Decision support for vessel traffic service (VTS): user needs for dynamic risk management in the VTS.
Vessel Traffic Service (VTS) is a shore-side service implemented by a "Competent Authority to improve the safety and efficiency of vessel traffic and to protect the environment". It is a service that operates through VTS centers, from which VTS operators monitor traffic, assist in navigational matters and provide information to all ships in a designated area. As VTS is provided by operators located on shore, they usually make use of several decision support systems to be able to monitor the traffic and to provide information to the vessels. Although several new tools and approaches have been introduced in the VTS domain, there is still room for improvements. This paper summarizes the results from three studies conducted within the EfficienSea project to approach user needs for dynamic risk management in the VTS domain. Data was collected by conducting study visits and observations at VTS centers, a focus group interview as well as several semi-structured interviews. The paper summarizes the results and presents technical and organizational user needs for dynamic risk management within the VTS domain.


Assessing factors associated with HIV testing among adolescents in Malawi.
Despite being at high risk of HIV/AIDS, most young people do not know their HIV status. Using survey data (n = 2428) and applying multilevel models, this paper assesses factors associated with HIV testing among adolescents in Northern Malawi. The results show that among both boys (OR = 0.39) and girls (OR = 0.47), orphan status is associated with low likelihood of HIV testing. Correct knowledge about HIV/AIDS (OR = 2.55) and having secondary education (OR = 3.24) are associated with HIV testing among boys and girls, respectively. At the household level, living in a household whose head has secondary or higher education is positively associated with testing for boys (OR = 2.63), while residing together with biological siblings predicts higher odds of testing (OR = 2.67) for girls. Notably, orphaned girls' disadvantage regarding HIV testing loses significance when residential arrangement is controlled. At the community level, having HIV testing facility (OR = 2.70) or post-test club (OR = 1.40) is positively associated with HIV testing for boys, while girls from areas where religious leaders hold judgmental views about HIV/AIDS are less likely (OR = 0.45) to test. These findings suggest that efforts to scale up HIV testing among youth could benefit greatly from an understanding of how individual and community factors operate to influence adolescents to know their sero-status.


Catalytic growth of ZnO nanostructures by r.f. magnetron sputtering.
The catalytic effect of gold seed particles deposited on a substrate prior to zinc oxide (ZnO) thin film growth by magnetron sputtering was investigated. For this purpose, selected ultra thin gold layers, with thicknesses close to the percolation threshold, are deposited by thermal evaporation in ultra high vacuum (UHV) conditions and subsequently annealed to form gold nanodroplets. The ZnO structures are subsequently deposited by r.f. magnetron sputtering in a UHV chamber, and possible morphological differences between the ZnO grown on top of the substrate and on the gold are investigated. The results indicate a moderate catalytic effect for a deposited gold underlayer of 4 nm, quite close to the gold thin film percolation thickness.


Hyperexcretion of homocitrulline in a Malaysian patient with lysinuric protein intolerance.
Lysinuric protein intolerance (LPI; MIM 222700) is an inherited aminoaciduria with an autosomal recessive mode of inheritance. Biochemically, affected patients present with increased excretion of the cationic amino acids: lysine, arginine, and ornithine. We report the first case of LPI diagnosed in Malaysia presented with excessive excretion of homocitrulline. The patient was a 4-year-old male who presented with delayed milestones, recurrent diarrhea, and severe failure to thrive. He developed hyperammonemic coma following a forced protein-rich diet. Plasma amino acid analysis showed increased glutamine, alanine, and citrulline but decreased lysine, arginine and ornithine. Urine amino acids showed a marked excretion of lysine and ornithine together with a large peak of unknown metabolite which was subsequently identified as homocitrulline by tandem mass spectrometry. Molecular analysis confirmed a previously unreported homozygous mutation at exon 1 (235 G > A, p.Gly79Arg) in the SLC7A7 gene. This report demonstrates a novel mutation in the SLC7A7 gene in this rare inborn error of diamino acid metabolism. It also highlights the importance of early and efficient treatment of infections and dehydration in these patients. The diagnosis of LPI is usually not suspected by clinical findings alone, and specific laboratory investigations and molecular analysis are important to get a definitive diagnosis.


Botulinum A toxin injected into the gastric wall for the treatment of class III obesity: a pilot study.
Obesity represents a major public health problem in western countries. Initial studies suggest that injection of botulinum A toxin (Btx-A) into the antropyloric region inhibits propulsive contractions of the antral pump, with delay in gastric emptying, early satiety and weight loss. After approval by the University Ethics Committee, we prospectively evaluated 12 patients with class III obesity divided into 4 groups of 3 patients each. In groups I and II, 200 U Btx-A were injected into the antropyloric region at 8 and 16 sites, respectively. Groups III and IV received 300 U Btx-A into the antropyloric region at 16 and 24 sites, respectively. Body weight and gastric emptying time (GET) of solids and semi-solids using 13C-octanoic acid breath test and 13C-acetic acid breath test, respectively, were determined before and after injection over a period of 12 weeks. Pre- and post-treatment body weight or solid and semi-solid GET did not differ significantly between groups (P>0.05). All patients reported a feeling of early satiety. No adverse effects related to BtxA or complications resulting from the endoscopic procedure were observed. The injection of different doses of BtxA at different sites in the antropyloric region of patients with class III obesity did not interfere significantly with the solid and semi-solid GET or body weight of these individuals. However, early satiety was reported by all patients, the procedure was safe and no side-effects of the treatment were observed. Further controlled studies involving different methodologies regarding dosage of Btx-A and sites of injection are necessary.


Maintenance treatment with cyclosporin in atopic eczema.
We have studied two reducing-dose regimens intended to minimize toxicity of cyclosporin A (CyA) while maintaining its capacity to control atopic eczema following induction of remission. Twenty-four patients with severe chronic atopic eczema were first treated in a double-blind randomized placebo-controlled cross-over study of CyA (5 mg/kg/day). All 19 who completed the study showed the expected highly significant improvements, compared with placebo, in area involved, erythema, excoriation, lichenification, itch and requirement for topical steroid. In 17 of the 19 patients, control was re-established with CyA 5 mg/kg/day, and they were then re-randomized to stepwise reduction at 2-week intervals in either (i) the dose of CyA given daily, or (ii) the frequency with which the 5 mg/kg dose was given. Fifteen patients (seven continuous reducing dose, eight intermittent fixed dose) completed the planned reduction to either 1 mg/kg/day or 5 mg/kg every fifth day. In both groups the response was sustained despite dose reduction, although control was less good at a continuous dose of 1 mg/kg. Intermittent treatment was as good as or better than continuous reducing dosage in this study, and in both groups there was further deterioration after the drug was stopped. The findings suggest that the dose of CyA required to control atopic eczema is less than that required to achieve remission, and that the therapeutic index can be further improved by alternative dosing strategies. This offers a new approach to maintenance treatment of eczema and other chronic refractory dermatoses.


Understanding social inequalities in health.
A prominent feature of health in all industrialized countries is the social gradient in health and disease. Many observers believe that this gradient is simply a matter of poor health for the disadvantaged and good health for everyone else, but this is an inadequate analysis. The Whitehall Study documented a social gradient in mortality rates, even among people who are not poor, and this pattern has been confirmed by data from the United States and elsewhere. The social gradient in health is influenced by such factors as social position; relative versus absolute deprivation; and control and social participation. To understand causality and generate policies to improve health, we must consider the relationship between social environment and health and especially the importance of early life experiences.


Delivery of cellular factors to regulate bone healing.
Bone tissue has a strong intrinsic regenerative capacity, thanks to a delicate and complex interplay of cellular and molecular processes, which tightly involve the immune system. Pathological settings of anatomical, biomechanical or inflammatory nature may lead to impaired bone healing. Innovative strategies to enhance bone repair, including the delivery of osteoprogenitor cells or of potent cytokines/morphogens, indicate the potential of 'orthobiologics', but are not fully satisfactory. Here, we review different approaches based on the delivery of regenerative cues produced by cells but in cell-free, possibly off-the-shelf configurations. Such strategies exploit the paracrine effect of the secretome of mesenchymal stem/stromal cells, presented in soluble form, shuttled through extracellular vesicles, or embedded within the network of extracellular matrix molecules. In addition to osteoinductive molecules, attention is given to factors targeting the resident immune cells, to reshape inflammatory and immunity processes from scarring to regenerative patterns.


A multi-day environmental study of polycyclic aromatic hydrocarbon exposure in a high-risk region for esophageal cancer in China.
Linzhou, China has one of the highest rates of esophageal squamous cell carcinoma in the world. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), may have a role in this increased risk. To better understand PAH sources, we measured PAHs in the air and food of 20 non-smokers over multiple days and compared the concentrations with a urinary PAH biomarker, 1-hydroxypyrene glucuronide (1-OHPG). Sampling occurred over 4 consecutive days. Kitchen air samples (days 2-3) and duplicate diet samples (days 1-4) were analyzed for 14 or more unique PAHs, including BaP. Daily urine samples (days 1-3) were analyzed for 1-OHPG. Mixed-effects models were used to evaluate the associations between air or food PAH concentrations and urine 1-OHPG concentrations. The median kitchen air BaP concentration was 10.2 ng/m(3) (interquartile range (IQR): 5.1-20.2 ng/m(3)). The median daily food BaP concentration and intake were 0.08 ng/g (IQR=0.04-0.16 ng/g) and 86 ng/day (IQR=41-142 ng/day), respectively. The median 1-OHPG concentration was 3.36 pmol/ml (IQR=2.09-6.98 pmol/ml). In mixed-effects models, 1-OHPG concentration increased with same-day concentration of food BaP (P=0.07). Although PAH concentrations in air were not associated with 1-OHPG concentrations, the high concentrations of PAHs in both air and food suggest that they are both important routes of exposure to PAHs in this population. Further evaluation of the role of PAH exposure from air and food in the elevated rates of esophageal cancer in this region is warranted.


