal controlled vocabularies suitable for describing the domains of human gene expression data including Anatomical System, Cell Type, Pathology and Developmental Stage. We have curated and annotated 7016 cDNA libraries represented in dbEST, as well as 104 SAGE libraries,with expression information,and provide this as an integrated, public resource that allows the linking of transcripts and libraries with expression terms. Both the vocabularies and the vocabulary-annotated libraries can be retrieved from http://www.sanbi.ac.za/evoc/. Several groups are involved in developing this resource with the aim of unifying transcript expression information.


Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data.
Mycobacterium tuberculosis rapid diagnostic tests (RDTs) are widely employed in routine laboratories and national surveys for detection of rifampicin-resistant (RR)-TB. However, as next-generation sequencing technologies have become more commonplace in research and surveillance programs, RDTs are being increasingly complemented by whole genome sequencing (WGS). While comparison between RDTs is difficult, all RDT results can be derived from WGS data. This can facilitate continuous analysis of RR-TB burden regardless of the data generation technology employed. By converting WGS to RDT results, we enable comparison of data with different formats and sources particularly for low- and middle-income high TB-burden countries that employ different diagnostic algorithms for drug resistance surveys. This allows national TB control programs (NTPs) and epidemiologists to utilize all available data in the setting for improved RR-TB surveillance. We developed the Python-based MycTB Genome to Test (MTBGT) tool that transforms WGS-derived data into laboratory-validated results of the primary RDTs-Xpert MTB/RIF, XpertMTB/RIF Ultra, GenoType MDRTBplus v2.0, and GenoscholarNTM+MDRTB II. The tool was validated through RDT results of RR-TB strains with diverse resistance patterns and geographic origins and applied on routine-derived WGS data. The MTBGT tool correctly transformed the single nucleotide polymorphism (SNP) data into the RDT results and generated tabulated frequencies of the RDT probes as well as rifampicin-susceptible cases. The tool supplemented the RDT probe reactions output with the RR-conferring mutation based on identified SNPs. The MTBGT tool facilitated continuous analysis of RR-TB and Xpert probe reactions from different platforms and collection periods in Rwanda. Overall, the MTBGT tool allows low- and middle-income countries to make sense of the increasingly generated WGS in light of the readily available RDT results, and assess whether currently implemented RDTs adequately detect RR-TB in their setting. With its feature to transform WGS to RDT results and facilitate continuous RR-TB data analysis, the MTBGT tool may bridge the gap between and among data from periodic surveys, continuous surveillance, research, and routine tests, and may be integrated within the national information system for use by the NTP and epidemiologists to improve setting-specific RR-TB control. The MTBGT source code and accompanying documentation are available at https://github.com/KamelaNg/MTBGT.


Cargo transport: two motors are sometimes better than one.
Molecular motor proteins are crucial for the proper distribution of organelles and vesicles in cells. Much of our current understanding of how motors function stems from studies of single motors moving cargos in vitro. More recently, however, there has been mounting evidence that the cooperation of multiple motors in moving cargos and the regulation of motor-filament affinity could be key mechanisms that cells utilize to regulate cargo transport. Here, we review these recent advances and present a picture of how the different mechanisms of regulating the number of motors moving a cargo could facilitate cellular functions.


Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency.
Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed to control this current pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV). RDV shows broad-spectrum antiviral activity against RNA viruses, and previous studies with RdRps from Ebola virus and Middle East respiratory syndrome coronavirus (MERS-CoV) have revealed that delayed chain termination is RDV's plausible mechanism of action. Here, we expressed and purified active SARS-CoV-2 RdRp composed of the nonstructural proteins nsp8 and nsp12. Enzyme kinetics indicated that this RdRp efficiently incorporates the active triphosphate form of RDV (RDV-TP) into RNA. Incorporation of RDV-TP at position i caused termination of RNA synthesis at position i+3. We obtained almost identical results with SARS-CoV, MERS-CoV, and SARS-CoV-2 RdRps. A unique property of RDV-TP is its high selectivity over incorporation of its natural nucleotide counterpart ATP. In this regard, the triphosphate forms of 2'-C-methylated compounds, including sofosbuvir, approved for the management of hepatitis C virus infection, and the broad-acting antivirals favipiravir and ribavirin, exhibited significant deficits. Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed. These results collectively provide a unifying, refined mechanism of RDV-mediated RNA synthesis inhibition in coronaviruses and define this nucleotide analogue as a direct-acting antiviral.


Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation.
Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside.


Adult pancreatic hemangioma in pregnancy--concerns and considerations of a rare case.
Pancreatic tumors in pregnancy are rare but clinically challenging. Careful diagnostic workup, including appropriate imaging examinations, should be performed to evaluate surgery indications and timing . In the present case a diagnosis of an adult pancreatic hemangioma was made. We were not able to identify a similar case in the very sparse literature on this rare disease. A 30-year-old woman at 12 weeks of gestation was diagnosed with a large pancreatic tumor having a cystic pattern based on imaging. Although the preoperative diagnosis was uncertain, patient preference and clinical symptoms and signs suggested surgery. Open distal pancreatic resection including splenectomy was performed, and complete resection of the large cystic tumor was successfully achieved, with no postoperative complications. Although a solid pseudopapillary epithelial neoplasm (SPEN) was suspected, specimen morphology, including immunohistochemistry, supported the diagnosis of an adult benign pancreatic hemangioma. Although mucinous cystic neoplasm (MCN) and adenocarcinoma are the most common pancreatic tumors during pregnancy, various other malignant and benign lesions can be encountered. This report adds to the very small number of pancreatic hemangiomas reported in the literature and involves the first patient diagnosed with this rare condition during pregnancy. Careful clinical considerations regarding diagnostic workup and treatments are required to ensure that mother and child receive the best possible care.


Whole genome sequence analysis of blood lipid levels in >66,000 individuals.
Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.


Improving handoff communications in critical care: utilizing simulation-based training toward process improvement in managing patient risk.
A patient admitted to the medical step-down unit experienced severe hypoglycemia due to an infusion of a higher-than-ordered insulin dose. The event could have been prevented if the insulin syringe pump was checked during the nursing shift handoff. Risk management exploration included direct observations of nursing shift handoffs, which highlighted common deficiencies in the process. This led to the development and implementation of a handoff protocol and the incorporation of handoff training into a simulation-based teamwork and communication workshop. A second round of observations took place 6 to 8 weeks following training. The intervention demonstrated an increase in the incidence of nurses communicating crucial information during handoffs, including patient name, events that had occurred during the previous shift, and treatment goals for the next shift. However, there was no change in the incidence of checking the monitor alarms and the mechanical ventilator. Simulation-based training can be incorporated into the risk management process and can contribute to patient safety practice.


Quality-factor enhancement of supermodes in coupled microdisks.
We investigate the optical modes in a coupled pair of semiconductor microdisks in symmetric and asymmetric configurations both experimentally and theoretically. While the quality factors of coupled first- and second-order whispering gallery modes (WGMs) show a conventional crossing, the quality factors of the same-order WGMs reveal an interesting splitting behavior, leading to the formation of high- and low-quality supermodes. Our results are reproduced by numerical simulations, and an explanation based on optical interference is suggested. Quality-factor splitting is a subtle phenomenon that might help to design microarchitectures for efficient optical coupling in cavity quantum electrodynamic experiments.


