Pulsed Radiofrequency as a Minimally Invasive Treatment Option in Anterior Cutaneous Nerve Entrapment Syndrome: A Retrospective Analysis of 26 Patients.
Chronic abdominal pain is occasionally due to entrapped intercostal nerve endings (ACNES, abdominal cutaneous nerve entrapment syndrome). If abdominal wall infiltration using an anesthetic agent is unsuccessful, a neurectomy may be considered. Pulsed radiofrequency (PRF) is a relatively new treatment option for various chronic pain syndromes. Evidence regarding a beneficial effect of this minimally invasive technique in ACNES is lacking. The aim was to assess the effectiveness of PRF treatment in ACNES patients. A series of ACNES patients undergoing PRF treatment between January 2014 and December 2015 in two hospitals were retrospectively evaluated. Pain was recorded prior to treatment and after 6 weeks using a numerical rating scale (NRS, 0 (no pain) to 10 (worst possible pain)). Successful treatment was defined as > 50% NRS pain reduction. Patient satisfaction was scored by patient global impression of change (PGIC, 1 = very much worse, to 7 = very much improved). Twenty-six patients were studied (17 women, median age 47 years, range 18 - 67 years). After 6 weeks, mean NRS score had dropped from 6.7 ± 1.2 to 3.8 ± 2.3 (P < 0.001). A mean 4.9 ± 1.4 PGIC score was reported by then. Short term treatment success (6 - 8 weeks) was 50% (n = 13, 95% CI: 29 - 71), while 8% was pain-free on the longer term (median 15 months). Median effect duration was 4 months (range 2 - 26). PRF is temporarily effective in half of patients with ACNES. PRF is safe and may be favored in neuropathic pain syndromes as nerve tissue destruction is possibly limited. A randomized controlled trial determining the potential additional role of PRF in the treatment strategy for ACNES is underway.


Geographic variation in device use for intertrochanteric hip fractures.
Hip fractures in the elderly are a common and costly problem, with intertrochanteric fractures accounting for almost half of these fractures. Most intertrochanteric fractures are treated with either a plate-and-screw device or an intramedullary nail device. We assessed the degree of geographic variation in use of intramedullary nailing for intertrochanteric femoral fractures among Medicare beneficiaries between 2000 and 2002. Medicare 100% files (hospital and physician claims, and enrollment) for 2000 through 2002 were used to identify beneficiaries, sixty-five years of age or older, who had undergone inpatient surgery for the treatment of an intertrochanteric femoral fracture with a plate-and-screw device or an intramedullary nail. We used multiple logistic regression analysis to model the use of an intramedullary nail (as opposed to a plate-and-screw device) by state and year, after adjusting for patient age, sex, race, subtrochanteric fracture, comorbidities, and Medicaid-administered assistance. The odds ratios of receiving an intramedullary nail device are reported. The adjusted state rates of intramedullary nailing per 100 Medicare patients with an intertrochanteric fracture are reported for 2000 through 2002. In this study, 212,821 claims for operations to treat patients with an intertrochanteric fracture from 2000 through 2002 met the inclusion criteria. There was considerable geographic variation in intramedullary nail use by state across all years. The mean adjusted intramedullary nailing rate per 100 Medicare patients with an intertrochanteric fracture increased nationally from 7.84 in 2000 to 16.98 in 2002. In 2000, surgeons in sixteen states used an intramedullary nail in fewer than one of every twenty Medicare patients with an intertrochanteric fracture. By 2002, surgeons in only two states used an intramedullary nail in fewer than one of every twenty patients with an intertrochanteric fracture, and in eight states they used an intramedullary nail in more than one of every four patients with an intertrochanteric fracture. There was substantial geographic variation in the use of intramedullary nailing by state from 2000 through 2002 that was largely not explained by patient-related factors.


Running with a powered knee and ankle prosthesis.
This paper presents a running control architecture for a powered knee and ankle prosthesis that enables a transfemoral amputee to run with a biomechanically appropriate running gait and to intentionally transition between a walking and running gait. The control architecture consists firstly of a coordination level controller, which provides gait biomechanics representative of healthy running, and secondly of a gait selection controller that enables the user to intentionally transition between a running and walking gait. The running control architecture was implemented on a transfemoral prosthesis with powered knee and ankle joints, and the efficacy of the controller was assessed in a series of running trials with a transfemoral amputee subject. Specifically, treadmill trials were conducted to assess the extent to which the coordination controller provided a biomechanically appropriate running gait. Separate trials were conducted to assess the ability of the user to consistently and reliably transition between walking and running gaits.


Standardized approach for developing probabilistic exposure factor distributions.
The effectiveness of a probabilistic risk assessment (PRA) depends on the quality and relevance of the output from exposure and risk models, which, in turn, depends on the critical inputs to the assessment. These critical inputs are often in the form of probabilistic exposure factor distributions that are derived for the given risk scenario. Deriving probabilistic distributions for model inputs can be time consuming and subjective. The absence of a standard approach for developing these distributions can result in PRAs that are inconsistent and difficult to review by regulatory agencies. We present an approach that reduces subjectivity in the distribution development process without limiting the flexibility needed to prepare relevant PRAs. The approach requires two steps. First, we analyze data pooled at a population scale to (i) identify the most robust demographic descriptors within the population for a given exposure factor, (ii) partition the data into subsets based on these variables, and (iii) construct archetypal distributions for each subpopulation. Second, we sample from these archetypal distributions according to site- or scenario-specific conditions to simulate exposure factor values and use these values to construct the scenario-specific input distribution. The archetypal distributions developed through Step 1 provide a consistent basis for developing scenario-specific distributions so risk assessors will not have to repeatedly collect and analyze raw data for each new assessment. We demonstrate the approach for two commonly used exposure factors--body weight (BW) and exposure duration (ED)--using data that are representative of the U.S. population. For these factors we provide a first set of subpopulation-based archetypal distributions and demonstrate methods for using these distributions to construct relevant scenario-specific probabilistic exposure factor distributions.


Identification of tolerance levels on the cold-water coral Desmophyllum pertusum (Lophelia pertusa) from realistic exposure conditions to suspended bentonite, barite and drill cutting particles.
Cold-water coral (CWC) reefs are numerous and widespread along the Norwegian continental shelf where oil and gas industry operate. Uncertainties exist regarding their impacts from operational discharges to drilling. Effect thresholds obtained from near-realistic exposure of suspended particle concentrations for use in coral risk modeling are particularly needed. Here, nubbins of Desmophyllum pertusum (Lophelia pertusa) were exposed shortly (5 days, 4h repeated pulses) to suspended particles (bentonite BE; barite BA, and drill cuttings DC) in the range of ~ 4 to ~ 60 mg.l-1 (actual concentration). Physiological responses (respiration rate, growth rate, mucus-related particulate organic carbon OC and particulate organic nitrogen ON) and polyp mortality were then measured 2 and 6 weeks post-exposure to assess long-term effects. Respiration and growth rates were not significantly different in any of the treatments tested compared to control. OC production was not affected in any treatment, but a significant increase of OC:ON in mucus produced by BE-exposed (23 and 48 mg.l-1) corals was revealed 2 weeks after exposure. Polyp mortality increased significantly at the two highest DC doses (19 and 49 mg.l-1) 2 and 6 weeks post-exposure but no significant difference was observed in any of the other treatments compared to the control. These findings are adding new knowledge on coral resilience to short realistic exposure of suspended drill particles and indicate overall a risk for long-term effects at a threshold of ~20 mg.l-1.


Complete Genome Sequence of Prevotella intermedia Strain 17-2.
Prevotella intermedia, a Gram-negative black-pigmented anaerobic rod, is frequently isolated from not only periodontal pockets but also purulent infections. We report here the complete genome sequence of P. intermedia strain 17-2, which is a non-exopolysaccharide-producing variant obtained from exopolysaccharide (EPS)-producing P. intermedia strain 17 stock culture.


Competency to Proceed to Trial Evaluations and Rational Understanding.
In Dusky v. United States, the United States Supreme Court established "rational understanding" as a necessary component of a defendant's competency to stand trial. Yet, rational understanding has engendered misunderstanding, stemming from inconsistent court rulings and lack of systematic attention given to definitions of rationality. The purpose of this article is to assist with the conceptualization of rational understanding as it relates to competency to proceed to trial. This will be accomplished through a review of legal decisions and scholarly papers that provide various definitions of rationality. We discuss the suitability of standardized instruments of competency and how they may assist in providing a valid metric for evaluating rational abilities. We also provide discussion of how case law, in conjunction with psycholegal research, can be used to gain nuanced insight into operationalizations of rational understanding. By gaining a thorough understanding of rationality in competency to proceed to trial evaluations, clinicians may improve on the quality and foundation of their evaluations.


PI3Kδ inhibition augments the efficacy of rapamycin in suppressing proliferation of Epstein-Barr virus (EBV)+ B cell lymphomas.
Posttransplant lymphoproliferative disorder (PTLD) continues to be a devastating and potentially life-threatening complication in organ transplant recipients. PTLD is associated with EBV infection and can result in malignant B cell lymphomas. Here we demonstrate that the PI3K/Akt/mTOR pathway is highly activated in EBV+ B cell lymphoma lines derived from patients with PTLD. Treatment with the mTORC1 inhibitor Rapamycin (RAPA) partially inhibited the proliferation of EBV+ B cell lines. Resistance to RAPA treatment correlated with high levels of Akt phosphorylation. An mTORC1/2 inhibitor and a PI3K/mTOR dual inhibitor suppressed Akt phosphorylation and showed a greater anti-proliferative effect on EBV+ B lymphoma lines compared to RAPA. EBV+ B cell lymphoma lines expressed high levels of PI3Kδ. We demonstrate that PI3Kδ is responsible for Akt activation in EBV+ B cell lymphomas, and that selective inhibition of PI3Kδ by either siRNA, or a small molecule inhibitor, augmented the anti-proliferative effect of RAPA on EBV+ B cell lymphomas. These results suggest that PI3Kδ is a novel, potential therapeutic target for the treatment of EBV-associated PTLD and that combined blockade of PI3Kδ and mTOR provides increased efficacy in inhibiting proliferation of EBV+ B cell lymphomas.


