Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.
To standardize the use of phototherapy consistent with the American Academy of Pediatrics clinical practice guideline for the management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Relevant literature was reviewed. Phototherapy devices currently marketed in the United States that incorporate fluorescent, halogen, fiber-optic, or blue light-emitting diode light sources were assessed in the laboratory. The efficacy of phototherapy units varies widely because of differences in light source and configuration. The following characteristics of a device contribute to its effectiveness: (1) emission of light in the blue-to-green range that overlaps the in vivo plasma bilirubin absorption spectrum (~460-490 nm); (2) irradiance of at least 30 μW · cm(-2) · nm(-1) (confirmed with an appropriate irradiance meter calibrated over the appropriate wavelength range); (3) illumination of maximal body surface; and (4) demonstration of a decrease in total bilirubin concentrations during the first 4 to 6 hours of exposure. RECOMMENDATIONS (SEE APPENDIX FOR GRADING DEFINITION): The intensity and spectral output of phototherapy devices is useful in predicting potential effectiveness in treating hyperbilirubinemia (group B recommendation). Clinical effectiveness should be evaluated before and monitored during use (group B recommendation). Blocking the light source or reducing exposed body surface should be avoided (group B recommendation). Standardization of irradiance meters, improvements in device design, and lower-upper limits of light intensity for phototherapy units merit further study. Comparing the in vivo performance of devices is not practical, in general, and alternative procedures need to be explored.


Inactivation of Staphylococcus aureus and Escherichia coli O157:H7 on fresh kashar cheese with pulsed ultraviolet light.
Pulsed ultraviolet light is a potential postprocessing decontamination method which is able to reduce pathogens on solid food surfaces. Cheese surfaces may become easily contaminated with pathogens due to improper handling or contact with unhygienic surfaces during or after processing. In this study, the effects of pulsed ultraviolet light on Staphylococcus aureus and Escherichia coli O157:H7 on fresh kashar cheese were investigated. Pulsed ultraviolet light was applied to kashar cheese for different times (5, 15, 30, 45, 60 s) at 5, 8, and 13 cm from the quartz window in a pulsed ultraviolet light system. Based on the inactivation level, time, and visual evaluation, the most favorable treatment was determined as the 45 s-13 cm treatment (∼44 J/cm2). This treatment yielded about 1.62 and 3.02 log10 reductions (cfu/cm2) for S. aureus and E. coli O157:H7, respectively, while did not alter (p>0.05) the pH, lipid oxidation, and moisture content of kashar cheese, except the color parameters. When 0.5 cm thick kashar cheese was treated with pulsed ultraviolet light at a distance of 5 cm from the quartz window, the highest energy transmittance was found to be about 9.16%. These findings demonstrate that pulsed ultraviolet light has the potential for postprocessing decontamination of semi-hard cheese surfaces.


Tracheobronchial smooth muscle atrophy and separation.
We report a case series involving 4 patients with chronic obstructive pulmonary disease who were on an appropriate medical regimen including a high dose of inhaled corticosteroids (ICS). During bronchoscopy, patients were found to have an excessive dynamic collapse of the posterior wall and its separation from the ends of the adjacent cartilaginous rings. This was causing a near-total occlusion of the tracheal and bronchial lumen during exhalation, thereby presenting with an obstructive pattern on the pulmonary functions. We suspect that this was caused by the atrophy of the smooth muscles of the tracheobronchial wall. We reviewed the literature to explore the mechanisms causing atrophy of the bronchial smooth muscle, focusing on the potential role of long-term ICS use.


Measurement of antibodies to the Borrelia burgdorferi flagellum improves serodiagnosis in Lyme disease.
The isolation of Borrelia burgdorferi flagella and an enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin G (IgG) and IgM to the B. burgdorferi flagellum are described. The diagnostic performance of the flagellum ELISA for serodiagnosis of Lyme disease was compared with the performance of a traditional whole cell B. burgdorferi sonic extract ELISA. We examined sera and cerebrospinal fluid (CSF) from 56 patients with lymphocytic meningoradiculitis (Bannwarth's syndrome), the most frequent secondary-stage manifestation of Lyme disease in Europe. Two hundred healthy individuals and patients with aseptic meningitis, encephalitis, Guillain-Barré syndrome, and syphilis served as controls. The flagellum ELISA was significantly more sensitive than the sonic extract ELISA. The diagnostic sensitivities were increased from 41.1 to 76.8% (P less than 0.01) for IgG and from 35.7 to 67.9% (P less than 0.05) for IgM detection in serum. The increase in sensitivity was most pronounced in patients with a short duration of disease (less than 20 days after onset). The diagnostic specificity increased for IgG detection but was almost unaltered for IgM. The flagellum ELISA did not improve the diagnostic sensitivity of measuring antibodies to borreliae in CSF, most likely owing to the low level of unspecific antibodies in CSF compared with serum. The cross-reactivity of sera and CSF from patients with syphilis decreased significantly. The flagellum antigen of B. burgdorferi shows no strain variation, is easy to purify in sufficient quantity, and is therefore a suitable reference antigen for routine serodiagnosis of Lyme disease.


On the catalase-peroxidase gene, katG, of Mycobacterium leprae and the implications for treatment of leprosy with isoniazid.
The toxicity of the potent tuberculocidal agent, isoniazid, is mediated by the heme-containing enzyme, catalase-peroxidase, encoded by the katG gene. Although isoniazid has been used for the treatment of leprosy, it is shown here that the katG gene of Mycobacterium leprae is a pseudogene, which has probably been inactivated by multiple mutations. Inactive genes were detected by the polymerase chain reaction in several isolates of M. leprae, of different geographical origins, and attempts to complement an isoniazid-resistant strain of Mycobacterium smegmatis with the katG pseudogene were unsuccessful. Isoniazid is thus likely to be of no therapeutic benefit to leprosy patients.


Bacterial carbon use plasticity, phylogenetic diversity and the priming of soil organic matter.
Microorganisms perform most decomposition on Earth, mediating carbon (C) loss from ecosystems, and thereby influencing climate. Yet, how variation in the identity and composition of microbial communities influences ecosystem C balance is far from clear. Using quantitative stable isotope probing of DNA, we show how individual bacterial taxa influence soil C cycling following the addition of labile C (glucose). Specifically, we show that increased decomposition of soil C in response to added glucose (positive priming) occurs as a phylogenetically diverse group of taxa, accounting for a large proportion of the bacterial community, shift toward additional soil C use for growth. Our findings suggest that many microbial taxa exhibit C use plasticity, as most taxa altered their use of glucose and soil organic matter depending upon environmental conditions. In contrast, bacteria that exhibit other responses to glucose (reduced growth or reliance on glucose for additional growth) clustered strongly by phylogeny. These results suggest that positive priming is likely the prototypical response of bacteria to sustained labile C addition, consistent with the widespread occurrence of the positive priming effect in nature.


Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium.
Infusion of epinephrine-activated human sickle erythrocytes (SS RBCs) into nude mice promotes both SS RBC and murine leukocyte adhesion to vascular endothelium in vivo. We hypothesized that interaction of epinephrine-stimulated SS RBCs with leukocytes leads to activation of leukocytes, which then adhere to endothelial cells (ECs). In exploring the underlying molecular mechanisms, we have found that coincubation in vitro of epinephrine-treated SS RBCs with human peripheral blood mononuclear cells (PBMCs) results in robust adhesion of PBMCs to ECs. Sham-treated SS RBCs had a similar but less pronounced effect, whereas neither sham- nor epinephrine-treated normal RBCs activated PBMC adhesion. PBMC activation was induced via at least 2 RBC adhesion receptors, LW and CD44. In response to SS RBCs, leukocyte CD44 and beta2 integrins mediated PBMC adhesion to ECs, a process that involved endothelial E-selectin and fibronectin. SS RBCs activated adhesion of both PBMC populations, lymphocytes and monocytes. Thus, our findings reveal a novel mechanism that may contribute to the pathogenesis of vaso-occlusion in sickle cell disease, in which SS RBCs act via LW and CD44 to stimulate leukocyte adhesion to endothelium, and suggest that RBC LW and CD44 may serve as potential targets for antiadhesive therapy designed to prevent vaso-occlusion.


New Insights into the State Trapping of UV-Excited Thymine.
After UV excitation, gas phase thymine returns to a ground state in 5 to 7 ps, showing multiple time constants. There is no consensus on the assignment of these processes, with a dispute between models claiming that thymine is trapped either in the first (S₁) or in the second (S₂) excited states. In the present study, a nonadiabatic dynamics simulation of thymine is performed on the basis of ADC(2) surfaces, to understand the role of dynamic electron correlation on the deactivation pathways. The results show that trapping in S₂ is strongly reduced in comparison to previous simulations considering only non-dynamic electron correlation on CASSCF surfaces. The reason for the difference is traced back to the energetic cost for formation of a CO π bond in S₂.


