Genetic determinants and cellular constraints in noisy gene expression.
In individual cells, transcription is a random process obeying single-molecule kinetics. Often, it occurs in a bursty, intermittent manner. The frequency and size of these bursts affect the magnitude of temporal fluctuations in messenger RNA and protein content within a cell, creating variation or "noise" in gene expression. It is still unclear to what degree transcriptional kinetics are specific to each gene and determined by its promoter sequence. Alternative scenarios have been proposed, in which the kinetics of transcription are governed by cellular constraints and follow universal rules across the genome. Evidence from genome-wide noise studies and from systematic perturbations of promoter sequences suggest that both scenarios-namely gene-specific versus genome-wide regulation of transcription kinetics-may be present to different degrees in bacteria, yeast, and animal cells.


Do Indian women receive adequate information about contraception?
This study analysed the recent changes and patterns of information received about contraceptive methods by contraceptive users in India - an important indicator of quality of care in family planning services. Data were taken from the third and fourth rounds of National Family and Health Surveys (NFHS) conducted in India during 2005-06 and 2015-16. The Method Information Index (MII) was used to capture the information received by respondents on three aspects of contraceptive method use: information about the side-effects of the method, what to do if they experienced any complication from using the method and information received about other methods of contraception. A separate analysis of information received by users about the permanency of sterilization was also carried out. Logistic regression models were applied to assess the independent effects of users' background characteristics and their states and union territories of residence on method information received by them. The value of the MII nearly doubled from about 16% in 2004-05 to 31% in 2015-16, indicating a marked increase in the information received by contraceptive users in India over the period between 2005-06 and 2015-16. In addition, the percentage of sterilized women who received information about the permanency of the method also increased, from 67% to 80%, over the period. While considerable progress has been made in the last decade, there is still plenty of scope for improvement in the information received by contraceptive users to advance a voluntary approach to family planning.


Does the Integrated Management of Childhood Illness cost more than routine care? Results from the United Republic of Tanzania.
The Integrated Management of Childhood Illness (IMCI) strategy is designed to address the five leading causes of childhood mortality, which together account for 70% of the 10 million deaths occurring among children worldwide annually. Although IMCI is associated with improved quality of care, which is a key determinant of better health outcomes, it has not yet been widely adopted, partly because it is assumed to be more expensive than routine care. Here we report the cost of IMCI compared with routine care in four districts in the United Republic of Tanzania. Total district costs of child care were estimated from the societal perspective as the sum of child health-care costs incurred in a district at the household level, primary health-facility level and hospital level. We also included administrative and support costs incurred by national and district administrations. The incremental cost of IMCI is the difference in costs of child health-care between districts with and without IMCI, after standardization for population size. The annual cost per child of caring for children less than five years old in districts with IMCI was USD 11.19, 44% lower than the cost in the districts without IMCI (USD 16.09). Much of the difference was due to higher rates of hospitalization of children less than 5 years old in the districts without IMCI. Not all of this difference can be attributed to IMCI but even when differences in hospitalization rates are excluded, the cost per child was still 6% lower in IMCI districts. IMCI was not associated with higher costs than routine child health-care in the four study districts in the United Republic of Tanzania. Given the evidence of improved quality of care in the IMCI districts, the results suggest that cost should not be a barrier to the adoption and scaling up of IMCI.


Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors.
We have used a yeast genetic system to isolate cDNAs encoding proteins that specifically interact with the ligand-binding domain of human retinoid X receptor-alpha (RXR alpha). A number encoded portions of two known RXR heterodimer partners, the retinoic acid receptor (RAR) and the peroxisome proliferator activated receptor. Of four additional RXR-interacting proteins (RIPs) selected for further study two, RIP14 and RIP15, are previously unidentified orphan members of the nuclear receptor superfamily. Two others, RIP110 and RIP13, do not show significant similarities to previously reported proteins. RIP110 interacts with LexA-RXR only in yeast cells grown in the presence of the RXR ligand 9-cis-RA, while the interaction of the four receptor superfamily members and RIP13 is unaffected by the presence or absence of 9-cis-RA. RIP110 and RIP13 also interact in yeast with several other members of the receptor superfamily, but RIP14 and RIP15 interact only with RXR. Analysis of larger cDNA clones demonstrates that there are at least two isoforms of RIP14 that differ in the N-terminal (A and B) and hinge (D) domains. Northern blot analysis indicates that RIP14 is expressed specifically in liver and kidney, while RIP15 is expressed in every tissue tested. Both RIP14 and 15 bind as heterodimers with RXR to the RA response element (RARE) from the promoter of the RAR beta 2 isoform (the beta RARE), and RIP14 and RXR heterodimers also bind the ecdysone response element from the Drosophila heat shock protein 27 promoter. Both heterodimers also bind to several synthetic RAREs and other elements. In cotransfections, neither RIP14 nor RIP15 trans-activates a reporter containing multiple copies of the beta RARE under any of a variety of conditions, suggesting that their activities are dependent on the binding of as yet unidentified specific ligands or on activation by other processes.


Changing roles of population-based cancer registries in Australia.
Registries have key roles in cancer incidence, mortality and survival monitoring and in showing disparities across the population. Incidence monitoring began in New South Wales in 1972 and other jurisdictions soon followed. Registry data are used to evaluate outcomes of preventive, screening, treatment and support services. They have shown decreases in cancer incidence following interventions and have been used for workforce and other infrastructure planning. Crude markers of optimal radiotherapy and chemotherapy exist and registry data are used to show shortfalls against these markers. The data are also used to investigate cancer clusters and environmental concerns. Survival data are used to assess service performance and interval cancer data are used in screening accreditation. Registries enable determination of risk of multiple primary cancers. Clinical quality registries are used for clinical quality improvement. Population-based cancer registries and linked administrative data complement clinical registries by providing high-level system-wide data. The USA Commission on Cancer has long used registries for quality assurance and service accreditation. Increasingly population-based registry data in Australia are linked with administrative data on service delivery to assess system performance. Addition oftumour stage and otherprognostic indicators is important forthese analyses and is facilitated by the roll-out of structured pathology reporting. Data linkage with administrative data, following checks on the quality of these data, enables assessment of patterns of care and other performance indicators for health-system monitoring. Australian cancer registries have evolved and increasingly are contributing to broader information networks for health system management.


Opportunities and obstacles to the elimination of malaria from Peninsular Malaysia: knowledge, attitudes and practices on malaria among aboriginal and rural communities.
Despite continuous efforts by the government and private sectors, malaria is still a public health problem in rural Peninsular Malaysia. This study investigated household knowledge, attitude and practices (KAP) regarding malaria in two malaria endemic communities, forest-aboriginal and rural communities, in the Lipis district of Pahang state, Malaysia. A descriptive cross-sectional study with a semi-structured questionnaire was carried out among 100 and 123 households from forest-aboriginal and rural areas, respectively. Knowledge about malaria and its transmission is significantly higher among the rural participants than the aborigines (86.2% vs 76%, p < 0.01). However, use of medicinal plants and beliefs in witchcraft and sorcery in treating febrile diseases were significantly higher among the aboriginal population (p < 0.01). There were no significant differences between the two communities in terms of the knowledge about malaria symptoms, attitudes towards its severity and practices in preventive measures against malaria by using mosquito bed nets. However, the knowledge and practice of different preventive measures to combat malaria, such as insecticide and the elimination of breeding areas, was significantly higher among the rural population than the aborigines (p < 0.001). Both communities were aware of malaria as a disease, but knowledge, attitudes and practices were inadequate. Providing efficient health education to people residing in malaria endemic areas would improve their understanding about malaria prevention in order to bring about the elimination of malaria from the country.


Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2.
There are several endocytic pathways, which are either dependent on or independent of clathrin. This study focuses on a poorly characterized mechanism-clathrin- and caveolae-independent endocytosis-used by the interleukin-2 receptor beta (IL-2R beta). We address the question of its regulation in comparison with the clathrin-dependent pathway. First, we show that Ras-related C3 botulinum toxin substrate 1 (Rac1) is specifically required for IL-2R beta entry, and we identify p21-activated kinases (Paks) as downstream targets. By RNA interference, we show that Pak1 and Pak2 are both necessary for IL-2R beta uptake, in contrast to the clathrin-dependent route. We observe that cortactin, a partner of actin and dynamin-two essential endocytic factors-is required for IL-2R beta uptake. Furthermore, we find that cortactin acts downstream from Paks, suggesting control of its function by these kinases. Thus, we describe a cascade composed of Rac1, Paks and cortactin specifically regulating IL-2R beta internalization. This study indicates Paks as the first specific regulators of the clathrin-independent endocytosis pathway.


Transverse myelitis and acute motor sensory axonal neuropathy due to Legionella pneumophila: a case report.
Guillain-Barré syndrome is a rapidly progressive symmetrical muscle weakness associated with acute inflammatory disease. Transverse myelitis (TM) is the inflammation of the spinal cord characterized by rapidly evolving muscle weakness in the lower extremities, defects in sensory level and sphincter dysfunction. Guillain-Barré syndrome, and TM association occurs very rarely in childhood. A 7-year-old girl presented with complaints of neck pain, spout-style vomiting, cough, shortness of breath, and acute paraparesis with sensory and sphincter disturbance. The patient was intubated because of increased respiratory distress. A positive direct fluorescein antigen test in bronchoalveolar lavage confirmed Legionella pneumophila infection. Imaging and neurophysiologic studies were diagnostic for TM with acute motor and sensory axonal neuropathy. She was treated with a combination of high-dose methylprednisolone and intravenous immunoglobulins, and we observed incomplete recovery. The presented case is the first child with concomitant TM and acute motor and sensory axonal neuropathy related to L. pneumophila infection.