A mixed methods study of the work patterns of full-time nurse practitioners in nursing homes.
The aim of this study was to explore the integration of the nurse practitioner role in Canadian nursing homes to enable its full potential to be realised for resident and family care. The objective was to determine nurse practitioners' patterns of work activities. Nurse practitioners were introduced in Canadian nursing homes a decade ago on a pilot basis. In recent years, government and nursing home sector interest in the role has grown along with the need for data to inform planning efforts. The study used a sequential mixed methods design using a national survey followed by case studies. A national survey of nurse practitioners included demographic items and the EverCare Nurse Practitioner Role and Activity Scale. Following the survey, case studies were conducted in four nursing homes. Data were collected using individual and focus group interviews, document reviews and field notes. Twenty-three of a target population of 26 nurse practitioners responded to the survey, two-thirds of whom provided services in nursing homes with one site and the remainder in nursing homes with as many as four sites. On average, nurse practitioners performed activities in communicator, clinician, care manager/coordinator and coach/educator subscales at least three to four times per week and activities in the collaborator subscale once a week. Of the 43 activities, nurse practitioners performed daily, most were in the clinician and communicator subscales. Case study interviews involved 150 participants. Findings complemented those of the survey and identified additional leadership activities. Nurse practitioners undertake a range of primary health care and advanced practice activities which they adapt to meet the unique needs of nursing homes. Knowledge of work patterns enables nursing homes to implement the full range of nurse practitioner roles and activities to enhance resident and family care.


Comprehensive meta-analysis, co-expression, and miRNA nested network analysis identifies gene candidates in citrus against Huanglongbing disease.
Huanglongbing (HLB), the most devastating disease of citrus, is associated with infection by Candidatus Liberibacter asiaticus (CaLas) and is vectored by the Asian citrus psyllid (ACP). Recently, the molecular basis of citrus-HLB interactions has been examined using transcriptome analyses, and these analyses have identified many probe sets and pathways modulated by CaLas infection among different citrus cultivars. However, lack of consistency among reported findings indicates that an integrative approach is needed. This study was designed to identify the candidate probe sets in citrus-HLB interactions using meta-analysis and gene co-expression network modelling. Twenty-two publically available transcriptome studies on citrus-HLB interactions, comprising 18 susceptible (S) datasets and four resistant (R) datasets, were investigated using Limma and RankProd methods of meta-analysis. A combined list of 7,412 differentially expressed probe sets was generated using a Teradata in-house Structured Query Language (SQL) script. We identified the 65 most common probe sets modulated in HLB disease among different tissues from the S and R datasets. Gene ontology analysis of these probe sets suggested that carbohydrate metabolism, nutrient transport, and biotic stress were the core pathways that were modulated in citrus by CaLas infection and HLB development. We also identified R-specific probe sets, which encoded leucine-rich repeat proteins, chitinase, constitutive disease resistance (CDR), miraculins, and lectins. Weighted gene co-expression network analysis (WGCNA) was conducted on 3,499 probe sets, and 21 modules with major hub probe sets were identified. Further, a miRNA nested network was created to examine gene regulation of the 3,499 target probe sets. Results suggest that csi-miR167 and csi-miR396 could affect ion transporters and defence response pathways, respectively. Most of the potential candidate hub probe sets were co-expressed with gibberellin pathway (GA)-related probe sets, implying the role of GA signalling in HLB resistance. Our findings contribute to the integration of existing citrus-HLB transcriptome data that will help to elucidate the holistic picture of the citrus-HLB interaction. The citrus probe sets identified in this analysis signify a robust set of HLB-responsive candidates that are useful for further validation.


Leptin promotes wound healing in the oral mucosa.
Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa. Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively. Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin. Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the oral mucosa.


FGF signaling regulates Wnt ligand expression to control vulval cell lineage polarity in C. elegans.
The interpretation of extracellular cues leading to the polarization of intracellular components and asymmetric cell divisions is a fundamental part of metazoan organogenesis. The Caenorhabditis elegans vulva, with its invariant cell lineage and interaction of multiple cell signaling pathways, provides an excellent model for the study of cell polarity within an organized epithelial tissue. Here, we show that the fibroblast growth factor (FGF) pathway acts in concert with the Frizzled homolog LIN-17 to influence the localization of SYS-1, a component of the Wnt/β-catenin asymmetry pathway, indirectly through the regulation of cwn-1. The source of the FGF ligand is the primary vulval precursor cell (VPC) P6.p, which controls the orientation of the neighboring secondary VPC P7.p by signaling through the sex myoblasts (SMs), activating the FGF pathway. The Wnt CWN-1 is expressed in the posterior body wall muscle of the worm as well as in the SMs, making it the only Wnt expressed on the posterior and anterior sides of P7.p at the time of the polarity decision. Both sources of cwn-1 act instructively to influence P7.p polarity in the direction of the highest Wnt signal. Using single molecule fluorescence in situ hybridization, we show that the FGF pathway regulates the expression of cwn-1 in the SMs. These results demonstrate an interaction between FGF and Wnt in C. elegans development and vulval cell lineage polarity, and highlight the promiscuous nature of Wnts and the importance of Wnt gradient directionality within C. elegans.


Communicating with the workforce during emergencies: developing an employee text messaging program in a local public health setting.
Short message service (SMS) text messaging can be useful for communicating information to public health employees and improving workforce situational awareness during emergencies. We sought to understand how the 1,500 employees at Public Health--Seattle & King County, Washington, perceived barriers to and benefits of participation in a voluntary, employer-based SMS program. Based on employee feedback, we developed the system, marketed it, and invited employees to opt in. The system was tested during an ice storm in January 2012. Employee concerns about opting into an SMS program included possible work encroachment during non-work time and receiving excessive irrelevant messages. Employees who received messages during the weather event reported high levels of satisfaction and perceived utility from the program. We conclude that text messaging is a feasible form of communication with employees during emergencies. Care should be taken to design and deploy a program that maximizes employee satisfaction.


The impact of seasonal and year-round transmission regimes on the evolution of influenza A virus.
Punctuated antigenic change is believed to be a key element in the evolution of influenza A; clusters of antigenically similar strains predominate worldwide for several years until an antigenically distant mutant emerges and instigates a selective sweep. It is thought that a region of East-Southeast Asia with year-round transmission acts as a source of antigenic diversity for influenza A and seasonal epidemics in temperate regions make little contribution to antigenic evolution. We use a mathematical model to examine how different transmission regimes affect the evolutionary dynamics of influenza over the lifespan of an antigenic cluster. Our model indicates that, in non-seasonal regions, mutants that cause significant outbreaks appear before the peak of the wild-type epidemic. A relatively large proportion of these mutants spread globally. In seasonal regions, mutants that cause significant local outbreaks appear each year before the seasonal peak of the wild-type epidemic, but only a small proportion spread globally. The potential for global spread is strongly influenced by the intensity of non-seasonal circulation and coupling between non-seasonal and seasonal regions. Results are similar if mutations are neutral, or confer a weak to moderate antigenic advantage. However, there is a threshold antigenic advantage, depending on the non-seasonal transmission intensity, beyond which mutants can escape herd immunity in the non-seasonal region and there is a global explosion in diversity. We conclude that non-seasonal transmission regions are fundamental to the generation and maintenance of influenza diversity owing to their epidemiology. More extensive sampling of viral diversity in such regions could facilitate earlier identification of antigenically novel strains and extend the critical window for vaccine development.


From Intelligent Energy Management to Value Economy through a Digital Energy Currency: Bahrain City Case Study.
The transition of the energy system into a more efficient state requires innovative ideas to finance new schemes and engage people into adjusting their behavioural patterns concerning consumption. Effective energy management combined with Information and Communication Technologies (ICTs) open new opportunities for local and regional authorities, but also for energy suppliers, utilities and other obligated parties, or even energy cooperatives, to implement mechanisms that allow people to become more efficient either by producing and trading energy or by reducing their energy consumption. In this paper, a novel framework is proposed connecting energy savings with a digital energy currency. This framework builds reward schemes where the energy end-users could benefit financially from saving energy, by receiving coins according to their real consumption compared to the predicted consumption if no actions were to take place. A pilot appraisal of such a scheme is presented for the case of Bahrain, so as to simulate the behaviour of the proposed framework in order for it to become a viable choice for intelligent energy management in future action plans.


Role of myristoylation in the intracellular targeting of neuronal calcium sensor (NCS) proteins.
The control of the intracellular localization of NCS (neuronal calcium sensor) proteins is of importance for their ability to respond appropriately to differing calcium signals. We examine the localization of three NCS proteins: NCS-1, KChIP-1 (potassium-channel-interacting protein 1) and hippocalcin. Additionally, the [Ca(2+)] dependency of the calcium-induced translocation of hippocalcin is investigated. The implications of the differential targeting of these proteins on calcium signal interpretation are considered.


DIFFUSE CHORIORETINAL ATROPHY IN CHINESE HIGH MYOPIA: The ZOC-BHVI High Myopia Cohort Study.
To explore the associations between diffuse chorioretinal atrophy (DCA) and age, sex, axial length, spherical equivalent, and best-corrected visual acuity (BCVA) among highly myopic eyes. This study included right eyes of 857 bilaterally highly myopic individuals from the ZOC-BHVI Cohort Study. Participants underwent examinations, including BCVA, ocular biometry, autorefraction, and color fundus photography. An Early Treatment Diabetic Retinopathy Study grid was applied on the fundus photographs to evaluate the location of DCA, which was graded into four categories (D0-D3). The characteristics and ocular biometry were compared between participants' eyes with and without DCA. Diffuse chorioretinal atrophy was found in 177 (20.6%) eyes. The proportion of participants with DCA in age groups of 7 to 11, 12 to 18, 19 to 39, and ≥ 40 years old was 20.9%, 9.2%, 23.1%, and 52.9%, respectively. The proportion of DCA significantly increased with longer axial length and worse myopic spherical equivalent. Eyes with DCA had poorer BCVA (Snellen visual acuity 20/36, logarithm of minimal angle of resolution 0.26 ± 0.25) than those without DCA (Snellen visual acuity 20/23, logarithm of minimal angle of resolution 0.06 ± 0.14) (P < 0.001). The BCVA gradually declined as the lesion got closer to the fovea (P for trend < 0.001). The proportion of DCA increased with older age, longer axial length, and more myopic spherical equivalent. Diffuse chorioretinal atrophy is a vision-threatening complication of high myopia where BCVA gradually worsens with foveal involvement.