Extracorporeal Membrane Oxygenation (ECMO) for Lung Injury in Severe Acute Respiratory Distress Syndrome (ARDS): Review of the Literature.
Despite advances in mechanical ventilation, severe acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality rates ranging from 26% to 58%. Extracorporeal membrane oxygenation (ECMO) is a modified cardiopulmonary bypass circuit that serves as an artificial membrane lung and blood pump to provide gas exchange and systemic perfusion for patients when their own heart and lungs are unable to function adequately. ECMO is a complex network that provides oxygenation and ventilation and allows the lungs to rest and recover from respiratory failure while minimizing iatrogenic ventilator-induced lung injury. In critical care settings, ECMO is proven to improve survival rates and outcomes in patients with severe ARDS. This review defines severe ARDS; describes the ECMO circuit; and discusses recent research, optimal use of the ECMO circuit, limitations of therapy including potential complications, economic impact, and logistical factors; and discusses future research considerations.


Sex practices and awareness of Ebola virus disease among male survivors and their partners in Guinea.
Towards the end of the 2013-2016 West African outbreak, sexually-transmitted Ebola virus re-emerged from Ebola virus disease (EVD) survivors in all three hardest hit countries. We explore sex practices and awareness of the risk of Ebola virus transmission among EVD survivors and their partners. In this cross-sectional study, we recruited a convenience sample of study participants aged >15 years who were male EVD survivors, their sexual partners and a comparison group. We administered a questionnaire to all respondents, estimated self-reported sexual practices and risk awareness and conducted in-depth interviews. We recruited 234 EVD survivors, 256 sexual partners of survivors and 65 individuals in the comparison group from five prefectures in Guinea. The prevalence of safe sexual behaviour (regular condom use or sexual abstinence >12 months) and regular condom use in EVD survivors was 38% (95% CI 31% to 44%) and 21% (95% CI 16% to 27%), respectively. Among partners, these prevalences were lower (11%, 95% CI 7% to 15% and 9%, 95% CI 5% to 12%, respectively). EVD survivors were more than five times as likely to engage in safe sexual behaviour compared with the comparison group (aOR 5.59, 95% CI 2.36 to 13.2). One-hundred and thirty one EVD survivors (57%) and 94 partners (37%) were aware of the risk of Ebola virus re-emergence associated with having unsafe sex. Partners who reported not being informed by their husband/boyfriend (EVD survivor) were more likely to be unaware of this risk (aOR 20.5, 95% CI 8.92 to 47.4). We disclose here a need to improve knowledge of the disease and close the gap between knowledge and practice found in EVD survivors and their partners. Current and future survivors' follow-up programmes should include partners and be more effective at communicating sex-related risks. Community-level fears and attitudes that enable stigmatisation should be addressed. Safe sex interventions targeting EVD survivors and their partners should be prioritised.


Pseudomonas aeruginosa interacts with epithelial cells rapidly forming aggregates that are internalized by a Lyn-dependent mechanism.
Growing evidence is pointing to the importance of multicellular bacterial structures in the interaction of pathogenic bacteria with their host. Transition from planktonic to host cell-associated multicellular structures is an essential infection step that has not been described for the opportunistic human pathogen Pseudomonas aeruginosa. In this study we show that P. aeruginosa interacts with the surface of epithelial cells mainly forming aggregates. Dynamics of aggregate formation typically follow a sigmoidal curve. First, a single bacterium attaches at cell-cell junctions. This is followed by rapid recruitment of free-swimming bacteria and association of bacterial cells resulting in the formation of an aggregate on the order of minutes. Aggregates are associated with phosphatidylinositol 3,4,5-trisphosphate (PIP3)-enriched host cell membrane protrusions. We further show that aggregates can be rapidly internalized into epithelial cells. Lyn, a member of the Src family tyrosine kinases previously implicated in P. aeruginosa infection, mediates both PIP3-enriched protrusion formation and aggregate internalization. Our results establish the first framework of principles that define P. aeruginosa transition to multicellular structures during interaction with host cells.


A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype.
Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the importance of identifying these patients. Despite the large number of samples analyzed and their clear association with unifying biological programs and clinical features, single-driver mutations could not be identified and patients are heterogeneous with regard to currently used clinical markers. We therefore set out to define the regulatory mechanisms underlying the distinct gene expression profiles using a network-based approach involving multiple molecular modalities such as gene expression, methylation levels and microRNA (miR) expression. The miR-200 family presented as the most powerful determinant of CMS4-specific gene expression, tuning the majority of genes differentially expressed in the poor prognosis subtype, including genes associated with the epithelial-mesenchymal transition program. Furthermore, our data show that two epigenetic marks, namely the methylation of the two miR-200 promoter regions, can identify tumors belonging to the mesenchymal subtype and is predictive of disease-free survival in CRC patients. Importantly, epigenetic silencing of the miR-200 family is also detected in epithelial CRC cell lines that belong to the mesenchymal CMS. We thus show that determining regulatory networks is a powerful strategy to define drivers of distinct cancer subtypes, which possess the ability to identify subtype affiliation and to shed light on biological behavior.


Hair cortisol and cognitive performance in working age adults.
It has been hypothesized that prolonged exposure to high cortisol levels results in cognitive impairment. However, previous research into the relationship between cortisol and cognition has produced mixed results, most likely due to difficulties achieving valid estimates of long-term cortisol exposure based on salivary or plasma cortisol assessments at a single time point. Furthermore, there has been little research on the cognitive effects of long-term cortisol exposure in working-age adults. In the present study, hair samples were collected from 246 nurses (89.8% female) aged from 21 to 62 (M=42.0, SD=11.2). Hair cortisol concentrations (HCC) in the proximal 3-cm hair segment were analyzed providing an estimate of integrated cortisol secretion over the 3 month-period prior to hair sampling. Cognition was measured using a battery of 15 neuropsychological tests, measuring core dimensions of memory, inductive reasoning, processing speed, crystalized intelligence and major aspects of executive functioning. HCC was not significantly related to any of the cognitive abilities measured, either before or after controlling for potential moderators such as age, sex, education, health, well-being, work ability and burnout. Tests for nonlinear relationships also yielded non-significant results. Thus, despite the study being well powered, long term cortisol exposure did not appear to be related to cognitive performance in this sample of working-age adults, suggesting that long term cortisol exposure may be less relevant to cognition in younger and middle-aged adults than was previously thought.


Investigating public perceptions of carbon dioxide utilisation (CDU) technology: a mixed methods study.
Carbon dioxide utilisation (CDU) technologies hold promise for helping to limit atmospheric releases of CO2 while generating saleable products. However, while there is growing investment in the research and development required to bring CDU to the market, to date there has been very little systematic research into public perceptions of the technology. The current research reports upon the findings of a series of six qualitative focus groups (and an associated questionnaire) held with members of the UK public in order to discuss the perceived benefits and risks of CDU technology. The findings reveal that public awareness of CDU is currently very low and that there is a desire to learn more about the technology. While our participants did, on average, appear to develop an overall positive attitude towards CDU, this attitude was tentative and was associated with a number of caveats. The implications for the findings in terms of the development of communication and broader strategies of public engagements are outlined.


Psychological effects of intensification of diabetic control.
We studied the psychological effects of a program of intensification of glycemic control, using three different insulin regimens: (1) twice-daily regular and lente insulin; (2) multiple preprandial doses of regular insulin coupled with long-acting ultralente insulin; and (3) continuous subcutaneous insulin infusion (CSII). Ten patients used each of the regimens for periods of 2 mo. Patients monitored blood glucose 4-7 times daily. Using the Hopkins Symptom Checklist, there were significant reductions in depression, interpersonal sensitivity, and anxiety during all three treatment programs. Self-concept scores were more positive following CSII therapy. Positive self-concept ratings were correlated with positive attitudes about diabetes, medical care, persons with diabetes, and current diabetes regimens. After all subjects had experienced CSII, self-concept was positively related to attitudes regarding the insulin pump. Patients reporting more positive attitudes toward their current diabetes regimens had lower glycosylated hemoglobin levels. Thus, there were no adverse psychological effects of blood glucose monitoring, intensification of therapy, or use of infusion pumps by the parameters measured.


Sorafenib in advanced hepatocellular carcinoma.
No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.)


An investigation of barriers and enablers to advanced nursing roles in Australian general practice.
Over the past decade, there has been substantial increase in nurses' roles in primary health care, particularly in general practice settings. Simultaneously, there has been an expansion of advanced roles for nurses across a range of clinical environments. This paper draws upon findings from a study that sought to develop a framework to support development of advanced nursing roles in general practice. It presents findings from one part of that study that explored barriers and facilitators to the development of these roles. Twenty-three key leaders from nursing, general practice and professional organisations participated in semi-structured interviews. Data were analysed using thematic analysis. A range of factors was identified as key to developing advanced roles in general practice. These included increasing awareness and attractiveness of practice nursing, health reform activities, practice limitations, education and professional development. Understanding complex systems and workforce issues is required to promote active intervention that can facilitate development of advanced nursing roles in Australian general practice.