Breast spindle cell tumours: about eight cases.
Breast spindle cell tumours (BSCTs), although rare, represent a heterogeneous group with different treatment modalities. This work was undertaken to evaluate the utility of fine needle aspiration cytology (FNAC), histopathology and immunohistochemistry (IHC) in differentiating BSCTs. FNAC of eight breast masses diagnosed cytologically as BSCTs was followed by wide excision biopsy. IHC using a panel of antibodies against vimentin, pan-cytokeratin, s100, desmin, smooth muscle actin, CD34, and CD10 was evaluated to define their nature. FNAC defined the tumors as benign (n = 4), suspicious (n = 2) and malignant (n = 3), based on the cytopathological criteria of malignancy. Following wide excision biopsy, the tumors were reclassified into benign (n = 5) and malignant (n = 3). In the benign group, the diagnosis was raised histologically and confirmed by IHC for 3 cases (one spindle cell lipoma, one myofibroblastoma and one leiomyoma). For the remaining two cases, the diagnosis was set up after IHC (one fibromatosis and one spindle cell variant of adenomyoepithelioma). In the malignant group, a leiomyosarcoma was diagnosed histologically, while IHC was crucial to set up the diagnosis of one case of spindle cell carcinoma and one malignant myoepithelioma. FNAC in BSCTs is an insufficient tool and should be followed by wide excision biopsy. The latter technique differentiate benign from malignant BSCTs and is able in 50% of the cases to set up the definite diagnosis. IHC is of value to define the nature of different benign lesions and is mandatory in the malignant ones for optimal treatment. Awareness of the different types of BSCTs prevents unnecessary extensive therapeutic regimes.


Bereavement and marriage are associated with antibody response to influenza vaccination in the elderly.
Stressful life events exposure including bereavement, an event commonly experienced by elderly people, social support, marital status, and satisfaction were examined in relation to antibody response to the annual trivalent influenza vaccination in an elderly community sample (N=184). Antibody response was assessed at baseline, and at 1 and 12 months following vaccination. Taking into account baseline antibody titer, overall life events exposure and social support were not associated with response to any of the influenza strains. However, bereavement in the year prior to vaccination was negatively associated with the 1-month response to the A/Panama and B/Shangdong strains. Being married and having higher marital satisfaction was also associated with higher peak responses to the A/Panama influenza strain at 1 month. The positive association between marital satisfaction and A/Panama response was particularly evident in the younger half of the married sample. These associations largely withstood adjustment for potential confounders. Thus, in the elderly, peak antibody response was associated with bereavement and marriage, and not the more general factors, life events and social support, related to antibody response in student samples. This suggests the importance of taking a life course approach to examining relationships between psychosocial factors and immunity, and that interventions to modify the impact of these factors should address those most salient for each age group.


Do the Footwear Profiles and Foot-Related Problems Reported by Netball Players Differ Between Males and Females?
We explored the footwear profiles and foot-related problems reported by netball players and whether these differed between males and females. Two thousand nine hundred and twenty-five amateur, sub-elite and elite netball players (men n = 279; women n = 2646; age 26.4 ± 10.0 years) completed a custom-designed online survey with questions related to netball experience, current netball footwear habits and history of foot-related problems. Footwear profiles and foot-related problems were considered in logistic regressions against sex and competition level to ascertain significant relationships (p < 0.05) and predictive values (odds ratio). Although 80.4% of respondents reported wearing netball-specific shoes, females were 13.2 times more likely to wear netball-specific shoes than males. Foot-related problems and foot pain were reported by 84.3% and 56.8% of netball players, respectively; with blisters, ankle sprain/strains and calluses being most common. Although women were significantly more likely to suffer from foot-related problems than men, males were significantly more likely to believe their foot pain was caused by the footwear they wore for netball. The high prevalence of foot-related problems and pain reported by all netball players suggests that the shoes players are currently wearing for netball are not meeting the requirements of players, particularly regarding fit, comfort and functionality. As male netball players have significantly different footwear profiles to female players, men are likely to require netball-specific footwear that differs to the netball-specific shoes designed for female players.


Effect of garlic on cardiovascular disorders: a review.
Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficacy of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic.


Systems Proteomics View of the Endogenous Human Claudin Protein Family.
Claudins are the major transmembrane protein components of tight junctions in human endothelia and epithelia. Tissue-specific expression of claudin members suggests that this protein family is not only essential for sustaining the role of tight junctions in cell permeability control but also vital in organizing cell contact signaling by protein-protein interactions. How this protein family is collectively processed and regulated is key to understanding the role of junctional proteins in preserving cell identity and tissue integrity. The focus of this review is to first provide a brief overview of the functional context, on the basis of the extensive body of claudin biology research that has been thoroughly reviewed, for endogenous human claudin members and then ascertain existing and future proteomics techniques that may be applicable to systematically characterizing the chemical forms and interacting protein partners of this protein family in human. The ability to elucidate claudin-based signaling networks may provide new insight into cell development and differentiation programs that are crucial to tissue stability and manipulation.


Currents induced by magnetic impurities in superconductors with spin-orbit coupling.
We show that superconducting currents are generated around magnetic impurities and ferromagnetic islands proximity coupled to superconductors with finite spin-orbit coupling. Using the Ginzburg-Landau theory, T-matrix calculation, as well as self-consistent numerical simulation on a lattice, we find a strong dependence of the current on the direction and magnitude of the magnetic moment. We establish that in the case of point magnetic impurities, the current is carried by the induced Yu-Shiba-Rusinov (YSR) subgap states. In the vicinity of the phase transition, where the YSR states cross at zero energy, the current increases dramatically. Furthermore, we show that the currents are orthogonal to the local spin polarization and, thus, can be probed by measuring the spin-polarized local density of states.


Gonadal abnormalities in frogs (Lithobates spp.) collected from managed wetlands in an agricultural region of Nebraska, USA.
Nebraska's Rainwater Basin (RWB) provides important wetland habitat for North American migratory birds. Concern exists that pesticide and nutrient runoff from surrounding row-crops enters wetlands degrading water quality and adversely affecting birds and wildlife. Frogs may be especially vulnerable. Plains leopard (Lithobates blairi) metamorphs from RWB wetlands with varying concentrations of pesticides were evaluated for a suite of biomarkers of exposure to endocrine active chemicals. Froglets had ovarian dysgenesis, high rates of testicular oocytes, and female-biased sex ratios however, there was no clear statistical association between pesticide concentrations and biomarkers. Data interpretation was hindered because timing and duration of exposures were unknown and due to an incomplete understanding of L. blairi sexual development. Emphasis is on describing the complex developmental biology of closely-related leopard frogs, how this understanding can explain RWB L. blairi anomalies, and the need for sampling at the appropriate life stage.


Organic carbon hidden in urban ecosystems.
Urbanization is widely presumed to degrade ecosystem services, but empirical evidence is now challenging these assumptions. We report the first city-wide organic carbon (OC) budget for vegetation and soils, including under impervious surfaces. Urban soil OC storage was significantly greater than in regional agricultural land at equivalent soil depths, however there was no significant difference in storage between soils sampled beneath urban greenspaces and impervious surfaces, at equivalent depths. For a typical U.K. city, total OC storage was 17.6 kg m(-2) across the entire urban area (assuming 0 kg m(-2) under 15% of land covered by buildings). The majority of OC (82%) was held in soils, with 13% found under impervious surfaces, and 18% stored in vegetation. We reveal that assumptions underpinning current national estimates of ecosystem OC stocks, as required by Kyoto Protocol signatories, are not robust and are likely to have seriously underestimated the contributions of urban areas.


Mouse Sperm Cryopreservation and Recovery of Genetically Modified Mice.
Highly definable genetically, the humble mouse is the "reagent" mammal of choice with which to probe and begin to understand the human condition in all its complexities. With the recent advance in direct genome editing via targeted nucleases, e.g., TALEN and CRISPR/Cas9, the possibilities in using these sophisticated tools have increased substantially leading to a massive increase in the variety of strain numbers of genetically modified lines. With this increase comes a greater need to economically and creatively manage their numbers. Further, once characterized, lines may be of limited use but still need to be archived in a format allowing their rapid resurrection. Further, maintaining colonies on "the shelf" is financially draining and carries potential risks including natural disaster loss, disease, and strain contamination. Here we outline a simple and economic protocol to cryopreserve mouse sperm from many different genetic backgrounds, and outline its recovery via in vitro fertilization (IVF). The combined use of sperm cryopreservation and IVF now allows a freedom and versatility in mouse management facilitating rapid line close down with the option to later recover and rapidly expand as needed.


Increased Brain Exposure of an Alpha-Synuclein Fibrillization Modulator by Utilization of an Activated Ester Prodrug Strategy.
Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (α-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood-brain barrier permeability in nonhuman primates (NHP) in vivo. For this purpose, 2-pyridone 12 was prepared and found to accelerate α-syn fibrillization in vitro. Acid 12, and its acetoxymethyl ester analogue 14, were then radiolabeled with 11C ( t1/2 = 20.4 min) at high radiochemical purity (>99%) and high specific radioactivity (>37 GBq/μmol). Following intravenous injection of each compound in NHP, a 4-fold higher radioactivity in brain was observed for [11C]14 compared to [11C]12 (0.8 vs 0.2 SUV, respectively). [11C]14 was rapidly eliminated from plasma, with [11C]12 as the major metabolic product observed by radio-HPLC. The presented prodrug approach paves the way for future development of 2-pyridones as imaging biomarkers for in vivo imaging of α-synuclein deposits in brain.


