The Swedish reflux trial: review of a randomized, controlled trial in children with dilating vesicoureteral reflux.
To evaluate prophylaxis and endoscopic injection for children with dilating vesicoureteral reflux (VUR) compared to surveillance, regarding urinary tract infection (UTI) recurrence, new renal damage, VUR outcome, and impact of lower urinary tract (LUT) dysfunction on these outcomes. 203 children (128 girls and 75 boys), aged 1 to <2 years, with VUR grade III or IV were randomized to antibiotic prophylaxis (n = 69), endoscopic injection (n = 66) or surveillance (n = 68). Voiding cystourethrography, dimercaptosuccinic acid scintigraphy and optional LUT function assessment were performed before randomization and after 2 years. There were 67 febrile UTIs in 42 girls and 8 in 7 boys (p = 0.0001). In girls, recurrence rate was 19% on prophylaxis, 23% with endoscopic treatment and 57% on surveillance (p = 0.0002). In boys, there was no difference between treatment groups. New damage was seen in 13 girls: 8 on surveillance, 5 in the endoscopic group and none on prophylaxis (p = 0.0155), and in 2 boys. In 13 children with no or non-dilating VUR after 1 injection, dilating VUR reappeared at the 2-year follow up. LUT dysfunction at follow up was associated with persistence of VUR. In girls, prophylaxis reduced the rate of UTI recurrence and new renal damage, and endoscopic injection the rate of UTI recurrence. Boys did not benefit from active treatment.


Metal-Organic Framework-Based Lithium-Oxygen Batteries.
Rechargeable lithium-oxygen batteries (LOBs) are considered to be the next-generation energy technology owing to their high theoretical energy density. However, the sluggish cathode kinetics and degradation of Li anodes result in large voltage hysteresis and low coulombic efficiency. Various materials have been applied to promote the electrochemical performance of LOBs. Metal-organic frameworks (MOFs) possessing porous structures, open active sites and adjustable pore sizes have been attempted as promising materials for catalysts and separators of LOBs. This concept presents an overview of different MOF-based catalysts for LOBs, including traditional, conductive, semi-conductive and soluble MOFs, as well as our recently proposed photo-involved LOBs. Recent advances in MOF-based separators to restrain the shuttling of redox mediators between cathodes and anodes and suppress the formation of lithium dendrites are also discussed. Finally, perspectives on the development of MOF-based LOBs for future research are presented.


[Quality assurance of faculty examinations: Optimization of examination management in the Heidelberg Curriculum Medicinale (HeiCuMed)].
Examinations are a central element of the medical curriculum: they contribute significantly to the quality assurance of medical training and subsequent medical care. In order to meet the high expectations placed on examinations in terms of content, legal and organizational aspects, continuous quality assurance measures are necessary. The aim of this paper was to record and analyze the quality assurance measures implemented at the medical faculty of Heidelberg. We investigated quality indicators that are relevant to medical examinations - adequate choice of examination formats, blueprint/validity, reliability and distribution of grades, feedback to students, consequences of examinations - within the faculty examinations in the decentrally organized Heidelberg Curriculum Medicinale (HeiCuMed). In addition, the organizational structures in examination management were examined. For this purpose, interviews were conducted with teaching staff, students and the technical examination administration. The surveys show that the quality indicators in HeiCuMed have already been met in many areas. Optimization work remains to be done concerning the criteria "adequate choice of examination formats", "feedback to students" as well as the documentation of the examination process and the definition of substitution regulations. Training courses, statistical analysis and accompanying research are essential for establishing additional innovative, practice-oriented examination formats. In order to improve feedback to students, formative assessments should be more intensively integrated into the curriculum. As a measure for structured quality-oriented examination management, it is also helpful to document the examination procedure and the staff assigned to it using templates. Especially with decentralized examination management, the internal coordination of individual departments is of great importance in order to guarantee the quality of examinations. Regular surveys of the parties involved can be of support by collecting best-practice examples and deliver the respective information in handouts encouraging interdisciplinary exchange.


Collagenous colitis: oral low-dose methotrexate for patients with difficult symptoms: long-term outcomes.
To perform a qualitative retrospective review of identified cases of collagenous colitis within the patient databases of local clinicians, with particular attention to the use and effectiveness of oral low-dose methotrexate. Gastroenterologists in the referral area were invited to identify collagenous colitis cases from their own databases for inclusion in the study. Patients were considered eligible if they had a symptom history and colonic mucosal histology consistent with collagenous colitis. The retrospective analysis identified age at diagnosis, previous therapies, date of commencement and duration and effectiveness of methotrexate, side-effects, and repeat colonic mucosal histology (if available) after a period of treatment. Between 1986 and 2003, 43 eligible patients were identified, ranging in age from 32 years to 88 years at the time of diagnosis. Nineteen of the 43 received methotrexate over varying periods, and in 16 of these the clinical response was considered either 'Good' (14) or 'Partial' (2). In the methotrexate group 10 of the 19 underwent repeat colonoscopy and mucosal biopsy at some stage after commencing methotrexate. Of these, five had normal histology in comparison with pretreatment abnormal histology, two had improvement but not normalization of histology, and three had unchanged abnormal histology. The data from this retrospective review suggest that methotrexate may have a beneficial effect on symptoms of collagenous colitis and may improve the underlying histological abnormality. A controlled trial of adequate power and duration is needed to further clarify the usefulness of methotrexate in this condition.


A Novel Multisystem Proteinopathy Caused by a Missense ANXA11 Variant.
Protein misfolding plays a central role not only in amyotrophic lateral sclerosis (ALS), but also in other conditions, such as frontotemporal dementia (FTD), inclusion body myopathy (hIBM) or Paget's disease of bone. The concept of multisystem proteinopathies (MSP) was created to account for those rare families that segregate at least 2 out of these 4 conditions in the same pedigree. The calcium-dependent phospholipid-binding protein annexin A11 was recently associated to ALS in European pedigrees. Herein, we describe in detail 3 Brazilian families presenting hIBM (isolated or in combination with ALS/FTD) caused by the novel p.D40Y change in the gene encoding annexin A11 (ANXA11). We collected clinical, genetic, pathological and skeletal muscle imaging from 11 affected subjects. Neuroimaging was also obtained from 8 patients and 8 matched controls. Clinico-radiological phenotype of this novel hIBM reveals a slowly progressive predominant limb-girdle syndrome, but with frequent axial (ptosis/dropped head) and distal (medial gastrocnemius) involvement as well. Muscle pathology identified numerous rimmed vacuoles with positive annexin A11, TDP-43 and p62 inclusions, but no inflammation. Central nervous system was also involved: two patients had FTD, but diffusion tensor imaging uncovered multiple areas of cerebral white matter damage in the whole group (including the corticospinal tracts and frontal subcortical regions). These findings expand the phenotypic spectrum related to ANXA11. This gene should be considered the cause of a novel multisystem proteinopathy (MSP type 6), rather than just ALS. ANN NEUROL 2021;90:239-252.


Effects of GaN/AlGaN/Sputtered AlN nucleation layers on performance of GaN-based ultraviolet light-emitting diodes.
We report on the demonstration of GaN-based ultraviolet light-emitting diodes (UV LEDs) emitting at 375 nm grown on patterned sapphire substrate (PSS) with in-situ low temperature GaN/AlGaN nucleation layers (NLs) and ex-situ sputtered AlN NL. The threading dislocation (TD) densities in GaN-based UV LEDs with GaN/AlGaN/sputtered AlN NLs were determined by high-resolution X-ray diffraction (XRD) and cross-sectional transmission electron microscopy (TEM), which revealed that the TD density in UV LED with AlGaN NL was the highest, whereas that in UV LED with sputtered AlN NL was the lowest. The light output power (LOP) of UV LED with AlGaN NL was 18.2% higher than that of UV LED with GaN NL owing to a decrease in the absorption of 375 nm UV light in the AlGaN NL with a larger bandgap. Using a sputtered AlN NL instead of the AlGaN NL, the LOP of UV LED was further enhanced by 11.3%, which is attributed to reduced TD density in InGaN/AlInGaN active region. In the sputtered AlN thickness range of 10-25 nm, the LOP of UV LED with 15-nm-thick sputtered AlN NL was the highest, revealing that optimum thickness of the sputtered AlN NL is around 15 nm.


Phosphatidylserine-specific phospholipase A1: A friend or the devil in disguise.
Various human tissues and cells express phospholipase A1 member A (PLA1A), including the liver, lung, prostate gland, and immune cells. The enzyme belongs to the pancreatic lipase family. PLA1A specifically hydrolyzes sn-1 fatty acid of phosphatidylserine (PS) or 1-acyl-lysophosphatidylserine (1-acyl-lysoPS). PS externalized by activated cells or apoptotic cells or extracellular vesicles is a potential source of substrate for the production of unsaturated lysoPS species by PLA1A. Maturation and functions of many immune cells, such as T cells, dendritic cells, macrophages, and mast cells, can be regulated by PLA1A and lysoPS. Several lysoPS receptors, including GPR34, GPR174 and P2Y10, have been identified. High serum levels and high PLA1A expression are associated with autoimmune disorders such as Graves' disease and systemic lupus erythematosus. Increased expression of PLA1A is associated with metastatic melanomas. PLA1A may contribute to cardiometabolic disorders through mediating cholesterol transportation and producing lysoPS. Furthermore, PLA1A is necessary for hepatitis C virus assembly and can play a role in the antivirus innate immune response. This review summarizes recent findings on PLA1A expression, lysoPS and lysoPS receptors in autoimmune disorders, cancers, cardiometabolic disorders, antivirus immune responses, as well as regulations of immune cells.


Chemorefractory extranodal nasal-type natural-killer/T-cell lymphoma with great response to pembrolizumab in a young patient: a case report.
Extranodal, natural-killer/T-cell lymphoma of nasal type is a rare but aggressive disease usually presenting as progressive necrotic lesions in the nasal cavity that responds poorly to chemotherapy. In this paper, we report a relapsing, chemorefractory case of extranodal natural-killer/T-cell lymphoma responding to checkpoint inhibitor immunotherapy with pembrolizumab. A 32-year-old Hispanic woman with a history of recurrent sinusitis and preseptal abscess presented with a hoarse voice, swelling around the right eye, and diplopia. Laryngoscopy showed infiltrating tissue extending to bilateral laryngeal ventricles and false vocal cords. On immunohistochemical examination of laryngeal biopsy, the neoplastic cells showed positivity for CD3 (cytoplasmic), CD7, CD56, granzyme B, CD30, and Epstein-Barr virus-encoded ribonucleic acid (RNA). Extranodal natural-killer/T-cell lymphoma, nasal type, was confirmed. In the absence of distant organ involvement, the decision was to perform chemotherapy with etoposide, ifosfamide, mesna, cisplatin, and dexamethasone (VIPD protocol) followed by concurrent chemoradiation with weekly doses of cisplatin and two cycles of VIPD as adjuvant treatment. However, 1 month after completion of the treatment; disease recurrence was demonstrated. The patient was scheduled to receive salvage chemotherapy with steroid, methotrexate, ifosfamide, L- asparaginase, and etoposide (SMILE) protocol and CD30-targeting monoclonal antibodies. However, the mass was chemorefractory without response to either L-asparaginase-based salvage chemotherapy in combination with high-dose methotrexate or brentuximab vedotin. However, this case of chemorefractory extranodal natural-killer/T-cell lymphoma, nasal type, responded well to the novel drug pembrolizumab, which was able to control the disease. Checkpoint inhibitors are potential treatment option in selected chemorefractory extranodal natural-killer/T-cell lymphoma, nasal type, cases.


