Significance of commonly used prognostic factors differs for children with T cell acute lymphocytic leukemia (ALL), as compared to those with B-precursor ALL. A Pediatric Oncology Group (POG) study.
T cell acute lymphocytic leukemia (T-ALL) and B-precursor ALL differ significantly in the clinical characteristics of the patients at presentation and in laboratory-defined characteristics of the leukemic cells. We assessed for pediatric patients with T-ALL the relative importance of prognostic factors previously demonstrated to predict outcome in B-precursor ALL. Presenting clinical and laboratory features were correlated with outcome for 441 children 12 months to 21 years of age with previously untreated T-ALL, registered on the Pediatric Oncology Group (POG) T3 protocol between 1986 and 1992. These T-ALL prognostic factor analyses were then compared to similar analyses for 1993 patients with B-precursor ALL enrolled during the same time period on the POG ALinC 14 protocol. Quantitative interaction between phenotype and each prognostic factor was studied to determine the relative importance of the prognostic factor for each of the two major immunophenotypes. We also analyzed the importance of maturational stage as a T-ALL prognostic factor, using a modified Ludwig definition of maturational stage. We conclude that several of the clinical and laboratory prognostic factors, which are used reliably for B-precursor ALL, are much less predictive in T-ALL (ie age, WBC, consensus risk group, hyperdiploidy, presence of trans- locations and CALLA expression). There was no significant difference between the phenotypes in the prognostic importance of race or gender. Our data demonstrate a significant difference in outcome among the three maturational stages of T-cell ALL, with the intermediate group faring best. Using traditional risk group criteria to stratify patients with T-ALL for therapy may not be appropriate.


Trends in all cause and viral liver disease-related hospitalizations in people with hepatitis B or C: a population-based linkage study.
Previous studies have reported an excess burden of cancer and mortality in populations with chronic hepatitis B (HBV) or C (HCV), but there are limited data comparing hospitalization rates. In this study, we compared hospitalization rates for all causes and viral liver disease in people notified with HBV or HCV in New South Wales (NSW), Australia. HBV and HCV notifications were linked to their hospital (July 2000-June 2006), HIV and death records. Standardized hospitalization ratios (SHRs) were calculated using rates for the NSW population. Random effects Poisson regression was used to examine temporal trends. The SHR for all causes and non alcoholic liver disease was two-fold higher in the HCV cohort compared with the HBV cohort (SHRs 1.4 (95%CI: 1.4-1.4) v 0.6 (95%CI: 0.6-0.6) and 14.0 (95%CI: 12.7-15.4) v 5.4 (95%CI: 4.5-6.4), respectively), whilst the opposite was seen for primary liver cancer (SHRs 16.2 (95%CI: 13.8-19.1) v 29.1 (95%CI: 24.7-34.2)). HIV co-infection doubled the SHR except for primary liver cancer in the HCV/HIV cohort. In HBV and HCV mono-infected cohorts, all cause hospitalization rates declined and primary liver cancer rates increased, whilst rates for non alcoholic liver disease increased by 9% in the HCV cohort but decreased by 14% in the HBV cohort (P < 0.001). Hospital-related morbidity overall and for non alcoholic liver disease was considerably higher for HCV than HBV. Improved treatment of advanced HBV-related liver disease may explain why HBV liver-related morbidity declined. In contrast, HCV liver-related morbidity increased and improved treatments, especially for advanced liver disease, and higher levels of treatment uptake are required to reverse this trend.


Monitoring of Short-Term Erythropoietin Therapy in Rats with Acute Spinal Cord Injury Using Manganese-Enhanced Magnetic Resonance Imaging.
To evaluate the short-term outcome of erythropoietin (EPO) therapy in rats with spinal cord injury (SCI) using manganese-enhanced magnetic resonance imaging (MEMRI). Rats were divided in an EPO and a control group. Laminectomy at Th11 was performed, followed by SCI. MnCl2 was applied into the cisterna magna and functional recovery was examined after injury using BBB-scoring. Then, rats were euthanized and the spinal cord was extracted for MEMRI. Finally, histological analysis was performed and correlated with MEMRI. EPO-treated animals showed significantly better functional recovery (P = .008, r = .62) and higher mean signal-to-noise ratio (SNR) in MEMRI compared to controls for slices 10-13 (P = .017, R(2) = .31) at the level of the lesion epicenter. Functional recovery correlated significantly with higher SNR values, determined using the mean SNR between slices 10 and 13 (P = .047, R(2) = .36). In this region, histology revealed a significantly decreased number of microglia cells and apoptosis in EPO-treated animals. MEMRI successfully depicts the therapeutic effect of EPO in early SCI that leads to a significant recovery in rats, a significantly reduced immune response and significantly reduced number of apoptotic cells at the height of the lesion epicenter.


Prioritisation of surgery in the National Health Strategic Plans of Africa: a systematic review.
Disease amenable to surgical intervention accounts for 11-15% of world disability and there is increasing interest in surgery as a global public health issue. National Health Strategic Plans (NHSPs) have been established in most countries and reflect their long-term health priorities, plans, and targets. To assess surgery's perceived importance in Africa, we reviewed its place in all such available plans. We analysed all 43 of the 55 independent countries in Africa that had NHSPs available in the public domain in March, 2014, in English or French. We searched for policies electronically with the search terms "surg*", "ortho*", "trauma", "cancer", "appendic*", "laparotomy", "HIV", "tuberculosis", and "malaria" and included those from 2002 to 2030. We then searched manually for disease prevalence, targets, and human resources. Eight (19%)of 43 NHSPs had no mention of surgery or surgical conditions. 28 (65%) of 43 had five or less mentions of surgery. HIV and malaria had 3801 mentions across all the policies compared with surgery with only 379 mentions. Trauma had 243 mentions, while the common surgical conditions of appendicitis, laparotomy, and hernia had no mentions at all. More than 95% (41 of 43) of NHSPs specifically mentioned the prevalences of HIV, tuberculosis, malaria, infant mortality, and maternal mortality. The most commonly mentioned surgical condition for which a prevalence was given was trauma, in only 47% (23 of 43) of policies. All NHSPs had plans and measurable targets for the reduction of HIV and tuberculosis and all but one had targets for malaria, maternal mortality, and child mortality. Of the 4232 health targets across 43 NHSPs, only 96 (2·3%) were related to surgical conditions or surgical care. 14 (33%) of 43 policies had no surgical targets. NHSPs are the best available measure of health service and planning priorities. It is clear from our findings that surgery is poorly represented and that surgical conditions and surgical treatment are not widely recognised as a public health priority. A paradigm shift is required if surgery is to be considered a public health concern, which should include greater prioritisation in national health strategic policies. None.


Nutrition facts in multiple sclerosis.
The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.


Using ontology-based annotation to profile disease research.
Profiling the allocation and trend of research activity is of interest to funding agencies, administrators, and researchers. However, the lack of a common classification system hinders the comprehensive and systematic profiling of research activities. This study introduces ontology-based annotation as a method to overcome this difficulty. Analyzing over a decade of funding data and publication data, the trends of disease research are profiled across topics, across institutions, and over time. This study introduces and explores the notions of research sponsorship and allocation and shows that leaders of research activity can be identified within specific disease areas of interest, such as those with high mortality or high sponsorship. The funding profiles of disease topics readily cluster themselves in agreement with the ontology hierarchy and closely mirror the funding agency priorities. Finally, four temporal trends are identified among research topics. This work utilizes disease ontology (DO)-based annotation to profile effectively the landscape of biomedical research activity. By using DO in this manner a use-case driven mechanism is also proposed to evaluate the utility of classification hierarchies.


Biochemical analysis of ++Prospero protein during asymmetric cell division: cortical Prospero is highly phosphorylated relative to nuclear Prospero.
Drosophila neuroblasts are a model system for studying asymmetric cell division. Neuroblasts bud off a series of smaller progeny, called ganglion mother cells (GMCs). An essential regulator of GMC development is the Prospero homeodomain transcription factor: Prospero is asymmetrically localized to the basal cortex of the mitotic neuroblast and partitioned into the newborn GMC. Prospero is translocated into the GMC nucleus, where it is necessary to establish GMC-specific gene expression. Cortical localization of Prospero protein is observed only during mitosis; cortical localization requires entry into mitosis and cortical delocalization requires exit from mitosis. The tight correlation and functional requirement between mitosis and cortical Prospero localization suggests that mitosis-specific posttranslational modifications may be involved in regulating Prospero subcellular localization. Here we use monoclonals recognizing the N-terminal or C-terminal region of Prospero to explore its posttranslational regulation. One- and two-dimensional Western analysis reveal a complex pattern of Prospero isoforms; phosphatase assays show that there are several phosphoisoforms of Prospero. Developmental 2D Western blots, cell fractionation assays, and analysis of a missense prospero mutation show that cortical Prospero protein is highly phosphorylated compared to nuclear Prospero protein. Our results are consistent with two functions of Prospero phosphorylation: (i) phosphorylation may be required for Prospero cortical localization; or (ii) phosphorylation may be a consequence of Prospero cortical localization, in which case it may facilitate subsequent events, such as Prospero cortical release or nuclear localization.


Effects of condensation in clothing on heat transfer.
A condensation theory is presented that enables the calculation of the rate of vapour transfer with its associated effects on temperature and total heat transfer inside a clothing ensemble consisting of underclothing, enclosed air, and outer garment. The model is experimentally tested by three experiments: (1) impermeable garments worn by subjects with and without plastic wrap around the skin, blocking sweat evaporation underneath the clothing; (2) comparison of heat loss in impermeable and semi-permeable garments and the associated discomfort and strain; (3) subjects working in impermeable garments in cool and warm environments at two work rates, until tolerance. The measured heat exchange and temperatures are calculated with satisfying accuracy by the model (mean error = 11, SD = 10 Wm-2 for heat flows and 0.3 and 0.9 degree C for temperatures, respectively). A numerical analysis shows that for total heat loss the major determinants are vapour permeability of the outer garment, skin vapour concentration and air temperature. In the cold the condensation mechanism may completely compensate for the lack of permeability of the clothing as far as heat dissipation is concerned, but in the heat impermeable clothing is more stressful.