Strategies to Prevent Acute Kidney Injury after Pediatric Cardiac Surgery: A Network Meta-Analysis.
AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery. PubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed. Twenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis suggested a 80% relative risk reduction with dexmedetomidine and evidence of <57% relative risk reduction with remote ischemic preconditioning. Nonetheless, the network meta-analysis was unable to demonstrate any significant differences among the examined treatments, including also acetaminophen, aminophylline, levosimendan, milrinone, and normothermic cardiopulmonary bypass. Surface under the cumulative ranking curve probabilities showed that milrinone (76%) was most likely to result in the lowest risk of AKI, followed by dexmedetomidine (70%), levosimendan (70%), aminophylline (59%), normothermic cardiopulmonary bypass (57%), and remote ischemic preconditioning (55%), although all showing important overlap. Current evidence from randomized controlled trials does not support the efficacy of most strategies to prevent AKI in the pediatric population, apart from limited evidence for dexmedetomidine and remote ischemic preconditioning.


Denervating the pelvic suspensory ligaments of horses causes morphological and histological changes in the ligaments.
To examine changes occurring in normal pelvic suspensory ligaments (SLs) of horses after denervating these ligaments and to investigate the effect chronic inflammation might have on these changes. 10 horses. The SL of 1 randomly selected pelvic limb of each of 5 horses was injected with collagenase to induce desmitis, and 42 days later, the proximal aspect of both pelvic SLs were denervated. The SLs were harvested 120 days after being denervated, and the morphological and histological characteristics of each collagenase-injected, denervated SL were compared with those of the contralateral, non-injected, denervated SL. All denervated SLs were compared with non-denervated pelvic SLs harvested from 5 horses similar in weight and age. The mean width and the cross-sectional area of the musculature of all denervated SLs were significantly less than that of the non-denervated ligaments. The mean thickness of collagenase-injected denervated ligaments, but not that of the non-injected denervated ligaments, was significantly less than that of the non-denervated ligaments. Histological abnormalities typical of neurogenic muscular atrophy were observed in all denervated ligaments. Loss of motor neuronal input to the proximal aspect of the SL of the pelvic limb of horses causes neurogenic atrophy of the musculature in that portion of the ligament. Denervating a SL of a pelvic limb may weaken the ligament, increasing its risk of injury. Chronic inflammation of the SL before neurectomy may exacerbate atrophy of the musculature after neurectomy.


The Associations of Dyadic Coping and Relationship Satisfaction Vary between and within Nations: A 35-Nation Study.
Theories about how couples help each other to cope with stress, such as the systemic transactional model of dyadic coping, suggest that the cultural context in which couples live influences how their coping behavior affects their relationship satisfaction. In contrast to the theoretical assumptions, a recent meta-analysis provides evidence that neither culture, nor gender, influences the association between dyadic coping and relationship satisfaction, at least based on their samples of couples living in North America and West Europe. Thus, it is an open questions whether the theoretical assumptions of cultural influences are false or whether cultural influences on couple behavior just occur in cultures outside of the Western world. In order to examine the cultural influence, using a sample of married individuals (N = 7973) from 35 nations, we used multilevel modeling to test whether the positive association between dyadic coping and relationship satisfaction varies across nations and whether gender might moderate the association. RESULTS reveal that the association between dyadic coping and relationship satisfaction varies between nations. In addition, results show that in some nations the association is higher for men and in other nations it is higher for women. Cultural and gender differences across the globe influence how couples' coping behavior affects relationship outcomes. This crucial finding indicates that couple relationship education programs and interventions need to be culturally adapted, as skill trainings such as dyadic coping lead to differential effects on relationship satisfaction based on the culture in which couples live.


Supramolecular Additive-Initiated Controlled Atom Transfer Radical Polymerization of Zwitterionic Polymers on Ureido-pyrimidinone-Based Biomaterial Surfaces.
Surface-initiated controlled radical polymerization is a popular technique for the modification of biomaterials with, for example, antifouling polymers. Here, we report on the functionalization of a supramolecular biomaterial with zwitterionic poly(sulfobetaine methacrylate) via atom transfer radical polymerization from a macroinitiator additive, which is embedded in the hard phase of the ureido-pyrimidinone-based material. Poly(sulfobetaine methacrylate) was successfully polymerized from these surfaces, and the polymerized sulfobetaine content, with corresponding antifouling properties, depended on both the macroinitiator additive concentration and polymerization time. Furthermore, the polymerization from the macroinitiator additive was successfully translated to functional electrospun scaffolds, showing the potential for this functionalization strategy in supramolecular material systems.


PDZ Sample Quality Assessment by Biochemical and Biophysical Characterizations.
PDZ domains are small globular domains involved in protein-protein interactions. They participate in a wide range of critical cellular processes. These domains, very abundant in the human proteome, are widely studied by high-throughput interactomics approaches and by biophysical and structural methods. However, the quality of the results is strongly related to the optimal folding and solubility of the domains. We provide here a detailed description of protocols for a strict quality assessment of the PDZ constructs. We describe appropriate experimental approaches that have been selected to overcome the small size of such domains to check the purity, identity, homogeneity, stability, and folding of samples.


Life history change in response to fishing and an introduced predator in the East African cyprinid Rastrineobola argentea.
Fishing and introduced species are among the most important stressors affecting freshwaters and can also be strong selective agents. We examined the combined effects of commercial fishing and an introduced predator (Nile perch, Lates niloticus) on life history traits in an African cyprinid fish (Rastrineobola argentea) native to the Lake Victoria basin in East Africa. To understand whether these two stressors have driven shifts in life history traits of R. argentea, we tested for associations between life history phenotypes and the presence/absence of stressors both spatially (across 10 Ugandan lakes) and temporally (over four decades in Lake Victoria). Overall, introduced Nile perch and fishing tended to be associated with a suite of life history responses in R. argentea, including: decreased body size, maturation at smaller sizes, and increased reproductive effort (larger eggs; and higher relative fecundity, clutch volume, and ovary weight). This is one of the first well-documented examples of fisheries-induced phenotypic change in a tropical, freshwater stock; the magnitude of which raises some concerns for the long-term sustainability of this fishery, now the most important (by mass) in Lake Victoria.


Analysis of epithelial cell stress response during infection by Shigella flexneri.
Shigella flexneri-infected macrophage cells undergo an apoptotic-like death as early as one hour after infection (A. Zychlinsky, M. C. Prévost, and P. J. Sansonetti, Nature [London] 358:167-168, 1992). To determine the fate of infected epithelial cells, we characterized the viability, morphology, and several metabolic activities of HeLa cells after treatment with M90T, an invoffve isolate of S. flexneri serotype 5, or BS176, a noninvasive isolate cured of the 220-kb virulence plasmid. Using standard assays, we found that for at least 4 h after infection with M90T, HeLa cells remained viable and did not detach or lyse. The ultrastructural morphology of HeLa cells heavily infected with M90T was free of hallmarks associated with cells undergoing apoptosis. Consistent with the idea that intracellular bacterial growth is metabolically stressful to the host cell, we observed that, compared with BS176 treated-HeLa cells, M90T-treated HeLa cells showed (i) a significant decrease in the total pool size of nucleoside triphosphates, (ii) a reduced ability to incorporate extracellular radiolabeled methionine into the soluble and insoluble cell fractions, and (iii) a stimulation of glucose uptake. However, there was no detectable increase in expression of the stress-inducible hsp70 gene in M90T-infected HeLa cells or activation of the anaerobic metabolic pathway as determined by measuring total lactate levels. These results demonstrate clearly that the fate of S.flexneri-infected cells can vary dramatically between cell types and agree with the hypothesis that the destruction of epithelial cells observed in experimental models of shigellosis is due to the host inflammatory response and probably not bacterial intracellular multiplication per se.


Critical care nurses' experiences of providing care for adults in a highly technological environment: A qualitative evidence synthesis.
To synthesise the available body of qualitative evidence relating to nurses' perceptions and experiences of care provision in adult critical care environments. The study adhered to ENTREQ (Confidence in Evidence of Reviews of Qualitative Research) guidelines. See Appendix S1. A systematic search of the literature in nine databases was undertaken: CINAHL, Web of Science, MEDLINE, EMBASE, PsycINFO, Campbell Collaboration, ProQuest A & I, DART and Lenus. Blind screening to select relevant studies was undertaken, and each selected study was assessed for quality using the Critical Appraisal Skills Programme framework. Guided by Thomas and Harden's three-stage approach to thematic analysis, line-by-line coding of participants' verbatim accounts and the researchers' interpretations in the selected studies' findings was undertaken and then organised into higher order analytical themes. Confidence in the findings was reviewed using GRADE-CERQual. Twelve studies reported in thirteen papers, including 122 nurses, were selected in the final sample for synthesis. Three analytical themes were identified: (a) sometimes machines get all the attention, (b) with experience the patient becomes the focus and (c) technology can't save everybody. Providing care for adult patients in a highly technological environment is challenging particularly for novice nurses, who face the potential of technology drawing all their attention. Experienced critical care nurses learn to keep technology in abeyance and deliver person-centred care within the bounds of a technological environment. The review supports Locsin's theory of technological competence and highlights that providing care in critical care requires nurses to actively balance attention for the person while managing machines. Experienced nurses achieve this balance and can offer support to novice nurses. Critical care nurse orientation programmes should be underpinned by a holistic approach which addresses the dualism of technology and care.


