Passive Screening and Diagnosis of Sleeping Sickness with New Tools in Primary Health Services: An Operational Research.
The integration of human African trypanosomiasis (HAT) activities into primary health services is gaining importance as a result of the decreasing incidence of HAT and the ongoing developments of new screening and diagnostic tools. In the Democratic Republic of Congo, this integration process faces multiple challenges. We initiated an operational research project to document drivers and bottlenecks of the process. Three health districts piloted the integration of HAT screening and diagnosis into primary health services. We analysed the outcome indicators of this intervention and conducted in-depth interviews with health care providers, seropositives, community health workers and HD management team members. Our thematic interview guide focused on factors facilitating and impeding the integration of HAT screening. The study showed a HAT-RDT-positive rate of 2.2% in Yasa Bonga, 2.9% in Kongolo and 3% in Bibanga, while the proportion of reported seropositives that received confirmatory examinations was 76%, 45.6% and 68%, respectively. Qualitative analyses indicated that some seropositives were unable to access the confirmation facility. The main reasons that were given included distance, RDT rupture, lack of basic screening equipment and financial barriers (additional hospital fees not included in free treatment course), fear of lumbar puncture and the perception of HAT as a disease of supernatural origin. Passive screening using HAT RDTs in primary health services inevitably has some limitations. However, regarding the epidemiological context and some obstacles to integrated implementation, this cannot on its own be a relevant alternative to the elimination of HAT by 2020. We acknowledge the agency that provided financial support for this study, the Belgian Development Cooperation. The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Philippe Mulenga received financial support thanks to a doctoral grant from the Belgian Development Cooperation under the FA4 agreement. Funding for the study and Rapid Service Fees was provided by the Epidemiology and Tropical Diseases Unit of the Institute of Tropical Medicine, Antwerp.


Insights into the Reaction Mechanism of Ethanol Conversion into Hydrocarbons on H-ZSM-5.
Ethanol dehydration to ethene is mechanistically decoupled from the production of higher hydrocarbons due to complete surface coverage by adsorbed ethanol and diethyl ether (DEE). The production of C3+ hydrocarbons was found to be unaffected by water present in the reaction mixture. Three routes for the production of C3+ hydrocarbons are identified: the dimerization of ethene to butene and two routes involving two different types of surface species categorized as aliphatic and aromatic. Evidence for the different types of species involved in the production of higher hydrocarbons is obtained via isotopic labeling, continuous flow and transient experiments complemented by UV/Vis characterization of the catalyst and ab initio microkinetic modeling.


Toxic acute renal failure and hepatitis after ingestion of raw carp bile.
The raw carp bile has both nephrotoxic and hepatotoxic effects which are not well known. Recently, we studied 13 patients who had toxic acute renal failure and toxic hepatitis after ingestion of raw bile of carp in 3, grass carp in 8 and silver carp in 2 cases. The purpose of this report is to alert physicians to this very rare cause of toxic acute renal failure and hepatitis. All patients presented initially with gastrointestinal upset after eating. These symptoms were followed by oliguria in 7 patients (54%), hematuria was noted in 10 (77%) and jaundice in 8 patients (62%). Elevation of blood urea nitrogen, creatinine and transaminases lasted for about 3 weeks. The severity of the symptoms depended on the amount of bile ingested. All the patients recovered with conservative therapy and hemodialysis. Biopsy of the kidney revealed findings compatible with acute tubular necrosis similar to that produced by other nephrotoxins. Biopsy of the liver revealed findings consistent with acute toxic hepatitis. Both suggest toxic effects of carp bile as a cause of toxic acute renal failure and hepatitis.


Individual care plans can reduce hospital admission rate for patients who frequently attend the emergency department.
To investigate the impact, in terms of hospital admission and investigations, of individual care plans for patients who frequently attend the emergency department (ED). 32 patients who regularly attended the ED at St Thomas' Hospital were included in the study. After review of ED and hospital case records, an individual care plan was prepared for future attendances. The numbers of ED attendances, hospital admissions and investigations were collated from the electronic patient record system and compared for the 12 months prior to and 12 months after introduction of the care plan. Primary outcome measure was reduction in the number of hospital admissions (as a percentage of ED attendance). Secondary outcome measures were a reduction in the number of investigations and ED attendances. In the 12 months prior to introduction of the individual care plans, the 32 patients accounted for 858 ED attendances and 209 admissions to hospital. In 12 months after introduction of the care plans, the number of ED attendances fell to 517, with only 77 hospital admissions. Median number of hospital admissions (as a percentage of ED attendances) fell from 18.8% to 7.1% (p=0.014) after introduction of the care plan. There were also reductions in median number of ED attendances (19 vs. 5, p=0.001), median number of radiology tests (4 vs 1, p=0.001) and median number of blood tests (55 vs. 12, p<0.001). Individual care plans for a carefully selected group of patients who frequently attend the emergency department can result in a decrease in the number of hospital admissions and number of investigations.


[Microarray technology--potential in cancer research].
Researchers have worked for decades to solve the enigma of cancer. We know that essential checkpoints in the life cycle of cells have to be disrupted in order to create a tumour cell, and some of the genes and proteins involved have been identified. Most of the previous work on identifying these genes have been based on "educated guesswork", as the methods and technologies used have been limited to the examination of genes one by one, or a few at a time. Microarray technology allows tens of thousands of genes to be examined at the same time, without any previous information on the genes. Both expression levels and copy numbers of the genes can be evaluated. Our studies of breast cancer and bone tumours are presented, as well as examples from the literature. Microarray analyses have been used to produce molecular portraits of breast cancer, malignant melanomas and other cancers. These portraits may help in sub-classification of tumours, in prognosis, and in the general understanding of cancer. For example, studies of gene expression patterns of breast carcinomas, similar with respect to classic prognostic markers (such as ER status, grading and morphology), have identified subgroups of patients that show differences in survival.


Depressive symptoms, impaired glucose metabolism, high visceral fat, and high systolic blood pressure in a subgroup of women with recent gestational diabetes.
Women with gestational diabetes (GDM) are a high risk group for early type 2 diabetes (T2D). Depression is a risk factor for T2D in the general population. We investigated in women after a recent pregnancy with GDM and without a clinical diagnosis of depression, whether mild to moderate depressive symptoms associate with pathologic glucose metabolism. In a cross-sectional analysis, we examined 173 women, 9 ± 3 months after delivery with several psychopathological assessments, 5-point oral glucose tolerance test with insulin, anthropometrics, and laboratory chemistry. In a subgroup of 101 women, abdominal visceral fat was quantified by magnetic resonance imaging (MRI). A total of 22 women (13%) showed mild to moderate depressive symptoms, and the proportion of women with pathologic glucose metabolism (impaired fasting glucose, impaired glucose tolerance, or T2D) was higher in this group than in the women without depressive symptoms (59.1% vs. 33.1%, p = 0.018). Women with depressive symptoms also had higher body mass index (BMI), systolic blood pressure, plasma leptin, plasma resistin, and abdominal visceral fat volume. Pathologic glucose metabolism (OR = 2.594, 95% CI: 1.021-6.592), systolic blood pressure (OR = 1.076, 95% CI: 1.027-1.128), and abdominal visceral fat volume (OR = 2.491, 95% CI: 1.142-5.433) remained, even after adjustment for BMI, associated with the presence of depressive symptoms. Taken together, we found depressive symptoms at a level not generally diagnosed in clinical practice in a subgroup of women with recent GDM. This subgroup also showed an unfavorable metabolic profile. Mild to moderate depressive symptoms may therefore help to identify this special subgroup.


Neutron-induced light-ion production from Fe, Pb and U at 96 MeV.
Double-differential cross-sections for light-ion production (up to A = 4) induced by 96 MeV neutrons have been measured for Fe, Pb and U. The experiments have been performed at The Svedberg Laboratory in Uppsala, using two independent devices, MEDLEY and SCANDAL. The recorded data cover a wide angular range (20 degrees -160 degrees ) with low energy thresholds. The data have been normalised to obtain cross-sections using np elastic scattering events. The latter have been recorded with the same setup, and results for this measurement are reported. The work was performed within the HINDAS collaboration with the primary aim of improving the database for three of the most important nuclei for incineration of nuclear waste with accelerator-driven systems. The obtained cross-section data are of particular interest for the understanding of the so-called pre-equilibrium stage in a nuclear reaction and will be compared with model calculations.


Ecdysteroid profiles of two Ajuga species, A. iva and A. remota.
Phytoecdysteroids are plant analogues of insect moulting hormones and are used by plants to repel or disturb phytophagous insects. They are also active on mammals and present in many plants used in traditional medicine. The Ajuga genus contains several such species, which occur in various pharmacopoeias. We report the isolation and identification of major and minor ecdysteroids present in two Ajuga species, A. iva and A. remota, both of which are used as medicinal plants in Africa. Three minor ecdysteroids (abutasterone, ponasterone A and sidisterone) have been found for the first time in the Ajuga genus.