A Genome-Wide Perspective on the Persistence of Red Wolf Ancestry in Southeastern Canids.
The red wolf (Canis rufus), a legally recognized and critically endangered wolf, is known to interbreed with coyotes (Canis latrans). Declared extirpated in the wild in 1980, red wolves were reintroduced to northeastern North Carolina nearly a decade later. Interbreeding with coyotes was thought to be restricted to a narrow geographic region adjacent to the reintroduced population and largely believed to threaten red wolf recovery. However, red wolf ancestry was recently discovered in canids along the American Gulf Coast, igniting a broader survey of ancestry in southeastern canid populations. Here, we examine geographic and temporal patterns of genome-wide red wolf ancestry in 260 canids across the southeastern United States at over 164 000 SNP loci. We found that red wolf ancestry was most prevalent in canids sampled from Texas in the mid-1970s, although non-trivial amounts of red wolf ancestry persist in this region today. Further, red wolf ancestry was also observed in a subset of coyotes inhabiting North Carolina, despite management efforts to limit the occurrence of hybridization events. Lastly, we found no evidence of substantial red wolf ancestry in southeastern canids outside of these 2 admixture zones. Overall, this study provides a genome-wide survey of red wolf ancestry in canids across the southeastern United States, which may ultimately inform future red wolf restoration efforts.


(39)K NMR and EPR study of multiferroic K(3)Fe(5)F(15).
(39)K NMR spectra and relaxation times of polycrystalline K(3)Fe(5)F(15) have been used as a microscopic detector of the local magnetic fields at the magnetic transition at T(N) = 123 K. The NMR lineshape widens abruptly upon crossing T(N) due to the onset of internal magnetic fields, while we find no significant lineshift. The paraelectric to ferroelectric transition at T(c) = 490 K and the magnetic transition at T(N) have also been studied using X-band EPR (electron paramagnetic resonance). An increase and subsequent decrease in the EPR susceptibilities is observed on approaching T(N) from above. There is also a significant increase in the linewidth. At the same time the g-factor first decreases and then increases with decreasing temperature. The local magnetic field is different at different K sites and is much smaller than the magnetic field around the Fe sites. This seems to be consistent with the behaviour of a weak ferrimagnet. The ferrimagnetism does not seem to be due to spin canting as the lattice is disordered, but may arise from thermal blocking of superparamagnetic percolation clusters. The ferroelectric transition at T(c) shows no electronic anomaly, demonstrating that we are dealing with a classical phonon anomaly as found in conventional oxides rather than an electronic transition.


On the mechanism of amiloride-sensitive nonelectrogenic Na+-H+ exchange in cell membranes: Na+/H+ antiport or Na+/OH- symport?
The amiloride-sensitive and nonelectrogenic Na+-H+ exchange system of eucaryotic cells is currently a topic of great interest. The results of membrane transport in the presence of protons are shown to be similar in two cases: when H+ is transferred in one direction or OH- -in the opposite direction. Therefore, in principle Na+-H+ exchange can be performed by two different mechanisms: Na+/H+ antiport or Na+/OH- symport. However, the kinetic properties of these mechanisms turn out to be quite different. The present study analyses the simplest models of antiport and symport and delineates their important differences. For this purpose the Lineweaver-Burk plot presented as Na+ reverse flow entering a cell 1/JNa (or H+ leaving a cell) versus the reverse concentration of Na+ outside 1/[Na+]0 is most useful. If a series of lines with external pH as a parameter have a common point of intersection placed on the ordinate, it indicates the availability of Na+/H+ antiport. In case of Na+/OH- symport a point of intersection is shifted to the left of the ordinate axis. According to data available in the literature, Na+/H+ antiport manifests itself in dog kidney cells and in hamster lung fibroblasts. In the skeletal muscles of chicken and in rat thymus lymphocytes however, a Na+/OH- symport is apparently present.


Interventions for Adolescent Mental Health: An Overview of Systematic Reviews.
Many mental health disorders emerge in late childhood and early adolescence and contribute to the burden of these disorders among young people and later in life. We systematically reviewed literature published up to December 2015 to identify systematic reviews on mental health interventions in adolescent population. A total of 38 systematic reviews were included. We classified the included reviews into the following categories for reporting the findings: school-based interventions (n = 12); community-based interventions (n = 6); digital platforms (n = 8); and individual-/family-based interventions (n = 12). Evidence from school-based interventions suggests that targeted group-based interventions and cognitive behavioral therapy are effective in reducing depressive symptoms (standard mean difference [SMD]: -.16; 95% confidence interval [CI]: -.26 to -.05) and anxiety (SMD: -.33; 95% CI: -.59 to -.06). School-based suicide prevention programs suggest that classroom-based didactic and experiential programs increase short-term knowledge of suicide (SMD: 1.51; 95% CI: .57-2.45) and knowledge of suicide prevention (SMD: .72; 95% CI: .36-1.07) with no evidence of an effect on suicide-related attitudes or behaviors. Community-based creative activities have some positive effect on behavioral changes, self-confidence, self-esteem, levels of knowledge, and physical activity. Evidence from digital platforms supports Internet-based prevention and treatment programs for anxiety and depression; however, more extensive and rigorous research is warranted to further establish the conditions. Among individual- and family-based interventions, interventions focusing on eating attitudes and behaviors show no impact on body mass index (SMD: -.10; 95% CI: -.45 to .25); Eating Attitude Test (SMD: .01; 95% CI: -.13 to .15); and bulimia (SMD: -.03; 95% CI: -.16 to .10). Exercise is found to be effective in improving self-esteem (SMD: .49; 95% CI: .16-.81) and reducing depression score (SMD: -.66; 95% CI: -1.25 to -.08) with no impact on anxiety scores. Cognitive behavioral therapy compared to waitlist is effective in reducing remission (odds ratio: 7.85; 95% CI: 5.31-11.6). Psychological therapy when compared to antidepressants have comparable effect on remission, dropouts, and depression symptoms. The studies evaluating mental health interventions among adolescents were reported to be very heterogeneous, statistically, in their populations, interventions, and outcomes; hence, meta-analysis could not be conducted in most of the included reviews. Future trials should also focus on standardized interventions and outcomes for synthesizing the exiting body of knowledge. There is a need to report differential effects for gender, age groups, socioeconomic status, and geographic settings since the impact of mental health interventions might vary according to various contextual factors.


High-resolution quantitative trait locus mapping reveals sign epistasis controlling ovariole number between two Drosophila species.
Identifying the genes underlying genetically complex traits is of fundamental importance for medicine, agriculture, and evolutionary biology. However, the level of resolution offered by traditional quantitative trait locus (QTL) mapping is usually coarse. We analyze here a trait closely related to fitness, ovariole number. Our initial interspecific mapping between Drosophila sechellia (8 ovarioles/ovary) and D. simulans (15 ovarioles/ovary) identified a major QTL on chromosome 3 and a minor QTL on chromosome 2. To refine the position of the major QTL, we selected 1038 additional recombinants in the region of interest using flanking morphological markers (selective phenotyping). This effort generated approximately one recombination event per gene and increased the mapping resolution by approximately seven times. Our study thus shows that using visible markers to select for recombinants can efficiently increase the resolution of QTL mapping. We resolved the major QTL into two epistatic QTL, QTL3a and QTL3b. QTL3a shows sign epistasis: it has opposite effects in two different genetic backgrounds, the presence vs. the absence of the QTL3b D. sechellia allele. This property of QTL3a allows us to reconstruct the probable order of fixation of the QTL alleles during evolution.


Lack of replicative senescence in cultured rat oligodendrocyte precursor cells.
Most mammalian somatic cells are thought to have a limited proliferative capacity because they permanently stop dividing after a finite number of divisions in culture, a state termed replicative cell senescence. Here we show that most oligodendrocyte precursor cells purified from postnatal rat optic nerve can proliferate indefinitely in serum-free culture if prevented from differentiating; various cell cycle-inhibitory proteins increase, but the cells do not stop dividing. The cells maintain high telomerase activity and p53- and Rb-dependent cell cycle checkpoint responses, and serum or genotoxic drugs induce them to acquire a senescence-like phenotype. Our findings suggest that some normal rodent precursor cells have an unlimited proliferative capacity if cultured in conditions that avoid both differentiation and the activation of checkpoint responses that arrest the cell cycle.


Potential risks and benefits of HIV treatment simplification: a simulation model of a proposed clinical trial.
In recent studies, subjects who had achieved suppression of the human immunodeficiency virus (HIV) RNA level while receiving an initial 3-drug antiretroviral regimen successfully maintained suppression while receiving treatment with a "boosted" protease inhibitor (PI) alone. We projected the long-term outcomes of this treatment simplification strategy to inform the design of a proposed multicenter, randomized clinical trial. We used published studies to estimate the efficacy, adverse effects, and cost of a sequence of HIV drug regimens for the simplification strategy, compared with those outcomes for the current standard-of-care (SOC) strategy. Using a published simulation model of HIV disease, we projected life expectancy, discounted quality-adjusted life expectancy (QALE), and discounted lifetime medical costs for each strategy. Subjects who have not developed PI-resistant HIV infection at the time of failure of the simplification regimen have a greater life expectancy (27.9 vs. 27.1 years) and QALE (14.9 vs. 14.7 years), compared with SOC subjects, because they receive an additional line of therapy without negative consequences for future treatment options. The QALE for the simplification strategy remains higher than that for the SOC, unless a large proportion of patients experiencing virologic failure while receiving the simplification regimen develop PI resistance. Depending on the probability of simplification regimen failure, the advantage is maintained even if HIV develops PI resistance in 42%-70% of subjects. Projected lifetime costs are $26,500-$72,400 per person lower for the simplification strategy than for the SOC strategy. An HIV treatment simplification strategy involving use of a boosted PI alone may lead to longer survival overall at lower cost, compared with the SOC combination therapy, because the simplification strategy potentially adds an additional line of therapy. The risk of emergence of PI resistance during treatment with a simplified regimen is a critical determinant of the viability of this strategy.