Effect of the Chain Length of a Modified Layer and Surface Roughness of an Electrode on Impedimetric Immunosensors.
An ultrasensitive label-free impedimetric immunosensor is constructed by modifying a 3-mercaptoproponic acid (MPA) monolayer on highly rough gold nanostructure (AuNS)-electrodeposited screen printed carbon electrodes (SPCEs) for the detection of small molecular weight drugs (SMWDs), such as salbutamol (SAL). The SPCEs preoxidized in a 0.1 M H2SO4 solution (called po-SPCEH2SO4) are electrodeposited with the AuNS to increase the roughness factor to 23.64 ± 1.76, larger than the AuNS/po-SPCENaOH or the AuNS/po-SPCEPBS. Furthermore, the MPA modified layer as a link for the anti-SAL immobilization to give the immunosensors an impedimetric signal-to-noise ratio larger than the 11-mercapto-undecanoic acid- and 16-mercaptohexadecanoic acid-modified layer, due to the lower interfacial impedance of the MPA monolayer. The MPA/AuNS/po-SPCEH2SO4-based immunosensors have a wide linear range of 1 fg mL-1 to 1 ng mL-1 and a limit of detection of 0.6 fg mL-1. Moreover, the immunosensors can practically quantify the SAL concentrations in 1000 times-diluted serum samples with good recovery.


Relaxed DM requirements during class II peptide loading and CD4+ T cell maturation in BALB/c mice.
Current ideas about DM actions have been strongly influenced by studies of mutant strains expressing the H-2(b) haplotype. To evaluate DM contributions to class II activities in BALB/c mice, we generated a novel mutation at the DMa locus via embryonic stem cell technology. Unlike long-lived A(b)/class II-associated invariant chain-derived peptide (CLIP) complexes, mature A(d) and E(d) molecules are loosely occupied by class II-associated invariant chain-derived peptide and are SDS unstable. BALB/c DM mutants weakly express BP107 conformational epitopes and toxic shock syndrome toxin-1 superantigen-binding capabilities, consistent with partial occupancy by wild-type ligands. Near normal numbers of mature CD4(+) T cells fail to undergo superantigen-mediated negative selection, as judged by TCR Vbeta usage. Ag presentation assays reveal consistent differences for A(d)- and E(d)-restricted T cells. Indeed, the mutation leads to decreased peptide capture by A(d) molecules, and in striking contrast causes enhanced peptide loading by E(d) molecules. Thus, DM requirements differ for class II structural variants coexpressed under physiological conditions in the intact animal.


Increasing suppression of saccade-related transients along the human visual hierarchy.
A key hallmark of visual perceptual awareness is robustness to instabilities arising from unnoticeable eye and eyelid movements. In previous human intracranial (iEEG) work (Golan et al., 2016) we found that excitatory broadband high-frequency activity transients, driven by eye blinks, are suppressed in higher-level but not early visual cortex. Here, we utilized the broad anatomical coverage of iEEG recordings in 12 eye-tracked neurosurgical patients to test whether a similar stabilizing mechanism operates following small saccades. We compared saccades (1.3°-3.7°) initiated during inspection of large individual visual objects with similarly-sized external stimulus displacements. Early visual cortex sites responded with positive transients to both conditions. In contrast, in both dorsal and ventral higher-level sites the response to saccades (but not to external displacements) was suppressed. These findings indicate that early visual cortex is highly unstable compared to higher-level visual regions which apparently constitute the main target of stabilizing extra-retinal oculomotor influences.


Iron deficiency anaemia and aspirin use in old age.
Aspirin is being increasingly prescribed for cardiovascular protection, but is also recognized to have significant gastrointestinal side-effects. Whether chronic aspirin consumption causes iron deficiency is undetermined, and there is little information available regarding iron deficiency and aspirin use in old age. We studied the relationship between iron deficiency anaemia and regular aspirin prescription in old age.


The shoulder in patients with muscular dystrophy.
Shoulder weakness and instability are not usually a major part of the clinical picture of muscular dystrophies. Problems usually do not arise until the patient is wheelchair bound, at which time assistive appliances may be required. The majority of orthopaedic intervention is confined to the rare facioscapulohumeral dystrophy. Facioscapulohumeral dystrophy causes muscular weakness of the face, shoulder girdle, and upper arm with selective sparing of the deltoid muscle. This leads to scapular winging and a marked decrease in flexion and abduction of the shoulder. As the muscles stabilizing the scapula become involved, the scapula starts to wing. The deltoid is spared, but its action is wasted because of the unstable scapula. The deltoid contracts and the arm attempts to move in a normal fashion, but because the scapula is no longer stable, it wings and rotates under the forces of the long lever arm of the upper limb and scapula complex. Mechanical fixation of the scapula to the thoracic wall provides a stable fulcrum on which the deltoid can exert its powerful action on the humerus and abduct the arm without rotation of the scapula. Twenty thoracoscapular fusions were performed on 13 patients. Ten patients (14 shoulders) were available for long term followup. The long term results showed that this operation is successful in achieving stability of the scapula, while greatly improving function and cosmesis. Although the course of this type of muscular dystrophy is variable, the benefits of surgery have not deteriorated with progression of the disease during a maximum followup of 44 years.


