Search

Leptospirosis is a bacterium with a worldwide distribution and belongs to the group of zoonoses that can affect both humans and animals. Most cases of leptospirosis present as a mild, anicteric infection. However, a small percentage of cases develop Weil’s disease, characterized by bleeding and elevated levels of bilirubin and liver enzymes. It can also cause inflammation of the gallbladder. Acute acalculous cholecystitis has been described as a manifestation of leptospirosis in a small percentage of cases; however, no association between leptospirosis and acute acalculous cholecystitis has been found in the literature.

Autonomous Vehicles (AVs) are anticipated to bring forth a multitude of advantages for upcoming mobility.These potential benefits and many others vary substantially by the market share of AVs. There are several articles that investigated AV market share with a variety of methods, however, they show a huge variation depending on the market specifications. The aim of this research is to calculate private AV adoption rates over time depending on the Hungarian automobile market characteristics. The research empirically estimates, using the Gompertz function, the projected growth rates of private autonomous passenger vehicles in Hungary using historical patterns of human-driven vehicle ownership data on the basis of projected per capita GDP.The study's findings suggest that, in an optimistic and moderate scenario, the Hungarian car market is projected to become saturated due to AVs by 2067 and 2076, respectively. However, a pessimistic estimation indicates that saturation is unlikely to occur before 2100. This study’s contribution to the literature is through a mathematical approach that predicts AVs market penetration rate and saturation year, in which the assumptions and the used parameters of the model can be modified depending on different case studies, or they can be updated due to the advancement in technology and improvement in knowledge of the studied market.

Despite recent advancements in antibiotic therapy and the progress made in critical care and modern diagnostic methods, acute mediastinitis continues to be a severe condition.

In this article automatization of road transport is investigated. In the first chapter relevant international trends were identified. In this paper the research hypothesis is that in the case of automatized road vehicles there is a significant likelihood of endangering human life. Secondly, the history of road safety is shortly described, especially focusing on vehicle design and sweep of system’s theory. In the third chapter evolution of drivers’ assistance systems were elaborated, emphasizing especially autonomous vehicles. Finally, in conclusion the authors warn that new technological solutions could pose new threats.

This contribution aims to examine the relationship between the transport sector and the macroeconomy, particularly in fossil energy use, capital and labour relations. The authors have investigated the transport related fossil fuel consumption 2003 -2010 in a macroeconomic context in Hungary and Germany. The Cobb-Douglas type of production function could be justified empirically, while originating from the general CES (Constant Elasticity of Substitution) production function. Furthermore, as a policy implication, the results suggest that a solution for the for the reduction of anthropogenic CO2 driven by the combustion of fossil fuels presupposes technological innovation to reach emission reduction targets. Other measures, such as increasing the fossil fuel price by levying taxes, would consequently lead to an undesirable GDP decline.

The aim of this study was to analyze the modal shift of passengers by analyzing their preferences. If the preferences of passengers are known it is possible to build up mathematically their utility function. This is the statistically correct way to simulate the modal shift of the investigated area. To capture the preferences of passengers stated preference method was used in online questionnaire. Five key factors were identified (from the point of passengers): travel cost, travel time, comfort, safety and environmental efficiency. In order to decrease the number of questions three levels were predefined these three questions made the base of the choice model. Every replier got three alternatives and they were told to choose the best for themselves. From the results of the questionnaire the formulas and the parameters of the mode choice utility function was derived. With the help of statistical sample an exponential utility function showed the best matching. For the validation process a probability model was set up to be compared to the proportions of the utilities. With this utility function it is possible to handle the changes in possible future transport services. Based on the introduced statistical approach the described method can be used to identify the effect of transport modes on regional development and tourism. The revealed utility function can help to develop proper regional development plans.

Underlying a fundamental diagram is a relation between traffic speed and density which roughly corresponds to drivers’ speed choices under varying car-following distances. Stochastic and deterministic models are mainly two different categories of speed-density models. The advantages of deterministic models are their mathematical simplicity and analytical tractability though their results will show just the average parameters. Although the stochastic models may represent more accurate results taking uncertainty into account, they are often hard to use and analytically not tractable. The aim of this paper is to investigate the possibility of presenting a model which is neither completely deterministic nor completely stochastic but easy to use and understand which incorporates different traffic conditions and speed distributions. Monte Carlo Method has been used to generate different speed distributions based on different traffic conditions and consequently generating their relevant densities. Surveying the relation between the mentioned speed distributions and the obtained densities kept the chance of presenting a model which is neither completely deterministic nor completely stochastic but easy to use and understand which incorporates different traffic conditions and speed distributions.

Autoimmune Disease, Multisystem, with Facial Dysmorphism (ADMFD) is an autosomal recessive disorder due to pathogenic variants in the ITCH gene. It is characterized by failure to thrive, dysmorphic facial features, developmental delay, and systemic autoimmunity that can manifest variably with autoimmune hepatitis, thyroiditis, and enteropathy, among other organ manifestations. It was originally described in 10 consanguineous Old Order Amish patients, and more recently in two patients of White British and Black German ethnicities. While the role of ITCH protein in apoptosis and inflammation has previously been characterized, a defect in cellular bioenergetics has not yet been reported in ITCH deficiency. Here we present a Caucasian female originally evaluated for possible mitochondrial respiratory chain deficiency, who ultimately was found to have two novel variants in ITCH with absence of ITCH protein in patient derived fibroblasts. Clinical studies of patient muscle showed mitochondrial DNA copy number of 57% compared to controls. Functional studies in skin fibroblasts revealed decreased activity of mitochondrial fatty acid oxidation and oxidative phosphorylation, and decreased overall ATP production. Our findings confirm mitochondrial energy dysfunction in a patient with ITCH deficiency offering the opportunity to assess alternative therapeutic options.