Facemasks for the prevention of infection in healthcare and community settings.
Facemasks are recommended for diseases transmitted through droplets and respirators for respiratory aerosols, yet recommendations and terminology vary between guidelines. The concepts of droplet and airborne transmission that are entrenched in clinical practice have recently been shown to be more complex than previously thought. Several randomised clinical trials of facemasks have been conducted in community and healthcare settings, using widely varying interventions, including mixed interventions (such as masks and handwashing), and diverse outcomes. Of the nine trials of facemasks identified in community settings, in all but one, facemasks were used for respiratory protection of well people. They found that facemasks and facemasks plus hand hygiene may prevent infection in community settings, subject to early use and compliance. Two trials in healthcare workers favoured respirators for clinical respiratory illness. The use of reusable cloth masks is widespread globally, particularly in Asia, which is an important region for emerging infections, but there is no clinical research to inform their use and most policies offer no guidance on them. Health economic analyses of facemasks are scarce and the few published cost effectiveness models do not use clinical efficacy data. The lack of research on facemasks and respirators is reflected in varied and sometimes conflicting policies and guidelines. Further research should focus on examining the efficacy of facemasks against specific infectious threats such as influenza and tuberculosis, assessing the efficacy of cloth masks, investigating common practices such as reuse of masks, assessing compliance, filling in policy gaps, and obtaining cost effectiveness data using clinical efficacy estimates.


P1 receptors and cytokine secretion.
Evidence has accumulated in the last three decades to suggest tissue protection and regeneration by adenosine in multiple different cell types. Adenosine produced in hypoxic or inflamed environments reduces tissue injury and promotes repair by receptor-mediated mechanisms. Among other actions, regulation of cytokine production and secretion by immune cells, astrocytes and microglia (the brain immunocytes) has emerged as a main mechanism at the basis of adenosine effects in diseases characterized by a marked inflammatory component. Many recent studies have highlighted that signalling through A(1) and A(2A) adenosine receptors can powerfully prevent the release of pro-inflammatory cytokines, thus inhibiting inflammation and reperfusion injury. However, the activation of adenosine receptors is not invariably protective of tissues, as signalling through the A(2B) adenosine receptor has been linked to pro-inflammatory actions which are, at least in part, mediated by increased release of pro-inflammatory cytokines from epithelial cells, astrocytes and fibroblasts. Here, we discuss the multiple actions of P1 receptors on cytokine secretion, by analyzing, in particular, the role of the various adenosine receptor subtypes, the complex reciprocal interplay between the adenosine and the cytokine systems, their pathophysiological significance and the potential of adenosine receptor ligands as new anti-inflammatory agents.


Efficient transmission of tick-borne encephalitis virus between cofeeding ticks.
Most of the data on oral infections of ticks with tick-borne encephalitis virus have been derived from experiments using animals infected by syringe inoculation. To mimic the natural conditions of virus transmission, tick-borne encephalitis virus-infected Ixodes ricinus (Linnaeus) or Rhipicephalus appendiculatus Neumann adults (donors) were cofed with uninfected nymphs (recipients) of either tick species on uninfected guinea pigs. Two tick-retaining cells were attached to each guinea pig: cell 1 contained uninfected nymphs and virus-infected adults, and cell 2 contained uninfected nymphs. Following engorgement, 55% of I. ricinus nymphs and 65% of R. appendiculatus nymphs were shown to have acquired the virus while cofeeding with I. ricinus donor ticks. Similarly, 66% of R. appendiculatus recipient nymphs that cofed with R. appendiculatus virus-infected adults were infected. Some of the guinea pigs on which the ticks cofed were apparently nonviremic. The results indicate that efficient transmission of tick-borne encephalitis virus can occur between cofeeding ticks even when the host on which they feed does not develop a detectable viremia.


Susceptibility mapping of the dural sinuses and other superficial veins in the brain.
Quantitative susceptibility mapping (QSM) is a means to obtain direct measurements of local tissue susceptibility distribution. Usually the focus is on imaging tissues in the brain, and the region of the brain studied is dictated by an eroded skull stripped mask. Producing the pristine local phase behavior for regions at the edge of the brain has been difficult in the past. For structures such as the superior sagittal sinus (SSS) that run alongside the surface of the brain and under the skull bones, a considerable part of the external phase from the dipole effect is lost due to the short T2* of the bones. In this paper, we propose a method that seeks to reconstruct the susceptibility distribution inside the dural sinuses by ensuring that the entire geometry of the dural sinuses is preserved with the help of an MR angiogram and venogram (MRAV). Having a geometrical model of the vessels makes it possible to estimate the missing phase outside the brain as well, by using the forward phase model and, hence, allowing a complete phase map to be reconstructed. Fifteen healthy volunteers were scanned using a susceptibility weighted imaging (SWI) sequence with interleaved rephased-dephased echoes. QSM results were compared between the conventional techniques and the proposed method of phase preservation outside the brain and inside the dural sinuses. This method demonstrates the reconstruction of the SSS, whereas conventional methods are either unable to preserve this structure or unable to provide complete phase information. The mean and standard deviation inside the SSS for all volunteers was 435 ± 5 ppb (this is the inter-subject error). To validate the proposed approach, the mean susceptibility inside the straight sinus showed good agreement between conventional approach and the proposed method. The results presented in this study indicate the potential of generating the susceptibility map for the whole brain, including the SSS (as well as potentially all the cortical veins).


Spinal metastases from renal cell carcinoma: effect of preoperative particle embolization on intraoperative blood loss.
Surgical repair of spinal metastases from renal origin is often complicated by excessive bleeding. The purpose of this study was to assess the effect of preoperative particulate embolization on intraoperative blood loss. Twenty spinal metastases from renal origin (17 patients) treated by preoperative embolization with polyvinyl alcohol particles were analyzed retrospectively. Surgical decompression was performed within 2 days after embolization. A control group of 10 patients with 11 spinal metastases of renal origin underwent surgery without embolization. The effect of preoperative embolization, of completeness of embolization, and of particle size on the estimated intraoperative blood loss was analyzed using nonparametric statistical tests. Complete embolization was achieved in 10 cases and partial embolization in the other 10. The estimated blood loss of 19 embolized and 11 control cases was available from the surgical report. Median intraoperative blood loss in 19 embolized lesions was 1500 mL (range, 300-8000 mL), compared with 5000 mL (range, 1440-15000 mL) in the control group. Even after partial embolization, blood loss (median, 2000 mL) was significantly lower than in the control group. No significant differences in estimated blood loss were noted between the use of particles smaller than 250 microm and those larger than 250 microm. No embolization-related permanent neurologic deficit or skin or muscle necrosis occurred. Preoperative embolization of spinal metastases of renal origin with polyvinyl alcohol particles is safe and might reduce intraoperative blood loss significantly. Even partial embolization seems to be effective.


Katatopygia gen. n., a monophyletic branch segregated from Boletina (Diptera, Mycetophilidae).
The genus Katatopygiagen. n. is proposed for the Boletina erythropyga/punctus-group that was first introduced by Garrett (1924, 1925) and currently comprises eight described species. Molecular studies have strongly indicated that this group forms a monophyletic sister-group to a clade consisting of all other Boletina, Coelosia and Gnoriste, and its monophyly is supported by morphological data as well. The new genus includes the following species: Katatopygia antoma (Garrett, 1924), comb. n., Katatopygia antica (Garrett, 1924), comb. n., Katatopygia erythropyga (Holmgren, 1883), comb. n.,Katatopygia hissarica (Zaitzev & Polevoi, 2002), comb. n., Katatopygia magna (Garrett, 1925), comb. n., Katatopygia laticauda (Saigusa, 1968), comb. n., Katatopygia neoerythropyga (Zaitzev & Polevoi, 2002), comb. n. andKatatopygia sahlbergi (Lundström, 1906), comb. n., all transferred from Boletina. Katatopygia sahlbergi is found to be a senior synonym of Boletina punctus Garrett, 1925, syn. n. A phylogeny based on morphological data and using parsimony analysis yielded four most parsimonious trees where the new genus is retrieved as monophyletic with high support. Katatopygia neoerythropyga is found to be the sister-taxon to all other species that form two clades, one with Katatopygia sahlbergi-like species and one with Katatopygia erythropyga-like species. A key to males of Katatopygia is provided.


Conformational sampling techniques.
The potential energy hyper-surface of a protein relates the potential energy of the protein to its conformational space. This surface is useful in determining the native conformation of a protein or in examining a statistical-mechanical ensemble of structures (canonical ensemble). In determining the potential energy hyper-surface of a protein three aspects must be considered; reducing the degrees of freedom, a method to determine the energy of each conformation and a method to sample the conformational space. For reducing the degrees of freedom the choice of solvent, coarse graining, constraining degrees of freedom and periodic boundary conditions are discussed. The use of quantum mechanics versus molecular mechanics and the choice of force fields are also discussed, as well as the sampling of the conformational space through deterministic and heuristic approaches. Deterministic methods include knowledge-based statistical methods, rotamer libraries, homology modeling, the build-up method, self-consistent electrostatic field, deformation methods, tree-based elimination and eigenvector following routines. The heuristic methods include Monte Carlo chain growing, energy minimizations, metropolis monte carlo and molecular dynamics. In addition, various methods to enhance the conformational search including the deformation or smoothing of the surface, scaling of system parameters, and multi copy searching are also discussed.