Secreted LOXL2 is a novel therapeutic target that promotes gastric cancer metastasis via the Src/FAK pathway.
The purpose of this study was to investigate invasion- and metastasis-related genes in gastric cancer. To this end, we used the transwell system to select a highly invasive subcell line from minimally invasive parent cells and compared gene expression in paired cell lines with high- and low-invasive potentials. Lysyl oxidase-like 2 (LOXL2) was overexpressed in the highly invasive subcell line. Immunohistochemical analysis revealed that LOXL2 expression was markedly increased in carcinoma relative to normal epithelia, and this overexpression in primary tumor was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Moreover, LOXL2 expression was further increased in lymph node metastases compared with primary cancer tissues. RNA interference-mediated knockdown and ectopic expression of LOXL2 showed that LOXL2 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo. Subsequent mechanistic studies showed that LOXL2 could activate both the Snail/E-cadherin and Src kinase/Focal adhesion kinase (Src/FAK) pathways. However, secreted LOXL2 induced gastric tumor cell invasion and metastasis exclusively via the Src/FAK pathway. Expression correlation analysis in gastric carcinoma tissues also revealed that LOXL2 promoted invasion via the Src/FAK pathway but not the Snail/E-cadherin pathway. We then evaluated secreted LOXL2 as a target for gastric carcinoma treatment and found that an antibody against LOXL2 significantly inhibited tumor growth and metastasis. Overall, our data revealed that LOXL2 overexpression, a frequent event in gastric carcinoma progression, contributes to tumor cell invasion and metastasis, and LOXL2 may be a therapeutic target for preventing and treating metastases.


Reduced Gut Acidity Induces an Obese-Like Phenotype in Drosophila melanogaster and in Mice.
In order to identify genes involved in stress and metabolic regulation, we carried out a Drosophila P-element-mediated mutagenesis screen for starvation resistance. We isolated a mutant, m2, that showed a 23% increase in survival time under starvation conditions. The P-element insertion was mapped to the region upstream of the vha16-1 gene, which encodes the c subunit of the vacuolar-type H+-ATPase. We found that vha16-1 is highly expressed in the fly midgut, and that m2 mutant flies are hypomorphic for vha16-1 and also exhibit reduced midgut acidity. This deficit is likely to induce altered metabolism and contribute to accelerated aging, since vha16-1 mutant flies are short-lived and display increases in body weight and lipid accumulation. Similar phenotypes were also induced by pharmacological treatment, through feeding normal flies and mice with a carbonic anhydrase inhibitor (acetazolamide) or proton pump inhibitor (PPI, lansoprazole) to suppress gut acid production. Our study may thus provide a useful model for investigating chronic acid suppression in patients.


The complementary brain: unifying brain dynamics and modularity.
How are our brains functionally organized to achieve adaptive behavior in a changing world? This article presents one alternative to the computer analogy that suggests brains are organized into independent modules. Evidence is reviewed that brains are in fact organized into parallel processing streams with complementary properties. Hierarchical interactions within each stream and parallel interactions between streams create coherent behavioral representations that overcome the complementary deficiencies of each stream and support unitary conscious experiences. This perspective suggests how brain design reflects the organization of the physical world with which brains interact. Examples from perception, learning, cognition and action are described, and theoretical concepts and mechanisms by which complementarity might be accomplished are presented.


Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR.
We show how dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy can be used to characterize polymorphs and solvates of organic solids. We applied DNP to three polymorphs and one hydrated form of the asthma drug molecule theophylline. For some forms of theophylline, sample grinding and impregnation with the radical-containing solution, which are necessary to prepare the samples for DNP, were found to induce polymorphic transitions or desolvation between some forms. We present protocols for sample preparation for solid-state magic-angle spinning (MAS) DNP experiments that avoid the polymorphic phase transitions in theophylline. These protocols include cryogrinding, grinding under inert atmosphere, and the appropriate choice of the impregnating liquid. By applying these procedures, we subsequently demonstrate that two-dimensional correlation experiments, such as (1)H-(13)C and (1)H-(15)N HETCOR or (13)C-(13)C INADEQUATE, can be obtained at natural isotopic abundance in reasonable times, thus enabling more advanced structural characterization of polymorphs.


Unexpected roles for ADH1 and SORD in catalyzing the final step of erythritol biosynthesis.
The low-calorie sweetener erythritol is endogenously produced from glucose through the pentose phosphate pathway in humans. Erythritol is of medical interest because elevated plasma levels of this polyol are predictive for visceral adiposity gain and development of type 2 diabetes. However, the mechanisms behind these associations remain unknown because the erythritol biosynthesis pathway, particularly the enzyme catalyzing the final step of erythritol synthesis (reduction of erythrose to erythritol), is not characterized. In this study, we purified two enzymes from rabbit liver capable of catalyzing the conversion of erythrose to erythritol: alcohol dehydrogenase 1 (ADH1) and sorbitol dehydrogenase (SORD). Both recombinant human ADH1 and SORD reduce erythrose to erythritol, using NADPH as a co-factor, and cell culture studies indicate that this activity is primarily NADPH-dependent. We found that ADH1 variants vary markedly in both their affinity for erythrose and their catalytic capacity (turnover number). Interestingly, the recombinant protein produced from the ADH1B2 variant, common in Asian populations, is not active when NADPH is used as a co-factor in vitro We also confirmed SORD contributes to intracellular erythritol production in human A549 lung cancer cells, where ADH1 is minimally expressed. In summary, human ADH1 and SORD catalyze the conversion of erythrose to erythritol, pointing to novel roles for two dehydrogenase proteins in human glucose metabolism that may contribute to individual responses to diet. Proteomics data are available via ProteomeXchange with identifier PXD015178.


The economics of limb salvage in diabetes.
Limb salvage requires early prevention therapy, knowledgeable use of wound care technology, and active management of peripheral vascular disease. This field has changed considerably over the past decade, with new advanced wound healing products and minimally invasive surgery for peripheral vascular disease. Treatment can be very costly in terms of medical and human resources. Evaluation of the clinical and economic impact of medical care is becoming more important as the population with diabetes and the need to contain the cost of health care simultaneously increase. The aim of this study was to review the economic impact of prevention therapies, wound care, and peripheral vascular disease interventions to prevent major lower extremity amputations. The authors reviewed the economic impact of prevention therapy, wound care, and peripheral vascular disease interventions to prevent lower extremity amputations. Length of stay in the hospital and intensive care drive the cost of treatment. Surgical intervention and complications for foot ulcers, amputations, and peripheral vascular disease are significant factors in the cost of limb salvage. Not surprisingly, prevention and evidenced-based treatments are the most cost-effective way of reducing the use of medical resources and improving and prolonging productive lifestyles. Future prospective studies need to be conducted to more accurately understand the financial impact of limb salvage.


The crisis of capitalism and the marketisation of health care: the implications for public health professionals.
The current economic crisis in Europe has challenged the basis of the economic model that currently prevails in much of the industrialised world. It has revealed a system that is managed not for the benefit of the people but rather for the corporations and the small elite who lead them, and which is clearly unsustainable in its present form. Yet, there is a hidden consequence of this system: an unfolding crisis in health care, driven by the greed of corporations whose profit-seeking model is also failing. Proponents of commodifying healthcare simultaneously argue that the cost of providing care for ageing populations is unaffordable while working to create demand for their health care products among those who are essentially healthy. Will healthcare be the next profit-fuelled investor bubble? In this paper, we call on health professionals to heed the warnings from the economic crisis and, rather than stand by while a crisis unfolds, act now to redirect increasingly market-oriented health systems to serve the common good.


Adapted J6/JFH1-based Hepatitis C virus recombinants with genotype-specific NS4A show similar efficacies against lead protease inhibitors, alpha interferon, and a putative NS4A inhibitor.
To facilitate studies of hepatitis C virus (HCV) NS4A, we aimed at developing J6/JFH1-based recombinants with genotype 1- to 7-specific NS4A proteins. We developed efficient culture systems expressing NS4A proteins of genotypes (isolates) 1a (H77 and TN), 1b (J4), 2a (J6), 4a (ED43), 5a (SA13), 6a (HK6a), and 7a (QC69), with peak infectivity titers of ∼3.5 to 4.5 log10 focus-forming units per ml. Except for genotype 2a (J6), growth depended on adaptive mutations identified in long-term culture. Genotype 1a, 1b, and 4a recombinants were adapted by amino acid substitutions F772S (p7) and V1663A (NS4A), while 5a, 6a, and 7a recombinants required additional substitutions in the NS3 protease and/or NS4A. We demonstrated applicability of the developed recombinants for study of antivirals. Genotype 1 to 7 NS4A recombinants showed similar responses to the protease inhibitors telaprevir (VX-950), boceprevir (Sch503034), simeprevir (TMC435350), danoprevir (ITMN-191), and vaniprevir (MK-7009), to alpha interferon 2b, and to the putative NS4A inhibitor ACH-806. The efficacy of ACH-806 was lower than that of protease inhibitors and was not influenced by changes at amino acids 1042 and 1065 (in the NS3 protease), which have been suggested to mediate resistance to ACH-806 in replicons. Genotype 1a, 1b, and 2a recombinants showed viral spread under long-term treatment with ACH-806, without acquisition of resistance mutations in the NS3-NS4A region. Relatively high concentrations of ACH-806 inhibited viral assembly, but not replication, in a single-cycle production assay. The developed HCV culture systems will facilitate studies benefitting from expression of genotype-specific NS4A in a constant backbone in the context of the complete viral replication cycle, including functional studies and evaluations of the efficacy of antivirals.