Adult pelvic sarcomas: a heterogeneous collection of sarcomas?
Introduction. Adult pelvic soft tissue sarcomas are a rare group of heterogeneous malignancies. These sarcomas differ from extremity and trunk soft tissue sarcomas in presentation, characteristics and response to treatment.Methods. A retrospective analysis of patient and tumor characteristics, treatment and prognosis and prognostic factors was performed.Results. Between 1977 and 1997, a total of 33 adult patients with soft tissue sarcomas involving the pelvis but excluding uterine leiomyosarcoma were identified. Leiomyosarcomas (18), including six GIST, and rhabdomyosarcomas (eight) were the most commonly seen tumors. At first presentation, nine patients already had metastases. The mean follow-up was 52 months (1-200). Recurrences developed in 15 of the 24 cases (63%) with tumors without metastases at first presentation; in six (25%) recurrence was locally only, in nine distant metastases occurred. The nine patients with metastatic disease at first presentation died of the disease, while eight of the 24 patients with localized disease at presentation died. One patient died of an unrelated cause, four were alive with disease, and 11 patients were alive and free of disease. The only identifiable prognostic factor of disease-free interval and overall survival was histological grade.Conclusion. Soft tissue sarcomas of the pelvis appear to be associated with increased rate of metastasis at the time of diagnosis and higher rates of local recurrence. In this study, multi-modality treatment for most primary tumors did not show a significant benefit in recurrence rate, DFI and OST, when compared to single modality approach. Although the number of patients in this study is small, and different types of sarcomas were studied, the only identifiable predictor for survival was low histological grade of the tumors. The differences of this heterogeneous group of pelvic sarcomas with retroperitoneal, trunk and extremity sarcomas should be taken into consideration in the management of these sarcomas.


Explaining paranoia: cognitive and social processes in the occurrence of extreme mistrust.
Paranoia-incorrectly thinking that others are deliberating trying to harm you-causes distress, undermines social interactions and leads to withdrawal. It presents across multiple psychiatric diagnoses. The primary aim was to determine the extent that cognitive and social processes may explain paranoia. The secondary aim was to identify explanatory factors that distinguished paranoia and social anxiety. 10 382 UK adults, quota sampled to match the population for age, gender, ethnicity, income and region, participated in a non-probability survey. All participants completed a paranoia measure and assessments of cognitive and social processes. Structural equation modelling was conducted. 2586 (24.9%) participants described being mistrustful of other people. 1756 (16.9%) participants wanted help to trust more. 66.7% of variance in paranoia was explained by a model comprising (in descending order of importance): within-situation defence behaviours, negative images, negative self-beliefs, discrimination, dissociation, aberrant salience, anxiety sensitivity, agoraphobic distress, worry, less social support, agoraphobic avoidance, less analytical reasoning and alcohol use. All explanatory factors were associated with paranoia and social anxiety. Ten factors were more closely associated with paranoia than social anxiety, including discrimination, hallucinations, negative images, aberrant salience and alcohol use. Nine factors were more closely associated with social anxiety, including less positive self-belief, an external locus of control, worry and less analytical reasoning. Multiple causes are likely to be involved in paranoia. Cognitive and social processes may explain a high degree of paranoia. Multiple clear targets for intervention to reduce paranoia are identified.


Mumps outbreak in a highly vaccinated school population. Evidence for large-scale vaccination failure.
To describe an outbreak and to identify risk factors for mumps occurring in a highly vaccinated high school population. (Note: Highly vaccinated means a population in which more than 95% have been vaccinated.) Survey and cohort study of 307 (97%) of 318 students. Mumps was defined as an illness with 2 or more days of parotid swelling. Serologic confirmation of infection was obtained in eight cases, seven of which were evaluated for presence of IgM antibody using immunofluorescent antibodies. Vaccination records were verified for 297 (97%) students. Between October 3 and November 23, 1990, clinical mumps developed in 54 students (attack rate, 18%), 53 of whom had been vaccinated. Most cases (40 [77%] of 52) occurred 12 to 20 days after a school-wide pep rally. Immunofluorescent antibody testing of all seven specimens demonstrated IgM antibody to mumps. Risk factors for clinical mumps identified in multivariate analyses included female gender (odds ratio, 3.0; 95% confidence interval, 1.6 to 5.7) and source of vaccination other than the local public health clinic (students vaccinated by private providers [odds ratio, 3.0; 95% confidence interval, 1.3 to 5.2] or in other districts [odds ratio, 2.4; 95% confidence interval, 1.1 to 5.3]). The overall attack rate is the highest reported to date (and to our knowledge) for a population demonstrating virtually complete mumps vaccine coverage. Even verified documentation of vaccination may not be an accurate indicator of an individual's protection against mumps. Vaccination failure may play an important role in contemporary mumps outbreaks. We found no evidence to indicate that waning immunity (secondary vaccine failure) contributed significantly to this outbreak. A second dose of mumps vaccine, as recommended using measles-mumps-rubella vaccine, could potentially prevent similar outbreaks in secondary school populations in the future.


High risk occupations for non-Hodgkin's lymphoma in New Zealand: case-control study.
Previous studies into occupational risk factors for non-Hodgkin's lymphoma (NHL) in New Zealand have indicated that farmers and meat workers are at increased risk for these neoplasms. A new nationwide case-control study was conducted to assess whether previously observed associations persist and to identify other occupations that may contribute to the risk of NHL in the New Zealand population. A total of 291 incident cases of NHL (age 25-70 years) notified to the New Zealand Cancer Registry during 2003 and 2004, and 471 population controls, were interviewed face-to-face. The questionnaire collected demographic information and a full occupational history. The relative risk for NHL associated with ever being employed in particular occupations and industries was calculated by unconditional logistic regression adjusting for age, sex, smoking, ethnicity and socioeconomic status. Estimates were subsequently semi-Bayes adjusted to account for the large number of occupations and industries being considered. An elevated NHL risk was observed for field crop and vegetable growers (OR 2.74, 95% CI 1.04 to 7.25) and horticulture and fruit growing (OR 2.28, 95% CI 1.37 to 3.79), particularly for women (OR 3.44, 95% CI 0.62 to 18.9; OR 3.15, 95% CI 1.50 to 6.61). Sheep and dairy farming was not associated with an increased risk of NHL. Meat processors had an elevated risk (OR 1.97, 95% CI 0.97 to 3.97), as did heavy truck drivers (OR 1.98, 95% CI 0.92 to 4.24), workers employed in metal product manufacturing (OR 1.92, 95% CI 1.12 to 3.28) and cleaners (OR 2.11, 95% CI 1.21 to 3.65). After semi-Bayes adjustment the elevated risks for horticulture and fruit growing, metal product manufacturing and cleaners remained statistically significant, representing the most robust findings of this study. This study has confirmed that crop farmers and meat workers remain high risk occupations for NHL in New Zealand, and has identified several other occupations and industries of high NHL risk that merit further study.


(Na+ + K+)-ATPase correlated with a major group of intramembrane particles in freeze-fracture replicas of cultured chick myotubes.
Immunofluorescence microscopy with a fluorescein-labeled monoclonal antibody was used to map the distribution of sodium- and potassium-ion stimulated ATPase [( Na,K]-ATPase) on the surface of tissue-cultured chick skeletal muscle. At this level of resolution it appeared that the (Na,K)-ATPase molecules were distributed nearly uniformly over the plasma membrane. These molecules could be cross-linked by use of the monoclonal antibody followed by a second antibody directed against the monoclonal antibody; the resulting fluorescent pattern was a set of small dots (patches) on the muscle surface. This pattern was stable over several hours, and there was little evidence of interiorization or of coalescence of the patches. Myotubes labeled with immunofluorescence were fixed in glutaraldehyde, cryoprotected with glycerin, then fractured and replicated by standard methods. Replicas of the immunofluorescence-labeled myotubes revealed clusters of intramembrane particles (IMP) only when the immunofluorescent images indicated a patching of the (Na,K)-ATPase molecules. Double antibody cross-linking of antigenic sites on myotubes with each of three other monoclonal antibodies to plasma membrane antigens likewise resulted in patched patterns of immunofluorescence, but in none of these cases were clusters of intramembrane particles found in freeze-fracture replicas. In each case it was shown that the (Na,K)-ATPase molecules were not patched. Other control experiments showed that patching of (Na,K)-ATPase molecules did not cause co-patching of one of the other plasma membrane proteins defined by a monoclonal antibody and did not cause detectable co-clustering of acetylcholine receptors. Detailed mapping showed that there was a one-to-one correspondence between immunofluorescent patches related to the (Na,K)-ATPase and clusters of IMP in a freeze-fracture replica of the same cell. We conclude that the intramembrane particles patched by double antibody cross-linkage of the (Na,K)-ATPase are caused by (Na,K)-ATPase molecules in the fracture plane. Quantification of the IMP indicated that the (Na,K)-ATPase-related particles account for up to 50% of particles evident in the replicas, or up to about 400 particles/micrometers2 of plasma membrane. Particles related to the (Na,K)-ATPase were similar to the average particle size and were as heterodisperse in size as the total population of IMP.(ABSTRACT TRUNCATED AT 400 WORDS)


Involving private voluntary health care providers in 'Better Health for Africa'.
In Sub-Saharan Africa private voluntary health care providers are mostly Church-related or social not for profit organizations. They provide between 40% and 60% of health care services. In the context of Health Care Reforms, the World Bank and others have (re)discovered these non governmental providers. The World Bank document 'Better Health for Africa', promotes prominent roles for them in the execution of basic package of services and public health tasks. Unfortunately, the World Bank does not outline clearly how these roles should be achieved. The danger exists that governments, under pressure to economize, will only take the privatization angle which is in contradiction with the aims and objectives of the not for profit private providers. Thus their potential to contribute to Public Health care will be left unused and the reforms harder to achieve. My argument is that the collaboration between government and NGOs should be approached in the perspective of delegation of public duties and partnership. Thus the autonomy of NGO providers can be respected while their technical capabilities can be used optimally.