Silencing an N-acyltransferase-like involved in lignin biosynthesis in Nicotiana attenuata dramatically alters herbivory-induced phenolamide metabolism.
In a transcriptomic screen of Manduca sexta-induced N-acyltransferases in leaves of Nicotiana attenuata, we identified an N-acyltransferase gene sharing a high similarity with the tobacco lignin-biosynthetic hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT) gene whose expression is controlled by MYB8, a transcription factor that regulates the production of phenylpropanoid polyamine conjugates (phenolamides, PAs). To evaluate the involvement of this HCT-like gene in lignin production as well as the resulting crosstalk with PA metabolism during insect herbivory, we transiently silenced (by VIGs) the expression of this gene and performed non-targeted (UHPLC-ESI/TOF-MS) metabolomics analyses. In agreement with a conserved function of N. attenuata HCT-like in lignin biogenesis, HCT-silenced plants developed weak, soft stems with greatly reduced lignin contents. Metabolic profiling demonstrated large shifts (up to 12% deregulation in total extracted ions in insect-attacked leaves) due to a large diversion of activated coumaric acid units into the production of developmentally and herbivory-induced coumaroyl-containing PAs (N',N''-dicoumaroylspermidine, N',N''-coumaroylputrescine, etc) and to minor increases in the most abundant free phenolics (chlorogenic and cryptochlorogenic acids), all without altering the production of well characterized herbivory-responsive caffeoyl- and feruloyl-based putrescine and spermidine PAs. These data are consistent with a strong metabolic tension, exacerbated during herbivory, over the allocation of coumaroyl-CoA units among lignin and unusual coumaroyl-containing PAs, and rule out a role for HCT-LIKE in tuning the herbivory-induced accumulation of other PAs. Additionally, these results are consistent with a role for lignification as an induced anti-herbivore defense.


Arterial Spin Labeling Perfusion Study in the Patients with Subacute Mild Traumatic Brain Injury.
This study uses a MRI technique, three-dimension pulse continuous arterial spin labeling (3D-PCASL), to measure the patient's cerebral blood flow (CBF) at the subacute stage of mild traumatic brain injury (MTBI) in order to analyze the relationship between cerebral blood flow and neurocognitive deficits. To provide the relationship between cortical CBF and neuropsychological dysfunction for the subacute MTBI patients. After MTBI, perfusion MR imaging technique (3D-PCASL) measures the CBF of MTBI patients (n = 23) within 1 month and that of normal controls (n = 22) to determine the quantity and location of perfusion defect. The correlation between CBF abnormalities and cognitive deficits was elucidated by combining the results of the neuropsychological tests of the patients. We observed a substantial reduction in CBF in the bilateral frontal and left occipital cortex as compared with the normal persons. In addition, there were correlation between post concussive symptoms (including dizziness and simulator sickness) and CBF in the hypoperfused areas. The more severe symptom was correlated with higher CBF in bilateral frontal and left occipital lobes. First, this study determined that despite no significant abnormality detected on conventional CT and MRI studies, hypoperfusion was observed in MTBI group using 3D-PCASL technique in subacute stage, which suggested that this approach may increase sensitivity to MTBI. Second, the correlation between CBF and the severity of post concussive symptoms suggested that changes in cerebral hemodynamics may play a role in pathophysiology underlies the symptoms.


Extracellular superoxide dismutase polymorphism in mice: Allele-specific effects on phenotype.
Extracellular superoxide dismutase (ecSOD) protects the extracellular matrix from oxidative stress. We previously reported a new allele for ecSOD, expressed in 129P3/J mice (129), which differs from the wild type (wt), expressed in C57BL/6J and other strains, by two amino acid substitutions and a 10-bp deletion in the 3' UTR of the mRNA (A. Pierce et al., 2003, Arterioscler. Thromb. Vasc. Biol.23:1820-1825). The newly discovered allele is associated with a phenotype of significantly increased circulating and heparin-releasable enzyme activities and levels. To examine the properties of the two forms of ecSOD in an identical environment we generated, by extensive backcrossing of ecSOD heterozygous progeny to C57BL/6J females, a congenic C57 strain with the 129 (or wt) allele of ecSOD. These mice are homozygous for nearly 5000 SNPs across all chromosomes, as determined by the Affymetrix Parallele Mouse 5K SNP panel. This study describes the generation of the congenic mice (genetically >99.8% identical) and their ecSOD phenotype. The congenic mouse plasma ecSOD activity before and after heparin administration recapitulates the differences reported in the founder mice. Tissue enzyme distribution is similar in both congenic groups, although the 129 allele is associated with higher levels of enzyme expression despite lower levels of enzyme mRNA. In these characteristics the phenotype is allele driven, with little impact from the rest of the genome. The congenic mice carrying the 129 allele have mRNA levels that are in between those in the founder 129P3/J and C57BL/6J strains. We conclude that the ecSOD phenotype in most aspects of enzyme expression is allele driven, with the exception of tissue mRNA levels, for which a significant contribution by the surrounding (host) genome is observed. These results also suggest potential allele-specific differences in the regulation of ecSOD synthesis and intracellular processing/secretion of ecSOD, independent of the genotype context. Most importantly, the congenic mice offer an excellent model to examine the regulatory mechanisms of ecSOD expression and the role of ecSOD in various diseases involving oxidative stress.


Speeded classification in simultaneous masking.
In simultaneous masking, flanking elements impair performance on a visual target. Previous studies on simultaneous masking have predominantly used discrimination threshold estimation to quantify performance on the target. Results based on thresholds suggest that an important factor in simultaneous masking is the strength of grouping between the target and the flankers. Recently Panis and Hermens (2014) showed that error rates in a speeded discrimination task, using the same simultaneous masking paradigm, provide a very similar pattern of results compared to thresholds from previous studies. In contrast, response times were found to deviate from the pattern in the error rates in some of the conditions, possibly providing a method to tap into low-level visual processes within the same paradigm. However, only a small number of masks was used, and it is therefore unclear to what extent differences can be found between thresholds, error rates, and response times. Here, we address this issue by examining speeded classification performance on a vernier target for a broad range of simultaneous mask layouts. Results suggest that thresholds and error rates are strongly associated, and that response times generally show the same pattern of results, although to a slightly weaker extent. We suggest that masking strength, defined by either measure, appears to be linked to target-flanker grouping rather than to low-level interactions.


Hypereosinophilic syndrome and clonal eosinophilia: point-of-care diagnostic algorithm and treatment update.
Acquired eosinophilia is operationally categorized into secondary, clonal, and idiopathic types. Causes of secondary eosinophilia include parasite infections, allergic or vasculitis conditions, drugs, and lymphoma. Clonal eosinophilia is distinguished from idiopathic eosinophilia by the presence of histologic, cytogenetic, or molecular evidence of an underlying myeloid malignancy. The World Health Organization classification system for hematologic malignancies recognizes 2 distinct subcategories of clonal eosinophilia: chronic eosinophilic leukemia, not otherwise specified and myeloid/lymphoid neoplasms with eosinophilia and mutations involving platelet-derived growth factor receptor alpha/beta or fibroblast growth factor receptor 1. Clonal eosinophilia might also accompany other World Health Organization-defined myeloid malignancies, including chronic myelogenous leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and systemic mastocytosis. Hypereosinophilic syndrome, a subcategory of idiopathic eosinophilia, is defined by the presence of a peripheral blood eosinophil count of 1.5 x 10(9)/L or greater for at least 6 months (a shorter duration is acceptable in the presence of symptoms that require eosinophil-lowering therapy), exclusion of both secondary and clonal eosinophilia, evidence of organ involvement, and absence of phenotypically abnormal and/or clonal T lymphocytes. The presence of the latter defines lymphocytic variant hyper eosinophilia, which is best classified under secondary eosinophilia. In the current review, we provide a simplified algorithm for distinguishing the various causes of clonal and idiopathic eosinophilia and discuss current therapy, including new drugs (imatinib mesylate, alemtuzumab, and mepolizumab).


Effect of rice-expressed amyloid β in the Tg2576 Alzheimer's disease transgenic mouse model.
One of the main hallmarks of Alzheimer's disease (AD) is senile plaques composed of amyloid β (Aβ). We developed a new edible vaccine: rice expressing GFP-Aβ42. In a previous report, we described the production of anti-Aβ antibodies in B6 mice fed Aβ rice mixed with cholera toxin B subunit (CTB). In this report, we investigated whether Aβ rice had therapeutic effects in the Tg2576 AD model mice. The anti-Aβ antibody titer was increased and levels of intracerebral Aβ (soluble and insoluble) and serum Aβ decreased. Because the value of IgG1/IgG2a in the Aβ feeding group was >1, immunization via Aβ rice may induce a non-inflammatory Th2 reaction. We also found that the Aβ vaccine improved memory, as assessed in a Y-maze test. The number of arm entries in the Y-maze test was lower in the Aβ feeding group than in the control group. These results suggest that the new edible vaccine Aβ rice may have therapeutic effects in AD.