HIV-1 diversity among inmates of Italian prisons.
In Italy, the prevalence of non-B HIV-1 subtypes ranges reportedly from 5.4% to 12.6%, yet there are no data on their circulation in prisons, where the prevalence of HIV infection is high. A retrospective study was conducted to evaluate the circulation of non-B subtypes and to characterize their determinants in five Italian prisons. To this end an aliquot of samples of blood was taken in the period 2001-2006 from all 262 HIV-positive inmates in whom antiretroviral treatment had failed. Complete HIV-1 PR and RT regions were sequenced for all samples and subjected to phylogenetic analysis; 250 (95.4%) sequences clustered with subtype B. The non-B subtype was found in 4% of Italian prison inmates and 16.7% of non-Italian prison inmates; the overall percentage increased from 1.8% for inmates infected in 1982-1990 to 4.4% in 1991-1999 and 21.9% in 2000-2006. Factors significantly associated with non-B subtypes were an exposure to other than injecting drug use and a first positive HIV test in 2000-2006. Non-B subtypes were distributed within five monophyletic clades. In all cases but one, it was possible to correlate the history of HIV-exposure to the origin of the clade, with high bootstrap values. In conclusion, although the sample may not be representative of the prison inmate population in Italy, the data suggest strongly that the circulation of non-B subtypes has apparently increased. Non-B subtypes were found to have been associated with heterosexual contact and time of the first HIV-positive test. Knowledge of the different subtypes circulating in prisons may be useful for tracking the epidemiology of HIV infection and for choosing antiretroviral therapy.


Comparative effects of posterior eye cup tissues from myopic and hyperopic chick eyes on cultured scleral fibroblasts.
The role of individual ocular tissues in mediating changes to the sclera during myopia development is unclear. The aim of this study was to examine the effects of retina, RPE and choroidal tissues from myopic and hyperopic chick eyes on the DNA and glycosaminoglycan (GAG) content in cultures of chick scleral fibroblasts. Primary cultures of fibroblastic cells expressing vimentin and α-smooth muscle actin were established in serum-supplemented growth medium from 8-day-old normal chick sclera. The fibroblasts were subsequently co-cultured with posterior eye cup tissue (full thickness containing retina, RPE and choroid) obtained from untreated eyes and eyes wearing translucent diffusers (form-deprivation myopia, FDM) or -15D lenses (lens-induced myopia, LIM) for 3 days (post-hatch day 5-8) (n = 6 per treatment group). The effect of tissues (full thickness and individual retina, RPE, and choroid layers) from -15D (LIM) versus +15D (lens-induced hyperopia, LIH) treated eyes was also determined. Refraction changes in the direction predicted by the visual treatments were confirmed by retinoscopy prior to tissue collection. Glycosaminoglycan (GAG) and DNA content of the scleral fibroblast cultures were measured using GAG and PicoGreen assays. There was no significant difference in the effect of full thickness tissue from either FDM or LIM treated eyes on DNA and GAG content of scleral fibroblasts (DNA 8.9 ± 2.6 μg and 8.4 ± 1.1 μg, p = 0.12; GAG 11.2 ± 0.6 μg and 10.1 ± 1.0 μg, p = 0.34). Retina from LIM eyes did not alter fibroblast DNA or GAG content compared to retina from LIH eyes (DNA 27.2 ± 1.7 μg versus 23.2 ± 1.5 μg, p = 0.21; GAG 28.1 ± 1.7 μg versus. 28.7 ± 1.2 μg, p = 0.46). Similarly, the choroid from LIH and LIM eyes did not produce a differential effect on DNA content (DNA LIM 46.9 ± 6.4 versus LIH 51.5 ± 4.7 μg, p = 0.31). In contrast, scleral fibroblast DNA was greater in co-culture with RPE from LIM eyes than the empty basket and DNA content less for co-culture with RPE from LIH eyes (LIM: 72.4 ± 6.3 μg versus empty basket: 46.03 ± 1.0 μg; p = 0.0005 and LIH: 27.9 ± 2.3 μg versus empty basket: 46.03 ± 1.0 μg; p = 0.0004). GAG content was lower with RPE from LIM eyes (LIM: 27.7 ± 0.9 μg versus empty basket: 29.5 ± 0.8 μg, p = 0.021) and was higher with RPE from LIH eyes (LIH: 33.7 ± 1.9 μg versus empty basket: 29.5 ± 0.8 μg, p = 0.010). Choroid from LIM eyes induce a relative increase in scleral GAG content e.g. (LIM: 32.5 ± 0.7 μg versus empty basket: 29.5 ± 0.8 μg, p = 0.0004) while, choroid from LIH eyes induced a relative decrease in scleral GAG content (LIH: 18.9 ± 1.2 μg versus empty basket: 29.5 ± 0.8 μg, p = 0.0034). GAG content of cells in co-culture with choroid from LIM versus LIH treated eyes was significantly different (32.5 ± 0.7 μg versus 18.9 ± 1.2 μg respectively, p = 0.0002). In conclusion, these experiments provide an evidence for a directional growth signal that is present (and remains) in the ex-vivo RPE/choroid, but that does not remain in the ex-vivo retina. The identity of this factor(s) that can modify scleral cell DNA and GAG content requires further research.


Source apportionment of trace contaminants in urban sewer catchments.
Sampling and analysis of Water Framework Directive priority chemicals were undertaken in nine urban catchments across the UK. Over 9000 samples were collected from a number of different catchment sources including tap water, domestic waste water, surface water runoff, trade discharges, town centre and light industrial estate wastewaters. Determinands included trace metals, polyaromatic hydrocarbons (PAHs), persistent organic pollutants and a number of common pharmaceuticals. Loads of the chemicals from each catchment entering the local wastewater treatment works (WwTW) were estimated and were shown to be relatively consistent between different catchments, after taking population into account. A Monte Carlo mixing model was used to combine the concentrations and flows from the different catchment sources and to predict concentrations and loads entering the WwTW. Based on the model output, the significance of the different sources could be evaluated. The study highlighted the importance of domestic wastewater as a source of contaminants, including metals and trace organic substances (such as ethylenediaminetetraacetic acid (EDTA), bisphenol A, nonylphenol and tributyl tin (TBT)). Concentrations in trade discharges were important in some locations in the case of nonylphenol, EDTA, TBT, as well as for some metals such as copper, zinc and nickel. Contributions to the total load from town centre and light industrial estate sources were generally less than 10% of the total.


Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice.
Respiratory diseases are a major cause of mortality and morbidity worldwide. Current treatments offer no prospect of cure or disease reversal. Transplantation of pulmonary progenitor cells derived from human embryonic stem cells (hESCs) may provide a novel approach to regenerate endogenous lung cells destroyed by injury and disease. Here, we examine the therapeutic potential of alveolar type II epithelial cells derived from hESCs (hES-ATIICs) in a mouse model of acute lung injury. When transplanted into lungs of mice subjected to bleomycin (BLM)-induced acute lung injury, hES-ATIICs behaved as normal primary ATIICs, differentiating into cells expressing phenotypic markers of alveolar type I epithelial cells. Without experiencing tumorigenic side effects, lung injury was abrogated in mice transplanted with hES-ATIICs, demonstrated by recovery of body weight and arterial blood oxygen saturation, decreased collagen deposition, and increased survival. Therefore, transplantation of hES-ATIICs shows promise as an effective therapeutic to treat acute lung injury.


Magnetization dynamics induced by the Rashba effect in ferromagnetic films.
Manipulating the magnetization of ferromagnets by the current-induced spin-orbit torque has great potential application in the design of low energy consumption spintronic devices. Normally, an external magnetic field is needed for the reversal of current assisted magnetization by the spin-orbit torque. Recently, the switching of magnetization driven by the spin-orbit torque in the absence of an external magnetic field was reported in a Ta/Co20Fe60B20/TaOx system with lateral structural asymmetry. To understand the physics behind this experiment, we performed first principles calculations on the potential profile at the interface between the ferromagnetic film and the wedge-shaped deposited metal oxide in the Ta/Co/TaO system. This revealed that the lateral structural asymmetry generates two additional Rashba interactions which can reduce the minimum external field required to reverse the magnetization. In addition, we derived the Landau-Lifshitz-Gilbert equation from a quantum transport perspective and numerically investigated the magnetization dynamics in ferromagnetic films induced by Rashba interactions including those generated by lateral asymmetry. Our theoretical simulation provides microscopic explanations of experimental observations of magnetization switching in the absence of an external field of devices with lateral structural asymmetry.


Impact of a high-deductible health plan on outpatient visits and associated diagnostic tests.
By shifting a greater share of out-of-pocket medical costs to consumers, high-deductible health plans (HDHP) might discourage use of essential outpatient services. The objective of the study was to examine the impact of an HDHP on outpatient visits and associated laboratory and radiology tests. We used a pre-post with comparison group study design to examine the differential change in outpatient service utilization among 7953 adults who were switched from a traditional Health Maintenance Organization plan to an HDHP compared with 7953 adults remaining in traditional plans. HDHP members had full coverage of preventive laboratory tests and modest copayments for outpatient visits, similar to controls, but faced full cost sharing under the deductible for radiology tests and laboratory tests not classified as preventive. Compared with controls, the HDHP group experienced moderate relative decreases in overall office visits (incidence rate ratios = 0.91, or a 9% relative reduction; 95% confidence interval: 0.88, 0.94) and visits for higher-priority (0.91; 0.85, 0.97) and lower-priority (0.89; 0.81, 0.99) chronic conditions. There were no significant differences in changes in visit rates for acute higher-priority or lower-priority conditions (both 0.93; 0.86, 1.01) or preventive laboratory tests (0.97; 0.93, 1.02). HDHP members showed moderate relative reductions in the use of general laboratory tests (0.91; 0.86, 0.97) but not radiology tests (0.97; 0.91, 1.03). Chronic outpatient visits declined among HDHP members, although preventive laboratory tests and acute visits remained unchanged. HDHP patients with chronic illnesses who have more contact with the health care system might be more likely to reduce utilization because of increased exposure to costs associated with ambulatory visits.


Measurement of the Lambdab0 lifetime in Lambdab0 --> Lambdac+pi- decays in pp collisions at square root of s = 1.96 TeV.
We report a measurement of the lifetime of the Lambda(b)(0) baryon in decays to the Lambda(c)(+)pi(-) final state in a sample corresponding to 1.1 fb(-1) collected in pp collisions at square root of s = 1.96 TeV by the CDF II detector at the Tevatron collider. Using a sample of about 3000 fully reconstructed Lambda(b)(0) events we measure tau(Lambda(b)(0)) = 1.401 +/- 0.046(stat) +/- 0.035(syst) ps (corresponding to ctau(Lambda(b)(0)) = 420.1 +/- 13.7(stat) +/- 10.6(syst) microm, where c is the speed of light). The ratio of this result and the world average B(0) lifetime yields tau(Lambda(b)(0))/tau(B(0)) = 0.918 +/- 0.038 (stat) and (syst), in good agreement with recent theoretical predictions.