Calcium binding and translocation properties of glucagon and its fragments.
Earlier studies have indicated that the N- and C-terminal regions of glucagon are functionally and structurally different. We have sought to understand this distinction in terms of the interaction of glucagon and its N- and C-terminal fragments with Ca2+, Mg2+, and Zn2+ in a nonpolar milieu. CD spectral data, in 98% (v/v) trifluoroethanol in water, reveal two binding sites for Ca2+ and Mg2+ and one site for Zn2+ in the intact hormone as well as in the C-terminal 19-29 fragment. The 1-6 fragment did not bind Zn2+ and formed a 2:1 peptide-Ca2+ or -Mg2+ complex. With glucagon and the 19-29 fragment, cation binding caused changes in the peptide's helix content. Fluorescence spectral changes involving Trp-25 in the 19-29 fragment and Trp-25 and Tyr-10 and/or Tyr-13 in glucagon were seen on Ca2+ binding to one of the two sites, while Zn2+ binding produced no change in fluorescence. The spectral data suggest that Ca2+ and Zn2+ binding sites (with Kd in the micromolar range in 98% trifluoroethanol) are distinct and are contained in the C-terminal domain of glucagon. Glucagon and the 19-29 fragment, but not the 1-6 fragment, caused an influx of Ca2+ (as monitored by spectral changes in arsenazo III) in unilamellar vesicles made of dimyristoyllecithin. Leakage of vesicle contents induced by the 19-29 fragment was minimal but was significant (approximately 10%) in the case of glucagon. The transport data suggest an interaction of the C-terminal domain of glucagon with Ca2+ at the lipid-water interface.(ABSTRACT TRUNCATED AT 250 WORDS)


Are the intrinsically disordered linkers involved in SSB binding to accessory proteins?
Escherichia coli single strand (ss) DNA binding (SSB) protein protects ssDNA intermediates and recruits at least 17 SSB interacting proteins (SIPs) during genome maintenance. The SSB C-termini contain a 9 residue acidic tip and a 56 residue intrinsically disordered linker (IDL). The acidic tip interacts with SIPs; however a recent proposal suggests that the IDL may also interact with SIPs. Here we examine the binding to four SIPs (RecO, PriC, PriA and χ subunit of DNA polymerase III) of three peptides containing the acidic tip and varying amounts of the IDL. Independent of IDL length, we find no differences in peptide binding to each individual SIP indicating that binding is due solely to the acidic tip. However, the tip shows specificity, with affinity decreasing in the order: RecO > PriA ∼ χ > PriC. Yet, RecO binding to the SSB tetramer and an SSB-ssDNA complex show significant thermodynamic differences compared to the peptides alone, suggesting that RecO interacts with another region of SSB, although not the IDL. SSB containing varying IDL deletions show different binding behavior, with the larger linker deletions inhibiting RecO binding, likely due to increased competition between the acidic tip interacting with DNA binding sites within SSB.


In vivo tracing of neural tracts in tiptoe walking Yoshimura mice by diffusion tensor tractography.
Basic imaging experiment. To determine whether in vivo diffusion tensor tractography (DTT) can be used to evaluate the axonal disruption of the chronically compressed spinal cord in tiptoe walking Yoshimura (twy) mice. In cervical ossification of the posterior longitudinal ligament, axonal disruption results in motor and sensory functional impairment. Twy mice develop spontaneous calcification in the cervical ligaments, which causes chronic compression of the spinal cord. DTT is emerging as a powerful tool for tracing axonal fibers in vivo. Five twy mice were subjected to DTT at 6, 15, and 20 weeks of age. Magnetic resonance imaging was performed using a 7.0-Tesla magnet (Biospec 70/16; Billerica, MA) with a CryoProbe. Diffusion tensor images were analyzed using TrackVis (Massachusetts General Hospital, MA). Motor performance was evaluated by Rotarod treadmill test and Digigait analysis. Histological analysis was performed by hematoxylin-eosin staining and immunostaining for RT-97 and SMI-31. High resolution DTT of twy mice in vivo was successful. A lower number of RT-97- or SMI-31-positive fibers were associated with more severe spinal cord compression, which was determined by observing the ligamentous calcification at the C2-C3 level in each twy mouse. The severity of canal stenosis based on magnetic resonance images was strongly correlated with the axial area of the spinal cord. The tract fiber (TF) ratio (the number of TFs at the C2-C3 level/the number of TFs at the C0-C1 level) was strongly correlated with the RT-97/SMI-31-positive area and with motor function (rotarod latency, stride length). Furthermore, a two-part linear regression analysis showed that canal stenosis around 50% to 60% caused a sharp decrease in the TF ratio before the deterioration of motor function. We conclude that DTT could be useful for detecting the early changes associated with the compressed spinal cord in cervical ossification of the posterior longitudinal ligament.


The functions of nonsuicidal self-injury: support for cognitive-affective regulation and opponent processes from a novel psychophysiological paradigm.
Although research on the reasons for engaging in nonsuicidal self-injury (NSSI) has increased dramatically in the last few years, there are still many aspects of this pernicious behavior that are not well understood. The purpose of this study was to address these gaps in the literature, with a particular focus on investigating whether NSSI (a) regulates affective valence in addition to affective arousal and (b) serves a cognitive regulation function in addition to an affect regulation function. To elucidate these issues, the present study utilized a sample of 112 participants (33 controls, 39 no pain controls, 16 NSSI individuals, and 24 controls matching the affect dysregulation levels of the NSSI group), employed psychophysiological measures of affective valence (startle-alone reactivity) and quality of information processing (prepulse inhibition), and used experimental methods involving an NSSI-proxy to model the NSSI process. Results largely were consistent with predictions, supporting the hypotheses that NSSI serves to regulate cognitive processing and affective valence. On this latter point, however, the control groups also showed a decrease in negative affective valence after the NSSI-proxy. This unexpected finding is consistent with the hypothesis that opponent processes may contribute to the development of self-injurious behaviors (Joiner, 2005). Overall, the present study represents an important extension of previous laboratory NSSI studies and provides a fertile foundation for future studies aimed at understanding why people engage in NSSI.


Evaluation of the cerebral hemodynamic response to rhythmic handgrip.
The response of the cerebral circulation to exercise has been studied with transcranial Doppler ultrasound (TCD) because this modality provides continuous measurements of blood velocity and is well suited for the exercise environment. The use of TCD as an index of cerebral blood flow, however, requires the assumption that the diameter of the insonated vessel is constant. Here, we examine this assumption for rhythmic handgrip using a spectral index designed to measure trends in vessel flow. Nineteen normal subjects were studied during 5 min of volitional maximum rhythmic right handgrip at 1 Hz. TCD velocities from both middle arteries (left and right), blood pressure, and end-tidal PCO(2) were recorded every 10 s. A spectral weighted sum was also calculated as a flow index (FI). Averages were computed from the last 2 min of handgrip. Relative changes in velocity, FI, and pressure were calculated. The validity of FI was tested by comparing the change in diameter derived from equations relating flow and diameter. Mean blood pressure increased 23.8 +/- 17.8% (SD), and velocity increased 13.3 +/- 9.8% (left) and 9.6 +/- 8.3% (right). Although the mean change in FI was small [2.0 +/- 18. 2% (left) and 4.7 +/- 29.7% (right)], the variation was high: some subjects showed a significant increase in FI and others a significant decrease. Diameter estimates from two equations relating flow and luminal area were not significantly different. Decreases in FI were associated with estimated diameter decreases of 10%. Our data suggest that the cerebral blood flow (CBF) response to rhythmic handgrip is heterogeneous and that middle cerebral artery flow can decrease in some subjects, in agreement with prior studies using the Kety-Schmidt technique. We speculate that the velocity increase is due to sympathetically mediated vasoconstriction rather than a ubiquitous flow increase. Our data suggest that the use of ordinary TCD velocities to interpret the CBF response during exercise may be invalid.


Electrophysiological and molecular identification of voltage-gated sodium channels in murine vascular myocytes.
A voltage-gated Na+ current was characterised in freshly dissociated mouse portal vein (PV) smooth muscle myocytes. The current was found superimposed upon the relatively slow L-type Ca2+ current and was resistant to conventional Ca2+ channel blockers but was abolished by external Na+ replacement and tetrodotoxin (TTX, 1 microM). The molecular identity of the channel responsible for this conductance was determined by RT-PCR where only the transcripts for Na+ channel genes SCN7a, 8a and 9a were detected. The presence of the protein counterparts to the SCN8a and 9a genes (NaV1.6 and NaV1.7, respectively) on the individual smooth muscle myocytes were confirmed in immunocytochemistry, which showed diffuse staining around a predominantly plasmalemmal location. TTX inhibited the action potential in individual myocytes generated in the current clamp mode but isometric tissue tension experiments revealed that TTX (1 and 5 microM) had no effect on the inherent mouse PV rhythmicity. However, the Na+ channel opener veratridine (10 and 50 microM) significantly increased the length of contraction and the interval between contractions. This effect was not influenced by pre-incubation with atropine, prazosin and propranolol, but was reversed by TTX (1 microM) and completely abolished by nicardipine (1 microM). Furthermore, preincubation with the reverse-mode Na+-Ca2+ exchange blocker KB-R7943 (10 microM) also inhibited the veratridine response. We have established for the first time the molecular identity of the voltage-gated Na+ channel in freshly dispersed smooth muscle cells and have shown that these channels can modulate contractility through a novel mechanism of action possibly involving reverse mode Na+-Ca2+ exchange.