Purification and characterization of a mannose-containing disaccharide obtained from human pregnancy urine. A new immunoregulatory saccharide.
Endogenous mammalian lectin-like sugar-binding molecules have been previously described that have immunoregulatory properties. Further, the addition of defined simple saccharides to lymphocyte cultures has been shown to inhibit a variety of in vitro lymphocyte functions, presumably because these sugars are able to compete with the binding of endogenous lectins to critical membrane receptors. In this report, we describe the isolation and characterization of a D-mannose-containing disaccharide in human pregnancy urine that inhibits the proliferative response of human T lymphocytes. The inhibitory disaccharide was purified to homogeneity by sequential steps including affinity chromatography on immobilized concanavalin A and molecular sizing on Sephadex G-75 and then Fractogel 40S columns, with final purification on high-performance thin-layer chromatography. By mass spectrometry of the purified material as its permethylated derivative, the deduced structure of this compound was alpha-D-Manp 1-6-D-Man. To confirm that this disaccharide was in fact immunosuppressive, an identical disaccharide was prepared by sequential digestion of yeast cell wall polysaccharide. The urinary and yeast disaccharides had identical immunosuppressive properties. It has been previously reported that D-mannose is inhibitory for antigen-specific proliferative assays in the range of 10-50 mM. The purified alpha-D-Manp 1-6-D-Man disaccharide was inhibitory at 100-fold-lower concentrations. Further, while D-mannose inhibits T cell proliferation when added at anytime up to 24 h before harvest of a 6-d lymphocyte culture, alpha-D-Manp 1-6-D-Man disaccharide was inhibitory only if added at the initiation of culture and had no inhibitory effect if added just 24 h later. These data support the concept that simple sugar compounds can exhibit marked immunoregulatory activity in vitro. The impact of these molecules on the regulation of immune responses in vivo is unknown, as is their precise mechanism of action, but structural and chemical identification should now permit a detailed analysis of these issues.


The Upper Paleolithic triple burial of Dolní Vestonice: pathology and funerary behavior.
This work focuses on paleopathological analysis of one of the skeletons from the Gravettian triple burial of Dolní Vestonice (Moravia) and addresses issues of Upper Paleolithic funerary behavior. The burial includes the well-preserved skeletons of three young individuals. The skeleton in the middle (DV 15) is pathological and very problematic to sex; the other two (DV 13 and DV 14) are males and lie in an unusual position. The young age, the possibility of a simultaneous interment, and the position of the three specimens have given rise to speculations about the symbolic significance of this spectacular and intriguing funerary pattern. The pathological condition of the skeleton in the middle further emphasizes its peculiarity. Main pathological changes of the DV 15 skeleton include: asymmetric shortening of the right femur and of left forearm bones, bowing of the right femur, right humerus, and left radius, elongation of fibulae, dysplasias of the vertebral column, and very marked enamel hypoplasias. Scrutiny of the medical literature suggests that the most likely etiology is chondrodysplasia calcificans punctata (CCP) complicated by trauma and early fractures of the upper limbs. CCP is a rare inherited disorder characterized by stippled ossification of the epiphyses. The cartilaginous stippling is a transient phenomenon that disappears during infancy, leaving permanent deformities on affected bones. Among the different forms of CCP, the X-linked dominant form is that resulting in asymmetric shortening and is lethal during early infancy in males. Thus, survival of DV 15 until young adult age would require the specimen to be a female. Clinical findings often associated with the disease (erythemas, ichthyosis, alopecia, cataracts, and joint contractures, among others) would emphasize the singular aspect of this individual, pointing to a condition that should be carefully taken into account when speculating on the significance of that peculiar burial.