The rotating-crystal method in femtosecond X-ray diffraction.
We report the first implementation of the rotating-crystal method in femtosecond X-ray diffraction. Applying a pump-probe scheme with 100 fs hard X-ray probe pulses from a laser-driven plasma source, the novel technique is demonstrated by mapping structural dynamics of a photoexcited bismuth crystal via changes of the diffracted intensity on a multitude of Bragg reflections. The method is compared to femtosecond powder diffraction and to Bragg diffraction from a crystal with stationary orientation.


Ultrasonographic changes of the liver in Schistosoma haematobium infection.
Abdominal ultrasonographic examination was performed in 61 hospitalized patients with chronic liver diseases and 253 school children from a village endemic for Schistosoma haematobium and were compared with 142 urban children without exposure to Schistosoma. The prevalence of ultrasound-detectable hepatomegaly and splenomegaly and the degree of periportal fibrosis was compared between those with and without S. haematobium infection. Among 13 patients with biopsy-proven schistosomal hepatic fibrosis, three with coarse changes secondary to S. mansoni infection showed grade III periportal fibrosis, while 10 patients with fine schistosomal hepatic fibrosis due to S. haematobium had borderline (two) or grade I (eight) changes. Ultrasound evidence of periportal fibrosis was not detected in patients with hepatic cirrhosis, chronic active hepatitis, or fatty infiltration. However, three of 14 patients with chronic persistent hepatitis had grade I periportal fibrosis and two had borderline changes. The frequency of ultrasound-detected hepatomegaly and splenomegaly was greater among rural S. haematobium-infected children (35.2% and 22.4%, respectively) than among noninfected rural (21.1% and 13.3%) and urban (16.9% and 4.9%) children. Also, the frequency of grade I periportal fibrosis was significantly greater (P less than 0.01) in S. haematobium-infected children (22.4%) than in noninfected rural (11.7%) and urban (0.7%) children. No patients with S. haematobium infections, either in the hospital or the village, had grade II or III periportal fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)


A joint matrix completion and filtering model for influenza serological data integration.
Antigenic characterization based on serological data, such as Hemagglutination Inhibition (HI) assay, is one of the routine procedures for influenza vaccine strain selection. In many cases, it would be impossible to measure all pairwise antigenic correlations between testing antigens and reference antisera in each individual experiment. Thus, we have to combine and integrate the HI tables from a number of individual experiments. Measurements from different experiments may be inconsistent due to different experimental conditions. Consequently we will observe a matrix with missing data and possibly inconsistent measurements. In this paper, we develop a new mathematical model, which we refer to as Joint Matrix Completion and Filtering, for HI data integration. In this approach, we simultaneously handle the incompleteness and uncertainty of observations by assuming that the underlying merged HI data matrix has low rank, as well as carefully modeling different levels of noises in each individual table. An efficient blockwise coordinate descent procedure is developed for optimization. The performance of our approach is validated on synthetic and real influenza datasets. The proposed joint matrix completion and filtering model can be adapted as a general model for biological data integration, targeting data noises and missing values within and across experiments.


Dependences of photoluminescence from P-implanted epitaxial Ge.
A systematic investigation has been carried out to study the influence of various annealings and implantations on the photoluminescence (PL) properties of phosphorus (P)-implanted Ge epitaxial films on Si substrate. For un-capped Ge samples, rapid thermal annealing (RTA) at 700 °C for 300 seconds yields the strongest PL emission peaked at 1550 nm. The influence of employing various capping layers (i.e., SiO(2), Si(3)N(4), and α-Si ) on the PL properties has been investigated. The capping layers are found to effectively decrease the dopant loss, leading to a significant PL enhancement. Si(3)N(4) is found to be the most efficient capping layer to prevent dopant out-diffusion and thus lead to strongest PL. Furthermore, it has been found that capping layers not only enhance the PL intensities but also make PL emission peak red- and blue- shift, depending on the stress type of the capping films. The effect of implantation dose on the PL has been also investigated.


Gingival overgrowth and dental alveolar alterations: possible mechanisms of cyclosporin-induced tooth migration. An experimental study in the rat.
The inter-incisal distance and dimension of the interdental papilla between the mandibular incisors were examined in cyclosporin A (CSA) fed rats over 6 weeks. Rats in the test group received CSA daily in mineral oil by gastric feeding (30 mg/kg body weight); the control group received mineral oil only. The inter-incisal distance and gingival dimensions, including bucco-lingual width and vertical height, were assessed biweekly from alginate impressed stone models. Animals were sacrificed at the end of the study and tissue sections were obtained from the anterior region of the mandible for histopathological evaluation. Both the inter-incisal distance and the dimension of the interdental papilla were significantly greater in CSA-exposed animals compared to control. The significant alteration appeared earlier in the papillary dimensions than that in the interdental distance. Particular histopathological alterations of the soft and hard tissues of the periodontium were observed in CSA-exposed animals. Within limitations of the study, we suggest that the CSA-induced gingival overgrowth may offer an active force contributing to observed tooth movement, however, remarkable alveolar remodeling should be considered as an undetermined factor for the movement.


Self-related health, physical activity and complaints in Swedish high school students.
The aim of this investigation was to study self-related health, physical activity and level of exertion, as well as body complaints in Swedish high school students. A total of 993 high school students aged 16-19 years participated in the study. A questionnaire was completed at school and included questions about self-related health, physical activity behavior, type of physical activity/sport, intensity, duration, possible injuries or complaints, and absence from physical training at school, during the last 3 months. The results showed that 26% of the high school students participated in sports on a regular basis. Males reported significantly better health than females (p < 0.0005). A significantly higher number of females participated in physical activities at a lower level of effort (p < 0.0005) and a higher number of males trained at a higher level of effort (p < 0.005). Sixty-one percent reported body pain during the last 3 months, representing a higher number of females than males (p = 0.03). A higher number of females than males reported complaints from the back (p = 0.002), the knees (p = 0.015), the neck (p = 0.001), and the hip (p = 0.015). Females with body complaints reported poorer health than those without complaints. There was a correlation between poor self-related health and a lower level of physical effort (0.219; p < 0.001). The results showed that the prevalence of musculoskeletal symptoms was high in this population and demonstrated a certain association with self-related health. Therefore, it is important to make it easy for adolescents to perform physical activity at school and during their leisure time in order to prevent chronic diseases.


Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model.
Neurodegeneration with brain iron accumulation (NBIA) comprises a group of neurodegenerative disorders characterized by high brain content of iron and presence of axonal spheroids. Mutations in the PANK2 gene, which encodes pantothenate kinase 2, underlie an autosomal recessive inborn error of coenzyme A metabolism, called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia, dysarthria, rigidity and pigmentary retinal degeneration. The pathogenesis of this disorder is poorly understood and, although PANK2 is a mitochondrial protein, perturbations in mitochondrial bioenergetics have not been reported. A knock-out (KO) mouse model of PKAN exhibits retinal degeneration and azoospermia, but lacks any neurological phenotype. The absence of a clinical phenotype has partially been explained by the different cellular localization of the human and murine PANK2 proteins. Here we demonstrate that the mouse Pank2 protein localizes to mitochondria, similar to its human orthologue. Moreover, we show that Pank2-defective neurons derived from KO mice have an altered mitochondrial membrane potential, a defect further corroborated by the observations of swollen mitochondria at the ultra-structural level and by the presence of defective respiration.


Acclimation of intestinal morphology and function in Djungarian hamsters (Phodopus sungorus) related to seasonal and acute energy balance.
Small mammals exhibit seasonal changes in intestinal morphology and function via increased intestine size and resorptive surface and/or nutrient transport capacity to increase energy yield from food during winter. This study investigated whether seasonal or acute acclimation to anticipated or actual energetic challenges in Djungarian hamsters also resulted in higher nutrient resorption capacities owing to changes in small intestine histology and physiology. The hamsters show numerous seasonal energy-saving adjustments in response to short photoperiod. As spontaneous daily torpor represents one of these adjustments related to food quality and quantity, it was hypothesized that the hamsters' variable torpor expression patterns are influenced by their individual nutrient uptake capacity. Hamsters under short photoperiod showed longer small intestines and higher mucosal electrogenic transport capacities for glucose relative to body mass. Similar observations were made in hamsters under long photoperiod and food restriction. However, this acute energetic challenge caused a stronger increase of glucose transport capacity. Apart from that, neither fasting-induced torpor in food-restricted hamsters nor spontaneous daily torpor in short photoperiod-exposed hamsters clearly correlated with mucosal glucose transport capacity. Both seasonally anticipated and acute energetic challenges caused adjustments in the hamsters' small intestine. Short photoperiod appeared to induce an integration of these and other acclimation processes in relation to body mass to achieve a long-term adjustment of energy balance. Food restriction seemed to result in a more flexible, short-term strategy of maximizing energy uptake possibly via mucosal glucose transport and reducing energy consumption via torpor expression as an emergency response.


