Effectiveness and acceptability of medical abortion provided through telemedicine.
To estimate the effectiveness and acceptability of telemedicine provision of early medical abortion compared with provision with a face-to-face physician visit at a Planned Parenthood affiliate in Iowa. Between November 2008 and October 2009, we conducted a prospective cohort study of women obtaining medical abortion by telemedicine or face-to-face physician visits. We collected clinical data, and women completed a self-administered questionnaire at follow-up. We also compared the prevalence of reportable adverse events between the two service delivery models among all patients seen between July 2008 and October 2009. Of 578 enrolled participants, follow-up data were obtained for 223 telemedicine patients and 226 face-to-face patients. The proportion with a successful abortion was 99% for telemedicine patients (95% confidence interval [CI] 96-100%) and 97% for face-to-face patients (95% CI 94-99%). Ninety-one percent of all participants were very satisfied with their abortion, although in multivariable analysis, telemedicine patients had a higher odds of saying they would recommend the service to a friend compared with face-to-face patients (odds ratio, 1.72; 95% CI 1.26-2.34). Twenty-five percent of telemedicine patients said they would have preferred being in the same room with the doctor. Younger age, less education, and nulliparity were significantly associated with preferring face-to-face communication. There was no significant difference in the prevalence of adverse events reported during the study period among telemedicine patients (n = 1,172) (1.3%; 95% CI 0.8-2.1%) compared with face-to-face patients (n = 2,384) (1.3%; 95% CI 0.9-1.8%) (82% power to detect difference of 1.3%). Provision of medical abortion through telemedicine is effective and acceptability is high among women who choose this model. II.


Ecotoxicological Assessment of Thermally- and Hydrogen-Reduced Graphene Oxide/TiO₂ Photocatalytic Nanocomposites Using the Zebrafish Embryo Model.
Advanced oxidation processes (AOPs) have recently attracted great interest in water pollution management. Using the zebrafish embryo model, we investigated the environmental impacts of two thermally (RGOTi)- and hydrogen (H₂RGOTi)-reduced graphene oxide/TiO₂ semiconductor photocatalysts recently employed in AOPs. For this purpose, acutoxicity, cardiotoxicity, neurobehavioral toxicity, hematopoietic toxicity, and hatching rate were determinate. For the RGOTi, the no observed effect concentration (NOEC, mortality/teratogenicity score <20%) and the median lethal concentration (LC50) were <400 and 748.6 mg/L, respectively. H₂RGOTi showed a NOEC similar to RGOTi. However, no significant mortality was detected at all concentrations used in the acutoxicity assay (up to1000 mg/L), thus indicating a hypothetical LC50 higher than 1000 mg/L. According to the Fish and Wildlife Service Acute Toxicity Rating Scale, RGOTi can be classified as "practically not toxic" and H₂RGOTi as "relatively harmless". However, both nanocomposites should be used with caution at concentration higher than the NOEC (400 mg/L), in particular RGOTi, which significantly (i) caused pericardial and yolk sac edema; (ii) decreased the hatching rate, locomotion, and hematopoietic activities; and (iii) affected the heart rate. Indeed, the aforementioned teratogenic phenotypes were less devastating in H₂RGOTi-treated embryos, suggesting that the hydrogen-reduced graphene oxide/TiO₂ photocatalysts may be more ecofriendly than the thermally-reduced ones.


A lack of standardization: the basis for the ethical issues surrounding quality and performance reports.
Consumers in the United States are taking advantage of the proliferation of publicly available, internet-based performance reports and quality appraisals of health plans, healthcare organizations, hospitals, and physicians to aid in their healthcare decision making. However, these appraisal practices have given rise to controversy and debate over certain distinctive ethical issues. This article advocates a standardized ethical framework to guide current and future development and implementation of performance reports. This framework, which would resolve a number of the major issues, includes the following ethical principles to guide the practice of public reporting on the Internet and facilitate enhanced quality improvement in the healthcare industry: legitimacy, data integrity and quality, transparency, informed understanding, equity, privacy and confidentiality, collaboration, accountability, and evaluation and continuous improvement.


Learning from observation, feedback, and intervention in linear and non-linear task environments.
This multiple-cue judgment study investigates whether we can manipulate the judgment strategy and increase accuracy in linear and non-linear cue-criterion environments just by changing the training mode. Three experiments show that accuracy in simple linear additive task environments are improved with feedback training and intervention training, while accuracy in complex multiplicative tasks are improved with observational training. The observed interaction effect suggests that the training mode invites different strategies that are adjusted as a function of experience to the demands from the underlying cue-criterion structure. Thus, feedback and the intervention training modes invite cue abstraction, an effortful but successful strategy in combination with simple linear task structures, and observational training invites exemplar memory processes, a simple but successful strategy in combination with complex non-linear task structures. The study discusses adaptive cognition and the implication of the different training modes across a life span and for clinical populations.


A second glutamine synthetase gene with expression in the gills of the gulf toadfish (Opsanus beta).
We characterized the expression of the nitrogen metabolism enzyme glutamine synthetase [GSase; L-glutamate: ammonia ligase (ADP-forming), E.C. 22.214.171.124] in tissues of the gulf toadfish Opsanus beta subjected to unconfined (ammonotelic) and confined (ureotelic) conditions. Enzymological results demonstrate that mass-specific GSase activities rank in the order of brain > liver > stomach approximately kidney > intestine > gill > heart/spleen > muscle. When tissue mass is used to calculate a glutamine synthetic potential, the liver has the greatest, followed by muscle > stomach and intestine, with minor contributions from the remaining tissues. Additionally, during confinement stress, GSase activity increases significantly only in liver (fivefold) and muscle (twofold), tissues that previously showed significant expression of the other enzymes of urea synthesis. Western analyses of samples on SDS gels demonstrated that GSase-specific protein content reflected enzyme activity, and all tissues except muscle had a single, similarly sized GSase subunit of 49.4 kDa; muscle showed staining of two bands of 36.8 and 98.9 kDa, which may possibly result from another gene product or post-translational modification. RT-PCR and RACE-PCR revealed the presence of a second GSase cDNA from gill tissue that shares only 73% nucleotide and amino acid sequence similarity with the GSase cDNA previously cloned from liver, and that lacks a mitochondrial leader-targeting sequence. RT-PCR and restriction digestion experiments demonstrated that mRNA from the original 'liver' GSase is expressed in all tissues examined (liver, gill, stomach, intestine, kidney, brain and muscle), whereas the new 'gill' form shows expression primarily in the gill. Gill GSase activity shows apparently exclusive expression in the soluble compartment, while other tissues expressing the 'liver' form show both cytoplasmic and mitochondrial activities. Phylogenetic analysis of a number of GSases demonstrates that the toadfish gill GSase has a greater affinity for a clade that includes the Xenopus GSase genes and one of two Fugu GSase genes, than it has for a clade containing the toadfish liver GSase and other described teleost GSase genes. The results are discussed in the context of a prior hypothesis on an ammonia-trapping mechanism in the gill of the toadfish.


Positive and negative functions of the SAGA complex mediated through interaction of Spt8 with TBP and the N-terminal domain of TFIIA.
A surface that is required for rapid formation of preinitiation complexes (PICs) was identified on the N-terminal domain (NTD) of the RNA Pol II general transcription factor TFIIA. Site-specific photocross-linkers and tethered protein cleavage reagents positioned on the NTD of TFIIA and assembled in PICs identified the SAGA subunit Spt8 and the TFIID subunit Taf4 as located near this surface. In agreement with these findings, mutations in Spt8 and the TFIIA NTD interact genetically. Using purified proteins, it was found that TFIIA and Spt8 do not stably bind to each other, but rather both compete for binding to TBP. Consistent with this competition, Spt8 inhibits the binding of SAGA to PICs in the absence of activator. In the presence of activator, Spt8 enhances transcription in vitro, and the positive function of the TFIIA NTD is largely mediated through Spt8. Our results suggest a mechanism for the previously observed positive and negative effects of Spt8 on transcription observed in vivo.


Protein elicitor GP1pro targets aquaporin NbPIP2;4 to activate plant immunity.
The novel protein elicitor GP1pro is the protein component of glycoprotein GP-1 isolated and identified from Streptomyces kanasensis ZX01. GP1pro induces the production of reactive oxygen species (ROS) and a hypersensitive response (HR), along with the accumulation of resistance-related genes and secondary metabolites. It ultimately regulates plant defence responses. Further analysis revealed that GP1pro interacts with the PIP2-family aquaporin protein NbPIP2;4 on the plant plasma membrane (PM) in Nicotiana benthamiana. PM localization is necessary for inducing GP1pro resistance. These results demonstrate that NbPIP2;4 acts as a H2 O2 transporter to positively regulate plant immunity and ROS accumulation. In summary, this study elucidates a conserved and novel pathway caused by GP1pro to initiate host cellular defences by targeting the plant aquaporin protein NbPIP2;4 and transporting apoplast-to-cytoplast H2 O2 to regulate plant immunity.


Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis.
The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique.


Will Trespassers Be Prosecuted or Assessed According to Their Merits? A Consilient Interpretation of Territoriality in a Group-Living Carnivore, the European Badger (Meles meles).
Socio-spatial interactions of Carnivores have traditionally been described using the vocabulary of territoriality and aggression, with scent marks interpreted as 'scent fences'. Here, we investigate the role of olfactory signals in assumed territorial marking of group-living solitary foragers using European badgers Meles meles as a model. We presented anal gland secretions (n = 351) from known individuals to identifiable recipients (n = 187), to assess response-variation according to familiarity (own-group, neighbours, strangers) and spatial context (in-context: at a shared border; out-of-context: at an unshared border/ the main sett). Sniffing and over-marking (with subcaudal gland secretion) responses were strongest to anal gland secretions from strangers, intermediate to neighbouring-group and weakest to own-group members. Secretions from both, strangers and neighbours, were sniffed for longer than were own-group samples, although neighbour-secretion presented out-of-context evoked no greater interest than in-context. On an individual level, responses were further moderated by the relevance of individual-specific donor information encoded in the secretion, as it related to the physiological state of the responder. There was a trend bordering on significance for males to sniff for longer than did females, but without sex-related differences in the frequency of subcaudal over-marking responses, and males over-marked oestrous female secretions more than non-oestrous females. There were no age-class related differences in sniff-duration or in over-marking. Evaluating these results in the context of the Familiarity hypothesis, the Threat-level hypothesis, and the Individual advertisement hypothesis evidences that interpretations of territorial scent-marks depicting rigid and potentially agonistic discrimination between own- and foreign-group conspecifics are overly simplistic. We use our findings to advance conceptual understanding of badger socio-spatial ecology, and the general context of territoriality and group-range dynamics.


The regulation and inhibition of 17beta-hydroxysteroid dehydrogenase in breast cancer.
17Beta-hydroxysteroid dehydrogenase Type 1 (17beta-HSD1) has a pivotal role in regulating the synthesis of oestradiol (E2) within breast tumours. In whole body studies in postmenopausal women with breast cancer the conversion of oestrone (E1) to E2 (4.4+/-1.1%) was much lower than the inactivation of E2 to E1 (17.3+/-5.0%). In contrast, an examination of in vivo oestrogen metabolism within breast tumours revealed that whereas little metabolism of E2 occurred, E1 was converted to E2 to a much greater extent in malignant (48+/-14%) than in normal (19+/-6%) breast tissue. Findings from these studies originally suggested that oestrogen metabolism within breast tumours may differ from the mainly oxidative direction found in most other body tissues and that the activity of 17beta-HSD1 might be regulated by tumour-derived factors. Several growth factors (e.g. IGF-I, IGF-II) and cytokines (e.g. IL-6, TNFalpha) have now been identified which can markedly stimulate the activity of 17beta-HSD1 and such a mechanism may account for the high concentrations of E2 found in most breast tumours. Cells of the immune system, which can infiltrate breast tumours, are thought to be a major source of the growth factors and cytokines which can modulate 17beta-HSD1 activity. Given the central role that 17beta-HSD1 has in regulating breast tumour E2 concentrations the development of potent inhibitors of this enzyme has recently attracted considerable attention. Our initial studies in this area explored the use of derivatives of E1 as inhibitors, with 2-ethyl- and 2-methoxy E1 being found to inhibit 17beta-HSD1 activity in T-47D breast cancer cells by 96+/-2 and 91+/-1% respectively at 10 microM, but with a lack of specificity. Using the E1 scaffold a number of potent, selective 17beta-HSD1 inhibitors have now been identified including E1- and 2-ethyl-E1 containing a side chain with a m-pyridylmethylamidomethyl functionality extending from the 16beta position of the steroid nucleus. At 10 microM these compounds both inhibited 17beta-HSD1 activity by >90%, however some inhibition of 17beta-HSD2 activity was exhibited by the E1 derivative (25%) but not the 2-ethyl analogue. It is now apparent that 17beta-HSD1 activity contributes to the high E2 concentrations found in most breast tumours. The identification of potent, selective novel 17beta-HSD1 inhibitors will allow their efficacy to be tested in in vitro and in vivo studies.


Web-Based Psychological Interventions for People Living With and Beyond Cancer: Meta-Review of What Works and What Does Not for Maximizing Recruitment, Engagement, and Efficacy.
Despite high levels of psychological distress experienced by many patients with cancer, previous research has identified several barriers to accessing traditional face-to-face psychological support. Web-based psychosocial interventions have emerged as a promising alternative. This meta-review aimed to synthesize evidence on recruitment challenges and enablers, factors that promote engagement and adherence to web-based intervention content, and factors that promote the efficacy of web-based psychosocial interventions for patients with cancer and cancer survivors. We conducted a systematic search of previous reviews that investigated the recruitment, engagement, and efficacy of web-based and app-based psychosocial interventions in adult patients with cancer and cancer survivors. We searched PubMed, CINAHL, PsycINFO, and the Cochrane Library database for relevant literature. The search terms focused on a combination of topics pertaining to neoplasms and telemedicine. Two independent authors conducted abstract screening, full text screening, and data extraction for each identified article. A total of 20 articles met eligibility criteria. There was inconsistency in the reporting of uptake and engagement data; however, anxiety about technology and perceived time burden were identified as 2 key barriers. Web-based psychosocial oncology interventions demonstrated efficacy in reducing depression and stress but reported weak to mixed findings for distress, anxiety, quality of life, and well-being. Although no factors consistently moderated intervention efficacy, preliminary evidence indicated that multicomponent interventions and greater communication with a health care professional were preferred by participants and were associated with superior effects. Several consistently cited barriers to intervention uptake and recruitment have emerged, which we recommend future intervention studies address. Preliminary evidence also supports the superior efficacy of multicomponent interventions and interventions that facilitate communication with a health care professional. However, a greater number of appropriately powered clinical trials, including randomized trials with head-to-head comparisons, are needed to enable more confident conclusions regarding which web-based psychosocial oncology interventions work best and for whom. PROSPERO CRD42020202633; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=202633.


Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.
To our knowledge the frequency and prognostic significance of PTEN protein expression in upper tract urothelial carcinoma have not yet been investigated in large studies. We analyzed PTEN protein status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma cohort. We retrospectively analyzed the records of 611 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy between 1991 and 2008 at a total of 7 institutions. Median followup was 23 months. Tissue microarrays and immunohistochemical PTEN staining (monoclonal antibody) were performed. Univariable and multivariable Cox regression models were created to address the association of PTEN protein expression with disease recurrence, and cancer specific and overall mortality. PTEN staining was absent in 45 cases (7.4%). Patients with PTEN loss had significantly advanced pathological tumor stage and grade (p <0.001), and higher rates of lymph node metastasis (p <0.01) and lymphovascular invasion (p <0.001) compared to patients with PTEN expression. PTEN loss was associated with disease recurrence, and cancer specific and overall mortality on univariable Cox regression analyses. However, on multivariable Cox regression analyses adjusted for the effect of standard clinicopathological features PTEN loss was only associated with overall mortality (HR 1.69, 95% CI 1.09-2.61, p = 0.02). In patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma loss of PTEN protein expression is rare but associated with features of biologically aggressive disease such as higher grade and stage as well as lymph node metastasis. Loss of PTEN expression was associated with overall mortality. PTEN loss seemed to promote worse outcomes in this relatively small group of patients.


CD3 and CD2 antigen-mediated CD3 gamma-chain phosphorylation in permeabilized human T cells. Regulation by cytosolic phosphatases.
The role of cytosolic and membrane-associated phosphatases in regulating dephosphorylation of the CD3 antigen gamma-chain has been investigated using streptolysin-O-permeabilized T lymphoblasts and Jurkat T leukaemia cells. Permeabilization of T cells caused a rapid extrusion of cytosolic type 2A phosphatases, but a membrane-associated phosphorylase phosphatase activity remained inside the cells. This activity had the properties characteristic of type 2A phosphatases, being resistant to inhibition by type 1 phosphatase inhibitors, though it was inhibited in a time-dependent manner by ATP or by non-hydrolysable ATP analogues, but not by GTP, CTP, ITP or PPi. The membrane-associated type 2A phosphatase in permeabilized cells did not dephosphorylate the CD3 antigen gamma-chain, suggesting that cytosolic phosphatases dephosphorylate the gamma-chain in situ. Cross-linking the CD2 and CD3 antigens with a bivalent monoclonal antibody in the absence of cytosolic phosphatases induced marked phosphorylation of the CD3 gamma-chain, immunoprecipitated using a novel gamma-chain peptide analogue directed antiserum (TG1). Phosphorylation was inhibited by a protein kinase C (PKC) pseudosubstrate inhibitor, indicating that CD2/CD3-induced gamma-chain phosphorylation is a PKC-mediated event. Activation of T cells either with phorbol 12,13-dibutyrate or by CD2-CD3 cross-linking caused [32P]Pi incorporation into the same gamma-chain Ser residues. The site-mapping data suggested that PKC in situ may incorporate phosphate at the CD3 gamma-chain Ser-123 and Ser-126 residues, but that phosphate is rapidly lost from Ser-123 by cytosolic phosphatase action. Our findings underline the importance of the dual actions of kinases and phosphatases as potential regulators of T cell antigen-receptor complex function.


