TU-G-BRB-01: Continuous Path Optimization for Non-Coplanar Variant SAD IMRT Delivery Using C-Arm Machines.
To develop and investigate a continuous path optimization methodology to traverse prescribed non-coplanar IMRT beams with variant SADs, by orchestrating the couch and gantry movement with zero-collision, minimal patient motion consequence and machine travel time. We convert the given collision zone definition and the prescribed beam location/angles to a tumor-centric coordinate, and represent the traversing path as a continuous open curve. We proceed to optimize a composite objective function consisting of (1) a strong attraction energy to ensure all prescribed beams are en-route, (2) a penalty for patient-motion inducing couch motion, and (3) a penalty for travel-time inducing overall path-length. Feasibility manifold is defined as complement to collision zone and the optimization is performed with a level set representation evolved with variational flows. The proposed method has been implemented and tested on clinically derived data. In the absence of any existing solutions for the same problem, we validate by: (1) visual inspecting the generated path rendered in the 3D tumor-centric coordinates, and (2) comparing with a traveling-salesman (TSP) solution obtained from relaxing the variant SADs and continuous collision-avoidance requirement. The proposed method has generated delivery paths that are smooth and intuitively appealing. Under relaxed settings, our results outperform the generic TSP solutions and agree with specially tuned versions. We have proposed a novel systematic approach that automatically determines the continuous path to cover non-coplanar, varying SAD IMRT beams. The proposed approach accommodates patient-specific collision zone definition and ensures its avoidance continuously. The differential penalty to couch and gantry motions allows customizable tradeoff between patient geometry stability and delivery efficiency. This development paves the path to achieve safe, accurate and efficient non-coplanar IMRT delivery with the advanced robotic controls in new-generation C-arm systems, enabling practical harvesting of the dose benefit offered by non-coplanar, variant SAD IMRT treatment.


Correlation coefficient mapping in fluorescence spectroscopy: tissue classification for cancer detection.
Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer detection.


The role of common viral ocular pathogens in Thygeson's superficial punctate keratitis.
The aetiology of Thygeson's superficial punctate keratitis (TSPK) remains elusive. A viral aetiology has been suggested by the absence of bacterial infection and clinical resemblance to other viral keratopathies. We report the results of polymerase chain reaction analysis for the detection of herpes simplex virus (HSV) 1 and 2, herpes zoster virus, varicella zoster virus (VZV) and adenovirus from corneal epithelial samples from patients with active signs and symptoms of TSPK. Schirmer strip impressions were taken from the epithelium of eight patients with a known history of TSPK and symptoms and signs of active disease. Three patients were recruited as positive controls (two with herpes simplex keratitis and one with herpes zoster ophthalmicus). Samples from a further three patients acted as negative controls. All 14 samples underwent polymerase chain reaction testing for HSV 1, HSV 2, VZV and adenovirus. DNA corresponding to the expected viral DNA was amplified from all three positive control samples. The three negative control samples showed no evidence of viral DNA. Similarly, all samples from patients with TSPK showed no evidence of the presence of HSV 1, HSV 2, VZV or adenovirus. We conclude that HSV, VZV and adenovirus are not present in the epithelium of patients with TSPK. These results are considered in light of existing theories regarding the aetiology and treatment of this condition.


How Ambient Environment Influences Olfactory Orientation in Search and Rescue Dogs.
Under natural conditions, an animal orienting to an air-borne odor plume must contend with the shifting influence of meteorological variables, such as air temperature, humidity, and wind speed, on the location and the detectability of the plume. Despite their importance, the natural statistics of such variables are difficult to reproduce in the laboratory and hence few studies have investigated strategies of olfactory orientation by mobile animals under different meteorological conditions. Using trained search and rescue dogs, we quantified the olfactory orientation behaviors of dogs searching for a trail (aged 1-3 h) of a hidden human subject in a natural landscape, under a range of meteorological conditions. Dogs were highly successful in locating the human target hidden 800 m from the start location (93% success). Humidity and air temperature had a significant effect on search strategy: as air conditions became cooler and more humid, dogs searched significantly closer to the experimental trail. Dogs also modified their speed and head position according to their search location distance from the experimental trail. When close to the trail, dogs searched with their head up and ran quickly but when their search took them farther from the trail, they were more likely to search with their nose to the ground, moving more slowly. This study of a mammalian species responding to localized shifts in ambient conditions lays the foundation for future studies of olfactory orientation, and the development of a highly tractable mammalian species for such research.


Evidence Associated with the Use of Oxazolidinones for the Treatment of Skin and Skin Structure Infections: A Retrospective Study.
Skin and skin structure infections are an increasing cause of hospitalization. Although mortality is relatively low, skin and skin structure infections are associated with prolonged hospital length of stay and high costs. Oxazolidinones have been suggested as a tool to treat infected patients in the ambulatory setting in order to decrease hospital length of stay. We wanted to address the evidence associated with the use of oxazolidinones in the treatment of skin and skin structure infections. In this observational retrospective study we analyzed the anonymized diagnosis related group coded information from the Portuguese database for hospital admissions, that included all adult patients with a diagnosis of oxazolidinone use and a SSSI, discharged between 2010 and 2015. During the study period, a total of 5518 patients had a diagnosis of oxazolidinone treatment. We selected 483 of those who were also diagnosed with a skin and skin structure infections. Their mean age was 64.9 years and 62.7% were male. The median hospital length of stay was 27 days (Inter quartile range 13 - 56) and the mortality rate was 12.6%. The prevalence of secondary anemia and of thrombocytopenia in the whole group treated with oxazolidinones was 2.5% and 3%, respectively. Despite the high bioavailability of oxazolidinones, we were not able to find evidence that its use was associated with a decrease of mortality or hospital length of stay (due to early discharge) of patients with skin and skin structure infections. In this study we were not able to find evidence that oxazolidinones had any clinically significant benefit. A structured approach, including antibiotics with favorable pharmacokinetic and safety profile as well as a carefully planned ambulatory follow up may be needed.


[Acute pulmonary edema as a first manifestation of hyperthyroidism in a pregnant woman. Report of one case].
We report a 36 year-old pregnant woman who presented with acute pulmonary edema in the absence of preexisting cardiac disease. On admission she was on sinus rhythm and her blood pressure was mildly elevated. No cardiac abnormalities were detected by color Doppler echocardiography and no ischemic changes were seen on the electrocardiogram. Cardiac enzymes were normal. Thyroid function tests were diagnostic for hyperthyroidism. She was treated with propylthiouracil and propranolol and discharged in good conditions seven days after admission. This case emphasizes the need to consider hyperthyroidism as the cause of unexplained pulmonary edema in young patients with no history of heart disease who present with heart failure.


Management of type 2 diabetes: new and future developments in treatment.
The increasing prevalence, variable pathogenesis, progressive natural history, and complications of type 2 diabetes emphasise the urgent need for new treatment strategies. Longacting (eg, once weekly) agonists of the glucagon-like-peptide-1 receptor are advanced in development, and they improve prandial insulin secretion, reduce excess glucagon production, and promote satiety. Trials of inhibitors of dipeptidyl peptidase 4, which enhance the effect of endogenous incretin hormones, are also nearing completion. Novel approaches to glycaemic regulation include use of inhibitors of the sodium-glucose cotransporter 2, which increase renal glucose elimination, and inhibitors of 11β-hydroxysteroid dehydrogenase 1, which reduce the glucocorticoid effects in liver and fat. Insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, and metabolic inhibitors of hepatic glucose output are being assessed. Early proof of principle has been shown for compounds that enhance and partly mimic insulin action and replicate some effects of bariatric surgery.


Subdiffractive light in bi-periodic arrays of modulated fibers.
We study theoretically the linear and nonlinear propagation of light in one-dimensional bi-periodic arrays of fibers, with the propagation constant periodically modulated along the propagation direction. We predict analytically and observe numerically subdiffractive propagation along such fiber arrays, and characterize the light propagation properties. We also predict novel subdiffractive discrete solitons in the presence of Kerr nonlinearity, both of focusing and defocusing cases, which are essentially different from the usual discrete solitons in waveguide arrays.


Brachyspira pilosicoli colonization in experimentally infected mice can be facilitated by dietary manipulation.
The purpose of this study was to determine whether defined dietary manipulations would enhance colonization of mice experimentally challenged with the intestinal spirochaete Brachyspira pilosicoli. Weanling C3H/HeJ mice (n = 48) were fed either a standard balanced mouse diet or a diet supplemented with 50 p.p.m. zinc bacitracin (ZnB), with 50 % (w/w) lactose or with both supplements. Eight mice from each group were challenged orally with a human strain of B. pilosicoli (WesB), whilst four in each group acted as uninfected controls to evaluate the effects of the diets alone. The mice were kept for 40 days following challenge and faeces were collected every 3-4 days and subjected to culture and PCR for B. pilosicoli. Feeding ZnB reduced total volatile fatty acid production in the caecum. Feeding lactose alone doubled the weight of the caecum and its contents compared with control mice, and resulted in a relatively greater production of acetate, but a reduction in propionate and isovalerate production. These effects were negated by the addition of ZnB with the lactose. None of the mice fed the standard diet or receiving ZnB alone became colonized following experimental challenge. One of the mice receiving lactose was culture and PCR positive for B. pilosicoli on one sampling 1 week after inoculation, and one was positive on three samplings taken 20, 25 and 29 days after inoculation. All mice receiving both lactose and ZnB became colonized and remained so, with all samples being positive over the last seven samplings. The colonization was not associated with an end-on attachment of the spirochaete to the epithelial cells of the caecum, but colonized mice developed a specific humoral antibody response to the spirochaete.