Hospital Prevalence of Retinopathy in Patients with Newly-Diagnosed Type 2 Diabetes.
To determine the period prevalence of diabetic retinopathy (DR) and the associated factors in patients with newly-diagnosed Type 2 diabetes mellitus (T2DM). In this prospective study, all newly-diagnosed T2DM patients who attended the ophthalmology clinic at King Fahad Hospital of the University between January 2012 and January 2015, were examined for DR. After pupillary dilation, the ophthalmic fundus was examined by a retina consultant using slit-lamp indirect ophthalmoscopy. Risk factors such as gender, age, hypertension, nephropathy, the level of glycated hemoglobin (Hb), microalbuminuria, and hyperlipidemia were evaluated for possible association with DR at the time of diagnosis. The study included 112 newly-diagnosed T2DM patients. DR was present in seven patients (6.25%) with a mean age of 53.4 ± 6.4 years, four of whom were females (57%). Nonproliferative DR was present in all patients with DR, two patients (28.6%) presented with bilateral clinically significant macular edema requiring laser photocoagulation treatment and intravitreal anti-vascular endothelial growth factor therapy. In the study cohort, elevated hemoglobin A1C levels (HbA1C) were detected in 55 patients (49.1%), microalbuminuria in 28 (25.0%), hypertension in 31 (27.6%), hyperlipidemia in 65 (58.0%) and obesity in 43 (38.1%). At the time of T2DM diagnosis, uncontrolled HbA1C levels were significantly associated with the presence of retinopathy (P = 0.045); however, no statistical significance was observed for the remaining risk factors. The frequency of retinopathy in newly-diagnosed T2DM patients was similar to previous reports. Vision-threatening maculopathy was present in two of seven patients, requiring further intervention. Therefore, early screening is strongly recommended for all newly-diagnosed T2DM patients. Prospective studies with a large sample size are needed to verify the risk factors for these patients.


An in vivo 1H magnetic resonance spectroscopy study of the deep cerebellar nuclei in children with fetal alcohol spectrum disorders.
Prenatal alcohol exposure has been linked to impairment in cerebellar structure and function, including eyeblink conditioning. The deep cerebellar nuclei, which play a critical role in cerebellar-mediated learning, receive extensive inputs from brain stem and cerebellar cortex and provide the point of origin for most of the output fibers to other regions of the brain. We used in vivo (1) H magnetic resonance spectroscopy (MRS) to examine effects of prenatal alcohol exposure on neurochemistry in this important cerebellar region. MRS data from the deep cerebellar nuclei were acquired from 37 children with heavy prenatal alcohol exposure and 17 non- or minimally exposed controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa. Increased maternal alcohol consumption around time of conception was associated with lower N-Acetylaspartate (NAA) levels in the deep nuclei (r = -0.33, p < 0.05). Higher levels of alcohol consumption during pregnancy were related to lower levels of the choline-containing metabolites (r = -0.37, p < 0.01), glycerophosphocholine plus phosphocholine (Cho). Alcohol consumption levels both at conception (r = 0.35, p < 0.01) and during pregnancy (r = 0.38, p < 0.01) were related to higher levels of glutamate plus glutamine (Glx). All these effects continued to be significant after controlling for potential confounders. The lower NAA levels seen in relation to prenatal alcohol exposure may reflect impaired neuronal integrity in the deep cerebellar nuclei. Our finding of lower Cho points to disrupted Cho metabolism of membrane phospholipids, reflecting altered neuropil development with potentially reduced content of dendrites and synapses. The alcohol-related alterations in Glx may suggest a disruption of the glutamate-glutamine cycling involved in glutamatergic excitatory neurotransmission.


The effect of acetazolamide on cerebral blood flow and oxygen utilization in the rhesus monkey.
The brain is critically dependent for its moment to moment function and survival on an adequate supply of oxygen. The enzyme carbonic anhydrase (EC 126.96.36.199) may play an important role in oxygen delivery to brain tissue by facilitating the hydration of metabolically produced carbon dioxide in erythrocytes in brain capillaries, thus permitting the Bohr effect to occur. We examined the effect of 30 mg/kg i.v. acetazolamide, a potent inhibitor of carbonic anhydrase, upon cerebral blood flow and oxygen consumption in lightly anesthetized, passively ventilated rhesus monkeys. Cerebral blood flow and oxygen consumption were measured with oxygen-15-labeled water and oxygen-15-labeled oxyhemoglobin, respectively, injected into the internal carotid artery and monitored externally. Acetazolamide produced an immediate and significant increase in cerebral blood flow (from a mean of 64.7 to 83.8 ml/100 g per min), an increase in arterial carbon dioxide tension (from a mean of 40.7 to 47.5 torr), and a decrease in cerebral oxygen consumption (from a mean of 4.16 to 2.82 ml/100 g per min). Because the change in cerebral oxygen consumption occurred within minutes of the administration of acetazolamide, we believe that this effect probably was not due to a direct action on brain cells but was achieved by an interference with oxygen unloading in brain capillaries. A resultant tissue hypoxia might well explain part of the observed increase in cerebral blood flow.


Epidemiology of injuries in English professional rugby union: part 1 match injuries.
To undertake a detailed, large scale epidemiological study of match injuries sustained by professional rugby union players in order to define their incidence, nature, severity, and causes. A two season prospective design was used to study match injuries associated with 546 rugby union players at 12 English Premiership clubs. Team clinicians reported all match injuries on a weekly basis and provided details of the location, diagnosis, severity, and mechanism of each injury. Match exposures for individual players were recorded on a weekly basis. Loss of time from training and match play was used as the definition of an injury. The overall incidence of injury was 91 injuries/1000 player-hours, and each injury resulted on average in 18 days lost time. Recurrences, which accounted for 18% of injuries, were significantly more severe (27 days) than new injuries (16 days). Thigh haematomas were the most common injury for forwards and backs, but anterior cruciate ligament injuries for forwards and hamstring injuries for backs caused the greatest number of days absence. Contact mechanisms accounted for 72% of injuries, but foul play was only implicated in 6% of injuries. The ruck and maul elements of the game caused most injuries to forwards, and being tackled caused most injuries to backs. The hooker and outside centre were the playing positions at greatest risk of injury. On average, a club will have 18% of their players unavailable for selection as a consequence of match injuries.


Nanostructured elliptical gradient-index microlenses.
We show theoretical and experimental characterizations of a nanostructured gradient-index lens. The elliptical lens is a nonguiding element fabricated using the mosaic method, which is widely used for the fabrication of photonic crystal fibers. For the first time we show experimental data in the optics regime that confirm the effective medium approximation for discrete mosaic structures with subwavelength feature size. This opens the door for the development of general asymmetric gradient-index materials.


Intervention to enhance empowerment in breast cancer self-help groups.
As arduous psychological reactions and loss of control almost inevitably represent a challenge for women diagnosed and treated for breast cancer, a participatory intervention study was initiated that aimed to enhance empowerment in breast cancer self-help groups. Women newly diagnosed with breast cancer were invited to participate. The intervention encompassed three professionally led self-help groups running sequentially, each group for approximately 4 months. Each group of five to seven participants met weekly. Several empowerment strategies were initiated by two professional facilitators, aiming to promote empowerment processes and to manage stress. The participants experienced group participation as both empowering and as a valuable source of support, and although the group processes developed very differently, a strong sense of fellowship developed in all three groups. The discussion highlights the findings in relation to several theoretical perspectives including social capital, social cohesion, risky agreements, helper-therapy and power/empowerment. We conclude that empowerment strategies that are implemented in professionally led breast cancer self-help groups can contribute to participant empowerment and function as an important source of re-discovery and confirmation of the participants' strengths and abilities.


Progranulin and granulin-like protein as novel VEGF-independent angiogenic factors derived from human mesothelioma cells.
Malignant mesothelioma is an aggressive tumor arising from the mesothelial cells of serous membranes and is associated with tumor angiogenesis, which is a prerequisite for tumor progression. Vascular endothelial growth factors (VEGFs) including VEGF-A have a crucial role in tumor angiogenesis. However, bevacizumab, a monoclonal antibody to VEGF-A, has recently been reported not to improve the progression-free survival of patients with malignant mesothelioma. Cell culture supernatant contains extracellular components such as serum, which can mask the existence of unknown cell-derived factors in the supernatant and make it difficult to detect the factors by subsequent protein analysis. We tried using serum-free culture for human mesothelioma cell lines, NCI-H28, NCI-H2452 and NCI-H2052, and only NCI-H2052 cells adapted to serum-free culture. We found that serum-free culture supernatant derived from NCI-H2052 cells induces the formation of capillary-like tube structures (tube formation) in three-dimensional culture, in which endothelial cells sandwiched between two layers of collagen or embedded in collagen are incubated with various angiogenic inducers. However, neither neutralization of VEGF-A nor RNA interference of VEGF receptor 2 (VEGFR2) suppressed the supernatant-induced tube formation. Using mass spectrometry, we identified a total of 399 proteins in the supernatant, among which interleukin-8 (IL-8), growth-regulated α-protein, midkine, IL-18, IL-6, hepatoma-derived growth factor, clusterin and granulin (GRN), also known as progranulin (PGRN), were included as a candidate protein inducing angiogenesis. Neutralizing assays and RNA interference showed that PGRN, but not the above seven candidate proteins, caused the supernatant-induced tube formation. We also found that NCI-H28 and NCI-H2452 cells express PGRN. Furthermore, we demonstrate that not only PGRN but also GRN-like protein have an important role in the supernatant-induced tube formation. Thus, mesothelioma-derived GRNs induce VEGF-independent angiogenesis.


Fast phenotyping of LFS-silenced (tearless) onions by desorption electrospray ionization mass spectrometry (DESI-MS).
Fast MS techniques have been applied to the analysis of sulfur volatiles in Allium species and varieties to distinguish phenotypes. Headspace sampling by proton transfer reaction (PTR) MS and surface sampling by desorption electrospray ionization (DESI) MS were used to distinguish lachrymatory factor synthase (LFS)-silenced (tearless; LFS-) onions from normal, LFS-active (tear-inducing; LFS+), onions. PTR-MS showed lower concentrations of the lachrymatory factor (LF, 3) and dipropyl disulfide 12 from tearless onions. DESI-MS of the tearless onions confirmed the decreased LF 3 and revealed much higher concentrations of the sulfenic acid condensates. Using DESI-MS with MS(2) could distinguish zwiebelane ions from thiosulfinate ions. DESI-MS gave reliable fast phenotyping of LFS+ versus LFS- onions by simply scratching leaves and recording the extractable ions for <0.5 min. DESI-MS leaf compound profiles also allowed the rapid distinction of a variety of Allium cultivars to aid plant breeding selections.