Surfactant-assisted microwave processing of ZnO particles: a simple way for designing the surface-to-bulk defect ratio and improving photo(electro)catalytic properties.
ZnO nanopowders were produced using microwave processing of a precipitate and applied as a photoanode for photoelectrochemical water splitting. Two different surfactants, cetyltrimethylammonium bromide (CTAB) as the cationic and Pluronic F127 as the non-ionic one, were employed to in situ adjust the surface-to-bulk defect ratio in the ZnO crystal structure and further to modify the photo(electro)catalytic activity of the ZnO photoanode. The crystal structure, morphological, textural, optical and photo(electro)catalytic properties of ZnO particles were studied in detail to explain the profound effects of the surfactants on the photoanode activity. The ZnO/CTAB photoanode displayed the highest photocurrent density of 27 mA g-1, compared to ZnO (10.4 mA g-1) and ZnO/F127 photoanodes (20 mA g-1) at 1.5 V vs. SCE in 0.1 M Na2SO4 under visible illumination of 90 mW cm-2. A significant shift of the overpotential toward lower values was also observed when photoanodes were illuminated. The highest shift of the overpotential, from 1.296 to 0.248 V vs. SCE, was recorded when the ZnO/CTAB photanode was illuminated. The ZnO/CTAB photoanode provides efficient charge transfer across the electrode/electrolyte interface, with a longer lifetime of photogenerated electron-hole pairs and reduced possibility of charge recombination. The photoconversion efficiency was improved from 1.4% for ZnO and 0.9% for ZnO/F127 to 4.2% for ZnO/CTAB at 0.510 mV. A simple procedure for the synthesis of ZnO particles with improved photo(electro)catalytic properties was established and it was found that even a small amount of CTAB used during processing of ZnO increases the surface-to-bulk defect ratio. Optimization of the surface-to-bulk defect ratio in ZnO materials enables increase of the absorption capacity for visible light, rendering of the recombination rate of the photogenerated pair, as well as increase of both the photocurrent density and photoconversion efficiency.


Bardoxolone Methyl Prevents Mesenteric Fat Deposition and Inflammation in High-Fat Diet Mice.
Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue.


Petrocarbon evolution: Ramped pyrolysis/oxidation and isotopic studies of contaminated oil sediments from the Deepwater Horizon oil spill in the Gulf of Mexico.
Hydrocarbons released during the Deepwater Horizon (DWH) oil spill weathered due to exposure to oxygen, light, and microbes. During weathering, the hydrocarbons' reactivity and lability was altered, but it remained identifiable as "petrocarbon" due to its retention of the distinctive isotope signatures (14C and 13C) of petroleum. Relative to the initial estimates of the quantity of oil-residue deposited in Gulf sediments based on 2010-2011 data, the overall coverage and quantity of the fossil carbon on the seafloor has been attenuated. To analyze recovery of oil contaminated deep-sea sediments in the northern Gulf of Mexico we tracked the carbon isotopic composition (13C and 14C, radiocarbon) of bulk sedimentary organic carbon through time at 4 sites. Using ramped pyrolysis/oxidation, we determined the thermochemical stability of sediment organic matter at 5 sites, two of these in time series. There were clear differences between crude oil (which decomposed at a lower temperature during ramped oxidation), natural hydrocarbon seep sediment (decomposing at a higher temperature; Δ14C = -912‰) and our control site (decomposing at a moderate temperature; Δ14C = -189‰), in both the stability (ability to withstand ramped temperatures in oxic conditions) and carbon isotope signatures. We observed recovery toward our control site bulk Δ14C composition at sites further from the wellhead in ~4 years, whereas sites in closer proximity had longer recovery times. The thermographs also indicated temporal changes in the composition of contaminated sediment, with shifts towards higher temperature CO2 evolution over time at a site near the wellhead, and loss of higher temperature CO2 peaks at a more distant site.


Comparison of job satisfaction and stress among male and female doctors in teaching hospitals of Karachi.
Job dissatisfaction and stress among doctors affect the quality of health care. We assessed the levels of satisfaction for workplace characteristics and job stress among doctors of three teaching hospitals in Karachi. A postal-survey was conducted between May to June 2002. Satisfaction for workplace characteristics and stress were inquired and graded by Likert scale (1 = very low to 5 = very high). Questions were also asked about its affect on their lives. In order to calculate the differences in means of job satisfaction and stress score by sex of doctors, chi-square and t-test with 95% confidence interval (CI) were used. Out of 270 doctors approached conveniently, 189 (70%) responded and 182 questionnaires were found complete for analysis. Majority (68%) of the doctors was not satisfied with their jobs. Overall, the mean scores for satisfaction were low for workplace characteristics. Lowest scores were found for pay and benefits 2.12 (SE 0.8), safety and security 2.15 (SE 0.8) and workload 2.69 (SE 0.9). Female doctors had significantly lower satisfaction about workload (mean job satisfaction score difference = 0.60; 95%CI, 0.24-0.97), relation with colleagues (mean job satisfaction score difference = 0.49: 95%CI, 0.11-0.87) and autonomy (mean job satisfaction score difference = 0.45; 95%CI, 0.07-0.82) as compared to their male counterparts. Overall, 48% of doctors graded job stress from high to very high levels. Majority of doctors working at these teaching hospitals of Karachi had poor satisfaction level for workplace characteristics and higher levels of job stress. This suggests that immediate steps should be taken for their control and management. This study invites further research to explore, implement and evaluate intervention strategies for prevention of stress and improvement in job satisfaction.


Improved Environment-Aware-Based Noise Reduction System for Cochlear Implant Users Based on a Knowledge Transfer Approach: Development and Usability Study.
Cochlear implant technology is a well-known approach to help deaf individuals hear speech again and can improve speech intelligibility in quiet conditions; however, it still has room for improvement in noisy conditions. More recently, it has been proven that deep learning-based noise reduction, such as noise classification and deep denoising autoencoder (NC+DDAE), can benefit the intelligibility performance of patients with cochlear implants compared to classical noise reduction algorithms. Following the successful implementation of the NC+DDAE model in our previous study, this study aimed to propose an advanced noise reduction system using knowledge transfer technology, called NC+DDAE_T; examine the proposed NC+DDAE_T noise reduction system using objective evaluations and subjective listening tests; and investigate which layer substitution of the knowledge transfer technology in the NC+DDAE_T noise reduction system provides the best outcome. The knowledge transfer technology was adopted to reduce the number of parameters of the NC+DDAE_T compared with the NC+DDAE. We investigated which layer should be substituted using short-time objective intelligibility and perceptual evaluation of speech quality scores as well as t-distributed stochastic neighbor embedding to visualize the features in each model layer. Moreover, we enrolled 10 cochlear implant users for listening tests to evaluate the benefits of the newly developed NC+DDAE_T. The experimental results showed that substituting the middle layer (ie, the second layer in this study) of the noise-independent DDAE (NI-DDAE) model achieved the best performance gain regarding short-time objective intelligibility and perceptual evaluation of speech quality scores. Therefore, the parameters of layer 3 in the NI-DDAE were chosen to be replaced, thereby establishing the NC+DDAE_T. Both objective and listening test results showed that the proposed NC+DDAE_T noise reduction system achieved similar performances compared with the previous NC+DDAE in several noisy test conditions. However, the proposed NC+DDAE_T only required a quarter of the number of parameters compared to the NC+DDAE. This study demonstrated that knowledge transfer technology can help reduce the number of parameters in an NC+DDAE while keeping similar performance rates. This suggests that the proposed NC+DDAE_T model may reduce the implementation costs of this noise reduction system and provide more benefits for cochlear implant users.


Influence of endocardial-epicardial crossover of muscle fibers on left ventricular wall mechanics.
The influence of variations of fiber direction on the distribution of stress and strain in the left ventricular wall was investigated using a finite element model to simulate the mechanics of the left ventricle. The commonly modelled helix fiber angle was defined as the angle between the local circumferential direction and the projection of the fiber path on the plane perpendicular to the local radial direction. In the present study, an additional angle, the transverse fiber angle, was used to model the continuous course of the muscle fibers between the inner and the outer layers of the ventricular wall. This angle was defined as the angle between the circumferential direction and the projection of the fiber path on the plane perpendicular to the local longitudinal direction. First, a reference simulation of left ventricular mechanics during a cardiac cycle was performed, in which the transverse angle was set to zero. Next, we performed two simulations in which the spatial distribution of either the transverse or the helix angle was varied with respect to the reference situation, the spatially averaged variations being about 3 and 14 degrees, respectively. The changes in fiber orientation hardly affected the pressure-volume relation of the ventricle, but significantly affected the spatial distribution of active muscle fiber stress (up to 50% change) and sarcomere length (up to 0.1 micron change). In the basal and apical region of the wall, shear deformation in the circumferential-radial plane was significantly reduced by introduction of a nonzero transverse angle. Thus, the loading of the passive tissue may be reduced by the endocardial-epicardial crossover of the muscle fibers.