High-Resolution Magnetic Resonance Imaging of the Regenerating Adult Zebrafish Heart.
The adult zebrafish is a well-established model for studying heart regeneration, but due to its tissue opaqueness, repair has been primarily assessed using destructive histology, precluding repeated investigations of the same animal. We present a high-resolution, non-invasive in vivo magnetic resonance imaging (MRI) method incorporating a miniature respiratory and anaesthetic perfusion set-up for live adult zebrafish, allowing for visualization of scar formation and heart regeneration in the same animal over time at an isotropic 31 µm voxel resolution. To test the method, we compared well and poorly healing cardiac ventricles using a transgenic fish model that exhibits heat-shock (HS) inducible impaired heart regeneration. HS-treated groups revealed persistent scar tissue for 10 weeks, while control groups were healed after 4 weeks. Application of the advanced MRI technique allowed clear discrimination of levels of repair following cryo- and resection injury for several months. It further provides a novel tool for in vivo time-lapse imaging of adult fish for non-cardiac studies, as the method can be readily applied to image wound healing in other injured or diseased tissues, or to monitor tissue changes over time, thus expanding the range of questions that can be addressed in adult zebrafish and other small aquatic species.


Examining the relationships between job control and health status: a path analysis approach.
To examine the pathways through which job control affects health status; to examine if the effects of job control on health status are attenuated by including other measures associated with lower socioeconomic status, and to examine if the relationship between job control and health status is consistent across socioeconomic status groups. A prospective observational cohort study over eight years (1994-2002). 4886 Respondents aged 25-60 years, who were non-self-employed labour force participants, working more than 20 hours per week, without physical or mental limitations restricting the type or amount of work they could do at baseline. After longitudinal attrition, the remaining study sample was 3411 (87% of the original study sample who did not die or become pregnant during the survey period). Low job control in 1994 was associated with worse than expected self-rated health in 2002, both directly and indirectly via a lower physical activity level in 1996. Adjustment for other factors associated with low socioeconomic status did not attenuate these relationships to a large extent. No differences were found in the effects of job control on physical activity or health status between socioeconomic groups (high and low education and high and low household income). The inclusion of other factors associated with lower socioeconomic status did not attenuate the direct and indirect effects of job control on health status. The finding that low job control is associated with lower physical activity levels deserves further investigation, given the increasing concern about rising levels of obesity in the developed world.


Peptides Derived of Kunitz-Type Serine Protease Inhibitor as Potential Vaccine Against Experimental Schistosomiasis.
Schistosomiasis is a significant public health problem in sub-Saharan Africa, China, Southeast Asia, and regions of South and Central America affecting about 189 million people. Kunitz-type serine protease inhibitors have been identified as important players in the interaction of other flatworm parasites with their mammalian hosts. They are involved in host blood coagulation, fibrinolysis, inflammation, and ion channel blocking, all of them critical biological processes, which make them interesting targets to develop a vaccine. Here, we evaluate the protective efficacy of chemically synthesized T- and B-cell peptide epitopes derived from a kunitz protein from Schistosoma mansoni. Putative kunitz-type protease inhibitor proteins were identified in the S. mansoni genome, and their expression was analyzed by RNA-seq. Gene expression analyses showed that the kunitz protein Smp_147730 (Syn. Smp_311670) was dramatically and significantly up-regulated in schistosomula and adult worms when compared to the invading cercariae. T- and B-cell epitopes were predicted using bioinformatics tools, chemically synthesized, and formulated in the Adjuvant Adaptation (ADAD) vaccination system. BALB/c mice were vaccinated and challenged with S. mansoni cercariae. Kunitz peptides were highly protective in vaccinated BALB/c mice showing significant reductions in recovery of adult females (89-91%) and in the numbers of eggs trapped in the livers (77-81%) and guts (57-77%) of mice. Moreover, liver lesions were significantly reduced in vaccinated mice (64-65%) compared to infected control mice. The vaccination regime was well-tolerated with both peptides. We propose the use of these peptides, alone or in combination, as reliable candidates for vaccination against schistosomiasis.


Strain-level genomic variation in natural populations of Lebetimonas from an erupting deep-sea volcano.
Chemolithoautotrophic Epsilonproteobacteria are ubiquitous in sulfidic, oxygen-poor habitats, including hydrothermal vents, marine oxygen minimum zones, marine sediments and sulfidic caves and have a significant role in cycling carbon, hydrogen, nitrogen and sulfur in these environments. The isolation of diverse strains of Epsilonproteobacteria and the sequencing of their genomes have revealed that this group has the metabolic potential to occupy a wide range of niches, particularly at dynamic deep-sea hydrothermal vents. We expand on this body of work by examining the population genomics of six strains of Lebetimonas, a vent-endemic, thermophilic, hydrogen-oxidizing Epsilonproteobacterium, from a single seamount in the Mariana Arc. Using Lebetimonas as a model for anaerobic, moderately thermophilic organisms in the warm, anoxic subseafloor environment, we show that genomic content is highly conserved and that recombination is limited between closely related strains. The Lebetimonas genomes are shaped by mobile genetic elements and gene loss as well as the acquisition of novel functional genes by horizontal gene transfer, which provide the potential for adaptation and microbial speciation in the deep sea. In addition, these Lebetimonas genomes contain two operons of nitrogenase genes with different evolutionary origins. Lebetimonas expressed nifH during growth with nitrogen gas as the sole nitrogen source, thus providing the first evidence of nitrogen fixation in any Epsilonproteobacteria from deep-sea hydrothermal vents. In this study, we provide a comparative overview of the genomic potential within the Nautiliaceae as well as among more distantly related hydrothermal vent Epsilonproteobacteria to broaden our understanding of microbial adaptation and diversity in the deep sea.


Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality.
Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males) who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents' inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent's secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.


Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.
Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT.


The effect of Rosmarinus herbal tea on occupational burnout in Iran Chemical Industry Investment company employees.
Burnout is one of the most important problems that the employees encounter. Many health problems arise due to burnout which is to be dealt with by the employees and the owners in the industry. Among many different ways of dealing with this problem, herbal therapy seems to be a promising solution. The present study intended to investigate the effect of Rosmarinus officinalis (RO) on burnout in employees who work in industrial environments. An experimental study was performed to see whether RO has an effect on burnout or not. A total of 66 employees, aged between 20 and 60 years, who had worked for at least 1 year in the technical wards of Iran Chemical Industry Investment Company took part in the study. The participants were randomly assigned to two groups of control (n = 33) and RO (n = 33). The RO group received 4 g of Rosemary in 150 cc water per day for 2 months. The control group, on the other hand, did not receive anything. The data were collected via Geldard (1989) Burnout Inventory before and after the treatment. A t-test was performed to analyze the collected data. The results of statistical tests showed that after intervention, the score of occupational burnout in RO group was better, and a significant difference was found between the control and experimental groups (P = 0.03), in favor of the experimental group. The results of the study revealed that Rosmarinus had a positive effect on burnout in employees in this study. Further studies in this field are suggested.


Posttranslational modifications in histones underlie heat acclimation-mediated cytoprotective memory.
We have demonstrated that heat acclimation (AC) causes selective, long-lasting, transcriptional changes in cytoprotective and chromatin remodeling-associated genes, which maintain their AC transcriptome profile, despite the loss of the AC phenotype (Tetievsky et al. Physiol Genomics 34: 78-87, 2008). We postulated that AC memory involves upstream epigenetic information, which predisposes to rapid reacclimation (ReAC) and cytoprotective memory. Here we tested the hypothesis that posttranslational histone modifications are linked to this process. Rats subjected to AC (34°C for 2 or 30 days), deacclimation (DeAC; 24°C, 30 days), and ReAC (34°C, 2 days), and untreated controls were used. Histone H4 lysine acetylation and histone H3 acetylation and phosphorylation in the heat shock element (HSE) of the promoters of heat shock protein-70 (hsp70) and -90 (hsp90) genes were examined. Histone acetyltransferase recruitment of TIP60 (60-kDa histone acetyltransferase-interactive protein), the catalytic subunit of NuH4, was used to validate acetylation. Heat shock factor-1 (HSF-1)-HSE binding to the hsp70 and hsp90 genes was measured to confirm HSF-1 binding to euchromatin. Our results indicate that, while histone H3Ser10 phosphorylation occurred during the AC 2-day phase, AC constitutively elevated histone H4 acetylation in the HSE of hsp70 and hsp90 promoters. HSF-1-HSE binding was detected in the hsp70 gene throughout AC-DeAC-ReAC. The hsp90 gene lacked HSF-1 binding during DeAC, but resumed a high binding level upon ReAC. HSP-90 is a critical cytoprotective protein, and the HSF-1-hsp90 binding profile matched levels of this protein. We conclude that, while early histone H3 phosphorylation is probably required for subsequent histone H4 acetylation, the constitutively acetylated histone H4 and the preserved euchromatin state throughout AC-DeAC-ReAC predispose to rapid cytoprotective acclimatory memory.


Vibrio vulnificus septicemia in a patient with the hemochromatosis HFE C282Y mutation.
Vibrio vulnificus is an extremely invasive gram-negative bacillus found in marine waters that causes overwhelming bacteremia and shock that is associated with high mortality. Impaired iron metabolism has been implicated in the susceptibility to V vulnificus bacterial infections. We report a case of fatal V vulnificus sepsis in a 56-year-old man who died within 1 to 3 days after consuming raw seafood. At autopsy, he was found to have micronodular cirrhosis and iron overload. Postmortem genetic analysis revealed the presence of the hemochromatosis gene (HFE) C282Y mutation. To our knowledge, this is this first documented fatal case of V vulnificus infection in a patient proven to carry the HFE C282Y mutation. Because this patient was heterozygous for the major hereditary hemochromatosis mutation and was not previously diagnosed with clinical iron overload, the spectrum of clinical susceptibilities to V vulnificus infection may include carriers of the C282Y mutation.