Conservation of oxidative protein stabilization in an insect homologue of parkinsonism-associated protein DJ-1.
DJ-1 is a conserved, disease-associated protein that protects against oxidative stress and mitochondrial damage in multiple organisms. Human DJ-1 contains a functionally essential cysteine residue (Cys106) whose oxidation is important for regulating protein function by an unknown mechanism. This residue is well-conserved in other DJ-1 homologues, including two (DJ-1α and DJ-1β) in Drosophila melanogaster. Because D. melanogaster is a powerful model system for studying DJ-1 function, we have determined the crystal structure and impact of cysteine oxidation on Drosophila DJ-1β. The structure of D. melanogaster DJ-1β is similar to that of human DJ-1, although two important residues in the human protein, Met26 and His126, are not conserved in DJ-1β. His126 in human DJ-1 is substituted with a tyrosine in DJ-1β, and this residue is not able to compose a putative catalytic dyad with Cys106 that was proposed to be important in the human protein. The reactive cysteine in DJ-1 is oxidized readily to the cysteine-sulfinic acid in both flies and humans, and this may regulate the cytoprotective function of the protein. We show that the oxidation of this conserved cysteine residue to its sulfinate form (Cys-SO(2)(-)) results in considerable thermal stabilization of both Drosophila DJ-1β and human DJ-1. Therefore, protein stabilization is one potential mechanism by which cysteine oxidation may regulate DJ-1 function in vivo. More generally, most close DJ-1 homologues are likely stabilized by cysteine-sulfinic acid formation but destabilized by further oxidation, suggesting that they are biphasically regulated by oxidative modification.


Oromucosal film preparations: points to consider for patient centricity and manufacturing processes.
According to the European Pharmacopoeia, oromucosal films comprise mucoadhesive buccal films and orodispersible films. Both oral dosage forms receive considerable interest in the recent years as commercially available pharmaceutical products and as small scale personalized extemporaneous preparations. In this review, technological issues such as viscosity of the casting liquid, mechanical properties of the film, upscaling and the stability of the casting solution and produced films will be discussed. Furthermore, patient-related problems like appearance, mucosal irritation, taste, drug load, safety and biopharmaceutics are described. Current knowledge and directions for solutions are summarized. The viscosity of the casting solution is a key factor for producing suitable films. This parameter is amongst others dependent on the polymer and active pharmaceutical ingredient, and the further excipients that are used. For optimal patient compliance, an acceptable taste and palatability are desirable. Safe and inert excipients should be used and appropriate packaging should be provided to produced films. Absorption through the oral mucosa will vary for each active compound, formulation and patient, which gives rise to pharmacokinetic questions. Finally, the European Pharmacopoeia needs to specify methods, requirement and definitions for oromucosal film preparations based on bio-relevant data.


Decreased telomere length in children with cartilage-hair hypoplasia.
Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia caused by RMRP (RNA component of mitochondrial RNA processing endoribonuclease) gene mutations. Manifestations include short stature, variable immunodeficiency, anaemia and increased risk of malignancies, all of which have been described also in telomere biology disorders. RMRP interacts with the telomerase RT (TERT) subunit, but the influence of RMRP mutations on telomere length is unknown. We measured relative telomere length (RTL) in patients with CHH, their first-degree relatives and healthy controls and correlated RTL with clinical and laboratory features. The study cohort included 48 patients with CHH with homozygous (n=36) or compound heterozygous RMRP mutations (median age 38.2 years, range 6.0-70.8 years), 86 relatives (74 with a heterozygous RMRP mutation) and 94 unrelated healthy controls. We extracted DNA from peripheral blood, sequenced the RMRP gene and measured RTL by qPCR. Compared with age-matched and sex-matched healthy controls, median RTL was significantly shorter in patients with CHH (n=40 pairs, 1.05 vs 1.21, p=0.017), but not in mutation carriers (n=48 pairs, 1.16 vs 1.10, p=0.224). RTL correlated significantly with age in RMRP mutation carriers (r=-0.482, p<0.001) and non-carriers (r=-0.498, p<0.001), but not in patients (r=-0.236, p=0.107). In particular children (<18 years) with CHH had shorter telomeres than controls (median RTL 1.12 vs 1.26, p=0.008). In patients with CHH, RTL showed no correlation with genotype, clinical or laboratory characteristics. Telomere length was decreased in children with CHH. We found no correlation between RTL and clinical or laboratory parameters.


The symptom complex of familial sinus node dysfunction and myocardial noncompaction is associated with mutations in the HCN4 channel.
Inherited arrhythmias were originally considered isolated electrical defects. There is growing evidence that ion channel dysfunction also contributes to myocardial disorders, but genetic overlap has not been reported for sinus node dysfunction (SND) and noncompaction cardiomyopathy (NCCM). The study sought to investigate a familial electromechanical disorder characterized by SND and NCCM, and to identify the underlying genetic basis. The index family and a cohort of unrelated probands with sinus bradycardia were examined by electrocardiography, Holter recording, exercise stress test, echocardiography, and/or cardiac magnetic resonance imaging. Targeted next-generation and direct sequencing were used for candidate gene analysis and mutation scanning. Ion channels were expressed in HEK293 cells and studied using patch-clamp recordings. SND and biventricular NCCM were diagnosed in multiple members of a German family. Segregation analysis suggested autosomal-dominant inheritance of the combined phenotype. When looking for potentially disease-causing gene variants with cosegregation, a novel hyperpolarization-activated cyclic nucleotide channel 4 (HCN4)-G482R mutation and a common cysteine and glycine-rich protein 3 (CSRP3)-W4R variant were identified. HCN4-G482R is located in the highly conserved channel pore domain. Mutant subunits were nonfunctional and exerted dominant-negative effects on wild-type current. CSRP3-W4R has previously been linked to dilated and hypertrophic cardiomyopathy, but was also found in healthy subjects. Moreover, different truncation (695X) and missense (P883R) HCN4 mutations segregated with a similar combined phenotype in an additional, unrelated family and a single unrelated proband respectively, which both lacked CSRP3-W4R. The symptom complex of SND and NCCM is associated with heritable HCN4 defects. The NCCM phenotype may be aggravated by a common CSRP3 variant in one of the families.


Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a.
Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 response. Yet, it has proved challenging to identify relevant peptide-based T cell antigens. Antigen-presenting Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A2 (PLA2) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells. In this study, we observed expression of a cytoplasmic PLA2 (PLA2G4D) in psoriatic mast cells but, unexpectedly, also found PLA2G4D activity to be extracellular. This was explained by IFN-α-induced mast cell release of exosomes, which transferred cytoplasmic PLA2 activity to neighboring CD1a-expressing cells. This led to the generation of neolipid antigens and subsequent recognition by lipid-specific CD1a-reactive T cells inducing production of IL-22 and IL-17A. Circulating and skin-derived T cells from patients with psoriasis showed elevated PLA2G4D responsiveness compared with healthy controls. Overall, these data present an alternative model of psoriasis pathogenesis in which lipid-specific CD1a-reactive T cells contribute to psoriatic inflammation. The findings suggest that PLA2 inhibition or CD1a blockade may have therapeutic potential for psoriasis.


Proximal and large hyperplastic and nondysplastic serrated polyps detected by colonoscopy are associated with neoplasia.
The family of serrated lesions includes hyperplastic polyps and sessile serrated adenomas without dysplasia, as well as traditional serrated adenoma with dysplasia. We investigated whether detection of proximal nondysplastic serrated polyps (ND-SP) at screening and surveillance colonoscopies is associated with advanced neoplasia. The study included 3121 asymptomatic patients (aged 50-75 years) who had screening colonoscopies; 1371 had subsequent surveillance. The proximal colon was defined as segments proximal to the descending colon. Large ND-SP were defined as ≥ 10 mm. We compared rates of detection of any neoplasia and advanced neoplasia at screening and surveillance colonoscopies (within 5.5 years) in patients with and without proximal or large ND-SP. At baseline screening, 248 patients (7.9%) had at least 1 proximal ND-SP. They were more likely than patients with no proximal ND-SP to have advanced neoplasia (17.3% vs 10.0%; odds ratio [OR], 1.90; 95% confidence interval [CI], 1.33-2.70). Patients with large ND-SP (n = 44) were also more likely to have synchronous advanced neoplasia (OR, 3.37; 95% CI, 1.71-6.65). During surveillance, 39 patients with baseline proximal ND-SP and no neoplasia were more likely to have neoplasia compared with subjects who did not have polyps (OR, 3.14; 95% CI, 1.59-6.20). Among patients with advanced neoplasia at baseline, those with proximal ND-SP (n = 43) were more likely to have advanced neoplasia during surveillance (OR, 2.17; 95% CI, 1.03-4.59). Detection of proximal and large ND-SP at a screening colonoscopy is associated with an increased risk for synchronous advanced neoplasia. Detection of proximal ND-SP in a baseline colonoscopy is associated with an increased risk for interval neoplasia during surveillance.