Acid-active supramolecular anticancer nanoparticles based on cyclodextrin polyrotaxanes damaging both mitochondria and nuclei of tumor cells.
As a supramolecular macrocyclic polymer, cyclodextrin (CD) polyrotaxanes (PRs) have many advantages for developing nanomedicines, such as stable chemical composition, abundant functionalized hydroxyl groups, moving across biological barriers, adjustable nanoparticle size and good biocompatibility. Herein, we synthesized a class of acid-active therapeutic nanoparticles comprising a α-CD-based PR polymeric prodrug of PRs-poly(doxorubicin)-co-poly[(ethylene glycol) methyl ether methacrylate] (PR-PDOX-co-POEGMA, denoted as PRMO@DOX) to reduce drug leakage and selectively deliver drugs into tumor cells, aiming to achieve maximal treatment efficacy of supramolecular therapeutics. The obtained PRMO@DOX showed desirable features of high drug loading rates (>25 wt%), fast cellular uptake, acid-active controlled release, effective anti-tumor activity and low systemic toxicity. Benefiting from its unique amphiphilic nanostructure, PRMO@DOX can form water-soluble prodrug nanoparticles in aqueous media. The acid-active hydrazone bond in the prodrug can break and thus release drug molecules precisely and in a timely manner under an acidic tumor microenvironment, damaging the nuclei and mitochondria of tumor cells. Both in vitro and in vivo experiments clearly demonstrated a remarkable antitumor efficacy of this therapeutic platform, which provided a new strategy for the development of polyrotaxane-based nanomedicine for enhanced cancer therapy.


Cadaveric Simulation of Otologic Procedures: An Analysis of Droplet Splatter Patterns During the COVID-19 Pandemic.
The otolaryngology community has significant concerns regarding the spread of SARS-CoV-2 through droplet contamination and viral aerosolization during head and neck examinations and procedures. The objective of this study was to investigate the droplet and splatter contamination from common otologic procedures. Cadaver simulation series. Dedicated surgical laboratory. Two cadaver heads were prepped via bilateral middle cranial fossa approaches to the tegmen (n = 4). Fluorescein was instilled through a 4-mm burr hole drilled into the middle cranial fossa floor, and presence in the middle ear was confirmed via microscopic ear examination. Myringotomy with ventilation tube placement and mastoidectomy were performed, and the distribution and distance of resulting droplet splatter patterns were systematically evaluated. There were no fluorescein droplets or splatter contamination observed in the measured surgical field in any direction after myringotomy and insertion of ventilation tube. Gross contamination from the surgical site to 6 ft was noted after complete mastoidectomy, though, when performed in standard fashion. Our results show that there is no droplet generation during myringotomy with ventilation tube placement in an operating room setting. Mastoidectomy, however, showed gross contamination 3 to 6 ft away in all directions measured. Additionally, there was significantly more droplet and splatter generation to the left of the surgeon when measured at 1 and 3 ft as compared with all other measured directions.


Biaxial mechanics and inter-lamellar shearing of stem-cell seeded electrospun angle-ply laminates for annulus fibrosus tissue engineering.
The annulus fibrosus (AF) of the intervertebral disk plays a critical role in vertebral load transmission that is heavily dependent on the microscale structure and composition of the tissue. With degeneration, both structure and composition are compromised, resulting in a loss of AF mechanical function. Numerous tissue engineering strategies have addressed the issue of AF degeneration, but few have focused on recapitulation of AF microstructure and function. One approach that allows for generation of engineered AF with appropriate (+/-)30° lamellar microstructure is the use of aligned electrospun scaffolds seeded with mesenchymal stem cells (MSCs) and assembled into angle-ply laminates (APL). Previous work indicates that opposing lamellar orientation is necessary for development of near native uniaxial tensile properties. However, most native AF tensile loads are applied biaxially, as the disk is subjected to multi-axial loads and is constrained by its attachments to the vertebral bodies. Thus, the objective of this study was to evaluate the biaxial mechanical response of engineered AF bilayers, and to determine the importance of opposing lamellar structure under this loading regime. Opposing bilayers, which replicate native AF structure, showed a significantly higher modulus in both testing directions compared to parallel bilayers, and reached ∼60% of native AF biaxial properties. Associated with this increase in biaxial properties, significantly less shear, and significantly higher stretch in the fiber direction, was observed. These results provide additional insight into native tissue structure-function relationships, as well as new benchmarks for engineering functional AF tissue constructs.


Nest predation of Cory's shearwater Calonectrisborealis (Aves, Procellariiformes) by introduced mammals on Terceira Island, Azores.
The Azores holds the largest population of Cory's shearwater Calonectrisborealis (Cory, 1881) (Aves, Procellariiformes) in the world. Apart from a few mammal-free islets, the bulk of the population breeds in coastal areas on the main human-inhabited islands, where several non-native predators have been introduced. Throughout the entire year of the 2019 breeding season, we used motion-triggered cameras and regularly visited three colonies of Cory's shearwater to identify nest predators and the factors affecting nest predation. A total of 292,624 photos were obtained, of which 97.7% were of Cory's shearwaters, 1.7% of non-target species (e.g. other birds, rabbits) and 0.52% of potential predators. Of the monitored nests, 25.7% were predated (n = 9), mainly by black rats (n = 8), but also by cats (n = 1). The relative abundance of black rats in the nests was the main factor explaining nest mortality. This variable was significantly and negatively related with the daily survival rate of Cory's shearwater nestlings. Identification of the main nest predators is crucial for the management and conservation of native bird populations, particularly on oceanic islands, which harbour an important number of threatened and endemic species.


Use of porcine renal capsule matrix as a full-thickness dermal wound-healing material in rats.
To compare the utility of porcine renal capsule matrix (RCM) with porcine small intestinal mucosa (SIS) in a rat full-thickness skin wound model. Groups of rats had surgically-created wounds filled with either SIS or RCM. On each rat a contralateral wound was left unfilled (RCM-U or SIS-U). Wound diameter was measured 3, 7, 12, 17, 26 and 30 days after creation. Wound sites sampled 3, 7, 14, 28, 42 and 56 days after wound creation were numerically graded for degree of histologic change and for collagen content, based on intensity of trichrome staining. Wounds in all groups rapidly contracted to less than 50% of the original diameter within 12 days. There were no differences in wound diameter between RCM- and SIS-treated wounds at any time point, but these wounds had significantly greater (p < 0.001) diameters than their unfilled counterparts on days 7, 12 and 17. There were no differences in histologic scores or trichrome-staining scores between RCM- and SIS-treated wounds and their unfilled counterparts at any time point, except for a greater (p < 0.05) histologic score in SIS-treated wounds compared with unfilled controls on day 14. In both treatment groups an acute inflammatory response at the wound site was soon replaced by an influx of macrophages and fibroblasts. The results show that RCM is equivalent to SIS for the treatment of full-thickness wounds and that these materials may enhance wound healing in terms of wound-tissue collagenisation and maturation. These materials therefore merit further study in other wound-care models.


The H+-sucrose cotransporter NtSUT1 is essential for sugar export from tobacco leaves
In many species translocation of sucrose from the mesophyll to the phloem is carrier mediated. A sucrose/H+-symporter cDNA, NtSUT1, was isolated from tobacco (Nicotiana tabacum) and shown to be highly expressed in mature leaves and at low levels in other tissues, including floral organs. To study the in vivo function of NtSUT1, tobacco plants were transformed with a SUT1 antisense construct under control of the cauliflower mosaic virus 35S promoter. Upon maturation, leaves of transformants expressing reduced amounts of SUT1 mRNA curled downward, and strongly affected plants developed chloroses and necroses that led to death. The leaves exhibited impaired ability to export recently fixed 14CO2 and were unable to export transient starch during extended periods of darkness. As a consequence, soluble carbohydrates accumulated and photosynthesis was reduced. Autoradiographs of leaves show a heterogenous pattern of CO2 fixation even after a 24-h chase. The 14C pattern does not change with time, suggesting that movement of photosynthate between mesophyll cells may also be impaired. The affected lines show a reduction in the development of the root system and delayed or impaired flowering. Taken together, the effects observed in a seed plant (tobacco) demonstrate the importance of SUT1 for sucrose loading into the phloem via an apoplastic route and possibly for intermesophyll transport as well.


Vortex formation and associated aneurysmogenic transverse rotational shear stress near the apex of wide-angle cerebral bifurcations.
Aneurysm formation preferentially occurs at the site of wide-angle cerebral arterial bifurcations, which were recently shown to have a high longitudinal positive wall shear stress (WSS) gradient that promotes aneurysm formation. The authors sought to explore the other components of the hemodynamic environment that are altered with increasing bifurcation angle in the apical region and the effects of these components on WSS patterns on the vessel wall that may modulate aneurysm genesis and progression. Parametric models of symmetrical and asymmetrical bifurcations were created with increasing bifurcation angles (45°-240°), and 3D rotational angiography models of 13 middle cerebral artery (MCA) bifurcations (7 aneurysmal, 6 controls) were analyzed using computational fluid dynamics. For aneurysmal bifurcations, the aneurysm was digitally removed to uncover hemodynamics at the apex. WSS vectors along cross-sectional planes distal to the bifurcation apex were decomposed as orthogonal projections to the cut plane into longitudinal and transverse (tangential to the cross-sectional plane) components. Transverse rotational WSS (TRWSS) and TRWSS gradients (TRWSSGs) were sampled and evaluated at the apex and immediately distal from the apex. In parametric models, increased bifurcation angle was associated with transverse flow vortex formation with emergence of an associated apical high TRWSS with highly aneurysmogenic positive TRWSSGs. While TRWSS decayed rapidly away from the apex in narrow-angle bifurcations, it remained greatly elevated for many radii downstream in aneurysm-prone wider bifurcations. In asymmetrical bifurcations, TRWSS was higher on the aneurysm-prone daughter vessel associated with the wider angle. Patient-derived models with aneurysmal bifurcations had wider angles (149.33° ± 12.56° vs 98.17° ± 8.67°, p < 0.001), with significantly higher maximum TRWSS (1.37 ± 0.67 vs 0.48 ± 0.23 Pa, p = 0.01) and TRWSSG (1.78 ± 0.92 vs 0.76 ± 0.50 Pa/mm, p = 0.03) compared to control nonaneurysmal bifurcations. Wider vascular bifurcations are associated with a novel and to the authors' knowledge previously undescribed transverse component rotational wall shear stress associated with a positive (aneurysmogenic) spatial gradient. The resulting hemodynamic insult, demonstrated in both parametric models and patient-based anatomy, is noted to decay rapidly away from the protection of the medial pad in healthy narrow-angle bifurcations but remain elevated distally downstream of wide-angle aneurysm-prone bifurcations. This TRWSS serves as a new contribution to the hemodynamic environment favoring aneurysm formation and progression at wide cerebral bifurcations and may have clinical implications favoring interventions that reduce bifurcation angle.