The highly conserved skb1 gene encodes a protein that interacts with Shk1, a fission yeast Ste20/PAK homolog.
The Shk1 protein kinase, a homolog of Saccharomyces cerevisiae Ste20 and mammalian p21Cdc42/Rac-activated kinases, is an essential component of a Ras- and Cdc42-dependent signaling cascade required for cell viability, normal morphology, and mitogen-activated protein kinase-mediated sexual responses in the fission yeast, Schizosaccharomyces pombe. To identify S. pombe proteins that modulate or mediate Shk1 functions, we conducted a two-hybrid screen for Shk1-interacting proteins. One of the genes identified as a result of this screen was skb1. We show that Skb1 interacts with a region of the N-terminal regulatory domain of Shk1 distinct from that to which Cdc42 binds, and that Shk1, Cdc42, and Skb1 are able to form a ternary complex in vivo. S.pombe cells carrying an skb1 null mutation are less elongate in morphology than wild-type cells and exhibit a moderate growth defect. The morphology defect of the skb1 deletion mutant is suppressed by overexpression of Shk1. Overexpression of Skb1 causes wild-type S. pombe cells to become hyperelongated. Additional genetic analyses described herein suggest that Skb1 is a component of the morphology control branch of the Ras signaling cascade in S. pombe and that it positively modulates Shk1 function. Homologs of Skb1 are encoded by open reading frames in the genomes of S. cerevisiae and Caenorhabditis elegans and by an uncharacterized human cDNA sequence. Thus, skb1 may be the first well-characterized member of a highly conserved family of genes encoding potential p21Cdc42/Rac-activated kinase regulators.


Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo.
Two diphosphonates containing the P-C-P bond, CH(3)C(OH)(PO(3)HNa)(2) and H(2)C(PO(3)HNa)(2), inhibit the crystallization of calcium phosphate in vitro and prevent aortic calcification of rats given large amounts of vitamin D(3). The diphosphonates therefore have effects similar to those described for compounds containing the P-O-P bond but are active when administered orally.


On-label and off-label use of high-dose influenza vaccine in the United States, 2010-2012.
High-dose inactivated, influenza vaccine was licensed by the FDA in December 2009 for adults aged 65 y and older. The ACIP did not issue or state a preference for a specific vaccine in the elderly population. The extent of its on-label and off-label use is unknown. Using the MarketScan Commercial Claims and Encounters and the Medicare Supplemental database, we identified individuals who received the high-dose influenza vaccine or the standard, seasonal trivalent influenza vaccine between January 1, 2010 and December 31, 2012. For people aged ≥65 y, we used multivariable regression to assess the association between patient and provider level variables and high-dose influenza vaccine versus standard influenza vaccine. We characterized all off-label high-dose vaccine administered to people younger than 65 y of age, and investigated whether sicker patients were targeted for off-label use by examining the association between various comorbid conditions and receipt of the high-dose vaccine among adults aged 18-64. Among patients aged ≥65 y who received an influenza vaccine, 18.4% received the high-dose vaccine. Uptake was minimal in 2010, but 25% and 32% of influenza shots were the high-dose formulation in 2011 and 2012, respectively. Almost 27,000 seniors received a second high-dose vaccine with a median of 368 d (IQR: 350-387 days) between doses. Older age, family practice physicians, and having PPO insurance were positively associated with receiving high-dose vaccine. There were 36,624 off-label high-dose vaccines administered. Half of the patients receiving off-label doses were aged 50-64. Adults aged 18-64 y receiving high-dose vaccine were more likely to have chronic comorbidities than people receiving standard influenza vaccine; however, there was not one specific illness that seemed to be targeted by physicians. In the first 3 y since licensure, use of the high-dose vaccine among seniors has been limited. The safety of this vaccine should be monitored closely among 2 groups of people - seniors receiving repeat doses and people <65.


Sustained drug release and cancer treatment by an injectable and biodegradable cyanoacrylate-based local drug delivery system.
Sustained drug release at specific sites is clinically favorable for the treatment of many diseases. The discovery of new polymeric materials suitable for prolonging drug release, improving therapeutic efficiency, and decreasing systemic toxicity is always of great interest in local sustained-release drug delivery systems (LSRDDSs). In this study, a new cross-linked cyanoacrylate (CA)-based LSRDDS is developed, in which the drug depot consists of a formulation of methoxyethyl cyanoacrylate (MOE-CA) with the cross-linking agent CA-PEG-CA. The MOE-CA endowed the CA polymer with good degradability. The drug-release profile could be affected by the structure and composition ratio of the MOE-CA/CA-PEG-CA monomer. The liquid CA monomer could dissolve the drug without using other solvents, and could polymerize into a solid glue just in a few seconds after injection. An optimal formulation loaded with 5-fluorouracil (J-Fu-1.25) showed excellent anticancer activity both in vitro and in vivo, with 50% survival of the mice and no significant systemic toxicity detected during the experiment. The CA depot might affect the blood flow in microvessels of tumors, thus contributing to the synergetic anticancer effect of 5-fluorouracil. We believe that this work provides a practical, biodegradable, and biocompatible LSRDDS for chemotherapeutic drug delivery that can also be applied universally with various drugs for certain therapeutic aims.


Identification of candidate chemosensory genes in Mythimna separata by transcriptomic analysis.
The oriental armyworm, Mythimna separata, is an economically important and common Lepidopteran pest of cereal crops. Chemoreception plays a key role in insect life, such as foraging, oviposition site selection, and mating partners. To better understand the chemosensory mechanisms in M. separata, transcriptomic analysis of antennae, labial palps, and proboscises were conducted using next-generation sequencing technology to identify members of the major chemosensory related genes. In this study, 62 putative odorant receptors (OR), 20 ionotropic receptors (IR), 16 gustatory receptors (GR), 38 odorant binding proteins (OBP), 26 chemosensory proteins (CSP), and 2 sensory neuron membrane proteins (SNMP) were identified in M. separata by bioinformatics analysis. Phylogenetic analysis of these candidate proteins was performed. Differentially expressed genes (DEGs) analysis was used to determine the expressions of all candidate chemosensory genes and then the expression profiles of the three families of receptor genes were confirmed by real-time quantitative RT-PCR (qPCR). The important genes for chemoreception have now been identified in M. separata. This study will provide valuable information for further functional studies of chemoreception mechanisms in this important agricultural pest.


Whole blood pumping with a microthrottle pump.
We have previously reported that microthrottle pumps (MTPs) display the capacity to pump solid phase suspensions such as polystyrene beads which prove challenging to most microfluidic pumps. In this paper we report employing a linear microthrottle pump (LMTP) to pump whole, undiluted, anticoagulated, human venous blood at 200 μl min(-1) with minimal erythrocyte lysis and no observed pump blockage. LMTPs are particularly well suited to particle suspension transport by virtue of their relatively unimpeded internal flow-path. Micropumping of whole blood represents a rigorous real-world test of cell suspension transport given blood's high cell content by volume and erythrocytes' relative fragility. A modification of the standard Drabkin method and its validation to spectrophotometrically quantify low levels of erythrocyte lysis by hemoglobin release is also reported. Erythrocyte lysis rates resulting from transport via LMTP are determined to be below one cell in 500 at a pumping rate of 102 μl min(-1).


A national survey of ambient air pollution health literacy among adult residents of Taiwan.
To investigate the level of and covariates associated with ambient air pollution health literacy (AAPHL) among adult residents of Taiwan. With a cross-sectional study design, we conducted telephone interviews using a Chinese version AAPHL scale, which consisted of 24 items assessing 12 subdomains of AAPHL formed by 4 information processing competence matrices (i.e., access, understand, appraise, and apply) and 3 health contexts (i.e., healthcare, disease prevention, and health promotion). The AAPHL was with the lowest and highest score at 1 to 4, respectively. Between September and November 2020, a sample of 1017 and 280 adults was successfully interviewed via home phones and mobile phones, respectively. We employed multiple linear regression models to identify covariates significantly associated with overall and 4 matric-specific AAPHL scores. The mean and standard deviation (±SD) of overall AAPHL score was considered as moderate at 2.90 (±0.56), with the highest and lowest metric-specific score for "apply" (3.07 ± 0.59) and "appraise" (2.75 ± 0.66). Lower education was significantly associated with a lower overall score; and living with children < 12 years and single were both significantly associated with higher overall scores. We also noted a significant geographic variation in overall score in which people living in the east/remote islands had highest scores. People in Taiwan had only moderate level of AAPHL; and covariates including education, living arrangement, marital status, and area of living were significantly associated with AAPHL. These covariates should be considered in future educational interventions aiming to improve the AAPHL in the community.


Paracetamol self-poisoning: Epidemiological study of trends and patient characteristics from the multicentre study of self-harm in England.
Paracetamol is frequently used for intentional self-poisoning, especially in the UK, despite pack size restrictions introduced in 1998. Knowing more about paracetamol self-poisoning may identify further approaches to prevention. We used data from the Multicentre Study of Self-harm in England for 2004-2014 to calculate incidence rates of presentations to Emergency Departments following self-poisoning with pure paracetamol alone. National estimates for England for 2011-2014 were extrapolated using indirect age-standardised rates. The characteristics of individuals taking paracetamol overdoses and the size of the overdoses were investigated. A third of 54,863 intentional overdoses presenting to the five Emergency Departments involved paracetamol without other drugs (N = 18,011), taken by 13,171 individuals (63.4% female). The proportion of paracetamol self-poisonings was similar in the three centres. Extrapolation suggested there were approximately 50,000 paracetamol overdoses in England annually during 2011-2014. Females had higher rates of paracetamol overdose than males. Males and older individuals took larger overdoses. Nearly a quarter of individuals (24.2%) consumed more than 32 tablets. Alcohol was involved in 53.7% of paracetamol overdoses. Data were collected in three centres with predominantly urban populations. Extrapolation from local to national rates should be interpreted with caution. Paracetamol overdose remains a major problem in the UK. It is more common in females and younger patients, but males and older patients consume larger overdoses. Consideration should be given to further restriction in pack sizes and sources of sales, in keeping with those of several other European countries.