Risk factors for spinal cord injury during surgery for spinal deformity.
Spinal cord monitoring is now considered standard care during surgery for spinal deformity. Combined somatosensory and motor evoked potential monitoring allows the detection of early spinal cord dysfunction in most patients. The purpose of the current study was to identify clinical factors that increase the risk of intraoperative electrophysical changes and to provide management recommendations. The records of 162 consecutive patients who underwent surgery for the treatment of spinal deformity at a tertiary referral center were reviewed. Electrophysical monitoring of these patients was considered to have been successful if reproducible signals had been obtained. Relevant electrophysical changes included a reduction, as compared with baseline, of >50% in the amplitude of the somatosensory evoked potentials; an increase, as compared with baseline, of >10% in the latency of the somatosensory evoked potentials; a loss of motor evoked potentials; and an abrupt decrease of >75% in the motor evoked potentials. One hundred and fifty-one (93%) of the 162 patients were monitored successfully. Four of the eleven patients with unsuccessful monitoring had neuromuscular scoliosis. Twelve of the 151 successfully monitored patients had a true electrophysical event, and two of them were found to have new postoperative neurologic deficits that represented a change from the findings of their preoperative neurologic examination. The determined causes of these electrophysical events included curve correction in eight patients, hypotension in two, direct cord trauma in one, and malposition of a pedicle screw in one. The patients with a true electrophysical event had a significantly higher rate of neurologic events than did the patients who did not have a true electrophysical event (p < 0.001). The rate of true electrophysical events was significantly higher in the patients with cardiopulmonary comorbidities than it was in the patients with no comorbidities (p = 0.011). Combined somatosensory and motor evoked potential monitoring effectively prevents neurologic injury in most children undergoing surgery for spinal deformity. Despite the potential for false-positive results, we recommend setting a low threshold for defining relevant electrophysical changes. Rapid intervention can reverse these changes and avoid potentially serious neurologic complications. Patients with cardiopulmonary comorbidities may be at a higher risk for having relevant electrophysical events.


Binocular Vision and the Stroop Test.
Recent studies report a link between optometric results, learning disabilities, and problems in reading. This study examines the correlations between optometric tests of binocular vision, namely, of vergence and accommodation, reading speed, and cognitive executive functions as measured by the Stroop test. Fifty-one students (mean age, 20.43 ± 1.25 years) were given a complete eye examination. They then performed the reading test L'Alouette and the Stroop interference test at their usual reading distance. Criteria for selection were the absence of significant refractive uncorrected error, strabismus, amblyopia, color vision defects, and other neurologic findings. The results show a correlation between positive fusional vergences (PFVs) at near distance and the interference effect (IE) in the Stroop test: the higher the PFV value is, the less the IE. Furthermore, the subgroup of 11 students presenting convergence insufficiency, according to Scheiman and Wick criteria (2002), showed a significantly higher IE during the Stroop test than the other students (N = 18) who had normal binocular vision without symptoms at near. Importantly, there is no correlation between reading speed and PFV either for the entire sample or for the subgroups. These results suggest for the first time a link between convergence capacity and the interference score in the Stroop test. Such a link is attributable to the fact that vergence control and cognitive functions mobilize the same cortical areas, for example, parietofrontal areas. The results are in favor of our hypothesis that vergence is a vector of attentional and cognitive functions.


Characterization of the Bull's Eye Rot of Apple in Chile.
Apple fruit in Chile are primarily produced for export to Asia, Europe, and the United States, which typically requires 15 to 40 days of maritime transportation. Therefore, Chilean apple production must fulfill the sanitization requirements imposed by the receiving countries. Under these circumstances, it was important to clarify the etiology of bull's eye rot that can severely affect 'Cripps Pink' apple and other late-harvest cultivars in Chile. Based on morphological characteristics and the partial sequence analysis of the internal transcribed spacer sequences and β-tubulin genes, Neofabraea alba was identified as the causal agent of the bull's eye rot of Chilean apple. These results were further corroborated using species-specific primers. The incidence of bull's eye rot varied considerably; for instance, in 2009, 0.0 to 58.7% in 38 Cripps Pink orchards surveyed in the relatively arid and humid apple-growing areas of Chile, respectively. There was no evidence for the presence of N. malicorticis or N. perennans, which are commonly identified as causal agents of bull's eye rot in other apple-producing countries. Altogether, these data suggest that N. alba might represent the predominant and possibly the only cause of bull's-eye rot of Chilean apple.


Traumatic aortic regurgitation combined with descending aortic pseudoaneurysm secondary to blunt chest trauma.
Rupture of the aorta is a relatively rare complication of blunt chest trauma, and traumatic rupture of the aortic valve is even rarer. Even though both result from blunt chest trauma, the causative mechanisms of aortic valve injury differ from those of descending aortic rupture. There are no previous reports in the literature of simultaneous injuries to both the descending aorta and the aortic valve. We report a case of a 70-year-old man who presented with traumatic aortic regurgitation combined with traumatic pseudoaneurysm of the aortic isthmus following blunt chest trauma, and its successful repair with a hybrid surgical strategy.


Astroglial overproduction of TGF-beta 1 enhances inflammatory central nervous system disease in transgenic mice .
Cerebral expression of the injury response cytokine transforming growth factor-beta 1 (TGF-beta 1) has been found to be increased in several neurological diseases but it remains unclear whether its function is primarily beneficial or detrimental. Here we show that transgenic (tg) mice that overexpress bioactive (TGF-beta 1 in the central nervous system (CNS) and show no overt phenotype in the unmanipulated state, are more susceptible to the immune-mediated CNS disease experimental autoimmune encephalomyelitis (EAE). TGF-beta 1 tg mice with EAE showed an earlier onset of clinical symptoms, more severe disease and increased mononuclear cell infiltration in their spinal cords compared with non-tg littermate controls with EAE. Whereas previous observations indicated that increased peripheral levels of TGF-beta 1 can suppress EAE, our findings demonstrate that local expression of TGF-beta 1 within the CNS parenchyma can enhance immune cell infiltration and intensify the CNS impairment resulting from peripherally triggered autoimmune responses.


Measuring patients' satisfaction with their anti-TNF treatment in severe Crohn's disease: scoring and psychometric validation of the Satisfaction for PAtients in Crohn's diseasE Questionnaire (SPACE-Q(©)).
Severe Crohn's disease management includes anti-tumor necrosis factor (anti-TNF) drugs that differ from early-stage treatments regarding efficacy, safety, and convenience. This study aimed to finalize and psychometrically validate the Satisfaction for PAtients in Crohn's diseasE Questionnaire (SPACE-Q(©)), developed to measure satisfaction with anti-TNF treatment in patients with severe Crohn's disease. A total of 279 patients with severe Crohn's disease receiving anti-TNF therapy completed the SPACE-Q 62-item pilot version at inclusion and 12 and 13 weeks after first anti-TNF injection. The final SPACE-Q scoring was defined using multitrait and regression analyses and clinical relevance considerations. Psychometric validation included clinical validity against Harvey-Bradshaw score, concurrent validity against Treatment Satisfaction Questionnaire for Medication (TSQM), internal consistency reliability, test-retest reliability, and responsiveness against the patient global impression of change (PGIC). Quality of completion was good (55%-67% of patients completed all items). Four items were removed from the questionnaire. Eleven scores were defined within the final 58-item SPACE-Q: disease control; symptoms, anal symptoms, and quality of life transition scales; tolerability; convenience; expectation confirmation toward efficacy, side effects, and convenience; satisfaction with treatment; and motivation. Scores met standards for concurrent validity (correlation between SPACE-Q satisfaction with treatment and TSQM satisfaction scores =0.59), internal consistency reliability (Cronbach's α=0.67-0.93), test-retest reliability (intraclass correlations =0.62-0.91), and responsiveness (improvement in treatment experience assessed by the SPACE-Q for patients reporting improvement on the PGIC). Significantly different mean scores were observed between groups of patients with different Harvey-Bradshaw disease severity scores. The SPACE-Q is a valid, reliable, and responsive instrument to measure satisfaction with anti-TNF treatment in patients with severe Crohn's disease and for use in future studies.


Performance and training standards for endovascular ischemic stroke treatment.
Stroke is the third leading cause of death in the USA, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, there are now 750,000 new strokes that occur each year, resulting in 200,000 deaths, or 1 of every 16 deaths, per year in the USA alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intra-arterial thrombolysis in selected patients. Intra-arterial thrombolysis has been studied in two randomized trials and numerous case series. Although two devices have been granted FDA approval with an indication for mechanical stroke thrombectomy, none of these thrombectomy devices has demonstrated efficacy for the improvement of patient outcomes. The purpose of the present document is to define what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and what performance standards should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies which historically have been directly involved in the medical, surgical and endovascular care of patients with acute stroke. The participating member organizations of the Neurovascular Coalition involved in the writing and endorsement of this document are the Society of NeuroInterventional Surgery, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section, and the Society of Vascular & Interventional Neurology.


2-36[K4,RYYSA(19-23)]PP a novel Y5-receptor preferring ligand with strong stimulatory effect on food intake.
Members of the neuropeptide Y (NPY) family regulate many physiological processes via interaction with at least four functional, pharmacologically distinct Y-receptors. However, selective antagonists developed for several subtypes have not been useful in defining particular Y-receptor functions in vivo. To identify critical residues within members of the NPY family required for Y-receptor subtype-selectivity we have determined the contribution of each residue within NPY to receptor binding by replacing them with L-alanine. In a second study, chimeric peptides where single or stretches of residues were interchanged between members of the NPY family were generated and tested in radioligand binding studies. Overall, substituted alanine analogues exhibited similar orders of affinities at each Y-receptor subtype with no obvious subtype-selectivity. Residues of particular interest are Leu30 which exhibited selectivity for the Y4-receptor, whereas Asp16 does not appear to play any role in ligand binding. Several chimeric peptides, e.g., [K4]pancreatic polypeptide ([K4]PP) and [RYYSA(19-23)]PP clearly showed higher affinity at the Y4 and Y5 subtypes compared to the Y1 and Y2 subtypes. In addition, the transfer of a proline residue from position 14 to 13 in peptide YY decreases its affinity at the Y1-, Y4- and Y5-receptors but is unchanged at the Y2 subtype. Combining these results, and with the help of molecular modelling, second generation chimeras were designed. The most significant improvement was achieved in chimera 2-36[K4,RYYSA(19-23)]PP where the affinity for the Y5 subtype increased by ninefold over that from NPY. Several of these compounds were also tested for their ability to stimulate food intake in a rat model. Interestingly, again 2-36[K4,RYYSA(19-23)]PP showed the most dramatic effect with a major increase on food intake over a range of doses compared to NPY suggesting a possible synergistic effect of several Y-receptors on feeding behaviour.


Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye.
To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation.


Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter.
The Edmonston vaccine strain of measles virus (MV-Edm) propagates efficiently in a broad range of human tumor cells, killing them selectively. However, the oncolytic potency of MV-Edm in different human tumor xenograft therapy models is highly variable and there is no convenient way to map the distribution of virus-infected tissues in vivo. To enhance the oncolytic potency of MV-Edm against radiosensitive malignancies and to facilitate noninvasive imaging of infected tissues, we generated a recombinant MV-Edm encoding the human thyroidal iodide symporter (NIS). MV-NIS replicated almost as efficiently as unmodified MV-Edm, and human tumor cells efficiently concentrated radioiodine when infected with MV-NIS. Intratumoral spread of MV-NIS was noninvasively demonstrated by serial gamma-camera imaging of iodine-123 (123I) uptake both in MV-sensitive KAS-6/1 myeloma xenografts, which regressed completely after a single intravenous dose of MV-NIS, and in MM1 myeloma xenografts, which were unresponsive to MVNIS therapy. However, MV-resistant MM1 tumors regressed completely when 131I was administered 9 days after a single intravenous injection of MV-NIS (radiovirotherapy). 131I alone had no effect on MM1 tumor growth. While the potential hematopoietic toxicity of this new therapy requires further evaluation, image-guided radiovirotherapy is a promising new approach to the treatment of multiple myeloma, an incurable but highly radiosensitive plasma cell malignancy. Testing in other radiosensitive cancers is warranted.


Effectiveness of herpes zoster vaccination in an older United Kingdom population.
Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK.


Uncooled 2.5 Gb/s operation of 1.3 mum GaInNAs DQW lasers over a wide temperature range.
Ridge waveguide 1.3 mum GaInNAs lasers were fabricated from high quality double quantum well material grown by molecular beam epitaxy. Short cavity (250 mum) lasers have low threshold currents and small temperature dependencies of threshold current and slope efficiency, with a characteristic temperature of the threshold current as high as 200 K. The temperature stability allows for uncooled 2.5 Gb/s operation up to temperatures as high as 110 degrees C with a constant modulation voltage and only the bias current adjusted for constant average output power. Under these conditions, an extinction ratio larger than 6 dB and a spectral rms-width smaller than 2 nm are obtained.


Bromodeoxyuridine induces keratin protein synthesis at a posttranscriptional level in human lung tumour cell lines.
Keratin intermediate filaments are formed in epithelial cells in a cell- and tissue-specific manner, but much remains unknown regarding the mechanisms which control the synthesis of these proteins. We examined the effect of the differentiation modulation agent, bromodeoxyuridine (BrdU), on two human keratin-negative (by immunocytochemistry) lung cell lines, DLKP and H82, and showed immunohistochemically that treatment with 10 microM BrdU over 7 days induced K8 and K18 protein synthesis in both lines. Immunoprecipitation and Western blot analyses revealed low levels of K8 and K18 proteins in untreated cell homogenates. These levels increased following treatment with BrdU for 7 days. K8 and K18 mRNAs were detected by Northern blot and reverse transcriptase polymerase chain reaction analyses in both lines before BrdU treatment, but no increase in mRNA levels was observed in either cell line over 21 days of treatment. This suggests, firstly, that keratin synthesis is normally blocked at a posttranscriptional level in DLKP and H82 cells, and secondly, that BrdU can reverse this block. A549 is a human lung cell line which contains K8 and K18 proteins. Treatment with BrdU increased K8 and K18 protein levels in these cells. No corresponding increase in K8 mRNA levels occurred, while an apparent increase in K18 mRNA levels was detected. HL-60 is a leukaemic cell-line of haematopoietic rather than epithelial lineage which contains K8 and K18 mRNA transcripts prior to BrdU treatment, but does not contain keratin proteins. Again, K8 and K18 mRNA levels remained unchanged during BrdU treatment. However, neither K8 nor K18 proteins were detected following treatment, although BrdU is known to alter expression of other genes in HL-60 cells. BrdU thus appears to act at a posttranscriptional level and in an epithelial-specific manner to reverse a block in keratin synthesis in keratin-negative lung cancer cells and increase synthesis in keratin-positive lung cancer cells. This may represent a regulatory step in early lung development or a mechanism whereby tumour cells downregulate expression of a differentiated phenotype.


A transcription factor from simian virus 40 chromosomes which activates the viral late promoter in vitro.
We have characterized a transcription factor, obtained from simian virus 40 (SV40) chromosomes, which activates transcription from the SV40 late promoter in vitro. The late promoter-activating factor was distinct from SV40 T antigen as judged by its behavior on chromatography on hydroxylapatite; it was not recognized by anti-T antibodies, while T antigen itself was recognized. T antigen from SV40 chromosomes, on the other hand, abolished transcription in vitro from the early promoter. In DNase I footprinting experiments, a partially purified late promoter-activating factor preparation protected a region of DNA centered on SV40 nucleotide 270, which is between the repeated 72-base-pair enhancer and the major late RNA start site. Proteins from HeLa cells did not give the same footprint at this position. Gel mobility shift assays showed that proteins from SV40-infected CV-1 cells form a complex with DNA containing this binding site. The complex has a different rate of gel migration and a higher stability than complexes formed with proteins from uninfected cells.


Mesoporous TiO2 Mesocrystals: Remarkable Defects-Induced Crystallite-Interface Reactivity and Their in Situ Conversion to Single Crystals.
Oriented self-assembly between inorganic nanocrystals and surfactants is emerging as a route for obtaining new mesocrystalline semiconductors. However, the actual synthesis of mesoporous semiconductor mesocrystals with abundant surface sites is extremely difficult, and the corresponding new physical and chemical properties arising from such an intrinsic porous mesocrystalline nature, which is of fundamental importance for designing high-efficiency nanostructured devices, have been rarely explored and poorly understood. Herein, we report a simple evaporation-driven oriented assembly method to grow unprecedented olive-shaped mesoporous TiO2 mesocrystals (FDU-19) self-organized by ultrathin flake-like anatase nanocrystals (∼8 nm in thickness). The mesoporous mesocrystals FDU-19 exhibit an ultrahigh surface area (∼189 m(2)/g), large internal pore volume (0.56 cm(3)/g), and abundant defects (oxygen vacancies or unsaturated Ti(3+) sites), inducing remarkable crystallite-interface reactivity. It is found that the mesocrystals FDU-19 can be easily fused in situ into mesoporous anatase single crystals (SC-FDU-19) by annealing in air. More significantly, by annealing in a vacuum (∼4.0 × 10(-5) Pa), the mesocrystals experience an abrupt three-dimensional to two-dimensional structural transformation to form ultrathin anatase single-crystal nanosheets (NS-FDU-19, ∼8 nm in thickness) dominated by nearly 90% exposed reactive (001) facets. The balance between attraction and electrostatic repulsion is proposed to determine the resulting geometry and dimensionality. Dye-sensitized solar cells based on FDU-19 and SC-FDU-19 samples show ultrahigh photoconversion efficiencies of up to 11.6% and 11.3%, respectively, which are largely attributed to their intrinsic single-crystal nature as well as high porosity. This work gives new understanding of physical and chemical properties of mesoporous semiconductor mesocrystals and opens up a new pathway for designing various single-crystal semiconductors with desired mesostructures for applications in catalysis, sensors, drug delivery, optical devices, etc.


A review of magnetic resonance imaging compatible manipulators in surgery.
Developments in magnetic resonance imaging (MRI), coupled with parallel progress in the field of computer-assisted surgery, mean that an ideal environment has been created for the development of MRI-compatible robotic systems and manipulators, capable of enhancing many types of surgical procedure. However, MRI does impose severe restrictions on mechatronic devices to be used in or around the scanners. In this article a review of the developments in the field of MRI-compatible surgical manipulators over the last decade is presented. The manipulators developed make use of different methods of actuation, but they can be reduced to four main groups: actuation transmitted through hydraulics, pneumatic actuators, ultrasonic motors based on the piezoceramic principle and remote manual actuation. Progress has been made concerning material selection, position sensing, and different actuation techniques, and design strategies have been implemented to overcome the multiple restrictions imposed by the MRI environment. Most systems lack the clinical validation needed to continue on to commercial products.


Variations of quantitative perfusion measurement on dynamic contrast enhanced CT for colorectal cancer: implication of standardized image protocol.
Tumor angiogenesis is considered an important prognostic factor. With an increasing emphasis on imaging evaluation of the tumor microenvironment, dynamic contrast enhanced-computed tomography (DCE-CT) has evolved as an important functional technique in this setting. Yet many questions remain as to how and when these functional measurements should be performed for each agent and tumor type, and what quantitative models should be used in the fitting process. In this study, we evaluated the variations of perfusion measurement on DCE-CT for rectal cancer patients from (1) different tracer kinetic models, (2) different scan acquisition lengths, and (3) different scan intervals. A total of seven commonly used models were studied: the adiabatic approximation to the tissue homogeneity (AATH) model, adiabatic approximation to the homogeneity tissue with fixed transit time (AATHFT) model, the Tofts model (TM), the extended Tofts model (ETM), Patlak model, Logan model, and the model-free deconvolution method. Akaike's information criterion was used to identify the best fitting model. The interchangeability of different models was further evaluated using Bland-Altman analysis. All models gave comparable blood volume (BV) measurements except the Patlak method. While for the volume transfer constant (Ktrans) estimation, AATHFT, AATH, and ETM generated reasonable agreement among each other but not for the other models. Regarding the blood flow (BF) measurement, no two models were interchangeable. In addition, the perfusion parameters were compared with four acquisition times (45, 65, 85, and 105 s) and four temporal intervals (1, 2, 3, and 4 s). No significant difference was observed in the volume transfer constant (Ktrans), BV, and BF measurements when comparing data acquired over 65 s with data acquired over 105 s using any of the DCE models in this study. Yet increasing the temporal interval led to a significant overestimation of BF in the deconvolution method. In conclusion, the perfusion measurement is indeed model dependent and the image acquisition/processing technique is dependent. The radiation dose of DCE-CT was an average of 1.5-2 times an abdomen/pelvic CT, which is not insubstantial. To take the DCE-CT forward as a biomarker in oncology, prospective studies should be carefully designed with the optimal image acquisition and analysis technique.


Warm-up effects from concomitant use of vibration and static stretching after cycling.
Static stretch is routinely used in traditional warm-up but impaired muscle performance. Combining vibration with static stretching as a feasible component may be an alternative to static stretching after submaximal aerobic exercise to improve jumping as well as flexibility. Therefore, the purpose of this study was to investigate and compare the effects of aerobic exercise, static stretching, and vibration with static stretching on flexibility and vertical jumping performance. A repeated measures experimental design was used in this study. Twelve participants randomly underwent 5 different warm-ups including cycling alone (C warm-up), static stretching alone (S warm-up), combining vibration with static stretching (VS warm-up), cycling followed by S (C+S warm-up), and cycling followed by VS (C+VS warm-up) on 5 separate days. Sit-and-reach, squat jump (SJ), and counter movement jump (CMJ) were measured for pre- and post- tests. The sit-and-reach scores after the S, VS, C+S and C+VS warm-ups were significantly enhanced (P<0.001), and were significantly greater than that of the C warm-up (P<0.05). The jumping height of SJ and CMJ after the C and C+VS warm-ups were significantly increased (P<0.05), whereas a significant reduction was found after the S warm-up (P<0.05). Vibration combined with stretching after submaximal cycling exercise (C+VS warm-up) could be a feasible warm-up protocol to improve both flexibility and vertical jump performance, compared with the traditional warm-up (C+S warm-up).


Design and simulation of resonant cavity enhanced corrugated quantum well infrared photodetectors.
The dipole selection rule limits the maximum achievable efficiency in corrugated quantum well infrared photodetectors (C-QWIPs) to 50%. We consider what is believed to be a novel design that utilizes a resonant cavity enhancement technique to increase the efficiency beyond 50% by rotating the photon polarization at each pass around the cavity. Simulation results show that the quantum efficiency of this device can be enhanced up to 38% compared to that of the standard C-QWIP device.


A systematic review of continuous positive airway pressure for obstructive sleep apnoea-hypopnoea syndrome.
We conducted a systematic review of current evidence on the effectiveness of continuous positive airway pressure (CPAP) for treatment of obstructive sleep apnoea-hypopnoea syndrome (OSAHS). The primary outcomes were subjective sleepiness, using Epworth Sleepiness Scale (ESS) and objective sleepiness using Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT). Mean difference (MD) in endpoints was used to compare CPAP to usual care, placebo and dental devices. The analysis was stratified by symptom and disease severity at baseline. CPAP significantly reduced ESS score compared to control (MD -2.7, 95% CI -3.45, -1.96). The benefit was greatest in patients whose symptoms were severe at baseline: severely symptomatic population (MD -5.0, -6.5, -3.5); moderate (MD -2.3, -3.0, -1.6); mild (MD -1.1, -1.8, -0.3). CPAP significantly improved MWT score compared to control (MD 3.3, 1.3, 5.3) but not on the MSLT. There was no statistically significant difference between CPAP and dental devices on the ESS, MWT or MSLT, in a population with moderate symptoms. There was some evidence of benefit for blood pressure with CPAP compared to control. CPAP is an effective treatment for OSAHS in moderate to severe symptomatic patients and there may be benefits for mild symptoms. Dental devices may be a treatment option for moderate symptoms.


Proportional assist ventilation decreases thoracoabdominal asynchrony and chest wall distortion in preterm infants.
Thoracoabdominal asynchrony (TAA) and chest wall distortion (CWD) are commonly seen in preterm infants secondary to a highly compliant rib cage and poor compensation of distorting forces by inspiratory rib cage muscles. Continuous positive airway pressure (CPAP) reduces TAA and CWD by stenting the chest wall. We hypothesized that application of positive airway pressure only during inspiration and in proportion to an infant's inspiratory effort should have a similar but more pronounced effect than CPAP alone. A ventilator providing airway pressure changes in proportion to flow and volume generated by an infant (proportional assist ventilation) was used to unload the respiratory pump during inspiration. Ten preterm infants were studied [birth weight, 745 (635-1175) g; gestational age, 26.5 (24-31) wk; postnatal age 3 (1-7) d; medium (range)]. TAA and CWD were determined by respiratory inductive plethysmography. TAA was expressed as the phase angle between the rib cage and abdominal motion and CWD as the total compartmental displacement ratio. In addition, we measured tidal volume with a pneumotachograph and esophageal and airway pressure deflections with pressure transducers. Measurements were obtained during alternating periods of CPAP and two different degrees of support (Gain 1 = 1.09 +/- 0.68, Gain 2 = 1.84 +/- 0.84 cm H(2)O/mL) that were provided by a proportional assist ventilator. Phase angle and the total compartmental displacement ratio decreased with increasing gain compared with CPAP alone. Peak airway pressure increased from 0.6 to 3.8 to 7.6 cm H(2)O above positive end-expiratory pressure (PEEP) with CPAP, Gain 1, and Gain 2, respectively, as tidal volume increased from 2.8 to 4.1 to 4.7 mL/kg. Esophageal pressure changes decreased only little with increasing gain. Chest wall excursion increased and abdominal movement decreased, indicating a redistribution of tidal volume between chest and abdomen. We conclude that proportional assist ventilation reduces TAA and CWD by generating a small increase in airway pressure that occurs in synchrony and in proportion to each inspiratory effort.


The prevalence of food allergy and other allergic diseases in early childhood in a population-based study: HealthNuts age 4-year follow-up.
The HealthNuts study previously reported interim prevalence data showing the highest prevalence of challenge-confirmed food allergy in infants internationally. However, population-derived prevalence data on challenge-confirmed food allergy and other allergic diseases in preschool-aged children remain sparse. This study aimed to report the updated prevalence of food allergy at age 1 year from the whole cohort, and to report the prevalence of food allergy, asthma, eczema, and allergic rhinitis at age 4 years. HealthNuts is a population-based cohort study with baseline recruitment of 5276 one-year-old children who underwent skin prick test (SPT) to 4 food allergens and those with detectable SPT results had formal food challenges. At age 4 years, parents completed a questionnaire (81.3% completed) and those who previously attended the HealthNuts clinic at age 1 year or reported symptoms of a new food allergy were invited for an assessment that included SPT and oral food challenges. Data on asthma, eczema, and allergic rhinitis were captured by validated International Study of Asthma and Allergies in Childhood questionnaires. The prevalence of challenge-confirmed food allergy at age 1 and 4 years was 11.0% and 3.8%, respectively. At age 4 years, peanut allergy prevalence was 1.9% (95% CI, 1.6% to 2.3%), egg allergy was 1.2% (95% CI, 0.9% to 1.6%), and sesame allergy was 0.4% (95% CI, 0.3% to 0.6%). Late-onset peanut allergy at age 4 years was rare (0.2%). The prevalence of current asthma was 10.8% (95% CI, 9.7% to 12.1%), current eczema was 16.0% (95% CI, 14.7% to 17.4%), and current allergic rhinitis was 8.3% (95% CI, 7.2% to 9.4%). Forty percent to 50% of this population-based cohort experienced symptoms of an allergic disease in the first 4 years of their life. Although the prevalence of food allergy decreased between age 1 year and age 4 years in this population-based cohort, the prevalence of any allergic disease among 4-year-old children in Melbourne, Australia, is remarkably high.


Do differences in age between sexual partners affect sexual risk behaviour among Australian gay and bisexual men?
To describe the relationships between HIV-negative Australian gay men's sexual behaviour and differences in age between them and their sex partners. Anonymous computer-assisted internet survey was administered. We used multinomial logistic regression to examine factors associated with reported differences in partners' age (10 years older, within 10 years and 10 years younger) among 1476 men. Two-thirds of the men reported their most recent casual sex partners were within 10 years of age to themselves, as were 79.3% of their regular partners. Neither men's own age nor relative differences in age with their partners was associated with the likelihood to engage in unprotected anal intercourse. Among men who reported sex with a regular partner, those with older partners tended to restrict themselves to the receptive position (adjusted ORs (AOR)=2.00; 95% CI 1.02 to 3.92; p=0.044). Among men who reported sex with a casual partner, those with younger partners tended to take the insertive position, both on occasions when a condom was used (AOR=2.42; 95% CI 1.39 to 4.20; p=0.002) and on occasions when a condom was not used (AOR=2.54; 95% CI 1.04 to 6.20; p=0.041). Age differences between gay men and their sex partners make little difference to the likelihood of engaging in sexual risk behaviour overall with either regular or casual partners. Those whose partners are substantially older than themselves are more likely, however, to take the receptive position during anal intercourse. Where risk of HIV infection among younger men is elevated this could be due to differences in sexual position, rather than differences in unprotected anal intercourse per se, during sex with men who are substantially older than themselves.


Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress.
Stress precipitates mood disorders, characterized by a range of symptoms present in different combinations, suggesting the existence of disease subtypes. Using an animal model, we previously described that repetitive stress via restraint or immobilization induced depressive-like behaviors in rats that were differentially reverted by a serotonin- or noradrenaline-based antidepressant drug, indicating that different neurobiological mechanisms may be involved. The forebrain astrocyte protein aldolase C, contained in small extracellular vesicles, was identified as a potential biomarker in the cerebrospinal fluid; however, its specific origin remains unknown. Here, we propose to investigate whether serum small extracellular vesicles contain a stress-specific protein cargo and whether serum aldolase C has a brain origin. We isolated and characterized serum small extracellular vesicles from rats exposed to restraint, immobilization, or no stress, and their proteomes were identified by mass spectrometry. Data available via ProteomeXchange with identifier PXD009085 were validated, in part, by western blot. In utero electroporation was performed to study the direct transfer of recombinant aldolase C-GFP from brain cells to blood small extracellular vesicles. A differential proteome was identified among the experimental groups, including aldolase C, astrocytic glial fibrillary acidic protein, synaptophysin, and reelin. Additionally, we observed that, when expressed in the brain, aldolase C tagged with green fluorescent protein could be recovered in serum small extracellular vesicles. The protein cargo of serum small extracellular vesicles constitutes a valuable source of biomarkers of stress-induced diseases, including those characterized by depressive-like behaviors. Brain-to-periphery signaling mediated by a differential molecular cargo of small extracellular vesicles is a novel and challenging mechanism by which the brain might communicate health and disease states to the rest of the body.