High OGT activity is essential for MYC-driven proliferation of prostate cancer cells.
O-GlcNAc transferase (OGT) is overexpressed in aggressive prostate cancer. OGT modifies intra-cellular proteins via single sugar conjugation (O-GlcNAcylation) to alter their activity. We recently discovered the first fast-acting OGT inhibitor OSMI-2. Here, we probe the stability and function of the chromatin O-GlcNAc and identify transcription factors that coordinate with OGT to promote proliferation of prostate cancer cells. Methods: Chromatin immunoprecipitation (ChIP) coupled to sequencing (seq), formaldehyde-assisted isolation of regulatory elements, RNA-seq and reverse-phase protein arrays (RPPA) were used to study the importance of OGT for chromatin structure and transcription. Mass spectrometry, western blot, RT-qPCR, cell cycle analysis and viability assays were used to establish the role of OGT for MYC-related processes. Prostate cancer patient data profiled for both mRNA and protein levels were used to validate findings. Results: We show for the first time that OGT inhibition leads to a rapid loss of O-GlcNAc chromatin mark. O-GlcNAc ChIP-seq regions overlap with super-enhancers (SE) and MYC binding sites. OGT inhibition leads to down-regulation of SE-dependent genes. We establish the first O-GlcNAc chromatin consensus motif, which we use as a bait for mass spectrometry. By combining the proteomic data from oligonucleotide enrichment with O-GlcNAc and MYC ChIP-mass spectrometry, we identify host cell factor 1 (HCF-1) as an interaction partner of MYC. Inhibition of OGT disrupts this interaction and compromises MYC's ability to confer androgen-independent proliferation to prostate cancer cells. We show that OGT is required for MYC-mediated stabilization of mitotic proteins, including Cyclin B1, and/or the increased translation of their coding transcripts. This implies that increased expression of mRNA is not always required to achieve increased protein expression and confer aggressive phenotype. Indeed, high expression of Cyclin B1 protein has strong predictive value in prostate cancer patients (p=0.000014) while mRNA does not. Conclusions: OGT promotes SE-dependent gene expression. OGT activity is required for the interaction between MYC and HCF-1 and expression of MYC-regulated mitotic proteins. These features render OGT essential for the androgen-independent, MYC-driven proliferation of prostate cancer cells. Androgen-independency is the major mechanism of prostate cancer progression, and our study identifies OGT as an essential mediator in this process.


Serum levels, ontogeny and heritability of chicken mannan-binding lectin (MBL).
Mannan-binding lectin (MBL) is a serum lectin found in mammals and recently also in birds. It is thought to play an important role in the innate immune defence through binding to surface carbohydrates on micro-organisms followed by complement activation via the MBL pathway. This results in opsonization or direct complement-mediated killing. To gain further knowledge about the physiology and function of the protein, we developed an enzyme-linked immunosorbent assay for chicken MBL and used this to investigate the level of MBL in different chicken strains during embryogenesis, early and adult life. The MBL concentrations in 308 chickens, representing 14 different strains, showed a non-Gaussian, unimodal distribution profile with a mean concentration of 5.8 micrograms/ml (range 0.4-37.8 micrograms/ml). No difference between the strains could be demonstrated and no chickens were found deficient in MBL. Ontogenetic studies showed that MBL is already detectable in embryos at a gestational age of 10 days (11 days before hatching). At hatching, the level is comparable to the level found in adult chickens. This level is fairly stable during the first weeks of life, but a deficiency state develops at 4 weeks of age, whereafter the level is normalized again at 5 weeks of age. Chickens with relatively low or high MBL levels were bred with cockerels having similar MBL levels and this resulted in F1 generations with significantly different MBL levels, suggesting that the protein level is genetically influenced.


Regime shifts in the anthropocene: drivers, risks, and resilience.
Many ecosystems can experience regime shifts: surprising, large and persistent changes in the function and structure of ecosystems. Assessing whether continued global change will lead to further regime shifts, or has the potential to trigger cascading regime shifts has been a central question in global change policy. Addressing this issue has, however, been hampered by the focus of regime shift research on specific cases and types of regime shifts. To systematically assess the global risk of regime shifts we conducted a comparative analysis of 25 generic types of regime shifts across marine, terrestrial and polar systems; identifying their drivers, and impacts on ecosystem services. Our results show that the drivers of regime shifts are diverse and co-occur strongly, which suggests that continued global change can be expected to synchronously increase the risk of multiple regime shifts. Furthermore, many regime shift drivers are related to climate change and food production, whose links to the continued expansion of human activities makes them difficult to limit. Because many regime shifts can amplify the drivers of other regime shifts, continued global change can also be expected to increase the risk of cascading regime shifts. Nevertheless, the variety of scales at which regime shift drivers operate provides opportunities for reducing the risk of many types of regime shifts by addressing local or regional drivers, even in the absence of rapid reduction of global drivers.


Week 96 outcomes of patients with less treatment experience versus more treatment experience receiving etravirine in the DUET trials.
The disease profile of treatment-experienced HIV-1 patients (TEPs) looks different today compared with that of 5 years ago. Because less highly treated DUET patients may more closely resemble today's TEPs, we conducted a post hoc efficacy and safety analysis of the pooled 96-week DUET data stratified by level of treatment experience. TEPs with HIV-1 were randomised to etravirine (ETR) 200mg twice daily (bid) or placebo bid with a background regimen for 48 weeks (plus optional 48-week extension). TEPs were categorized using 10 demographic and disease characteristics that in prior studies of treatment-experienced subjects had been associated with virologic response; patients meeting ≥5 criteria were categorized as less TEP. 183 patients (men, 87.4%) who received ETR were less TEP and 413 patients (men, 91.0%) were more TEP. At baseline, more TEPs had more advanced disease, more previous antiretroviral (ARV) exposures and fewer options for active ARVs. At Week 96, for patients receiving ETR, response rates for the less TEP group and more TEP group were 68.3% and 52.8%, respectively. Incidence of adverse events (AEs) was similar between groups. A greater proportion of nonresponders in the more TEP group discontinued due to AEs (9.0% vs 5.5%) and virologic failure (18.9% vs 5.5%) compared with the less TEP group. Less TEPs had higher virologic response rates with ETR compared with more TEPs. Because the less TEP population from DUET more closely resembles TEPs with HIV-1 today, data from this subgroup may provide valuable information for real-life treatment decisions.


Vocal fold elasticity of the Rocky Mountain elk (Cervus elaphus nelsoni) - producing high fundamental frequency vocalization with a very long vocal fold.
The vocal folds of male Rocky Mountain elk (Cervus elaphus nelsoni) are about 3 cm long. If fundamental frequency were to be predicted by a simple vibrating string formula, as is often done for the human larynx, such long vocal folds would bear enormous stress to produce the species-specific mating call with an average fundamental frequency of 1 kHz. Predictions would be closer to 50 Hz. Vocal fold histology revealed the presence of a large vocal ligament between the vocal fold epithelium and the thyroarytenoid muscle. In tensile tests, the stress-strain response of vocal fold epithelium and the vocal ligament were determined. Elasticity of both tissue structures reached quantitative values similar to human tissue. It seems unlikely that the longitudinal stress in elk vocal folds can exceed that in human vocal folds by an order of magnitude to overcome the drop in fundamental frequency due to a 3:1 increase in vocal fold length. Alternative hypotheses of how the elk produces high fundamental frequency utterances, despite its very long vocal fold, include a reduced effective vocal fold length in vibration, either due to bending properties along the vocal fold, or by actively moving the boundary point with muscle stiffening. The relationships between an individual's average fundamental frequency, vocal fold length and body size are discussed.


Sodium fluoride-assisted modulation of anodized TiO₂ nanotube for dye-sensitized solar cells application.
This work reports the use of sodium fluoride (in ethylene glycol electrolyte) as the replacement of hydrofluoric acid and ammonium fluoride to fabricate long and perpendicularly well-aligned TiO₂ nanotube (TNT) (up to 21 μm) using anodization. Anodizing duration, applied voltage and electrolyte composition influenced the geometry and surface morphologies of TNT. The growth mechanism of TNT is interpreted by analyzing the current transient profile and the total charge density generated during anodization. The system with low water content (2 wt %) yielded a membrane-like mesoporous TiO₂ film, whereas high anodizing voltage (70 V) resulted in the unstable film of TNT arrays. An optimized condition using 5 wt % water content and 60 V of anodizing voltage gave a stable array of nanotube with controllable length and pore diameter. Upon photoexcitation, TNTs synthesized under this condition exhibited a slower charge recombination rate as nanotube length increased. When made into cis-diisothiocyanato-bis(2,2̀-bipyridyl-4,4̀-dicarboxylato) ruthenium(II) bis (tetrabutyl-ammonium)(N719) dye-sensitized solar cells, good device efficiency at 3.33 % based on the optimized TNT arrays was achieved with longer electron time compared with most mesoporous TiO₂ films.


Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.
Systemic amyloidosis is a disease that often involves multiple organ systems, including the peripheral nervous system. Patients may present with severe, refractory neuropathic pain; however, the optimal treatment approach for pain for these patients remains unclear. A man with severe, refractory neuropathic pain in his bilateral upper and lower extremities and the trunk secondary to amyloid neuropathy is presented. Multiple medication trials, including neuropathic and opioid agents, produced considerable adverse effects and minimal relief. Scrambler therapy, a novel electrical stimulation modality, was used and was associated with substantial short-term but nonsustained benefit. Spinal cord stimulation was considered, but given his diffuse symptoms, it was deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery system was placed with infusion of hydromorphone, resulting in substantial pain reduction in all involved areas and with an improved adverse effect profile. This intervention resulted in immense improvement in the patient's quality of life, despite progression of his systemic amyloidosis. Severe pain in the setting of amyloid neuropathy is often difficult to treat. To our knowledge, this represents the first report of Scrambler therapy or an implanted intrathecal drug delivery system used for a patient with refractory amyloidosis-related neuropathic pain, resulting in substantial analgesic benefit and improved quality of life.


Genotyping of Theileria lestoquardi from sheep and goats in Sudan to support control of Malignant Ovine Theileriosis.
Theileriosis, caused by parasitic protozoa of the genus Theileria parasites, are among the major tick-borne diseases of ruminant livestock. The largest economic losses are attributed in particular to those caused by the leukoproliferative species of Theileria: T. parva, T. annulata and T. lestoquardi. Theileria lestoquardi is transmitted by Hyalomma ticks and causes malignant ovine theileriosis (MOT), a disease that is particularly prevalent in Sudan. The disease is considered of a high economic importance in Sudan, where export of sheep is a major component of the national economy. A live vaccine based on a Sudanese isolate of T. lestoquardi (Atbara strain) was previously developed for the control of MOT in Sudan, but not yet deployed in the field. The present study aims to genetically characterize and compare samples of T. lestoquardi circulating in Sudan as well as the live vaccine isolate in order to understand vaccine breakthroughs and failure that may occur. Sheep and goats blood samples were collected from six regions in Sudan that are known to be endemic for T. lestoquardi infection or have experienced outbreaks of MOT. Blood samples infected with T. lestoquardi were identified by PCR or RLB. Genotyping was carried out by (1) sequencing the homologues of two T. parva CD8+ T cell antigen genes, Tp1 and Tp2, and (2) using a panel of seven micro- and mini-satellite markers. A total of 100 T. lestoquardi positive field samples and the T. lestoquardi (Atbara) vaccine were genotyped. The results showed that all samples had mixed genotypes, with several alleles identified at one or more loci. The gene diversity ranged from 0.7840 (TS8) to 0.2133 (TS12) with mean values of 0.5470. PCA revealed three clusters of the parasite in Sudan; interestingly one independent cluster was clearly seen, corresponding to the vaccine isolate. The T. lestoquardi Tp1 homologue showed higher homology with T. annulata than with T. parva sequences included the defined single CD8+ T cell target epitope region. The result indicates that multiple genotypes are a common feature of T. lestoquardi infection in Sudan. Both genotyping and the sequencing results clearly showed that the vaccine isolate is highly distinct from the field samples. This finding raised the question whether vaccination with the prepared lived vaccine will effectively protect animals against challenges by the field isolates of T. lestoquardi. The results of this work will inform on the best approach for controlling MOT in Sudan.


Participation in curbside recycling schemes and its variation with material types.
Local authorities throughout the UK are refining or implementing curbside recycling schemes as they attempt to achieve challenging statutory recycling targets. Despite the importance of curbside schemes there are few published studies that have reported on actual measured levels and frequency of participation by residents, hindering transferability of lessons learned nationally and internationally. This paper reports measurements and analysis over at least four weeks for three different curbside recycling schemes operating in England, with at least 1400 samples in each. It is found that the participation rate is higher in schemes that collect more types of materials. Participation rates of 38%, 49% and 65% were measured for schemes that collected 1, 2 and 3 material types, respectively. The increase appears to be related not only to extra participants setting out the additional materials, but also increased participation for the common materials. It is found that for one scheme, more households tend to set out plastics and cans compared to newspapers.


McGill Brisbane Symptom Score for patients with resectable pancreatic head adenocarcinoma.
To evaluate the ability of the McGill Brisbane Symptom Score (MBSS) to predict survival in resectable pancreatic head adenocarcinoma (PHA) patients. All PHA patients (n = 83) undergoing pancreaticoduodenectomy at the McGill University Health Center, Quebec between 1/2001-1/2010 were evaluated. Data related to patient and cancer characteristics, MBSS variables, and treatment were collected; univariable and multivariable survival analyses were performed. We obtained complete follow-up until February 2011 in all patients through the database of the provincial health insurance plan of Quebec. The unique health insurance numbers of these patients were used to retrieve information from this database which captures all billable clinical encounters, and ensures 100% actual survival data. Median survival was 23 mo overall: 45 mo for patients with low MBSS, 17 mo for high MBSS (P = 0.005). At twelve months survival was 83.3% (95%CI: 66.6-92.1) vs 58.1% (95%CI: 42.1-71.2) in those with low vs high MBSS, and 24 mo survival was 63.8% (95%CI: 45.9-77.1) and 34.0% (95%CI: 20.2-48.2) respectively. In the multivariate Cox model (stratified by chemotherapy), after addition of clinically meaningful covariates, MBSS was the variable with the strongest association with survival (HR = 2.63; P = 0.001). Adjuvant chemotherapy interacted with MBSS category such that only high MBSS patients accrued a benefit. In univariate analysis we found a lower mortality in high MBSS but not low MBSS patients receiving adjuvant chemotherapy. This interaction variable, on Cox model, resulted in an adjusted mortality HR for the high MBSS (compared to low MBSS) of 4.14 (95%CI: 1.48-11.64) without chemotherapy and 2.11 (95%CI: 1.06-4.17) with chemotherapy. The MBSS is a simple prognostic tool for resectable PHA. Preoperative categorization of patients according to the MBSS allows effective stratification of patients to guide therapy.


A gene for non-specific X-linked mental retardation (MRX55) is located in Xp11.
A new family with a non-specific X-linked mental retardation (MRX55) is described. An X-linked recessive inheritance is suggested by the segregation from two healthy transmitting females of moderate mental retardation in three males, without any specific clinical, radiological or biological features. Two point linkage analysis demonstrated significant linkage between the disorder and several markers in Xp11 (Zmax = 2.11, theta = 0); multipoint linkage analyses confirmed the significant linkage with a maximum lod score (Z = 2.11 at theta = 0, at DXS8012). Recombination events observed with the flanking markers DXS1068 and DXS1275 delineate a 34 centimorgan interval in the pericentromeric region. The interval of assignment pointed out in this family overlaps with several MRX loci previously reported in Xp11 which are reviewed here in.


The accuracy of a simple, low-cost GPS data logger/receiver to study outdoor human walking in view of health and clinical studies.
Accurate and objective measurements of physical activity and lower-extremity function are important in health and disease monitoring, particularly given the current epidemic of chronic diseases and their related functional impairment. The aim of the present study was to determine the accuracy of a handy (lightweight, small, only one stop/start button) and low-cost (∼$75 with its external antenna) Global Positioning System (GPS) data logger/receiver (the DG100) as a tool to study outdoor human walking in perspective of health and clinical research studies. Methods. Healthy subjects performed two experiments that consisted of different prescribed outdoor walking protocols. Experiment 1. We studied the accuracy of the DG100 for detecting bouts of walking and resting. Experiment 2. We studied the accuracy of the DG100 for estimating distances and speeds of walking. Experiment 1. The performance in the detection of bouts, expressed as the percentage of walking and resting bouts that were correctly detected, was 92.4% [95% Confidence Interval: 90.6-94.3]. Experiment 2. The coefficients of variation [95% Confidence Interval] for the accuracy of estimating the distances and speeds of walking were low: 3.1% [2.9-3.3] and 2.8% [2.6-3.1], respectively. The DG100 produces acceptable accuracy both in detecting bouts of walking and resting and in estimating distances and speeds of walking during the detected walking bouts. However, before we can confirm that the DG100 can be used to study walking with respect to health and clinical studies, the inter- and intra-DG100 variability should be studied. ClinicalTrials.gov NCT00485147.


Does use of computer technology for perinatal data collection influence data quality?
Population health data, collected worldwide in an effort to monitor mortality and morbidity of mothers and babies, namely, perinatal data, are mandated at a federal level within Australia. The data are used to monitor patterns in midwifery, obstetric and neonatal practice, health outcomes, used for research purposes, funding allocation and education. Accuracy in perinatal data is most often reported via quantitative validation studies of perinatal data collections both internationally and in Australia. These studies report varying levels of accuracy and suggest researchers need to be more aware of the quality of data they use. This article presents findings regarding issues of concern identified by midwives relating to their perceptions of how technology affects the accuracy of perinatal data records. Perinatal data records are perceived to be more complete when completed electronically. However, issues regarding system functionality, the inconsistent use of terminology, lack of data standards and the absence of clear, written records contribute to midwives' perceptions of the negative influence of technology on the quality of perinatal data.


Host plant species determines symbiotic bacterial community mediating suppression of plant defenses.
Herbivore associated bacteria are vital mediators of plant and insect interactions. Host plants play an important role in shaping the gut bacterial community of insects. Colorado potato beetles (CPB; Leptinotarsa decemlineata) use several Solanum plants as hosts in their natural environment. We previously showed that symbiotic gut bacteria from CPB larvae suppressed jasmonate (JA)-induced defenses in tomato. However, little is known about how changes in the bacterial community may be involved in the manipulation of induced defenses in wild and cultivated Solanum plants of CPB. Here, we examined suppression of JA-mediated defense in wild and cultivated hosts of CPB by chemical elicitors and their symbiotic bacteria. Furthermore, we investigated associations between the gut bacterial community and suppression of plant defenses using 16 S rRNA amplicon sequencing. Symbiotic bacteria decreased plant defenses in all Solanum hosts and there were different gut bacterial communities in CPB fed on different host plants. When larvae were reared on different hosts, defense suppression differed among host plants. These results demonstrate that host plants influence herbivore gut bacterial communities and consequently affect the herbivore's ability to manipulate JA-mediated plant defenses. Thus, the presence of symbiotic bacteria that suppress plant defenses might help CPB adapt to host plants.