Differential stimulation of myofibrillar and sarcoplasmic protein synthesis with protein ingestion at rest and after resistance exercise.
We aimed to determine whether there is a differential stimulation of the contractile myofibrillar and the cellular sarcoplasmic proteins after ingestion of protein and how this is affected by resistance exercise. Fasted (FAST) muscle protein synthesis was measured in seven healthy young men with a primed constant infusion of L-[ring-(13)C(6)]phenylalanine. Participants then performed an intense bout of unilateral resistance exercise followed by the consumption of 25 g of whey protein to maximally stimulate protein synthesis. In the rested (FED) leg myofibrillar (MYO) protein synthesis was elevated (P < 0.01) above FAST at 3 h (approximately 163%) but not at 1 and 5 h (P > 0.05). In contrast, MYO protein synthesis in the exercised (FED-EX) leg was stimulated above FAST at 1, 3 and 5 h (approximately 100, 216, and 229%, respectively; P < 0.01) with the increase at 5 h being greater than FED (P < 0.01). Thus, the synthesis of muscle contractile proteins is stimulated by both feeding and resistance exercise early (1 h) but has a greater duration and amplitude after resistance exercise. Sarcoplasmic (SARC) protein synthesis was similarly elevated (P < 0.01) above FAST by approximately 104% at 3 h in both FED and FED-EX suggesting SARC protein synthesis is stimulated by feeding but that this response is not augmented by resistance exercise. In conclusion, myofibrillar and sarcoplasmic protein synthesis are similarly, but transiently, stimulated with protein feeding. In contrast, resistance exercise rapidly stimulates and sustains the synthesis of only the myofibrillar protein fraction after protein ingestion. These data highlight the importance of measuring the synthetic response of specific muscle protein fractions when examining the effects of exercise and nutrition.


Cortical potential distributions and information processing.
The use of sets of spatiotemporal cortical potential distributions (CPDs) as the basis for cognitive information processing results in a very large space of cognitive elements with natural metrics. Results obtained from current source density (CSD) analysis suggest that in the CPD picture, action potentials may make only a relatively minor contribution to the brain's code. In order to establish if two CPDs are close, we consider standard metrics in spaces of continuous functions, and these may be employed to ascertain if two stimuli will be identified as the same. The correspondence between the electrical activity within brain regions, including not only action potentials but all postsynaptic potentials (PSPs), and CPDs is considered. We examine the possibility of using the CSD approach to find potential distributions using the descriptive approach in which precise sets of times are ascribed to the occurrence of action potentials and PSPs. Using metrics in the multidimensional space of paths of collections of point processes, we show that closeness of CPDs is implied by closeness of sets of spike times and PSP times if a certain metric is used but not others. We also set forth a dynamical model consisting of a system of reaction-dif fusion equations for ionic concentrations coupled with nerve membrane potential equations and active transport systems. Making the approximation of a descriptive approach, the correspondence between sets of spike times and PSP times and CPDs is obtained as with the CSD method. However, since it is not possible to ascribe precise times to the occurrence of PSPs and action potentials, the descriptive approach cannot be used to describe the configuration of electrical activity in cortical regions accurately. We also discuss how the CPD framework relates to the binding problem and submillisecond timing.


Exogenous thyrotoxicosis in dogs attributable to consumption of all-meat commercial dog food or treats containing excessive thyroid hormone: 14 cases (2008-2013).
To describe findings in dogs with exogenous thyrotoxicosis attributable to consumption of commercially available dog foods or treats containing high concentrations of thyroid hormone. Retrospective and prospective case series. 14 dogs. Medical records were retrospectively searched to identify dogs with exogenous thyrotoxicosis attributable to dietary intake. One case was found, and subsequent cases were identified prospectively. Serum thyroid hormone concentrations were evaluated before and after feeding meat-based products suspected to contain excessive thyroid hormone was discontinued. Scintigraphy was performed to evaluate thyroid tissue in 13 of 14 dogs before and 1 of 13 dogs after discontinuation of suspect foods or treats. Seven samples of 5 commercially available products fed to 6 affected dogs were analyzed for thyroxine concentration; results were subjectively compared with findings for 10 other commercial foods and 6 beef muscle or liver samples. Total serum thyroxine concentrations were high (median, 8.8 μg/dL; range, 4.65 to 17.4 μg/dL) in all dogs at initial evaluation; scintigraphy revealed subjectively decreased thyroid gland radionuclide in 13 of 13 dogs examined. At ≥ 4 weeks after feeding of suspect food or treats was discontinued, total thyroxine concentrations were within the reference range for all dogs and signs associated with thyrotoxicosis, if present, had resolved. Analysis of tested food or treat samples revealed a median thyroxine concentration for suspect products of 1.52 μg of thyroxine/g, whereas that of unrelated commercial foods was 0.38 μg of thyroxine/g. Results indicated that thyrotoxicosis can occur secondary to consumption of meat-based products presumably contaminated by thyroid tissue, and can be reversed by identification and elimination of suspect products from the diet.


Outcomes in Hepatitis C Positive Liver Transplantation: Timing of Direct-Acting Antiviral Treatment and Impact on Graft Fibrosis.
Liver transplantation for hepatitis C virus (HCV)-related disease has the lowest five-year graft survival among all liver transplant recipients. Graft failure due to accelerated fibrosis from unrestrained HCV replication is common. Optimal timing of HCV treatment with direct-acting antiviral agents remains unknown. We compared HCV liver transplant recipients successfully treated for HCV before transplant to those treated within 1 year of transplant to determine if graft fibrosis, measured by Fib-4 scores, differs with timing of treatment. Fib-4 scores less than or equal to 1.45 defined minimal fibrosis and greater than 1.45 defined greater than minimal fibrosis. We identified 117 liver transplant recipients: 52 treated before transplantation and 65 treated within 1 year of transplantation. Overall, 34% of recipients had minimal fibrosis, and the likelihood of having minimal fibrosis following treatment and liver transplantation did not differ by timing of treatment. The odds ratio of having greater than minimal fibrosis was 0.65 (95% CI 0.30, 1.42) among those treated within 1 year after transplantation compared to those treated before transplantation (p-value 0.28). Importantly, nearly 2/3 of these patients had evidence of fibrosis progression one year after sustained virologic response, supporting recommendations for early antiviral-based treatment to prevent accumulation of HCV-related disease.


Serologic survey of orthopoxvirus infection among rodents in hungary.
As a result of discontinuing vaccination against smallpox after the late 1970s, different orthopoxviruses (OPVs), such as cowpox virus (CPXV), have become a re-emerging healthcare threat among zoonotic pathogens. In Hungary, data on OPV prevalence among its rodent host species have been absent. Here, rodents belonging to four species, i.e., striped field mouse (Apodemus agrarius), yellow-necked mouse (A. flavicollis), wood mouse (A. sylvaticus) and bank vole (Myodes glareolus), were live trapped at 13 sampling plots on a 149-ha area in the Mecsek Mountains, Hungary, from March to September in 2011 and 2012. Rodent sera were collected and screened for OPV-reactive antibodies with an immunfluorescence assay (IFA). Among the 1587 tested rodents, 286 (18.0%) harbored OPV-specific antibodies. Seroprevalence was the highest for the bank vole (71.4%) and the striped field mouse (66.7%). Due to a masting event in the autumn of 2011 across Central Europe, the abundance of bank voles increased drastically in the 2012 season, raising the overall OPV seroprevalence. We provide the first data on OPV occurrence and seroprevalence in rodents in Hungary. The circulation of OPV in rodents in densely populated areas warrants further studies to elucidate the zoonotic potential of OPV in humans.


Mechanisms underlying γδ T-cell subset perturbations in SIV-infected Asian rhesus macaques.
T cells that express the γδ T-cell receptor, which recognize microbial or stress-induced antigens, represent a minority of blood T cells but constitute a major proportion of intraepithelial lymphocytes in the gastrointestinal mucosa. As microbial products have been shown to translocate from the gastrointestinal tract into circulation in chronically HIV/Simian immunodeficiency virus (SIV)-infected individuals, we conducted a study of Vδ1 and Vδ2 T-cell frequency, phenotype, and function in blood, spleen, lymph nodes, gastrointestinal mucosa, and bronchoalveolar lavage of uninfected and chronically SIVsmE543-infected rhesus macaques (RMs). We found: (1) SIV-associated inversion of Vδ1/Vδ2 T cells occurs in blood and in several tissues; (2) γδ T cells are not infected by SIV in vivo; (3) the Vδ1/Vδ2 inversion involves expansion of Vδ1 T cells; (4) expanded Vδ1 T cells are phenotypically and functionally different from Vδ1 T cells from uninfected RMs; and (5) the stimulus underlying expansion of Vδ1 T cells appears to be microbial translocation. These data highlight the importance of microbial translocation-induced immune activation in chronically infected individuals and provide new insights into an immune dysregulation phenomenon that is a hallmark of HIV/SIV infection. These findings may lead to novel therapeutic interventions that improve the immune responses against microbial antigens, and thus, decrease microbial translocation-induced immune activation.


Toxic properties of the cell wall of gram-positive bacteria.
The biological activity of Odontomyces viscosus, which has been reported to cause periodontal disease in hamsters, was examined. The microorganism was cultured anaerobically in Brain Heart Infusion broth, and the cells were harvested. The washed cells were injected intradermally into the abdomen of rabbits. After 72 hr, a well-defined, firm, raised nodule (about 1.0 by 1.5 cm) with an erythematous border was seen at the injection site. Suspensions of cell wall and cytoplasmic material were injected intradermally, and the lesions appeared only at the site of cell wall injection. The cell walls, which were then treated with trypsin, pepsin, and ribonuclease, again produced the characteristic lesion. These nodular dermal lesions persisted for a minimal time of 10 days. The enzymatically treated cell walls were then hydrolyzed with 1 n HCl, and such hydrolysis up to 1 hr failed to alter the toxic activity of the cell walls. Similar dermal nodular lesions were obtained by injection of enzymatically treated cell walls of strains of Staphylococcus aureus, Streptococcus groups B, C, E, F, K, Lactobacillus casei, and Actinomyces israelii. Treatment with hot and cold trichloroacetic acid solutions and proteolytic enzymes, or with formamide, yielded insoluble fractions which produced the characteristic nodular lesions. The size of the lesion resulting from injection of these fractions was proportional to the amount of the injected material. The active fraction, which does not appear susceptible to hydrolysis by lysozyme, is thought to be cell wall mucopeptide. Histological studies showed skin abscesses due to the toxic reaction; however, in addition to the acute inflammatory reaction, there was local eosinophilia.


Understanding psychological distress in Meniere's disease: a systematic review.
It has long been suspected that psychological disturbance is common in Meniere's disease (MD), but there has been no systematic review of research on this topic since 1977. The aim of this review was to investigate whether components of post-traumatic stress disorder (PTSD) or health anxiety contribute to distress, so that support and psychological therapy can be tailored better to the particular problems of people with MD. We systematically identified all studies of psychological factors associated with MD between 1977 and 2004. We then tabulated the findings from each of the 28 studies to match them to the components of PTSD and health anxiety. Levels of psychosocial impairment and distress were comparable to patients with similar illness. Evidence was found for some of the components of both PTSD and health anxiety. We conclude that more specific research into PTSD-like symptoms and health anxiety in MD is needed. There was a general lack of research into psychological mechanisms contributing to distress in this population, many studies had methodological weaknesses, and only one qualitative and one longitudinal study had been carried out.


MERS-CoV vaccine candidates in development: The current landscape.
Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in more than 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of MERS-CoV have created an urgent need for effective public health countermeasures, paramount of which is an effective means of prevention through a vaccine or antibody prophylaxis. Despite the relatively few number of cases to-date, research and development of MERS-CoV vaccine candidates is advancing quickly. This review surveys the landscape of these efforts across multiple groups in academia, government and industry.


Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol.
Allopurinol, which lowers uric acid (UA) concentration, is increasingly being recognized for its benefits in cardiovascular and renal disease. However, response to allopurinol is variable. We gathered samples from 4,446 multiethnic subjects for a genome-wide association study of allopurinol response. Consistent with previous studies, we observed that the Q141K variant in ABCG2 (rs2231142), which encodes the efflux pump breast cancer resistance protein (BCRP), associated with worse response to allopurinol. However, for the first time this association reached genome-wide level significance (P = 8.06 × 10-11 ). Additionally, we identified a novel association with a variant in GREM2 (rs1934341, P = 3.22 × 10-6 ). In vitro studies identified oxypurinol, the active metabolite of allopurinol, as an inhibitor of the UA transporter GLUT9, suggesting that oxypurinol may modulate UA reabsorption. These results provide strong evidence for a role of BCRP Q141K in allopurinol response, and suggest that allopurinol may have additional hypouricemic effects beyond xanthine oxidase inhibition.


Passive acoustic monitoring of coastally associated Hawaiian spinner dolphins, Stenella longirostris, ground-truthed through visual surveys.
Effective decision making to protect coastally associated dolphins relies on monitoring the presence of animals in areas that are critical to their survival. Hawaiian spinner dolphins forage at night and rest during the day in shallow bays. Due to their predictable presence, they are targeted by dolphin-tourism. In this study, comparisons of presence were made between passive acoustic monitoring (PAM) and vessel-based visual surveys in Hawaiian spinner dolphin resting bays. DSG-Ocean passive acoustic recording devices were deployed in four bays along the Kona Coast of Hawai'i Island between January 8, 2011 and August 30, 2012. The devices sampled at 80 kHz, making 30-s recordings every four minutes. Overall, dolphins were acoustically detected on 37.1% to 89.6% of recording days depending on the bay. Vessel-based visual surveys overlapped with the PAM surveys on 202 days across the four bays. No significant differences were found between visual and acoustic detections suggesting acoustic surveys can be used as a proxy for visual surveys. Given the need to monitor dolphin presence across sites, PAM is the most suitable and efficient tool for monitoring long-term presence/absence. Concomitant photo-identification surveys are necessary to address changes in abundance over time.


Development of the System for Observing Student Movement in Academic Routines and Transitions (SOSMART).
National attention on whole-of-school approaches to decrease children's sedentary behavior and increase physical activity includes movement integration (MI) in classrooms. The purpose of this study was to describe instrument development, reliability, and validity of the System for Observing Student Movement in Academic Routines and Transitions (SOSMART), designed to assess MI in elementary classrooms. An a priori conceptual framework was developed based on existing literature. The framework was expanded/refined using videos from elementary classrooms and a Delphi survey. The survey, sent to 85 experts, yielded a 38% response rate. The final system includes 11 MI variables (three categories of teacher variables, two categories of student variables) and uses a 20-second continuous interval recording format. Reliability and validity data were collected in 12 classrooms across four elementary schools. Instrument reliability was tested using interval-by-interval percentage agreement for each category. Construct validity was tested by estimating multilevel random effects logistic regression models comparing student accelerometer derived activity with the presence/absence of each MI variable. Intraobserver reliability resulted in 97.5% agreement and exceeded 80% on all variables. Construct validity was supported for 8 out of 11 MI variables. SOSMART can provide valid, reliable, and objective data about MI in elementary schools.


Inspiratory muscle training in adults with chronic obstructive pulmonary disease: an update of a systematic review.
The purpose was to update an original systematic review to determine the effect of inspiratory muscle training (IMT) on inspiratory muscle strength and endurance, exercise capacity, dyspnea and quality of life for adults with chronic obstructive pulmonary disease (COPD). The original MEDLINE and CINAHL search to August 2003 was updated to January 2007 and EMBASE was searched from inception to January 2007. Randomized controlled trials, published in English, with adults with stable COPD, comparing IMT to sham IMT or no intervention, low versus high intensity IMT, and different modes of IMT were included. Nineteen of 274 articles in the original search met the inclusion criteria. The updated search revealed 17 additional articles; 6 met the inclusion criteria, all of which compared targeted, threshold or normocapneic hyperventilation IMT to sham IMT. An update of the sub-group analysis comparing IMT versus sham IMT was performed with 10 studies from original review and 6 from the update. Sixteen meta-analyses are reported. Results demonstrated significant improvements in inspiratory muscle strength (PI(max), PI(max) % predicted, peak inspiratory flow rate), inspiratory muscle endurance (RMET, inspiratory threshold loading, MVV), exercise capacity (Ve(max), Borg Score for Respiratory Effort, 6MWT), Transitional Dyspnea Index (focal score, functional impairment, magnitude of task, magnitude of effort), and the Chronic Respiratory Disease Questionnaire (quality of life). Results suggest that targeted, threshold or normocapneic hyperventilation IMT significantly increases inspiratory muscle strength and endurance, improves outcomes of exercise capacity and one measure of quality of life, and decreases dyspnea for adults with stable COPD.


Using a combined protection motivation theory and health action process approach intervention to promote exercise during pregnancy.
Despite the benefits of exercise during pregnancy, many expectant mothers are inactive. This study examined whether augmenting a protection motivation theory (PMT) intervention with a Health Action Process Approach can enhance exercise behavior change among pregnant women. Sixty inactive pregnant women were randomly assigned to one of three treatment groups: PMT-only, PMT + action-planning, and PMT + action-and-coping-planning. Week-long objective (accelerometer) and subjective (self-report) exercise measures were collected at baseline, and at 1- and 4-weeks post-intervention. Repeated-measures ANOVAs demonstrated that while all participants reported increased exercise from baseline to 1-week post-intervention, participants in both planning groups were significantly more active (p < .001) than those in the PMT-only group by 4-weeks post-intervention (η (2) = .13 and .15 for accelerometer and self-report data, respectively). In conclusion, augmenting a PMT intervention with action or action-and-coping-planning can enhance exercise behavior change in pregnant women.


Metal nanoinks as chemically stable surface enhanced scattering (SERS) probes for the analysis of blue BIC ballpoint pens.
Metal nanoinks constituted by Ag nanoparticles and Au nanorods were employed as probes for the Surface Enhanced Raman Scattering (SERS) analysis of a blue BIC ballpoint pen. The dye components of the pen ink were first separated by thin layer chromatography (TLC) and subsequently analysed by SERS at illumination wavelengths of 514 nm and 785 nm. Compared to normal Raman conditions, enhanced spectra were obtained for all separated spots, allowing easy identification of phthalocyanine Blue 38 and triarylene crystal violet in the ink mixture. A combination of effects such as molecular resonance, electromagnetic and chemical effects were the contributing factors to the generation of spectra enhanced compared to normal Raman conditions. Enhancement factors (EFs) between 5 × 103 and 3 × 106 were obtained, depending on the combination of SERS probes and laser illumination used. In contrast to previous conflicting reports, the metal nanoinks were chemically stable, allowing the collection of reproducible spectra for days after deposition on TLC plates. In addition and in advance to previously reported SERS probes, no need for additional aggregating agents or correction of electrostatic charge was necessary to induce the generation of enhanced SERS spectra.


Clinical usefulness of microsatellite instability for the prediction of gastric adenoma or adenocarcinoma in patients with chronic gastritis.
To assess a role of microsatellite instability (MSI) in the development of gastric adenocarcinoma or adenoma from chronic gastritis, we analysed mutations of five microsatellite loci in gastritis, adenoma and adenocarcinoma retrospectively. Gastric mucosa was biopsied from the same area in each patient at different periods and examined for MSI. Only one of 55 patients with chronic gastritis revealed MSI-H phenotype and the other 54 patients showed microsatellite stable (MSS) phenotypes. In six of 17 patients with gastric adenoma or well-differentiated adenocarcinoma, MSI-positive phenotypes were demonstrated. Interestingly, all of six patients showing MSI, including three high-level MSI (MSI-H) cases and three low-level (MSH-L) cases, had already revealed MSI at the stage of chronic gastritis. In two of three MSI-H cases, the identical MSI patterns had been observed at the stage of gastritis 1.5-7 years before the final diagnosis of adenocarcinoma. The adjacent gastritis mucosa within 10 mm from the carcinoma demonstrated MSI as well. MSI was not found in any of 35 patients with Helicobacter pylori infection, but found in one of 30 patients without infection. Moreover, two of three cases of gastric adenoma or well-differentiated adenocarcinoma with MSI-H at the stage of chronic gastritis showed no evidence of Helicobacter pylori infection throughout the observation periods. These results indicate that MSI in biopsy specimens at the stage of chronic gastritis may predict the risk of the progression to adenoma and well-differentiated adenocarcinoma, and that Helicobacter pylori infection itself may not induce MSI directly in the gastric mucosa.


Providing free maternal health care: ten lessons from an evaluation of the national delivery exemption policy in Ghana.
There is a growing movement, globally and in the Africa region, to reduce financial barriers to health care generally, but with particular emphasis on high priority services and vulnerable groups. This article reports on the experience of implementing a national policy to exempt women from paying for delivery care in public, mission and private health facilities in Ghana. Using data from a complex evaluation which was carried out in 2005-2006, lessons are drawn which can inform other countries starting or planning to implement similar service-based exemption policies. On the positive side, the experience of Ghana suggests that delivery exemptions can be effective and cost-effective, and that despite being universal in application, they can benefit the poor. However, certain 'negative' lessons are also drawn from the Ghana case study, particularly on the need for adequate funding, and for strong institutional ownership. It is also important to monitor the financial transfers which reach households, to ensure that providers are passing on benefits in full, while being adequately reimbursed themselves for their loss of revenue. Careful consideration should also be given to staff motivation and the role of different providers, as well as quality of care constraints, when designing the exemptions policy. All of this should be supported by a proactive approach to monitoring and evaluation. The recent movement towards making delivery care free to all women is a bold and timely action which is supported by evidence from within and beyond Ghana. However, the potential for this to translate into reduced mortality for mothers and babies fundamentally depends on the effectiveness of its implementation.


The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2.
Centrosome amplification (CA) contributes to carcinogenesis by generating aneuploidy. Elevated frequencies of CA in most benign breast lesions and primary tumors suggest a causative role for CA in breast cancers. Clearly, identifying which and how altered signal transduction pathways contribute to CA is crucial to breast cancer control. Although a causative and cooperative role for c-Myc and Ras in mammary tumorigenesis is well documented, their ability to generate CA during mammary tumor initiation remains unexplored. To answer that question, K-Ras(G12D) and c-Myc were induced in mouse mammary glands. Although CA was observed in mammary tumors initiated by c-Myc or K-Ras(G12D), it was detected only in premalignant mammary lesions expressing K-Ras(G12D). CA, both in vivo and in vitro, was associated with increased expression of the centrosome-regulatory proteins, cyclin D1 and Nek2. Abolishing the expression of cyclin D1, Cdk4 or Nek2 in MCF10A human mammary epithelial cells expressing H-Ras(G12V) abrogated Ras-induced CA, whereas silencing cyclin E1 or B2 had no effect. Thus, we conclude that CA precedes mammary tumorigenesis, and interfering with centrosome-regulatory targets suppresses CA.


Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations.
To present a systematic literature review (SLR) on efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD), aiming to provide a basis for updating the EULAR evidence-based recommendations. An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Outcome was determined by efficacy, immunogenicity and safety of vaccination in adult patients with AIIRD, including those receiving immunomodulating therapy. Furthermore, a search was performed on the effect of vaccinating household members of patients with AIIRD on the occurrence of vaccine-preventable infections in patients and their household members (including newborns). The literature search was performed using Medline, Embase and the Cochrane Library (October 2009 to August 2018). While most investigated vaccines were efficacious and/or immunogenic in patients with AIIRD, some were less efficacious than in healthy control subjects, and/or in patients receiving immunosuppressive agents. Adverse events of vaccination were generally mild and the rates were comparable to those in healthy persons. Vaccination did not seem to lead to an increase in activity of the underlying AIIRD, but insufficient power of most studies precluded arriving at definite conclusions. The number of studies investigating clinical efficacy of vaccination is still limited. No studies on the effect of vaccinating household members of patients with AIIRD were retrieved. Evidence on efficacy, immunogenicity and safety of vaccination in patients with AIIRD was systematically reviewed to provide a basis for updated recommendations.


Comparison of intensity-modulated continuous-wave lasers with a chirped modulation frequency to pulsed lasers for photoacoustic imaging applications.
Using a Green's function solution to the photoacoustic wave equation, we compare intensity-modulated continuous-wave (CW) lasers with a chirped modulation frequency to pulsed lasers for photoacoustic imaging applications. Assuming the same transducer is used in both cases, we show that the axial resolution is identical and is determined by the transducer and material properties of the object. We derive a simple formula relating the signal-to-noise ratios (SNRs) of the two imaging systems that only depends on the fluence of each pulse and the time-bandwidth product of the chirp pulse. We also compare the SNR of the two systems assuming the fluence is limited by the American National Standards Institute (ANSI) laser safety guidelines for skin. We find that the SNR is about 20 dB to 30 dB larger for pulsed laser systems for reasonable values of the parameters. However, CW diode lasers have the advantage of being compact and relatively inexpensive, which may outweigh the lower SNR in many applications.


Bioinformatic and functional analysis of RNA secondary structure elements among different genera of human and animal caliciviruses.
The mechanism and role of RNA structure elements in the replication and translation of Caliciviridae remains poorly understood. Several algorithmically independent methods were used to predict secondary structures within the Norovirus, Sapovirus, Vesivirus and Lagovirus genera. All showed profound suppression of synonymous site variability (SSSV) at genomic 5' ends and the start of the sub-genomic (sg) transcript, consistent with evolutionary constraints from underlying RNA structure. A newly developed thermodynamic scanning method predicted RNA folding mapping precisely to regions of SSSV and at the genomic 3' end. These regions contained several evolutionarily conserved RNA secondary structures, of variable size and positions. However, all caliciviruses contained 3' terminal hairpins, and stem-loops in the anti-genomic strand invariably six bases upstream of the sg transcript, indicating putative roles as sg promoters. Using the murine norovirus (MNV) reverse-genetics system, disruption of 5' end stem-loops produced approximately 15- to 20-fold infectivity reductions, while disruption of the RNA structure in the sg promoter region and at the 3' end entirely destroyed replication ability. Restoration of infectivity by repair mutations in the sg promoter region confirmed a functional role for the RNA secondary structure, not the sequence. This study provides comprehensive bioinformatic resources for future functional studies of MNV and other caliciviruses.


The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: an extended follow-up.
To assess the long-term recurrence risks after a first unprovoked seizure in childhood. In a prospective study, 407 children who presented with a first unprovoked seizure were then followed for a mean of 6.3 years from the time of first seizure. One hundred seventy-one children (42%) experienced subsequent seizures. The cumulative risk of seizure recurrence was 29%, 37%, 42%, and 44% at 1, 2, 5, and 8 years, respectively. The median time to recurrence was 5.7 months, with 53% of recurrences occurring within 6 months, 69% within 1 year, and 88% within 2 years. Only 5 recurrences (3%) occurred after 5 years. On multivariable analysis, risk factors for seizure recurrence included a remote symptomatic etiology, an abnormal electroencephalogram (EEG), a seizure occurring while asleep, a history of prior febrile seizures, and Todd's paresis. In cryptogenic cases, the risk factors were an abnormal EEG and an initial seizure during sleep. In remote symptomatic cases, risk factors were a history of prior febrile seizures and age of onset younger than 3 years. Risk factors for late recurrences (after 2 years) were etiology, an abnormal EEG, and prior febrile seizures in the overall group and an abnormal EEG in the cryptogenic group. These are similar to the risk factors for early recurrence. The majority of children with a first unprovoked seizure will not have recurrences. Children with cryptogenic first seizures and a normal EEG whose initial seizure occurs while awake have a particularly favorable prognosis, with a 5-year recurrence risk of only 21%. Late recurrences do occur but are uncommon.


The association between urinary glyphosate and aminomethyl phosphonic acid with biomarkers of oxidative stress among pregnant women in the PROTECT birth cohort study.
Glyphosate is a widely used herbicide in global agriculture. Glyphosate and its primary environmental degradate, aminomethyl phosphonic acid (AMPA), have been shown to disrupt endocrine function and induce oxidative stress in in vitro and animal studies. To our knowledge, these relationships have not been previously characterized in epidemiological settings. Elevated urinary levels of glyphosate and AMPA may be indicative of health effects caused by previous exposure via multiple mechanisms including oxidative stress. Glyphosate and AMPA were measured in 347 urine samples collected between 16 and 20 weeks gestation and 24-28 weeks gestation from pregnant women in the PROTECT birth cohort. Urinary biomarkers of oxidative stress, comprising 8-isoprostane-prostaglandin-F2α (8-iso-PGF2α), its metabolite 2,3-dinor-5,6-dihydro-15-F2 t-isoprostane (8-isoprostane metabolite) and prostaglandin-F2α (PGF2α), were also measured. Linear mixed effect models assessed the association between exposures and oxidative stress adjusting for maternal age, smoking status, alcohol consumption, household income and specific gravity. Potential nonlinear trends were also assessed using tertiles of glyphosate and AMPA exposure levels. No significant differences in exposure or oxidative stress biomarker concentrations were observed between study visits. An interquartile range (IQR) increase in AMPA was associated with 9.5% (95% CI: 0.5-19.3%) higher 8-iso-PGF2α metabolite concentrations. Significant linear trends were also identified when examining tertiles of exposure variables. Compared to the lowest exposure group, the second and third tertiles of AMPA were significantly associated with 12.8% (0.6-26.5%) and 15.2% (1.8-30.3%) higher 8-isoprostane metabolite, respectively. An IQR increase in glyphosate was suggestively associated with 4.7% (-0.9 to 10.7%) higher 8-iso-PGF2α. Urinary concentrations of the main environmental degradate of glyphosate, AMPA, were associated with higher levels of certain oxidative stress biomarkers. Associations with glyphosate reflected similar trends, although findings were not as strong. Additional research is required to better characterize the association between glyphosate exposure and biomarkers of oxidative stress, as well as potential downstream health consequences.