Complementary and alternative medicine use in thalassemia patients in Shiraz, southern Iran: A cross-sectional study.
This study aimed to determine the frequency and pattern of complementary and alternative medicine (CAM) use in thalassemia patients in south of Iran. The survey was done using a validated questionnaire which was distributed among 122 thalassemia patients. Only 108 questionnaires were completed and turned back (response rate 88.5%). Patients referred to an outpatient thalassemia clinic in Shiraz, southern Iran for blood transfusion. The mean age of the patients was 22.9 ± 7.9 years (range 4-45 years) with female/male ratio 1.84. Seventy four (68.5%) of the responders used CAM at least once during their life, and about half of them used it concurrently with their conventional treatments. The most reported CAM product was mint juice (50%). The most common reason of CAM use was increased general health. The most common information source about CAM was physicians who were the most trusted source as well. CAM is frequently being used in thalassemia patients to ensure their sense of well-being and help them overcome the complications of their illnesses.


The road to elimination of hepatitis C: analysis of cures versus new infections in 91 countries.
Hepatitis C (HCV) can only be eradicated if annual rates of cure (SVR) are consistently and significantly higher than new HCV infections, across many countries. In 2016, the WHO called for a 90% reduction in new HCV infection by 2030. Direct-acting antivirals (DAA) can cure the majority of those treated, at around 90% in most populations, at potentially very low prices. We compared the net annual change in epidemic size across 91 countries using data on SVR, new HCV infections, and deaths. In a further 109 countries, we projected this figure using regional averages of epidemic size. Epidemiological data for 2016 were extracted from national reports, publications and the Polaris Observatory. There were 91/210 countries with data on SVR, HCV-related deaths and new infections available for analysis; 109 countries had net change in epidemic size projected from the regional prevalence of HCV, extrapolated to their population size. 'Net cure' was defined as the number of people with SVR, minus new HCV infections, plus HCV-related deaths in 2016. For the 91 countries analysed, there were 57.3 million people with chronic HCV infection in 2016. In the remaining 109 countries, the projected epidemic size was 12.2 million, giving a global epidemic size of 69.6 million. Across the 91 countries, there was a fall from 57.3 to 56.9 million people in 2017, a 0.7% reduction. The projected global net change was from 69.6 to 69.3 million, a 0.4% reduction. Ten countries had at least five times more people reaching SVR than new HCV infections, including Egypt and USA. In 47/91 countries, there were more HCV infections than SVR in 2016. Very few countries are on target to achieve elimination of HCV as a public health problem by 2030. While the North American, North African/Middle East and Western European regions have shown small declines in prevalence, the epidemic is growing in sub-Saharan Africa and Eastern Europe. Far higher rates of DAA treatment are required for worldwide elimination of HCV.


Trends and Correlates of Hookah Use Among High School Students in North Carolina.
OBJECTIVES Although youth cigarette smoking has declined in the United States, use of alternative tobacco products, such as hookah, has increased. This study assesses changes in prevalence of use from 2011 to 2013, and examines factors associated with current hookah use among North Carolina high school students in 2013.METHODS Data came from the North Carolina Youth Tobacco Survey in 2011 (n = 4,791) and 2013 (n = 4,092). STATA (StataCorp LLC) logistic regression survey procedures account for the complex survey design and sampling weights.RESULTS Prevalence of reported current hookah use significantly increased from 3.6% (95% CI: 2.8-4.5) in 2011 to 6.1% (95% CI: 4.9-7.5) in 2013 while reported lifetime hookah use increased from 9.8% (95% CI: 8.0-12.0) in 2011 to 12.6% (95% CI: 11.0-14.4) in 2013. Correlates of current hookah use included having a weekly disposable income over $50 (adjusted odds ratio (AOR) = 2.05, 95% CI: 1.25-3.35), currently smoking cigarettes (AOR = 4.57, 95% CI: 1.80-11.62), and living with hookah users (AOR = 6.45, 95% CI: 3.21-12.93). Participant self-reports of "liking" or positively commenting on tobacco products on social media were associated with current hookah use (AOR = 1.83, 95% CI: 1.84-4.52). Frequent exposure to online tobacco advertisements (AOR = 1.61, 95% CI: 1.13-2.28) were also associated with current hookah use.CONCLUSIONS Comprehensive product specific communication and policy interventions are needed to educate youth about the dangers of hookah use and reduce social acceptability among youth. To decrease hookah use in North Carolina, policymakers should consider restoring funding for comprehensive tobacco prevention and control programs, and equalizing tobacco tax rates for all tobacco product types.


Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon.
Peptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.


Development of a technique for the in vivo assessment of flatulence in dogs.
To develop a noninvasive method for the in vivo assessment of flatulence in dogs. 8 adult dogs. Rectal gases were collected via a perforated tube held close to each dog's anus and attached to a monitoring pump fitted with a sensor that recorded hydrogen sulfide concentrations every 20 seconds. Patterns of flatulence were monitored for 14 hours after feeding on 4 days, and within- and between-dog variation was assessed over 4 hours on 4 consecutive days. Rate of hydrogen sulfide production (flatulence index) and frequency and number of emissions were evaluated as potential indicators of flatus characteristics. An odor judge assigned an odor rating to each flatulence episode, and the relationship between that rating and hydrogen sulfide concentration was determined. Flatulence patterns varied within and between dogs. Variation was most pronounced for flatulence index; mean coefficients of variance within dogs over time and between dogs on each day were 75 and 103%, respectively. Flatus with hydrogen sulfide concentrations > 1 parts per million could be detected by the odor judge, and severity of malodor was highly correlated with hydrogen sulfide concentration. Odor ratings were accurately predicted by use of the equation 1.51 X hydrogen sulfide concentration(0.28). The technique described in this report appears to provide sensitive, reliable, and relevant data and will enable further studies of the factors that influence flatulence in dogs. Use of this technique also has the potential to aid in investigations of colonic physiology and pathology.


De novo synthesis and degradation of Lx and V cycle pigments during shade and sun acclimation in avocado leaves.
The photoprotective role of the universal violaxanthin cycle that interconverts violaxanthin (V), antheraxanthin (A), and zeaxanthin (Z) is well established, but functions of the analogous conversions of lutein-5,6-epoxide (Lx) and lutein (L) in the selectively occurring Lx cycle are still unclear. We investigated carotenoid pools in Lx-rich leaves of avocado (Persea americana) during sun or shade acclimation at different developmental stages. During sun exposure of mature shade leaves, an unusual decrease in L preceded the deepoxidation of Lx to L and of V to A+Z. In addition to deepoxidation, de novo synthesis increased the L and A+Z pools. Epoxidation of L was exceptionally slow, requiring about 40 d in the shade to restore the Lx pool, and residual A+Z usually persisted overnight. In young shade leaves, the Lx cycle was reversed initially, with Lx accumulating in the sun and declining in the shade. De novo synthesis of xanthophylls did not affect alpha- and beta-carotene pools on the first day, but during long-term acclimation alpha-carotene pools changed noticeably. Nonetheless, the total change in alpha- and beta-branch carotenoid pools was equal. We discuss the implications for regulation of metabolic flux through the alpha- and beta-branches of carotenoid biosynthesis and potential roles for L in photoprotection and Lx in energy transfer to photosystem II and explore physiological roles of both xanthophyll cycles as determinants of photosystem II efficiency.