Increases in dentin-bond strength if doubling application time of an acetone-containing one-step adhesive.
This study investigated the microtensile bond strength (microTBS) of a one-step self-etching adhesive to human dentin and bovine enamel following different bonding treatments. Occlusal portions of human molars and labial surfaces of bovine incisors were ground flat to provide uniform dentin and enamel surfaces, respectively. Futurabond was used following five different protocols: 1) according to the manufacturer's directions, 2) acid etched with 36% phosphoric acid (H3PO4) for 15 seconds, 3) 10% sodium hypochlorite (NaOCl) treated for two minutes after H3PO4-etching, 4) doubling the application time of the adhesive and 5) doubling the number of adhesive coats. Composite build-ups (6 mm in height) were constructed incrementally with Arabesk resin composite. The specimens were stored in 100% humidity for 24 hours at 37 degrees C and sectioned into beams of 1.0 mm2 cross-sectional area. Each beam was tested in tension in an Instron machine at 0.5 mm/minute, and mean microTBS data (MPa) were analyzed by one-way ANOVA and post-hoc multiple comparisons tests (alpha = 0.05). Doubling the application time of Futurabond attained the highest microTBS to dentin; whereas, no differences among all bonding application parameters evaluated could be detected when the adhesive was applied to enamel.


Modulation of human dermal fibroblast extracellular matrix metabolism by the lymphokine leukoregulin.
The effect of leukoregulin, a 50-kD lymphokine with unique antitumor properties, was studied in vitro on several fibroblast functions. Leukoregulin did not inhibit fibroblast proliferation, as measured by cell enumeration and [3H]thymidine incorporation, and had no cytotoxic effect in terms of increased membrane permeability detected by trypan blue exclusion, two of the major leukoregulin actions on tumor cells. Leukoregulin induced a dose-dependent decrease in collagen synthesis, demonstrated by decreased [3H]proline incorporation into collagenase-digestible protein, as early as 6 h after the addition of the lymphokine to human fibroblasts. Leukoregulin inhibited the synthesis of both type I and type III collagen, as measured by SDS-PAGE and by specific radioimmunoassay. Neutralizing antibodies to interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interferon-gamma failed to alter the effect of leukoregulin on collagen synthesis, attesting that leukoregulin action was not due to contamination by these cytokines. Inhibition of collagen synthesis occurred concomitantly with increased secretion of prostaglandin E2 and a transient rise in intracellular cyclic AMP content, peaking at 6 h. However, blocking prostaglandin synthesis with indomethacin did not counteract inhibition of collagen synthesis by leukoregulin, demonstrating independence of this action of leukoregulin from cyclooxygenase metabolites. Leukoregulin also stimulated glycosaminoglycan production in a dose-dependent manner, affecting the synthesis of hyaluronic acid as the major fibroblast-derived extracellular glycosaminoglycan. In addition, secretion of neutral proteases (collagenase, elastase, caseinase) was increased. These observations indicate that leukoregulin is able to regulate synthesis of molecules critical to the deposition of the extracellular matrix by nontransformed nonmalignant fibroblasts.


Computer-extracted Features Can Distinguish Noncancerous Confounding Disease from Prostatic Adenocarcinoma at Multiparametric MR Imaging.
To determine the best features to discriminate prostate cancer from benign disease and its relationship to benign disease class and cancer grade. The institutional review board approved this study and waived the need for informed consent. A retrospective cohort of 70 patients (age range, 48-70 years; median, 62 years), all of whom were scheduled to undergo radical prostatectomy and underwent preoperative 3-T multiparametric magnetic resonance (MR) imaging, including T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging, were included. The digitized prostatectomy slides were annotated for cancer and noncancerous disease and coregistered to MR imaging with an interactive deformable coregistration scheme. Computer-identified features for each of the noncancerous disease categories (eg, benign prostatic hyperplasia [BPH], prostatic intraepithelial neoplasia [PIN], inflammation, and atrophy) and prostate cancer were extracted. Feature selection was performed to identify the features with the highest discriminatory power. The performance of these five features was evaluated by using the area under the receiver operating characteristic curve (AUC). High-b-value diffusion-weighted images were more discriminative in distinguishing BPH from prostate cancer than apparent diffusion coefficient, which was most suitable for distinguishing PIN from prostate cancer. The focal appearance of lesions on dynamic contrast-enhanced images may help discriminate atrophy and inflammation from cancer. Which imaging features are discriminative for different benign lesions is influenced by cancer grade. The apparent diffusion coefficient appeared to be the most discriminative feature in identifying high-grade cancer. Classification results showed increased performance by taking into account specific benign types (AUC = 0.70) compared with grouping all noncancerous findings together (AUC = 0.62). The best features with which to discriminate prostate cancer from noncancerous benign disease depend on the type of benign disease and cancer grade. Use of the best features may result in better diagnostic performance.


Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise.
Acylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding acyl-CoA precursors via the action of carnitine acetyltransferase (CrAT), a bidirectional mitochondrial matrix enzyme. We show here that contractile activity reverses acetylcarnitine flux in muscle, from net production and efflux at rest to net uptake and consumption during exercise. Disruption of this switch in mice with muscle-specific CrAT deficiency resulted in acetyl-CoA deficit, perturbed energy charge, and diminished exercise tolerance, whereas acetylcarnitine supplementation produced opposite outcomes in a CrAT-dependent manner. Likewise, in exercise-trained compared to untrained humans, post-exercise phosphocreatine recovery rates were positively associated with CrAT activity and coincided with dramatic shifts in muscle acetylcarnitine dynamics. These findings show acetylcarnitine serves as a critical acetyl buffer for working muscles and provide insight into potential therapeutic strategies for combatting exercise intolerance.


Cerebral vasculitis in Henoch-Schönlein purpura: a case report with sequential magnetic resonance imaging changes and treated with plasmapheresis alone.
Neurological complications are rare during the course of Henoch-Schönlein purpura (HSP). We report a 7-year-old girl with HSP who presented with seizures, loss of vision and disturbance of consciousness. Magnetic resonance imaging (MRI) showed high signal intensity in the gray and white matter over the left parietal and both occipital lobes, compatible with MRI findings of cerebral vasculitis. The eye fundi revealed multiple branches of retinal artery occlusion. Intravenous pulse methylprednisolone (MTP) followed by oral steroid therapy was initially administered for HSP nephritis. Cerebral vasculitis developed 10 days post-MTP treatment, with progressive worsening of consciousness. Oral steroid was discontinued and plasmapheresis was performed alone. Her level of consciousness dramatically improved after plasmapheresis. The brain MRI and eye fundi findings were consistent with her clinical improvement. To the best of our knowledge, this is the first description of MRI abnormalities and multiple retinal artery branch occlusion of cerebral vasculitis in a patient with HSP that was successfully treated by plasmapheresis alone. In conclusion, we propose that plasmapheresis may be used as a first-line therapy or rescue therapy for cerebral vasculitis in HSP.


Dynamically-Induced Spatial Dispersion of Repolarization and the Development of VF in an Animal Model of Sudden Death.
Spatial dispersion of refractoriness and discordant action potential duration (APD) alternans, resulting in local conduction block, have been shown to cause wavebreak that can lead to ventricular fibrillation (VF). Previously, we developed a theory, based on action potential restitution functions, that predicts when the requisite conduction block can be created through a series of premature beats. The theory was applied successfully to normal beagle dogs; however, restitution functions in these animals were similar, both between right and left ventricles in a given animal and across animals. Consequently, for the present study we tested the theory on a population of German shepherds that, due to inherited cardiac abnormalities, presented with a wide variation of APD restitution functions. We found that the theory, when applied to restitution functions determined individually for each animal, reliably generated premature stimulation predictions that frequently resulted in the induction of VF in in vivo experiments.


Clear cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor: two variants of a morphologic, immunohistochemical, and genetic distinct entity of renal cell carcinoma.
Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary RCC (pRCC). It is a matter of controversy whether their morphologic, immunophenotypic, and molecular features allow the definition of a separate renal carcinoma entity. The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT. We investigated 28 ccpRCC and 9 RAT samples by immunohistochemistry using 25 markers. VHL gene mutations and allele losses were investigated by Sanger sequencing and fluorescence in situ hybridization. Clinical follow-up data were obtained for a subset of the patients. No tumor recurrence or tumor-related death was observed in any of the patients. Immunohistochemistry and molecular analyses led to the reclassification of 3 tumors as ccRCC and TFE3 translocation carcinomas. The immunohistochemical profile of ccpRCC and RAT samples was very similar but not identical, differing from both ccRCC and pRCC. Especially, the parafibromin and hKIM-1 expression exhibited differences in ccpRCC/RAT compared with ccRCC and pRCC. Genetic analysis revealed VHL mutations in 2/27 (7%) and 1/7 (14%) ccpRCC and RAT samples, respectively. Fluorescence in situ hybridization analysis disclosed a 3p loss in 2/20 (10%) ccpRCC samples. ccpRCC and RAT have a specific morphologic and immunohistochemical profile, but they share similarities with the more aggressive renal tumors. On the basis of our results, we regard ccpRCC/RAT as a distinct entity of RCCs.