NIR/blue light emission optimization of NaY1-(x+y)YbxF4:Tmy upconversion nanoparticles via Yb3+/Tm3+ dopant balancing.
The increased applications of lanthanide-doped upconversion nanoparticles (UCNPs) in areas such as biomedical imaging and therapy have raised the demand for high quality nanocrystals with strong and controllable luminescence intensity. Whilst several different approaches including core/shell arrangement, dye sensitization and plasmonic metallic nanostructures have been employed to improve the upconversion luminescence of UCNPs, they may be impractical for scale-up production and applications. Herein, a mathematical model that was developed using multivariate statistical analysis shows that the key to optimising the NIR and blue light emission of NaY1-(x+y)YbxF4:Tmy UCNPs is dopant balancing, where the composition of both ytterbium (Yb3+) sensitizer and thulium (Tm3+) activator is controlled in a way that the concentration and proximity of the dopants to each other can reduce cross-relaxation between Tm3+ and self-quenching that is due to sub-optimal Yb3+ concentrations, and consequently, favours efficient energy transfer between the Yb3+ sensitizers and Tm3+ activators. The data driven approach gives better understanding of the role of dopant balancing in the upconversion process and presents a general yet effective strategy to enhance the optical properties of UCNPs by manipulating the relative concentrations of the lanthanide dopants. This systematic approach will have important implications and it can be integrated with other emission enhancing strategies to produce high quality UCNPs for diverse applications in photonics, imaging, sensing, drug delivery and solar energy conversion.


Rapid improvement in visual loss with cabergoline treatment in a giant prolactinoma case: 5 years survey.
Giant prolactinoma is a rare subset of macroadenomas. Limited studies demonstrated which therapy could be successfully used in the first-line therapy of giant prolactinoma. We presented a case with a 54 × 40 × 40 mm pituitary adenoma and optic chiasmatic compression with left sphenoid sinus invasion. The tumor caused a loss of visual field of the right side. Cabergoline treatment was started with dose of 1.5 mg/week. Fifteen days later, the clinical visual acuity examination showed a significant improvement in the patient with visual field defect. After the five years follow-up magnetic resonance imagining showed reduction of the adenoma size (17 × 12 mm) was significant. Our findings suggest that, cabergoline can be used as a first-line therapy in giant prolactinomas because tumoral shrinkage without a surgical procedure and rapid improvement in visual field defect is achieved with this medical treatment.


A Randomized Double-blind Controlled Trial of Lactobacillus acidophilus Plus Bifidobacterium bifidum versus Placebo in Patients with Hypercholesterolemia.
Hypercholesterolemia is a major risk factor for cardiovascular disease. Not all patients respond well to traditional cholesterol lowering medications. Probiotics have been evaluated for their cholesterol-lowering effects in humans with variable results. This study was performed to evaluate the efficacy of two probiotics in lowering the serum cholesterol of hypercholesterolemic patients. A randomized double-blind controlled trial was conducted comparing placebo to Lactobacillus acidophilus plus Bifidobacterium bifidum in patients diagnosed with hypercholesterolemia. Placebo or probiotic capsules were taken three times daily for six weeks. Pre- and post-treatment total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglyceride (TG) levels and demographic parameters of the two groups were compared. From a total of 70 participants, 64 completed the assigned treatment (31 in probiotics group and 33 in the control group).The two treatment groups were matched for age, sex, weight, height, BMI, waist and hip circumferences, and blood pressure. Baseline evaluation revealed no difference between the probiotics group and control group levels of TC, HDL-C, LDL-C and TG. TC levels in the probiotics group decreased during treatment (237.2 vs. 212.7 mg/dL, p<0.05). TC and LDL-C levels in the control group increased significantly from their baseline levels during treatment. TC (212.7 vs 252.8 mg/dL, p<0.001), HDL-C (52.0 vs 59.1 mg/dL, p=0.04) and LDL-C (153.9 vs 182.1 mg/dL, p<0.01) levels in the probiotics group were significantly lower at the end of treatment than the corresponding levels in the control group. A combination of Lactobacillus acidophilus and Bifidobacterium bifidum decreased serum total cholesterol, LDL-cholesterol and HDL-cholesterol levels in hypercholesterolemic patients over a six week period. There was no effect on serum triglyceride or fasting blood glucose levels.


Anxiety, movement kinematics, and visual attention in elite-level performers.
We tested the predictions of Attentional Control Theory (ACT) by examining the effect of anxiety on attention control and the subsequent influence on both performance effectiveness and performance efficiency within a perceptual-motor context. A sample (N = 16) of elite shotgun shooters was tested under counterbalanced low (practice) and high (competition) anxiety conditions. A head-mounted, corneal reflection system allowed point of gaze to be calculated in relation to the scene, while motion of the gun was evaluated using markers placed on the barrel which were captured by two stationary cameras and analyzed using optical tracking software. The quiet eye (QE) duration and onset were analyzed along with gun barrel displacement and variability; performance outcome scores (successful vs. unsuccessful) were also recorded. QE (Vickers, 1996) is defined as the final fixation or tracking gaze that is located on a specific location/object in the visual display for a minimum of 100 ms. Longer QE durations have been linked to successful performance in previous research involving aiming tasks. Participants demonstrated shorter quiet eye durations, and less efficient gun motion, along with a decreased performance outcome (fewer successful trials) under high compared with low anxiety conditions. The data support the predictions of ACT with anxiety disrupting control processes such that goal-directed attention was compromised, leading to a significant impairment in performance effectiveness.


Oral tolerance in experimental autoimmune uveoretinitis. Distinct mechanisms of resistance are induced by low dose vs high dose feeding protocols.
Studies of oral tolerance in LEW rat models of autoimmune diseases including S-antigen (S-Ag)-mediated experimental autoimmune uveoretinitis (EAU), and myelin basic protein-induced experimental autoimmune encephalomyelitis have produced conflicting evidence for the roles of clonal anergy and suppression. Using subpeptides from a region of S-Ag known to induce oral tolerance a protective site was localized to a nonamer of residues 347-355. This site was also uveitogenic, providing the basis for testable hypotheses for tolerance to be due to clonal anergy in pathogenic T cells specific for that site, or to suppression. Evidence for suppression was strongly supported by several observations. 1) Induction of oral tolerance with low dose feedings (250 micrograms/feeding) of peptide 343-362 conferred resistance to EAU induction by intact S-Ag, which should not be possible if only T cells specific for epitopes in 343-362 were rendered unresponsive, since there are several other pathogenic sites in S-Ag. 2) Low dose feeding induced resistance to EAU induction by a distinct, spatially separate peptide, residues 270-289, of S-Ag. 3) The requirement for linked recognition was shown by the inability of tolerance induced by feeding 343-362 to protect from EAU induction by a peptide, residues 521-540, derived from interphotoreceptor retinoid binding protein, a different uveitogenic retinal protein. 4) Resistance could be adoptively transferred. Conversely, induction of tolerance with high doses of peptide (5 mg/feeding) resulted in loss of resistance to EAU induced by S-Ag, although disease induction by the fed peptide was inhibited; observations that are consistent with clonal anergy. The apparent lack of suppression after high dose feeding could mean that suppressor T cells can also be rendered unresponsive or that induction of T suppressor cells is dependent on CD4+ Th cells, which were rendered anergic, leading to lack of T suppressor development. We suggest that oral tolerance operates by at least two distinct mechanisms that depend on the feeding dose; low doses induce suppression, whereas high doses induce unresponsiveness.


Unit Costs in Health Economic Evaluations: Quo Vadis, Austria?
Evidence-informed healthcare decision-making relies on high quality data inputs, including robust unit costs, which in many countries are not readily available. The objective of the Department of Health Economics' Unit Cost Online Database, developed based on systematic reviews of Austrian costing studies, is to make conducting economic evaluations from healthcare and societal perspectives more feasible with publicly available unit cost information in Austria. This article aims to describe trends in unit cost data sources and reporting using this comprehensive database as a case study to encourage relevant national and international methodological discussions. Database analysis and synthesis included publication/study characteristics and costing reporting details in line with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) with the year of the database launch as the cut-off point to assess how the methods have developed over time. Forty-two full economic evaluations and 278 unit costs were analyzed (2004-2016: 34 studies/232 unit costs, 2017-2022: 8 studies/46 unit costs). Although the reporting quality of costing details including the study perspective, unit cost sources and years has improved since 2017, the unit cost estimates and sources remained heterogeneous in Austria. While methodologically standardized national-level unit costs would be the gold standard, a systematically collated list of unit costs is a first step towards supporting health economic evaluations nationally.


Contact prediction is hardest for the most informative contacts, but improves with the incorporation of contact potentials.
Co-evolution between pairs of residues in a multiple sequence alignment (MSA) of homologous proteins has long been proposed as an indicator of structural contacts. Recently, several methods, such as direct-coupling analysis (DCA) and MetaPSICOV, have been shown to achieve impressive rates of contact prediction by taking advantage of considerable sequence data. In this paper, we show that prediction success rates are highly sensitive to the structural definition of a contact, with more permissive definitions (i.e., those classifying more pairs as true contacts) naturally leading to higher positive predictive rates, but at the expense of the amount of structural information contributed by each contact. Thus, the remaining limitations of contact prediction algorithms are most noticeable in conjunction with geometrically restrictive contacts-precisely those that contribute more information in structure prediction. We suggest that to improve prediction rates for such "informative" contacts one could combine co-evolution scores with additional indicators of contact likelihood. Specifically, we find that when a pair of co-varying positions in an MSA is occupied by residue pairs with favorable statistical contact energies, that pair is more likely to represent a true contact. We show that combining a contact potential metric with DCA or MetaPSICOV performs considerably better than DCA or MetaPSICOV alone, respectively. This is true regardless of contact definition, but especially true for stricter and more informative contact definitions. In summary, this work outlines some remaining challenges to be addressed in contact prediction and proposes and validates a promising direction towards improvement.