Initial experience suggests that the POLARx cryoballoon system (Boston Scientific) has a similar procedural efficacy and safety as Arctic Front Advance Pro (AFA-Pro, Medtronic). We performed an updated systematic review and meta-analysis comparing POLARx and AFA-Pro. Embase, MEDLINE, Web of Science, Cochrane, and Google Scholar databases were searched until 12/01/2022 for studies comparing POLARx versus AFA-Pro in patients undergoing pulmonary vein (PV) isolation for AF. A total of 8 studies, involving 1146 patients from 11 European centers were included (POLARx n = 317; AFA-Pro n = 819). There were no differences in acute PV isolation, procedure time, fluoroscopy time, ablation time, minimal esophageal temperature, and risk of phrenic nerve palsy or thromboembolic events. Balloon nadir temperatures were lower for POLARx in all PVs. Compared with AFA-Pro, POLARx had a higher rate of first freeze isolation in the left inferior PV (LIPV) (odds ratio [OR]: 2.60; 95 % confidence interval [CI]: 1.06 to 6.43; P = 0.04), higher likelihood of time-to-isolation (TTI) recording in LIPV (OR: 2.91; 95 % CI: 1.54 to 5.49; P = 0.001) and right inferior PV (OR: 3.23; 95 % CI: 1.35 to 7.74; P = 0.008). In contrast, the TTI in LIPV was longer with POLARx in comparison to AFA-Pro (mean difference: 7.61 sec; 95 % CI 2.43 to 12.8 sec; P = 0.004). In conclusion, POLARx and AFA-Pro have a similar acute outcome. Interestingly, there was a higher rate of TTI recording in the inferior PVs with POLARx. This updated meta-analysis provides new safety data on esophageal temperature and thromboembolic events.

Introduction: Implementation of evidence-based programs in school settings can be challenging, undermining the benefits these programs deliver for children. The primary aim of this study is to assess whether an enhanced implementation intervention increases adoption of the PAX Good Behaviour Game in New South Wales (NSW) primary schools in Australia. A secondary outcome is to investigate the impact of the PAX Good Behaviour Game on children's mental health in the Australian context. Methods and analysis: The study uses a cluster randomised hybrid type 3 effectiveness-implementation design and will involve 40 NSW primary schools. Randomisation will occur at the school level. All NSW primary schools trained in the PAX Good Behaviour Game are eligible for participation. The intervention is a multicomponent implementation strategy that has been iteratively co-designed by our research team and local stakeholders. Intervention schools will have access to eight implementation support strategies in addition to the training received as usual delivery to build knowledge and skills. Research staff will assess implementation and effectiveness outcomes using self-report online surveys with teachers and support staff at baseline, 6-weeks, 6-months and 12-months follow up. Semi-structured interviews with teachers and support staff will be used to examine which implementation strategies worked for whom and under what conditions. Discussion: If successful, this study will highlight effective strategies schools or education departments can use internationally to improve their translation of evidence-based programs into routine practices. This will lead to better outcomes for children and young people.

Objectives To assess practice in the care of adults with suspected community-acquired bacterial meningitis in the UK and Ireland.Design Retrospective cohort study.Setting 64 UK and Irish hospitals.Participants 1471 adults with community-acquired meningitis of any aetiology in 2017.Results None of the audit standards, from the 2016 UK Joint Specialists Societies guideline on diagnosis and management of meningitis, were met in all cases. With respect to 20 of 30 assessed standards, clinical management provided for patients was in line with recommendations in less than 50% of cases. 45% of patients had blood cultures taken within an hour of admission, 0.5% had a lumbar puncture within 1 hour, 26% within 8 hours. 28% had bacterial molecular diagnostic tests on cerebrospinal fluid. Median time to first dose of antibiotics was 3.2 hours (IQR 1.3–9.2). 80% received empirical parenteral cephalosporins. 55% ≥60 years and 31% of immunocompromised patients received anti-Listeria antibiotics. 21% received steroids. Of the 1471 patients, 20% had confirmed bacterial meningitis. Among those with bacterial meningitis, pneumococcal aetiology, admission to intensive care and initial Glasgow Coma Scale Score less than 14 were associated with in-hospital mortality (adjusted OR (aOR) 2.08, 95% CI 0.96 to 4.48; aOR 4.28, 95% CI 1.81 to 10.1; aOR 2.90, 95% CI 1.26 to 6.71, respectively). Dexamethasone therapy was weakly associated with a reduction in mortality in both those with proven bacterial meningitis (aOR 0.57, 95% CI 0.28 to 1.17) and with pneumococcal meningitis (aOR 0.47, 95% CI 0.20 to 1.10).Conclusion This study demonstrates that clinical care for patients with meningitis in the UK is not in line with current evidence-based national guidelines. Diagnostics and therapeutics should be targeted for quality improvement strategies. Work should be done to improve the impact of guidelines, understand why they are not followed and, once published, ensure they translate into changed practice.

Background: Sleep-disordered breathing (SDB) may hamper the outcome of catheter ablation of atrial fibrillation (AF). However, SDB is underdiagnosed in clinical practice and the relevancy of undiagnosed SDB on the outcome of catheter ablation is unclear. Objective: To evaluate if undiagnosed SDB has an impact on AF recurrence after catheter ablation. Methods: In this single-center cohort study we enrolled patients who had a catheter ablation of AF 12 to 18 months prior to enrolment. Patients with diagnosed SDB at the time of catheter ablation were excluded. Enrolled patients underwent screening using WatchPAT (WP). SDB was defined as an apnea-hypopnea index (AHI) ≥ 15. Results: A total of 164 patients were screened for eligibility. After exclusion of patients with previously diagnosed SDB (n = 30), 104 of 134 eligible patients were enrolled and underwent SDB screening. The median AHI was 11.5 (interquartile range 6.8–21.9) and 39 patients (38%) had SDB which was undiagnosed during the first year after ablation. AF recurrence in the first year after catheter ablation occurred in 40 patients (38%). The risk of AF recurrence was higher in the group with undiagnosed SDB in comparison to those without SDB (51% versus 31%, P = 0.04). Interestingly, the prevalence of AF recurrence was similar between patients with previously diagnosed and undiagnosed SDB (51% versus 50%, P = 0.92). Conclusion: A significant proportion of patients undergoing catheter ablation of AF have undiagnosed SDB which is associated with a twofold higher risk of AF recurrence. SDB screening may improve patient counselling regarding the efficacy of catheter ablation.

Background: Direct oral anticoagulants (DOACs) are the preferred choice of oral anticoagulation in patients with atrial fibrillation (AF). Randomized trials have demonstrated the efficacy and safety of DOAC in patients undergoing a cardiac implantable electronic device procedure (CIED); however, there is limited real-world data. Objective: To evaluate the outcome of patients undergoing an elective CIED procedure in a tertiary referral center with an interrupted DOAC or continued vitamin K antagonist (VKA) regimen. Methods: This was a retrospective single-center study of consecutive patients with AF undergoing an elective CIED procedure between January 2016 and June 2019. The primary endpoint was a clinically significant pocket hematoma

Purpose: Utilization of stereotactic radiosurgery (SRS) for brain metastases (BM) has increased, prompting reassessment of whole brain radiation therapy (WBRT). A pattern of care analysis of SRS and WBRT dose-fractionations was performed in patients presenting with BM at the time of cancer diagnosis. Methods and Materials: Adults with BM at cancer diagnosis between 2010 to 2015 and no prior malignancy were identified in the National Cancer Database. SRS was defined using published thresholds. Short (ShWBRT), standard (StWBRT), and extended (ExWBRT) dose-fractionations were defined as 4 to 9, 10 to 15, and >15 fractions. Radioresistant histology was defined as melanoma, renal cell carcinoma, sarcoma or spindle cell, or gastrointestinal primary. Results: Of 4,087,967 adults with their first lifetime cancer, 90,388 (2.2%) had BM at initial diagnosis. Of these, 11,486 (12.7%) received SRS and 24,262 (26.8%) WBRT as first-course radiation therapy. The proportion of annual WBRT use decreased from 27.8% to 23.5% of newly diagnosed patients, and SRS increased from 8.7% to 17.9%. Common dose-fractionations were 30 Gy in 10 fractions (56.8%) for WBRT and 20 Gy in 1 fraction (13.0%) for SRS. On multivariate analysis, factors significantly associated with SRS versus WBRT included later year of diagnosis (2015 vs 2010, adjusted odds ratio [aOR] = 2.4), radioresistance (aOR = 2.0), academic facility (aOR = 1.9), highest income quartile (aOR = 1.6), chemotherapy administration (aOR = 1.4), and longer travel distance (>15 vs

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95.1% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within- and between-host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.

Abstract Background For those who have experienced suicidal behaviour, discharge from the hospital emergency department and other acute settings represents a period of heightened vulnerability for future suicide risk. Current guidelines for suicide response in acute settings often fail to fully address the barriers faced by emergency department personnel who have contact with a person who presents for suicidal behaviour, and have been developed largely without the input of consumers or service users. The aim of the study was to use the Delphi expert consensus method to develop guidelines for staff responding to suicidal presentations in acute settings. Methods Systematic searches of academic and grey literature and interviews with key informants were conducted in order to develop a 525-item questionnaire, which comprised actions staff can take when responding to suicide-related presentations in acute settings. This was administered over three rounds to two panels consisting of Australian experts (39 health professionals, 50 consumers with lived experience). Items that reached consensus by at least 80% across both panels were included in the guidelines. Results A total of 420 items were rated as essential or important by at least 80% of both panels. The items included strategies that covered initial contact, assessment, referral, discharge and follow-up, staff training, and linkage with community aftercare services. Participation rate across all three rounds was 67.4% (78% consumers, 53.8% professionals). Conclusion The guidelines include strategies for responding to suicidal behaviour in acute settings. These guidelines can be used to inform policy development and address barriers to best practice for those working in the area. Future research should investigate ways to optimise implementation of these guidelines in order to improve equal access to quality care for who present to acute settings for suicidal behaviour.

The neonatal Fc receptor (FcRn) is responsible for recycling of IgG antibodies and albumin throughout the body. This mechanism has been exploited for pharmaceutic delivery across an array of diseases to either enhance or diminish this function. Monoclonal antibodies and albumin-bound nanoparticles are examples of FcRn-dependent anti-cancer therapeutics. Despite its importance in drug delivery, little is known about FcRn expression in circulating immune cells. Through time-of-flight mass cytometry (CyTOF) we were able to characterize FcRn expression in peripheral blood mononuclear cell (PBMC) populations of pancreatic ductal adenocarcinoma (PDAC) patients and non-cancer donors. Furthermore, we were able to replicate these findings in an orthotopic murine model of PDAC. Altogether, we found that in both patients and mice with PDAC, FcRn was elevated in migratory and resident classical dendritic cell type 2 (cDC2) as well as monocytic and granulocytic myeloid-derived suppressor cell (MDSC) populations compared to tumor-free controls. Furthermore, PBMCs from PDAC patients had elevated monocyte, dendritic cells and MDSCs relative to non-cancer donor PBMCs. Future investigations into FcRn activity may further elucidate possible mechanisms of poor efficacy of antibody immunotherapies in patients with PDAC.

COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns – outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.

Background: It is unclear who is at risk of being involved in a suicide cluster and whether suicide clusters are influenced by the social transmission of suicidal behaviour, assortative relating, or a combination of both. Methods: Suicide clusters involving two or more young people were identified from the free text of electronic police and coroners reports in Australia's National Coronial Information System in a nationwide cross-sectional study. The duration of survival among exposed cases were estimated using time-to-event methods. The casewise concordance of demographic, social and clinical characteristics and circumstances of death were examined among index and exposed cases. Findings: We identified links between 117 young people (51 suicide clusters). 50% of young people died within 90 days of the index suicide. Individuals exposed to railway suicide had an 80% probability of dying by the same method. Those exposed to the suicide of a person aged 10–18 years had an 86% probability of being from the same age group. Young people had a 67% and 60% probability of sharing the same characteristics as the index suicide when the index suicide resided in a remote community or was of Aboriginal and Torres Strait Islander descent. Interpretation: Suicide clusters may be associated with both the social transmission of suicidal behaviour and assortative relating. Individuals who were close to the deceased should be provided with access to postvention support, particularly within the first 90 days of exposure to an index suicide. Funding: Australian Rotary Health, National Health and Medical Research Council.

This study explores the characteristics of a micronized natural zeolitic volcanic tuff (MZ) as ingredient in cosmetic formulations. In particular, the purpose was to prepare and investigate the organoleptic and physicochemical properties of two representative cosmetic formulations containing MZ. The MZ samples were characterized using X-ray fluorescence (XRF), X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy. pH, cation exchange capacity (CEC), apparent density, chemical composition and particle size distribution of MZ samples were also determined. The micronization treatment applied did not produce significant structural and physicochemical changes with respect to the raw zeolitic volcanic tuff. The prepared formulations containing 5% MZ with different particle sizes (100–125 µm and 125–250 µm) were subjected to preliminary and accelerated stability tests, and the pH and organoleptic properties were also evaluated. The cosmetic formulations presented a pH of 4.3, a pleasant touch, good spreadability, easy application on skin, no color alteration and a good stability after 15, 30 and 60 days of storage at room temperature, low temperature and freezer during the accelerated stability tests. The obtained results endorse the MZ as suitable for the development of formulations exploiting the clinoptilolite properties as a cosmetic ingredient.

BackgroundSuicide is an unresolved psychiatric and public health emergency, claiming 800,000 lives each year, however, its neurobiological etiology is still not understood. In spite of original reports concerning the involvement of 5-HTTLPR in interaction with recent stress in the appearance of suicidal ideation and attempts, replication studies have yielded contradictory results. In our study, we analyzed the association between 5-HTTLPR and lifetime suicide attempts, current suicidal ideation, hopelessness and thoughts of death as main effects, and in interaction with childhood adversities, recent stress, and different types of recent life events in a general population sample.MethodsTwo thousand and three hundred fifty-eight unrelated European volunteers were genotyped for 5-HTTLPR, provided phenotypic data on previous suicide attempts, and current suicidal ideation, hopelessness and thoughts about death, and information on childhood adversities and recent life events. Logistic and linear regression models were run with age, gender, and population as covariates to test for the effect of 5-HTTLPR as a main effect and in interaction with childhood adversities and recent life events on previous suicide attempts and current suicidal ideation. Benjamini-Hochberg FDR Q values were calculated to correct for multiple testing.Results5-HTTLPR had no significant effect on lifetime suicide attempts either as a main effect on in interaction with childhood adversities. 5-HTTLPR had a significant main effect on current suicidal ideation in the dominant model (Q=0.0344). 5-HTTLPR did not interact with childhood adversities or total number of recent life events on any phenotypes related to current suicidal risk, however, a significant interaction effect between 5-HTTLPR and current relationship problems emerged in the case of current suicidal ideation in the dominant model (Q=0.0218) and in the case of thoughts about death and dying in the dominant (Q=0.0094) and additive models (Q=0.0281).ConclusionWhile 5-HTTLPR did not influence previous suicide attempts or interacted with childhood adversities, it did influence current suicidal ideation with, in addition, an interaction with recent relationship problems supporting the involvement of 5-HTTLPR in suicide. Our findings that 5-HTTLPR impacts only certain types of suicide risk-related behaviors and that it interacts with only distinct types of recent stressors provides a possible explanation for previous conflicting findings.

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.

Coffee is an important agricultural raw material and part of international trade. Although global production is extremely concentrated, it is mainly sold to developed markets. The aim of the paper is to analyse the comparative advantages of the biggest producers. Results suggest that coffee trade has increased recently with important changes in the key players. Brazil, Vietnam and Colombia are currently the biggest exporters, giving the majority of global trade. However, Balassa indices were the highest for Uganda, Ethiopia and Honduras, suggesting unreasonable specialisation patterns. Furthermore, stability and duration tests show significantly changing trends, implying fierce competition in these markets.Keywords: coffee trade, revealed comparative advantages, competitivenessJEL Classifications: Q17, Q13https://doi.org/10.32479/ijefi.6692

Hepatic infiltration of neutrophils is a hallmark of steatohepatitis; however, the role of neutrophils in the progression of steatohepatitis remains unknown. Methods: A clinically relevant mouse model of steatohepatitis induced by high-fat diet (HFD) plus binge ethanol feeding was used. Liver fibrosis was examined. In vitro cell culture was used to analyze the interaction of hepatic stellate cells (HSCs) and neutrophils. Results: HFD plus one binge ethanol (HFD+1B) feeding induced significant hepatic neutrophil infiltration, liver injury, and fibrosis. HFD plus multiple binges of ethanol (HFD+mB) caused more pronounced liver fibrosis. Microarray analyses showed that the most highly activated signaling pathway in this HFD+1B model was related to liver fibrosis and HSC activation. Blockade of chemokine (C-X-C motif) ligand 1 or intercellular adhesion molecule-1 expression reduced hepatic neutrophil infiltration and ameliorated liver injury and fibrosis. Disruption of the p47phox gene (also called neutrophil cytosolic factor 1), a critical component of reactive oxygen species producing nicotinamide adenine dinucleotide phosphate-oxidase in neutrophils, diminished HFD+1B–induced liver injury and fibrosis. Co-culture of HSCs with neutrophils, but not with neutrophil apoptotic bodies, induced HSC activation and prolonged neutrophil survival. Mechanistic studies showed that activated HSCs produce granulocyte-macrophage colony-stimulating factor and interleukin-15 to prolong the survival of neutrophils, which may serve as a positive forward loop to promote liver damage and fibrosis. Conclusions: The current data from a mouse model of HFD plus binge ethanol feeding suggest that obesity and binge drinking synergize to promote liver fibrosis, which is partially mediated via the interaction of neutrophils and HSCs. Microarray data in this article have been uploaded to NCBI’s Gene Expression Omnibus (GEO accession number: GSE98153).

Abstract Background Rates of suicide appear to be increasing, indicating a critical need for more effective prevention initiatives. To increase the efficacy of future prevention initiatives, we examined the spatial distribution of suicide deaths and suicide attempts in New South Wales (NSW), Australia, to identify where high incidence ‘suicide clusters’ were occurring. Such clusters represent candidate regions where intervention is critically needed, and likely to have the greatest impact, thus providing an evidence-base for the targeted prioritisation of resources. Methods Analysis is based on official suicide mortality statistics for NSW, provided by the Australian Bureau of Statistics, and hospital separations for non-fatal intentional self-harm, provided through the NSW Health Admitted Patient Data Collection at a Statistical Area 2 (SA2) geography. Geographical Information System (GIS) techniques were applied to detect suicide clusters occurring between 2005 and 2013 (aggregated), for persons aged over 5 years. The final dataset contained 5466 mortality and 86,017 non-fatal intentional self-harm cases. Results In total, 25 Local Government Areas were identified as primary or secondary likely candidate regions for intervention. Together, these regions contained approximately 200 SA2 level suicide clusters, which represented 46% (n = 39,869) of hospital separations and 43% (n = 2330) of suicide deaths between 2005 and 2013. These clusters primarily converged on the Eastern coastal fringe of NSW. Conclusions Crude rates of suicide deaths and intentional self-harm differed at the Local Government Areas (LGA) level in NSW. There was a tendency for primary suicide clusters to occur within metropolitan and coastal regions, rather than rural areas. The findings demonstrate the importance of taking geographical variation of suicidal behaviour into account, prior to development and implementation of prevention initiatives, so that such initiatives can target key problem areas where they are likely to have maximal impact.

The term ”plankton” refers to those microscopic aquatic forms having little or no resistance to currents and living free-floating and suspended, in open or pelagic waters. Phytoplankton development has different consequences depending on biomass quality and quantity, the overgrowth result being eutrophication process. The eutrophication intensity can cause both a lower water transparency, by excessive algal growth, to fish death in the area. In this study, it was presented the ecological status and phytoplankton biomass dynamic, in the Danube branches from upstream to downstream. The measurements have been made in 2013, in March, June, September and November, using spectrofluorometer for algal biomass determination and a microscope for qualitative analyses of phytoplankton species. Shannon-Wiener index was calculated to compare phytoplankton species diversity. Also, the biodegradable organic matter loading the ecosystem was determined by computing the Saprobic index. The values obtained do not exceed the eutrophication limits according to the Water Framework Directive, transposed into Romanian legislation by Order 161/2006, with normal concentrations for rheophile ecosystems, as Danube's branches. In this area, water currents and high water turbidity inhibit phytoplankton growth, in contrast to lacustrine ecosystems, where light penetration to depths favors the development of different phytoplankton groups.

Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ranging from muscle to the central nervous system. Although developmental origins have been hypothesized, evidence points to LS as a systemic autoimmune disorder, as there is a strong correlation to family history of autoimmune disease, the presence of shared HLA types with rheumatoid arthritis, high frequency of auto-antibodies, and elevated circulating chemokines and cytokines associated with T-helper cell, IFNγ, and other inflammatory pathways. This inflammatory phenotype of the peripheral blood is reflected in the skin via microarray, RNA Sequencing and tissue staining. Research is underway to identify the key players in the pathogenesis of LS, but close approximation of inflammatory lymphocytic and macrophage infiltrate with collagen and fibroblasts deposition supports the notion that LS is a disease of inflammatory driven fibrosis. The immune system is dynamic and undergoes changes during childhood, and we speculate on how the unique features of the immune system in childhood could potentially contribute to some of the differences in LS between children and adults. Interestingly, the immune phenotype in pediatric LS resembles to some extent the healthy adult cellular phenotype, possibly supporting accelerated maturation of the immune system in LS. We discuss future directions in better understanding the pathophysiology of and how to better treat pediatric LS.

Initial enteric microbial colonisation influences animal health and disease, hence an understanding of the first microbial colonisers within the piglet is important. The spiral colon of piglets that were stillborn (n = 20), born-alive (n = 10), and born alive and had sucked (n = 9) were collected from 28 sows to investigate whether initial microbial colonisation occurs pre- or post-partum and how it develops during the first 24 h post-partum. To examine this, DNA was extracted and 16S rRNA amplicon analysis was performed to allow analysis of microbial communities. The results indicate that microbial colonisation of the spiral colon had occurred in stillborn pigs, suggesting microbial exposure prior to birth. Alpha diversity metrics indicated that the number of taxa and community richness were higher in piglets that sucked (p < 0.001) and community evenness was lower in stillborns in comparison to born-alive (p < 0.001) but was not affected by colostrum consumption (p < 0.001). Additionally, when compared with stillborn piglets, the bacteria colonising the spiral colon during the first 24 h post-partum included the potentially pathogenic bacteria Escherichia coli, Clostridium perfringens and Clostridium celatum, and potentially beneficial bacteria Lactobacillus reutueri and Faecalibacterium prausnitzii. The relative presence of Archaea was high in stillborn piglets but decreased with post-natal environmental exposure. It is evident that stillborn piglets have bacteria present within their spiral colon, however further studies are needed in order to determine the time at which colonisation is initiated and the mechanisms determining how colonisation occurs. Additionally, as expected, the immediate post-natal environment largely influences the microorganisms colonising, while colostrum consumption further contributes to the microbial community enrichment.

Weaning is a stressful time for piglets, often leading to weight loss and is associated with increased morbidity and mortality. A leading cause for these post-weaning problems is enteric dysbiosis and methods to improve piglet health at this crucial developmental stage are needed. This study aimed to determine whether an enteric dysbiosis caused by weaning could be corrected via a faecal microbiota transplantation (FMT) from healthy piglets from a previous wean. Two or four focal piglets per litter were assigned to one of two treatments; FMT two days post weaning (n = 21; FMT) or a control which received saline two days post weaning (n = 21; CON). FMT consisted of homogenised donor faeces administered orally at 3 mL/kg. Weaning occurred at 18 days of age and weights and faecal samples were collected on days 18, 20, 24 and 35. 16S rRNA amplicon analysis was used to assess the faecal microbiota of piglets. FMT increased Shannon’s diversity post weaning (p < 0.001) and reduced the scratch score observed at 24 days of age (p < 0.001). The bacterial populations significantly differed in composition at each taxonomic level. In FMT pigs, significant increases in potentially pathogenic Escherichia coli were observed. However, increases in beneficial bacteria Lactobacillus mucosae and genera Fibrobacteres and Bacteroidetes were also observed in FMT treated animals. To our knowledge, this is the first study to observe a significant effect on piglet faecal microbiota following a single FMT administered post weaning. Therefore, FMT post weaning can potentially alleviate enteric dysbiosis.

We consider the following semigroup problem: is the closure of a semigroup S in a topological vector space X a group when S does not lie on “one side” of any closed hyperplane of X? Whereas for finite dimensional spaces, the answer is positive, we give a new example of infinite dimensional spaces where the answer is negative.

Antimicrobial use in animals and the potential development of antimicrobial resistance is a global concern. So, non-antimicrobial techniques for animal disease control are needed. This study aimed to determine whether neonatal ceftiofur (CF) treatment affects piglet faecal microbiomes and whether faecal microbiome transplantation (FMT) can correct it. Two focal piglets per sow were assigned to treatments as follows: cffresh (n = 6) received CF (3 mg/kg intramuscular) at 7 d and fresh FMT at 13 d; cffrozen (n = 7) received CF at 7 d and frozen FMT at 13 d; CF (n = 8) received CF at 7 d and no FMT; and no CF (n = 5) received no CF or FMT. DNA was extracted from faecal samples collected on days 7, 13, and 18 for 16S rRNA amplicon analysis. All faecal blends used for the FMT consisted of pooled donor pig faeces at 1:2 ratio with saline, delivered orally at 3 mL/kg. Alpha and beta diversity metrics increased with age (p < 0.05). However, no effect of antibiotic or FMT treatment was evident in 13 and 18 d old piglets (p > 0.05). Although no effect of treatment was observed, information regarding microbial membership during lactation was gained.

Pulmonary arterial hypertension (PAH) is a rare and highly fatal disease that has been reported in 8 patients with glycogen storage disease type I (GSDI). We describe an additional case of an acute presentation of PAH in a 14-year-old patient with GSDI, which was successfully treated with inhaled nitric oxide and sildenafil. We investigated the incidence of PAH in 28 patients with GSDI on routine echocardiography and found no evidence of PAH and no significant cardiac abnormalities. This study highlights that PAH is a rare disease overall, but our case report and those previously described suggest an increased incidence in patients with GSDI. Should cardiopulmonary symptoms develop, clinicians caring for patients with GSDI should have a high degree of suspicion for acute PAH and recognize that prompt intervention can lead to survival in this otherwise highly fatal disease.

The paper deals with the economical and ecological use of inhalation anesthetics in low-flow anesthesia (LFA, 1—0.5 l/ min) and high-flow anesthesia (HFA, more than 2—6 l/min). Four hundred and ninety six inhalational anesthesias lasting at least 80 minutes were analyzed in each group under consideration. The concentration of inhalation anesthetics was measures in the atmosphere of an operative theatre if inhalational anesthesia lasted more than 4 hours. There is evidence for the economical and ecological benefits in the use of LFA in terms of the availability of appropriate anesthesiological equipment, monitoring, and a highly skilled anesthesiologist.

We are developing a laboratory-scale model to improve our understanding and capacity to assess the biological risks of genetically engineered bacteria and their genetic elements in the natural environment. Our hypothetical scenario concerns an industrial bioreactor failure resulting in the introduction of genetically engineered bacteria to a downstream municipal wastewater treatment plant (MWWTP). As the first step towards developing a model for this scenario, we sampled microbial communities from the aeration basin of a MWWTP at three seasonal time points. Having established a baseline for community composition, we investigated how the community changed when propagated in the laboratory, including cell culture media conditions that could provide selective pressure in future studies. Specifically, using PhyloChip 16S-rRNA-gene targeting microarrays, we compared the compositions of sampled communities to those of inocula propagated in the laboratory in simulated wastewater conditionally amended with various carbon sources (glucose, chloroacetate, D-threonine) or the ionic liquid 1-ethyl-3-methylimidazolium chloride ([C2mim]Cl). Proteobacteria, Bacteroidetes, and Actinobacteria were predominant in both aeration basin and laboratory-cultured communities. Laboratory-cultured communities were enriched in γ-Proteobacteria. Enterobacteriaceae, and Aeromonadaceae were enriched by glucose, Pseudomonadaceae by chloroacetate and D-threonine, and Burkholderiacea by high (50 mM) concentrations of chloroacetate. Microbial communities cultured with chloroacetate and D-threonine were more similar to sampled field communities than those cultured with glucose or [C2mim]Cl. Although observed relative richness in operational taxonomic units (OTUs) was lower for laboratory cultures than for field communities, both flask and reactor systems supported phylogenetically diverse communities. These results importantly provide a foundation for laboratory models of industrial bioreactor failure scenarios.

Idiopathic outflow tract ventricular arrhythmias (VAs) represent a significant proportion of all VAs. The mechanism is thought to be catecholamine-mediated delayed after depolarizations and triggered activity, although other etiologies should be considered. In the adult cardiac conduction system it has been demonstrated that sometimes an embryonic branch, the so-called “dead-end tract”, persists beyond the bifurcation of the right and left bundle branch (LBB). Several findings suggest an involvement of this tract in idiopathic VAs (IVAs). The aim of this review is to summarize our current knowledge and the possible clinical significance of this tract.

This paper contributes in the form of a theoretical discussion and also, by the presentation of a practical example, brings information about the utilization possibilities of elements of augmented reality for the creation of programs for the control of a robotic workplace and for their simulated verification. In the beginning it provides an overview of the current state in the area of robotic systems with the use of unreal objects and describes existing and assumed attitudes. The next part describes an experimental robotic workplace. Then it clarifies the realization of a new way of verification of the program for robotic workplace control and provides information about the possibilities for further development of created functioning concepts.

Stromal Derived Factor 1 (SDF1 or CXCL12), is a chemokine known to be critical for the migration of cells in several tissue systems including the homing of the hematopoietic stem cell (HSC) to its niche in the bone marrow. A comparative analysis of miRNA expression profiles of two stromal cell lines, distinguishable by function and by CXCL12 expression (CXCL12+ and CXCL12-), revealed that the CXCL12- cells expressed>40 fold more miR-886-3p than the CXCL12+ cells. Screening studies showed that when miR-886-3p was transfected into the CXCL12+ stromal cells, the expression of CXCL12 was down-regulated by as much as 85% when compared to appropriate controls, and results in the loss of CXCL12-directed chemotaxis. Similar reductions in CXCL12 were obtained with the transfection of miR-886-3p into primary stromal cell cultures. Additional studies showed that miR-886-3p specifically targeted the 3' untranslated region (UTR) of CXCL12 mRNA. These data suggest a role for miRNA in modulating the expression of CXCL12, a gene product with a critical role in hematopoietic regulation.

The aim of this study was to demonstrate the effectiveness of the use of expulsion and impulsion nozzle high frequency ventilation (VFDV) for cleansing respiratory system during long-term mechanical ventilation. Material and methods. Retrospective study. In the group of 198 patients presenting its own procedures and the application of inpulsive and expulsive effect of the nozzle frequency ventilation (VFDV) for cleansing and maintaining a patent airway. They used high frequency jet ventilation with the possibility of expulsion and epulsion programming and assessed a total of over 8000 expulsion procedures. Changes in lung mechanics, hemodynamics, effectiveness of expulsion and the need for suction beforeexpulsion and in regular application of VFDV were monitored. Results. We statistically compared and evaluated the effectiveness of expulsion in the VFDV group of 198 patients on long-term UVP, which was effective in average of 94.9% of patients. The impact of expulsion regime on circulatory, ventilation systems and gas exchange in the lungs, including lung mechanics, were analyzed. The authors found that the application of VFDV had a substantial and statistically significant effect on hemodynamics. Application of expulsion and lavage (a technique is described) statistically significantly reduced airway resistance Raw (p

Objective: to compare the efficiency of continuous positive airway pressure (CPAP) and high-frequency jet ventilation by means of a mask (HFJV-M) in the treatment of cardiogenic edema of the lung. Design: a retrospective study. Setting: Department of Anesthesiology and Intensive Medicine, Hospital NsP, Vranov, Slovakia. Subjects and methods. A hundred and ninety-six patients with varying cardiogenic edema of the lung were divided into 3 groups according to the severity of pulmonary edema (PE). By taking into account comparable pharmacotherapy, mean airway pressure, and FiO2, the authors compared the efficiency of CPAP (n=64) and HFJV-M (n=101) from the rate of changes in respiration rate, blood oxygenation, acid-base balance, and the duration of ventilation support and the length of stay in the intensive care unit (ICU). The results were assessed by the unpaired Student’s test. The procedure of artificial ventilation via HFJV-M was approved by the Professional and Ethics Committee, Ministry of Health in the Republic of Slovakia, in 1989 for clinical application. Results. Comparison of CPAP or HFJV-M used in mild PE that was called Phase 1 of PE revealed no statistically significant differences in the parameters being assessed. In severer forms of PE characterized as Phases 2 and 3, the use of HFJV-M in the first 3 hours of ventilation maintenance caused a rapider reduction in spontaneous respiration rate from 25—33 per min to 18—22 per min (p>0.01). The application of HFJV-M also showed a statistically significant difference in the correction rate of PaO2, pH, and oxygenation index (PaO2/FIO2) (p>0.01) predominantly within the first 2 hours of therapy. Comparison of the mean duration of necessary ventilation maintenance (CPAP versus HFJV-M: 10.9 versus 6.8 hours) and the mean length of stay in the ICU (CPAP versus HFJV-N: 2.7 versus 2 days) revealed a statistically significant difference (p>0.01 and p>0.05, respectively). Only 6.6% of the HFJV-M group patients needed intubation and routine ventilation modes. Conclusion. The statistical analysis of controlled parameters (oxygenation, acid-base balance, duration of ventilation maintenance, length of hospital stay, and intubation needs) established that ventilation maintenance by HFJV-M versus CPAP was more effective just in the first 2—5 hours of therapy. When HFJV-M was used, the duration of required ventilation maintenance and the length of stay in the ICU were less since the need for intubation decreased to 6.6%.

Considering the issues of artificial ventilation (AV) in non-homogenous pathological lung processes (acute lung injury, acute respiratory distress syndrome, pneumonia, etc.), the authors created a mathematical model of multicompartment non-homogenous injured lungs that were ventilated by a new mode of AV, the so-called three-level ventilation. Multilevel ventilation was defined a type (modification) of ALV whose basic ventilation level was produced by the modes CMV, PCV or PS (ASB) and add-on level, and the so-called background ventilation was generated by the levels of PEEP and high PEEP (PEEPh) with varying frequency and duration. Multi-level ventilation on 3 pressure levels was realized by the mathematical model as a combination of pressure-controlled ventilation (PCV) and two levels of PEEP and PEEPh. The objective was to prove that in cases of considerably non-homogenous gas distribution in acute pathological disorders of lungs, gas entry into the so-called slow bronchoalveolar compartments could be improved by multilevel AV, without substabtially changing the volume of so-called fast compartments. Material and Method. Multi-level ventilation at 3 pressure levels was realized by the mathematical model as a combination of PCV and two levels of PEEP and PEEPh. Results. By comparing the single-level AV in the PCV mode with the so-called three-level ventilation defined as a combination of PCV+PEEPh/PEEP, the authors have discovered that the loading of slow compartments in the model was considerably improved by 50—60% as compared with the baseline values. In absolute terms, this difference was as many as 2—10 times of the volume. Conclusion. The mathematical model may demonstrate that the application of the so-called three-level AV causes considerable changes in gas distribution in the lung parenchyma disordered by a non-homogenous pathological process. The authors state that the proposed mathematical model requires clinical verification in order to evaluate the efficiency of this modification of AV. Key words: artificial ventilation, multilevel artificial ventilation, acute lung injury, acute respiratory distress syndrome.

Considering the issues of artificial ventilation (AV) in non-homogenous pathological lung processes (acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pneumonia, etc.), the authors applied the three-level lung ventilation to a group of 12 patients with non-homogenous lung injury. Three-level ventilation was defined as a type (modification) of AV whose basic ventilation level was produced by the modes CMV, PCV or PS (ASB) and add-on level, the so-called background ventilation was generated by two levels of PEEP. PEEP (constant) and PEEPh (PEEP high) with varying frequency and duration of transition between the individual levels of PEEP. Objective: to elucidate whether in cases of considerably non-homogenous gas distribution in acute pathological disorders, three-level ventilation (3LV) can correct gas distribution into the so-called slow bronchoalveolar compartments, by decreasing the volume load of the so-called fast compartments and to improve lung gas exchange, by following the principles of safe ventilation. Results. 3LV was applied to 12 patients with severe non-homogenous lung injury/disorder (atypic pneumonia and ARDS/ALI) and low-success PCV ventilation after recruitment manoeuvre (PaO2 (kPA) /FiO2 = 5—6). There were pronounced positive changes in pulmonary gas exchange within 1—4 hours after initiation of 3LV at a fPCV of 26±4 breaths/min-1 and PEEPh at a fPEEPH of 7±2 breaths/min-1 with a minute ventilation of 12±4 l/min. 3LV reduced a intrapulmonary shunt fraction 50±5 to 30±5%, increased CO2 elimination, with PaCO2 falling to the values below 6±0.3 kPa, and PaO2 to 7.5±1.2 kPa, with FiO2 being decreased to 0.8—0.4. Lung recruitment also improved gas exchange: with PEEP=1.2±0.4 kPa, static tho-racopulmonary compliance (Cst) elevated from 0.18±0.02 l/kPa to 0.3±0.02 l/kPa and then to 0.38±0.05 l/kPa. Airways resistance (Raw) decreased by more than 30%. Improved lung aeration was also estimated as a manifestation of gas distribution with a long time constant. After 5±1-day 3LV, the patients were switched to PS ventilation; after gradually reduction of ventilation maintenance, they were disconnected from a ventilator and transferred to a specialized unit. Conclusion. The small study group made it impossible to statistically assess outcomes; the clinical results are not at least contrary to the results of theoretical mathematic simulation of 3LV in mathematical and physical models. 3LV as compared with PCV applied within the first 2—4 hours of AV improved lung gas exchange. It can be a promising mode of ventilation for the lungs afflicted by a diffusive non-homogenous pathological process. Key words: artificial ventilation, three-level ventilation, acute lung injury, acute respiratory distress syndrome.

The servoventilator allows, apart from the standard modes, the application of several special modes of artificial lung ventilation (ALV) and the use of some new set-up features of the servoventilator. In his first part, the author describes and analyzes the so-called two-level ventilation 2-level+PS, which constitutes one of the progressive ventilation modes, at some other ventilators called as BiPAP, Bilevel, BiPAP-SIMV. This mode allows a patient to breathe in two pressure levels (Ppc/PEEP), whereas in the lower pressure level (PEEP) it allows the effective ventilatory support of spontaneous breathing by the pressure support (PS) mode. In this case, the mode is identical to the BiPAP-SIMV one. Further, the author describes a new mode of three-level ventilation (multilevel ventilation, MLV), in which patient breathes in three programmed levels of pressure that are PEEP, Phigh, and Ppc. This ventilation mode allows one to improve gas distribution in the non-homogenous injured lung. The further new mode that is implemented in the ventilator is so-called continuous flow ventilatory support (CFVS). It is unique in such a feature that catheter is introduced into the trachea of a spontaneously breathing patient, through which the gas flow from the ventilator flows and by washing out the dead space it decreases its volume and increases alveolar ventilation, without any need to intubate the patient or to perform relaxation. The patient is at his full consciousness. The author also describes the functionality of the new mode of intelligent ventilation regulation in pressure modes, a so-called minute ventilation servosystem that after the set-up of ventilatory parameters maintains the patient’s minute ventilation that is set by a doctor. Further, the author describes an adjustable Bias flow that is advantageous in such a feature that the negative inspiration peaks in the hyperventilating patient are eliminated and, thus, significantly relieves the work of an assistor. The ventilator also keeps at its disposal a monitor of mechanical properties of the lung, indicating the static compliance, airways resistance, inadvertent (auto) PEEPi and alveolar pressures. The Q/V and V/P loops are also naturally included. In conclusion, the author draws attention to the fact that the ventilator does not require compressed air for its operation and that it constitutes a step forward in the new modes of ALV. Key words: multilevel ventilation, lung mechanical properties, PEEPi, Cst, Bias flow, CFVS.

Abstract Takayasu’s arteritis (TA) is a form of chronic vasculitis that typically occurs in young adult Asian females, but it can also present in younger patients not fitting this classic profile. In these cases, the sequelae are generally similar to those found in adults. The disease predominantly affects the aorta and its primary branches. However, the coronary arteries are also affected in up to 20% of cases, which may precipitate myocardial infarction. Imaging of the coronary arteries therefore becomes critically important in the evaluation of a patient with possible Takayasu’s arteritis. We present a case of a pediatric patient with TA who had no symptoms of angina but who was found to have significant coronary artery involvement on diagnostic imaging. This necessitated tailoring of traditional management.

Abstract Background The purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA). Methods This study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired t-test (critical P value < 0.05) was performed on individuals who answered both questionnaires. Results There were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (P < 0.0001). Individuals scored the lowest (49%) on the question that addressed MTX's impact on pregnancy and fertility. Conclusions MTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a family's understanding of their child's medications.

Abstract Background Children are commonly referred to a pediatric rheumatology center for the laboratory finding of an Anti-nuclear antibody (ANA) of undetermined significance. Previous studies regarding adult rheumatology patients have supported an association between ANA and anti-thyroid antibodies, with the prevalence of thyroid antibodies being significantly higher in patients referred to a rheumatology center for an ANA without evidence of connective tissue disease compared to the general population. The purpose of the present study was to determine the frequency of thyroid antibodies in children referred to a pediatric rheumatology center for a positive ANA without evidence of a connective tissue disease. Methods A retrospective chart review was performed on children who were referred to our pediatric rheumatology center between August 2003 and March 2007 for positive ANA with concurrent thyroid antibody and thyroid function tests performed who did not fulfill criteria for a specific connective tissue disease. Laboratory and clinical features were recorded and analyzed. Mean and standard deviation were used to describe continuous data. Chi-square or Fisher's exact tests were used to compare proportions between variables. Results One-hundred and four ANA-positive patients with concurrent thyroid studies were evaluated (88% female, 93% Caucasian, mean age 11.9 ± 4.0 years). Half of patients had an ANA titer ≥ 1:320. The ANA pattern was speckled in 60% of the patients. Thyroid antibodies were detected in 30% of the patients. Anti-Thyroglobulin (ATG) was detected in 29% and Anti-thyroid peroxidase (ATPO) in 21% of the patients; of these children, 14% had hypothyroidism. ANA pattern and titer were not associated with anti-thyroid antibody positivity. Conclusion Thyroid antibodies associated with chronic lymphocytic thyroiditis, ATG and ATPO, were detected significantly higher in ANA-positive children without a rheumatologic condition (30%) as compared to the general pediatric population (1.3 - 3.4%). ANA titer and pattern did not help predict the presence or absence of thyroid antibodies. Given the high frequency of thyroid antibodies and increased risk of developing hypothyroidism over time, routine evaluation of ATG and ATPO with thyroid function tests in ANA-positive children is recommended.

Abstract Background Myocardial contrast echocardiography (MCE) allows visualization of radiofrequency (RF) ablation lesions in the left ventricle in an animal model. Aim: To test whether MCE allows visualization of RF and cryo ablation lesions in the human right atrium using three-dimensional echocardiography. Methods 18 patients underwent catheter ablation of a supraventricular tachycardia and were included in this prospective single-blind study. Twelve patients were ablated inside Koch's triangle and 6, who served as controls, outside this area. Three-dimensional echocardiography of Koch's triangle was performed before and after the ablation procedure in all patients, using respiration and ECG gated pullback of a 9 MHz ICE transducer, with and without continuous intravenous echocontrast infusion (SonoVue, Bracco). Two independent observers analyzed the data off-line. Results MCE identified ablation lesions as a low contrast area within the normal atrial myocardial tissue. Craters on the endocardial surface were seen in 10 (83%) patients after ablation. Lesions were identified in 11 out of 12 patients (92%). None of the control patients were recognized as having been ablated. The confidence score of the independent echo reviewer tended to be higher when the number of applications increased. Conclusions 1. MCE allows direct visualization of ablation lesions in the human atrial myocardium. 2. Both RF and cryo energy lesions can be identified using MCE.