Fusion of intravenous contrast-enhanced C-arm CT and pretreatment imaging for ablation margin assessment of liver tumors: A preliminary study.
The aim of this preliminary study was to evaluate the feasibility of assessing ablation margins after radiofrequency ablation (RFA) of liver tumors from fusion images of post-treatment C-arm computed tomography (CT) images fused to pretreatment images. Five patients with liver tumors underwent RFA. Intravenous contrast-enhanced C-arm CT images were obtained for all patients immediately after RFA, and multi-detector CT (MDCT) images were obtained 3-7 days later. The C-arm CT and MDCT images were fused to pretreatment images using a multimodality image fusion software. The minimum ablation margins were assessed in the C-arm CT and MDCT fusion images. Ablation margins after RFA of liver tumors can be measured using intravenous contrast-enhanced C-arm CT images fused with pretreatment images. This technique has the potential for use in the intra-procedural assessment of liver tumor ablation.


The Association Between Protein Intake by Source and Osteoporotic Fracture in Older Men: A Prospective Cohort Study.
Dietary protein is a potentially modifiable risk factor for fracture. Our objectives were to assess the association of protein intake with incident fracture among older men and whether these associations varied by protein source or by skeletal site. We studied a longitudinal cohort of 5875 men (mean age 73.6 ± 5.9 years) in the Osteoporotic Fractures in Men (MrOS) study. At baseline, protein intake was assessed as percent of total energy intake (TEI) with mean intake from all sources = 16.1%TEI. Incident clinical fractures were confirmed by physician review of medical records. There were 612 major osteoporotic fractures, 806 low-trauma fractures, 270 hip fractures, 193 spine fractures, and 919 non-hip non-spine fractures during 15 years of follow-up. We used Cox proportional hazards models with age, race, height, clinical site, TEI, physical activity, marital status, osteoporosis, gastrointestinal surgery, smoking, oral corticosteroids use, alcohol consumption, and calcium and vitamin D supplements as covariates to compute hazard ratios (HRs) with 95% confidence intervals (CIs), all expressed per unit (SD = 2.9%TEI) increase. Higher protein intake was associated with a decreased risk of major osteoporotic fracture (HR = 0.92; 95% CI, 0.84 to 1.00) with a similar association found for low-trauma fracture. The association between protein and fracture varied by protein source; eg, increased dairy protein and non-dairy animal protein were associated with a decreased risk of hip fracture (HR = 0.80 [95% CI, 0.65 to 0.98] and HR = 0.84 [95% CI, 0.72 to 0.97], respectively), whereas plant-source protein was not (HR = 0.99 [95% CI, 0.78 to 1.24]). The association between protein and fracture varied by fracture site; total protein was associated with a decreased risk of hip fracture (HR = 0.84 [95% CI, 0.73 to 0.95]), but not clinical spine fracture (HR = 1.06 [95% CI, 0.92 to 1.22]). In conclusion, those with high protein intake (particularly high animal protein intake) as a percentage of TEI have a lower risk of major osteoporotic fracture. © 2016 American Society for Bone and Mineral Research.


The effects of aromatherapy in relieving symptoms related to job stress among nurses.
Workplace-related stress has become today's most serious occupational hazard. Aromatherapy is a simple, convenient and non-invasive method of stress relief. There is little research regarding the efficacy of aromatherapy by means of inhaling essential oil in reducing workplace stress-related symptoms among nurses. Therefore, this study was to examine the effectiveness of lavender oil inhalation in reducing job stress-related symptoms among nurses. The 53 nurses in the experimental group pinned small bottles containing 3% lavender oil on the clothes of their right chests, whereas 57 participants in the control group pinned bottles with no lavender oil. Aromatherapy was shown to be effective in the reduction of the number of stress symptoms for 3 or 4 days. The stress symptoms of the experimental group decreased from 6.1 to 2.8 after aromatherapy was carried out (P = 0.126, 0.159, 0.035 and 0.026). This represented a significant decrease in stress, whereas the stress symptoms in the control group increased from 5.6 to 5.8. Hospital staff managers are still encouraged to include aromatherapy concepts and techniques in the continuing education of nursing staff. Concurrently, future research should focus on the possible side effects of aromatherapy to assure safety.


Sequence context-specific profiles for homology searching.
Sequence alignment and database searching are essential tools in biology because a protein's function can often be inferred from homologous proteins. Standard sequence comparison methods use substitution matrices to find the alignment with the best sum of similarity scores between aligned residues. These similarity scores do not take the local sequence context into account. Here, we present an approach that derives context-specific amino acid similarities from short windows centered on each query sequence residue. Our results demonstrate that the sequence context contains much more information about the expected mutations than just the residue itself. By employing our context-specific similarities (CS-BLAST) in combination with NCBI BLAST, we increase the sensitivity more than 2-fold on a difficult benchmark set, without loss of speed. Alignment quality is likewise improved significantly. Furthermore, we demonstrate considerable improvements when applying this paradigm to sequence profiles: Two iterations of CSI-BLAST, our context-specific version of PSI-BLAST, are more sensitive than 5 iterations of PSI-BLAST. The paradigm for biological sequence comparison presented here is very general. It can replace substitution matrices in sequence- and profile-based alignment and search methods for both protein and nucleotide sequences.


The effects of microenvironment on wound healing by keratinocytes derived from mesenchymal stem cells.
Embryonic stem cells (ESCs) are pluripotent cells that can differentiate into various cell types, including keratinocyte-like cells, within suitable microniches. In this study, we aimed to investigate the effects of culture media, cell coculture, and a tissue-engineering biocomposite on the differentiation of mouse ESCs (MESCs) into keratinocyte-like cells and applied these cells to a surgical skin wound model. MESCs from BALB/c mice (ESC26GJ), which were transfected using pCX-EGFP expressing green fluorescence, were used to track MESC-derived keratinocytes. Weak expression of the keratinocyte early marker Cytokeratin 14 (CK-14) was observed up to 12 days when MESCs were cultured in a keratinocyte culture medium on tissue culture plastic and on a gelatin/collagen/polycaprolactone (GCP) biocomposite. MESCs cocultured with human keratinocyte cells (HKCs) also expressed CK-14, but did not express CK-14 when cocultured with human fibroblast cells (HFCs). Furthermore, CK-14 expression was observed when MESCs were cocultured by seeding HKCs or HFCs on the same or opposite side of the GCP biocomposite. The highest CK-14 expression was observed by seeding MESCs and HKCs on the same side of the GCP composite and with HFCs on the opposite side. To verify the effectiveness of wound healing in vivo, adipose-derived stem cells were applied to treat surgical wounds in nude mice. An obvious epidermis multilayer and better collagen deposition during wound healing were observed, as assessed by Masson staining. This study demonstrated the potential of keratinocyte-like differentiation from mesenchymal stem cells for use in promoting wound closure and skin regeneration.


Enzyme-replacement therapy in life-threatening hypophosphatasia.
Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease. There is no approved medical therapy. ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the manifestations of hypophosphatasia in Tnsalp knockout mice. We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040. Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment. ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.).


Towards an understanding of radiation damage in cryocooled macromolecular crystals.
Interest in radiation damage is growing rapidly owing to the surge in macromolecular crystallography experiments carried out at modern brilliant synchrotron macromolecular crystallography beamlines. Work on the characterization of radiation damage in cryocooled protein crystals is starting to have some impact on our understanding of the problem and of how damage might be affecting both the process of structure solution and the actual structure obtained. A brief review of the most recent developments is given together with an assessment of the remaining problems. Although progress is being made, the understanding of radiation damage is far from complete. Methods for recognizing the damage and treating the data are being made available but they are still at an early stage of development.


env1 Mutant of VPS35 gene exhibits unique protein localization and processing phenotype at Golgi and lysosomal vacuole in Saccharomyces cerevisiae.
The yeast vacuole is functionally and structurally equivalent to the mammalian lysosome. Delivery of resident and cargo proteins to the lysosome is vital for proper cellular operations, and failure to correctly target proteins to the organelle is correlated with the development of neurodegenerative and lysosomal storage diseases. We previously reported a novel mutant screen for vacuolar trafficking defects in yeast Saccharomyces cerevisiae that resulted in the isolation of env1, an allelic mutant of VPS35. As a member of the retromer complex, Vps35p binds directly to cargos and facilitates their retrograde transport to trans Golgi from endosomes. Our previous studies established that env1 exhibits unique pleiotropic phenotype in comparison to other tested VPS35 alleles including severe growth sensitivity to hygromycin B and internal accumulation of the precursor form of the vacuolar enzyme carboxypeptidase Y. Here, through a combination of sub-cellular fractionation and indirect immunofluorescence microscopy, we confirm and extend the unique phenotype of env1 to processing and localization of additional proteins within the vacuolar trafficking pathway. In comparative studies with a null and an allelic mutant of VPS35, env1 exhibited unique processing defects of retromer-independent vacuolar membrane enzyme alkaline phosphatase at the vacuole and significant Golgi localization of retromer cargos Vps10p and Kex2p despite compromised trafficking at the Golgi and late endosome interface.