The effects of environmental factors in waiting rooms on anxiety among patients undergoing coronary angiography: A randomized controlled trial.
According to Florence Nightingale's hypothesis, the environment can play a central role in the healing of the patient's body and mind. The nurse should, therefore, strive to provide a healing and stress-reducing environment for patients about to undergo invasive procedures. This study aimed to investigate the effects of environmental factors on anxiety as experienced by patients in waiting rooms prior to coronary angiography. In this randomized controlled trial, 200 patients undergoing coronary angiography in an urban area of Iran were assigned randomly to the following intervention groups: (1) nature sounds; (2) nature sounds and daylight; (3) nature sounds, daylight, and colour enhancements; and (4) control. Portable monitors were used to measure the patients' physiological indices upon admission and 30 and 60 minutes thereafter. Patients who experienced environmental affecting interventions had significantly lower physiological indices of anxiety than the control group (P < 0.001). Some significance was demonstrated between the three interventions groups, with patients in the intervention group that experienced maximum environmental interventions demonstrating the most overall reduction in anxiety indices. Environmental factors were shown to have a positive effect on the indices of anxiety experienced by patients waiting for the procedure of coronary angiography; this is therefore an area of study and practice worthy of further development.


Synergistic effect of social support and self-efficacy on physical exercise in older adults.
The purpose of the current study was to examine whether the effects of social support on physical exercise in older adults depend on individual perceptions of self-efficacy. Three hundred nine older German adults (age 65-85) were assessed at 3 points in time (3 months apart). In hierarchical-regression analyses, support received from friends and exercise self-efficacy were specified as predictors of exercise frequency while baseline exercise, sex, age, and physical functioning were controlled for. Besides main effects of self-efficacy and social support, an interaction between social support and self-efficacy emerged. People with low self-efficacy were less likely to be active in spite of having social support. People with low support were less likely to be active even if they were high in self-efficacy. This points to the importance of both social support and self-efficacy and implies that these resources could be targets of interventions to increase older adults' exercise.


Fish farming affects the abundance and diversity of the mercury resistance gene merA in marine sediments.
Microbes in sediments below fish farming cages are exposed to a variety of compounds used in aquaculture, such as antifoulants, antimicrobials and mercury. Here, we assessed the abundance of the mercury resistance gene merA in the sediment of four fish farms and four pristine sites using quantitative PCR, and at three fish farms and two pristine sites by constructing clone libraries and sequencing merA amplicons. The abundance of merA was consistently greater at fish farm sites than at pristine sites, and the merA phylotypes were different between fish farm and pristine sites. Mercury concentrations were too low to cause selection pressure and did not differ significantly among samples. The primers designed specifically for this study were capable of detecting two new potential merA clades.


HSV infection induces production of ROS, which potentiate signaling from pattern recognition receptors: role for S-glutathionylation of TRAF3 and 6.
The innate immune response constitutes the first line of defense against infections. Pattern recognition receptors recognize pathogen structures and trigger intracellular signaling pathways leading to cytokine and chemokine expression. Reactive oxygen species (ROS) are emerging as an important regulator of some of these pathways. ROS directly interact with signaling components or induce other post-translational modifications such as S-glutathionylation, thereby altering target function. Applying live microscopy, we have demonstrated that herpes simplex virus (HSV) infection induces early production of ROS that are required for the activation of NF-κB and IRF-3 pathways and the production of type I IFNs and ISGs. All the known receptors involved in the recognition of HSV were shown to be dependent on the cellular redox levels for successful signaling. In addition, we provide biochemical evidence suggesting S-glutathionylation of TRAF family proteins to be important. In particular, by performing mutational studies we show that S-glutathionylation of a conserved cysteine residue of TRAF3 and TRAF6 is important for ROS-dependent activation of innate immune pathways. In conclusion, these findings demonstrate that ROS are essential for effective activation of signaling pathways leading to a successful innate immune response against HSV infection.


Automated live cell imaging systems reveal dynamic cell behavior.
Automated time-lapsed microscopy provides unique research opportunities to visualize cells and subcellular components in experiments with time-dependent parameters. As accessibility to these systems is increasing, we review here their use in cell science with a focus on stem cell research. Although the use of time-lapsed imaging to answer biological questions dates back nearly 150 years, only recently have the use of an environmentally controlled chamber and robotic stage controllers allowed for high-throughput continuous imaging over long periods at the cell and subcellular levels. Numerous automated imaging systems are now available from both companies that specialize in live cell imaging and from major microscope manufacturers. We discuss the key components of robots used for time-lapsed live microscopic imaging, and the unique data that can be obtained from image analysis. We show how automated features enhance experimentation by providing examples of uniquely quantified proliferation and migration live cell imaging data. In addition to providing an efficient system that drastically reduces man-hours and consumes fewer laboratory resources, this technology greatly enhances cell science by providing a unique dataset of temporal changes in cell activity.


Treatment of Geographic Atrophy with Intravitreal Sirolimus: The Age-Related Eye Disease Study 2 Ancillary Study.
To evaluate efficacy and safety of monthly intravitreal injections of sirolimus, an immunosuppressive drug, for the treatment of age-related macular degeneration associated geographic atrophy (GA). Randomized, controlled, single-masked multi-center phase 2 clinical trial of intravitreal sirolimus vs. sham therapy in AREDS2 clinical centers. Participants with GA. Participants eligible in one eye were randomly assigned to a monthly intravitreal injection of sirolimus (20 µL [440 µg]) or sham treatment while participants with two study eyes were assigned to a monthly intravitreal injection in a randomly-selected eye. Best-corrected visual acuities (BVCA), spectral domain optical coherence tomography (OCT), fundus color photography and fundus autofluorescence (FAF) images were obtained at baseline and every 6 months until visit month 24. Rate of progression of GA (mm2/year) measured on color fundus photograph from baseline to 24 months. Secondary outcome measures include change in BVCA, worsening of vision by ≥3 lines, and changes in area of GA measured on FAF and OCT. 52 participants (mean age 79 years) were enrolled with 27 study eyes assigned to sirolimus from May 2012 to March 2014. The baseline median area of GA was 4.73 DA (12.01 mm2). The mean (standard deviation) growth rates of GA detected on color fundus photographs were 2.27 (2.17) mm2 and 1.91 (2.27) mm2 at month 12, and 4.94 (2.96) mm2 and 5.72 (3.97) mm2 at month 24, for the sirolimus and sham groups, respectively. There was no statistically significant difference in the GA growth rates between the two treatment groups (P=0.33). Median visual acuity changes and incidence of 15-letter loss from baseline were not different between the 2 treatment groups (p=0.19). The intervention was stopped early because of sterile endophthalmitis that occurred in 3 participants in the sirolimus group. Participants were followed for safety until the study was closed in May 2015 due to lack of efficacy. Sirolimus did not result in different rates of GA growth in this phase 2 study. Immunosuppression may be important for some stages of the AMD process but may not necessarily be the main pathway for the development of GA.


Lactobacillus rhamnosus GG increases cyclooxygenase-2 expression and prostaglandin E2 secretion in colonic myofibroblasts via a MyD88-dependent mechanism during homeostasis.
Prostaglandin E2 (PGE2 ) plays a critical role in intestinal mucosal tolerance and barrier integrity. Cyclooxygenase-2 (COX-2)-dependent PGE2 production involves mobilisation of arachidonic acid. Lactobacillus rhamnosus GG (LbGG) is one of the most widely used probiotics reported to colonise the colonic mucosa. LbGG contributes to the protection of the small intestine against radiation injury through the repositioning of mucosal COX-2 expressing cells. However, it is unknown if LbGG modulates PGE2 production in the colonic mucosa under homeostasis and the major cellular elements involved in these processes. Colonic epithelial and CD90+ mesenchymal stromal cells, also known as (myo) fibroblasts (CMFs), are abundant innate immune cells in normal colonic mucosa able to produce PGE2 . Herein, we tested the hypothesis that under colonic mucosal homeostasis, LbGG modulates the eicosanoid pathway resulting in increased PGE2 production in both epithelial and stromal cells. Among the five tested human colonic epithelial cell lines, only exposure of Caco-2 to LbGG for 24 hr led to the mobilisation of arachidonic acid with concomitant increase in the components within the leukotriene and COX-2-dependent PGE2 pathways. By contrast, CMFs isolated from the normal human colonic mucosa responded to LbGG with increased expression of COX-2 and PGE2 in the prostaglandin pathway, but not 5-LO in the leukotriene pathway. Oral gavage of C57BL/6 mice for 5 days with LbGG (5 × 108 Colony-Forming Unit (CFU)/dose) increased COX-2 expression in the colonic mucosa. The majority of cells upregulating COX-2 protein expression were located in the colonic lamina propria and colocalised with α-SMA+ cells corresponding to the CMF phenotype. This process was myeloid differentiation factor-88-dependent, because silencing of myeloid differentiation factor-88 expression in CMFs abrogated LbGG-induced upregulation of COX-2 in culture and in vivo. Taken together, our data suggest that LbGG increases release of COX-2-mediated PGE2 , contributing to the maintenance of mucosal homeostasis in the colon and CMFs are among the major contributors to this process.