To be or not to be oxidized: A case study of olivine behavior in the fusion crust of ureilite A 09368 and H chondrites A 09004 and A 09502.
Meteorite fusion crusts are quenched melt layers formed during meteoroid atmospheric entry, mostly preserved as coating on the meteorite surface. Antarctic ureilite Asuka (A) 09368 and H chondrites A 09004 and A 09502 exhibit well preserved thick fusion crusts, characterized by extensive olivine crystallization. As olivine is one of the major components of most meteorites and its petrologic behavior is well constrained, it can be roughly considered as representative for the bulk meteorite. Thus, in this work, the evolution of olivine in fusion crusts of the above-listed selected samples is investigated. The different shape and chemistry of olivine crystallized in the fusion crust, both as overgrown rim on relic olivine clasts and as new crystals, suggest a general temperature and cooling rate gradient. The occurrence of reverse and oscillatory zoning in individual olivine grains within the fusion crust suggests complex redox reactions. Overall, the investigated fusion crusts exhibit a general oxidation of the relatively reduced initial material. However, evidence of local reduction is preserved. Reduction is likely triggered by the presence of carbon in the ureilite or by overheating during the atmospheric entry. Constraining these processes provides a potential analog for interpreting features observed in cosmic spherules and micrometeorites and for calibrating experiments and numerical models on the formation of fusion crusts.


Shoulder Stretching Intervention Reduces the Incidence of Shoulder and Elbow Injuries in High School Baseball Players: a Time-to-Event Analysis.
We prospectively evaluated the effects of a prevention program on the incidence of shoulder and elbow injuries in high school baseball pitchers. Ninety-two pitchers participated in this study and were taught to perform stretching and strength exercises aimed at improving shoulder external rotation strength in the preseason. The pitchers freely chose to participate in one of four groups [SM-group: performed both exercises, S-group: performed stretching exercise only, M-group: performed strength training only, and N-group: performed neither intervention]. Injury was defined as inability to play for ≥8 days because of shoulder/elbow symptoms. Kaplan-Meier survival curves were generated and hazard ratios (HRs) for injury occurrence were calculated using multivariate Cox regression. Log-rank test was used for between-group comparisons of survival distributions. The injuries occurred in 25, 35, and 57% of participants and median times to injury were 89, 92, and 29.5 days in the S- (n = 32), SM- (n = 46), and N- (n = 14) group, respectively. Nobody chose M-group. HRs were 0.36 and 0.47 for the S- and SM-group, respectively, based on the N-group. The incidence of injury was significantly lower in the S-group than in the N-group (p = 0.04). Daily posterior shoulder stretching may reduce the incidence of the injuries in high school baseball pitchers.


Suppression of the migration and invasion is mediated by triptolide in B16F10 mouse melanoma cells through the NF-kappaB-dependent pathway.
Melanoma cancer is one of the major causes of death in humans worldwide. Triptolide is one of the active components of Tripterygium wilfordii Hook F, and has biological activities including induced cell cycle arrest and induction of apoptosis but its antimetastatic effects on murine melanoma cells have not yet been elucidated. Herein, we investigated the effect of triptolide on the inhibition of migration and invasion and possible associated signal pathways in B16F10 murine melanoma cancer cells. Wound healing assay and Matrigel Cell Migration Assay and Invasion System demonstrated that triptolide marked inhibiting the migration and invasion of B16F10 cells. Gelatin zymography assay demonstrated that triptolide significantly inhibited the activities of matrix metalloproteinases-2 (MMP-2). Western blotting showed that triptolide markedly reduced CXCR4, SOS1, GRB2, p-ERK, FAK, p-AKT, Rho A, p-JNK, NF-κB, MMP-9, and MMP-2 but increased PI3K and p-p38 and COX2 after compared to the untreated (control) cells. Real time PCR indicated that triptolide inhibited the gene expression of MMP-2, FAK, ROCK-1, and NF-κB but did not significantly affect TIMP-1 and -2 gene expression in B16F10 cells in vitro. EMSA assay also showed that triptolide inhibited NF-κB DNA binding in a dose-dependent manner. Confocal laser microscopy examination also confirmed that triptolide inhibited the expression of NF-κB in B16F10 cells. Taken together, we suggest that triptolide inhibited B16F10 cell migration and invasion via the inhibition of NF-κB expression then led to suppress MMP-2 and -9 expressions. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1974-1984, 2016.


Electrochemical X-ray fluorescence spectroscopy for trace heavy metal analysis: enhancing X-ray fluorescence detection capabilities by four orders of magnitude.
The development of a novel analytical technique, electrochemical X-ray fluorescence (EC-XRF), is described and applied to the quantitative detection of heavy metals in solution, achieving sub-ppb limits of detection (LOD). In EC-XRF, electrochemical preconcentration of a species of interest onto the target electrode is achieved here by cathodic electrodeposition. Unambiguous elemental identification and quantification of metal concentration is then made using XRF. This simple electrochemical preconcentration step improves the LOD of energy dispersive XRF by over 4 orders of magnitude (for similar sample preparation time scales). Large area free-standing boron doped diamond grown using microwave plasma chemical vapor deposition techniques is found to be ideal as the electrode material for both electrodeposition and XRF due to its wide solvent window, transparency to the XRF beam, and ability to be produced in mechanically robust freestanding thin film form. During electrodeposition it is possible to vary both the deposition potential (Edep) and deposition time (tdep). For the metals Cu(2+) and Pb(2+) the highest detection sensitivities were found for Edep = -1.75 V and tdep (=) 4000 s with LODs of 0.05 and 0.04 ppb achieved, respectively. In mixed Cu(2+)/Pb(2+) solutions, EC-XRF shows that Cu(2+) deposition is unimpeded by Pb(2+), across a broad concentration range, but this is only true for Pb(2+) when both metals are present at low concentrations (10 nM), boding well for trace level measurements. In a dual mixed metal solution, EC-XRF can also be employed to either selectively deposit the metal which has the most positive formal reduction potential, E(0), or exhaustively deplete it from solution, enabling uninhibited detection of the metal with the more negative E(0).


Efficacy of Two Chlamydia abortus Subcellular Vaccines in a Pregnant Ewe Challenge Model for Ovine Enzootic Abortion.
Chlamydia abortus, the aetiological agent of enzootic abortion of ewes, is a major cause of reproductive loss in small ruminants worldwide, accounting for significant economic losses to the farming industry. Disease can be managed through the use of commercial inactivated or live whole organism-based vaccines, although both have limitations particularly in terms of efficacy, safety and disease-associated outbreaks. Here we report a comparison of two experimental vaccines (chlamydial outer membrane complex (COMC) and octyl glucoside (OG)-COMC) based on detergent extracted outer membrane preparations of C. abortus and delivered as prime-boost immunisations, with the commercial live vaccine Cevac® Chlamydia in a pregnant sheep challenge model. No abortions occurred in either experimental vaccine group, while a single abortion occurred in the commercial vaccine group. Bacterial shedding, as a measure of potential risk of transmission of infection to naïve animals, was lowest in the COMC vaccinated group, with reductions of 87.5%, 86.4% and 74% observed for the COMC, OG-COMC and live commercial vaccine groups, respectively, compared to the unvaccinated challenge control group. The results show that the COMC vaccine performed the best and is a safer efficacious alternative to the commercial vaccines. However, to improve commercial viability, future studies should optimise the antigen dose and number of inoculations required.


Establishment of norms of the beta angle to assess the sagittal discrepancy for Nellore district population.
In orthodontic diagnosis and treatment planning, assessment of anteroposterior discrepancy is of importance to the orthodontist. Both angular and linear measurements have been incorporated into various cephalometric analyses to help the clinician diagnose anteroposterior discrepancies and establish the most appropriate treatment plan. Hence the present study is designed to establish the norms of Beta angle to assess the sagittal discrepancy for Nellore district population. The sample was screened from the old records of the Orthodontic department of Narayana Dental College and Hospital. One hundred and fifty pretreatment cephalometric radiographs (50 each of Class I, II, and III) were subdivided based on ANB, Wits appraisal, and Beta angle into skeletal Class I, II, III. The same cephalograms were again classified into skeletal Class I, II, and III based purely on Beta angle. Each group was again divided into 2 subgroups consisting of 25 male and 25 female subjects with a mean age limit between 15 and 45 years old. The Newman-keuls post hoc test and ANOVA showed that the 3 groups were significantly different (P ≤ 0.001). The Newman-keuls post hoc test also found the groups to be significantly different. There was statistically significant difference for, the mean values and the standard deviation for Beta angle within the three skeletal patterns (Class I, Class II and Class III skeletal patterns). There was no statistically significant difference among the mean values of beta angle between Nellore district population and Caucasian norms and between male and female sex groups.


ON THE COMPOSITION OF YOUNG, DIRECTLY IMAGED GIANT PLANETS.
The past decade has seen significant progress on the direct detection and characterization of young, self-luminous giant planets at wide orbital separations from their host stars. Some of these planets show evidence for disequilibrium processes like transport-induced quenching in their atmospheres; photochemistry may also be important, despite the large orbital distances. These disequilibrium chemical processes can alter the expected composition, spectral behavior, thermal structure, and cooling history of the planets, and can potentially confuse determinations of bulk elemental ratios, which provide important insights into planet-formation mechanisms. Using a thermo/photochemical kinetics and transport model, we investigate the extent to which disequilibrium chemistry affects the composition and spectra of directly imaged giant exoplanets. Results for specific "young Jupiters" such as HR 8799 b and 51 Eri b are presented, as are general trends as a function of planetary effective temperature, surface gravity, incident ultraviolet flux, and strength of deep atmospheric convection. We find that quenching is very important on young Jupiters, leading to CO/CH4 and N2/NH3 ratios much greater than, and H2O mixing ratios a factor of a few less than, chemical-equilibrium predictions. Photochemistry can also be important on such planets, with CO2 and HCN being key photochemical products. Carbon dioxide becomes a major constituent when stratospheric temperatures are low and recycling of water via the H2 + OH reaction becomes kinetically stifled. Young Jupiters with effective temperatures ≲700 K are in a particularly interesting photochemical regime that differs from both transiting hot Jupiters and our own solar-system giant planets.


Genetic polymorphisms influence recovery from traumatic brain injury.
Traumatic brain injury (TBI) is a major public health concern in both civilian and military populations. Recently, genetics studies have begun to identify individual differences in polymorphisms that could affect recovery and outcome of cognitive and social processes following TBI. This review considers the potential for polymorphisms to influence six specific cognitive and social functions, which represent the most prominent domains of impairment following TBI: working memory, executive function, decision making, inhibition and impulsivity, aggression, and social and emotional function. Examining the influence of polymorphisms on TBI outcome has the potential to contribute to an understanding of variations in TBI outcome, aid in the triaging and treatment of TBI patients, and ultimately lead to targeted interventions based on genetic profiles.


Pacing by winners of a 161-km mountain ultramarathon.
To examine pacing among the most successful runners in the 161-km Western States Endurance Run (WSER) to determine if variations in segmental speed relate to performance, ambient temperature, and calendar year. Segmental speed and coefficient of variation (CV) in speed were analyzed for 10 race segments of 24 races from 1985 through 2013. Segmental speeds did not differ between the eventual winners and lead runners and only differed between the 1st and 2nd finishers in the 2nd half of the race. Mean CV in speed was lower (P < .01) for the winners (12%) than for the other top-5 finishers (14-15%). CV in speed was related (r = .80, P = .006) to finish time for the fastest 10 finish times at the WSER. Multiple linear-regression analysis revealed mean CV in speed for the top-5 runners to be related to maximum ambient temperature (coefficient =.14, P < .05) and calendar year (coefficient = -.086, P = .034). Mountain trail running is characterized by wide variations in speed, but the fastest times are achieved when speed fluctuations are limited. This is generally accomplished by the winners remaining relatively close behind the lead runners before taking the lead in the middle half of the race, and then avoiding slowing as much as the other top runners in the latter race stages. Variations in speed increase with high ambient temperatures, and the small decrease in segmental speed variability among top runners across the nearly 30 y of this study suggests that the best runners have improved at pacing this race.


Effects of a competitive wrestling season on body composition, endocrine markers, and anaerobic exercise performance in NCAA collegiate wrestlers.
Few data exist examining the body composition, endocrine, and anaerobic exercise performance changes over a competitive wrestling season. Eighteen NCAA wrestlers were tested for endocrine markers, body composition, hydration, grip strength, and power on four occasions: prior to pre-season training (T1); after pre-season training 3 days prior to the first seasonal meet (T2); mid-season one day prior to a meet (T3); and at the end of the season 2-3 days following the last meet (T4). Body mass, percent body fat (BF %), and fat mass were significantly lower (P ≤ 0.05) at T2 and T3 compared to T1 but were not different between T1 and T4. Lean body mass was significantly reduced at T2 only. Urine specific gravity was significantly elevated at T3 compared to T1, T2, and T4. Resting cortisol concentrations did not change but resting testosterone concentrations were significantly reduced at T2, T3, and T4. Maximal grip strength was significantly reduced at T2. Vertical jump peak power was significantly reduced at T2, T3, and T4. Wingate peak power was significantly reduced at T2 and T3. However, Wingate average power and total work did not significantly change. Fatigue rate during the Wingate test was significantly improved at T2, T3, and T4 compared to T1. In conclusion, body mass, BF %, and measures of peak force and power were reduced for most of the competitive wrestling season. Competitive wrestling reduces resting total testosterone concentrations throughout the entire season.


Human herpesvirus 8 infection contributes to a T helper 2 immune response in men from Tobago with prostate cancer.
To compare the cytokine profile between human herpesvirus 8 seropositive and seronegative men with and without prostate cancer. The study sample was obtained from the Tobago Prostate Survey, an ongoing study of prostate cancer in the Caribbean island of Tobago. Participants in the study were recruited mostly by public service announcement and by word of mouth. For analyses of circulating levels of pro-inflammatory cytokines, participants with biopsy-confirmed prostate cancer (n = 79) were compared with control participants (n = 87). Cytokine analyses showed a T helper 2 response with suppressed T helper 1 response in prostate cancer patients, as evidenced by significantly increased levels of interleukin-13 and reduced levels of interleukin-12p70. Herpesvirus 8 seropositive men showed significantly increased levels of interleukin-13 and interleukin-10. At logistic regression analyses, interleukin-12p70 predicted prostate cancer in 94.4% of human herpesvirus 8 seropositive men. These findings show that prostate cancer elicits an antitumor, T helper 2 response with a suppressed T helper 1 response. Human herpesvirus 8 infection results in a similar immune response supporting the hypothesis that in Tobago, human herpesvirus 8 establishes a chronic infection that can contribute to an immune response favoring the formation and survival of prostate cancer.


Association of adherence to lifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study.
To evaluate the association between a simple lifestyle index based on the recommendations for five lifestyle factors and the incidence of colorectal cancer, and to estimate the proportion of colorectal cancer cases attributable to lack of adherence to the recommendations. Prospective cohort study. General population of Copenhagen and Aarhus, Denmark. 55 487 men and women aged 50-64 years at baseline (1993-7), not previously diagnosed with cancer. Risk of colorectal cancer in relation to points achieved in the lifestyle index (based on physical activity, waist circumference, smoking, alcohol intake, and diet (dietary fibre, energy percentage from fat, red and processed meat, and fruits and vegetables)) modelled through Cox regression. During a median follow-up of 9.9 years, 678 men and women had colorectal cancer diagnosed. After adjustment for potential confounders, each additional point achieved on the lifestyle index, corresponding to one additional recommendation that was met, was associated with a lower risk of colorectal cancer (incidence rate ratio 0.89 (95% confidence interval 0.82 to 0.96). In this population an estimated total of 13% (95% CI 4% to 22%) of the colorectal cancer cases were attributable to lack of adherence to merely one additional recommendation among all participants except the healthiest. If all participants had followed the five recommendations 23% (9% to 37%) of the colorectal cancer cases might have been prevented. Results were similar for colon and rectal cancer, but only statistically significant for colon cancer. Adherence to the recommendations for physical activity, waist circumference, smoking, alcohol intake, and diet may reduce colorectal cancer risk considerably, and in this population 23% of the cases might be attributable to lack of adherence to the five lifestyle recommendations. The simple structure of the lifestyle index facilitates its use in public health practice.


Advances in the etiology and mechanisms of type 1 diabetes.
Type 1 diabetes (T1D) is an insulin-dependent form of diabetes resulting from the autoimmune destruction of pancreatic beta cells. The past few decades have seen tremendous progress in our understanding of the molecular basis of the disease, with the identification of susceptibility genes and autoantigens, the demonstration of several abnormalities affecting various cell types and functions, and the development of improved assays to detect and monitor autoimmunity and beta cell function. New findings about the disease pathology and pathogenesis are emerging from extensive studies of organ donors with T1D promoted by the JDRF nPOD (Network for the Pancreatic Organ Donor with Diabetes). Furthermore, the establishment of extensive collaborative projects including longitudinal follow-up studies in relatives and clinical trials are setting the stage for a greater understanding of the role of environmental factors, the natural history of the disease, and the discovery of novel biomarkers for improved prediction, which will positively impact future clinical trials. Recent studies have highlighted the chronicity of islet autoimmunity and the persistence of some beta cell function for years after diagnosis, which could be exploited to expand therapeutic options and the time window during which a clinical benefit can be achieved.


Role of deformation imaging in left ventricular non-compaction and hypertrophic cardiomyopathy: an Indian perspective.
Speckle tracking echocardiography (STE) has emerged as a novel feasible tool for the assessment of left ventricular rotational parameters. Since hypertrophic cardiomyopathy(HCM) shares morphologic features with left ventricular non-compaction (LVNC), we used this imaging modality to compare rotational mechanics between these two entities. We compared global and regional LV function and rotational mechanics between LVNC, HCM, and healthy subjects using STE. Longitudinal strain and torsion were obtained from echocardiographic images from parasternal short axis as well as standard LV apical views. Twelve patients with LVNC [mean age 46.12 ± 14.66 years; median 47.5 IQR (39.25-58.5) years] were compared with 18 HCM patients [mean age 49.48± 17.22 years; median 56 IQR (33-65) years] and 18 healthy subjects [mean age: 51.50± 12.51 years; median 51(45.75-58) years]. LVNC group showed a significantly reduced longitudinal strain at the apical region compared to HCM group (- 12.18 ± 6.25 vs - 18.37 ± 3.67; P < 0.05). Rigid body rotation(RBR) was found in 50% of patients whereas the other half had a normal rotation at the apex and the base. Among the patients with RBR, all patients had a uniform counterclockwise rotation. Longitudinal strain was impaired in both the forms of cardiomyopathy; however, LVNC showed a more significant reduction in the apical region compared to patients with HCM suggesting a development abnormality in these regions. A reduction in left ventricular torsion was specifically noted among patients with LVNC with a uniform anticlockwise rotation of LV base and apex.


Influence of posture and handgrip on the QT interval in left ventricular hypertrophy and in chronic heart failure.
In certain disease states prolongation of the QT interval has been shown to be arrhythmogenic. Whether QTc interval changes with position and thus whether certain positions are more arrhythmogenic than others is not known for different diseases that predispose to arrhythmias, and was therefore studied. Patients with left ventricular hypertrophy and heart failure, and the appropriate matched controls, were recruited. Subjects were studied in the lying, sitting, standing and squatting positions and had QT intervals determined by computer algorithm 2 min after each position change. After resting, QT interval was determined while the subjects performed maximum handgrip exercise with their dominant hand. QT intervals were rate-corrected using Bazett's method. QTc interval is prolonged in heart failure patients compared with either left ventricular hypertrophy or control subjects in the lying and sitting position, but not in the standing or squatting position. The QTc intervals for heart failure and control subjects were, respectively, 443+/-7 ms versus 421+/-6 ms when lying (P<0.05), 451+/-10 ms versus 419+/-6 ms when sitting (P<0.05), 429+/-10 versus 414+/-7 ms when standing (P not significant) and 437+/-10 versus 419+/-8 ms when squatting (P not significant). The values for patients with hypertrophy did not differ from control values. Maximum handgrip does not affect the QTc interval in heart failure, but prolongs it in both the hypertrophy and control groups. Position and static exercise are important modifiers of QTc interval and their effect depends on the condition of the left ventricle.