Automatic tracking of individual fluorescence particles: application to the study of chromosome dynamics.
We present a new, robust, computational procedure for tracking fluorescent markers in time-lapse microscopy. The algorithm is optimized for finding the time-trajectory of single particles in very noisy dynamic (two- or three-dimensional) image sequences. It proceeds in three steps. First, the images are aligned to compensate for the movement of the biological structure under investigation. Second, the particle's signature is enhanced by applying a Mexican hat filter, which we show to be the optimal detector of a Gaussian-like spot in 1/omega2 noise. Finally, the optimal trajectory of the particle is extracted by applying a dynamic programming optimization procedure. We have used this software, which is implemented as a Java plug-in for the public-domain ImageJ software, to track the movement of chromosomal loci within nuclei of budding yeast cells. Besides reducing trajectory analysis time by several 100-fold, we achieve high reproducibility and accuracy of tracking. The application of the method to yeast chromatin dynamics reveals different classes of constraints on mobility of telomeres, reflecting differences in nuclear envelope association. The generic nature of the software allows application to a variety of similar biological imaging tasks that require the extraction and quantitation of a moving particle's trajectory.


Limb development takes a measured step toward systems analysis.
Growth and patterning of the embryonic vertebrate limb is regulated by feedback loops signaling between the epithelium and mesenchyme of the limb bud. Fibroblast growth factor (FGF) signaling from the epithelium regulates Sonic hedgehog (Shh) expression in the mesenchyme. In turn, SHH activity maintains the expression of Gremlin1, which encodes a bone morphogenetic protein (BMP) antagonist; the interaction between BMP and Gremlin1 regulates Fgf gene expression. A computational model using data from complex genetic analysis and quantitative measurements of gene induction kinetics demonstrates that limb development is robust and thus buffered against certain mutational alterations and epigenetic changes because of these feedback loops.


Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): colloidal stability, cytotoxicity, and cellular uptake studies.
The influence of the composition of the polymer coated polyvinyl alcohol (PVA), vinyl alcohol/vinyl amine copolymer (A-PVA) and polyethylenimine (PEI) coated superparamagnetic iron oxide nanoparticles (SPIONs) on the colloidal stability, cytotoxicity and cellular uptake of these particles in different cell media is reported in this paper. Although all examined polymer coated SPIONs were stable in water and PBS buffer these colloidal systems had different stabilities in DMEM or RPMI media without and supplemented with fetal calf serum (FCS). We found that A-PVA coating onto the surface of the SPIONs decreased the cytotoxicity of the polymer compared to the same concentration of A-PVA alone. As well, polyplexes of PEI-SPIONs with DNA in concentration used for transfection experiments showed no cytotoxicity compared to PEI and PEI-SPIONs. Our data show that the choice of medium largely influences the uptake of these particles by HeLa cells. The optimal medium is different for the different examined polymer coated SPIONs and it should be determined in each case, individually.


Timing and causes of mid-Holocene mammoth extinction on St. Paul Island, Alaska.
Relict woolly mammoth (Mammuthus primigenius) populations survived on several small Beringian islands for thousands of years after mainland populations went extinct. Here we present multiproxy paleoenvironmental records to investigate the timing, causes, and consequences of mammoth disappearance from St. Paul Island, Alaska. Five independent indicators of extinction show that mammoths survived on St. Paul until 5,600 ± 100 y ago. Vegetation composition remained stable during the extinction window, and there is no evidence of human presence on the island before 1787 CE, suggesting that these factors were not extinction drivers. Instead, the extinction coincided with declining freshwater resources and drier climates between 7,850 and 5,600 y ago, as inferred from sedimentary magnetic susceptibility, oxygen isotopes, and diatom and cladoceran assemblages in a sediment core from a freshwater lake on the island, and stable nitrogen isotopes from mammoth remains. Contrary to other extinction models for the St. Paul mammoth population, this evidence indicates that this mammoth population died out because of the synergistic effects of shrinking island area and freshwater scarcity caused by rising sea levels and regional climate change. Degradation of water quality by intensified mammoth activity around the lake likely exacerbated the situation. The St. Paul mammoth demise is now one of the best-dated prehistoric extinctions, highlighting freshwater limitation as an overlooked extinction driver and underscoring the vulnerability of small island populations to environmental change, even in the absence of human influence.


Psychometric Properties of the Chinese (Putonghua) Version of the Oxford Cognitive Screen (OCS-P) in Subacute Poststroke Patients without Neglect.
Oxford Cognitive Screen is designed for assessing cognitive functions of poststroke patients. This study was aimed to assess the psychometric properties of the Chinese (Putonghua) version of the Oxford Cognitive Screen-Putonghua (OCS-P) for use among poststroke patients without neglect. Expert review panel evaluated content validity of the Chinese-translated items. After pilot tested the translated items, the patients and healthy participants completed the OCS-P as well as the Montreal Cognitive Assessment (MoCA-ChiB) and Goldenberg's test. A group of patients completed OCS-P for the second time within seven days. Data analyses included confirmatory factor analysis, item difficulty and item-total correlation, inter- and intrarater reliability, internal consistency, and between-group discrimination. One hundred patients and 120 younger (n = 60) or older (n = 60) healthy participants completed all the tests. Modifications were required for items in the "Picture Naming", "Orientation", and "Sentence Reading" subscales. Confirmatory factor analysis revealed a three-factor structure for the OCS-P subscales. The internal consistency coefficients for the three identified test dimensions were 0.30 to 0.52 (Cronbach's alpha). Construct validity coefficients between the OCS-P and MoCA-ChiB subscales were 0.45 < r < 0.79 (p < 0.001) and the "Praxis" subscale of OCS-P and Goldenberg's test was r = 0.72 (p < 0.001). The interrater reliability coefficients for the subscales were in general higher than the intrarater reliability coefficients. The "Picture Naming" and "Numerical Cognition" subscales were the most significant (p = 0.003) for differentiating patient participants from their older healthy counterpart. This study generated satisfactory evidence on the content validity, substantive validity, construct validity, inter- and intrarater reliability, and known-group discrimination of the OCS-P. They support its application among poststroke patients who speak Putonghua. Future studies could review the existing five-dimension domains for improving its structural validity and internal consistency as well as generate evidence of the OCS-P for use among the poststroke patients with neglect.


Impact of carpal tunnel surgery according to pre-operative abnormality of sensory conduction in median nerve: a longitudinal study.
We have previously proposed that sensory nerve conduction (SNC) in the median nerve should be classed as abnormal when the difference between conduction velocities in the little and index fingers is > 8 m/s. In a prospective longitudinal study, we investigated whether this case definition distinguished patients who were more likely to benefit from surgical treatment. We followed up 394 patients (response rate 56%), who were investigated by a neurophysiology service for suspected carpal tunnel syndrome. Information about symptoms, treatment and other possible determinants of outcome was obtained through questionnaires at baseline and after follow-up for a mean of 19.2 months. Analysis focused on 656 hands with numbness, tingling or pain at baseline. Associations of surgical treatment with resolution of symptoms were assessed by Poisson regression, and summarised by prevalence rate ratios (PRRs) and associated 95% confidence intervals (95% CIs). During follow-up, 154 hands (23%) were treated surgically, and sensory symptoms resolved in 241 hands (37%). In hands with abnormal median SNC, surgery was associated with resolution of numbness, tingling and pain (PRR 1.5, 95% CI 1.0-2.2), and of numbness and tingling specifically (PRR 1.8, 95% CI 1.3-2.6). In contrast, no association was apparent for either outcome when median SNC was classed as normal. Our definition of abnormal median SNC distinguished a subset of patients who appeared to benefit from surgical treatment. This predictive capacity gives further support to its validity as a diagnostic criterion in epidemiological research.


A randomised controlled trial of bumetanide in the treatment of autism in children.
Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study,(1) we have now performed a double-blind clinical trial using the diuretic, chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition. Sixty children with autism or Asperger syndrome (3-11 years old) received for 3 months placebo or bumetanide (1 mg daily), followed by 1-month wash out. Determination of the severity of autism was made with video films at day 0 (D0) and D90 by blind, independent evaluators. Bumetanide reduced significantly the Childhood Autism Rating Scale (CARS) (D90-D0; P<0.004 treated vs placebo), Clinical Global Impressions (P<0.017 treated vs placebo) and Autism Diagnostic Observation Schedule values when the most severe cases (CARS values above the mean ± s.d.; n=9) were removed (Wilcoxon test: P-value=0.031; Student's t-test: P-value=0.017). Side effects were restricted to an occasional mild hypokalaemia (3.0-3.5 mM l(-1) K(+)) that was treated with supplemental potassium. In a companion study, chronic bumetanide treatment significantly improved accuracy in facial emotional labelling, and increased brain activation in areas involved in social and emotional perception (Hadjikhani et al., submitted). Therefore, bumetanide is a promising novel therapeutic agent to treat autism. Larger trials are warranted to better determine the population best suited for this treatment.


Antecedents and consequences of intra-group conflict among nurses.
To test a theoretical model linking selected antecedent variables to intra-group conflict among nurses, and subsequently conflict management style, job stress and job satisfaction. A contributing factor to the nursing shortage is job dissatisfaction as a result of conflict among nurses. To develop strategies to reduce conflict, research is needed to understand the causes and outcomes of conflict in nursing work environments. A predictive, non-experimental design was used in a random sample of 277 acute care nurses. Structural equation modelling was used to analyse the hypothesised model. Nurses' core self-evaluations, complexity of care and relationships with managers and nursing colleagues influenced their perceived level of conflict. Conflict management style partially mediated the relationship between conflict and job satisfaction. Job stress had a direct effect on job satisfaction and core self-evaluation had a direct effect on job stress. Conflict and its associated outcomes is a complex process, affected by dispositional, contextual and interpersonal factors. How nurses manage conflict may not prevent the negative effects of conflict, however, learning to manage conflict using collaboration and accommodation may help nurses experience greater job satisfaction. Strategies to manage and reduce conflict include building interactional justice practices and positive interpersonal relationships.


Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis.
Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers. Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH. The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%). Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.


Differential expression of gill Na+,K+-ATPase alpha- and beta-subunits, Na+,K+,2Cl- cotransporter and CFTR anion channel in juvenile anadromous and landlocked Atlantic salmon Salmo salar.
This study examines changes in gill Na(+),K(+)-ATPase (NKA) alpha- and beta-subunit isoforms, Na(+),K(+),2Cl(-) cotransporter (NKCC) and cystic fibrosis transmembrane conductance regulator (CFTR I and II) in anadromous and landlocked strains of Atlantic salmon during parr-smolt transformation, and after seawater (SW) transfer in May/June. Gill NKA activity increased from February through April, May and June among both strains in freshwater (FW), with peak enzyme activity in the landlocked salmon being 50% below that of the anadromous fish in May and June. Gill NKA-alpha1b, -alpha3, -beta(1) and NKCC mRNA levels in anadromous salmon increased transiently, reaching peak levels in smolts in April/May, whereas no similar smolt-related upregulation of these transcripts occurred in juvenile landlocked salmon. Gill NKA-alpha1a mRNA decreased significantly in anadromous salmon from February through June, whereas alpha1a levels in landlocked salmon, after an initial decrease in April, remained significantly higher than those of the anadromous smolts in May and June. Following SW transfer, gill NKA-alpha1b and NKCC mRNA increased in both strains, whereas NKA-alpha1a decreased. Both strains exhibited a transient increase in gill NKA alpha-protein abundance, with peak levels in May. Gill alpha-protein abundance was lower in SW than corresponding FW values in June. Gill NKCC protein abundance increased transiently in anadromous fish, with peak levels in May, whereas a slight increase was observed in landlocked salmon in May, increasing to peak levels in June. Gill CFTR I mRNA levels increased significantly from February to April in both strains, followed by a slight, though not significant increase in May and June. CFTR I mRNA levels were significantly lower in landlocked than anadromous salmon in April/June. Gill CFTR II mRNA levels did not change significantly in either strain. Our findings demonstrates that differential expression of gill NKA-alpha1a, -alpha1b and -alpha3 isoforms may be important for potential functional differences in NKA, both during preparatory development and during salinity adjustments in salmon. Furthermore, landlocked salmon have lost some of the unique preparatory upregulation of gill NKA, NKCC and, to some extent, CFTR anion channel associated with the development of hypo-osmoregulatory ability in anadromous salmon.


Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs.
Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases.


Prescription drug monitoring programs operational characteristics and fatal heroin poisoning.
Prescription drug monitoring programs (PDMP), by reducing access to prescribed opioids (POs), may contribute to a policy environment in which some people with opioid dependence are at increased risk for transitioning from POs to heroin/other illegal opioids. This study examines how PDMP adoption and changes in the characteristics of PDMPs over time contribute to changes in fatal heroin poisoning in counties within states from 2002 to 2016. Latent transition analysis to classify PDMPs into latent classes (Cooperative, Proactive, and Weak) for each state and year, across three intervals (1999-2004, 2005-2009, 2010-2016). We examined the association between probability of PDMP latent class membership and the rate of county-level heroin poisoning death. After adjustment for potential county-level confounders and co-occurring policy changes, adoption of a PDMP was significantly associated with increased heroin poisoning rates (22% increase by third year post-adoption). Findings varied by PDMP type. From 2010-2016, states with Cooperative PDMPs (those more likely to share data with other states, to require more frequent reporting, and include more drug schedules) had 19% higher heroin poisoning rates than states with Weak PDMPs (adjusted rate ratio [ARR] = 1.19; 95% CI = 1.14, 1.25). States with Proactive PDMPs (those more likely to report outlying prescribing and dispensing and provide broader access to law enforcement) had 6% lower heroin poisoning rates than states with No/Weak PDMPs (ARR = 0.94; 95% CI = 0.90, 0.98). There is a consistent, positive association between state PDMP adoption and heroin poisoning mortality. However, this varies by PDMP type, with Proactive PDMPs associated with a small reduction in heroin poisoning deaths. This raises questions about the potential for PDMPs to support efforts to decrease heroin overdose risk, particularly by using proactive alerts to identify patients in need of treatment for opioid use disorder. Future research on mechanisms explaining the reduction in heroin poisonings after enactment of Proactive PDMPs is merited.


Genomic and network patterns of schizophrenia genetic variation in human evolutionary accelerated regions.
The population persistence of schizophrenia despite associated reductions in fitness and fecundity suggests that the genetic basis of schizophrenia has a complex evolutionary history. A recent meta-analysis of schizophrenia genome-wide association studies offers novel opportunities for assessment of the evolutionary trajectories of schizophrenia-associated loci. In this study, we hypothesize that components of the genetic architecture of schizophrenia are attributable to human lineage-specific evolution. Our results suggest that schizophrenia-associated loci enrich in genes near previously identified human accelerated regions (HARs). Specifically, we find that genes near HARs conserved in nonhuman primates (pHARs) are enriched for schizophrenia-associated loci, and that pHAR-associated schizophrenia genes are under stronger selective pressure than other schizophrenia genes and other pHAR-associated genes. We further evaluate pHAR-associated schizophrenia genes in regulatory network contexts to investigate associated molecular functions and mechanisms. We find that pHAR-associated schizophrenia genes significantly enrich in a GABA-related coexpression module that was previously found to be differentially regulated in schizophrenia affected individuals versus healthy controls. In another two independent networks constructed from gene expression profiles from prefrontal cortex samples, we find that pHAR-associated schizophrenia genes are located in more central positions and their average path lengths to the other nodes are significantly shorter than those of other schizophrenia genes. Together, our results suggest that HARs are associated with potentially important functional roles in the genetic architecture of schizophrenia.


The effect of different volumes of acute resistance exercise on elderly individuals with treated hypertension.
Acute resistance exercise can reduce the blood pressure (BP) of hypertensive subjects. The aim of this study was to evaluate the effect of different volumes of acute low-intensity resistance exercise over the magnitude and the extent of BP changes in treated hypertensive elderly individuals. Sixteen participants (7 men, 9 women), with mean age of 68 ± 5 years, performed 3 independent randomized sessions: Control (C: 40 minutes of rest), Exercise 1 (E1: 20 minutes, 1 lap in the circuit), and Exercise 2 (E2: 40 minutes, 2 laps in the circuit) with the intensity of 40% of 1 repetition maximum. Blood pressure was measured before (during 20 minutes) and after each session (every 5 minutes during 60 minutes) using both a mercury sphygmomanometer and a semiautomatic device (Omrom-HEM-431). After that, 24-hour ambulatory blood pressure monitoring was performed (Dyna-MAPA). Blood pressure decreased during the first 60 minutes (systolic: p < 0.01, diastolic: p < 0.05) after all exercise sessions. Only the highest volume session promoted a reduction of mean systolic 24-hour BP and awake BP (p < 0.05) after exercise, with higher diastolic BP during sleep (p < 0.05). Diastolic 24-hour BP and both systolic and diastolic BP during sleep were higher after E1 (p < 0.05). Concluding, acute resistive exercise sessions in a circuit with different volumes reduced BP during the first 60 minutes after exercise in elderly individuals with treated hypertension. However, only the highest volume promoted a reduction of mean 24-hour and awake systolic BP.


Antibiotic resistance genes in treated wastewater and in the receiving water bodies: A pan-European survey of urban settings.
There is increasing public concern regarding the fate of antibiotic resistance genes (ARGs) during wastewater treatment, their persistence during the treatment process and their potential impacts on the receiving water bodies. In this study, we used quantitative PCR (qPCR) to determine the abundance of nine ARGs and a class 1 integron associated integrase gene in 16 wastewater treatment plant (WWTP) effluents from ten different European countries. In order to assess the impact on the receiving water bodies, gene abundances in the latter were also analysed. Six out of the nine ARGs analysed were detected in all effluent and river water samples. Among the quantified genes, intI1 and sul1 were the most abundant. Our results demonstrate that European WWTP contribute to the enrichment of the resistome in the receiving water bodies with the particular impact being dependent on the effluent load and local hydrological conditions. The ARGs concentrations in WWTP effluents were found to be inversely correlated to the number of implemented biological treatment steps, indicating a possible option for WWTP management. Furthermore, this study has identified blaOXA-58 as a possible resistance gene for future studies investigating the impact of WWTPs on their receiving water.