Treatment recommendation differences for schizophrenia and major depression: a population-based study in a Vietnamese cohort.
In Vietnam, the mental health care infrastructure is on the verge of transformation with an increase in the demand for access to adequate and effective mental health care services. Public attitudes towards mental illness, as well as corresponding treatment options influence help-seeking behaviors of patients and caregivers, affecting the course of their treatment. This study assesses attitudes towards treatment options for depression and schizophrenia, as the two most common psychiatric disorders in Vietnam, accounting for at least 75% of all psychiatric inpatients. A general population-based survey was conducted in Hanoi, Vietnam between April and August 2013. Participants received a description of a person with symptoms of either depression (n = 326) or schizophrenia (n = 403) and were asked to give recommendations for adequate sources of mental health support and treatment options. Multiple analyses on a single item level compared the likelihood of recommendation between schizophrenia and depression. Overall, respondents recommended health care services, ranging from seeking mental health care professionals, psychotherapists, and psychiatrists for both disorders. Psychotherapy was the most favored treatment method, whereas further treatment options, such as concentration and relaxation exercises, meditation or yoga and psychotropic medication were also endorsed as helpful. For the schizophrenia vignette condition, psychotherapy, visiting a psychiatrist or psychotherapist received stronger endorsement rates as compared to the depression vignette. Furthermore, ECT, Feng Shui-based practices, praying and visiting natural healers were recommended less by respondents for the depression vignette in comparison with the schizophrenia vignette. The Vietnamese public endorsed evidence-based treatment recommendations from a variety of treatments options. Differences in the treatment recommendations between depression and schizophrenia reflected the perceived severity of each disorder. Further developments of the Vietnamese mental health care system concerning mental health care providers, as well as the legal regulations surrounding the provision of psychotherapy are needed.


In-situ polymerisation of fully bioresorbable polycaprolactone/phosphate glass fibre composites: In vitro degradation and mechanical properties.
Fully bioresorbable composites have been investigated in order to replace metal implant plates used for hard tissue repair. Retention of the composite mechanical properties within a physiological environment has been shown to be significantly affected due to loss of the integrity of the fibre/matrix interface. This study investigated phosphate based glass fibre (PGF) reinforced polycaprolactone (PCL) composites with 20%, 35% and 50% fibre volume fractions (Vf) manufactured via an in-situ polymerisation (ISP) process and a conventional laminate stacking (LS) followed by compression moulding. Reinforcing efficiency between the LS and ISP manufacturing process was compared, and the ISP composites revealed significant improvements in mechanical properties when compared to LS composites. The degradation profiles and mechanical properties were monitored in phosphate buffered saline (PBS) at 37°C for 28 days. ISP composites revealed significantly less media uptake and mass loss (p<0.001) throughout the degradation period. The initial flexural properties of ISP composites were substantially higher (p<0.0001) than those of the LS composites, which showed that the ISP manufacturing process provided a significantly enhanced reinforcement effect than the LS process. During the degradation study, statistically higher flexural property retention profiles were also seen for the ISP composites compared to LS composites. SEM micrographs of fracture surfaces for the LS composites revealed dry fibre bundles and poor fibre dispersion with polymer rich zones, which indicated poor interfacial bonding, distribution and adhesion. In contrast, evenly distributed fibres without dry fibre bundles or polymer rich zones, were clearly observed for the ISP composite samples, which showed that a superior fibre/matrix interface was achieved with highly improved adhesion.


Me against myself: motivational conflicts and emotional development in adulthood.
Two studies investigated adult age differences in the frequency and emotional consequences of motivational conflicts (i.e., feeling that one wants to or should do something else in a given situation). Study 1 compared younger and older adults. Study 2 included a more age-heterogeneous sample ranging from 20 to 70 years. Data were obtained using diary and experience-sampling methods. Multilevel regression showed that motivational conflict was associated with lower emotional well-being. With age, the frequency of motivational conflict decreased, while emotional well-being increased. Importantly, the age-related decrease in motivational conflicts partly accounted for the age-related increase in emotional well-being. Findings were consistent across studies and robust after the authors controlled for age differences in a number of control variables including time use. The authors conclude that an age-related decrease in motivational conflicts in daily life may be among the factors underlying the positive development of emotional well-being into older adulthood.