Subsite structure of Saccharomycopsis alpha-amylase secreted from Saccharomyces cerevisiae.
The kinetic parameters (kcat/Km) and the cleaved-bond distributions for the hydrolysis of linear maltooligosaccharides Gn (3 less than or equal to n less than or equal to 9) by Saccharomycopsis alpha-amylase (Sfamy) secreted from Saccharomyces cerevisiae were determined at pH 5.25 and 25 degrees C. The subsite affinities of Sfamy were also evaluated from these data. The subsite structure of Sfamy is characteristic of the active site of an endo-cleavage type enzyme, consisting of internal repulsive sites with the catalytic residues and external attractive sites. Moreover, the pKa values of the catalytic residues were calculated from the pH dependence plot of the kinetic parameter (kcat/Km). The amino acid residues which contribute to the subsite affinities and the catalytic activity of Sfamy are proposed and compared with those of Taka-amylase A.


Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study.
Autoimmune Inner Ear Disease (AIED) is an idiopathic progressive, often bilateral, sensironeural hearing loss that occurs over weeks to months, generally resulting in significant auditory disability. Response to treatment with immunomodulators other than corticosteroids has been poor. Data from a guinea pig model of AIED and a recent open label trial of etanercept suggested potential treatment benefit. Based on these preliminary results, we conducted a pilot placebo controlled trial of etanercept in AIED patients. Twenty AIED patients were enrolled in a 12-week blinded placebo (PLA) controlled randomized clinical trial of etanercept (ETA) with 25 mg SC twice weekly. Patients received treatment for 8 weeks with a 4-week follow-up off-treatment. The primary study endpoint was an improvement in pure tone threshold (PTA) of 10 Db in two consecutive frequencies and/or improvement in speech discrimination of >12% at week 8. Patient demographics were similar for the ETA and PLA patients. Seventeen subjects (8 ETA, 9 PLA) completed the trial. The 3 dropouts were due to lack of efficacy. One ETA and 2 PLA subjects achieved the primary endpoint (p > 0.999). One ETA and 1 PLA pt demonstrated improved in hearing loss and vertigo severity by VAS and hearing disability. No safety issues were observed. The results of this pilot trial demonstrate that etanercept 25 mg twice weekly for 8 weeks was no better than placebo for treatment of AIED in this patient population.


β-blockers, calcium antagonists, and mortality in stable coronary artery disease: an international cohort study.
The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain. We analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009-2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84-1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79-1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91-1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50-0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37-0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52-0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality. In this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI.


Effects of oxidized LDL on mononuclear phagocytes: inhibition of induction of four inflammatory cytokine gene RNAs, release of NO, and cytolysis of tumor cells.
A critical step in development of atherosclerosis is the interaction of oxidized low-density lipoprotein (LDL) with mononuclear phagocytes. Oxidized LDL, as well as acetyl-LDL, is rapidly taken up into macrophages via a family of scavenger receptors. We report that macrophages treated with oxidized LDL have markedly lower levels of mRNA specific for the genes MCP-1, TNF-alpha, IL-1 alpha, and KC as measured by Northern blot analyses of lipopolysaccharide (LPS)-stimulated macrophages. By contrast, acetyl-LDL does not inhibit these genes at the doses at which oxidized-LDL is effective. Similar effects are observed whether the LDL is oxidized in the presence of Cu2+ or of Fe2+. Such inhibition also occurs when maleylated bovine serum albumin (BSA), which also clears by one or more scavenger receptors on macrophages, is used as the stimulant. Fe2+ or Cu2+ oxidized LDL inhibits release of nitric oxide when triggered by LPS and direct cytolysis of tumor cells when triggered by maleylated BSA or LPS. Taken together, the data presented indicate that oxidized LDL inhibits induction of several important gene RNAs as well as functional markers that characterize the development of inflammatory and fully activated macrophages.


Coronary-subclavian steal syndrome presenting with ventricular tachycardia.
Coronary-subclavian steal through the left internal mammary graft is a rare cause of myocardial ischemia in patients who have had a coronary bypass surgery. We report a 70-year-old man who presented with sustained monomorphic ventricular tachycardia 5 years after the surgical creation of a left internal mammary to the left anterior descending artery. Cardiac catheterization illustrated that the left subclavian artery was occluded proximally and that the distal course was visualized by retrograde filling through the left internal mammary graft. Clinical ventricular tachycardia was reproducibly induced with a single ventricular extrastimulus, and antitachycardia pacing terminated the tachycardia. Restoration of blood flow by way of a Dacron graft placed between the descending aorta and the subclavian artery resulted in the total relief of symptoms. Ventricular tachycardia could not be induced during the control electrophysiologic study after surgical revascularization.


Portion size matters: Carrion ecology lessons for medicolegal death investigations-A study in Cape Town, South Africa.
Forensic taphonomic studies are regionally specific and improve time since death estimates for medico-legal casework. Within forensic taphonomy and carrion ecology, vertebrate scavengers are under-researched with many studies conducted using multiple, unclothed carcasses. This is a forensically unrealistic experimental design choice with unknown impact. The effect of variation in carrion biomass on the decomposition ecosystem, particularly where vertebrate scavengers are concerned, requires clarification. To assess the effect of carrion biomass load on vertebrate scavenging and decomposition rate, seasonal baseline data for single, clothed ~60 kg porcine carcasses were compared to clothed multiple-carcass deployments, in a forensically relevant habitat of Cape Town, South Africa. Decomposition was tracked via weight loss and bloat progression and scavenging activity via motion-activated cameras. The single carcasses decayed more quickly, particularly during the cooler, wetter winter, strongly correlated with concentrated Cape gray mongoose (Galerella pulverulenta) scavenging activity. On average and across seasons, the single carcasses lost 68% of their mass by day 32 (567 accumulated degree days [ADD]), compared to 80 days (1477 ADD) for multi-carcass deployments. The single carcasses experienced substantially more scavenging activity, with longer visits by single and multiple mongooses, totaling 53 h on average compared to 20 h for the multi-carcass deployments. These differences in scavenging activity and decay rate demonstrate the impact of carrion biomass load on decomposition for forensic taphonomy research. These findings need corroboration. However, forensic realism requires consideration in taphonomic study design. Longitudinally examining many single carcasses may produce more forensically accurate, locally appropriate, and usable results.


Physiological characteristics of sprint and endurance Masters runners.
Data were obtained from 13 sprint (age range 41-58) and 13 distance (age range 4-78) Masters track athletes. The mean VO2max value for the distance runners was 54.4 +/- 3 ml kg min compared with 47.2 +/- 2 ml kg min for the sprinters. The highest VO2max (71.0 ml kg min) was obtained on a 45-year-old distance runner while the lowest (27.3 ml kg min) was obtained on the oldest (78 years) distance runner. VO2max decreased by 34.5% from age 40 to 70 in the distance runner in spite of continued training that ranged from 40 to 120 miles/week. Maximum ventilation rates were 122.5 +/- 6.8 and 116.8 +/- 7.0 1 min for the sprint and distance runners, respectively. Percentage of body fat was 16.5 +/- 0.5 for the sprinters and 18.0 +/- 1.1 for the distance runners. Serum cholesterol values were 218.7 +/- 8.7 and 203.0 +/- 13.8 ml/dl, while triglyceride values were 101.5 +/- 8.2 and 84.1 +/- 9.3 mg/dl for the sprint and distance groups, respectively. These data indicate that, VO2max decreases significantly with aging despite the continuation of long distance training. Percent body fat and serum lipid levels were significantly lower in these athletes compared to those for sedentary adults, suggesting a protective effect against coronary heart disease. Only one subject had S-T segment depression during the exercise test.


A method to standardize the blood flow restriction pressure by an elastic cuff.
Blood flow restriction training using a practical (non-pneumatic) elastic cuff has recently increased in popularity. However, a criticism of this method is that the pressure applied and the amount of blood flow restriction induced is unknown. The aim was to quantify blood flow following the application of an elastic cuff and compare that to what is observed using a more traditional pressurized nylon cuff. Thirty-five young participants (16 men and 19 women) visited the laboratory once for testing. In a randomized order (one condition per arm), an elastic cuff (5 cm wide) was applied to one arm and blood flow was measured following the cuff being pulled to two distinct lengths; 10% and 20% of the resting length based on arm circumference. The other arm would follow a similar protocol but use a pressurized nylon cuff (5 cm wide) and be inflated to 40% and 80% of the individuals resting arterial occlusion pressure. There was a main effect of pressure for blood flow with it decreasing in a pressure-dependent manner (High < Low, P < 0.001). The mean difference (95% CI) in blood flow between cuffs was -5.9 (-18.9, 7.0) % for the lower pressure and -4.0 (-13.2, 5.1) % for the higher pressure. When the relative changes for each cuff were separated by sex, there were no differences in the changes from Pre (P ≥ 0.509). The application of a pressure relative to the initial belt length, which is largely dependent upon arm circumference, appears to provide one method to standardize the practical blood flow restriction pressure for future research.


Performance of physical activities by adolescents with cerebral palsy.
Mobility and self-care are important considerations for successful transition of adolescents with cerebral palsy to adulthood. The purpose of this study was to characterize performance of physical activities from the perspective of adolescents themselves. The subjects were 156 adolescents with cerebral palsy, 11.6 to 17.7 years of age. A therapist completed the Gross Motor Function Classification System (GMFCS). Adolescents completed the Activities Scale for Kids-Performance Version (ASKp) twice over a 1-year period. A repeated-measures analysis of variance indicated a main effect for GMFCS level. The main effect for time and the GMFCS level x time interaction were not significant. Post hoc comparisons indicated that ASKp scores differed among all GMFCS levels. Performance of physical activities by adolescents with cerebral palsy differed based on GMFCS level and did not change over 1 year. The ASKp scores of adolescents in levels II through V suggest the need for physical assistance at times throughout the day. The results have implications for the role of the physical therapist in transition planning.


[Hyperbaric oxygenation in experimental toxic brain edema].
Hyperbaric oxygenation (HO) was used to treat the brain toxic edema excited by triethyltin++ chloride. Microscopic examination of the brains of two groups of animals (with and without HO) revealed the decay of pathologic signs of brain edema and reparative responses in the nervous tissue induced by HO.


Gene expression and cAMP.
By comparing the 5'-flanking region of the porcine gene for the urokinase form of plasminogen activator with those of other cAMP-regulated genes, we identify a 29-nucleotide sequence that is tentatively proposed as the cAMP-regulatory unit. Homologous sequences are present (i) in the cAMP-regulated rat tyrosine aminotransferase, prolactin, and phosphoenolpyruvate carboxykinase genes and (ii) 5' to the transcription initiation sites of cAMP-regulated Escherichia coli genes. From this we conclude that the expression of cAMP-responsive genes in higher eukaryotes may be controlled, as in E. coli, by proteins that form complexes with cAMP and then show sequence-specific DNA-binding properties. The complex formed by cAMP and the regulatory subunit of the type II mammalian protein kinase might be one candidate for this function. Based on several homologies we suggest that this subunit may have retained both the DNA-binding specificity and transcription-regulating properties in addition to the nucleotide-binding domains of the bacterial cAMP-binding protein. If this were so, dissociation of protein kinase by cAMP would activate two processes: (i) protein phosphorylation by the catalytic subunit and (ii) transcription regulation by the regulatory subunit.


Patterns of cross-sectional and predictive physical activity in Swiss adults aged 52+: results from the SAPALDIA cohort.
Non-communicable diseases (NCDs) account for the vast majority of deaths in Switzerland. Insufficient physical activity (PA) is an established NCD risk factor and PA is known to be beneficial for physical and mental wellbeing. Sedentary behaviour (SB) is an additional, independent risk factor and associated with frailty in older adults. This study aimed at describing cross-sectional PA patterns in a general population sample of subjects aged 52 years and older (52+) from eight areas across different language regions of Switzerland. Additionally, the predictive association of self-reported PA for objectively measured PA was tested. Participants 52+ of the Swiss Cohort Study on Air Pollution And Lung and Heart Disease In Adults (SAPALDIA) who completed accelerometer data collection at the most recent follow-up (SAPALDIA4 in 2017/18) and provided information on determinants of interest (sex, age, body mass index [BMI], language region, education, employment status, civil status, smoking) were included in the analysis (n = 1314). The accelerometer-derived average time spent in different PA intensities (SB, light PA [LPA], moderate-to-vigorous PA [MVPA]) was estimated according to participant characteristics with control for season and wear time using multiple linear regressions. In further analyses, the predictive effect of changes in self-reported PA over roughly ten years between SAPALDIA2 (2001/02) and SAPALDIA3 (2010/11) (remaining inactive [RI]; becoming inactive [BI]; becoming active [BA]; remaining active [RA]) on the objectively measured SB, LPA and MVPA obtained seven years later by accelerometry (SAPALDIA4), was assessed using multiple linear regression models. Overall, 21.7% of 52+ participants met the Swiss recommendations for subjectively assessed PA. Obese participants, 75+ year-olds, smokers and subjects living alone spent more time in SB and less time in LPA and MVPA compared with participants with a BMI below 25 kg/m2, between 52 and 64 years old, not smoking and being married, respectively. Residents living in the French-speaking part of Switzerland were less likely to engage in MVPA compared with residents from the German-speaking part and thus were less likely to meet the PA recommendations. A trend for increasing PA and decreasing SB was observed consistently across the four groups (RI, BI, BA, RA) of predictive self-reported PA patterns with participants remaining active over the course of roughly ten years showing highest levels of PA and lowest levels of SB measured objectively at SAPALDIA4. The high proportion of SB points to the need of physical activity promotion for the older part of the population in Switzerland. According to our data, behavioural changes in PA are possible and sustainable as we can see in the group of participants becoming active and this is essential for health promotion recommendations.


Is the difference in neonatal blood glucose concentration of caesarian and vaginally delivered term infants requiring separated reference intervals?
Mode of delivery has been reported to affect the cord blood glucose level of newborns. Vaginally delivered (VD) newborns were found to have relatively increased concentration of cord blood glucose than those delivered by cesarean section (CS). The aim of this study is thus to determine whether the difference in cord blood glucose concentration among VD and CS newborns is necessitating partitioned reference intervals (RIs) for the laboratory diagnosis of neonatal hypoglycemia. A total of 60 newborns were included from Tikur Anbessa Specialized Hospital (TASH). Cord blood samples were collected and analyzed for glucose by Glucose-oxidase (GOD-PAP) method in TASH laboratory using HumaStar 300 from November 2010 to April 2011. All pre-analytical, analytical and post-analytical aspects were thoroughly controlled. A robust method was used for the determination of reference intervals using MedCalc® software Version 11.6.1. VD newborns accounted for 71.7% (n = 43) while the CS newborns accounted for 28.3% (n = 17). No statistically significant difference was noted in the studied demographic variables among VD and CS newborns except for blood glucose level. The RIs were then determined to be 2.46-6.85 mmol/l and 2.46-5.04 mmol/l for VD and CS newborns respectively. The combined RI was 2.24-6.48 mmol/l. Combined RI better be used for the interpretation of cord blood glucose values in VD and CS newborns. Cord blood glucose concentrations of 2.24 mmol/l can be used as statistical estimates of cut off points for neonatal hypoglycemia in newborns irrespective of their mode of deliveries.


Kinetic studies on sex difference in susceptibility to chronic benzene intoxication--with special reference to body fat content.
The sex difference in the susceptibility to haematopoietic disorders induced by benzene was studied kinetically with a special reference to its relation with the body fat content. In rats of both sexes with a large body fat content, benzene was eliminated more slowly and remained in the body for a longer time than in rats with a small body fat content. In accord with this finding, the decrease in white blood cell numbers during a chronic benzene exposure was observed only in the groups of rats which had a large volume of fat tissue. In an experimental human exposure, the elimination of benzene was slower in the females than in the males. The kinetic study revealed that the slower elimination in the females is due primarily to the bulky distribution of body fat tissue in that sex. From these results obtained from the experimental exposure of men and rats to benzene, it was concluded that the human female, with her massive body fat tissue, shows an inherent disposition to be susceptible to a chemical such as benzene which has a high affinity with fat tissue.


Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC).
RATIONALE : Preclinical work demonstrates that the transcription factor peroxisome proliferator-activated receptor gamma plays an important role in augmenting phagocytosis while modulating oxidative stress and inflammation. We propose that targeted stimulation of phagocytosis to promote efficient removal of the hematoma without harming surrounding brain cells may be a therapeutic option for intracerebral hemorrhage. AIMS : The primary objective is to assess the safety of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in increasing doses for three-days followed by a maintenance dose, when administered to patients with spontaneous intracerebral hemorrhage within 24 h of symptom onset compared with standard care. We will determine the maximum tolerated dose of pioglitazone. STUDY DESIGN : This is a prospective, randomized, blinded, placebo-controlled, dose-escalation safety trial in which patients with spontaneous intracerebral hemorrhage are randomly allocated to placebo or treatment. The Continual Reassessment Method for dose finding is used to determine the maximum tolerated dose of pioglitazone. Hematoma and edema resolution is evaluated with serial magnetic resonance imaging (MRI) at specified time points. Functional outcome will be evaluated at three- and six-months. OUTCOMES : The primary safety outcome is mortality at discharge. Secondary safety outcomes include mortality at three-months and six-months, symptomatic cerebral edema, clinically significant congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Radiographic outcomes will explore the time frame for resolution of 25%, 50%, and 75% of the hematoma. Clinical outcomes are measured by the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, modified Rankin Scale, Stroke Impact Scale-16, and EuroQol at three- and six-months.


Collagen type I expression in experimental anaplastic thyroid carcinoma: regulation and relevance for tumorigenicity.
Fibrosis in solid malignancies plays a significant role in tumor pathophysiology. Potential mechanisms for collagen type I deposition in anaplastic thyroid carcinoma (ATC) were investigated using 6 characterized ATC cell lines. Three of these cell lines, which produced collagen type I, had, as a group, a poor tumorigenicity when inoculated in athymic mice. This group of cells generated tumors in 4 of 24 injected animals (17%). Pro-alpha 1(I) collagen mRNA-expressing carcinoma and stromal cells were interdispersed in the tumors generated by these ATC cells. By contrast, the 3 noncollagen-producing ATC cell lines were all tumorigenic with a tumor take of 60% in the whole group. In the latter tumors, pro-alpha 1(I) collagen mRNA-expressing cells were confined to the stromal compartment, well delineated from carcinoma cell islets. To study the influence of ATC cells on collagen type I synthesis by fibroblasts, we used AG 1518 diploid human fibroblasts cultured on poly-(2-hydroxyethyl methacrylate) (poly[HEMA])-coated plates. This culture condition allows the study of the effect of collagen mRNA translation in the regulation of collagen type I synthesis. Conditioned media from the 6 ATC cell lines did not influence collagen synthesis. The ATC cell line KAT-4 stimulated fibroblast synthesis of collagen type I when the two cell types were cocultured on poly[HEMA]-coated substrates. Specific inhibitors of PDGF and TGF-beta reduced the KAT 4 carcinoma cell-induced stimulation of collagen type I synthesis. Our data suggest that collagen type I production by carcinoma cells correlates negatively with tumorigenicity and that the formation of a well-defined stroma is of importance for tumor growth. Furthermore, our data suggest that tumor cells are able to stimulate collagen mRNA translation in stromal fibroblasts in direct cell-cell contact by, at least in part, transferring PDGF or TGF-beta.


Evidence for massive bulk Dirac fermions in Pb₁-xSnxSe from Nernst and thermopower experiments.
Topological surface states protected by mirror symmetry are of interest for spintronic applications. Such states were predicted to exist in the rocksalt IV-VI semiconductors, and several groups have observed the surface states in (Pb,Sn)Te, (Pb,Sn)Se and SnTe using photoemission. An underlying assumption in the theory is that the surface states arise from bulk states describable as massive Dirac states, but this assumption is untested. Here we show that the thermoelectric response of the bulk states displays features specific to the Dirac spectrum. By relating the carrier density to the peaks in the quantum oscillations, we show that the first (N=0) Landau level is non-degenerate. This finding provides robust evidence that the bulk states are indeed massive Dirac states. In the lowest Landau level, Sxx displays a striking linear increase versus magnetic field characteristic of massive Dirac fermions. In addition, the Nernst signal displays a sign anomaly in the gap-inverted phase at low temperatures.


[Immunology in clinical practice. VI. Current immunosuppressive drugs].
Immunosuppressive drugs are agents capable of modulating at least one type of immune response in vivo at doses with tolerable side-effects. Classical immunosuppressive drugs include corticosteroids, azathioprine, cyclophosphamide, methotrexate and cyclosporine. In the past two years tacrolimus and mycophenolate mofetil were registered as immunosuppressive drugs. Tacrolimus interferes with the calcium-dependent signal transduction of T-lymphocytes. Mycophenolate mofetil is an inhibitor of purine synthesis by inhibition of the enzyme inosine monophosphate dehydrogenase. Both tacrolimus and mycophenolate mofetil have proven efficacy in both prevention and treatment of acute allograft rejection. The new drugs are stronger than the classical ones but do not cause more adverse reactions. The value in clinical medicine of some new, promising immunosuppressive drugs, i.e. sirolimus (rapamycin), mizoribine, brequinar and leflunomide remains to be proven.


Outcomes of Cyanoacrylate Closure Versus Radiofrequency Ablation for the Treatment of Incompetent Great Saphenous Veins.
Evaluation of the efficacy and safety of cyanoacrylate closure (CAC) for treating incompetent great saphenous veins (GSVs) compared to radiofrequency ablation (RFA). In this prospective, randomized controlled study, 248 symptomatic subjects with incompetent GSVs were assigned to either CAC or RFA. The primary end point, complete closure of the target GSV, was determined using a duplex ultrasound examination. In this study, 248 patients (mean age 33.64 ± 8.06 years including 71% women) were treated with either CAC (n = 128) or RFA (n = 120) between August 2018 to May 2022. As a follow-up, after a 1-month duration, the closure rates were 128/128 at the CAC and 154/158 at the RFA. At month 24, closure rates were 122/128 at CAC and 146/158 at RFA. Apart from phlebitis and pigmentation, the incidences of bruising, skin burn, and paresthesia were lower in the CAC group compared to the RFA group. The mean procedural times were shorter for CAC. The satisfaction level with the treatment was moderately higher among CAC patients than RAF patients. This study suggests that Cyanoacrylate glue closure of the GSV and RFA are effective techniques for managing primary varicose veins. Cyanoacrylate glue closure of the GSV appears to have a lower rate of complications and higher satisfaction levels, rapid return to normal activities, and improved procedure time without the need for perivenous tumescent anesthesia and postprocedure compression stockings when compared to RFA.


Narcotic withdrawal syndrome in young adults after the therapeutic use of opiates.
Five young adults with malignant neoplasms developed symptoms of narcotic withdrawal six to 48 hours after the abrupt discontinuation of narcotic therapy that had been administered for six to 21 days. The symptoms, which included agitation, irritability, muscular jerks, abdominal pain, diarrhea, burning sensations, "gooseflesh," and itching, rapidly resolved when narcotic therapy was reinstituted. Four patients were then successfully weaned from opiates without recurrence of their withdrawal symptoms; the fifth patient continues to receive methadone hydrochloride treatment for continuing pain.


[Opinions of healthcare professionals on the definition of severe mental illness: a qualitative study].
Over the years, a number of definitions of severe mental illness (SMI) have been proposed and substantial controversy about the definition still remains. The aim of this study was to evaluate the views of a group of mental health professionals on the appropriate criteria for defining SMI. This was a qualitative study, based on five focus groups with mental health professionals (psychiatrists, psychologists, nurses, general practitioners, monitors and social workers) from Carlos Haya Hospital in Malaga, Spain. A content analysis was performed on the transcriptions by three independent researchers. The professionals agreed that a certain degree of dysfunctionality must be present for a definition of SMI. There was some disagreement between the different categories of professionals regarding the inclusion of dimensions such as diagnosis, family and social support, use of healthcare resources and duration of the illness as necessary and sufficient criteria for the definition of SMI. From the professionals' discourse, some personal patient variables such as age of onset of illness, lack of insight and level of education emerged as relevant for the definition of SMI. Apart from the dimensions considered in the literature, the interviewed mental health professionals discussed other criteria that could be taken into account in the definition of SMI. Perceptions differ between categories of professional and work settings in which they operate.


First report of a disease caused by Bacillus cereus in cultured loach Paramisgurnus dabryanus.
Bacillus cereus is commonly considered a bacterium pathogenic to mammals, but several studies have suggested that it also induces diseases in fish. In 2017 and 2018, 2 strains of B. cereus, NQ-2017-17 and NQ-2018-8, were isolated from diseased large-scale loach Paramisgurnus dabryanus in Tianjin, China, and were considered to be the pathogens responsible for the disease. These stains were identified as B. cereus based on the results of 16S rDNA gene sequence analysis, Vitek biochemical tests, physiological and biochemical tests, and B. cereus group species-specific PCR. Strains NQ-2017-7 and NQ-2018-8 were found to contain virulence genes (e.g. hblA, hblC, hblD, entFM, and bceT) causing pathological damage to the spleen, kidneys, liver, and gills of loach. The median lethal dose (LD50) of NQ-2017-7 and NQ-2018-8 for loach were 1.0 ×106.64 and 1.0 ×106.49 CFU ml-1, respectively. To our knowledge, this is the first report of loach disease caused by a member of the genus Bacillus.


Assessment of a new instrument for detecting preventable adverse drug reactions.
Pharmacovigilance centres (PVCs) in the World Health Organization (WHO) Programme for International Drug Monitoring have demonstrated their ability to detect preventable adverse drug reactions (ADRs) in their databases. In this field, there is no gold-standard method for detecting medication errors and evaluating ADR preventability. Therefore, we developed, from existing tools, a preventability assessment method: the 'P Method' (PM). To present the PM and to evaluate its inter-rater reliability. The PM includes 20 explicit criteria for assessing ADR preventability. This approach is based on identification of any potentially preventable risk factor that increases the likelihood of ADR occurrence. The outcome of the preventability assessment results in one of three possible scores: 'preventable', 'non-preventable' or 'not assessable'. The PM was tested in a multicentre study involving nine national PVCs. Two experienced reviewers at each participating PVC independently analysed the preventability of 183 ADRs, applying the PM. The overall agreement between all reviewers for assessment of ADR preventability was 'fair', with a kappa value of 0.27 [95 % confidence interval (CI) 0.21-0.40]. The level of agreement between reviewer pairs ranged from 'slight', with a kappa value of 0.12 (95 % CI -0.03 to 0.27), to 'substantial', with a kappa value of 0.69 (95 % CI 0.48-0.89). The analysis of the agreements and disagreements between reviewers highlighted where improvements might be made. Given that no standard assessment tool exists in the WHO Programme, the transparency of the assessment process in this method provides a substantial basis for further development and for support in signalling possible preventability.


Scabies: important clinical consequences explained by new molecular studies.
In 2004, we reviewed the status of disease caused by the scabies mite Sarcoptes scabiei at the time and pointed out that very little basic research had ever been done. The reason for this was largely the lack of availability of mites for experimental purposes and, to a degree, a consequent lack of understanding of its importance, resulting in the trivial name 'itch mite'. Scabies is responsible for major morbidity in disadvantaged communities and immunocompromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by bacterial pathogens such as Streptococcus pyogenes and Staphylococcus aureus via skin lesions, resulting in severe downstream disease such as in a high prevalence of rheumatic fever/heart disease in affected communities. We now have further evidence that in disadvantaged populations living in tropical climates, scabies rather than 'Strep throat' is an important source of S. pyogenes causing rheumatic fever and eventually rheumatic heart disease. In addition, our work has resulted in two fundamental research tools that facilitate much of the current biomedical research efforts on scabies, namely a public database containing ~45,000 scabies mite expressed sequence tags and a porcine in vivo model. Here we will discuss novel and unexpected proteins encountered in the database that appear crucial to mite survival with regard to digestion and evasion of host defence. The mode(s) of action of some of these have been at least partially revealed. Further, newly discovered molecules that may well have a similar role, such as a family of inactivated cysteine proteases, are yet to be investigated. Hence, there are now whole families of potential targets for chemical inhibitors of S. scabiei. These efforts put today's scabies research in a unique position to design and test small molecules that may specifically interfere with mite-derived molecules, such as digestive proteases and mite complement inhibitors. The porcine scabies model will be available to trial in vivo treatment with potential inhibitors. New therapies for scabies may be developed from these studies and may contribute to reduce the spread of scabies and the subsequent prevalence of bacterial skin infections and their devastating sequelae in the community.


Disaster Metrics: Evaluation of de Boer's Disaster Severity Scale (DSS) Applied to Earthquakes.
Quantitative measurement of the medical severity following multiple-casualty events (MCEs) is an important goal in disaster medicine. In 1990, de Boer proposed a 13-point, 7-parameter scale called the Disaster Severity Scale (DSS). Parameters include cause, duration, radius, number of casualties, nature of injuries, rescue time, and effect on surrounding community. Hypothesis This study aimed to examine the reliability and dimensionality (number of salient themes) of de Boer's DSS scale through its application to 144 discrete earthquake events. A search for earthquake events was conducted via National Oceanic and Atmospheric Administration (NOAA) and US Geological Survey (USGS) databases. Two experts in the field of disaster medicine independently reviewed and assigned scores for parameters that had no data readily available (nature of injuries, rescue time, and effect on surrounding community), and differences were reconciled via consensus. Principle Component Analysis was performed using SPSS Statistics for Windows Version 22.0 (IBM Corp; Armonk, New York USA) to evaluate the reliability and dimensionality of the DSS. A total of 144 individual earthquakes from 2003 through 2013 were identified and scored. Of 13 points possible, the mean score was 6.04, the mode = 5, minimum = 4, maximum = 11, and standard deviation = 2.23. Three parameters in the DSS had zero variance (ie, the parameter received the same score in all 144 earthquakes). Because of the zero contribution to variance, these three parameters (cause, duration, and radius) were removed to run the statistical analysis. Cronbach's alpha score, a coefficient of internal consistency, for the remaining four parameters was found to be robust at 0.89. Principle Component Analysis showed uni-dimensional characteristics with only one component having an eigenvalue greater than one at 3.17. The 4-parameter DSS, however, suffered from restriction of scoring range on both parameter and scale levels. Jan de Boer's DSS in its 7-parameter format fails to hold statistically in a dataset of 144 earthquakes subjected to analysis. A modified 4-parameter scale was found to quantitatively assess medical severity more directly, but remains flawed due to range restriction on both individual parameter and scale levels. Further research is needed in the field of disaster metrics to develop a scale that is reliable in its complete set of parameters, capable of better fine discrimination, and uni-dimensional in measurement of the medical severity of MCEs.


Prevalence of antigen receptor variants in human T cell lines and tumors.
Previously, we have shown that a human T acute lymphoblastic leukemia cell line, HPB-ALL, exhibits clonal heterogeneity within its Ag receptor, as revealed by varying reactivity patterns with a panel of anti-idiotype mAb. We now extend these findings to another human T acute lymphoblastic leukemia cell line, SUP-T13, and to two fresh human chronic lymphocytic leukemias, JE and EF. In the two cell lines, two types of Ag receptor variants could be found: those that retained a receptor molecule but lost reactivity with an anti-idiotype mAb (idiotype variants), and those which had lost surface receptor expression completely (receptor-negative variants). The idiotype variants, at least in HPB-ALL, have differentially glycosylated receptor alpha-chains from the parent. The receptor-negative cells, in HPB-ALL as well as in SUP-T13, produce cytoplasmic receptor and CD3 proteins but do not transport them to the surface. Neither idiotype nor receptor-negative variants could be detected in either of the fresh tumors of chronic lymphocytic leukemias. The limit of sensitivity in these analyses was about 0.05%. We conclude that antigen receptor variants can spontaneously occur in cell lines derived from acute lymphoblastic leukemias, but are infrequent in chronic lymphocytic leukemias in vivo, and that therapy with anti-idiotype mAb may be a viable strategy for these malignancies.


Regulation of p73 by Hck through kinase-dependent and independent mechanisms.
p73, a p53 family member is a transcription factor that plays a role in cell cycle, differentiation and apoptosis. p73 is regulated through post translational modifications and protein interactions. c-Abl is the only known tyrosine kinase that phosphorylates and activates p73. Here we have analyzed the role of Src family kinases, which are involved in diverse signaling pathways, in regulating p73. Exogenously expressed as well as cellular Hck and p73 interact in vivo. In vitro binding assays show that SH3 domain of Hck interacts with p73. Co-expression of p73 with Hck or c-Src in mammalian cells resulted in tyrosine phosphorylation of p73. Using site directed mutational analysis, we determined that Tyr-28 was the major site of phosphorylation by Hck and c-Src, unlike c-Abl which phosphorylates Tyr-99. In a kinase dependent manner, Hck co-expression resulted in stabilization of p73 protein in the cytoplasm. Activation of Hck in HL-60 cells resulted in tyrosine phosphorylation of endogenous p73. Both exogenous and endogenous Hck localize to the nuclear as well as cytoplasmic compartment, just as does p73. Ectopically expressed Hck repressed the transcriptional activity of p73 as determined by promoter assays and semi-quantitative RT-PCR analysis of the p73 target, Ipaf and MDM2. SH3 domain- dependent function of Hck was required for its effect on p73 activity, which was also reflected in its ability to inhibit p73-mediated apoptosis. We also show that Hck interacts with Yes associated protein (YAP), a transcriptional co-activator of p73, and shRNA mediated knockdown of YAP protein reduces p73 induced Ipaf promoter activation. We have identified p73 as a novel substrate and interacting partner of Hck and show that it regulates p73 through mechanisms that are dependent on either catalytic activity or protein interaction domains. Hck-SH3 domain-mediated interactions play an important role in the inhibition of p73-dependent transcriptional activation of a target gene, Ipaf, as well as apoptosis.


Barriers and facilitators to exchanging health information: a systematic review.
We conducted a systematic review of studies assessing facilitators and barriers to use of health information exchange (HIE). We searched MEDLINE, PsycINFO, CINAHL, and the Cochrane Library databases between January 1990 and February 2015 using terms related to HIE. English-language studies that identified barriers and facilitators of actual HIE were included. Data on study design, risk of bias, setting, geographic location, characteristics of the HIE, perceived barriers and facilitators to use were extracted and confirmed. Ten cross-sectional, seven multiple-site case studies, and two before-after studies that included data from several sources (surveys, interviews, focus groups, and observations of users) evaluated perceived barriers and facilitators to HIE use. The most commonly cited barriers to HIE use were incomplete information, inefficient workflow, and reports that the exchanged information that did not meet the needs of users. The review identified several facilitators to use. Incomplete patient information was consistently mentioned in the studies conducted in the US but not mentioned in the few studies conducted outside of the US that take a collective approach toward healthcare. Individual patients and practices in the US may exercise the right to participate (or not) in HIE which effects the completeness of patient information available to be exchanged. Workflow structure and user roles are key but understudied. We identified several facilitators in the studies that showed promise in promoting electronic health data exchange: obtaining more complete patient information; thoughtful workflow that folds in HIE; and inclusion of users early in implementation.


MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients.
Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients. IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium. Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells. These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.


Autophagy proteins play cytoprotective and cytocidal roles in leucine starvation-induced cell death in Saccharomyces cerevisiae.
Autophagy is essential for prolonging yeast survival during nutrient deprivation; however, this report shows that some autophagy proteins may also be accelerating population death in those conditions. While leucine starvation caused YCA1-mediated apoptosis characterized by increased annexin V staining, nitrogen deprivation triggered necrotic death characterized by increased propidium iodide uptake. Although a Δatg8 strain died faster than its parental strain during nitrogen starvation, this mutant died slower than its parent during leucine starvation. Conversely, a Δatg11 strain died slower than its parent during nitrogen starvation, but faster during leucine starvation. Curiously, although GFP-Atg8 complemented the Δatg8 mutation, this protein made ATG8 cells more sensitive to nitrogen starvation, and less sensitive to leucine starvation. These results were difficult to explain if autophagy only extended life but could be an indication that a second form of autophagy could concurrently facilitate either apoptotic or necrotic cell death.


Performance Evaluation of Hybrid Crowdsensing and Fixed Sensor Systems for Event Detection in Urban Environments.
Crowdsensing offers a cost-effective way to collect large amounts of environmental sensor data; however, the spatial distribution of crowdsensing sensors can hardly be influenced, as the participants carry the sensors, and, additionally, the quality of the crowdsensed data can vary significantly. Hybrid systems that use mobile users in conjunction with fixed sensors might help to overcome these limitations, as such systems allow assessing the quality of the submitted crowdsensed data and provide sensor values where no crowdsensing data are typically available. In this work, we first used a simulation study to analyze a simple crowdsensing system concerning the detection performance of spatial events to highlight the potential and limitations of a pure crowdsourcing system. The results indicate that even if only a small share of inhabitants participate in crowdsensing, events that have locations correlated with the population density can be easily and quickly detected using such a system. On the contrary, events with uniformly randomly distributed locations are much harder to detect using a simple crowdsensing-based approach. A second evaluation shows that hybrid systems improve the detection probability and time. Finally, we illustrate how to compute the minimum number of fixed sensors for the given detection time thresholds in our exemplary scenario.