Suppression of plasma renin activity in a boy with chronic hyperkalemia.
Chronic hyperkalemia (6.8 mmol/L [6.8 mEq/L]) was discovered in a boy, aged 13 years 7 months, with short stature, delayed puberty, and normal blood pressure. Additional studies revealed hyperchloremic metabolic acidosis (serum values: sodium ion, 139 mmol/L [139 mEq/L]; chloride, 113 mmol/L [113 mEq/L]; bicarbonate, 18 mmol/L [18 mEq/L]), a normal glomerular filtration rate, a subnormal renal threshold for bicarbonate reabsorption, and normal serum thyroxine, growth hormone, and cortisol values. Renal excretion of potassium ion was subnormal for the prevailing serum concentration of potassium ion but was increased normally by infusion of sodium sulfate. The serum aldosterone concentration was appropriate for a normokalemic subject, despite marked suppression of plasma renin activity (PRA) (supine/upright: aldosterone, 140/580 pmol/L [5/21 ng/dL]; PRA, 0.0/0.03 ng/L X s [0.0/0.1 ng/mL/h]). Treatment with chlorothiazide and sodium chloride resulted in correction of the abnormal electrolyte concentrations and an increase in linear growth velocity. Serum aldosterone concentrations did not change significantly during treatment, even though the PRA had increased (supine/upright: aldosterone, 110/920 pmol/L [4/33 ng/dL]; PRA, 0.89/2.17 ng/L X s [3.2/7.8 ng/mL/h]). In this patient, we conclude that (1) hyperkalemia was due to inadequate renal excretion of potassium ion; (2) the serum potassium ion concentration was the major stimulus to aldosterone secretion before treatment; (3) suppression of PRA was more likely due to hyperkalemia than to extracellular volume expansion.


Patient concerns regarding chronic hepatitis C infections.
Counselling of patients with chronic hepatitis C infections is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counselling strategies and content. Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them. The most common volunteered concerns of newly diagnosed patients in decreasing order were: disease progression (27%), premature death (19%), infecting family members (13%), side-effects of treatment (11%) and miscellaneous others. In decreasing order, prioritized concerns included: infecting family members, development of liver cancer, infecting others, development of cirrhosis, social stigma of having liver disease, need for liver transplant and loss of employment. The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, modes of viral acquisition and in the case of follow-up patients, duration of follow-up. These results indicate that health care providers who focus counselling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection.


Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro.
Curcumin, a polyphenolic compound derived from turmeric, protects against myocardial injury by alleviating oxidative stress, inflammation, apoptosis, and fibrosis. However, the role of curcumin and its mechanism of action on interstitial fibrosis after myocardial infarction (MI) are poorly understood. To clarify, MI was induced by a permanent ligation of the left anterior descending coronary artery in adult mice, and the effects of curcumin were evaluated 4 weeks after the MI event. In vitro, we treated cardiac fibroblasts (CFs) with Ang II, and investigated the anti-fibrotic mechanism of curcumin. Our results showed that curcumin significantly attenuated collagen deposition in vivo and inhibited CF proliferation and migration, and MMP expression. In addition, we found that the down-regulation of SIRT1 after MI was attenuated by curcumin pretreatment, which indicated that the activation of SIRT1 might be involved in the protective action of curcumin. This hypothesis was confirmed by genetic inhibition of SIRT1 (siRNA-SIRT1) in Ang II-treated CFs. Our results provide new insights into the mechanism underlying the anti-fibrotic effects of curcumin in the heart.


The Biological and Social Determinants of Childhood Obesity: Comparison of 2 Cohorts 50 Years Apart.
To determine whether the same relationships between early-life risk factors and socioeconomic status (SES) with childhood body mass index (BMI) are observed in a modern cohort (2000) compared with a historic cohort (1947). The relationships between early-life factors and SES with childhood BMI were examined in 2 prospective birth cohorts from the same region, born 50 years apart: 711 children in the 1947 Newcastle Thousand Families Study (NTFS) and 475 from the 2000 Gateshead Millennium Study (GMS). The associations between birth weight, breastfeeding, rapid infancy growth (0-12 months), early-life adversity (0-12 months), and parental SES (birth and childhood) with childhood BMI z-scores and whether overweight/obese (BMI >91st percentile using UK 1990 reference) aged 9 years were examined using linear regression, path analyses, and logistic regression. In the NTFS, the most advantaged children were taller than the least (+0.91 height z-score, P = .001), whereas in GMS they had lower odds of overweight/obese than the least (0.35 [95% CI 0.14-0.86]). Rapid infancy growth was associated with increased BMI z-scores in both cohorts, and with increased likelihood of overweight/obese in GMS. This study suggests that children exposed to socioeconomic disadvantage or who have rapid infancy growth in modern environments are now at lower risk of growth restriction but greater risk of overweight.


Safety and efficacy of the oral direct factor xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation. -The ARISTOTLE-J study-.
Guidelines recommend warfarin as the standard of care for patients with atrial fibrillation (AF) at moderate or high risk for stroke. This phase II study assessed the effects of 2 doses of the factor Xa inhibitor apixaban vs. warfarin in Japanese patients with non-valvular AF. The composite primary endpoint was major and clinically relevant non-major (CRNM) bleeding. Two hundred and twenty-two patients with AF and 1 or more additional risk factors for stroke were randomized (1:1:1) to double-blind apixaban 2.5 or 5mg b.i.d. or open-label warfarin (target international normalized ratio 2.0-3.0; 2.0-2.6 if age ≥ 70 years) for 12 weeks. The primary endpoint occurred in 1 patient (1.4%) in each apixaban group and 4 (5.3%) warfarin patients. There were no strokes, systemic emboli, myocardial infarctions, or deaths in either apixaban group. The warfarin group had 2 ischemic strokes and 1 subarachnoid hemorrhage, but there were no deaths. Major and CRNM bleeds each occurred with higher frequency in the warfarin group vs. either apixaban group. Most adverse events were mild or moderate. No patients had hepatic aminotransferase elevations greater than 3 times the upper limit of normal. In Japanese patients with AF, apixaban 2.5 and 5mg b.i.d. were well tolerated over 12 weeks. A global phase III trial, which includes Japanese patients, is ongoing (ClinicalTrials.gov Identifier NCT00787150).


High-accuracy and high-sensitivity spectroscopic measurement of dinitrogen pentoxide (N2O5) in an atmospheric simulation chamber using a quantum cascade laser.
A spectroscopic instrument based on a mid-infrared external cavity quantum cascade laser (EC-QCL) was developed for high-accuracy measurements of dinitrogen pentoxide (N2O5) at the ppbv-level. A specific concentration retrieval algorithm was developed to remove, from the broadband absorption spectrum of N2O5, both etalon fringes resulting from the EC-QCL intrinsic structure and spectral interference lines of H2O vapour absorption, which led to a significant improvement in measurement accuracy and detection sensitivity (by a factor of 10), compared to using a traditional algorithm for gas concentration retrieval. The developed EC-QCL-based N2O5 sensing platform was evaluated by real-time tracking N2O5 concentration in its most important nocturnal tropospheric chemical reaction of NO3 + NO2 ↔ N2O5 in an atmospheric simulation chamber. Based on an optical absorption path-length of Leff = 70 m, a minimum detection limit of 15 ppbv was achieved with a 25 s integration time and it was down to 3 ppbv in 400 s. The equilibrium rate constant Keq involved in the above chemical reaction was determined with direct concentration measurements using the developed EC-QCL sensing platform, which was in good agreement with the theoretical value deduced from a referenced empirical formula under well controlled experimental conditions. The present work demonstrates the potential and the unique advantage of the use of a modern external cavity quantum cascade laser for applications in direct quantitative measurement of broadband absorption of key molecular species involved in chemical kinetic and climate-change related tropospheric chemistry.


Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway.
The Fat mass and obesity gene (FTO) has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI). However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression. We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2), cAMP-dependent protein kinase catalytic subunit beta (Prkacb), Brain derived neurotrophic factor (Bdnf), neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2), Signal transducer and activator of transcription 3 (Stat3), and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation. Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein β (C/EBPβ).


Cost of dialysis therapies in rural and remote Australia - a micro-costing analysis.
Maintenance dialysis is a costly and resource intense activity. In Australia, inadequate health infrastructure and poor access to technically skilled staff can limit service provision in remote areas where many Aboriginal dialysis patients live. With most studies based on urban service provision, there is little evidence to guide service development. However permanent relocation to an urban area for treatment can have significant social and financial impacts that are poorly quantified. This study is part of a broader project to quantify the costs and benefits of dialysis service models in urban and remote locations in Australia's Northern Territory (NT). We undertook a micro-costing analysis of dialysis service delivery costs in urban, rural and remote areas in the NT from the payer perspective. Recurrent maintenance costs (salaries, consumables, facility management and transportation) as well as capital costs were included. Missing and centralised costs were standardised; results were inflated to 2017 values and reported in Australian dollars. There was little difference between the average annual cost for urban and rural services with respective median costs of $85,919 versus $84,629. However remote service costs were higher ($120,172 - $124,492), driven by higher staff costs. The inclusion of capital costs did not add substantially to annual costs. Annual home haemodialysis costs ($42,927) were similar to other jurisdictions despite the significant differences in program delivery and payment of expenses not traditionally borne by governments. Annual peritoneal dialysis costs ($58,489) were both higher than home and in-centre haemodialysis by recent national dialysis cost studies. The cost drivers for staffed services were staffing models and patient attendance rates. Staff salaries and transport costs were significantly higher in remote models of care. Opportunities to reduce expenditure exist by encouraging community supported services and employing local staff. Despite the delivery challenges of home haemodialysis including high patient attrition, the program still provides a cost benefit compared to urban staffed services. The next component of this study will examine patient health service utilisation and costs by model of care to provide a more comprehensive analysis of the overall cost of providing services in each location.