DFT insights into the electronic structure, mechanical behaviour, lattice dynamics and defect processes in the first Sc-based MAX phase Sc2SnC.
Here we employed the density functional theory calculations to investigate some physical properties of first Sc-based MAX phase Sc2SnC including defect processes to compare with those of existing M2SnC phases. The calculated structural properties are in good agreement with the experimental values. The new phase Sc2SnC is structurally, mechanically and dynamically stable. Sc2SnC is metallic with a mixture of covalent and ionic character. The covalency of Sc2SnC including M2SnC is mostly controlled by the effective valence. Sc2SnC in M2SnC family ranks second in the scale of deformability and softness. The elastic anisotropy level in Sc2SnC is moderate compared to the other M2SnC phases. The hardness and melting point of Sc2SnC, including M2SnC, follows the trend of bulk modulus. Like other members of the M2SnC family, Sc2SnC has the potential to be etched into 2D MXenes and has the potential to be a thermal barrier coating material.


Juvenile hormone analogue counteracts growth stimulation and inhibition by ecdysones in clonal Drosophila cell line.
Depending on concentration, ecdysones either stimulate or inhibit proliferation of a clonal Drosophila cell line. Both effects are counteracted by ethyl dichlorofarnesoate, a juvenile hormone analogue, which by itself is growth inhibitory. Qualitatively no difference was seen between alpha- and beta-ecdysone.


The association of efficacy, optimism, uncertainty and health anxiety with inflammatory bowel disease activity.
Positive and negative psychological attributes have been shown to influence disease outcomes in many chronic health conditions. We aimed to evaluate the association between self-efficacy, optimism, health anxiety and intolerance of uncertainty and disease activity in inflammatory bowel disease (IBD). Adults with confirmed and recently active IBD enrolled in a prospective cohort study. Demographics, disease information, validated measures of psychological functioning related to general self-efficacy, optimism, health anxiety and intolerance of uncertainty were collected at baseline, week 26 and week 52. Clinical disease activity was assessed using the Inflammatory Bowel Disease Symptom Inventory (IBDSI), self-reported flares, and intestinal inflammation using fecal calprotectin (FCAL), collected at baseline, weeks 26 and 52. Generalized estimating equations were used to test the association between psychological functioning and disease activity. Participants' (n = 154) mean age was 43.4 years (SD 12.5), 69.5% were women and 64.1% had Crohn's disease. Adjusting for demographic variables, higher self-efficacy was associated with lower likelihood of flare by self-report (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.71, 0.91) and IBDSI (OR 0.89, 95% CI 0.80, 0.99), while higher health anxiety was associated with greater likelihood of flare by self-report (OR 1.07, 95% CI 1.01, 1.18) and higher symptomatic disease activity (IBDSI; OR 1.14, 95% CI 1.05, 1.24). The psychological attributes were not significantly associated with active disease as measured by inflammation (FCAL). General self-efficacy and health anxiety are relevant in understanding patient experience with disease activity, and may be appropriate targets for psychological intervention in the care of individuals with IBD.


A Case Study on Reviewing Specialist Services Commissioning in Wales: TAVI for Severe Aortic Stenosis.
The Welsh Health Specialised Services Committee (WHSSC) is responsible for planning, commissioning and funding specialised healthcare in Wales. Investment in new technologies or services is based on clinical and economic evidence, using a consistent and transparent process. This is accomplished in three stages. The first stage is the preparation of a rapid evidence review. This then informs the development or update of the relevant Commissioning Policy. The final stage is to prioritise the Commissioning Policy recommendations against all other new services and interventions, to inform WHSSC's annual commissioning intentions. In 2017, a review was conducted of the WHSSC Commissioning Policy for transcatheter aortic valve implantation for severe aortic stenosis. Prior to this only high-risk patients were eligible for transcatheter aortic valve implantation. The rapid evidence review identified three randomised controlled trials and two economic analyses relevant to the decision problem. Transcatheter aortic valve implantation was generally found to be more expensive and more effective than medical management or surgical aortic valve replacement, with incremental cost-effectiveness ratios around £10,500-£36,000 for inoperable groups and £17,000-£24,000 in high-risk groups. The rapid evidence review, expert advice and stakeholder feedback informed the revision process of the Commissioning Policy for transcatheter aortic valve implantation. This recommended the addition of patients unsuitable for surgical aortic valve replacement and the removal of explicit risk scoring. This recommendation was subject to the prioritisation process (carried out annually). The updated transcatheter aortic valve implantation recommendation was ranked second out of 23 technologies and services competing for additional WHSSC funding. The WHSSC Integrated Commissioning Plan for specialised services in Wales (2019) therefore included funding to support the new criteria for transcatheter aortic valve implantation treatment.


Cross-cultural differences in driving skills: a comparison of six countries.
The first aim of the present study was to investigate the applicability of the two-factor structure (perceptual-motor skills by 11 items, e.g., "fluent driving"; safety skills by 9 items, e.g., "conforming to the speed limits") of the Driver Skill Inventory (DSI) among British, Dutch, Finnish, Greek, Iranian, and Turkish drivers. It was also hypothesized that the combination of self reported high ratings of perceptual-motor skills and low ratings of safety skills creates a serious risk for dangerous driving and road accident involvement. The second aim of this study was, therefore, to investigate this asymmetric relationship between perceptual-motor and safety skills in traffic penalties and accident involvement. Two hundred and forty two drivers were chosen from each of the six countries, matched for age and sex. The results of exploratory factor analyses together with target rotation showed that the two-factor structure of DSI found in "safe" Northern and Western European countries were highly congruent. However, the safety skills factor of DSI in Greece, Iran, and Turkey was relatively incongruent in spite of high factor similarity found in perceptual-motor skills. The asymmetric relationship between perceptual-motor and safety skills on traffic penalties was found in Finland and Turkey. A negative relationship between safety skills and the number of accidents was found both in Greece and Iran while a positive relationship between perceptual-motor skills and the number of accidents was found only in Iran.


Electroanalytical methods for determination of the metal content and acetic-acid-available metal fractions in soils.
The pseudo-total and available arsenic, cadmium, and lead content of soils have been determined by stripping voltammetry with a hanging-mercury-drop electrode and by atomic absorption spectrometry with electrothermal atomization. For determination of pseudo-total metals microwave digestion with a mixture of HNO3 and HClO4, with and without addition of HF, was investigated. The single-extraction procedure with 0.43 mol L-1 CH3COOH, proposed by BCR, was used to assess the availability of metals in soils. The results obtained were validated by analysis of a certified reference material.


Chronic eosinophilic leukaemia presenting with erythroderma, mild eosinophilia and hyper-IgE: clinical, immunological and cytogenetic features and therapeutic approach. A case report.
A 23-year-old, white male metallurgist presented with pruritic erythematous maculo-papules over the trunk and upper limbs and 6 months later developed erythroderma, eosinophilia and multi-organ dysfunction. A diagnosis of chronic eosinophilic leukaemia was made on the basis of myeloproliferative involvement of both peripheral blood and bone marrow, associated with eosinophilic differentiation and a t(5;12)(q33;p13) translocation. The initial therapeutic approach was interferon alfa-2b plus cytosine arabinoside, for 13 months, followed by hydroxyurea plus vincristine. There was improvement of skin lesions, disappearance of eosinophilia and decrease of serum immunoglobulin E, towards normal values.


A multiparametric extraction method for Vn96-isolated plasma extracellular vesicles and cell-free DNA that enables multi-omic profiling.
Extracellular vesicles (EVs) have been recognized as a rich material for the analysis of DNA, RNA, and protein biomarkers. A remaining challenge for the deployment of EV-based diagnostic and prognostic assays in liquid biopsy testing is the development of an EV isolation method that is amenable to a clinical diagnostic lab setting and is compatible with multiple types of biomarker analyses. We have previously designed a synthetic peptide, known as Vn96 (ME kit), which efficiently isolates EVs from multiple biofluids in a short timeframe without the use of specialized lab equipment. Moreover, it has recently been shown that Vn96 also facilitates the co-isolation of cell-free DNA (cfDNA) along with EVs. Herein we describe an optimized method for Vn96 affinity-based EV and cfDNA isolation from plasma samples and have developed a multiparametric extraction protocol for the sequential isolation of DNA, RNA, and protein from the same plasma EV and cfDNA sample. We are able to isolate sufficient material by the multiparametric extraction protocol for use in downstream analyses, including ddPCR (DNA) and 'omic profiling by both small RNA sequencing (RNA) and mass spectrometry (protein), from a minimum volume (4 mL) of plasma. This multiparametric extraction protocol should improve the ability to analyse multiple biomarker materials (DNA, RNA and protein) from the same limited starting material, which may improve the sensitivity and specificity of liquid biopsy tests that exploit EV-based and cfDNA biomarkers for disease detection and monitoring.


Total and immunologically reacting muscle enolase in blood serum of Duchenne muscular dystrophy patients and carriers.
All of 12 patients with Duchenne muscular dystrophy manifested raised activity of serum enolase but only 10 showed elevation of immunologically reacting muscle enolase (IRM-enolase). Total enolase was raised in 4 of 12 mothers and one of 8 sisters of the affected subjects but IRM-enolase was elevated in only one mother. These results are consistent with the view that enolase, unlike creatine phosphokinase which showed much more pronounced increase in the serum of patients and their female relatives, is associated with a structural component of the muscle cell distinct from the presumed site of molecular abnormality in this disease.