The behind-the-scenes activity of parental decision-making discourse regarding childhood vaccination.
Vaccine compliance has long been a cause for concern for health authorities throughout the world. However very little effort has been made to examine parental discourse during the decision-making process. An online survey was conducted (N = 437) to examine predictors of parents' attitudes regarding childhood vaccination. Hesitant parents were 4 times more likely to conduct intrafamily discussion regarding vaccination compared with provaccination parents (Exp[B] = 4.26). There were no significant differences between hesitant and antivaccination parents with respect to intrafamily discussion. Hesitant parents were also 4 times more likely than provaccination parents to report intrafamily disagreements regarding vaccination (Exp[B] = 4.27). They were also twice as likely as antivaccination parents to express disagreements regarding vaccination within their families (Exp[B] = 2.33). Likewise, Jewish parents were significantly more likely to define themselves as vaccination-hesitant, whereas Muslim parents were significantly more likely to be provaccination. To improve the way health organizations communicate information about vaccines and increase parental trust in immunization programs, we should not only look at the level of understanding, perceptions, and biases of different groups, but also thoroughly examine parents' decision-making processes and the discourse during this process. We must communicate risk to all groups, including the provaccination group, to improve parents' decision making and the process of informed consent.


Outcomes of robot-assisted simple enucleation of renal masses: A single European center experience.
The aim of this study was to assess the ability of pre-and intraoperative parameters, to predict the risk of perioperative complications after robot-assisted laparoscopic simple enucleation (RASE) of renal masses, and to evaluate the rate of trifecta achievement of this approach stratifying the cohort according to the use of ischemia during the enucleation.From April 2009 to June 2016, 129 patients underwent RASE at our Institution. We stratified the procedures in 2 groups: clamping and clamp-less RASE. After RASE, all specimens were retrospectively reviewed to assess the surface-intermediate-base (SIB) scoring system. Patients were followed-up according to the European Association of Urology guidelines recommendations. All pre-, intra-, and postoperative outcomes were prospectively collected in a customized database and retrospectively analyzed.A total of 112 (86.8%) patients underwent a pure RASE and 17 (13.2%) had a hybrid according to SIB classification system. The mean age was 61.17 years. In 21 patients (16.3%), complications occurred, 13 (61.9%) were Clavien 1 and 2, while 8 were Clavien 3a and b complications. Statistical significant association with complications was found in patients with American Society of Anestesiology (ASA) score 3 (44.5%, P = .04), longer mean operative time (OT) 195 versus 161.36 minutes (P =.03), mean postoperative hemoglobin (Hb) 10.1 versus 11.8 (P <.001), and mean ΔHb 3.59 versus 2.18 (P <.001). In multivariate logistic regression, only longer OT and ΔHb were statistical significant predictive factors for complications. In sub-group analysis, clamp-less RASE was safe in terms of complications (14.1%), positive surgical margins (1.3%), and mid-term local recurrence (1.3%). Although in this approach there is higher EBL (P = .01), this had no impact on ΔHb (P = .28). A clamp-less approach was associated with a higher rate of SIB 0 (71.8% vs 51%, P = .02), higher trifecta achievement (84.6% vs 62.7%, P = .004), and better impact on serum creatinine (mean 0.83 vs 0.91, P = .01).RASE of renal tumors is a safe technique with very good postoperative outcomes. Complication rate is low and associated with ASA score >3, longer OT, and ΔHb. RASE is suitable for the clamp-less approach, which allows to perform easier the pure enucleation (SIB 0) and to obtain higher rates of trifecta outcomes.


Acute and chronic mitochondrial respiratory chain deficiency differentially regulate lysosomal biogenesis.
Mitochondria are key cellular signaling platforms, affecting fundamental processes such as cell proliferation, differentiation and death. However, it remains unclear how mitochondrial signaling affects other organelles, particularly lysosomes. Here, we demonstrate that mitochondrial respiratory chain (RC) impairments elicit a stress signaling pathway that regulates lysosomal biogenesis via the microphtalmia transcription factor family. Interestingly, the effect of mitochondrial stress over lysosomal biogenesis depends on the timeframe of the stress elicited: while RC inhibition with rotenone or uncoupling with CCCP initially triggers lysosomal biogenesis, the effect peaks after few hours and returns to baseline. Long-term RC inhibition by long-term treatment with rotenone, or patient mutations in fibroblasts and in a mouse model result in repression of lysosomal biogenesis. The induction of lysosomal biogenesis by short-term mitochondrial stress is dependent on TFEB and MITF, requires AMPK signaling and is independent of calcineurin signaling. These results reveal an integrated view of how mitochondrial signaling affects lysosomes, which is essential to fully comprehend the consequences of mitochondrial malfunction, particularly in the context of mitochondrial diseases.


Quantifying egocentric spatial neglect with cancellation tasks: A theoretical validation.
Spatial neglect is characterized by a spatial bias in response to stimuli. The disorder is often assessed with a cancellation task, where several measures can be used to quantify the spatial bias of cancellation responses (e.g., the difference between cancellations on the left and right side, the average location of cancelled targets, and the total number of omissions). Typically, measures of cancellation performance are validated by studying the correlation with measures derived from other tasks to assess neglect (e.g., the directional bisection error derived from performance on the line bisection task). However, the foundation of cancellation performance measures is often more intuitive than theoretical. For instance, it is assumed that measures of cancellation performance isolate the spatial (e.g., the ipsilesional preference typical of spatial neglect) from the non-spatial (e.g., deficits in working memory or sustained attention) sources of error, but this assumption has not been tested yet. Here we formulated a simple model with conceptually meaningful parameters to predict cancellation performance. Our model parameterizes the spatial and non-spatial components of cancellation responses. This model allowed us to study the construct representation of commonly used measures of spatial neglect through the use of Monte Carlo simulations. The results showed that most of the cancellation performance measures are also dependent on non-spatial error sources. The results deepen our understanding of the construct representation of cancellation performance measures, while also having implications for studies focused on the relationship between the spatial and non-spatial attention deficits in spatial neglect.


Image-guided Navigation of Single-element Focused Ultrasound Transducer.
The spatial specificity and controllability of focused ultrasound (FUS), in addition to its ability to modify the excitability of neural tissue, allows for the selective and reversible neuromodulation of the brain function, with great potential in neurotherapeutics. Intra-operative magnetic resonance imaging (MRI) guidance (in short, MRg) has limitations due to its complicated examination logistics, such as fixation through skull screws to mount the stereotactic frame, simultaneous sonication in the MRI environment, and restrictions in choosing MR-compatible materials. In order to overcome these limitations, an image-guidance system based on optical tracking and pre-operative imaging data is developed, separating the imaging acquisition for guidance and sonication procedure for treatment. Techniques to define the local coordinates of the focal point of sonication are presented. First, mechanical calibration detects the concentric rotational motion of a rigid-body optical tracker, attached to a straight rod mimicking the sonication path, pivoted at the virtual FUS focus. The spatial error presented in the mechanical calibration was compensated further by MRI-based calibration, which estimates the spatial offset between the navigated focal point and the ground-truth location of the sonication focus obtained from a temperature-sensitive MR sequence. MRI-based calibration offered a significant decrease in spatial errors (1.9±0.8 mm; 57% reduction) compared to the mechanical calibration method alone (4.4±0.9 mm). Using the presented method, pulse-mode FUS was applied to the motor area of the rat brain, and successfully stimulated the motor cortex. The presented techniques can be readily adapted for the transcranial application of FUS to intact human brain.


Impact of 18F-choline PET/CT in prostate cancer patients with biochemical recurrence: influence of androgen deprivation therapy and correlation with PSA kinetics.
We evaluated the potential of (18)F-fluoromethyldimethyl-2-hydroxyethyl-ammonium (FCH) PET/CT in the detection of recurrent disease or distant metastases and correlated its diagnostic accuracy with prostate-specific antigen (PSA) levels in prostate cancer patients with biochemical evidence of recurrence. Furthermore, the influences of androgen deprivation therapy (ADT) and its duration on (18)F-FCH PET were assessed in this study. This prospective study included 250 prostate cancer patients with PSA relapse who underwent (18)F-FCH PET/CT. At the time of (18)F-FCH PET/CT imaging, the mean PSA level was 46.9 ± 314.7 ng/mL and 55.2% (138/250) of patients were receiving ADT. Overall, ADT was performed on 67.2% (168/250) of patients after initial treatment. Imaging was performed on an integrated PET/CT system. Acquisition started 1 min after intravenous injection of (18)F-FCH (4.07 MBq/kg of body weight) with dynamic PET images in the pelvic region during 8 min (1 min/frame) followed by a static semi-whole-body acquisition. The final diagnosis of positive PET lesions was based on histopathology or a consensus of clinical findings, additional imaging, or follow-up imaging modalities. (18)F-FCH PET/CT was able to correctly detect malignant lesions in 74% (185/250) of patients but was negative in 26% (65/250). In 28% of patients, only 1 lesion was detected (69/250); from these, 65.2% (45 patients) had a local recurrence, 18.8% (13 patients) a single lymph node, and 15.9% (11 patients) a solitary bone metastasis. The sensitivity of the (18)F-FCH PET was significantly higher (P = 0.001) in patients with ongoing ADT (85%; confidence interval, 80%-91%) than in patients without ADT (59.5%; confidence interval, 50%-69%). (18)F-FCH PET sensitivity was 77.5%, 80.7%, 85.2%, and 92.8% for the trigger PSA levels of more than 0.5, 1.0, 2.0, and 4.0 ng/mL, respectively. Scan sensitivity was 33% in patients with a trigger PSA level of less than 0.3 ng/mL and 77% in patients with a trigger PSA level of greater than 0.3 ng/mL, respectively (P = 0.001). Using a binary logistic regression analysis model, we showed trigger PSA and ADT to be the only significant predictors of positive PET findings. (18)F-FCH PET/CT proved its potential as a noninvasive 1-stop diagnostic modality enabling us to correctly detect occult disease in 74% of patients and to differentiate localized from systemic disease. In patients with biochemical recurrence, it also guides to an optimal treatment approach after initial treatment. Trigger PSA and ADT are the 2 significant predictors of (18)F-FCH-positive PET lesions. ADT seems not to impair (18)F-FCH uptake in hormone-refractory prostate cancer patients.


Gastrostomy Tube Feeding in Children With Developmental or Acquired Disorders: A Longitudinal Comparison on Healthcare Provision and Eating Outcomes 4 Years After Gastrostomy.
Studies on long-term feeding and eating outcomes in children requiring gastrostomy tube feeding (GT) are scarce. The aim of this study was to describe children with developmental or acquired disorders receiving GT and to compare longitudinal eating and feeding outcomes. A secondary aim was to explore healthcare provision related to eating and feeding. This retrospective cohort study reviewed medical records of children in 1 administrative region of Sweden with GT placement between 2005 and 2012. Patient demographics, primary diagnoses, age at GT placement, and professional healthcare contacts prior to and after GT placement were recorded and compared. Feeding and eating outcomes were assessed 4 years after GT placement. The medical records of 51 children, 28 boys and 23 girls, were analyzed and grouped according to "acquired" (n = 13) or "developmental" (n = 38) primary diagnoses. At 4 years after GT placement, 67% were still using GT. Only 6 of 37 (16%) children with developmental disorders transferred to eating all orally, as opposed to 10 of 11 (91%) children with acquired disorders. Children with developmental disorders were younger at the time of GT placement and displayed a longer duration of GT activity when compared with children with acquired disorders. This study demonstrates a clear difference between children with developmental or acquired disorders in duration of GT activity and age at GT placement. The study further shows that healthcare provided to children with GT is in some cases multidisciplinary, but primarily focuses on feeding rather than eating.


Occurrence and sorption properties of arsenicals in marine sediments.
The content of total arsenic, the inorganic forms: arsenite (As(III)) and arsenate (As(V)), the methylated forms: monomethylarsonic acid and dimethylarsinic acid (DMA), trimethylarsenic oxide, tetramethylarsenonium ion and arsenobetaine was measured in 95 sediment samples and 11 pore water samples from the Baltic Sea near the island of Bornholm at depths of up to 100 m. As(III+V) and DMA were detected in the sediment and As(III+V) was detected in the sediment pore water. Average total As concentration of 10.6 ± 7.4 mg/kg dry matter (DM) in the sediment corresponds to previously reported values in the Baltic Sea and other parts of the world. Existing data for on-site measurements of sorption coefficients (Kd) of arsenicals in marine and freshwater sediments show large variability from <1 to >1,000 L/kg. In this work, calculated sorption coefficients (Kd and Koc) for As(III+V) showed significant correlation with depth, dissolved oxygen (DO), salinity and sediment classification; for depths <70 m, salinity <11 %, DO >9 mg/L and sand/silt/clay sediments the Kd was 118 ± 76 L/kg DM and for depths >70 m, salinity >11 %, DO < 9 mg/L and muddy sediments the Kd was 513 ± 233 L/kg DM. The authors recommend using the found Kd value for arsenic in marine sediments when conditions are similar to the Baltic Sea. At locations with significant anthropogenic point sources or where the local geology contains volcanic rock and sulphide mineral deposits, there may be significantly elevated arsenic concentrations, and it is recommended to determine on-site Kd values.


Evaluation of Human Esophageal Epithelium Permeability in Presence of Different Formulations Containing Hyaluronic Acid and Chondroitin Sulphate.
New medical devices that contain hyaluronic acid (HA) and chondroitin sulphate (CS), with or without antacid components, have been developed for the treatment of gastroesophageal reflux disease (GERD) with the aim of improving oesophageal mucosal defences by creating a film on the oesophageal mucosa and acting as a mechanical barrier against the noxious components of refluxate, both acidic and basic. The film-forming and protective efficacy of medical device A based on HA and CS plus aluminium hydroxide, device B combining HA and CS with magnesium trisilicate and device C with only the combination of HA and CS was tested on a reconstructed human oesophageal epithelium (HO2E/S/5) as a biological model in 2 different pH environments, neutral and acidic, to mimic realistic conditions. Caffeine penetration kinetics and Lucifer yellow (LY) permeability modifications induced by these products were compared to those induced by a negative control series (saline solution, code NC) and positive control series (white Vaseline, code V) under neutral and acidic pH conditions. Under neutral and acidic pH conditions, compared to the negative control, all the products tested reduced (>80% and 85-90%, respectively) the caffeine passage, and no significant difference was observed among the products tested. Under neutral and acidic conditions, the LY permeabilities registered with device A and device C were not different from that registered with the negative control, while an LY flux% increase was calculated after 2 hrs of treatment (21.1%) with device B under acidic conditions. These results confirm the ability of the products tested to interact with the oesophageal epithelium in order to adhere and create a stable protective film for at least 2 hours after their homogeneous distribution on the epithelium surface. Further clinical studies are needed to test these devices in the topical treatment of gastroesophageal reflux symptoms.


Group supervision to strengthen nurses in their preceptor role in the bachelor nursing education--perceptions before and after participation.
A collaborative project was carried out at four bachelor nursing colleges in Sweden and Norway, to support preceptors in the clinical fields by means of group supervision. The aim of this study was to investigate the preceptors' views on their own ability and satisfaction in the role before and after taking part in group supervision during one year and to describe their perception of the supervision model used. Forty-five preceptors participated in the study. Baseline and endpoint questionnaires were used for data collection. Before taking part in group supervision most preceptors expressed that they were content with their ability and knowledge with regards to the preceptor role. Despite this most of them considered that the participation had increased their ability to supervise students, and more than half of them considered that it also had promoted to their personal development. At the end of the project a majority of them had positive experiences of group supervision. Most of the structure and climate factors in the supervision model were considered important and almost all were highly realised. The study showed that group supervision could be a valuable tool to provide support to clinical preceptors in bachelor nursing education.


The influence of race in older adults with infective endocarditis.
Age is a risk factor for infective endocarditis, and almost half of diagnosed patients are age ≥ 60 years. Large national studies have not evaluated inpatient mortality and surgical valvular interventions between older White and Black patients hospitalized with infective endocarditis. We used the Nationwide Inpatient Sample database to identify older adults ≥60 years in North America with a principle diagnosis of infective endocarditis. Multivariate logistic regression was used to compare in-hospital mortality and valvular repairs/replacement between older Black and White patients. Of 10,390 adults, age ≥ 60 years hospitalized for infective endocarditis during 2013 and 2014, 7356 were White and 1089 Black. Blacks were younger (mean age: 70.5 ± 0.5 vs. 73.5 ± 0.2 years, p < 0.01), lived in more zip codes with a median annual income <$39,000/yr. (40.4% vs 18.8%, p < 0.01), and had higher co-morbidity burden (Charlson comorbidity score ≥ 3: 54.6% vs 40.7%, p < 0.01). After multivariate adjustment, Blacks had higher odds for in-hospital mortality (Odds Ratio (OR) = 2.0, [Confidence Interval (CI) 1.1-3.8]; p = 0.020), and lower odds for mitral valve repairs/replacements (OR = 0.53, CI: 0.29-0.99, p = 0.049). Blacks age ≥ 60 years hospitalized in North America with infective endocarditis are less likely to undergo mitral valvular repairs/replacement and had higher in-hospital mortality compared to White patients.


Understanding HIV risks of chronic drug-using men who have sex with men.
Focus groups and individual structured interviews were conducted in six cities with 98 predominantly street-recruited men who had a recent history of smoking crack or injecting drugs and who reported having had sex with other men (MSM) in the past year. Twenty-six focus groups explored the cultural and social context of participant's drug use and sexual activity and addressed outreach and HIV prevention issues pertinent to this population. Narrative summaries developed from verbatim focus group transcripts identified seven themes: (a) sexual orientation and gender identity; (b) interactions within and between MSM networks; (c) drug use, sexual activity and personal relationships; (d) HIV transmission bridges; (e) preferred HIV information sources; (f) HIV knowledge, prevention practices and risk behaviours; and (g) availability of HIV and drug-related services. Of the 98 MSM drug users, 42% identified publicly as gay or homosexual; 35% identified publicly, but only 21% privately, as heterosexual. A total of 51% had one or more female sex partners in the past year. There was a high frequency of unprotected sex in conjunction with drug use and a distinct preference for having sex when high. For most participants, drug use rather than sexual orientation formed the core of personal identity. Participants reported associating primarily with other drug users, usually MSM, and had limited contact with people who did not use drugs and the mainstream gay community. Participants' sexual and drug-injecting activities were judged to be a bridge for transmission of HIV to both people who used drugs and those who did not.


Optical turbulence on underwater image degradation in natural environments.
It is a well-known fact that the major degradation source on electro-optical imaging underwater is from scattering by particles of various origins and sizes. Recent research indicates that, under certain conditions, the apparent degradation could also be caused by the variations of index of refraction associated with temperature and salinity microstructures in the ocean and lakes. The combined impact has been modeled previously through the simple underwater imaging model. The current study presents the first attempts in quantifying the level of image degradation due to optical turbulence in natural waters in terms of modulation transfer functions using measured turbulence dissipation rates. Image data collected from natural environments during the Skaneateles Optical Turbulence Exercise are presented. Accurate assessments of the turbulence conditions are critical to the model validation and were measured by two instruments to ensure consistency and accuracy. Optical properties of the water column in the field were also measured in coordination with temperature, conductivity, and depth. The results show that optical turbulence degrades the image quality as predicted and on a level comparable to that caused by the particle scattering just above the thermocline. Other contributing elements involving model closure, including temporal and spatial measurement scale differences among sensors and mitigation efforts, are discussed.