Multilevel modelling of the incidence of visceral leishmaniasis in Teresina, Brazil.
Epidemics of visceral leishmaniasis (VL) in major Brazilian cities are new phenomena since 1980. As determinants of transmission in urban settings probably operate at different geographic scales, and information is not available for each scale, a multilevel approach was used to examine the effect of canine infection and environmental and socio-economic factors on the spatial variability of incidence rates of VL in the city of Teresina. Details on an outbreak of greater than 1200 cases of VL in Teresina during 1993-1996 were available at two hierarchical levels: census tracts (socio-economic characteristics, incidence rates of human VL) and districts, which encompass census tracts (prevalence of canine infection). Remotely sensed data obtained by satellite generated environmental information at both levels. Data from census tracts and districts were analysed simultaneously by multilevel modelling. Poor socio-economic conditions and increased vegetation were associated with a high incidence of human VL. Increasing prevalence of canine infection also predicted a high incidence of human VL, as did high prevalence of canine infection before and during the epidemic. Poor socio-economic conditions had an amplifying effect on the association between canine infection and the incidence of human VL. Focusing interventions on areas with characteristics identified by multilevel analysis could be a cost-effective strategy for controlling VL. Because risk factors for infectious diseases operate simultaneously at several levels and ecological data usually are available at different geographical scales, multilevel modelling is a valuable tool for epidemiological investigation of disease transmission.


Indirect measurement of a laser communications bit-error-rate reduction with low-order adaptive optics.
In experimental measurements of the bit-error rate for a laser communication system, we show improved performance with the implementation of low-order (tip/tilt) adaptive optics in a free-space link. With simulated atmospheric tilt injected by a conventional piezoelectric tilt mirror, an adaptive optics system with a Xinetics tilt mirror was used in a closed loop. The laboratory experiment replicated a monostatic propagation with a cooperative wave front beacon at the receiver. Owing to constraints in the speed of the processing hardware, the data is scaled to represent an actual propagation of a few kilometers under moderate scintillation conditions. We compare the experimental data and indirect measurement of the bit-error rate before correction and after correction, with a theoretical prediction.


Acousto-optic interaction in alpha-BaB(2)O(4)and Li(2)B(4)O(7) crystals.
Experimental studies and analysis of acousto-optic diffraction in alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals are given. Ultrasonic wave velocity, elastic compliance and stiffness coefficients, and piezo-optic and photoelastic coefficients of alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals are determined. The acousto-optic figure of merit has been estimated for different possible geometries of acousto-optic interaction. It is shown that the acousto-optic figures of merit for alpha-BaB(2)O(4) crystals reach the value M(2)=(270 +/- 70) x 10(-15) s(3)/kg for the case of interaction with the slowest ultrasonic wave. The directions of propagation and polarization of those acoustic waves are obtained on the basis of construction of acoustic slowness surfaces. The acousto-optic diffraction is experimentally studied for alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals.


Hyaloperonospora camelinae on Camelina sativa in Washington State: Detection, Seed Transmission, and Chemical Control.
Camelina (Camelina sativa) plants with symptoms of downy mildew were obtained from three different locations in Washington State. Based on polymerase chain reaction (PCR) and sequencing of the internal transcribed spacer (ITS)1-5.8S-ITS2 region, the causal pathogen was identified as Hyaloperonospora camelinae. The PCR primers consistently amplified 699-bp bands from the infected plants but not from the asymptomatic plants. A comparison of the sequences with those in GenBank revealed 100% sequence similarity to H. camelinae. Growth and development of the H. camelinae was observed in different tissues using light microscopy and scanning electron microscopy (SEM). Light microscopic observation revealed the presence of oospores in the infected leaves and SEM revealed the presence of conidia and conidiophores on the seed surface. To determine whether H. camelinae is a seed-transmitted pathogen, seed collected from infected plants were planted in Sunshine professional growing mix maintained in a growth chamber. Disease symptoms were observed in 96% of the seedlings compared with 3% of the seedlings grown from seed from asymptomatic plants, which indicates that H. camelinae is a seed-transmitted pathogen. Seed treated with mefenoxam, a fungicide specific for Oomycetes, significantly reduced the incidence of the disease.


Contribution of IL-18 to eosinophilic airway inflammation induced by immunization and challenge with Staphylococcus aureus proteins.
We previously reported that intranasal challenge with ovalbumin (OVA) plus IL-18 induces airway hyperresponsiveness (AHR) and eosinophilic airway inflammation in mice with OVA-specific T(h)1 cells. These two conditions can be prevented by neutralizing anti-IFN-gamma and anti-IL-13 antibodies, respectively. The mice develop AHR and eosinophilic airway inflammation after challenge with OVA plus LPS instead of IL-18 and endogenous IL-18 is known to be involved. In contrast, IL-18 does not facilitate these changes in mice possessing OVA-specific T(h)2 cells. Here, we investigated whether IL-18 is involved in the development of asthma in mice immunized and challenged with bacterial proteins. Upon intranasal exposure to protein A (SpA) derived from Staphylococcus aureus, mice immunized with SpA exhibited AHR and peribronchial eosinophilic inflammation if IFN-gamma or IL-13 were present, respectively. The CD4(+) T cells from draining lymph nodes (DLNs) of the SpA-immunized and -challenged mice produced a robust IFN-gamma and IL-13 in response to immobilized anti-CD3 antibodies. Treatment with neutralizing anti-IL-18 antibodies prevented asthmatic inflammation concomitant with their impaired potential to express IFN-gamma and IL-13. Furthermore, naive mice that received the CD4(+) T cells from DLNs of SpA-immunized mice developed airway inflammation depending upon the presence of IL-18. Immunodeficient mice that received human PBMCs, which had been stimulated with SpA in vitro, developed dense peribronchial accumulation of human CD4(+) T cells upon SpA challenge. Neutralizing anti-human IL-18 antibodies protected against this airway inflammation. These results suggest the importance of IL-18 for the development of asthmatic inflammation associated with airway exposure to bacterial proteins.


Analysis of three-dimensional SAR distributions emitted by mobile phones in an epidemiological perspective.
The three-dimensional distribution of the specific absorption rate of energy (SAR) in phantom models was analysed to detect clusters of mobile phones producing similar spatial deposition of energy in the head. The clusters' characteristics were described from the phones external features, frequency band and communication protocol. Compliance measurements with phones in cheek and tilt positions, and on the left and right side of a physical phantom were used. Phones used the Personal Digital Cellular (PDC), Code division multiple access One (CdmaOne), Global System for Mobile Communications (GSM) and Nordic Mobile Telephony (NMT) communication systems, in the 800, 900, 1500 and 1800 MHz bands. Each phone's measurements were summarised by the half-ellipsoid in which the SAR values were above half the maximum value. Cluster analysis used the Partitioning Around Medoids algorithm. The dissimilarity measure was based on the overlap of the ellipsoids, and the Manhattan distance was used for robustness analysis. Within the 800 MHz frequency band, and in part within the 900 MHz and the 1800 MHz frequency bands, weak clustering was obtained for the handset shape (bar phone, flip with top and flip with central antennas), but only in specific positions (tilt or cheek). On measurements of 120 phones, the three-dimensional distribution of SAR in phantom models did not appear to be related to particular external phone characteristics or measurement characteristics, which could be used for refining the assessment of exposure to radiofrequency energy within the brain in epidemiological studies such as the Interphone.


Involvement of the cannabinoid system in chronic inflammatory intestinal diseases: opportunities for new therapies.
The components of the endogenous cannabinoid system are widely expressed in the gastrointestinal tract contributing to local homeostasis. In general, cannabinoids exert inhibitory actions in the gastrointestinal tract, inducing anti-inflammatory, antiemetic, antisecretory, and antiproliferative effects. Therefore, cannabinoids are interesting pharmacological compounds for the treatment of several acute intestinal disorders, such as dysmotility, emesis, and abdominal pain. Likewise, the role of cannabinoids in the treatment of chronic intestinal diseases, such as irritable bowel syndrome and inflammatory bowel disease, is also under investigation. Patients with chronic intestinal inflammatory diseases present impaired quality of life, and mental health issues are commonly associated with long-term chronic diseases. The complex pathophysiology of these diseases contributes to difficulties in diagnosis and, therefore, in the choice of a satisfactory treatment. Thus, this article reviews the involvement of the cannabinoid system in chronic inflammatory diseases that affect the gastrointestinal tract and highlights possible therapeutic approaches related to the use of cannabinoids.


Prospective Comparative Study of Oral Versus Vaginal Misoprostol for Second-Trimester Termination of Pregnancy.
Various medical methods for second-trimester medical termination of pregnancy (MTP) exist. Misoprostol alone has been used with myriad variations in route and dosage. Comparison between oral and vaginal routes of misoprostol forms the basis of this study. This was a prospective comparative study of misoprostol for second-trimester (14-20 weeks) MTP, comparing oral versus vaginal routes. Sixty patients were randomly allotted to two groups; 30 received oral misoprostol 400 µg 4 h up to a maximum of five doses (2000 µg), and 30 received vaginal misoprostol in the same dose and duration. In both groups, oxytocin infusion was started if abortion did not occur. Efficacy of oral versus vaginal misoprostol, induction-abortion interval (AI) and need for surgical intervention were analyzed. Both groups were well matched in terms of age, parity, previous LSCS, mean gestational age and indication for MTP. Overall mean induction-abortion interval was 19.59 h (21.66 vs. 18.57 h, oral vs. vaginal, respectively), with vaginal group taking lesser time (p 0.09). Sixty percentage in oral group required five doses, while 70% in vaginal group required 3-4 doses of misoprostol (p 0.010). 23.7 versus 6.7% in oral versus vaginal group required check curettage (p 0.038). There were no major complications, and there was only one failure in oral group. Though both oral and vaginal misoprostol are safe, vaginal route appears to be more efficacious for second-trimester MTP.


Type-II myocardial infarction--patient characteristics, management and outcomes.
Type-II MI is defined as myocardial infarction (MI) secondary to ischemia due to either increased oxygen demand or decreased supply. This categorization has been used for the last five years, yet, little is known about patient characteristics and clinical outcomes. In the current work we assessed the epidemiology, causes, management and outcomes of type II MI patients. A comparative analysis was performed between patients with type-I and type-II MI who participated in two prospective national Acute Coronary Syndrome Israeli Surveys (ACSIS) performed in 2008 and 2010. The surveys included 2818 patients with acute MI of whom 127 (4.5%) had type-II MI. The main causes of type-II MI were anemia (31%), sepsis (24%), and arrhythmia (17%). Patients with type-II MI tended to be older (75.6±12 vs. 63.8±13, p<0.0001), female majority (43.3% vs. 22.3%, p<0.0001), had more frequently impaired functional level (45.7% vs. 17%, p<0.0001) and a higher GRACE risk score (150±32 vs. 110±35, p<0.0001). Patients with type-II MI were significantly less often referred for coronary interventions (36% vs. 89%, p<0.0001) and less frequently prescribed guideline-directed medical therapy. Mortality rates were substantially higher among patients with type-II MI both at thirty-day (13.6% vs. 4.9%, p<0.0001) and at one-year (23.9% vs. 8.6%, p<0.0001) follow-ups. Patients with type-II compared to type-I MI have distinct demographics, increased prevalence of multiple comorbidities, a high-risk cardiovascular profile and an overall worse outcome. The complex medical condition of this cohort imposes a great therapeutic challenge and specific guidelines with recommended medical treatment and invasive strategies are warranted.


RNA interference inhibits replication of tick-borne encephalitis virus in vitro.
Each year, up to 10,000 cases of infections with the flavivirus tick-borne encephalitis (TBE) virus that affect the central nervous system are reported in Europe and Asia. Due to the potentially severe adverse effects of post-exposure prophylaxis with TBE virus hyperimmunoglobulin, TBE can currently only be treated symptomatically. An RNA interference (RNAi) approach to inhibit TBE virus replication was therefore developed. In this study we demonstrate for the first time that small interfering RNAs (siRNAs) targeted at the TBE virus genome reduce the quantity of infectious TBE virus particles, TBE virus genome, and TBE virus protein in vitro by up to 85%. The 50% inhibitory dose (DI(50)) of the shRNA plasmid was only 0.05μg/ml. As RNAi-based therapeutics for other diseases are already being evaluated in phases II and III clinical trials, it is possible that RNAi could become valuable tool for controlling TBE virus infection.


Dune-slope activity due to frost and wind throughout the north polar erg, Mars.
Repeat, high-resolution imaging of dunes within the Martian north polar erg have shown that these dune slopes are very active, with alcoves forming along the dune brink each Mars year. In some areas, a few hundred cubic metres of downslope sand movement have been observed, sometimes moving the dune brink 'backwards'. Based on morphological and activity-timing similarities of these north polar features to southern dune gullies, identifying the processes forming these features is likely to have relevance for understanding the general evolution/modification of dune gullies. To determine alcove-formation model constraints, we have surveyed seven dune fields, each over 1-4 Mars winters. Consistent with earlier reports, we found that alcove-formation activity occurs during the autumn-winter seasons, before or while the stable seasonal frost layer is deposited. We propose a new model in which alcove formation occurs during the autumn, and springtime sublimation activity then enhances the feature. Summertime winds blow sand into the new alcoves, erasing small alcoves over a few Mars years. Based on the observed rate of alcove erasure, we estimated the effective aeolian sand transport flux. From this, we proposed that alcove formation may account for 2-20% of the total sand movement within these dune fields.


NOX4 (NADPH Oxidase 4) and Poldip2 (Polymerase δ-Interacting Protein 2) Induce Filamentous Actin Oxidation and Promote Its Interaction With Vinculin During Integrin-Mediated Cell Adhesion.
Objective- Actin cytoskeleton assembly and organization, as a result of focal adhesion (FA) formation during cell adhesion, are dependent on reactive oxygen species and the cellular redox environment. Poldip2 (polymerase δ-interacting protein 2), a novel regulator of NOX4 (NADPH oxidase 4), plays a significant role in reactive oxygen species production and cytoskeletal remodeling. Thus, we hypothesized that endogenous reactive oxygen species derived from Poldip2/NOX4 contribute to redox regulation of actin and cytoskeleton assembly during integrin-mediated cell adhesion. Approach and Results- Using vascular smooth muscle cells, we verified that hydrogen peroxide (H2O2) levels increase during integrin-mediated cell attachment as a result of activation of NOX4. Filamentous actin (F-actin) was oxidized by sulfenylation during cell attachment, with a peak at 3 hours (0.80±0.04 versus 0.08±0.13 arbitrary units at time zero), which was enhanced by overexpression of Poldip2. Depletion of Poldip2 or NOX4 using siRNA, or scavenging of endogenous H2O2 with catalase, inhibited F-actin oxidation by 78±26%, 99±1%, and 98±1%, respectively. To determine the consequence of F-actin oxidation, we examined the binding of F-actin to vinculin, a protein involved in FA complexes that regulates FA maturation. Vinculin binding during cell adhesion as well as migration capacity were inhibited after transfection with actin containing 2 oxidation-resistant point mutations (C272A and C374A). Silencing of Poldip2 or NOX4 also impaired actin-vinculin interaction, which disturbed maturation of FAs and inhibited cell migration. Conclusions- These results suggest that integrin engagement during cell attachment activates Poldip2/Nox4 to oxidize actin, which modulates FA assembly.


Protective effects of hydrogen-rich saline against erectile dysfunction in a streptozotocin induced diabetic rat model.
Hydrogen has antioxidative stress and anti-inflammatory effects. We investigated the effect of hydrogen on erectile dysfunction in streptozotocin induced diabetic rats. Diabetes was induced in Sprague-Dawley® rats by a single intravenous injection of streptozotocin. Diabetic rats were then randomized to a diabetes mellitus group and to a diabetic group that received hydrogen saline. The latter 8 rats were fed saturated hydrogen saline (5 ml/kg per day) by intragastric administration for 8 weeks. At the end of week 8 erectile function was assessed by measuring the increase in intracavernous pressure after cavernous nerve electrostimulation. We measured nitric oxide synthase activity, and malondialdehyde, 8-hydroxydeoxyguanosine, and nitrite and nitrate in the corpus cavernosum. eNOS protein immunolocalization in cavernous tissues was detected by immunohistochemistry. eNOS, Bcl-2 and Bax protein expression was determined by Western blot. We determined eNOS, Bcl-2 and Bax mRNA using real-time reverse transcriptase-polymerase chain reaction. Oxidative stress is involved in the pathophysiological mechanism of erectile dysfunction. Maximum intracavernous pressure in diabetic rats decreased significantly compared to controls and increased significantly compared to untreated diabetic rats after hydrogen-rich saline treatment. Decreased nitric oxide synthase activity, nitrite and nitrate, and eNOS expression as well as increased 8-hydroxydeoxyguanosine and malondialdehyde were found in the diabetic group compared to controls. Hydrogen-rich saline improved nitric oxide synthase activity, and malondialdehyde, nitrite and nitrate, and 8-hydroxydeoxyguanosine levels in the diabetic rat corpus cavernosum. Decreased eNOS in diabetic rats was ameliorated by hydrogen-rich saline. Also, apoptosis in the diabetic rat corpus cavernosum was significantly enhanced compared with controls. Hydrogen-rich saline therapy may decrease apoptosis in cavernous tissues and it ameliorated erectile dysfunction in diabetic rats by inhibiting oxidative stress and apoptosis. Hydrogen-rich saline effectively improved erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction.


Age Does Not Affect the Material Properties of Expanded Polystyrene Liners in Field-Used Bicycle Helmets.
Bicycle helmet foam liners absorb energy during impacts. Our goal was to determine if the impact attenuation properties of expanded polystyrene (EPS) foam used in bicycle helmets change with age. Foam cores were extracted from 63 used and unused bicycle helmets from ten different models spanning an age range of 2-20 yrs. All cores were impact tested at a bulk strain rate of 195 s(-1). Six dependent variables were determined from the stress-strain curve derived from each impact (yield strain, yield stress, elastic modulus, plateau slope, energy at 65% compression, and stress at 65% compression), and a general linear model was used to assess the effect of age on each dependent variable with density as a covariate. Age did not affect any of the dependent variables; however, greater foam density, which varied from 58 to 100 kg/m(3), generated significant increases in all of the dependent variables except for yield strain. Higher density foam cores also exhibited lower strains at which densification began to occur, tended to stay within the plateau region of the stress-strain curve, and were not compressed as much compared with the lower density cores. Based on these data, the impact attenuation properties of EPS foam in field-used bicycle helmets do not degrade with the age.


Ultrasound-guided catheterization of the radial artery: a systematic review and meta-analysis of randomized controlled trials.
Ultrasound guidance commonly is used for the placement of central venous catheters (CVCs). The Agency for Healthcare Research and Quality recommends the use of ultrasound for CVC placement as one of its 11 practices to improve patient care. Despite increased access to portable ultrasound machines and comfort with ultrasound-guided CVC access, fewer clinicians are familiar with ultrasound-guided techniques of arterial catheterization. The goal of this systematic review and meta-analysis was to determine the utility of real-time two-dimensional ultrasound guidance for radial artery catheterization. A comprehensive literature search of Medline, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials by two independent reviewers identified prospective, randomized controlled trials comparing ultrasound guidance with traditional palpation techniques of radial artery catheterization. Data were extracted on study design, study size, operator and patient characteristics, and the rate of first-attempt success. A meta-analysis was constructed to analyze the data. Four trials with a total of 311 subjects were included in the review, with 152 subjects included in the palpation group and 159 in the ultrasound-guided group. Compared with the palpation method, ultrasound guidance for arterial catheterization was associated with a 71% improvement in the likelihood of first-attempt success (relative risk, 1.71; 95% CI, 1.25-2.32). The use of real-time two-dimensional ultrasound guidance for radial artery catheterization improved first-pass success rate.


Reliability and validity of a brief questionnaire to assess television viewing and computer use by middle school children.
Sedentary behaviors, like television viewing, are positively associated with overweight among young people. To monitor national health objectives for sedentary behaviors in young adolescents, this project developed and assessed the reliability and validity of a brief questionnaire to measure weekly television viewing, usual television viewing, and computer use by middle school children. Reliability and validity of the Youth Risk Behavior Survey (YRBS) question on weekday television viewing also were examined. A brief, five-item television and computer use questionnaire was completed twice by 245 middle school children with one week apart. To concurrently assess validity, students also completed television and computer use logs for seven days. Among all students, Spearman correlations for test-retest reliability for television viewing and computer use ranged from 0.55 to 0.68. Spearman correlations between the first questionnaire and the seven-day log produced the following results: YRBS question for weekday television viewing (0.46), weekend television viewing (0.37), average television viewing over the week (0.47), and computer use (0.39). Methods comparison analysis showed a mean difference (hours/week) between answers to questionnaire items and the log of -0.04 (1.70 standard deviation [SD]) hours for weekday television, -0.21 (2.54 SD) for weekend television, -0.09 (1.75 SD) for average television over the week, and 0.68 (1.26 SD) for computer use. The YRBS weekday television viewing question, and the newly developed questions to assess weekend television viewing, average television viewing, and computer use, produced adequate reliability and validity for surveillance of middle school students.


The p97 ATPase associates with EEA1 to regulate the size of early endosomes.
The AAA (ATPase-associated with various cellular activities) ATPase p97 acts on diverse substrate proteins to partake in various cellular processes such as membrane fusion and endoplasmic reticulum-associated degradation (ERAD). In membrane fusion, p97 is thought to function in analogy to the related ATPase NSF (N-ethylmaleimide-sensitive fusion protein), which promotes membrane fusion by disassembling a SNARE complex. In ERAD, p97 dislocates misfolded proteins from the ER membrane to facilitate their turnover by the proteasome. Here, we identify a novel function of p97 in endocytic trafficking by establishing the early endosomal autoantigen 1 (EEA1) as a new p97 substrate. We demonstrate that a fraction of p97 is localized to the early endosome membrane, where it binds EEA1 via the N-terminal C2H2 zinc finger domain. Inhibition of p97 either by siRNA or a pharmacological inhibitor results in clustering and enlargement of early endosomes, which is associated with an altered trafficking pattern for an endocytic cargo. Mechanistically, we show that p97 inhibition causes increased EEA1 self-association at the endosome membrane. We propose that p97 may regulate the size of early endosomes by governing the oligomeric state of EEA1.


Evidence-based mixture containing Lactobacillus strains and lactoferrin to prevent recurrent bacterial vaginosis: a double blind, placebo controlled, randomised clinical trial.
Bacterial vaginosis (BV) is the most common cause of vaginal discomfort in women. It is characterised by abnormal vaginal microbiota with a depletion of lactobacilli and predominance of anaerobic microorganisms, mainly Gardnerella vaginalis and Atopobium vaginae. Although antibiotics represent an effective therapeutic option in the short-term, recurrent infections still remain a serious problem. Nowadays, evidence exists about the efficacy of probiotics for the management of BV. The aim of the current double blind, randomised clinical trial was to assess the efficacy of a probiotic mixture, including Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001, in combination with bovine lactoferrin, as adjuvant therapy to metronidazole in women with recurrent BV. In particular, normalisation of Nugent score, remission of symptoms and recurrences during a six-months follow-up were assessed. 48 adult women received metronidazole (500 mg twice daily) for 7 days and randomly assigned to take simultaneously either probiotics plus lactoferrin or placebo (2 capsules/day for 5 days followed by 1 capsule/day for 10 consecutive days; induction phase). The verum or placebo administration (1 capsule/day for 10 consecutive days) was repeated each month (maintenance phase) during the six months of follow-up starting the first day of menstrual cycle since the menstrual blood increases the vaginal pH and contributes to increase the risk of recurrences. The results showed that symptoms (vaginal discharge and itching), Nugent score and recurrence rate were significantly improved by probiotics mixture in association with lactoferrin. This alternative approach may represent a safe and effective remedy for the restoration of healthy vaginal microbiota in preventing recurrent BV.


Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner.
Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. We assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA levels, and total glutathione (GSH) levels were determined for all five regions. Although most brain regions in the three groups of animals were unaffected by manganese exposure in terms of GS protein levels, there was significantly increased protein (p<0.05) in the hippocampus and decreased protein in the hypothalamus of young male rats exposed to manganese phosphate as well as in the aged rats exposed to 0.1 mg/m3 MnSO4. Conversely, GS protein was elevated in the olfactory bulb of females exposed to the high dose of MnSO4. Statistically significant decreases (p<0.05) in MT and GS mRNA as a result of manganese exposure were observed in the cerebellum, olfactory bulb, and hippocampus in the young male rats, in the hypothalamus in the young female rats, and in the hippocampus in the senescent males. Total GSH levels significantly (p<0.05) decreased in the olfactory bulb of manganese exposed young male rats and increased in the olfactory bulb of female rats exposed to manganese. Both the aged and young female rats had significantly decreased (p<0.05) GSH in the striatum resulting from manganese inhalation. The old male rats also had depleted GSH levels in the cerebellum and hypothalamus as a result of the 0.1-mg/m3 manganese phosphate exposure. These results demonstrate that age and sex are variables that must be considered when assessing the neurotoxicity of manganese.


Predictors of change in housing status over 12 months among individuals using emergency shelters, temporary housing or permanent housing in Quebec, Canada.
Homelessness is an ongoing societal and public health problem in Canada and other countries. Housing services help homeless individuals along the transition towards stable housing, yet few studies have assessed factors that predict change in individual housing trajectories. This study identified predictors of change in housing status over 12 months for a sample of 270 currently or formerly homeless individuals using emergency shelters, temporary housing (TH) or permanent housing (PH) resources in Quebec. Participants recruited from 27 community or public organisations were interviewed between January and September 2017, and again 12 months later. Sociodemographic variables, housing history, health conditions, service use and client satisfaction were measured. Directors and programme coordinators from the selected organisations also completed a baseline questionnaire measuring strictness in residential codes of living/conduct, interorganisational collaboration and overall budget. Independent variables were organised into predisposing, enabling and needs factors, based on the Gelberg-Andersen Behavioral Model. Multilevel logistic regressions were used to test associations with the dependent variable: change in housing status over 12 months, whether positive (e.g. shelter to TH) or negative (e.g. PH to shelter). Predictors of positive change in housing status were as follows: residing in PH, being female, having children (predisposing factors); having consulted a psychologist, higher frequency in use of public ambulatory services (enabling factors); and not having physical illnesses (needs factor). The findings support strategies for helping this clientele obtain and maintain stable housing. They include deploying case managers to promote access to public ambulatory services, mainly among men or individuals without children who are less likely to seek help; greater use of primary care mental health teams; the establishment of more suitable housing for accommodating physical health problems; and reinforcing access to subsidised PH programmes.


Aurora A, Aurora B and survivin are novel targets of transcriptional regulation by histone deacetylase inhibitors in non-small cell lung cancer.
Analysis of biopsies from a recent clinical trial suggested that Depsipeptide FK228 (DP) inhibits Aurora kinase expression in lung cancer cells. The present study was undertaken to confirm and extend these observations. Aurora A and B mRNA levels in lung cancer cells were considerably higher than levels in normal pulmonary epithelia. DP, TSA and SAHA inhibited Aurora A, Aurora B and survivin expression with kinetics that were remarkably similar within individual cell lines, and appeared to coincide with p53 expression status. These effects were not observed following treatment with geldanamycins. Inhibition of Aurora B transcription coincided with decreased H3K9Ac and H3K4Me2 activation marks, and accumulation of H3K9Me3, as well as MBD1, MBD2 and MBD3 repression marks within the minimal Aurora B promoter. Knockdown of MBD1, -2 or -3 did not reproducibly abrogate inhibition of Aurora or survivin expression by DP or TSA. DP and TSA decreased expression and altered localization of Aurora kinases and survivin, resulting in mitotic catastrophe in lung cancer cells. Aurora A, and Aurora B levels in lung cancer cells and normal respiratory epithelia were assessed using quantitative RT-PCR techniques. These methods, as well as as Western blots were used to examine expression of Auroras A/B, and several related genes/proteins in lung cancer cells exposed to DP, TSA, SAHA and geldanamycins. Transient transfection promoter-reporter assays, and chromatin immunoprecipitation (ChIP) techniques were used to examine DP-mediated changes in activity and chromatin structure of the Aurora B promoter. Confocal imaging techniques were used to examine the effects of DP and TSA on mitotic progression in lung cancer cells. Novel transcriptional regulatory mechanisms involving Aurora kinase and survivin appear to contribute to cytotoxicity mediated by HDAC inhibitors in lung cancer cells.


Study design attributes influenced patients' willingness to participate in clinical research: a randomized vignette-based study.
To identify characteristics of clinical research projects that influence patients' willingness to participate in research. We surveyed all patients discharged during 1 month from a Swiss public teaching hospital. We described four hypothetical studies and asked patients whether they would agree to participate. We randomly manipulated three study attributes in each vignette, using a factorial design. All studies were not equally acceptable to the 1,277 respondents. A higher willingness to participate was found when a new drug had no side effects, no additional visit was required, balanced information was given, results were in the public domain, and the project was approved by a research ethics committee. In contrast, destruction of blood samples at the end of the project, use of placebo controls, and random allocation to study arms were associated with a lower likelihood of participation. The origin of funds, financial reward, the need to complete a questionnaire, and clinical vs. economic purpose of the study did not influence willingness to participate. Patients valued safety, convenience, oversight, and open communication in research. However, they were put off by some aspects that are valued by health care professionals. Educating the public about research methods may improve participation.