Differential placental gene expression in severe preeclampsia.
We investigated the global placental gene expression profile in severe preeclampsia. Twenty-one women were randomly selected from 50 participants with uncomplicated pregnancies to match 21 patients with severe preeclampsia. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate the gene expression profile. After RNA isolation, five preeclamptic placentas were excluded due to poor RNA quality. The series composed of 37 hybridizations in a one-channel detection system of chemiluminescence emitted by the microarrays. An empirical Bayes analysis was applied to find differentially expressed genes. In preeclamptic placentas 213 genes were significantly (fold-change>or=2 and p<or=0.01) up-regulated and 82 were down-regulated, compared with normal placentas. Leptin (40 fold), laeverin (10 fold), different isoforms of beta-hCG (3-6 fold), endoglin (4 fold), FLT1 (3 fold) and FLT4 (2 fold) were up-regulated. PDGFD was down-regulated (2 fold). Several differentially expressed genes were associated with Alzheimer disease, angiogenesis, Notch-, TGFbeta- and VEGF-signalling pathways. Sixteen genes best discriminated preeclamptic from normal placentas. Comparison between early- (<34 weeks) and late-onset preeclampsia showed 168 differentially expressed genes with oxidative stress, inflammation, and endothelin signalling pathways mainly involved in early-onset disease. Validation of the microarray results was performed by RT-PCR, quantitative urine hCG measurement and placental histopathologic examination. In summary, placental gene expression is altered in preeclampsia and we provide a comprehensive list of the differentially expressed genes. Placental gene expression is different between early- and late-onset preeclampsia, suggesting differences in pathophysiology.


Experimental autoimmune encephalomyelitis relapses are reduced in heterozygous golli MBP knockout mice.
Increased golli MBP (golli) expression has been observed in the peripheral immune system of mice in the relapsing phase of EAE, raising the possibility that golli MBP expression in the periphery may contribute to relapses. Here we describe the generation of golli MBP-deficient mice and a comparison of the clinical course of EAE between heterozygous (golli(+/-)) and wild-type (golli(+/+)) mice. There was no difference between the two groups in incidence of disease, severity of the first episode of disease, or remission after the first episode. However, there was a significant reduction in relapses in golli(+/-) mice vs. controls, suggesting a role for golli proteins in the relapses in EAE.


Secondary metabolite toxins and nutrition of plant pathogenic fungi.
Fungal pathogens derive nutrition from the plants they invade. Some fungi can subvert plant defence responses such as programmed cell death to provide nutrition for their growth and colonisation. Secondary metabolite toxins produced by fungi often play a role in triggering these responses. Knowledge of the biosynthesis of these toxins, and the availability of fungal genome sequences and gene disruption techniques, allows the development of tools for experiments aimed at discovering the role of such toxins in triggering plant cell death and plant disease.


Use of human patient simulation and validation of the Team Situation Awareness Global Assessment Technique (TSAGAT): a multidisciplinary team assessment tool in trauma education.
Situation awareness (SA) is a vital construct for decision making in intense, dynamic environments such as trauma resuscitation. Human patient simulation (HPS) allows for a safe environment where individuals can develop these skills. Trauma resuscitation is performed by multidisciplinary teams that are traditionally difficult to globally assess. Our objective was to create and validate a novel tool to measure SA in multidisciplinary trauma teams using a HPS--the Team Situation Awareness Global Assessment Technique (TSAGAT). Memorial University Simulation Centre. Using HPS, 4 trauma teams completed 2 separate trauma scenarios. Student, junior resident, senior resident, and attending staff teams each had 3 members (trauma team leader, nurse, and airway manager). Individual SAGATs were developed by experts in each respective field and contained shared and complimentary knowledge questions. Teams were assessed with SAGAT in real time and with traditional checklists using video review. TSAGAT was calculated as the sum of individual SAGAT scores and was compared with the traditional checklist scores. Shared, complimentary, and TSAGAT scores improved with increasing team experience. Differences between teams for TSAGAT and complimentary knowledge were statistically significant (p < 0.05). Mean checklist differences between teams also reached statistical significance (p < 0.05). TSAGAT scores correlated strongly with traditional checklist scores (Pearson correlation r = 0.996). Interrater reliability for the checklist tool was high (Pearson correlation r = 0.937). TSAGAT is the first valid and reliable assessment tool incorporating SA and HPS for multidisciplinary team performance in trauma resuscitation. TSAGAT could compliment or improve on current assessment methods and curricula in trauma and critical care and provides a template for team assessment in other areas of surgical education.


Nitric oxide-dependent killing of aerobic, anaerobic and persistent Burkholderia pseudomallei.
Burkholderia pseudomallei infections are fastidious to treat with conventional antibiotic therapy, often involving a combination of drugs and long-term regimes. Bacterial genetic determinants contribute to the resistance of B. pseudomallei to many classes of antibiotics. In addition, anaerobiosis and hypoxia in abscesses typical of melioidosis select for persistent populations of B. pseudomallei refractory to a broad spectrum of antibacterials. We tested the susceptibility of B. pseudomallei to the drugs hydroxyurea, spermine NONOate and DETA NONOate that release nitric oxide (NO). Our investigations indicate that B. pseudomallei are killed by NO in a concentration and time-dependent fashion. The cytoxicity of this diatomic radical against B. pseudomallei depends on both the culture medium and growth phase of the bacteria. Rapidly growing, but not stationary phase, B. pseudomallei are readily killed upon exposure to the NO donor spermine NONOate. NO also has excellent antimicrobial activity against anaerobic B. pseudomallei. In addition, persistent bacteria highly resistant to most conventional antibiotics are remarkably susceptible to NO. Sublethal concentrations of NO inhibited the enzymatic activity of [4Fe-4S]-cofactored aconitase of aerobic and anaerobic B. pseudomallei. The strong anti-B. pseudomallei activity of NO described herein merits further studies on the application of NO-based antibiotics for the treatment of melioidosis.


The Effect of Demonstrator Social Rank on the Attentiveness and Motivation of Pigs to Positively Interact with Their Human Caretakers.
In this study, we addressed the social attentiveness, as well as the phenomenon of social facilitation and inhibition in the context of a positive human-pig relationship. Specifically, we investigated whether the social rank of an experienced pig (termed "demonstrator") has an effect on the attentiveness of the remaining pen mates (N = 40) when they observe the demonstrator being gently handled by a stockperson from behind an acrylic panel. We found that pigs preferentially attended to dominant demonstrators rather than subordinate demonstrators during their gentle handling sessions with the stockperson. Additionally, we also examined whether the presence of a demonstrator pig of different social rank, who previously established a positive relationship with the stockperson in presence of conspecifics, affects the behavior and motivation of their pen mates to positively interact with the stockperson. To test for the effect of the presence and demonstrator's social rank on pen mate interactions with the stockperson, we evaluated the behavior of domestic pigs (N = 65) toward the stockperson using a human-approach test in their home-pen. Pigs showed a decrease in their motivation to positively interact with the stockperson when a socially dominant demonstrator was present, behaving similarly to animals receiving minimal human contact (control group). Overall, they exhibited a greater latency to physical contact, a lower acceptance of stroking, and spent more time looking at the stockperson compared to pigs exposed to subordinate demonstrators. Taken together, these findings expand our current understanding of pigs' cognition and social behavior, and the nature of social attention bias in farm animals. Our findings indicate that positive handling of previously selected subordinate demonstrators seems to be the best strategy to reduce the level of fear in large groups of pigs.


Dural arteriovenous malformation of the transverse and sigmoid sinus with special reference to its pathological features.
A case of posterior fossa dural arteriovenous malformation (AVM) is reported. In the surgical specimen the internal elastic lamina of the dura mater around the sinus was defective in places where nests of dural vascular anomalies protruded into the sinus lumen, suggesting that the AVM was congenital in origin.


Effects of high-calorie diet on blood pressure and sodium retention in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.
Previous reports from our laboratory have documented that spontaneously hypertensive rats (SHR) have insulin resistance and that insulin resistance is enhanced by high-caloric diet (HCD) feeding. The aim of this study was to elucidate the effect of HCD on blood pressure and sodium retention in both SHR and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were divided into two groups. One group of rats was fed normal diet (ND). The other rats were fed HCD. After the 8-week feeding period, insulin suppression tests were performed. The animals were individually housed in metabolic cages for the last 2 days of the experiment. Food consumption was recorded for 24 h, and a 24-h urine was collected to calculate the sodium excretory ratio. In both strains, body weight was significantly increased by HCD feeding. Blood pressure was significantly elevated in SHR by HCD feeding, whereas that of WKY was not affected by HCD feeding. In both strains, steady-state plasma glucose (SSPG) during the insulin suppression test was higher in the HCD group than in the ND group. SSPG was consistently higher in SHR than in WKY treated with HCD. Urinary sodium excretion ratio was significantly decreased in SHR by HCD, and plasma potassium concentrations were significantly lower in SHR with HCD than in SHR with ND, whereas those of WKY were not affected by HCD feeding. SHR are more sensitive to the induction of insulin resistance than WKY, resulting in sodium retention and elevation of blood pressure.


Angiosarcoma of the abdominal wall after dermolipectomy in a morbidly obese man. A rare form of presentation of Stewart-Treves syndrome.
Angiosarcoma is a rare malignant tumor, with a predilection for skin in the head and neck region, although it has been described in many other locations. Its association with chronic lymphedema is well known, mainly in the setting of postmastectomy lymphedema of the arm in breast cancer patients (termed Stewart-Treves syndrome). However, angiosarcoma can appear in lower limbs with chronic lymphedema and rarely in other locations such as the abdominal wall. Herein, we present a unique case of angiosarcoma developing in the abdominal wall of a morbidly obese patient after extensive dermolipectomy.


Biofilm formation and virulence factor analysis of Staphylococcus aureus isolates collected from ovine mastitis.
To perform a phenotypic and genotypic characterization of 258 Staphylococcus aureus isolates from clinical ovine mastitis and used for the preparation of inactivated autogenous vaccines. The potential for biofilm production was determined by phenotypic test of Congo Red Agar (CRA) and by PCR for the detection of icaA/D genes. Isolates were also screened by PCR for the presence of enterotoxins (sea, seb, sec, sed and see), toxic shock syndrome toxin (tsst), leukotoxins (lukD-E, lukM and lukPV83), haemolysins (hly-β and hly-γ), autolysin (atlA) genes and encoding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs: clfA, clfB, fnbA, fnbB, bbp, cna, eno, fib, epbs, sdrC, sdrD and SdrE). None of the 258 isolates showed biofilm-forming ability on CRA and harboured icaA/D genes. The most frequent pyrogenic toxin superantigen genes amplified were sec plus tsst-1, which were found strictly in combination with 71·3% of the Staph. aureus isolates tested. None of the isolates harboured the genes encoding sea and see. Of the 258 isolates tested, 159 (61·6%) possessed all lukD-E/lukM/lukPV83 genes, 123 (47·7%) harboured both hly-β/hly-γ genes, whereas almost all (97·3%) were PCR positive for atlA gene. With respect to adhesion determinants, 179 (69·4%) isolates presented simultaneously four genes (fnbA, fib, clfA and clfB) for fibronectin- and fibrinogen-binding proteins. In this search, several putative virulence determinants have been identified in ovine Staph. aureus isolates collected in Sardinia. Some of the putative virulence determinants could be considered as components of a vaccine because of their role in ovine mastitis pathogenesis.