The roles of NF-kB in the development of lung injury after one-lung ventilation.
To explore the roles of NF-kB in the development of lung injury after one-lung ventilation. Eighteen Sprague-Dawley (SD) rats were randomly divided into 3 groups including control group, one-lung ventilation (OL) group and NF-kB inhibitor pyrrolidine dithiocarbamate (PDTC) group, with 6 rats in each group. Rats in OL and PDTC groups were used to establish one-lung ventilation model, and rats in PDTC group were subjected to intravenous injection of NF-kB specific inhibitor PDTC at 30 min before model construction. One-lung ventilation was performed for 3 h, and arterial blood gas analyzer was used for blood gas analysis. The hemodynamics and respiratory mechanics parameters were detected. The respiratory index (RI) and oxygenation index (OI) were calculated. The pathological changes of lung tissue were observed by HE staining. The levels of TNF-α, IL-1β, IL-6, and IL-8 in lung tissue were detected by ELISA. The expression levels of p65, p-p65, p-IκBα and IκBα and the activity of NF-Kβ in lung tissue were detected by Western Blot. Compared with OL group, HR, RI and W/D were significantly reduced and MAP and OI were significantly increased in PDTC group (p<0.05). Compared with OL group, alveolar fluid exudation, pulmonary interstitial thickening and inflammatory cell infiltration were significantly improved in PDTC group. The levels of TNF-α, IL-1β, IL-6 and IL-8 in PDTC group were significantly lower than in OL group (p<0.05). The ratios of p-p65/p65 and p-IκBα/IκBα and the activity of NF-kB in OL group were significantly reduced than in PDTC group (p<0.05). NF-kB can promote lung injury after one-lung ventilation, and the inhibition of NF-kB may be a new way for the treatment of this disease.


Graphene Quantum Dots Doping of MoS2 Monolayers.
Graphene quantum dots (GQDs) interacting with molybdenum disulfide (MoS2 ) monolayers induce an effective photoexcited charge transfer at the interface. Both the photoluminescence (PL) and valley polarization of this GQDs/MoS2 heterostructure can be modulated under various doping charge densities. The photon-exciton interaction is used to explain and calculate the heterostructure PL control, and is further applied to the valley-polarization tuning.


The Canadian approach to elder financial abuse from a legal and clinical perspective: A narrative review.
Elder financial abuse is a growing problem, with significant consequences for society. It is unclear if differences exist in the clinical and legal approach to financial abuse across Canada, thus the purpose of this review. Five databases were searched during the primary literature search. Secondary literature search involved searching grey literature and handpicking references from selected articles. Only articles in English were included. From 10,260 articles initially screened, 30 were included in the review. No literature was identified describing differences in the clinical approach to financial abuse, and no single definition or legislation on financial abuse was identified. Mandatory reporting is required for individuals in a hospital or care facility by only five provinces. This review has identified several important knowledge gaps on the differences in the clinical management of financial abuse, and a lack of definition, legislation and overall mandatory reporting across Canada, which requires further research.


Combined high degree of carboxylation and electronic conduction in graphene acid sets new limits for metal free catalysis in alcohol oxidation.
Graphene oxide, the most prominent carbocatalyst for several oxidation reactions, has severe limitations due to the overstoichiometric amounts required to achieve practical conversions. Graphene acid, a well-defined graphene derivative selectively and homogeneously covered by carboxylic groups but maintaining the high electronic conductivity of pristine graphene, sets new activity limits in the selective and general oxidation of a large gamut of alcohols, even working at 5 wt% loading for at least 10 reaction cycles without any influence from metal impurities. According to experimental data and first principles calculations, the selective and dense functionalization with carboxyl groups, combined with excellent electron transfer properties, accounts for the unprecedented catalytic activity of this graphene derivative. Moreover, the controlled structure of graphene acid allows shedding light upon the critical steps of the reaction and regulating precisely its selectivity toward different oxidation products.


Second record of Lasiurus ebenus (Chiroptera, Vespertilionidae), with comments on its taxonomic status.
Lasiurus ebenus was known only from the holotype, which was collected in 1991, in an Atlantic Forest remnant of Ilha do Cardoso State Park, southeastern Brazil. The species was described based on qualitative and quantitative morphological features. Since its original description, based on a single individual, the taxonomic status of Lasiurus ebenus has been questioned. Here we report a second record for the species that comes from Carlos Botelho State Park, São Paulo, ca. 100 km north from the type locality. This new record allowed us to confirm the validity of the species, by presenting additional data that fits in the distinction from sympatric congeners proposed on the original description of L. ebenus.


Applied systems thinking: unlocking theory, evidence and practice for health policy and systems research.
While systems thinking has been generally acknowledged as important to the field of health policy and systems research (HPSR), it remains underutilized. In particular, systems thinking has been perceived as predominantly conceptual, with fewer applications of systems thinking documented. This commentary makes three key points, namely that (1) advances in applied systems thinking in HPSR have been hindered by an imprecision in terminology, conflating '[health] systems approaches' with complex adaptive systems theory; (2) limited examples of applied systems thinking have been highlighted and recognized in research, but have not been fully and equally appreciated in policymaking and practice and (3) explicit use of theory, long-term research-policy collaborations and better documentation of evidence can increase the use and usefulness of applied systems thinking in HPSR. By addressing these matters, the potentials of systems thinking in HPSR can be truly unlocked.


Youth participatory research and evaluation to inform a Chagas disease prevention program in Ecuador.
This qualitative study engaged a group of young people in participatory research and evaluation activities in order to study to what extent engaging youth in health interventions can inform research and evaluation processes. We applied a youth participatory research and evaluation approach (PRE) to inform research and evaluation on the impact of a Chagas disease control program in southern Ecuador. Our main interest was to examine the methodological contributions of PRE to knowledge sharing for health intervention planning in the context of global health and neglected tropical diseases. The results of this study suggest that by demystifying research and evaluation practices and rendering them accessible and relevant, marginalized youth can develop critical and reflexive thinking skills that could be useful for decision-making on health promotion. Our findings also reveal the potential of youth as active participants in project development in ways that enhance, validate, and improve health interventions. Young people are interested in learning about and sharing local knowledge that can benefit research and evaluation processes. Despite the numerous strengths demonstrated by PRE, the inherent complexities of international development, such as cultural differences, asymmetrical power relations, and the ongoing challenges of sustainability, remain.


[Influence of wind, cold and dampness on clinical manifestation of knee osteoarthritis patients based on the stratifications of traditional Chinese medicine constitution].
To explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. A cross-sectional stratified study was performed to select 108 patients with GradeⅡKOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m-2 with an average of (23.80±2.86) kg·m-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m-2 with an average of(23.42±2.97) kg·m-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m-2 with an average of (24.15±2.33) kg·m-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m-2 with an average of (23.79±2.49) kg·m-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.


Effects of Blood Coagulate Removal Method on Aedes albopictus (Diptera: Culicidae) Life Table Characteristics and Vector Competence for Dengue Virus.
Commercially available blood can be used as an alternative to live animals to maintain mosquito colonies and deliver infectious bloodmeals during research studies. We analyzed the extent to which two methods for blood coagulate removal (defibrination or addition of sodium citrate) affected life table characteristics (i.e., fecundity, fertility, hatch rate, and adult survival) and vector competence (infection, dissemination, and transmission) of Aedes albopictus (Skuse) for dengue virus (DENV). Two types of bovine blood were tested at two extrinsic incubation temperatures (27 or 30°C) for DENV-infected and uninfected mosquitoes. Fully engorged mosquitoes were transferred to individual cages containing an oviposition cup and a substrate. Eggs (fecundity) and hatched larvae (fertility) were counted. At 14 and 21 d post feeding on a DENV-infected bloodmeal, 15 mosquitoes were sampled from each group, and vector competence was analyzed (bodies [infection], legs [dissemination], and saliva [transmission]). Differences in life table characteristics and vector competence were analyzed for mosquitoes fed blood processed using different methods for removal of coagulates. The method for removal of coagulates significantly impacted fecundity, fertility, and hatch time in the uninfected group, but not DENV-infected group. Infected mosquitoes showed significantly higher fecundity and faster hatch time than uninfected mosquitoes. We show no significant differences in infection or dissemination rates between groups; however, horizontal transmission rate was significantly higher in mosquitoes fed DENV-infected citrated compared with defibrinated blood. We expect the findings of this study to inform research using artificial blood delivery methods to assess vector competence.


Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells.
Increasing evidence suggests that microRNAs are involved in human carcinogenesis as tumor suppressors or oncogenes. A growing number of reports has shown that an interest has been sparked in aberrant microRNA expression and how they can be used to treat human diseases, including cancer. However, their precise biological role remains largely unknown. In the present study, we aimed to identify micro-RNA species involved in the regulation of tumor growth. By performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, we demonstrated that mir-663 was downregulated in human gastric cancer cell lines unlike in normal cells. A transient introduction of mir-663 into the human gastric cancer cell lines BGC823 and SNU5 induced morphology changes and suppression of proliferation of these cells. In addition, mir-663 alters the DNA content and induces phenotypes of mitotic catastrophe in tumor cells. Moreover, the liposome-mediated delivery of mir-663 suppressed the in vivo growth of the BGC823 and SNU5 cells. Western blot analyses performed after the introduction of mir-663 revealed upregulation of cyclin B following transfection with mir-663. Our results provide evidence that downregulation of mir-663 in tumor cells may contribute to aberrant cell hyperplasia, leading to the development of gastric cancer. Therefore, mir-663 might function as a potent suppressor of tumor growth.


Direct measurement of thermodynamic and kinetic parameters of DNA triple helix formation by fluorescence spectroscopy.
Direct measurement of thermodynamic and kinetic parameters of oligonucleotide-directed DNA triple helix formation has been achieved by fluorescence spectroscopic methods. Fluorescence resonance energy transfer (FRET) was used to study the binding of an acceptor-labeled single-stranded oligonucleotide to a donor-labeled DNA duplex. Equilibrium binding constants and association rate constants for triplex formation between 5'-tetramethylrhodamine-labeled 11-mer, 13-mer, and 15-mer homopyrimidine oligonucleotides and a 5'-fluorescein-labeled, 25-bp DNA duplex containing a 15-bp homopurine site were determined by FRET measurements, and the values were in close agreement with those determined by established methods. The thermal dissociation profile of the triplex-to-duplex transition was also directly observed by FRET and was consistent with the triplex melting curves obtained by UV absorbance measurements. In addition, a homogeneous fluorescence anisotropy assay is described which enables determination of the binding constants between 5'-tetramethylrhodamine-labeled 11-mer and 13-mer homopyrimidine oligonucleotides and unlabeled 25-, 30-, and 50-bp double-stranded DNA containing a homopurine target site. These results demonstrate the utility of nonradioactive fluorescence measurements as an efficient method for studying triple helix formation under homogeneous solution conditions and highlight the uniqueness of the FRET method for obtaining equilibrium, kinetic, and thermal dissociation data in a straightforward manner.


Accuracy of Chlamydia trachomatis antigen detection methods in a low-prevalence population in a primary care setting.
We compared a direct fluorescent-antibody stain (DFA) and an enzyme immunoassay (EIA) with a standard cell culture technique for the detection of Chlamydia trachomatis infection in women in an urban family practice setting. We also evaluated a DFA sample in a commercial laboratory to determine the interlaboratory reliability of this test. There were 268 women in the study; the EIA provided a higher sensitivity (83 versus 50%) and a higher positive predictive value (83 versus 69%) than the DFA test and comparably high specificity (99 versus 98%). Concordance between the two laboratories on the DFA test was not high when data were adjusted for chance agreement (kappa coefficient = 0.64). DFA validity was optimal with an elementary body cutoff of greater than 5, while EIA validity was optimal at the recommended cutoff of 0.1 optical density unit. None of 11 women with negative cultures after treatment had false-positive antigen tests. False-negative results with both tests were associated with low culture inclusion counts but were not strongly associated with the presence or absence of symptoms, menses, pregnancy, or recent antibiotic use. False-positive results with EIA were seen only for three women who had a chief complaint of vaginal discharge. Although the positive predictive value of DFA could be increased in high-prevalence subpopulations, EIA was still more valid in two such groups: teenagers and prenatal patients. These results indicate that EIA might be preferable for low- or moderate-prevalence populations in primary care settings and that a falloff in DFA sensitivity could be explained by lower infection burdens in low-prevalence groups.


Intraspinal transplantation and modulation of donor neuron electrophysiological activity.
Rat fetal spinal cord (FSC) tissue, naturally enriched with interneuronal progenitors, was introduced into high cervical, hemi-resection (Hx) lesions. Electrophysiological analyses were conducted to determine if such grafts exhibit physiologically-patterned neuronal activity and if stimuli which increase respiratory motor output also alter donor neuron bursting. Three months following transplantation, the bursting activity of FSC neurons and the contralateral phrenic nerve were recorded in anesthetized rats during a normoxic baseline period and brief respiratory challenges. Spontaneous neuronal activity was detected in 80% of the FSC transplants, and autocorrelation of action potential spikes revealed distinct correlogram peaks in 87% of neurons. At baseline, the average discharge frequency of graft neurons was 13.0 ± 1.7 Hz, and discharge frequency increased during a hypoxic respiratory challenge (p<0.001). Parallel studies in unanesthetized rats showed that FSC tissue recipients had larger inspiratory tidal volumes during brief hypoxic exposures (p<0.05 vs. C2Hx rats). Anatomical connectivity was explored in additional graft recipients by injecting a transsynaptic retrograde viral tracer (pseudorabies virus, PRV) directly into matured transplants. Neuronal labeling occurred throughout graft tissues and also in the host spinal cord and brainstem nuclei, including those associated with respiratory control. These results underscore the neuroplastic potential of host-graft interactions and training approaches to enhance functional integration within targeted spinal circuitry.


Time-modified confounding.
According to the authors, time-modified confounding occurs when the causal relation between a time-fixed or time-varying confounder and the treatment or outcome changes over time. A key difference between previously described time-varying confounding and the proposed time-modified confounding is that, in the former, the values of the confounding variable change over time while, in the latter, the effects of the confounder change over time. Using marginal structural models, the authors propose an approach to account for time-modified confounding when the relation between the confounder and treatment is modified over time. An illustrative example and simulation show that, when time-modified confounding is present, a marginal structural model with inverse probability-of-treatment weights specified to account for time-modified confounding remains approximately unbiased with appropriate confidence limit coverage, while models that do not account for time-modified confounding are biased. Correct specification of the treatment model, including accounting for potential variation over time in confounding, is an important assumption of marginal structural models. When the effect of confounders on either the treatment or outcome changes over time, time-modified confounding should be considered.


Comparison of the postoperative analgesic efficacy of an ultrasound-guided fascia iliaca compartment block versus 3 in 1 block in hip prosthesis surgery.
In this study, we aimed to compare the postoperative analgesic efficiency of an ultrasound-guided fascia iliaca compartment block and a 3 in 1 block in patients who underwent hip prosthesis surgery as a result of hip fracture. With approval from the local ethics committee, 70 patients, aged 20 to 80, undergoing hip prosthesis surgery under elective conditions were included in this randomized, prospective, controlled study. They were informed of the patient-controlled analgesia (PCA) device and visual analog scale (VAS). All patients were separated randomly into three groups. Anaesthesia induction was standardized for all groups. An ultrasound guidance fascia iliaca compartment block (FICB) was applied to the first group before anaesthesia induction. For the second group, a 3 in 1 block was applied, while for the control group no block was applied. After incision on all patients, 20 mg tenoxicam and 1 mg/kg tramadol were injected intravenously. Following surgery, IV tramadol PCA was begun on all patients routinely. In our study, the presence of cortisol and ACTH levels, hemodinamical parameters, nausea and sedation were determined. We observed a decrease in VAS values and opioid consumption, no adverse effects on nausea and sedation, and a suppression of stress hormones in both the ultrasound-guided FICB and 3 in 1 block groups. We believe that the safe and efficient application of the ultrasound-guided 3 in 1 block and the FICB is necessary in multimodal analgesic treatment in order to enable postoperative analgesia in hip prosthesis surgery.


Carbon innumeracy.
Individuals must have a quantitative understanding of the carbon footprint tied to their everyday decisions to make efficient sustainable decisions. We report research of the innumeracy of individuals as it relates to their carbon footprint. In three studies that varied in terms of scale and sample, respondents estimate the quantity of CO2 released when combusting a gallon of gasoline in comparison to several well-known metrics including food calories and travel distance. Consistently, respondents estimated the quantity of CO2 from gasoline compared to other metrics with significantly less accuracy while exhibiting a tendency to underestimate CO2. Such relative absence of carbon numeracy of even a basic consumption habit may limit the effectiveness of environmental policies and campaigns aimed at changing individual behavior. We discuss several caveats as well as opportunities for policy design that could aid the improvement of people's quantitative understanding of their carbon footprint.


Can autism be diagnosed accurately in children under 3 years?
This study investigated the reliability and stability of an autism diagnosis in children under 3 years of age who received independent diagnostic evaluations from two clinicians during two consecutive yearly evaluations. Strong evidence for the reliability and stability of the diagnosis was obtained. Diagnostic agreement between clinicians was higher for the broader discrimination of autism spectrum vs. no autism spectrum than for the more specific discrimination of autism vs. PDD-NOS. The diagnosis of autism at age 2 was more stable than the diagnosis of PDD-NOS at the same age. Social deficits and delays in spoken language were the most prominent DSM-IV characteristics evidenced by very young children with autism.


A highly efficient and accurate method of detecting and subtyping Influenza A pdm H1N1 and H3N2 viruses with newly emerging mutations in the matrix gene in Eastern Taiwan.
The rapid identification of Influenza A virus and its variants, which cause severe respiratory diseases, is imperative to providing timely treatment and improving patient outcomes. Conventionally, two separate assays (total test duration of up to 6 h) are required to initially differentiate Influenza A and B viruses and subsequently distinguish the pdm H1N1 and H3N2 serotypes of Influenza A virus. In this study, we developed a multiplex real-time RT-PCR method for simultaneously detecting Influenza A and B viruses and subtyping Influenza A virus, with a substantially reduced test duration. Clinical specimens from hospitalized patients and outpatients with influenza-like symptoms in Eastern Taiwan were collected between 2011 and 2015, transported to Hualien Tzu Chi Hospital, and analyzed. Conventional RT-PCR was used to subtype the isolated Influenza A viruses. Thereafter, for rapid identification, the multiplex real-time RT-PCR method was developed and applied to identify the conserved regions that aligned with the available primers and probes. Accordingly, a multiplex RT-PCR assay with three groups of primers and probes (MAF and MAR primers and MA probe; InfAF and InfAR primers and InfA probe; and MBF and MBR primers and MB probe) was established to distinguish these viruses in the same reaction. Thus, with this multiplex RT-PCR assay, Influenza B, Influenza A pdm H1N1, and Influenza A H3N2 viruses were accurately detected and differentiated within only 2.5 h. This multiplex RT-PCR assay showed similar analytical sensitivity to the conventional singleplex assay. Further, the phylogenetic analyses of our samples revealed that the characteristics of these viruses were different from those reported previously using samples collected during 2012-2013. In conclusion, we developed a multiplex real-time RT-PCR method for highly efficient and accurate detection and differentiation of Influenza A and B viruses and subtyping Influenza A virus with a substantially reduced test duration for diagnosis.