Transcriptional Dynamics Driving MAMP-Triggered Immunity and Pathogen Effector-Mediated Immunosuppression in Arabidopsis Leaves Following Infection with Pseudomonas syringae pv tomato DC3000.
Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally to suppress defense responses. A major challenge to understanding disease and defense responses is discriminating between transcriptional reprogramming associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) and that orchestrated by effectors. A high-resolution time course of genome-wide expression changes following challenge with Pseudomonas syringae pv tomato DC3000 and the nonpathogenic mutant strain DC3000hrpA- allowed us to establish causal links between the activities of pathogen effectors and suppression of MTI and infer with high confidence a range of processes specifically targeted by effectors. Analysis of this information-rich data set with a range of computational tools provided insights into the earliest transcriptional events triggered by effector delivery, regulatory mechanisms recruited, and biological processes targeted. We show that the majority of genes contributing to disease or defense are induced within 6 h postinfection, significantly before pathogen multiplication. Suppression of chloroplast-associated genes is a rapid MAMP-triggered defense response, and suppression of genes involved in chromatin assembly and induction of ubiquitin-related genes coincide with pathogen-induced abscisic acid accumulation. Specific combinations of promoter motifs are engaged in fine-tuning the MTI response and active transcriptional suppression at specific promoter configurations by P. syringae.


Assessing the Mental Health Impact of the 2011 Great Japan Earthquake, Tsunami, and Radiation Disaster on Elementary and Middle School Children in the Fukushima Prefecture of Japan.
On March 11, 2011, a magnitude 9.0 earthquake occurred off of Japan's Pacific coast, which was followed by huge tsunamis that destroyed many coastal cities in the area. Due to the earthquake and subsequent tsunami, malfunctions occurred at the Fukushima Daiichi (Fukushima I) nuclear power plant, resulting in the release of radioactive material in the region. While recent studies have investigated the effects of these events on the mental health of adults in the region, no studies have yet been performed investigating similar effects among children. This study aims to fill that gap by: 1) assessing the mental health of elementary and middle school children living within the Fukushima prefecture of Japan, and 2) identifying risk and protective factors that are associated with the children's mental health scores. These factors were quantified using an original demographics survey, the Strengths and Difficulties Questionnaire (SDQ), and the Impact of Event Scale-Revised (IES-R), the latter two of which have been previously validated in a Japanese setting. The surveys were distributed to approximately 3,650 elementary and middle school students during the months of February and March, 2012. The data suggests that those children who had been relocated to the city of Koriyama had significantly higher SDQ scores than those children who were native to Koriyama (p < .05) as well as a control group that lived outside of the Fukushima prefecture (p < .01). Using a multivariate regression, we also found that younger age and parental trauma were significantly correlated with higher SDQ scores (p < .001), while gender, displacement from one's home, and exposure to violence were not. These results suggest that, among children affected by natural disasters, younger children and those with parents suffering from trauma-related distress are particularly vulnerable to the onset of pediatric mental disturbances.


THE CHARACTER OF THE PNEUMONIC LESIONS PRODUCED BY INTRABRONCHIAL INSUFFLATION OF VIRULENT STREPTOCOCCI.
Comparing the pneumonic lesions produced by this very virulent streptococcus with those caused by a mildly virulent strain of the same organism, we find that with one exception the differences between them are only of a quantitative nature and not striking. There are the same intense leucocytic exudation into the alveoli and the leucocytic infiltration of the framework of the lungs. Macroscopically the pneumonia produced by the virulent organism was, as a rule, lobular in character. Occasionally, however, especially when large doses of the culture had been given, the gross appearance of the lesion gave the impression of a lobar pneumonia. But even in these cases the cut surface showed that the solid areas were separated by softer and lighter areas of aerated, congested, or edematous lung substance. Pleurisy was practically absent from the lungs in this series of experiments; only one case showed a narrow strip of fibrinous exudate on the pleura. Although in some instances large doses of the cultures were given and some dogs were permitted to live six or seven days, there was no mortality among the dogs in these experiments, just as there had been none among the animals experimented upon with the streptococcus of very low virulence. The course of the pneumonia caused by the virulent organism seemed to be somewhat longer than that produced by the less virulent one; areas of resolving pneumonia were found to persist on the sixth and seventh days after the injection, and in one such instance the solid focus contained viable organisms. There was some difference in the amount of fibrin present in the exudate caused by the two strains of streptococci. Although even in these experiments the amount of fibrin present was less than that found in the lesion produced by the virulent pneumococcus, it was perceptibly larger than the very small amount found in the lesions caused by the less virulent strain of streptococcus. It should be mentioned that there was no difference in the degree of phagocytosis observed in these two series of experiments. It was not marked in either case. One point of difference in the two series was noted: during the first forty-eight hours after insufflation of the virulent strain of streptococcus the blood of the animals obtained from the jugular vein during life and from the heart after death contained living organisms, while in the experiments with the slightly virulent streptococcus no living cocci were recovered from the blood. The virulence of the strain of streptococcus employed in the present investigation was, as has been pointed out, similar to that of the pneumococcus employed in the investigation of Lamar and Meltzer and in many of our own experiments, as far as mice were concerned, since both killed mice weighing fifteen grams in doses of 0.000,001 of a cubic centimeter in twenty-four to thirty-six hours. The findings in the lesions caused by these two organisms are comparable and therefore some deductions may be drawn regarding the similarity or dissimilarity of their actions. One of the first things we wish to bring out is the correction of our former statement regarding the presence of the cocci in the blood. As our new investigation shows, there is evidently no difference in this respect between the streptococcus and the pneumococcus. When both organisms are highly virulent they can be found in the circulating blood of the living dog or in the heart's blood of the dead dog during the first twenty-four or forty-eight hours after an intrabronchial insufflation. On the other hand, the present investigation rather confirms in a general way our first contention that the pneumonic lesions produced by the two different organisms differ distinctly in many ways. There is the difference in the mortality; even with fairly large quantities of the culture of the virulent streptococcus the mortality was nil in this series, although some of the dogs were kept alive for six and seven days. The mortality of the pneumococcus infection depends upon the quantity insufflated and may amount, as Lamar and Meltzer pointed out, to 16 per cent. The gross appearance of the lesion produced by the pneumococcus is, as frequently stated, that of a lobar pneumonia, frequently accompanied by a fibrinous exudate on the pleura. The gross appearance of the lesion produced even by a virulent streptococcus is, as a rule, that of a lobular pneumonia and is practically never accompanied by pleurisy. In the few instances in which large quantities of the streptococcus were given and the outward appearance of the lungs approached that of a lobar pneumonia, it was found that on section of the consolidated lung the solid foci proved to be separated by lighter areas of aerated, congested lung. In the lesions produced by the virulent streptococci the walls of the finer bronchi and the framework of the lung were markedly infiltrated with leucocytes, while in the lobar pneumonia produced by the pneumococcus the framework remained free from such infiltration. Finally there is the unmistakable difference in the amount of fibrin present in the alveolar exudate. While in the exudate of the lesion produced by the virulent streptococcus the amount was perceptibly larger than the insignificant amount present in the lesion caused by a slightly virulent strain, it is not to be compared with the large amount of fibrin which exists in the exudate of pneumococcus pneumonia. The several investigations which we have carried out seem to show conclusively that in general the streptococcus causes a lobular pneumonia which, besides the leucocytic intra-alveolar exudation, is characterized by a leucocytic infiltration of the lung framework, and that the pneumococcus causes a lobar pneumonia, which is practically free from leucocytic infiltration of the interstitial tissue of the lung. Furthermore, a virulent pneumococcus causes a lesion in which fibrin is a prominent element in the exudate and that element distinguishes the exudate sharply from the exudate of the lesion caused by a virulent streptococcus in which fibrin is present only in moderate amount. It distinguishes it in a still more striking manner from the exudates of the lesions caused by non-virulent pneumococci or streptococci, in which fibrin is present only in very small amounts. It seems that the formation of fibrin is connected in some specific way with the pneumococcus on the one hand, and with the virulence of the organism on the other. For even with the relatively small amounts of fibrin present in the exudates of lesions caused by the streptococcus there is a perceptible difference in the quantity according to the virulence of the organism. Whether fibrin is a means which enhances virulence, or whether it is a reaction product against it, our experiments so far do not entitle us to discuss.


[The effect of exposure factors on the concentration of heavy metals in residents near abandoned metal mines].
This study assessed the factors that have an influence on the residents exposed to heavy metals, and we utilized the findings to establish the proper management of abandoned metal mines in the future. For a total of 258 residents who lived close to abandoned mines in Gangwon-province and Gyeonggi-province, the exposure factors and biomarkers in their blood and urine were comparatively analyzed via multiple regression analysis. The blood levels of lead and mercury and the cadmium levels in urine were found to be higher in the study group than that in the average Korean. For the blood levels of heavy metals according to each exposure factor, all of them were found to be significantly higher in both of the group residing for a longer period of time and the group living closer to the source of pollutants. Multiple regression analysis disclosed that all the heavy metals, except lead, in their blood were significantly reduced in proportion to the increased distance of inhabitancy from the mines. Their other biomarkers were within the normal ranges. We found that the distance between the residential village and the mines was a factor that affects the blood level of heavy metals in the villagers. This finding could be an important factor when developing a management model for the areas that surround abandoned metal mines. (ED note: I much like this important study.).