Metabolically Active Prokaryotes and Actively Transcribed Antibiotic Resistance Genes in Sewer Systems: Implications for Public Health and Microbially Induced Corrosion.
Sewer systems are reservoirs of pathogens and bacteria carrying antibiotic resistance genes (ARGs). However, most recent high-throughput studies rely on DNA-based techniques that cannot provide information on the physiological state of the cells nor expression of ARGs. In this study, wastewater and sewer sediment samples were collected from combined and separate sanitary sewer systems. The metabolically active prokaryote community was evaluated using 16S rRNA amplicon sequencing and actively transcribed ARG abundance was measured using mRNA RT-qPCR. Three (sul1, blaTEM, tet(G)) of the eight tested ARGs were quantifiable in select samples. Sewer sediment samples had greater abundance of actively transcribed ARGs compared to wastewater. Microbiome analysis showed the presence of metabolically active family taxa that contain clinically relevant pathogens (Pseudomonadaceae, Enterobacteraceae, Streptococcaceae, Arcobacteraceae, and Clostridiaceae) and corrosion-causing prokaryotes (Desulfobulbaceae and Desulfovibrionaceae) in both matrices. Spirochaetaceae and methanogens were more common in the sediment matrix while Mycobacteraceae were more common in wastewater. The microbiome obtained from 16S rRNA sequencing had a significantly different structure from the 16S rRNA gene microbiome. Overall, this study demonstrates active transcription of ARGs in sewer systems and provides insight into the abundance and physiological state of taxa of interest in the different sewer matrices and sewer types relevant for wastewater-based epidemiology, corrosion, and understanding the hazard posed by different matrices during sewer overflows.


Population-based comparison of cancer survival outcomes in patients with and without psychiatric disorders.
Individuals with psychiatric disorders (PD) have a high prevalence of tobacco use. Patients with PD also potentially receive substandard care in comparison to the general population. Previous research has shown that individuals with PD have a decreased risk of receiving a tobacco related (TR) cancer diagnosis. To further assess this trend, this study assesses the survival of patients with a TR cancer with or without a PD. Our study utilized multiple databases, with methods described elsewhere,6 to identify people in British Columbia that have been diagnosed with psychiatric disorders and appendicitis (our control group). From these groups, we selected individuals who also had a TR cancer. We subsequently extracted information pertaining to these patients from these databases. Thirty-nine thousand eight hundred forty-one patients with cancer were included in our study. Analyses of these patients were controlled for by age, gender, cancer type and diagnosis year. This analysis displayed shorter survival time among patients who were diagnosed with depression (HR = 1.16; p = 0.01; 95% CI: 1.04-1.29), schizophrenia (HR = 1.62; p < 0.01; 95% CI: 1.43-1.84), or bipolar disorder (HR = 1.35; p < 0.01; 95% CI: 1.12-1.64) compared to the cancer patients without a PD, all of which were statistically significant. People that were diagnosed with anxiety disorders did not have a survival time that was significantly different from our control population (HR = 1.07; p = 0.22; 95% CI: 0.96-1.19). Individuals with PD, except for those with anxiety, were found to have a shorter survival time following diagnosis with a TR cancer as compared to our control group. We hypothesize several factors, which may account for this statistically significant difference: (1) delayed diagnosis, (2) poor access to care, (3) poor assessment or follow-up, or (4) physician beliefs of poor treatment adherence.


Pledget reinforcement and traction compression as adjunctive techniques for suture-based closure of arterial cannulation sites in percutaneous endovascular aneurysm repair-initial experience.
Suture-based vascular closure devices are used in percutaneous endovascular procedures. However, failures are not uncommon. We have described our initial experience with two adjunct techniques to reinforce the suture-based vascular closure device (ProGlide; Abbot Vascular, Santa Clara, Calif) after percutaneous endovascular aneurysm repair. The threads of the ProGlide device (Abbot Vascular) were passed through a pledget with the help of a needle, which was secured to the puncture site to allow for traction compression. The use of the techniques can be helpful if the suture-based vascular closure devices fail to achieve immediate and complete hemostasis. The use of these adjuncts could reduce the incidence of closure-related complications after percutaneous endovascular procedures.


History of small-cell lung cancer.
The history of small-cell lung cancer (SCLC) is one of the more fascinating stories of medicine, a story of hope and disappointment that characterizes it as 1 of the most elusive cancers. Its history can be divided into 3 intervals. The first interval encompassed the 30 years after the initial reports from Bernard in 1926 during which SCLC was characterized. The second interval, from the 1960s-1980s, introduced advances in staging and treatment of SCLC and the advent of chemotherapy and radiation therapy (RT) as the primary forms of therapy. The final interval covers the past 25 years, which is considered a dormant period, although there are some shimmers of hope from the emergence of several new active drugs that are currently undergoing clinical trials.


Chasing the "Killer" Phonon Mode for the Rational Design of Low-Disorder, High-Mobility Molecular Semiconductors.
Molecular vibrations play a critical role in the charge transport properties of weakly van der Waals bonded organic semiconductors. To understand which specific phonon modes contribute most strongly to the electron-phonon coupling and ensuing thermal energetic disorder in some of the most widely studied high-mobility molecular semiconductors, state-of-the-art quantum mechanical simulations of the vibrational modes and the ensuing electron-phonon coupling constants are combined with experimental measurements of the low-frequency vibrations using inelastic neutron scattering and terahertz time-domain spectroscopy. In this way, the long-axis sliding motion is identified as a "killer" phonon mode, which in some molecules contributes more than 80% to the total thermal disorder. Based on this insight, a way to rationalize mobility trends between different materials and derive important molecular design guidelines for new high-mobility molecular semiconductors is suggested.


Effectiveness and Safety of Different Once-Daily Doses of Adrenocorticotropic Hormone for Infantile Spasms.
Adrenocorticotropic hormone (ACTH) has been commonly used as a first-line treatment for infantile spasms (IS), but its optimal dose and duration are still unclear. This study is the largest retrospective cohort to document the therapeutic efficacy and tolerability for three gradient doses of ACTH in IU/kg/day units in Chinese patients. The aim of our study was to elucidate the effectiveness and safety of three different low doses and duration of ACTH treatment for IS in China. We conducted a retrospective, chart review of IS cases that were treated with biologic short-acting ACTH and followed up for at least 6 months at a single center in China between June 2010 and June 2016. In total, 200 children met the inclusion criteria. Cases were divided into three groups according to dosage (1, 1.1-1.9, and 2-4 IU/kg/day). Furthermore, we divided the 2-4 IU/kg/day group into 2-3 and 3.1-4 IU/kg/day subgroups. All groups were evaluated for response rates, relapse rates, and adverse effects. Electroclinical remission by day 14 occurred in 41.4% of infants given 2-4 IU/kg/day and 36.4% of infants given 1.1-1.9 IU/kg/day, compared with only 14.7% of patients given 1 IU/kg/day (p = 0.004 and 0.03, respectively). Prolonging ACTH treatment for up to 28 days improved response by 24% in all 200 infants. Overall, 73.9% of infants receiving 2-4 IU/kg/day responded, significantly higher than the 52.7% responding to 1.1-1.9 IU/kg/day and the 23.5% responding to 1 IU/kg/day (p < 0.01). There was no significant difference in the number of relapses or adverse effects in the three groups. Moreover, in the 2-4 IU/kg/day group, 74.7% of children receiving 2-3 IU/kg/day of ACTH responded, compared with 70% who responded to 3.1-4 IU/kg/day (p = 0.78). ACTH at a dosage of 2-3 IU/kg/day is superior to 1.1-1.9 and 1 IU/kg/day dosages, is as good as a 3.1-4 IU/kg/day dosage in terms of response rate, and causes no more adverse effects or relapses than other dosages. In addition, prolonging the duration of ACTH treatment can improve response.


Thulium fiber laser recanalization of occluded ventricular catheters in an ex vivo tissue model.
Hydrocephalus is a chronic medical condition that occurs in individuals who are unable to reabsorb cerebrospinal fluid (CSF) created within the ventricles of the brain. Treatment requires excess CSF to be diverted from the ventricles to another part of the body, where it can be returned to the vascular system via a shunt system beginning with a catheter within the ventricle. Catheter failures due to occlusion by brain tissues commonly occur and require surgical replacement of the catheter. In this preliminary study, minimally invasive clearance of occlusions is explored using an experimental thulium fiber laser (TFL), with comparison to a conventional holmium: yttrium aluminium garnet (YAG) laser. The TFL utilizes smaller optical fibers ( < 200 - ? m OD) compared with holmium laser ( > 450 - ? m OD), providing critical extra cross-sectional space within the 1.2-mm-inner-diameter ventricular catheter for simultaneous application of an endoscope for image guidance and a saline irrigation tube for visibility and safety. TFL ablation rates using 100 - ? m core fiber, 33-mJ pulse energy, 500 - ? s pulse duration, and 20- to 200-Hz pulse rates were compared to holmium laser using a 270 - ? m core fiber, 325-mJ, 300 - ? s , and 10 Hz. A tissue occluded catheter model was prepared using coagulated egg white within clear silicone tubing. An optimal TFL pulse rate of 50 Hz was determined, with an ablation rate of 150 ?? ? m / s and temperature rise outside the catheter of ? 10 ° C . High-speed camera images were used to explore the


Investigation of in vitro odonto/osteogenic capacity of cannabidiol on human dental pulp cell.
Vital pulp treatment (VPT) maintains tooth vitality with certain dental materials by protecting pulp from noxious stimulation and promoting repair through enhancing cell proliferation/differentiation, migration, and inducing odontogenesis. As a non-psychotropic cannabis constituent, cannabidiol (CBD) possesses the properties of analgesic, anti-inflammation, and osteogenesis. Therefore, we hypothesize that CBD may induce the odonto/osteogenesis of human dental pulp cells (HDPCs), a critical feature using as effective pulp capping agent for VPT. In this in vitro study, the cytotoxicity of CBD on HDPCs was determined by MTT assay. Scratch assay was performed to analyze HDPC migration. The biomineralization was examined by collagen synthesis and calcium nodule formation and related odonto/osteogenic and angiogenic genes. Cannabinoid receptor (CB) specificity was evaluated by Western blotting and Von Kossa staining using specific antagonists AM251 for cannabinoid receptor 1 (CB1) and AM 630 targeted at cannabinoid receptor 2 (CB2). In addition, the underlying molecular mechanism of CBD-induced biomineralization were investigated by examining CB-dependent MAPK signaling pathways. CBD demonstrated bi-phasic effects on HDPC viability in tested concentrations. We found CBD significantly promoted cell migration, enhanced collagen synthesis and mineralized deposits in HDPCs when treated by 1 μM CBD supplemented in the differentiation media. RT-PCR revealed CBD increased the expression of angiogenic and odontogenic genes, such as DSPP, DMP-1, OPN, ALP, Runx2, VEGFR1 and ICAM-1. These effects were via MAPK activation in a manner mainly mediated by CB2. The results from this study suggested that CBD can induce odonto/osteogenesis from HDPCs and has the potential to develop new therapeutics in VPT in dentistry.


Genetic association analysis of ERBB4 polymorphisms with the risk ofschizophrenia susceptibility in a Jordanian population of Arab descent.
The ERBB4 gene encodes a transmembrane tyrosine kinase and is considered to be one of the risk genes of schizophrenia. Although there is evidence of the roles of genes and the environment in the etiology of schizophrenia, a comprehensive biological and genetic background of the disease is still lacking. The aim of this study is to assess whether genetic variation in the human ERBB4 gene is associated with vulnerability to schizophrenia in the Jordanian Arab population. A total of 185 inpatients with schizophrenia participated in this study and 195 healthy genetically homogeneous individuals were also used as controls. Two genetic variants, rs839523 (G/A, intron 2) and rs3748962 (A/G, exon 27), encompassing the ERBB4 gene were genotyped using DNA sequencing. The results revealed a strong and statistically significant genetic association of rs839523 with schizophrenia (P = 0.002 for allele and P = 0.006 for genotype). This study provides strong statistical evidence that there is an association between the ERBB4 gene and schizophrenia in a Jordanian population of Arab descent.


LncRNA SNHG6 accelerates nasopharyngeal carcinoma progression via modulating miR-26a-5p/ARPP19 axis.
Long noncoding RNAs (lncRNAs) have been reported to be involved in multiple cancer progression, yet the biological role of lncRNA SNHG6 in nasopharyngeal carcinoma (NPC) is still unclear. This research aims to explore the molecular mechanism of SNHG6 in the development and progression of NPC. Prospective feasibility study. The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital. Long noncoding RNAs (lncRNAs) have been reported to be involved in multiple cancer progression, yet the biological role of lncRNA SNHG6 in nasopharyngeal carcinoma (NPC) is still unclear. This research aims to explore the molecular mechanism of SNHG6 in the development and progression of NPC. RT-qPCR assay was used to examine the expression of SNHG6, miR-26a-5p, and ARPP19 in NPC. CCK-8 and transwell assays were employed to detect NPC cell viability, migration, and invasion. The interaction between miR-26a-5p and SNHG6 or ARPP19 was determined by the luciferase reporter, RIP and RNA pull-down assays. We observed that SNHG6 expression was enhanced in NPC tissues and cells. SNHG6 deletion attenuated NPC cell viability and metastasis. MiR-26a-5p was predicted and validated to interact with SNHG6, and miR-26a-5p expression was markedly elevated in NPC after SNHG6 silence. Moreover, miR-26a-5p inhibitor rescued the suppressive effect of SNHG6 depletion on NPC cell viability, migration and invasion. Besides, ARPP19 was a target of SNHG6 and positively regulated by SNHG6. ARPP19 overexpression neutralized the repressive effect of SNHG6 knockdown on NPC progression. Our results indicated that SNHG6 regulated NPC progression through modulating miR-26a-5/ARPP19 axis, which might provide new insights into NPC diagnosis and treatment.


Swimming Training Mitigates Neurological Impairment of Intracerebral Haemorrhage in Mice via the Serine-Threonine Kinase/Glycogen Synthase Kinase 3β Signalling Pathway.
Swimming training (ST) can mitigate functional disorders in neurological diseases, but the effect and mechanism of ST in improving the neurological function of intracerebral haemorrhage (ICH) have not been reported. Our study aimed to explore the protective effect of early ST on ICH mice and its relationship with the serine-threonine kinase (Akt)/glycogen synthase kinase 3β (GSK3β) pathway. Our findings showed that the ICH model mice had poor behavioural manifestations in the Y maze test and open field test compared to the ST group and sham group. The modified neurological severity score was increased in the ICH mice, and 7 days of ST intervention significantly attenuated the neurological deficits. The ratios of myo-inositol/creatine, lactate/creatine and glutamate/creatine were decreased, and the ratios of N-acetylaspartate/creatine and choline/creatine were increased in the ICH mice with ST intervention. ST intervention decreased the expression of Iba1 and GFAP. Seven days of ST significantly increased the expression of p-Akt/Akt compared to that in the ICH mice. Furthermore, the Akt kinase inhibitor GSK690693 exacerbated neurological impairment, increased the expression of Iba1, GFAP and Bax/Bcl-2, and reversed the anti-apoptotic effects and anti-glia activation of ST, which was associated with the inhibition of p-Akt/Akt and p-GSK3β/GSK3β expression. These results indicated that the protective role of ST in ICH was mediated via the Akt/GSK3β pathway. In conclusion, ST displayed neuroprotection by inhibiting apoptosis and glial activation in ICH mice by activating the Akt/GSK3β signalling pathway.


Cost effects of nurse led triage at an emergency department with the advice to consult the adjacent general practice cooperative for low-risk patients, a cluster randomised trial.
During the TRIAGE trial, emergency nurses diverted 13.3% of patients with low-risk complaints from a Belgian emergency department (ED) to the adjacent general practitioner cooperative (GPC). We examined the effects of this diversion on the total cost, insurance costs and patient costs, as charged on the invoice. Changes in the cost composition and the direct impact on revenues of both locations were examined as a secondary objective. The differences in costs between intervention and control weekends were tested with two-sample t-tests and Kolmogorov-Smirnov (KS) tests. For the main outcomes an additional generalised linear model was created. Proportions of patients charged with certain costs were examined using Pearson's chi-square tests. Average revenues per weekend were compared using pooled t-tests. During intervention weekends, total costs increased by 3% (€3.3). The costs decreased by 8% (€2.2) for patients and increased by 6% (€5.5) for insurance, mainly driven by differences in physician fees. More patients were charged a consultation fee only (25% vs. 19%, p-value<0.01). The GPC's revenues increased by 13% (p-value=0.06); no change was found for the ED's revenues. The intervention reduced costs slightly for patients, while total costs and insurance costs slightly increased. When implementing triage systems with primary care involvement, the effects on the costs and revenues of the stakeholders should be monitored.


Human factor VIII inhibitor alloantibodies with a C2 epitope inhibit factor Xa-catalyzed factor VIII activation: a new anti-factor VIII inhibitory mechanism.
Factor VIII (FVIII) inhibitor alloantibodies react with the A2, C2, or A3-CI domains of FVIII and inactivate FVIII activity. We recently demonstrated that an anti-C2 monoclonal antibody with a Val2248-Gly2285 epitope, inhibited factor Xa (FXa)-catalyzed FVIII activation, and that a FXa binding site for FVIII was located within residues Thr2253-Gln2270. In this study, we investigated whether anti-C2 alloantibodies inhibit FXa-catalyzed FVIII activation. Anti-C2 alloantibodies from four patients inhibited FVIII activation by FXa in one-stage clotting assay. Furthermore, analysis by SDS-PAGE showed that all alloantibodies inhibited FVIII proteolytic cleavage by FXa independently of phospholipid. To confirm direct inhibition of FVIII and FXa interaction, we examined the effect of alloantibodies on FVIII binding to anhydro-FXa, a catalytically inactive FXa, in ELISA. All alloantibodies and C2-affinity purified F(ab)'2 preparations inhibited FVIII binding to anhydro-FXa dose-dependently. Our results revealed a new inhibitory mechanism of FVIII, mediated by inhibition of FXa in the presence of anti-C2 alloantibodies.


Effect of increased oxygen tension on flicker-induced vasodilatation in the human retina.
In the retina, blood flow and neural activity are tightly coupled. Stimulation of the retina with flickering light is accompanied by an increase in blood flow. The current study seeks to investigate whether an increase in oxygen tension modulates flicker (FL)-induced vasodilatation in the human retina. A total of 52 healthy volunteers were included. Via a breathing mask, 100% oxygen (O(2)) was administered in one, a mixture of 8% carbon dioxide and 92% oxygen (C/O) in a second cohort. Retinal vessel diameters were measured with a Vessel Analyzer and FL responses were assessed before and during the breathing periods. At baseline, FL stimulation increased retinal vessel diameters by +3.7±2.3% in arteries and by +5.1±3.7% in veins. Breathing of C/O led to a decrease in arterial (-9.0±6.9%) and venous (-11.3±5.9%) vessel calibers. Flicker response was increased to 5.7±2.5% in arteries and to 8.6±4.1% in veins. Breathing of pure O2 induced a vasoconstriction of vessel diameters by -14.0±5.3% in arteries and -18.4±7.0% in veins and increased FL responses in arteries (+6.2±2.8%) and veins (+7.2±3.1%). Systemic hyperoxia increases FL-induced retinal vasodilatation in the retina. The mechanism by which oxygen modulates the hyperemic response to FL stimulation remains to be elucidated.


EGF-R and overexpression of the oncogene c-erbB-2 in ovarian cancer: immunohistochemical findings and prognostic value.
The purpose of this study was to investigate the prognostic value of EGF-R (c-erbB-1) compared to the overexpression of the c-erbB-2 oncogene product p185 in ovarian cancer. The study was conducted on 266 previously untreated ovarian cancer patients with FIGO stage I-IV disease. EGF-R and c-erbB-2 oncogene product p185 have been evaluated using immunohistochemistry. Survival times were analyzed according to the method described by Kaplan and Meier. For the simultaneous evaluation of the prognostic relevance of the analyzed factors, a Cox proportional hazards regression was performed. EGF-R was detected in 13%, and c-erbB-2 oncogene product p185 in 18% of primary tumors. EGF-R showed no significant impact on the survival time, whereas c-erbB-2 oncogene product p185 positive patients had a significantly worse prognosis compared to p185 negative cases (p = 0.002). In the multivariate analysis, c-erbB-2 oncogene product p185, like tumor stage, histological grade and age, was found to be a significant prognostic factor. These data confirm the prognostic importance of the c-erbB-2; oncogene product p185 in ovarian cancer at the time of primary surgery, while EGF-R does not seem to have prognostic relevance.


Preventing iron deficiency in preschool children by implementing an educational and screening programme in an inner city practice.
To assess the feasibility and acceptability of screening young children for iron deficiency in a deprived inner city practice and to assess the effects of a programme of dietary education. Prospective study of children in general practice, comparison with historical controls. A deprived inner city practice. 127 Children aged 13-24 months. Findings were compared with those in 110 children of the same age studied previously. All mothers received dietary education antenatally and in the first year after giving birth. Screening for iron deficiency (defined as mean cell volume less than 75 fl and haemoglobin concentration less than 105 g/l) and haemoglobinopathy (when appropriate) was offered for all children attending for immunisation against measles, mumps, and rubella over 12 months; capillary blood samples were taken after immunisation. Uptake of the screening programme expressed as the percentage of all children eligible for immunisation who were screened, and the effectiveness of the dietary education as shown by the prevalence of iron deficiency in the two groups. Altogether, 122 of the 127 (96%) children who attended for immunisation had their haemoglobin concentration and mean cell volume measured; 90% of all children aged 13-24 months in the practice were screened. Dietary education, clinical procedures, and counselling were incorporated successfully into the clinic's work. Ten children (8%) were iron deficient, all of whom responded to iron supplements, and eight had a haemoglobinopathy trait. In the previous study 110 children (70%) had been screened and 28 children (25%) had been iron deficient. The two groups were similar in terms of sex, social class, and ethnic group. Screening young children for iron deficiency, sickle cell disease, and thalassaemia when they attended for immunisation was acceptable and successful in a socially deprived inner city practice. Dietary education may have accounted for some of the reduction in the prevalence of iron deficiency that occurred over the two years.


Prognosis and Outcome of Fit Patients with Acute Myeloid Leukemia in Kuwait.
Acute myeloid leukemia (AML) data from the Middle East are limited to single-center studies. We report leukemia-free survival (LFS) and overall survival (OS) of young (≤70 years) patients with AML treated in Kuwait. This study investigated prognostic markers among 172 young and fit patients with de novo nonacute promyelocytic leukemia AML treated with intensive induction protocols from a tertiary cancer center. The median age was 44 years (interquartile range, 32-51) and 67% of cases were Arab. A greater proportion of males was found in the 2017 European Leukemia Net-defined unfavorable-risk group (20% vs 9%, respectively; P = .02). Most patients (94%) were treated by a standard 7 × 3 regimen; 72.5% of cases achieved complete remission. The 24-month LFS was 44% (95% confidence interval, 30-65), 36% (95% confidence interval, 26-50), and 23% (95% confidence interval, 10-53) for the favorable-, intermediate-, and adverse-risk groups, respectively (P = .018). The 24-month OS was 70% (95% confidence interval, 60-90), 65% (95% confidence interval, 53-79), and 49% (95% confidence interval, 31-78), respectively (P = .05). Multivariable factor analysis identified male gender (hazard ratio [HR], 1.66; P = .029) and older age (HR, 1.02; P = .05) with poor LFS outcome, whereas favorable-risk classification predicated better outcome (HR, 0.49; P = .03). Favorable-risk classification was the only predictor of OS (HR, 0.39; P = .029). Fit patients with AML in the favorable-risk group treated with intensive chemotherapy fare well, whereas patients in the adverse-risk group have poor survival.


Single-molecule chemiluminescent photosensitizer for a self-activating and tumor-selective photodynamic therapy of cancer.
While photodynamic therapy is known for significant advantages over conventional cancer therapies, its dependence on light has limited it to treating tumors on or just under the skin or on the outer lining of organs/cavities. Herein, we have developed a single-molecule photosensitizer capable of intracellular self-activation and with potential tumor-selectivity due to a chemiluminescent reaction involving only a cancer marker. Thus, the photosensitizer is directly chemiexcited to a triplet excited state capable of generating singlet oxygen, without requiring either a light source or any catalyst/co-factor. Cytotoxicity assays involving the photosensitizer show significant toxicity toward tumor cells, even better than reference drugs, while not inducing toxicity toward normal cells. This work provides a proof-of-concept for a novel type of photosensitizer that eliminates the current restrictions that photodynamic therapy presents regarding tumor size and localization.


The Influence of Initial Hard and Soft Tissue Dimensions on Initial Crestal Bone Loss of Immediately Loaded Dental Implants.
The aim of this case-control study was to evaluate the influence of soft tissue thickness at implant placement (thin [< 3 mm] vs thick [≥ 3 mm]) and bone volume (abundant vs limited) on initial crestal bone remodeling of immediate postextraction and delayed (healed site) implants in immediate loading situations. A total of 67 patients with 133 implants could be evaluated, of which 77 were placed immediately after extraction and 56 in healed ridges. If sufficient bone volume is present and primary stability is achieved, immediate loading of the implant yields good clinical and radiographic outcomes, yet implants placed in healed ridges with thin soft tissues are more prone to initial crestal bone loss.


Phosphorylation of histone H3 serine 28 modulates RNA polymerase III-dependent transcription.
Deregulation of RNA polymerase III (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, leading to an increase in translational capacity to promote cell proliferation, transformation and tumor formation. Phosphorylation of histone H3 (H3ph) is induced by tumor promoters (EGF, UV and TPA) and immediate early genes, such as c-myc, c-jun and c-fos. However, it remains to be determined whether H3ph is involved in RNA Pol III transcription. Here, we report that EGF strongly induced H3ph at serine 28 (H3S28ph). EGF significantly increased transcription of RNA Pol III-dependent genes (Pol III genes), tRNA(Leu), tRNA(Tyr), 5S rRNA and 7SL RNA. Inhibition of EGFR, but not PI3K, reduced both H3S28ph and tRNA(Leu) and 5S rRNA transcription. EGF enhanced occupancy of H3S28ph in the promoters of tRNA(Leu) and 5S rRNA. Further analysis indicates that EGF augmented cellular levels of protein and mRNA of TFIIIB subunits, Brf1 and TATA box-binding protein (TBP). Brf1 is a specific transcription factor for RNA Pol III genes. EGF enhanced occupancy of H3S28ph in the Brf1 and TBP promoters. Inhibition of H3S28ph by mutant H3S28A repressed Brf1, TBP and tRNA(Leu) and 5S rRNA expression and decreased occupancy of H3S28ph in their promoters. Reduction of Brf1 significantly decreased tRNA(Leu) and 5S rRNA transcription and repressed EGF-induced anchorage-independent growth. Blocking H3S28ph signaling by using mutant H3S28A reduced EGF-induced cell transformation. Together, these results indicate that EGF activates EGFR signaling to induce H3S28ph, which, in turn, upregulates tRNA(Leu) and 5S rRNA transcription through Brf1 and TBP and promotes cell transformation. The studies demonstrate that epigenetic modification of H3S28ph has a critical role in the activity of Pol III genes.


Clonal diversity of Acinetobacter baumannii clinical isolates in Myanmar: identification of novel ST1407 harbouring blaNDM-1.
Recent Acinetobacter baumannii clinical isolates in a teaching hospital in Myanmar comprised three major sequence types (ST2, ST16 and ST23) and two sporadic STs, showing a high resistance rate to carbapenem associated with blaOXA-23 . The NDM-1 encoding gene was identified in only one isolate exhibiting novel ST1407 (a triple-locus variant of ST16).


Elongation of C20 polyunsaturated fatty acids by human skin fibroblasts.
Human skin fibroblasts actively elongate a portion of incorporated C20 polyunsaturated fatty acids to their respective C22 derivatives. As much as 40% of incorporated [14C]eicosapentaenoate is elongated within 8 h and 85% by 48 h. Elongation of [14C]arachidonate is initially less than half that of [14C]eicosapentaenoate and plateaus at 20-30% of incorporated 14C-labeled fatty acid. The elongation of 5,8,11-[14C]eicosatrienoate is intermediate between that of 20:4(n-6) and 20:5(n-3). Docosatetraenoate is not an effective inhibitor of the elongation of arachidonate, thus suggesting that the observed plateau is not due to product inhibition. When concentrations of exogenous fatty acids are increased, these cells elongate substantial quantities of C20 polyunsaturated fatty acids; elongation of eicosapentaenoate is consistently more extensive than that of arachidonate. Eicosapentaenoate is also an effective inhibitor of the elongation of [14C]arachidonate. Increases in exogenous arachidonate up to 10 microM result in an increase in elongation of [14C]arachidonate both in absolute quantities and as a percentage of that incorporated; the arachidonate thus acts as a positive modulator of its own elongation. Increased eicosapentaenoate also enhances the elongation of [14C]eicosapentaenoate, but only at lower concentrations (0.02-0.15 microM). The factors which regulate the elongation of C20 polyunsaturated fatty acids in human skin fibroblasts serve to permit extensive elongation of eicosapentaenoate while retaining incorporated arachidonate primarily in its C20 form.


Advances in the metabolic engineering of Saccharomyces cerevisiae and Yarrowia lipolytica for the production of β-carotene.
β-Carotene is one kind of the most important carotenoids. The major functions of β-carotene include the antioxidant and anti-cardiovascular properties, which make it a growing market. Recently, the use of metabolic engineering to construct microbial cell factories to synthesize β-carotene has become the latest model for its industrial production. Among these cell factories, yeasts including Saccharomyces cerevisiae and Yarrowia lipolytica have attracted the most attention because of the: security, mature genetic manipulation tools, high flux toward carotenoids using the native mevalonate pathway and robustness for large-scale fermentation. In this review, the latest strategies for β-carotene biosynthesis, including protein engineering, promoters engineering and morphological engineering are summarized in detail. Finally, perspectives for future engineering approaches are proposed to improve β-carotene production.


Bisphosphonates are associated with increased risk for jaw surgery in medical claims data: is it osteonecrosis?
Bisphosphonates (BPs) have recently been associated with increased risk of osteonecrosis of the jaw. Using a large automated insurance database, we searched the medical claims for common procedure codes (CPT codes) denoting major surgery to the mandible or the maxilla. The primary aim of this pilot study was to alert readers to clinically relevant but preliminary information regarding the risk of jaw surgery among patients who received BPs, as compared with patients who did not. The study utilized 2001-2004 claims data from a large nationwide medical insurer. Medical claims from 255,757 cancer patients with breast, lung, or prostate malignancies, or multiple myeloma were analyzed for CPT codes 21015, 21025, 21026, 21034, 21040, 21045, 21046, and 21047. We identified 224 cases of jaw surgery; of those, 39 cases were found among 26,288 BP users and 185 cases were found among 229,469 never-users. The odds ratio of jaw surgery for intravenous BP users was 4.24 (P<.05). Breast cancer patients experienced a 6-fold increase in risk as compared with nonusers. A trend of increased risk was noted for those on orally administered BPs, but the association was not significant. A significant association was noted between the administration of IV BPs and oral surgery in cancer patients. More studies are needed to understand the role of BPs in bone biology and necrosis along with the associated biologic pathways.


Constrictive pericarditis after myocardial revascularization: report of three cases.
Although postoperative constrictive pericarditis is rare, the diagnosis should be considered when unexplained right-sided heart failure develops after cardiac surgery. Within a 6 week interval, evidence of constrictive pericarditis developed in three patients who had recently undergone myocardial revascularization. One patient presented with biventricular failure, pericardial effusion and suspected tamponade. Severe constrictive pericarditis was demonstrated at subsequent operation. An apparent postpericardiotomy syndrome preceded evidence of right heart failure in the other two patients. Etiologic considerations include the possibility that pericardial irrigation with povidone-iodine (Betadine) solution may have contributed to subsequent fibrosis.