Distinct patterns of phosphatidylserine localization within the Rab11a-containing recycling system.
The Rab11 GTPases and Rab11 family-interacting proteins (Rab11-FIPs) define integrated yet distinct compartments within the slow recycling pathway. The lipid content of these compartments is less well understood, although past studies have indicated phosphatidylserine (PS) is an integral component of recycling membranes. We sought to identify key differences in the presence of PS within Rab and Rab11-FIP containing membranes. We used live cell fluorescence microscopy and structured illumination microscopy to determine whether the previously published LactC2 probe for PS displays differential patterns of overlap with various Rab GTPases and Rab11-FIPs. Selective overlap was observed between the LactC2 probe and Rab GTPases when co-expressed in HeLa cells. Rab11-FIP1 proteins consistently overlapped with LactC2 along peripheral and pericentriolar compartments. The specificity of Rab11-FIP1 association with LactC2 was further confirmed by demonstrating that additional Rab11-FIPs (FIP2, FIP3, and FIP5) exhibited selective association with LactC2 containing compartments. Live cell dual expression studies of Rab11-FIPs with LactC2 indicated that PS is enriched along tubular compartments of the Rab11a-dependent recycling system. Additionally, we found that the removal of C2 domains from the Rab11-FIPs induced an accumulation of LactC2 probe in the pericentriolar region, suggesting that inhibition of trafficking through the recycling system can influence the distribution of PS within cells. Finally, we confirmed these findings using structured illumination microscopy suggesting that the overlapping fluorescent signals were on the same membranes. These results suggest distinct associations of Rab GTPases and Rab11-FIPs with PS-containing recycling system membrane domains.


Irritable bowel syndrome - an evidence-based approach to diagnosis.
Irritable bowel syndrome (IBS) represents one of the most common reasons for primary care visits and consultation with a gastroenterologist. It is characterized by abdominal discomfort, bloating and disturbed defecation in the absence of any identifiable physical, radiologic or laboratory abnormalities indicative of organic gastrointestinal disease. IBS is a costly disorder, responsible for significant direct and indirect costs to patients and society. Much of the cost attributed to IBS arises from the time and resources used to establish the diagnosis. Historically IBS has been viewed by many as a diagnosis of exclusion rather than as a primary diagnosis, and many patients with typical symptoms will undergo an extensive array of diagnostic tests and procedures prior to the eventual diagnosis of IBS. Recent reviews addressing the management of such patients have cast doubt on the necessity for this degree of testing. Current best evidence does not support the routine use of blood tests, stool studies, breath tests, abdominal imaging or lower endoscopy in order to exclude organic gastrointestinal disease in patients with typical IBS symptoms without alarm features. Serological testing for celiac sprue in this population may eventually prove useful but validation of studies indicating an increased prevalence of this disease in patients with suspected IBS is needed. The development and refinement of symptom-based criteria defining the clinical syndrome of IBS has greatly facilitated the diagnosis of this condition, which can be confidently diagnosed through the identification of typical symptoms, normal physical examination and the exclusion of alarm features. The presence of alarm features or persistent non-response to symptom-directed therapies should prompt a more detailed diagnostic evaluation dictated by the patient's predominant symptoms.


Detection and characterization of focal liver lesions: a Japanese phase III, multicenter comparison between gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced computed tomography predominantly in patients with hepatocellular carcinoma and chronic liver disease.
To prospectively evaluate the safety and efficacy of combined unenhanced and gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging compared with unenhanced MR imaging and triphasic contrast-enhanced spiral computed tomography (CT) for the detection and characterization of focal liver lesions. The study was reviewed and approved by the institutional review board at each of the 15 centers involved in the study, and informed written consent was given by all patients. In total, 178 patients with suspected focal hepatic lesions (based, in most patients, on CT, tumor marker and ultrasound examinations) underwent combined MR imaging with a single, rapid injection of Gd-EOB-DTPA 0.025 mmol/kg, including T1-weighted dynamic and delayed MR images 20 to 40 minutes postinjection. Triphasic contrast-enhanced CT, the comparator examination, was performed within 4 weeks of MR imaging. Standard of references (SOR) were resection histopathology and intraoperative ultrasonography, or combined CT during arterial portography and CT hepatic arteriography; in cases where, although the major lesions were treated, some lesion(s) were not treated, follow-up superparamagnetic iron oxide-enhanced MR imaging was additionally performed. All images were assessed for differences in lesion detection and characterization (specific lesion type) by on-site readers and 3, blinded (off-site) reviewers. All adverse events (AEs) occurring within 72 hours after Gd-EOB-DTPA administration were reported. Overall, 9.6% of patients who received Gd-EOB-DTPA reported 21 drug-related AEs. A total of 151 patients were included in the efficacy analysis. Combined MR imaging showed statistically higher sensitivity in lesion detection (67.5%-79.5%) than unenhanced MR imaging (46.5%-59.1%; P < 0.05 for all). Combined MR imaging also showed higher sensitivity in lesion detection than CT (61.1%-73.0%), with the results being statistically significant (P < 0.05) for on-site readers and 2 of 3 blinded readers. Higher sensitivity in lesion detection with combined MR imaging compared with CT was also clearly demonstrated in the following subgroups: lesions with a diameter <or=20 mm (lesions <or=10 mm: 38.0%-55.4% vs. 26.1%-47.3%, respectively; lesions 10-20 mm: 71.1%-87.3% vs. 65.7%-78.4%, respectively); in cirrhotic patients (64.5%-75.4% vs. 54.5%-70.3%, respectively); and in patients with hepatocellular carcinoma (66.6%-78.6% vs. 59.1%-71.6%, respectively). Combined MR imaging demonstrated a higher proportion of correctly characterized lesions (50.5%-72.1%) than unenhanced MR imaging (30.2%-50.0%; P < 0.05 for all), whereas there were no significant differences compared with CT (49.0%-68.1%), except for one blinded reader (P < 0.05). In this study, hepatocyte-specific Gd-EOB-DTPA was shown to be safe and to improve the detection and characterization of focal hepatic lesions compared with unenhanced MR imaging. When compared with spiral CT, Gd-EOB-DTPA enhanced MRI seems to be beneficial especially for the detection for smaller lesions or hepatocellular carcinoma underlying cirrhotic liver.


Predictors of tobacco use initiation in adolescents: a two-year prospective study and theoretical discussion.
To test whether baseline data from a randomised clinical trial are predictive of initiation of tobacco use over a two-year follow-up interval, and to discuss results in the context of a theoretical model. Secondary, non-experimental analyses of data collected from a prospective cluster-randomised clinical trial comparing an intervention with a control condition for reduction of tobacco incidence rates. Orthodontic offices in southern California were recruited and randomised to an experimental or control group. Patient participants were sampled within each office, and completed a short survey, repeated two years later. 13,923 patients, 11-18 years of age, randomly sampled from each office. The ability of baseline data to predict initiation of tobacco use over the two-year follow-up interval was tested through a series of logistic regression models. Significant predictors and their interactions were identified in fixed-effects models, and verified in a mixed-effects logistic regression model to account for cluster randomisation. Clinician advice against tobacco use was associated with a lower rate of tobacco use initiation among young people whose peer group considered smoking socially desirable. Rates of initiation increased with age, but this association differed by gender and by whether the adolescent had been offered tobacco within 30 days prior to the baseline assessment. People from minority groups were less likely to initiate tobacco use than whites, and young people engaging in other risk practices were more likely to initiate tobacco use. Findings support predictions based on learning theory that social processes are critical in the development of health-risk behaviours. Future preventive efforts should target changing the density with which young people encounter pro- and anti-tobacco prompts and consequences in the community.


Large-scale identification of yeast integral membrane protein interactions.
We carried out a large-scale screen to identify interactions between integral membrane proteins of Saccharomyces cerevisiae by using a modified split-ubiquitin technique. Among 705 proteins annotated as integral membrane, we identified 1,985 putative interactions involving 536 proteins. To ascribe confidence levels to the interactions, we used a support vector machine algorithm to classify interactions based on the assay results and protein data derived from the literature. Previously identified and computationally supported interactions were used to train the support vector machine, which identified 131 interactions of highest confidence, 209 of the next highest confidence, 468 of the next highest, and the remaining 1,085 of low confidence. This study provides numerous putative interactions among a class of proteins that have been difficult to analyze on a high-throughput basis by other approaches. The results identify potential previously undescribed components of established biological processes and roles for integral membrane proteins of ascribed functions.


Copper systematics in arc magmas and implications for crust-mantle differentiation.
Arc magmas are important building blocks of the continental crust. Because many arc lavas are oxidized, continent formation is thought to be associated with oxidizing conditions. On the basis of copper's (Cu's) affinity for reduced sulfur phases, we tracked the redox state of arc magmas from mantle source to emplacement in the crust. Primary arc and mid-ocean ridge basalts have identical Cu contents, indicating that the redox states of primitive arc magmas are indistinguishable from that of mid-ocean ridge basalts. During magmatic differentiation, the Cu content of most arc magmas decreases markedly because of sulfide segregation. Because a similar depletion in Cu characterizes global continental crust, the formation of sulfide-bearing cumulates under reducing conditions may be a critical step in continent formation.