Systematic review and meta-analysis of training mode, imaging modality and body size influences on the morphology and function of the male athlete's heart.
The athlete's heart (AH) remains a popular topic of study. Controversy related to training-specific cardiac adaptation in male athletes, and continuing developments in imaging technology and scaling prompted this systematic review and meta-analysis. To provide new insight in relation to: 1) cardiac adaptation to divergent training patterns in male athletes, 2) a developing research database using cardiac magnetic resonance (CMR) in athletes; 3) functional data derived from tissue-Doppler analysis as well as right ventricular (RV) and left atrial (LA) measurements in athletes; and 4) an awareness of the impact of body size on cardiac dimensions. Systematic review and meta-analysis of prospective trials. Data extraction performed by two researchers. Pub Med, Medline, Scopus and ISI Web of knowledge scholarly data base. Prospective studies were included if they were echocardiographic or CMR trials of elite young male athletes, with clear indication of type of sports and passed a quality criteria checklist. All left ventricular (LV) structural parameters were higher in athletes than in controls. Only LV end-diastolic diameter and volume were higher in endurance athletes than in resistance athletes: 54.8 mm (95% CI 54.1 to 55.6) vs 52.4 mm (95% CI 51.2 to 53.6); p<0.001 and 171 ml (95% CI 157 to 185) vs 131 ml (95% CI 120 to 142); p<0.001, respectively. RV end-diastolic volume, mass and LA diameter were higher in endurance athletes than controls. LV end-diastolic volume was larger when CMR was used rather than echocardiography: 178 ml (95% CI Q7 162 to 194) vs 135 ml (95% CI 128 to 142); p<0.001. Meta-analysis regression models demonstrated positive and significant associations between body surface area (BSA) and LV mass, RV mass and LA diameter. Morphological features of the male AH were noted in both athlete groups. A training-specific pattern of concentric hypertrophy was not discerned in resistance athletes. Both imaging mode and BSA can have a significant impact on the interpretation of AH data.


Estimating the relationship between exposure to tar volatiles and the incidence of bladder cancer in aluminum smelter workers.
A previously reported case-referent study of 85 incident cases of bladder cancer among aluminum smelter workers and 255 matched referents revealed an excess risk among workers exposed to coal-tar pitch volatiles. For the study reported in the present investigation these data have been augmented by estimates of past workplace exposure to total tar (benzene-soluble matter) and to benzo-a-pyrene (BaP). From these new data, exposure-response relationships have been estimated by maximum likelihood. A linear relationship between cumulative exposure and relative risk and a minimum latency period of ten years were assumed on a priori grounds and found compatible with the data. Under these assumptions, relative risk increased for each year of exposure to benzene-soluble matter at a concentration of 1 mg/m3 by 13%, the 95% confidence interval being 5-31. The corresponding figure for BaP (as micrograms/m3 X year) was 2.3%. On the basis of these estimates, 40 years of exposure to benzene-soluble matter at the current exposure limit of 0.2 mg/m3 would lead to a relative risk of 2.4. There was suggestive but not conclusive evidence that relative risks due to exposure to tar volatiles and to cigarette smoke combined multiplicatively.


Anterior Choroidal Thickness Increased in Primary Open-Angle Glaucoma and Primary Angle-Closure Disease Eyes Evidenced by Ultrasound Biomicroscopy and SS-OCT.
To compare the anterior and posterior choroid thickness (ACT and PCT, respectively) in primary open-angle glaucoma (POAG), primary angle-closure disease (PACD), and healthy control subjects. A total of 29 POAG patients (56 eyes), 37 PACD patients (64 eyes), and 34 healthy volunteers (68 eyes) were enrolled in this study; 50 POAG eyes were divided into 25 early/moderate-stage and 25 advanced-stage eyes by visual field loss, while 64 PACD eyes were classified as primary angle-closure suspect (PACS), 8 eyes; primary angle closure (PAC), 18 eyes; and primary angle-closure glaucoma (PACG), 38 eyes. Ultrasound biomicroscopy (UBM) was used to measure the ACT at a distance of 4 mm from the root of iris in all participants. ACT and PCT were measured using UBM and swept-source optical coherence tomography (SS-OCT), respectively. A 4-mm distance from the iris root was self-defined as the anterior choroid that well matched the real anterior choroid. The mean ACT measured by UBM was 0.45 ± 0.057 mm in POAG eyes, 0.38 ± 0.050 mm in PACD eyes, and 0.30 ± 0.050 mm in healthy eyes. Both the POAG and PACD eyes had a thicker anterior choroid than healthy eyes (P < 0.01). Compared to early/moderate-stage eyes of POAG, advanced-stage eyes had similar ACT (P > 0.05). PACG eyes had a thinner anterior choroid than PAC/PACS eyes (P < 0.05). However, no statistically significant difference was noted for POAG, PACD, and normal control eyes' PCT using SS-OCT (P > 0.05). POAG/PACD eyes had a thicker anterior choroid than the controls. However, there was no significant difference in the PCT among the groups. The anterior choroid might play a role in the pathogenesis of glaucoma, warranting further investigation.


Age Differences in Striatal Delay Sensitivity during Intertemporal Choice in Healthy Adults.
Intertemporal choices are a ubiquitous class of decisions that involve selecting between outcomes available at different times in the future. We investigated the neural systems supporting intertemporal decisions in healthy younger and older adults. Using functional neuroimaging, we find that aging is associated with a shift in the brain areas that respond to delayed rewards. Although we replicate findings that brain regions associated with the mesolimbic dopamine system respond preferentially to immediate rewards, we find a separate region in the ventral striatum with very modest time dependence in older adults. Activation in this striatal region was relatively insensitive to delay in older but not younger adults. Since the dopamine system is believed to support associative learning about future rewards over time, our observed transfer of function may be due to greater experience with delayed rewards as people age. Identifying differences in the neural systems underlying these decisions may contribute to a more comprehensive model of age-related change in intertemporal choice.


Development and Validation of a Measure of Attitudes toward Fluffy Women.
There is an absence of research on the newly evolved term "fluffy" which describes body image and personality features among women. Research on "fluffiness" among Caribbean peoples has been limited by the lack of valid and reliable measures of the concept. This project addresses this problem by exploring the internal consistency reliability and the concurrent and discriminant validity of the Attitudes toward Fluffy Women Scale (ATFW) using a mixture of past and present students from The University of the West Indies (UWI), Mona, and the University of Technology (UTech), Kingston. Past or present students from The UWI, Mona, and UTech, Kingston, were recruited for the study through the use of convenience sampling. A total of 80 students (38 males, 47.5%; 42 females, 52.5%) participated in the study. Overall, the ATFW was found to have an acceptable degree of internal consistency reliability (α = 0.90). The scale also had reasonably good concurrent validity as evidenced by moderate correlations with scores on the Attitudes Toward Obese Persons Scale (r = -0.42) and acceptable discriminant validity as demonstrated through low correlations with a Bogardus Social Distance Scale designed to assess prejudice toward people living with the human immunodeficiency virus [HIV] (r = 0.29). This pattern of scores suggests that the majority of the stable variance underlying the ATFW assesses the "fluffy" concept (17.6%) while a smaller degree of the variability (8%) measures a conceptually similar but distinct concept. The Attitudes toward Fluffy Women scale was found to be a reliable and valid scale for assessing the attitudes of young adults toward fluffy women.


Role of compassion competence among clinical nurses in professional quality of life.
The study aimed to explore measurable compassion competence among nurses and to examine the relationships between nurses' compassion competence and levels of compassion satisfaction, compassion fatigue and secondary traumatic stress. Compassion is a vital asset in the nursing profession. It is necessary to explore whether compassion competence is a factor influencing professional quality of life. This study utilized a multicenter descriptive cross-sectional survey. Data were collected from 680 nurses. Professional quality of life based on nurses' general characteristics showed a significant difference in the subjects' age, marital status, education, and total clinical experience. In addition, compassion competence had a significant positive correlation with compassion satisfaction and STS, whereas it had a significant negative correlation with burnout. Compassion competence was a factor influencing compassion satisfaction and burnout in professional quality of life. Our study included nurses with at least 1 year of clinical experience in a single cultural area, which limits its widespread applicability. To improve generalizability, future studies should include clinical nurses of various races, working in diverse cultural areas and with various levels of experience (including entry-level nurses and nursing students). Compassion competence of clinical nurses was a predictive factor for professional quality of life. Hospital administrators, nurse leaders and policy makers should develop and adopt nurse-retaining strategies that focus on improving nurses' compassion competence in order to reduce their burnout. We recommend the development of educational programmes to improve nurses' compassion competence and thereby enhance their professional quality of life.


Seasonal and Spatial Variations of Saltmarsh Benthic Foraminiferal Communities from North Norfolk, England.
Time series foraminiferal data were obtained from samples collected from three sites at Brancaster Overy Staithe, Burnham Overy Staithe and Thornham on the North Norfolk coast over a 1-year period. At each collection point, six environmental variables-temperature, chlorophyll, sand, mud, pH and salinity-were also measured. The principle aim of this study was to examine the benthic foraminiferal fauna in regard to the temporal variability of foraminiferal abundance, seasonal trend, dominant species, species diversity and the impact of environmental variables on the foraminiferal communities in the top 1 cm of sediment over a 1-year time series. The foraminiferal assemblages at the three sites were dominated by three species: Haynesina germanica, Ammonia sp. and Elphidium williamsoni. Foraminiferal species showed considerable seasonal and temporal fluctuation throughout the year at the three investigated sites. The foraminiferal assemblage at the three low marsh zones showed a maximum abundance in autumn between September and November and a minimum abundance observed between July and August. There were two separate peaks in the abundance of Ammonia sp. and E. williamsoni, one in spring and another in autumn. In contrast, H. germanica showed a single peak in its abundance in autumn. A generalized additive modelling approach was used to explain the variation in the observed foraminiferal abundance and to estimate the significant impact of each of the environmental variables on living foraminiferal assemblages, with taxa abundance as the dependent variable. When included in the model as predictors, most of the environmental variables contributed little in explaining the observed variation in foraminiferal species abundance. However, the hypotheses for differences amongst sites, salinity and pH were significant and explained most of the variability in species relative abundance.


Efficient fluorescence inhibition patterns for RESOLFT microscopy.
By exploiting the saturation of a reversible single photon transition, RESOLFT microscopy is capable of resolving three dimensional structures inside specimen with a resolution that is no longer limited by the wavelength of the light in use. The transition is driven by a spatially varying intensity distribution that features at least one isolated point, line or plane with zero intensity and the resolution achieved depends critically on the field distribution around these zeros. Based on a vectorial analysis of the image formation in a RESOLFT microscope, we develop a method to effectively search for optimal zero intensity point patterns under typical experimental conditions. Using this approach, we derived a spatial intensity distribution that optimizes the focal plane resolution. Moreover, we outline a general strategy that allows optimization of the resolution for a given experimental situation and present solutions for the most common cases in biological imaging.


National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: 24-month outcomes of treatment strategies for attention-deficit/hyperactivity disorder.
In the Multimodal Treatment Study of ADHD (MTA), the effects of medication management (MedMgt) and behavior modification therapy (Beh) and their combination (Comb) and usual community comparison (CC) in the treatment of attention-deficit/hyperactivity disorder (ADHD) differed at the 14-month assessment as a result of superiority of the MTA MedMgt strategy (Comb or MedMgt) over Beh and CC and modest additional benefits of Comb over MedMgt alone. Here we evaluate the persistence of these beneficial effects 10 months beyond the 14 months of intensive intervention. Of 579 children who entered the study, 540 (93%) participated in the first follow-up 10 months after the end of treatment. Mixed-effects regression models explored possible persisting effects of the MTA medication strategy, the incremental benefits of Comb over MedMgt alone, and the possible superiority of Beh over CC on 5 effectiveness and 4 service use domains. The MTA medication strategy showed persisting significant superiority over Beh and CC for ADHD and oppositional-defiant symptoms at 24 months, although not as great as at 14 months. Significant additional benefits of Comb over MedMgt and of Beh over CC were not found. The groups differed significantly in mean dose (methylphenidate equivalents 30.4, 37.5, 25.7, and 24.0 mg/day, respectively). Continuing medication use partly mediated the persisting superiority of Comb and MedMgt. The benefits of intensive MedMgt for ADHD extend 10 months beyond the intensive treatment phase only in symptom domains and diminish over time.


Quantification of endogenous steroid sulfates and glucuronides in human urine after intramuscular administration of testosterone esters.
For an effective detection of doping with pseudo-endogenous anabolic steroids, the urinary steroid profile is of high value. In this work, the aim was to investigate steroid metabolism disruption after exogenous intramuscular administration of different testosterone esters. The investigation focused on both sulfo - and glucoro conjugated androgens. A single intramuscular injection of either 1000 mg testosterone undecanoate (Nebido®) or a mixture of 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate, and 100 mg testosterone decanoate (Sustanone®), was given to six healthy volunteers. Urine was collected throughout a testing period of 60 days. A LC-MS method was developed and validated for the analysis of eight conjugated steroids in their intact form. The results show that urinary changes in both sulfo - and glucuro conjugated steroid levels are prominent after the injection of testosterone esters. A promising potential marker for the intake of exogenous testosterone is the combined ratio of epitestosterone sulfate/epitestosterone glucuronide to testosterone sulfate/testosterone glucuronide ((ES/EG)/(TS/TG)) as a complementary biomarker for testosterone abuse. This represents a new piece of evidence to detect testosterone doping, representing a new approach and being independent from the metabolic connections of the markers in the steroid passport.


Animal models of COPD: What do they tell us?
COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.


Altered CD45 isoform expression affects lymphocyte function in CD45 Tg mice.
Transgenic mice have been constructed expressing high (CD45RABC) and low (CD45R0) molecular weight CD45 isoforms on a CD45-/- background. Phenotypic analysis and in vivo challenge of these mice with influenza and lymphocytic choriomeningitis viruses shows that T cell differentiation and peripheral T cell function are related to the level of CD45 expression but not to which CD45 isoform is expressed. In contrast, B cell differentiation is not restored, irrespective of the level of expression of a single isoform. All CD45 trangenic mice have T cells with an activated phenotype and increased T cell turnover. These effects are more prominent in CD8 than CD4 cells. The transgenic mice share several properties with humans expressing variant CD45 alleles and provide a model to understand immune function in variant individuals.


Reduced dietary salt for the prevention of cardiovascular disease.
An earlier Cochrane review of dietary advice identified insufficient evidence to assess effects of reduced salt intake on mortality or cardiovascular events. 1. To assess the long term effects of interventions aimed at reducing dietary salt on mortality and cardiovascular morbidity.2. To investigate whether blood pressure reduction is an explanatory factor in any effect of such dietary interventions on mortality and cardiovascular outcomes. The Cochrane Library (CENTRAL, Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effect (DARE)), MEDLINE, EMBASE, CINAHL and PsycInfo were searched through to October 2008. References of included studies and reviews were also checked. No language restrictions were applied. Trials fulfilled the following criteria: (1) randomised with follow up of at least six-months, (2) intervention was reduced dietary salt (restricted salt dietary intervention or advice to reduce salt intake), (3) adults, (4) mortality or cardiovascular morbidity data was available. Two reviewers independently assessed whether studies met these criteria. Data extraction and study validity were compiled by a single reviewer, and checked by a second. Authors were contacted where possible to obtain missing information. Events were extracted and relative risks (RRs) and 95% CIs calculated. Seven studies (including 6,489 participants) met the inclusion criteria - three in normotensives (n=3518), two in hypertensives (n=758), one in a mixed population of normo- and hypertensives (n=1981) and one in heart failure (n=232) with end of trial follow-up of seven to 36 months and longest observational follow up (after trial end) to 12.7 yrs. Relative risks for all cause mortality in normotensives (end of trial RR 0.67, 95% CI: 0.40 to 1.12, 60 deaths; longest follow up RR 0.90, 95% CI: 0.58 to 1.40, 79 deaths) and hypertensives (end of trial RR 0.97, 95% CI: 0.83 to 1.13, 513 deaths; longest follow up RR 0.96, 95% CI; 0.83 to 1.11, 565 deaths) showed no strong evidence of any effect of salt reduction. Cardiovascular morbidity in people with normal blood pressure (longest follow-up RR 0.71, 95% CI: 0.42 to 1.20, 200 events) or raised blood pressure at baseline (end of trial RR 0.84, 95% CI: 0.57 to 1.23, 93 events) also showed no strong evidence of benefit. Salt restriction increased the risk of all-cause death in those with congestive heart failure (end of trial relative risk: 2.59, 95% 1.04 to 6.44, 21 deaths). We found no information on participants health-related quality of life. Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Further RCT evidence is needed to confirm whether restriction of sodium is harmful for people with heart failure. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.


Wanted: role models--medical students' perceptions of professionalism.
Transformation of medical students to become medical professionals is a core competency required for physicians in the 21st century. Role modeling was traditionally the key method of transmitting this skill. Medical schools are developing medical curricula which are explicit in ensuring students develop the professional competency and understand the values and attributes of this role. The purpose of this study was to determine student perception of professionalism at the University of Ottawa and gain insights for improvement in promotion of professionalism in undergraduate medical education. Survey on student perception of professionalism in general, the curriculum and learning environment at the University of Ottawa, and the perception of student behaviors, was developed by faculty and students and sent electronically to all University of Ottawa medical students. The survey included both quantitative items including an adapted Pritzker list and qualitative responses to eight open ended questions on professionalism at the Faculty of Medicine, University of Ottawa. All analyses were performed using SAS version 9.1 (SAS Institute Inc. Cary, NC, USA). Chi-square and Fischer's exact test (for cell count less than 5) were used to derive p-values for categorical variables by level of student learning. The response rate was 45.6% (255 of 559 students) for all four years of the curriculum. 63% of the responses were from students in years 1 and 2 (preclerkship). Students identified role modeling as the single most important aspect of professionalism. The strongest curricular recommendations included faculty-led case scenario sessions, enhancing interprofessional interactions and the creation of special awards to staff and students to "celebrate" professionalism. Current evaluation systems were considered least effective. The importance of role modeling and information on how to report lapses and breaches was highlighted in the answers to the open ended questions. Students identify the need for strong positive role models in their learning environment, and for effective evaluation of the professionalism of students and teachers. Medical school leaders must facilitate development of these components within the MD education and faculty development programs as well as in clinical milieus where student learning occurs.


Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells.
Skeletal muscle damaged by injury or by degenerative diseases such as muscular dystrophy is able to regenerate new muscle fibers. Regeneration mainly depends upon satellite cells, myogenic progenitors localized between the basal lamina and the muscle fiber membrane. However, other cell types outside the basal lamina, such as pericytes, also have myogenic potency. Here, we discuss the main properties of satellite cells and other myogenic progenitors as well as recent efforts to obtain myogenic cells from pluripotent stem cells for patient-tailored cell therapy. Clinical trials utilizing these cells to treat muscular dystrophies, heart failure, and stress urinary incontinence are also briefly outlined.


Oxygen sensing, anaesthesia and critical care: a narrative review.
In 2019, the scientists who discovered how cells sense and adapt to oxygen availability were awarded the Nobel Prize. This elegant sensing pathway is conserved throughout evolution, and it underpins the physiology and pathology that we, as clinicians in anaesthesia and critical care, encounter on a daily basis. The purpose of this review is to bring hypoxia-inducible factor, and the oxygen-sensing pathway as a whole, to the wider clinical community. We describe how this unifying mechanism was discovered, and how it orchestrates diverse changes such as erythropoiesis, ventilatory acclimatisation, pulmonary vascular remodelling and altered metabolism. We explore the lessons learnt from genetic disorders of oxygen sensing, and the wider implications in evolution of all animal species, including our own. Finally, we explain how this pathway is relevant to our clinical practice, and how it is being manipulated in new treatments for conditions such as cancer, anaemia and pulmonary hypertension.


Brevibacillus levickii sp. nov. and Aneurinibacillus terranovensis sp. nov., two novel thermoacidophiles isolated from geothermal soils of northern Victoria Land, Antarctica.
Thirteen strains of endospore-forming bacteria were isolated from geothermal soils at Cryptogam Ridge, the north-west slope of Mt Melbourne, and at the vents and summit of Mt Rittmann in northern Victoria Land, Antarctica. 16S rRNA gene sequencing, SDS-PAGE and routine phenotypic characterization tests indicated that the seven isolates from the north-west slope of Mt Melbourne represent a novel species of Brevibacillus and that the six isolates from Cryptogam Ridge and the vents and summit of Mt Rittmann represent a novel species of Aneurinibacillus. Brevibacillus strains were not isolated from the sites at Mt Rittmann or Cryptogam Ridge and Aneurinibacillus strains were not isolated from the north-west slope of Mt Melbourne. Preliminary metabolic studies revealed that L-glutamic acid, although not essential for growth, was utilized by both species. The Brevibacillus species possessed an uptake system specific for L-glutamic acid, whereas the Aneurinibacillus species possessed a more general uptake system capable of transporting other related amino acids. Both species utilized a K(+) antiport system and similar energy systems for the uptake of l-glutamic acid. The rate of uptake by the Brevibacillus species type strain was 20-fold greater than that shown by the Aneurinibacillus species type strain. The names Brevibacillus levickii sp. nov. and Aneurinibacillus terranovensis sp. nov. are proposed for the novel taxa; the type strains are Logan B-1657(T) (= LMG 22481(T) = CIP 108307(T)) and Logan B-1599(T) (LMG 22483(T) = CIP 108308(T)), respectively.


Continent-Scale Sampling Reveals Fine-Scale Turnover in a Beneficial Bug Symbiont.
Many members of animal-associated microbial communities, including the gut flora, are acquired from their host's environment. While many of these communities are species rich, some true bugs (Hemiptera) in the superfamilies Lygaeoidea and Coreidae allow only ingested Burkholderia to colonize and reproduce in a large portion of the midgut. We studied the spatial structuring of Burkholderia associated with a widespread omnivorous bug genus, Jalysus (Berytidae). We sampled Wickham's stilt bug, Jalysus wickhami, across the United States and performed limited sampling of its sister species, the spined stilt bug Jalysus spinosus. We asked: (1) What Burkholderia strains are hosted by Jalysus at different locations? (2) Does host insect species, host plant species, or location influence the strain these insects acquire? (3) How does Burkholderia affect the development and reproductive fitness of J. wickhami? We found: (1) Sixty-one Burkholderia strains were present across a sample of 352 individuals, but one strain dominated, accounting for almost half of all symbiont reads. Most strains were closely related to other hemipteran Burkholderia symbionts. (2) Many individuals hosted more than one strain of Burkholderia. (3) J. wickhami and J. spinosus did not differ in the strains they hosted. (4) Insects that fed on different plant species tended to host different Burkholderia, but this accounted for only 4% of the variation in strains hosted. In contrast, the location at which an insect was collected explained 27% of the variation in symbiont strains. (5) Burkholderia confers important fitness benefits to J. wickhami. In laboratory experiments, aposymbiotic (Burkholderia-free) insects developed more slowly and laid fewer eggs than symbiotic (Burkholderia-colonized) insects. (6) In the lab, nymphs sometimes acquired Burkholderia via indirect exposure to adults, indicating that horizontal symbiont transmission can occur via adult insect-mediated enrichment of Burkholderia in the local environment - a phenomenon not previously reported in bug-Burkholderia relationships. Taken together, the results suggest that for these bugs, critical nutritional requirements are outsourced to a highly diverse and spatially structured collection of Burkholderia strains acquired from the environment and, occasionally, from conspecific adults.


Enhanced light emission in blue light-emitting diodes by multiple Mie scattering from embedded silica nanosphere stacking layers.
We demonstrate enhanced light emission in blue light-emitting diodes (LEDs) by multiple Mie scattering from embedded silica nanosphere stacking layers (SNSL). A honeycomb cone structure is introduced in the GaN epilayer to confine a maximum number of silica nanospheres (SNs). We found that the light is predominantly directed vertically by scattering and geometrical effect in SNSL embedded LEDs. Consequently, the light output power is enhanced by 2.7 times, which we attribute to the improvement in light extraction efficiency due to the multiple Mie scattering of light from the embedded SNSL. The experimental results are verified by simulation using finite difference time domain method (FDTD).


Influence of ionizing radiation and cell density on the kinetics of autocrine destruction and intercellular induction of apoptosis in precancerous cells.
Intercellular induction of apoptosis (IIA) represents a well-defined signaling model by which precancerous cells are selectively eradicated through reactive oxygen/nitrogen species and cytokine signaling from neighbour normal cells. Previously, we demonstrated that the IIA process could be enhanced by exposure of normal cells to very low doses of ionizing radiation as a result of perturbing the intercellular signaling. In this study, we investigate the kinetic behaviour of both autocrine destruction (AD) and IIA as a function of cell density of both precancerous and normal cells using an insert co-culture system and how exposure of normal cells to ionizing radiation influence the kinetics of apoptosis induction in precancerous cells. Increasing the seeding density of transformed cells shifts the kinetics of AD towards earlier times with the response plateauing only at high seeding densities. Likewise, when co-culturing precancerous cells with normal cells, increasing the seeding density of either normal or precancerous cells also shifts the kinetics of IIA response towards earlier times and plateau only at higher seeding densities. Irradiation of normal cells prior to co-culture further enhances the kinetics of IIA response, with the degree of enhancement dependent on the relative cell densities. These results demonstrate the pivotal role of the cell seeding density of normal and precancerous cells in modulating both AD and IIA. These results further support the proposition that ionizing radiation could result in an enhancement in the rate of removal of precancerous cells through the IIA process.


Modelling the impact of a Schistosoma mansoni vaccine and mass drug administration to achieve morbidity control and transmission elimination.
Mass drug administration (MDA) is, and has been, the principal method for the control of the schistosome helminths. Using MDA only is unlikely to eliminate the infection in areas of high transmission and the implementation of other measures such as reduced water contact improved hygiene and sanitation are required. Ideally a vaccine is needed to ensure long term benefits and eliminate the need for repeated drug treatment since infection does not seem to induce lasting protective immunity. Currently, a candidate vaccine is under trial in a baboon animal model, and very encouraging results have been reported. In this paper, we develop an individual-based stochastic model to evaluate the effect of a vaccine with similar properties in humans to those recorded in baboons in achieving the World Health Organization (WHO) goals of morbidity control and elimination as a public health problem in populations living in a variety of transmission settings. MDA and vaccination assuming different durations of protection and coverage levels, alone or in combination, are examined as treatment strategies to reach the WHO goals of the elimination of morbidity and mortality in the coming decade. We find that the efficacy of a vaccine as an adjunct or main control tool will depend critically on a number of factors including the average duration of protection it provides, vaccine efficacy and the baseline prevalence prior to immunization. In low prevalence settings, simulations suggest that the WHO goals can be achieved for all treatment strategies. In moderate prevalence settings, a vaccine that provides 5 years of protection, can achieve both goals within 15 years of treatment. In high prevalence settings, by vaccinating at age 1, 6 and 11 we can achieve the morbidity control with a probability of nearly 0.89 but we cannot achieve elimination as a public health problem goal. A combined vaccination and MDA treatment plan has the greatest chance of achieving the WHO goals in the shorter term.


Fish mercury and surface water sulfate relationships in the Everglades Protection Area.
Few published studies present data on relationships between fish mercury and surface or pore water sulfate concentrations, particularly on an ecosystem-wide basis. Resource managers can use these relationships to identify the sulfate conditions that contain fish with health-concerning total mercury (THg) levels and to evaluate the role of sulfate in methyl-mercury (MeHg) production. In this study, we derived relationships between THg in three fish trophic levels (mosquitofish, sunfish, and age-1 largemouth bass) and surface water sulfate from 1998 to 2009 for multiple stations across the Everglades Protection Area (EPA). Results show the relationship between sulfate and fish THg in each fish type is nonlinear and largely skewed, similar to the relationship between MeHg production and sulfate concentration in peatland sediment pore water identified by other researchers. Peak fish THg levels occurred in ~1 to 12 mg/L sulfate conditions. There was significant variability in the fish THg data, and there were several instances of high-fish THg levels in high-sulfate conditions (>30 mg/L). Health-concerning fish THg levels were present in all surface water sulfate conditions; however, most of these levels occurred in 1-20 mg/L sulfate. The data in this study, including recent studies, show consistent and identifiable areas of high- and low-fish THg across the spectrum of surface water sulfate concentration, therefore, applying an ecosystem-wide sulfur strategy may be an effective management approach as it would significantly reduce MeHg risk in the EPA.


Temporal behavior of the laser pulse for intracavity optical parametric oscillator.
We describe a compact, end-pumped all-solid-state, and Q-switched intracavity optical parametric oscillator (OPO). With this design, the relaxation oscillation type of multi-pulses produced in the intracavity OPO is eliminated. The intracavity OPO is based on periodically poled RbTiOAsO(4) (PPRTA) as the nonlinear material and is pumped by a compact diode-pumped Yb:YAG Q-switched laser at a wavelength of 1.030 microm. The pulse width (FWHM) is about 11 ns at the full pump power for both the signal and idler pulses. Output energies of 384 microJ at idler wavelength and 615 microJ at signal wavelength are obtained. We demonstrate a Q-switched IPOPO oscillator that operates the signal and idler wavelengths without relaxation oscillation type multi-pulses and with fast wavelength tuning ability for both signal and idler wavelength.


Identification of the best complete blood count-based predictors for bladder cancer outcomes in patients undergoing radical cystectomy.
We sought to determine which parsimonious combination of complete blood count (CBC)-based biomarkers most efficiently predicts oncologic outcomes in patients undergoing radical cystectomy (RC) for bladder cancer (BC). Using our institutional RC database (1992-2012), nine CBC-based markers (including both absolute cell counts and ratios) were evaluated based on pre-treatment measurements. The outcome measures were recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Time-dependent receiver-operating characteristics curves were used to characterise each biomarker. The CBC-based biomarkers, along with several clinical predictors, were then considered for inclusion in predictive multivariable Cox models based on the Akaike Information Criterion. Our cohort included 418 patients. Neutrophil-lymphocyte ratio (NLR) was the only biomarker satisfying criteria for inclusion into all models, independently predicting RFS (HR per 1-log unit=1.52, 95% CI=1.17-1.98, P=0.002), CSS (HR=1.47, 95% CI=1.20-1.80, P<0.001), and OS (HR=1.56, 95% CI=1.16-2.10, P=0.004). Haemoglobin was also independently predictive of CSS (HR per 1 g/dl=0.91, 95% CI=0.86-0.95, P<0.001) and OS (HR=0.90, 95% CI=0.88-0.93, P<0.001), but not RFS. Among CBC biomarkers studied, NLR was the most efficient marker for predicting RFS, whereas NLR and haemoglobin were most efficient in predicting CSS and OS. NLR and haemoglobin are promising, cost-effective, independent biomarkers for predicting oncologic BC outcomes following RC. Various CBC-based biomarkers have separately been shown to be predictive of oncologic outcomes in patients undergoing cystectomy for BC. Our study evaluated these biomarkers, and determined that NLR is the best CBC-based biomarker for predicting RFS, whereas NLR and haemoglobin are most efficient for predicting CSS and OS.


Expression of IL-8 during reperfusion of renal allografts is dependent on ischemic time.
Ischemia/reperfusion injury is an inherent consequence of solid organ transplantation that increases tissue inflammation and negatively impacts organ transplant function and survival. This study investigated the expression levels of chemokine and chemokine receptor genes in living versus cadaver donor renal allografts before and after reperfusion. This study involved 39 renal transplant patients (19 cadaveric and 20 living donor). The ischemia biopsy was taken just before graft declamping and the reperfusion biopsy 30 min after declamping. Whole-cell RNA was isolated and chemokine (IL-8, CCL2/MCP-1, CXCL10/IP-10 and CCL5/RANTES) and chemokine receptor (CCR2 and CCR5) expression was tested by quantitative PCR. Just prior to declamping, ischemic cadaveric donor grafts had higher expression of CXCL10/IP-10 but not IL-8 or CCL2/MCP-1 than living donor grafts. IL-8 expression increased 50% from ischemia to reperfusion in living donor grafts but increased more than 13-fold during reperfusion of cadaver donor grafts. Increased total ischemia time induced greater IL-8 expression during reperfusion. MCP-1 expression also increased during reperfusion of living and cadaver donor grafts but differences were not observed between the two groups of grafts. RANTES, CCR2, and CCR5 expression did not change in ischemic vs. reperfusion biopsies. The expression of chemokines directing neutrophil and macrophage recruitment increases during reperfusion of living and cadaveric donor renal allografts. Expression levels of IL-8 correlate with the ischemic time imposed on the renal graft. Early tissue injury may be attenuated by strategies antagonizing chemokines directing the recruitment of neutrophils and macrophages into kidney grafts.


Toxicities of organs at risk in the mediastinal and hilar regions following stereotactic body radiotherapy for centrally located lung tumors.
We investigated tolerable doses to organs at risk (OARs) in the mediastinum and pulmonary hilum following stereotactic body radiotherapy for centrally located lung tumors. Between 2005 and 2012, 381 patients with lung tumors were treated with stereotactic body radiotherapy of 40 to 60 Gy in five fractions. From among these patients, we extracted those who received greater than 25 Gy irradiation to OARs and analyzed dosimetric factors in relation to grade 3 to 5 toxicities. In total, 398 OARs in 133 patients were analyzed, with a median follow-up of 33 (range, 3-87) months. The numbers receiving greater than 25 Gy irradiation to the aorta, vena cava, pulmonary artery, pulmonary vein, bronchus, trachea, heart, and esophagus were 72, 33, 73, 60, 55, 13, 69, and 23, respectively. The corresponding median Dmax 0.5 ml were 43.8, 32.0, 32.2, 29.1, 28.4, 28.7, 41.1, and 21.7 Gy. Of these patients, two developed grade 5 and one grade 3 hemoptysis, and two had grade 3 obstructive pneumonia. Two patients with grade 5 hemoptysis received high doses at the pulmonary artery and bronchus (59.2 and 54.4 Gy, and 61.3 and 59.6 Gy, respectively). No other grade 3 to 5 toxicities occurred. Therapeutic indications and dose-intensity should be carefully determined for patients with central tumors, especially when doses to the pulmonary artery and bronchus in the pulmonary hilum exceed 50 Gy. Tolerable doses for other OARs might, however, be higher than in this study, though longer follow-up is necessary to assess this possibility.


Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.
Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest a possible association of oxidative stress and perhaps CYP pathway with smoking-mediated increased viral load in HIV positive individuals.


Improving heart healthy lifestyles among participants in a Salud para su Corazón promotores model: the Mexican pilot study, 2009-2012.
In Mexico, cardiovascular disease and its risk factors are growing problems and major public health concerns. The objective of this study was to implement cardiovascular health promotion and disease prevention activities of the Salud para su Corazón model in a high-risk, impoverished, urban community in Mexico City. We used a pretest-posttest (baseline to 12-week follow-up) design without a control group. Material from Salud para su Corazón was validated and delivered by promotores (community health workers) to community members from 6 geographic areas. Two validated, self-administered questionnaires that assessed participants' knowledge and behaviors relating to heart health were administered. We used t tests and χ(2) tests to evaluate pretest and posttest differences, by age group (≤60 and >60 years), for participants' 3 heart-healthy habits, 3 types of physical activity, performance skills, and anthropometric and clinical measurements. A total of 452 (82%) adult participants completed the program. Heart-healthy habits from pretest to posttest varied by age group. "Taking action" to modify lifestyle behaviors increased among adults aged 60 or younger from 31.5% to 63.0% (P < .001) and among adults older than 60 from 30.0% to 45.0% (P < .001). Positive responses for cholesterol and fat consumption reduction were seen among participants 60 or younger (P = .03). Among those older than 60, salt reduction and weight control increased (P = .008). Mean blood glucose concentration among adults older than 60 decreased postintervention (P = .03). Significant improvements in some heart-healthy habits were seen among adult participants. The model has potential to improve heart-healthy habits and facilitate behavioral change among high-risk adults.


Consistency in the histological diagnosis of epithelial abnormalities of the cervix uteri.
A group of pathologists, all working in the same laboratory and all applying the same diagnostic criteria to the diagnosis of epithelial abnormalities in the uterine cervix, have studied the consistency with which they have applied these criteria. Epithelial abnormalities were ranked, and a series of sections were diagnosed separately by each pathologist at various times over a number of years. Both consistency and trend were studied by a graphed statistical method and it was shown that not only were there serious inconsistencies in diagnosis between the various pathologists but also between the diagnoses made by individual pathologists studying the same section at various times. It is suggested that this inconsistency in the application of agreed diagnostic criteria is of importance when considering discrepancies between reported series of cervical epithelial abnormalities and that the type of study described is of value in assessing both variations in diagnostic criteria between different laboratories and the consistency of pathologists in training. Any slight change in the application of diagnostic criteria for any individual pathologist with the passage of time may also be detected by this technique.


Neurophysiological Processing of an Emotional Task is Sensitive to Time-of-Day.
Previous work from our laboratory has shown that a measure of attention to emotionally-charged stimuli, the late positive potential (LPP) event related potential (ERP), distinguished neutral from emotional pictures on a baseline day, but not after sleep deprivation. Here we sought to extend these findings and address the uncertainty about the effect of time-of-day on emotion processing by testing a morning group (8:00-10:00 a.m., n = 30) and an evening group (8:00-10:00 p.m., n = 30). We also examined the extent of diurnal changes in cortisol related to the emotion processing task. Results from this study mirrored those found after one night of sleep deprivation. Compared to the morning group, the LPP generated by the evening group (who had a greater homeostatic sleep drive) did not distinguish neutral from emotionally-charged stimuli. New to this study, we also found that there was a time-of-day effect on positive, but not negative pictures. While, as expected, cortisol levels were higher in the morning relative to the evening group, there was no relationship between cortisol and the LPP ERP emotion measure. In addition, neither time-of-day preference nor sleep quality was related to the LPP measure. These findings show that, similar to what occurs after sleep deprivation, increased sleep pressure throughout the day interferes with attention processing to emotional stimuli.


Simultaneous prediction of protein secondary structure and transmembrane spans.
Prediction of transmembrane spans and secondary structure from the protein sequence is generally the first step in the structural characterization of (membrane) proteins. Preference of a stretch of amino acids in a protein to form secondary structure and being placed in the membrane are correlated. Nevertheless, current methods predict either secondary structure or individual transmembrane states. We introduce a method that simultaneously predicts the secondary structure and transmembrane spans from the protein sequence. This approach not only eliminates the necessity to create a consensus prediction from possibly contradicting outputs of several predictors but bears the potential to predict conformational switches, i.e., sequence regions that have a high probability to change for example from a coil conformation in solution to an α-helical transmembrane state. An artificial neural network was trained on databases of 177 membrane proteins and 6048 soluble proteins. The output is a 3 × 3 dimensional probability matrix for each residue in the sequence that combines three secondary structure types (helix, strand, coil) and three environment types (membrane core, interface, solution). The prediction accuracies are 70.3% for nine possible states, 73.2% for three-state secondary structure prediction, and 94.8% for three-state transmembrane span prediction. These accuracies are comparable to state-of-the-art predictors of secondary structure (e.g., Psipred) or transmembrane placement (e.g., OCTOPUS). The method is available as web server and for download at www.meilerlab.org.


Randomized Trial of Reduced-Nicotine Standards for Cigarettes.
The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.).


Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy.
Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography-mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome.


Use of bondable reinforcement fiber for post and core build-up in an endodontically treated tooth: maximizing strength and aesthetics.
Post/core placements in endodontically treated teeth are utilized as a means to retain a core or foundation for the final restoration. The question of whether a post placed in an endodontically treated tooth actually increases its strength is still being debated. Prefabricated metal posts have been used in most clinical situations in the past. Due to the reflection of metal through the remaining tooth structure, these posts present some concerns involving aesthetics. To address these concerns, this article presents a method of post fabrication using a bondable reinforcement fiber as the dowel post material. The learning objective of this article is to introduce this new post fabrication technique along with the materials utilized. A clinical case is used to present the technique.


Unionisation and injury risk in construction: a replication study.
To replicate, in a more recent time period, a previous cross-sectional study to estimate the association between unionisation and the risk of workers' compensation injury claims. The sampling frame was workers' compensation company account records in the industrial, commercial and institutional construction sector in the province of Ontario, Canada, 2012-2018. Company unionisation status was determined through linkage with records of unionised contractors. Outcomes were cumulative counts of workers' compensation injury claims, aggregated to company business. Risk ratios were estimated with multivariable negative binomial regression models. Models were also fit separately to lost-time claims stratified by company size. Business unionisation was associated with a lower lost-time claim incidence (crude risk ratio, CRR=0.69, 95% CI 0.65 to 0.74); adjusted risk ratio, ARR=0.75, 95% CI 0.71 to 0.80). In subgroup analyses, the magnitude of the ARR declined as company size decreased and was not statistically significant for the smallest-sized companies of ≤4 full-time equivalent employees. Unionisation was associated (positively) with the incidence of no-lost-time claims in a crude model, but not in an adjusted one (CRR=1.80, 95% CI 1.71 to 1.89; ARR=1.04, 95% CI 0.98 to 1.09). Company unionisation was associated with a lower risk of lost-time workers' compensation injury claims, corroborating a similar study from an earlier time period. The protective effect of unionisation declined as company size decreased. In contrast to the previous study, a positive relationship between company unionisation and no-lost-time claim incidence was not found, due in part to a methodological refinement.


Grey seals use anthropogenic signals from acoustic tags to locate fish: evidence from a simulated foraging task.
Anthropogenic noise can have negative effects on animal behaviour and physiology. However, noise is often introduced systematically and potentially provides information for navigation or prey detection. Here, we show that grey seals (Halichoerus grypus) learn to use sounds from acoustic fish tags as an indicator of food location. In 20 randomized trials each, 10 grey seals individually explored 20 foraging boxes, with one box containing a tagged fish, one containing an untagged fish and all other boxes being empty. The tagged box was found after significantly fewer non-tag box visits across trials, and seals revisited boxes containing the tag more often than any other box. The time and number of boxes needed to find both fish decreased significantly throughout consecutive trials. Two additional controls were conducted to investigate the role of the acoustic signal: (i) tags were placed in one box, with no fish present in any boxes and (ii) additional pieces of fish, inaccessible to the seal, were placed in the previously empty 18 boxes, making possible alternative chemosensory cues less reliable. During these controls, the acoustically tagged box was generally found significantly faster than the control box. Our results show that animals learn to use information provided by anthropogenic signals to enhance foraging success.


Clonal markers in the study of the origin and growth of human atherosclerotic lesions.
The X-linked enzyme, glucose-6-phosphate dehydrogenase (G-6-PD) was used as a cellular marker to study the clonal characteristics of human atherosclerotic lesions from females heterozygous for G-6-PD isoenzymes. Portions of uninvolved aortic wall contained both isoenzyme types (A and B), and their isoenzyme patterns were used to establish criteria for polyclonal lesions. Portions of uterine leiomyomas contained predominantly one isoenzyme type (either all A or all B) and their isoenzyme patterns were used to establish criteria for monoclonal lesions. These techniques were used to address three questions concerning atherogenesis. First, evidence for the monoclonal origin of fibrous-capped plaques was provided by the findings that small plaques had G-6-PD isoenzyme distributions similar to those of leimyomas; that in large plaques with multiple portions assayed for G-6-PD, a large proportion (25 of 26, 96%) of plaques had monoclonal characteristics; and that multiple monoclonal portions were present in the same plaque. Second, the role of the fatty streak as a precursor of fibrous plaques was supported by the demonstration that a proportion (11 of 66, 16.7%) of fatty streaks contained isoenzyme patterns intermediate between those of polyclonal uninvolved aortic wall and monoclonal leiomyomas. Increased cellularity of fatty streaks correlated with increased deviation of isoenzyme pattern toward monoclonality. Third, the assay of portions of both small and large plaques provided no evidence for clonal selection as plaques increase in size.


The REFLECT statement: reporting guidelines for Randomized Controlled Trials in livestock and food safety: explanation and elaboration.
Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest that similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996, with a revised edition published in 2001. The CONSORT statement consists of a 22-item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies; the use of deliberate challenge models in some trials and the common use of non-clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.


Delayed emergence of a global temperature response after emission mitigation.
A major step towards achieving the goals of the Paris agreement would be a measurable change in the evolution of global warming in response to mitigation of anthropogenic emissions. The inertia and internal variability of the climate system, however, will delay the emergence of a discernible response even to strong, sustained mitigation. Here, we investigate when we could expect a significant change in the evolution of global mean surface temperature after strong mitigation of individual climate forcers. Anthropogenic CO2 has the highest potential for a rapidly measurable influence, combined with long term benefits, but the required mitigation is very strong. Black Carbon (BC) mitigation could be rapidly discernible, but has a low net gain in the longer term. Methane mitigation combines rapid effects on surface temperature with long term effects. For other gases or aerosols, even fully removing anthropogenic emissions is unlikely to have a discernible impact before mid-century.


Interaction of single- and double-stranded DNA with multilayer MXene by fluorescence spectroscopy and molecular dynamics simulations.
The integration of nucleic acids with nanomaterials has attracted great attention from various research communities in search of new nanoscale tools for a range of applications, from electronics to biomedical uses. MXenes are a new class of multielement 2D materials baring exciting properties mostly directed to energy-related fields. These advanced materials are now beginning to enter the biomedical field given their biocompatibility, hydrophilicity and near-infrared absorption. Herein, we elucidate the interaction of MXene Ti3C2T x with fluorophore-tagged DNA by fluorescence measurements and molecular dynamics simulations. The system showed potential for biosensing with unequivocal detection at picomole levels and single-base discrimination. We found that this material possesses a kinetically unique entrapment/release behavior, with potential implications in time-controlled biomolecule delivery. Our findings present MXenes as platforms for binding nucleic acids, contributing to their potential for hybridization-based biosensing and related bio-applications.


Role of cystathionine beta-lyase in catabolism of amino acids to sulfur volatiles by genetic variants of Lactobacillus helveticus CNRZ 32.
Catabolism of sulfur-containing amino acids plays an important role in the development of cheese flavor. During ripening, cystathionine beta-lyase (CBL) is believed to contribute to the formation of volatile sulfur compounds (VSCs) such as methanethiol and dimethyl disulfide. However, the role of CBL in the generation of VSCs from the catabolism of specific sulfur-containing amino acids is not well characterized. The objective of this study was to investigate the role of CBL in VSC formation by Lactobacillus helveticus CNRZ 32 using genetic variants of L. helveticus CNRZ 32 including the CBL-null mutant, complementation of the CBL-null mutant, and the CBL overexpression mutant. The formation of VSCs from methionine, cystathionine, and cysteine was determined in a model system using gas chromatography-mass spectrometry with solid-phase microextraction. With methionine as a substrate, CBL overexpression resulted in higher VSC production than that of wild-type L. helveticus CNRZ 32 or the CBL-null mutant. However, there were no differences in VSC production between the wild type and the CBL-null mutant. With cystathionine, methanethiol production was detected from the CBL overexpression variant and complementation of the CBL-null mutant, implying that CBL may be involved in the conversion of cystathionine to methanethiol. With cysteine, no differences in VSC formation were observed between the wild type and genetic variants, indicating that CBL does not contribute to the conversion of cysteine.


Characterization of the Humoral Immune Response Induced after Infection with Atypical Porcine Pestivirus (APPV).
Atypical porcine pestivirus (APPV) is a widely distributed pathogen causing congenital tremor (CT) in piglets. So far, no data are available regarding the humoral immune response against APPV. In this study, piglets and their sows from an affected herd were tested longitudinally for viral genome and antibodies. APPV genome was detected in the majority of the piglets (14/15) from CT affected litters. Transient infection of gilts was observed. Kinetics of Erns- and E2-specific antibodies and their neutralizing capacity were determined by recently (Erns) and newly (E2) developed antibody ELISAs and virus neutralization assays. Putative maternally derived antibodies (MDA) were detected in most piglets, but displayed only low to moderate neutralizing capacity (ND50 ≤ 112). Horizontal APPV transmission occurred when uninfected and infected piglets were mingled on the flat deck. Horizontally infected piglets were clinically inapparent and showed only transient viremia with subsequently consistently high E2 antibody levels. For piglets from CT affected litters, significantly lower neutralizing antibody titers were observed. Results indicate that E2 represents the main target of neutralizing antibodies. Characterization of the humoral immune response against APPV will help to provide valuable serological diagnosis, to understand the epidemiology of this novel pathogen, and to implement tailored prevention strategies.


Use of online clinical videos for clinical skills training for medical students: benefits and challenges.
Multimedia learning has been shown effective in clinical skills training. Yet, use of technology presents both opportunities and challenges to learners. The present study investigated student use and perceptions of online clinical videos for learning clinical skills and in preparing for OSCE (Objective Structured Clinical Examination). This study aims to inform us how to make more effective us of these resources. A mixed-methods study was conducted for this study. A 30-items questionnaire was administered to investigate student use and perceptions of OSCE videos. Year 3 and 4 students from 34 Korean medical schools who had access to OSCE videos participated in the online survey. Additionally, a semi-structured interview of a group of Year 3 medical students was conducted for an in-depth understanding of student experience with OSCE videos. 411 students from 31 medical schools returned the questionnaires; a majority of them found OSCE videos effective for their learning of clinical skills and in preparing for OSCE. The number of OSCE videos that the students viewed was moderately associated with their self-efficacy and preparedness for OSCE (p < 0.05). One-thirds of those surveyed accessed the video clips using mobile devices; they agreed more with the statement that it was convenient to access the video clips than their peers who accessed the videos using computers (p < 0.05). Still, students reported lack of integration into the curriculum and lack of interaction as barriers to more effective use of OSCE videos. The present study confirms the overall positive impact of OSCE videos on student learning of clinical skills. Having faculty integrate these learning resources into their teaching, integrating interactive tools into this e-learning environment to foster interactions, and using mobile devices for convenient access are recommended to help students make more effective use of these resources.


Experimental techniques in making multicolor white light reconstructed holograms.
Because of the characteristics of the available white light sources, lasers and photographic emulsions, as well as the environmental condition of a laboratory, many practical problems are often encountered in making high quality multicolor holograms reconstructed in white light. The nature of the difficulties is discussed. Techniques useful to the solutions of these problems are presented, such as increasing the coherence length of a laser with little sacrifice in power, improving the signal-to-noise ratio in the reconstruction, controlling the shrinkage of the emulsion to eliminate color shift, and increasing the speed of Kodak 649F emulsion.


Impact of carbon nanotubes and graphene on immune cells.
It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine.


Multi-dimensional clinical phenotyping of a national cohort of adult cystic fibrosis patients.
Cystic Fibrosis (CF) is a multi-systemic disorder resulting from genetic variation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene which can result in bronchiectasis, chronic sinusitis, pancreatic malabsorption, cholestatic liver disease and distal intestinal obstructive syndrome. This study generates multi-dimensional clinical phenotypes that capture the complexity and spectrum of the disease manifestations seen in adult CF patients using statistically robust techniques. Pre-transplant clinical data from adult (age ≥18 years) CF patients (n = 992) seen in six regionally distinct US CF centers between 1/1/2014 and 6/30/2015 were included. Demographic, spirometry, nutritional, microbiological and therapy data were used to generate clusters using the Random Forests statistical-learning and Partitioning around Medoids (PAM) clustering algorithms. Five commonly measured demographic, physiological and nutritional parameters were needed to create the final phenotypes that are highly similar to a regionally matched group of patients from the CF Foundation Patient Registry RESULTS: This approach identified high-risk phenotypes with expected characteristics including high rates of pancreatic insufficiency, diabetes and Pseudomonas aeruginosa colonization. It also identified unexpected populations including a) a male-dominated, well-nourished group with good lung function with a high prevalence of severe genotypes (i.e. 60% subjects had two minimal function CFTR variations), b) and an older, "survivor" phenotype that had high rates of chronic P. aeruginosa infection. This study identified recognizable phenotypes that capture the clinical complexity in a statistically robust manner and which may aide in the identification of specific genetic and environmental factors responsible for these disease manifestation patterns.