A randomized trial to determine the distribution of four topical gel formulations in the human vagina.
There is an urgent need for the development of a topical microbicide to protect against sexually transmitted infections. We compared distribution and acceptability of four different gel formulations to be used as a vehicle for a microbicide. This is a randomized, double-blind comparative study. Six women tested each of the four gels at two different time points. Magnetic resonance imaging (MRI) scans were taken both within 10-15 min following intravaginal gel insertion and 4 h following gel insertion, before and after simulated intercourse at both time points. Vaginal surface contact immediately after insertion ranged from 68% to 92%. Simulated intercourse increased surface contact for all gels (range, 90-106%). After 4 h, surface contact ranged from 86% to 102%. Simulated intercourse at that time resulted in decreased coverage for two gels and increased coverage for two gels. One gel was noted to have consistent broad coverage of the vagina both immediately and 4 h after insertion, increased coverage with simulated intercourse at both time points and the lowest standard deviation of disruption at all time points. MRI used in combination with qualitative assessments of acceptability can be used to select optimal gels for use as vehicles for potential spermicides or microbicides. We conclude that a gel consisting of 3% hydroxypropyl methylcellulose and 1.5% of methyl cellulose is the most promising candidate gel.


Developing self-aware mindfulness to manage countertransference in the nurse-client relationship: an evaluation and developmental study.
Nursing students, and even the nurses they become, bring not only caring to their wounded clients but also at times their own unresolved personal stress. Especially without mindful awareness, projection of the nurse's unacknowledged emotional encumbrances (countertransference) threatens the effectiveness of the nurse-client relationship. The purpose of this study was to evaluate whether Scheick's (2004) earlier instruction and use of a self-awareness development guide affected the self-control and sense of vibrant aliveness of students in a psychiatric nursing course, then use the information gained to develop a self-aware mindfulness template for managing countertransference in the nurse-client relationship. As gleaned from the literature, self-concept behaviors such as being fully vibrantly alive in the present moment, exercising self-control, and enacting self-awareness dovetail with qualities of mindfulness. Building on earlier findings pertinent to increasing self-awareness, this research used developmental mixed methodology to evaluate ex post facto data on the sense of vibrant full aliveness and self-control of 15 psychiatric nursing students who used a self-awareness development guide compared with seven final semester nursing students who lacked focused self-awareness instructional experiences. Both groups took Schutz's (1992) Element S: Self concept assessment. The quantitative research portion used inferential statistical analysis via the t test to evaluate student scores yielding information pertinent to the qualitative developmental part of the study. Formative and summative committees comprised of expert nursing and other psychologically oriented faculty then developed self-awareness and mindfully oriented teaching-learning tools that together formed a template highlighted by a mnemonic model termed STEDFAST. Although mitigated by the small sample and the use of intact groups, the experimental group, when exposed to self-awareness focused learning experiences, showed not only statistically significant changes in self-awareness, which had been determined in Scheick's (2004) earlier study, but also statistically significant changes in vibrant aliveness and self-control. The outcome that deliberate learning experiences using a self-awareness development model likely affected all three mindful behaviors prompted the expert formative and summative committees to specifically target self-awareness and mindfulness for the template. Students implementing the template anecdotally report increased self-aware mindfulness especially as they readily use the STEDFAST Self-Aware Mindfulness mnemonic portion in clinical encounters. The limitations of the study mandate that statistical assumptions be downplayed in favor of simply exploring data trends. Nevertheless, students using the template components describe growing in their ability to mindfully self-monitor toward better managing of not only countertransference in psychiatric nursing but also their own learning in other areas of nursing practice.


Toxicity of emerging contaminant antibiotics in soil to Capsicum annuum L. growth and their effects on it accumulating copper.
Antibiotics are a kind of emerging contaminant in soil. Tetracycline (TC) and oxytetracycline (OTC) in soil are often detected, even with very high concentration in the soils of facility agriculture due to their good effect, low price and large usage. Copper (Cu) is common heavy metal pollutant in soil. The toxicity roles of TC, OTC and/or Cu in soil on a commonly consumed vegetable Capsicum annuum L. and its Cu accumulation were not clear till now. The results of pot experiment showed that the TC or OTC added in soil alone didn't produce poison effects for C. annuum after 6 weeks and 12 weeks growth reflected by some physiological index like SOD, CAT and APX activities changes, while the biomass changes affirmed them either. Cu contaminated soil significantly inhibited the growth of C. annuum. Furthermore, combined pollution of Cu with TC or OTC was with more serious suppression of C. annuum growth. The suppression role of OTC was heavier than TC in Cu and TC or OTC contaminated soil. Such phenomenon was relevant with the role of TC or OTC increased Cu concentration in C. annuum. The improvement role of TC or OTC on Cu accumulation in C. annuum caused by the increased extractable Cu concentration in soil. The study demonstrated that TC or OTC added in soil alone was without any toxicity to C. annuum. But they may aggravate the hurt of C. annuum caused by Cu through increased its accumulation from soil. Thus, such combine pollution should be avoided in safe agricultural product.


Implication of anti-parietal cell antibody levels in gastrointestinal diseases, including gastric carcinogenesis.
We investigated serum levels of anti-parietal cell antibody (APCA) in relation to various gastric diseases. Subjects were 224 Japanese patients including 58 with gastric cancer. All patients underwent gastroscopy, and APCA was investigated by enzyme-linked immunosorbent assay. Unexpectedly, there was no difference in APCA levels between patients with gastric cancer and those with gastritis. Among H. pylori-positive patients, APCA levels were closely correlated with grades of atrophy when no gastric cancer was present, but no correlation was found when gastric cancer was present. APCA-negative gastric cancer was found mainly in males and was characterized by massive infiltration of neutrophils in the background mucosa. The 24 patients with gastric cancer were APCA-negative and showed low pepsinogen levels. The odds ratio for the incidence of gastric cancer in these patients was 7.90 (95% CI 3.4-18.4). This suggests APCA-negative gastric cancer is the predominant form of gastric cancer in Japan.


Testing different methods of estimating edaphic inputs in moss biomonitoring.
Although soil is known to contribute to the concentrations of elements in moss, protocols for atmospheric biomonitoring with terrestrial moss do not include recommendations on how to address this factor. As a result, researchers indiscriminately use a wide range of detection/correction methods without considering whether the results are equivalent. In this study, three of these methods were compared: i) use of the enrichment factor (EF) index; ii) calculation of the ratios of different elements in soil and moss, and subtraction of the contribution of soil concentrations from the raw concentrations of elements in mosses (SCS); and iii) positive matrix factorization (PMF), a receptor modelling method for source apportioning based on multivariate analysis techniques. The aim of the comparison was to determine whether the methods produce equivalent results and, if not, which method is the most appropriate for use in moss biomonitoring surveys. The data used corresponded to 146 samples of Pseudoscleropodium purum collected from a regular sampling grid of 15 × 15 km in Galicia (NW Spain). Comparison of the methods revealed that, although they yield relatively similar results, the corresponding interpretations are not equivalent and none of the methods provides a reliable estimate of the soil contribution to the concentrations of elements in moss samples. Independently of the technique applied, use of Ti as a reference element is not recommended, because, at least in this study, it was present at unusually high levels in moss. Given the absence of a reliable correction method and the fact that most elements are present in fairly high amounts in the soil, we recommend using atmospheric biomonitoring with moss only for Cu, Zn and Cd, i.e. for those elements in moss for which the soil contributes very low amounts and corrections are not therefore necessary.


A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation.
This study examines the intranasal instillation of lipopolysaccharide (LPS) into BALB/c mice causing acute pulmonary damage, due to neutrophil infiltration and sepsis. A dose response with LPS showed that an intranasal instillation of 167 microg/ml (10 microg/mouse) caused acute lung injury within 2-4 h and reached maximal damage at 24-48 h. We found the method of LPS administration for induction of acute pulmonary damage to be crucial. After 24 h post-LPS injection, a comparison showed a substantial increase in pulmonary damage with intranasal instillation of LPS. As for intravenous injection, it showed a baseline effect. This study indicates that LPS administered intranasally causes acute pulmonary damage, whereas with intravenous and intraperitoneal endotoxin administration a tissue-specific or similar degree of pulmonary injury may not develop.


Psoriasis patient preferences for topical drugs: a systematic review.
Topical drugs are recommended first-line treatment for mild-to-moderate psoriasis. However, patient preferences for the topical drugs differ, since a wide variety of topical drugs and topical drug formulations are available. The aim of this study was to investigate psoriasis patient preferences for topical drugs. A systematic literature search was performed for English-language articles in Embase, Medline, PsycINFO, Cinahl, Scopus, and the Cochrane Library. Four surveys, six randomized controlled trials, and two prospective studies of mainly good quality were included. Seven of the studies investigated patient preferences for topical drug formulations, while five studies investigated their preferences for different topical drugs. Overall, patients preferred drugs that are easy to apply, less messy, and have a pleasant scent. Psoriasis patient preferences for topical drugs differ. There is no one topical drug or topical drug formulation that suits everyone, which shows the importance of individualized prescriptions for topical drugs that are based on shared decision-making between the prescriber and patient.


End-of-life flows of multiple cycle consumer products.
Explicit expressions for the end-of-life flows (EOL) of single and multiple cycle products (MCPs) are presented, including deterministic and stochastic EOL exit. The expressions are given in terms of the physical parameters (maximum lifetime, T, annual cycling frequency, f, number of cycles, N, and early discard or usage loss). EOL flows are also obtained for hi-tech products, which are rapidly renewed and thus may not attain steady state (e.g., electronic products, passenger cars). A ten-step recursive procedure for obtaining the dynamic EOL flow evolution is proposed. Applications of the EOL expressions and the ten-step procedure are given for electric household appliances, industrial machinery, tyres, vehicles and buildings, both for deterministic and stochastic EOL exit, (normal, Weibull and uniform exit distributions). The effect of the physical parameters and the stochastic characteristics on the EOL flow is investigated in the examples: it is shown that the EOL flow profile is determined primarily by the early discard dynamics; it also depends strongly on longevity and cycling frequency: higher lifetime or early discard/loss imply lower dynamic and steady state EOL flows. The stochastic exit shapes the overall EOL dynamic profile: Under symmetric EOL exit distribution, as the variance of the distribution increases (uniform to normal to deterministic) the initial EOL flow rise becomes steeper but the steady state or maximum EOL flow level is lower. The steepest EOL flow profile, featuring the highest steady state or maximum level, as well, corresponds to skew, earlier shifted EOL exit (e.g., Weibull). Since the EOL flow of returned products consists the sink of the reuse/remanufacturing cycle (sink to recycle) the results may be used in closed loop product lifecycle management operations for scheduling and sizing reverse manufacturing and for planning recycle logistics. Decoupling and quantification of both the full age EOL and of the early discard flows is useful, the latter being the target of enacted legislation aiming at increasing reuse.


Host genotype changes bidirectional to unidirectional cytoplasmic incompatibility in Nasonia longicornis.
Wolbachia are the most abundant maternally inherited endosymbionts of insects and cause various reproductive alterations in their hosts. One such manipulation is cytoplasmic incompatibility (CI), which is a sperm-egg incompatibility typically resulting in zygotic death. Nasonia longicornis (Hymenoptera: Pteromalidae) has an A supergroup and two closely related B supergroup Wolbachia infections. The B supergroup bacteria co-diverged in this host genus. Both triple (wNlonAwNlonB1wNlonB2) and double infections (wNlonAwNlonB1, wNlonAwNlonB2) have been obtained from the field. In the present study, CI was determined among the three Wolbachia types in different host genetic backgrounds. Results show that host genetic background determines whether bidirectional CI or unidirectional CI occurs between the two closely related B group Wolbachia. Results show that the wNlonB1-infected males are bidirectionally incompatible with wNlonB2 in their 'native' nuclear genetic background, whereas wNlonB1 males are compatible with wNlonB2 in two other N. longicornis genetic backgrounds, resulting in unidirectional CI. In contrast, wNlonB2-infected males are incompatible with wNlonB1 females in all three host genetic backgrounds. These changes in incompatibility are not due to the loss of the bacteria. We hypothesize that a repressor gene for sperm modification by wNlonB1 is segregating in N. longicornis populations. The relevance of these findings to the potential role of Wolbachia in host-reproductive divergence and speciation is discussed.


Cytogenetic analysis of posterior uveal melanoma.
Cytogenetic analysis was performed on short-term cultures of primary tumor samples from seven patients with posterior uveal melanoma. Informative data were obtained from four patients, all of whom had a near-diploid chromosomal number and clonal chromosomal alterations. Analysis of one patient's tumor revealed monosomy 3 as the only cytogenetically distinguishable aberration. Trisomies of chromosome 8 and i(8)(q10) were detected in two other patients in combination with monosomy of chromosome 3. The fourth patient's karyotype displayed two different translocations. One translocation, der(6)t(6;8)(q12;q13.1), resulted in the over-representation of 8q13.1-->qter and a partial monosomy of 6q12-->qter; the other translocation, der(9)t(6;9)(p12;p23), produced a partial trisomy of 6p12-->pter and a partial monosomy of 9p23-->pter. These results support the view that the recurring pattern of chromosomal rearrangements in ocular melanoma is unique from that associated with cutaneous malignant melanoma. Furthermore, these results help confirm that chromosomes 3, 6, and 8 are nonrandomly altered in ocular melanoma.


Inhibition of immune responses against rabies virus by monoclonal antibodies directed against rabies virus antigens.
Treatment of mice with a cocktail of murine anti-rabies monoclonal antibodies (mAb-C) interfered with the ability of these animals to mount a virus-neutralizing antibody response to rabies vaccine. Administered mAb-C did not affect the induction of rabies virus-specific T-helper cells. The magnitude of the inhibition of rabies virus-specific B-cell response was dependent on the concentration of the mAb-C and the duration of the mAb-mediated interference was inversely proportional to the biological half-life of the mAb. As long as the serum titres were above a critical threshold, the suppression could not be overcome even by multiple vaccinations. Since injection of mice with immunocomplexes consisting of inactivated rabies virus and mAb rendered the animals non-responsive to a subsequent vaccination with inactivated rabies virus, it is concluded that the mAb-induced suppression might be caused by the formation of antigen-antibody complexes which exert a negative signalling effect to premature B cells.


SIGIRR inhibits toll-like receptor 4, 5, 9-mediated immune responses in human airway epithelial cells.
Human airway epithelial cells (HAEC) may contribute to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) through toll-like receptors (TLRs)-mediated molecular mechanisms. TLRs exist on the surface of HAEC where binding to their cognate ligands initiates airway inflammation. Single immunoglobulin interleukin-1 receptor-related protein (SIGIRR) is a member of the toll-interleukin-1 receptor (TIR) family that can negatively modulate the immune response. We carried out studies to characterize SIGIRR modulation of TLR-mediated immune response in HAEC and to define its mechanisms of action. Following treatment with various concentrations of LPS, flagellin and CpG DNA, the levels of cognate TLRs 4, 5, and 9 were measured in the supernatants of HAEC over-expressing the SIGIRR molecule. Moreover, the interaction of the TLR adaptor myeloid differentiation factor 88 (MyD88) with SIGIRR in response to LPS-, flagellin- and CpG DNA-stimulation was examined by co-immunoprecipitation. The findings from this study revealed that overexpression of SIGIRR in HAEC stimulated by LPS, flagellin or CpG DNA resulted in attenuated production of the inflammatory mediators IL-6 and TNF-α. This attenuation was not the result of decreased expression of TLR4, 5 or 9, but rather a sequestration of MyD88 to the TLRs. In conclusion, SIGIRR can inhibit TLR4, 5, and 9-mediated immune responses in HAEC and may be a valuable therapeutic target for the prevention of ALI/ARDS.


Childhood posterior reversible encephalopathy syndrome.
Posterior Reversible Encephalopathy Syndrome (PRES) is a clinicoradiologic syndrome characterised clinically by headaches, altered consciousness, visual disturbances and seizures and radiological changes which can resolve. However left untreated it can be fatal and not all cases are reversible. It can occur in many settings, the most common being hypertensive crisis. We discuss the clinical and radiological features of this increasingly diagnosed condition among children and current thinking on its pathogenesis. A brief case is used to highlight the variable presentation of PRES. PRES is often unsuspected by the clinician and radiologists may be first to suggest the diagnosis. Accurate assessment including blood pressure measurement, appropriate imaging and rapid treatment is required to avoid a devastating outcome.


Nail cosmetics.
Disorders of the nails may be brought about by systemic disease or outside influences. Although many of the products available on the market may be of great benefit in offering palliation of abnormalities of the nail plate, they may also be a source of significant adverse effects. Treatment of nail disorders must be predicated on a well-focused history, physical examination, and proper tissue samples.


Physiological and cognitive responses to hyperoxic exercise in full water submersion.
The positive effects of combined hyperoxia and physical exercise on physiological parameters and cognitive functioning are established for normobaric laboratory contexts. Still, increased practicability exists in hyperbaric settings like underwater activities and SCUBA diving, where environmental and sport-specific factors might moderate effects. Improved cognition, reduced ventilation (V̇E), and lower blood lactate concentrations [Lac-] are highly relevant, especially during high-stress and rescue scenarios. Fifteen participants performed 3 × 8 min of continuous underwater fin-swimming at 25 % (low), 45 % (moderate), and 75 % (vigorous) heart rate reserve (HRR) in each test. Three separate test days differed solely by the inspiratory oxygen partial pressure (PIO2: 29 kPa, 56 kPa, and 140 kPa). V̇E was measured continuously, whereas breathing gas analysis, blood sampling, and Eriksen Flanker tasks for inhibitory control (100 stimuli) were performed post-exercise. Two-way ANOVAs with repeated measures on the factors PIO2 and exercise intensity analyzed physiological outcome variables and reactions times (RT) and accuracy (ACC) of inhibitory control. V̇E was significantly reduced for 140 kPa during moderate and vigorous and for 56 kPa during vigorous compared to 29 kPa. 56 kPa and 140 kPa showed no differences. [Lac-], post-exercise V̇CO2, and velocity were unaffected by PIO2. Faster RTs but lower ACC of inhibitory control were observed following exercise at 75 % HRR compared to rest, 25 %, and 45 % HRR, while PIO2 produced no effects. Underwater performance in hyperoxia presents reduced V̇E, possible by dampened chemoreceptor sensitivity, and effects on cognition that differ from laboratory results and emphasise the moderating role of sport-specific factors.


The role of single sample detection of specific anti-Toxoplasma IgM in accurate evaluation of seroconversion during acquired toxoplasmosis.
Specific IgM anti-Toxoplasma antibodies were sought in 94 serum samples by means of D.S. IgM ELISA. These antibodies were detected in all cases of acute toxoplasmic lymphadenopathy, but up to 13 months from onset of symptoms and in out of 20 patients with chronic toxoplasmosis and in one out of 20 seronegative individuals. They were neither detected in samples from 4 infants with high IgG IFAT titres associated with hydrocephalus and cerebral calcification, nor in samples from patients containing rheumatoid factors and those with lymphoma or infectious mononucleosis. Thus the detection of IgM antibodies seems non decisive mean for identifying infected infants and for determination of the exact date of acquiring the infection.


Hourly global horizontal irradiance data of three stations in Punjab, Pakistan.
This paper presents hourly Global Horizontal Irradiance (GHI) measured data at three stations (Lahore, Multan, Bahawalpur) in Punjab, Pakistan. The estimated GHI data from three reanalysis datasets have also been presented. Clearness index (KT ), Solar zenith angle (θsza) and Periodicity factor (Pf) were calculated and used to develop bias correction models. The estimated corrected GHI data using best model M20 for years 2015 and 2016 is also presented.


Up-regulated circBACH2 contributes to cell proliferation, invasion, and migration of triple-negative breast cancer.
An increasing amount of evidence has proven the vital role of circular RNAs (circRNAs) in cancer progression. However, there remains a dearth of knowledge on the function of circRNAs in triple-negative breast cancer (TNBC). Utilizing a circRNA microarray dataset, four circRNAs were identified to be abnormally expressed in TNBC. Among them, circBACH2 was most significantly elevated in TNBC cancerous tissues and its high expression was positively correlated to the malignant progression of TNBC patients. In normal human mammary gland cell line, the overexpression of circBACH2 facilitated epithelial to mesenchymal transition and cell proliferation. In TNBC cell lines, circBACH2 knockdown suppressed the malignant progression of TNBC cells. Mechanistically, circBACH2 sponged miR-186-5p and miR-548c-3p, thus releasing the C-X-C chemokine receptor type 4 (CXCR4) expression. The interference of miR-186-5p/miR-548c-3p efficiently promoted the cell proliferation, migration, and invasion suppressed by circBACH2 knockdown in the TNBC cell lines. Finally, circBACH2 knockdown repressed the growth and lung metastasis of TNBC xenografts in nude mice. In summary, circBACH2 functions as an oncogenic circRNA in TNBC through a novel miR-186-5p/miR-548c-3p/CXCR4 axis.