Targeted capture of homoeologous coding and noncoding sequence in polyploid cotton.
Targeted sequence capture is a promising technology in many areas in biology. These methods enable efficient and relatively inexpensive sequencing of hundreds to thousands of genes or genomic regions from many more individuals than is practical using whole-genome sequencing approaches. Here, we demonstrate the feasibility of target enrichment using sequence capture in polyploid cotton. To capture and sequence both members of each gene pair (homeologs) of wild and domesticated Gossypium hirsutum, we created custom hybridization probes to target 1000 genes (500 pairs of homeologs) using information from the cotton transcriptome. Two widely divergent samples of G. hirsutum were hybridized to four custom NimbleGen capture arrays containing probes for targeted genes. We show that the two coresident homeologs in the allopolyploid nucleus were efficiently captured with high coverage. The capture efficiency was similar between the two accessions and independent of whether the samples were multiplexed. A significant amount of flanking, nontargeted sequence (untranslated regions and introns) was also captured and sequenced along with the targeted exons. Intraindividual heterozygosity is low in both wild and cultivated Upland cotton, as expected from the high level of inbreeding in natural G. hirsutum and bottlenecks accompanying domestication. In addition, levels of heterozygosity appeared asymmetrical with respect to genome (A(T) or D(T)) in cultivated cotton. The approach used here is general, scalable, and may be adapted for many different research inquiries involving polyploid plant genomes.


6-Hydroxydopamine injections into the nigrostriatal pathway attenuate striatal malonate and 3-nitropropionic acid lesions.
The mitochondrial inhibitors malonate and 3-nitropropionic (3NP) acid are potent neurotoxins in vivo. Administration of these compounds results in neuronal loss similar to that seen in Huntington's disease. Although the mechanism of cell death produced by these compounds likely involves activation of N-methyl-D-aspartate receptors, it remains unclear why the striatum demonstrates regional susceptibility to the toxicity of these and other mitochondrial poisons. We hypothesized that dopamine, a weak neurotoxin that occurs in high concentrations in the striatum, may contribute to the neuronal damage caused by mitochondrial inhibition. We investigated whether depletion of striatal dopamine using the catecholaminergic toxin 6-hydroxydopamine would attenuate lesions induced by mitochondrial inhibition. We found that dopamine depletion reduced significantly the extent of histological damage in the striatum elicited by both intraparenchymal injections of 0.8 micromol malonate and 20 mg/kg systemic administration of 3NP. These data suggest that dopamine or one of its metabolites may contribute to mitochondrial toxin-induced cell death.


Perceptions of soil-eating and anaemia among pregnant women on the Kenyan coast.
After a clinical study at Kilifi District hospital had shown a high prevalence of geophagy among pregnant women, and a strong association of geophagy, anaemia and iron depletion, 52 pregnant women from the same hospital, and 4 traditional healers from the surroundings of Kilifi in Kenya were interviewed on the topic of soil-eating and its perceived causes and consequences. The findings were substantiated by results from an earlier anthropological study on maternal health and anaemia in the same study area. Most of the pregnant women (73%) ate soil regularly. They mainly ate the soil from walls of houses, and their estimated median daily ingestion was 41.5 g. They described soil-eating as a predominantly female practice with strong relations to fertility and reproduction. They made associations between soil-eating, the condition of the blood and certain bodily states: pregnancy, lack of blood (upungufu wa damu), an illness called safura involving "weak" blood, and worms (minyolo). The relationships the women described between soil-eating and illness resemble to some extent the causalities explored in biomedical research on soil-eating, anaemia and intestinal worm infections. However the women did not conceptualise the issue in terms of the single causal links characteristic of most scientific thought. Instead, they acknowledged the existence of multiple links between phenomena which they observed in their own and other women's bodies. The women's ideas about soil-eating and their bodies shows the significance of both social and cultural context on the ways in which women derive knowledge from, and make sense of their bodily states. The cultural associations of soil-eating with blood, fertility and femininity exist alongside knowledge of its links to illness. Our findings show that soil-eating is more than just a physiologically induced behaviour; it is a rich cultural practice.


Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma.
The ubiquitous Epstein-Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells and is associated with various lymphoid malignancies. Recent studies have reported that histone deacetylase (HDAC) inhibitors exert anticancer effects against various tumor cells. In the present study, we have evaluated both the in vitro and in vivo effects of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on EBV-positive and EBV-negative T and NK lymphoma cells. Several EBV-positive and EBV-negative T and NK cell lines were treated with various concentrations of SAHA. SAHA suppressed the proliferation of T and NK cell lines, although no significant difference was observed between EBV-positive and EBV-negative cell lines. SAHA induced apoptosis and/or cell cycle arrest in several T and NK cell lines. In addition, SAHA increased the expression of EBV-lytic genes and decreased the expression of EBV-latent genes. Next, EBV-positive NK cell lymphoma cells were subcutaneously inoculated into severely immunodeficient NOD/Shi-scid/IL-2Rγnull mice, and then SAHA was administered intraperitoneally. SAHA inhibited tumor progression and metastasis in the murine xenograft model. SAHA displayed a marked suppressive effect against EBV-associated T and NK cell lymphomas through either induction of apoptosis or cell cycle arrest, and may represent an alternative treatment option.


Evolving role of biomarkers in acute cerebrovascular disease.
The development of a clinically validated biomarker of acute cerebral ischemia would have the potential to facilitate the use of time-sensitive reperfusion strategies, allow for individualization of patient care by predicting relative risk of hemorrhage and volume of penumbral tissue, and add valuable prognostic information for patients presenting with acute stroke. Additionally, a stroke biomarker might benefit early stage clinical research by serving as a surrogate measure of ischemic injury. Although at present there are no clinically validated biomarkers of acute stroke, previous studies have focused on markers associated with different components of the ischemic cascade, including microglial activation, inflammation, oxidative stress, neuronal injury, hemostasis, and endothelial dysfunction. Evolving technologies have provided high throughput approaches to investigate potential gene and protein signatures, and methods to measure newly discovered markers of cell death and immune responses. Prior to defining the clinical utility of stroke biomarkers, it is critical to understand the inherent limitations of a biomarker-based approach and define its potential value for providing adjunctive diagnostic and prognostic information. The identification and validation of a clinically relevant biomarker, or panel of markers, of stroke will ultimately require incorporation of both stringent research design and assessment in the clinical context in which the marker will be used.


Complexus adhaerentes, a new group of desmoplakin-containing junctions in endothelial cells: II. Different types of lymphatic vessels.
In diverse mammalian species, including (man, cow and rat) the very flat endothelial cells of lymphatic vessels of various organs, including the retothelial meshwork of sinus of lymph nodes, are connected by zonula-like plaque-bearing junctions which differ from the similarly structured junctions of blood vessel endothelia by the presence of desmoplakin or an as yet unknown but closely related plaque protein. These extended junctions, which also contain plakoglobin but none of the presently known desmogleins and desmocollins, are therefore different from the spot-like desmosomes (maculae adhaerentes) present in epithelia, myocardium and dendritic reticulum cells of lymphatic follicles, and are collectively subsumed under the new category of complexus adhaerentes, including the 'syndesmos' connecting the processes of the retothelial cells. The lymphatic endothelial cells possessing these special desmoplakin-containing junctions also contain the calcium-dependent transmembrane glycoproteins, V-cadherin and cadherin 5, of which the latter has also been partly localized to regions with desmoplakin-positive junctions. Possible functional reasons for the formation and maintenance of complexus adhaerentes are discussed as well as the potential value of reagents which allow their identification in relation to physiology and pathology.


Organization and nucleotide sequence of the DNA polymerase gene from the archaeon Pyrococcus furiosus.
We cloned the gene encoding the thermostable DNA polymerase from the archaeon Pyrococcus furiosus. The DNA fragment of 2785 base pair (bp) containing the structural gene for DNA polymerase was sequenced. DNA polymerase (Pfu polymerase), as deduced from the DNA sequence, consisted of 775 amino acids, had a molecular weight of 90, 109, and was structurally homologous to the alpha-like DNA polymerases (family B) represented by human DNA polymerase alpha and Escherichia coli DNA polymerase II. An unrooted phylogenetic tree of the alpha-like DNA polymerases based on the amino acid sequence alignment was constructed. Pfu polymerase, with two other archaeon polymerases, constitutes a group with some animal viruses. The transcription initiation sites of the pol gene were identified by analysis of in vivo transcripts of both from P. furiosus and E. coli, and the promoters were assigned upstream of the pol coding region. A typical promoter sequence for the archaeon was found at a reasonable distance from the transcription initiation site in P. furiosus.


A Clinician's Guide to PTSD Treatments for Returning Veterans.
What options are available to mental health providers helping clients with posttraumatic stress disorder (PTSD)? In this paper we review many of the current pharmacological and psychological interventions available to help prevent and treat PTSD with an emphasis on combat-related traumas and Veteran populations. There is strong evidence supporting the use of several therapies including prolonged exposure (PE), eye movement desensitization and reprocessing (EMDR), and cognitive processing therapies (CPT), with PE possessing the most empirical evidence in favor of its efficacy. There have been relatively fewer studies of non-exposure based modalities (e.g., psychodynamic, interpersonal, and dialectical behavior therapy perspectives), but there is no evidence that these treatments are less effective. Pharmacotherapy is promising (especially paroxetine, sertraline, and venlafaxine), but more research comparing the relative merits of medication vs. psychotherapy and the efficacy of combined treatments is needed. Given the recent influx of combat-related traumas due to ongoing conflicts in Iraq and Afghanistan, there is clearly an urgent need to conduct more randomized clinical trials research and effectiveness studies in military and Department of Veterans Affairs PTSD samples. Finally, we provide references to a number of PTSD treatment manuals and propose several recommendations to help guide clinicians' treatment selections.


Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy.