[The use of magnetic-laser therapy in the combined treatment of osteoarthrosis in workers exposed to inorganic fluoride compounds].
The present study included 67 patients who had been exposed to the impact of inorganic fluoride compounds. It demonstrated beneficial effect of magnetolaser therapy in combination with whole body iodine-bromide-sodium chlorine baths, physical exercises, and massage on clinical manifestations of the primary disease and concomitant pathologies. Simultaneously, metabolic processes in the articular cartilage and bone tissue were normalized, lipid peroxidation was improved and optimization of antioxidative protection achieved. These changes are indicative of high therapeutic efficiency of the combined treatment employed in this study and its favourable influence on the quality of life of the patients.


Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs.
CD8+ cytotoxic T lymphocytes (CTLs) mediate resistance to infectious agents and tumours. Classically, CTLs recognize antigens that are localized in the cytoplasm of target cells, processed and presented as peptide complexes with class I molecules of the major histocompatibility complex (MHC). However, there is evidence for an exogenous pathway whereby antigens that are not expected to gain access to the cytoplasm are presented on MHC class I molecules. The most dramatic example is the in vivo phenomenon of cross-priming: antigens from donor cells are acquired by bone-marrow-derived host antigen-presenting cells (APCs) and presented on MHC class I molecules. Two unanswered questions concern the identity of this bone-marrow-derived cell and how such antigens are acquired. Here we show that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs. Our findings suggest a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of CTLs.


Root branching plasticity: collective decision-making results from local and global signalling.
Cells within tissues can be regarded as autonomous entities that respond to their local environment and to signals from neighbours. Coordination between cells is particularly important in plants, as the architecture of the plant adapts to environmental cues. To explain the architectural plasticity of the root, we propose to view it as a swarm of coupled multi-cellular structures, rhizomers, rather than a large set of autonomous cells. Each rhizomer contains a primed site with the potential to develop a single lateral root. Rhizomers are spaced through oscillatory genetic events that occur at the basal root tip. The decision whether or not to develop a lateral root primordium results from the interplay between local interactions of the rhizomer with its immediate environment, such as local nutrient availability, long-range interactions between the rhizomers and global cues, such as overall nutrient uptake. It can halt lateral root progression through its developmental stages, resulting in the observed complex root architecture.


Specific inhibition of eIF-5A and collagen hydroxylation by a single agent. Antiproliferative and fibrosuppressive effects on smooth muscle cells from human coronary arteries.
Restenosis occurs in 35% of patients within months after balloon angioplasty, due to a fibroproliferative response to vascular injury. These studies describe a combined fibrosuppressive/antiproliferative strategy on smooth muscle cells cultured from human primary atherosclerotic and restenotic coronary arteries and from normal rat aortas. L-Mimosine suppressed the posttranslational hydroxylation of the precursors for collagen and for eukaryotic initiation factor-5A (eIF-5A) by directly inhibiting the specific protein hydroxylases involved, prolyl 4-hydroxylase (E.C. 184.108.40.206) and deoxyhypusyl hydroxylase (E.C. 22.214.171.124), respectively. Inhibition of deoxyhypusyl hydroxylation correlated with a dose-dependent inhibition of DNA synthesis. Inhibition of prolyl hydroxylation caused a dose-dependent reduction in the secretion of hydroxyproline-containing protein and decreased the formation of procollagen types I and III. The antifibroproliferative action could not be attributed to nonspecific or toxic effects of mimosine, appeared to be selective for the hydroxylation step in the biosynthesis of the procollagens and of eIF-5A, and was reversible upon removal of the compound. The strategy of targeting these two protein hydroxylases has important implications for the pathophysiology of restenosis and for the development of agents to control fibroproliferative diseases.


A cycle of brain gain, waste and drain - a qualitative study of non-EU migrant doctors in Ireland.
Ireland is heavily reliant on non-EU migrant health workers to staff its health system. Shortages of locally trained health workers and policies which facilitate health worker migration have contributed to this trend. This paper provides insight into the experiences of non-EU migrant doctors in the Irish health workforce. In-depth interviews were conducted with 37 non-EU migrant doctors in Ireland in 2011/2012. Respondents believed they had been recruited to fill junior hospital doctor 'service' posts. These posts are unpopular with locally trained doctors due to the limited career progression they provide. Respondents felt that their hopes for career progression and postgraduate training in Ireland had gone unrealised and that they were becoming de-skilled. As a result, most respondents were actively considering onward migration from Ireland. Failure to align the expectations of non-EU migrant doctors with the requirements of the health system has resulted in considerable frustration and a cycle of brain gain, waste and drain. The underlying reasons for high mobility into and out of the Irish medical workforce must be addressed if this cycle is to be broken. The heavy reliance on non-EU migrant doctors to staff the medical workforce has distracted from the underlying workforce challenges facing the Irish medical workforce.


Protection of Metal Artifacts with the Formation of Metal-Oxalates Complexes by Beauveria bassiana.
Several fungi present high tolerance to toxic metals and some are able to transform metals into metal-oxalate complexes. In this study, the ability of Beauveria bassiana to produce copper oxalates was evaluated. Growth performance was tested on various copper-containing media. B. bassiana proved highly resistant to copper, tolerating concentrations of up to 20 g L(-1), and precipitating copper oxalates on all media tested. Chromatographic analyses showed that this species produced oxalic acid as sole metal chelator. The production of metal-oxalates can be used in the restoration and conservation of archeological and modern metal artifacts. The production of copper oxalates was confirmed directly using metallic pieces (both archeological and modern). The conversion of corrosion products into copper oxalates was demonstrated as well. In order to assess whether the capability of B. bassiana to produce metal-oxalates could be applied to other metals, iron and silver were tested as well. Iron appears to be directly sequestered in the wall of the fungal hyphae forming oxalates. However, the formation of a homogeneous layer on the object is not yet optimal. On silver, a co-precipitation of copper and silver oxalates occurred. As this greenish patina would not be acceptable on silver objects, silver reduction was explored as a tarnishing remediation. First experiments showed the transformation of silver nitrate into nanoparticles of elemental silver by an unknown extracellular mechanism. The production of copper oxalates is immediately applicable for the conservation of copper-based artifacts. For iron and silver this is not yet the case. However, the vast ability of B. bassiana to transform toxic metals using different immobilization mechanisms seems to offer considerable possibilities for industrial applications, such as the bioremediation of contaminated soils or the green synthesis of chemicals.


Plasma wave observations at comet giacobini-zinner.
The plasma wave instrument on the International Cometary Explorer (ICE) detected bursts of strong ion acoustic waves almost continuously when the spacecraft was within 2 million kilometers of the nucleus of comet Giacobini-Zinner. Electromagnetic whistlers and low-level electron plasma oscillations were also observed in this vast region that appears to be associated with heavy ion pickup. As ICE came closer to the anticipated location of the bow shock, the electromagnetic and electrostatic wave levels increased significantly, but even in the midst of this turbulence the wave instrument detected structures with familiar bow shock characteristics that were well correlated with observations of localized electron heating phenomena. Just beyond the visible coma, broadband waves with amplitudes as high as any ever detected by the ICE plasma wave instrument were recorded. These waves may account for the significant electron heating observed in this region by the ICE plasma probe, and these observations of strong wave-particle interactions may provide answers to longstanding questions concerning ionization processes in the vicinity of the coma. Near closest approach, the plasma wave instrument detected broadband electrostatic noise and a changing pattern of weak electron plasma oscillations that yielded a density profile for the outer layers of the cold plasma tail. Near the tail axis the plasma wave instrument also detected a nonuniform flux of dust impacts, and a preliminary profile of the Giacobini-Zinner dust distribution for micrometer-sized particles is presented.


Radiologic, Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions.
Proposed as a safer alternative to smoking, the use of electronic cigarettes has not proven to be innocuous. With numerous deaths, there is an increasing degree of public interest in understanding the symptoms, imaging appearances, causes of, and treatment of electronic cigarette or vaping product use-associated lung injury (EVALI). Patients with EVALI typically have a nonspecific clinical presentation characterized by a combination of respiratory, gastrointestinal, and constitutional symptoms. EVALI is a diagnosis of exclusion; the patient must elicit a history of recent vaping within 90 days, other etiologies must be eliminated, and chest imaging findings must be abnormal. Chest CT findings in EVALI most commonly show a pattern of acute lung injury on the spectrum of organizing pneumonia and diffuse alveolar damage. The pathologic pattern found depends on when in the evolution of the disease process the biopsy sample is taken. Other less common forms of lung injury, including acute eosinophilic pneumonia and diffuse alveolar hemorrhage, have also been reported. Radiologists and pathologists help play an important role in the evaluation of patients suspected of having EVALI. Accurate and rapid identification may decrease morbidity and mortality by allowing for aggressive clinical management and glucocorticoid administration, which have been shown to decrease the severity of lung injury in some patients. In this review, the authors summarize the current state of the art for the imaging and pathologic findings of this disorder and outline a few of the major questions that remain to be answered.


Folate supplementation in people with sickle cell disease.
Sickle cell disease (SCD) is a group of disorders that affects haemoglobin, which causes distorted sickle- or crescent-shaped red blood cells. It is characterized by anaemia, increased susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with SCD, it is hypothesized that they are at an increased risk for folate deficiency. For this reason, children and adults with SCD, particularly those with sickle cell anaemia, commonly take 1 mg of folic acid orally every day on the premise that this will replace depleted folate stores and reduce the symptoms of anaemia. It is thus important to evaluate the role of folate supplementation in treating SCD. To analyse the efficacy and possible adverse effects of folate supplementation (folate occurring naturally in foods, provided as fortified foods or additional supplements such as tablets) in people with SCD. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also conducted additional searches in both electronic databases and clinical trial registries.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 17 November 2017. Randomised, placebo-controlled trials of folate supplementation for SCD. Four review authors assessed We used the standard Cochrane-defined methodological procedures.Four review authors independently assessed the eligibility and risk of bias of the included trials and extracted and analysed the data included in the review. The quality of the evidence was assessed using GRADE. One trial, undertaken in 1983, was eligible for inclusion in the review. This was a double-blind placebo-controlled quasi-randomised triaI of supplementation of folic acid in people with SCD. A total of 117 children with homozygous sickle cell (SS) disease aged six months to four years of age participated over a one-year period (analysis was restricted to 115 children).Serum folate measures, obtained after trial entry at six and 12 months, were available in 80 of 115 (70%) participants. There were significant differences between the folic acid and placebo groups with regards to serum folate values above 18 µg/L and values below 5 µg/L (low-quality evidence). In the folic acid group, values above 18 µg/L were observed in 33 of 41 (81%) compared to six of 39 (15%) participants in the placebo (calcium lactate) group. Additionally, there were no participants in the folic acid group with serum folate levels below 5 µg/L, whereas in the placebo group, 15 of 39 (39%) participants had levels below this threshold. Haematological indices were measured in 100 of 115 (87%) participants at baseline and at one year. After adjusting for sex and age group, the investigators reported no significant differences between the trial groups with regards to total haemoglobin concentrations, either at baseline or at one year (low-quality evidence). It is important to note that none of the raw data for the outcomes listed above were available for analysis.The proportions of participants who experienced certain clinical events were analysed in all 115 participants, for which raw data were available. There were no statistically significant differences noted; however, the trial was not powered to investigate differences between the folic acid and placebo groups with regards to: minor infections, risk ratio (RR) 0.99 (95% confidence interval (CI) 0.85 to 1.15) (low-quality evidence); major infections, RR 0.89 (95% CI 0.47 to 1.66) (low-quality evidence); dactylitis, RR 0.67 (95% CI 0.35 to 1.27) (low-quality evidence); acute splenic sequestration, RR 1.07 (95% CI 0.44 to 2.57) (low-quality evidence); or episodes of pain, RR 1.16 (95% CI 0.70 to 1.92) (low-quality evidence). However, the investigators reported a higher proportion of repeat dactylitis episodes in the placebo group, with two or more attacks occurring in 10 of 56 participants compared to two of 59 in the folic acid group (P < 0.05).Growth, determined by height-for-age and weight-for-age, as well as height and growth velocity, was measured in 103 of the 115 participants (90%), for which raw data were not available. The investigators reported no significant differences in growth between the two groups.The trial had a high risk of bias with regards to random sequence generation and incomplete outcome data. There was an unclear risk of bias in relation to allocation concealment, outcome assessment, and selective reporting. Finally, There was a low risk of bias with regards to blinding of participants and personnel. Overall the quality of the evidence in the review was low.There were no trials identified for other eligible comparisons, namely: folate supplementation (fortified foods and physical supplementation with tablets) versus placebo; folate supplementation (naturally occurring in diet) versus placebo; folate supplementation (fortified foods and physical supplementation with tablets) versus folate supplementation (naturally occurring in diet). One doubIe-blind, placebo-controlled triaI on folic acid supplementation in children with SCD was included in the review. Overall, the trial presented mixed evidence on the review's outcomes. No trials in adults were identified. With the limited evidence provided, we conclude that, while it is possible that folic acid supplementation may increase serum folate levels, the effect of supplementation on anaemia and any symptoms of anaemia remains unclear.If further trials were conducted, these may add evidence regarding the efficacy of folate supplementation. Future trials should assess clinical outcomes such as folate concentration, haemoglobin concentration, adverse effects and benefits of the intervention, especially with regards to SCD-related morbidity. Such trials should include people with SCD of all ages and both sexes, in any setting. To investigate the effects of folate supplementation, trials should recruit more participants and be of longer duration, with long-term follow-up, than the trial currently included in this review. However, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.


Exhaustive matching of the entire protein sequence database.
The entire protein sequence database has been exhaustively matched. Definitive mutation matrices and models for scoring gaps were obtained from the matching and used to organize the sequence database as sets of evolutionarily connected components. The methods developed are general and can be used to manage sequence data generated by major genome sequencing projects. The alignments made possible by the exhaustive matching are the starting point for successful de novo prediction of the folded structures of proteins, for reconstructing sequences of ancient proteins and metabolisms in ancient organisms, and for obtaining new perspectives in structural biochemistry.


Using an epidemiological model to investigate unwarranted variation: the case of ventilation tubes for otitis media with effusion in England.
To investigate unwarranted variation in ventilation tube insertions for otitis media with effusion in children in England. This procedure is known to be 'overused' from clinical audits, as only one in three ventilation tube insertions conforms to the appropriateness criteria of the National Institute for Health and Care Excellence (NICE); but audits cannot identify the scale of 'underuse' - i.e. patients who would benefit but are not treated. To explore both 'underuse' and 'overuse' of ventilation tubes for otitis media with effusion, we developed an epidemiological model based on: definitions of children with otitis media with effusion expected to benefit from ventilation tubes according to NICE guidance; epidemiological and clinical information from a systematic review; and expert judgement. A range of estimates was derived using Monte Carlo simulation and compared with the number of ventilation tubes provided in the English National Health Service in 2010. About 32,200 children in England would be expected to benefit from ventilation tubes for otitis media with effusion per year (between 20,411 and 45,231 with 90% certainty). The observed number of ventilation tubes for otitis media with effusion-associated diagnoses was 16,824. The expected population capacity to benefit from ventilation tubes for otitis media with effusion based on NICE guidance appeared to exceed, by far, the number of ventilation tubes provided in the English National Health Service. So, while there is known 'overuse', there also may be substantial 'underuse' of ventilation tubes for otitis media with effusion if NICE criteria were applied. Future investigations of unwarranted variation should, therefore, not only focus on the patients who are treated but also consider the potential for benefit at the population level.


Waiting for coronary artery bypass surgery: a qualitative analysis.
Waiting lists for coronary artery bypass surgery (CABS) are common in many developed countries. Yet, there is limited information available regarding patients' health care needs at this time. This paper reports on a prospective study which aimed to investigate the experience of waiting for CABS from a qualitative perspective. An inductive research approach was used to conduct interviews with 70 randomly selected patients at three intervals over the first year on the waiting list - referral for surgery, again after waiting 6 months (n=49), and finally after waiting for 1 year (n=28). Attrition was mainly caused by surgery having been performed (n=36), although death (n=4) and refusal to participate (n=2) also contributed. Domicilliary interviews were taped and transcribed verbatim. Thematic content analysis identified three central themes in this experience - uncertainty, chest pain and anxiety; with six secondary themes - powerless, dissatisfaction with treatment, anger/frustration, physical incapacity, reduced self-esteem, and altered family and social relationships. The nature and meaning inherent in each theme is described using interview quotations, and a model is proposed which summarizes this data and the relationship between themes. From this analysis, uncertainty, chest pain and anxiety emerge as important indicators of a negative outcome for these patients. This report strongly suggests that patients awaiting bypass surgery require more information regarding the waiting time for such a surgery. Nurses should also offer advice regarding pain management to help improve patients' skills and decrease the fear associated with angina. Nursing intervention and support should also be directed at reducing patients' anxiety levels. This is the first known qualitative study which specifically examines patients' perception of the waiting period prior to bypass surgery. It may therefore provide new evidence on which to base practice for nurses in both hospital and community, and may also stimulate further research in this area.


[Experience with the use of a subcutaneous venous access system in 57 pediatric patients].
Since May of 1983 to December of 1988, 62 subcutaneous venous reservoires were implanted in 57 pediatric patients; 29 were boys and the remaining 28 were girls between the ages of 2 and 18 years. Fifty-one patients had malignant illnesses and seven other pathologies. The reservoir was used for the endovenous administration of cytotoxic chemotherapy and antibiotics, hidration, nutrition, the transfusion of blood product and the extraction of samples for laboratory tests. In our experience the most important complication was the infection of the system, on the average 0.06 episodes of infections occurred for every 100 days per reservoir. Other complications observed were less frequent. In our opinion the subcutaneous reservoir represents an useful tool for the care of the pediatric patients who require a central venous catheter for long periods of time.


The inhibition of first-pass metabolism of ethanol by H2-receptor antagonists: a tabulated review.
In the 1980s-1990s numerous studies were performed on H2-receptor antagonist inhibition of ethanol first-pass metabolism. Blood alcohol concentrations warranting possible driving under the influence citations in the United States have subsequently dropped from ≥100 mg/dL to 50 mg/dL (Utah in 2019) (30 mg/dL or zero tolerance in some parts of the world). A reexamination of these studies seemed important. Papers were compiled that addressed the effect of cimetidine, ranitidine, famotidine, and nizatidine on ethanol metabolism first from a PubMed search and then from citations within these papers. Studies were tabulated for fasting versus fed, ethanol and H2-receptor antagonist dose and a summary of pharmacokinetic changes. At doses of 0.15-0.30 mg/kg in the postprandial state (primarily after breakfast), the H2-receptor antagonists: cimetidine, ranitidine, famotidine, and nizatidine have all been found to increase the first-pass metabolism of ethanol. With cimetidine, there were sufficient studies to suggest it might be inhibitory outside these restricted states. While the role of inhibition of alcohol dehydrogenase has not been clearly defined, there is circumstantial evidence to support this mechanism. Further studies are required to elucidate the ability of H2-receptor antagonists to inhibit first-pass metabolism of ethanol.


Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span.
A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging, including reduced albuminuria, decreased inflammation, and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.


Validating skinfold thickness as a proxy to estimate total body fat in wild toque macaques (Macaca sinica) using the mass of dissected adipose tissue.
Skinfold thickness (SFT) has been used often in non-human primates and humans as a proxy to estimate fatness (% body fat). We intended to validate the relation between SFT (in recently deceased specimens) and the mass of adipose tissue as determined from dissection of fresh carcasses of wild toque macaques (Macaca sinica). In adult male and female toque macaques body composition is normally 2% adipose tissue. Calipers for measuring SFT were suitable for measuring only some subcutaneous deposits of adipose tissue but were not suitable for measuring large fat deposits within the body cavity or minor intermuscular ones. The anatomical distribution of 13 different adipose deposits, in different body regions (subcutaneous, intra-abdominal and intermuscular) and their proportional size differences, were consistent in this species (as in other primates), though varying in total mass among individuals. These consistent allometric relationships were fundamental for estimating fatness of different body regions based on SFT. The best fit statistically significant correlations and regressions with the known masses of dissectible adipose tissue were evident between the SFT means of the seven sites measured, as well as with a single point on the abdomen anterior to the umbilicus. SFT related to total fat mass and intra-abdominal fat mass in curvilinear regressions and to subcutaneous fat mass in a linear relationship. To adjust for differences in body size among individuals, and to circumvent intangible variations in total body mass allocated, for example to the gastro-intestinal contents, dissected fat mass was estimated per unit body size (length of crown-rump)(3). SFT had greater coefficients of correlation and regressions with this Fat Mass Index (g/dm(3)) than with Percent Body Fat.


Discovering transcription factor regulatory targets using gene expression and binding data.
Identifying the target genes regulated by transcription factors (TFs) is the most basic step in understanding gene regulation. Recent advances in high-throughput sequencing technology, together with chromatin immunoprecipitation (ChIP), enable mapping TF binding sites genome wide, but it is not possible to infer function from binding alone. This is especially true in mammalian systems, where regulation often occurs through long-range enhancers in gene-rich neighborhoods, rather than proximal promoters, preventing straightforward assignment of a binding site to a target gene. We present EMBER (Expectation Maximization of Binding and Expression pRofiles), a method that integrates high-throughput binding data (e.g. ChIP-chip or ChIP-seq) with gene expression data (e.g. DNA microarray) via an unsupervised machine learning algorithm for inferring the gene targets of sets of TF binding sites. Genes selected are those that match overrepresented expression patterns, which can be used to provide information about multiple TF regulatory modes. We apply the method to genome-wide human breast cancer data and demonstrate that EMBER confirms a role for the TFs estrogen receptor alpha, retinoic acid receptors alpha and gamma in breast cancer development, whereas the conventional approach of assigning regulatory targets based on proximity does not. Additionally, we compare several predicted target genes from EMBER to interactions inferred previously, examine combinatorial effects of TFs on gene regulation and illustrate the ability of EMBER to discover multiple modes of regulation. All code used for this work is available at http://dinner-group.uchicago.edu/downloads.html.


How the mass media report social statistics: a case study concerning research on end-of-life decisions.
The issue of whether it is right to be concerned about the accuracy with which mass media report social scientific research is explored through a detailed case study of media reporting of two surveys of UK doctors' end-of-life decision-making. Data include press releases, emails and field notes taken during periods of media interest supplemented by a collection of print and broadcast media reports. The case study contributes to existing knowledge about the ways in which mass media establish, exaggerate and otherwise distort the meaning of statistical findings. Journalists ignored findings that did not fit into existing media interest in the 'assisted dying' story and were subject to pressure from interest groups concerned to promote their own interpretations and viewpoints. Rogue statistics mutated as they were set loose from their original research report context and were 'laundered' as they passed from one media report to another. Yet media accounts of the research, fuelling an already heated public debate about ethical issues in end-of-life care, arguably acted as a conduit for introducing new considerations into this debate, such as the role played by sedation at the end of life, the extent to which euthanasia is practiced outside the law, and the extent of medical opposition to the legalisation of assisted dying. The expectation that accuracy and comprehensiveness should be the sole criteria for judging journalists' reports is, finally, considered to be unrealistic and it is argued that social scientists need to understand and adapted to the conditions under which mass media reporting operates if they are to succeed in introducing the findings of social research into public debates.


Cut-off levels for breath carbon monoxide as a marker for cigarette smoking.
Current clinical studies often use a breath carbon monoxide (BCO) cut-off level of 8 parts per million (p.p.m.) or higher to identify smoking. In this study, the cut-off level of BCO as an indicator of smoking over the past 24 hours was re-examined. BCO and self-reported smoking were obtained each weekday for up to 14 weeks in 213 subjects paid to deliver reduced BCO values. Analysis of 12 386 paired values for reported smoking and BCO were analyzed. The 25% quartile, median and 75% quartile values for BCO were 1, 1 and 2 p.p.m. on non-smoking days and 2, 5 and 12 p.p.m. on smoking days, respectively. Receiver-operating characteristic (ROC) analysis indicated that BCO provided high diagnostic accuracy to distinguish between smoking and non-smoking days [area under the curve (AUC) = 0.853, P < 0.0001]. The highest combined sensitivity and specificity was observed at a BCO cut-off level of 3 p.p.m. (sensitivity = 71.5%; specificity = 84.8%). At a BCO cut-off of 8 p.p.m. sensitivity and specificity were 40.6% and 98.2%, respectively, indicating that many smokers would be falsely classified as abstinent. Finally, the percentage of true tests (positive and negative) was highest at a BCO cut-off of 2 p.p.m. (80.2%). BCO cut-off levels well below 8 p.p.m and as low as 2-3 p.p.m. may be more useful when it is important to maximize identification of smoking abstinence with a high degree of certainty.


Circulating inflammatory biomarkers, adipokines and breast cancer risk-a case-control study nested within the EPIC cohort.
Inflammation has been hypothesized to play a role in the development and progression of breast cancer and might differently impact breast cancer risk among pre and postmenopausal women. We performed a nested case-control study to examine whether pre-diagnostic circulating concentrations of adiponectin, leptin, c-reactive protein (CRP), tumour necrosis factor-α, interferon-γ and 6 interleukins were associated with breast cancer risk, overall and by menopausal status. Pre-diagnostic levels of inflammatory biomarkers were measured in plasma from 1558 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We used conditional logistic regression to estimate the odds ratios (ORs) of breast cancer at blood collection, per one standard deviation increase in biomarker concentration. Cases were diagnosed at a mean age of 61.4 years on average 8.6 years after blood collection. No statistically significant association was observed between inflammatory markers and breast cancer risk overall. In premenopausal women, borderline significant inverse associations were observed for leptin, leptin-to-adiponectin ratio and CRP [OR= 0.89 (0.77-1.03), OR= 0.88 (0.76-1.01) and OR= 0.87 (0.75-1.01), respectively] while positive associations were observed among postmenopausal women [OR= 1.16 (1.05-1.29), OR= 1.11 (1.01-1.23), OR= 1.10 (0.99-1.22), respectively]. Adjustment for BMI strengthened the estimates in premenopausal women [leptin: OR = 0.83 (0.68-1.00), leptin-to-adiponectin ratio: OR = 0.80 (0.66-0.97), CRP: OR = 0.85 (0.72-1.00)] but attenuated the estimates in postmenopausal women [leptin: OR = 1.09 (0.96-1.24), leptin-to-adiponectin ratio: OR = 1.02 (0.89-1.16), CRP: OR = 1.04 (0.92-1.16)]. Associations between CRP, leptin and leptin-to-adiponectin ratio with breast cancer risk may represent the dual effect of obesity by menopausal status although this deserves further investigation.


Association between mortality and implantable cardioverter-defibrillators by aetiology of heart failure: a propensity-matched analysis of the WARCEF trial.
There is debate on whether the beneficial effect of implantable cardioverter-defibrillators (ICDs) is attenuated in patients with non-ischaemic cardiomyopathy (NICM). We assess whether any ICD benefit differs between patients with NICM and those with ischaemic cardiomyopathy (ICM), using data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. We performed a post hoc analysis using WARCEF (N = 2293; ICM, n = 991 vs. NICM, n = 1302), where participants received optimal medical treatment. We developed stratified propensity scores for having an ICD at baseline using 41 demographic and clinical variables and created 1:2 propensity-matched cohorts separately for ICM patients with ICD (N = 223 with ICD; N = 446 matched) and NICM patients (N = 195 with ICD; N = 390 matched). We constructed a Cox proportional hazards model to assess the effect of ICD status on mortality for patients with ICM and those with NICM and tested the interaction between ICD status and aetiology of heart failure. During mean follow-up of 3.5 ± 1.8 years, 527 patients died. The presence of ICD was associated with a lower risk of all-cause death among those with ICM (hazard ratio: 0.640; 95% confidence interval: 0.448 to 0.915; P = 0.015) but not among those with NICM (hazard ratio: 0.984; 95% confidence interval: 0.641 to 1.509; P = 0.941). There was weak evidence of interaction between ICD status and the aetiology of heart failure (P = 0.131). The presence of ICD is associated with a survival benefit in patients with ICM but not in those with NICM.


Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.
In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib. We randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety. A total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups. Progression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.).


Treatment and outcomes of post-transplant lymphoproliferative disease: a single institution study.
Post-transplant lymphoproliferative disorders (PTLD) complicate up to 10% of solid organ transplants. This retrospective study was conducted to review the PTLD experience among 2,300 recipients of solid organ or allogeneic bone marrow transplants from a single institution. Twenty-seven cases of PTLD were identified, leading to an overall incidence of 1.2%. Polymorphic B cell hyperplasia/lymphoma was the most common type. The median time to development of PTLD was 8.4 months. Ten patients had localized (stage I or II) disease, and 12 patients presented with B symptoms. Nine patients each were treated with systemic chemotherapy or surgical resection as part of the initial therapy. After a median follow-up duration of 2.6 years, the median survival has not been reached. There were no late relapses of PTLD, and 17 patients remain alive. Age, sex, organ source, LDH, stage, presence of extranodal disease, or presentation with B symptoms did not influence overall survival when examined by Cox proportional hazard model. Thirteen patients retained their graft function throughout PTLD treatment. This study confirms the ability to treat a significant proportion of PTLD patients with chemotherapy or surgical resection (depending on presentation), without sacrificing graft function in those receiving chemotherapy.


Acupuncture treatment for psoriasis: a retrospective case report.
We treated 61 cases of psoriasis with acupuncture, including 25 patients with complications of joint involvement and two cases with scleroderma additionally. All of the patients had failed to respond to their prior conventional western medical management. 25 patients were males and 36 were females. Their ages ranged from 22 to 84 years, with an average of about 52 years. There was no significant difference of the average ages between the sexes. Most of them (about 61%) had quite extensive involvement of the body. The average of duration of their illness was over 16 years, ranging from two to 65 years. They received an average of about nine sessions of acupuncture treatment, ranging from one to 15. Almost one third (19) of them had eleven to thirteen sessions. With the acupuncture treatment, about one-half (30) of the 61 patients had complete or almost complete clearance of the skin lesions. About a quarter (14 patients) of them had a clearance of about two thirds of the skin lesions. Eight of them had a clearance of one third of the skin lesions. Nine patients had minimal or no improvement. Our experience indicates that acupuncture is induced an effective therapeutic modality for psoriasis, particularly when the western medical management is unsuccessful. We speculated about the possible involvement of the cutaneous reticuloendothelial system in the clearance of the skin lesions.


Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial.
Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. Injections in 10 LV sites with an infusion catheter. Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6% to 56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95% CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95% CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95% CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95% CI, -15.7% to 1.7%; within-group, P = .11) or placebo (-5.2%; 95% CI, -16.8% to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95% CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95% CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. clinicaltrials.gov Identifier: NCT00768066.


Physical and numerical constraints in source modeling for finite difference simulation of room acoustics.
In finite difference time domain simulation of room acoustics, source functions are subject to various constraints. These depend on the way sources are injected into the grid and on the chosen parameters of the numerical scheme being used. This paper addresses the issue of selecting and designing sources for finite difference simulation, by first reviewing associated aims and constraints, and evaluating existing source models against these criteria. The process of exciting a model is generalized by introducing a system of three cascaded filters, respectively, characterizing the driving pulse, the source mechanics, and the injection of the resulting source function into the grid. It is shown that hard, soft, and transparent sources can be seen as special cases within this unified approach. Starting from the mechanics of a small pulsating sphere, a parametric source model is formulated by specifying suitable filters. This physically constrained source model is numerically consistent, does not scatter incoming waves, and is free from zero- and low-frequency artifacts. Simulation results are employed for comparison with existing source formulations in terms of meeting the spectral and temporal requirements on the outward propagating wave.


Curcuma longa activates NF-kappaB and promotes adhesion of neutrophils to human umbilical vein endothelial cells.
Upregulation of expression of cell adhesion molecules, such as ICAM-1, VCAM-1 and E-selectin, is important for immune surveillance. Extravasation and migration of body's effector cells to the site of immune activation is controlled by the expression of cell adhesion molecules on endothelial cells. We demonstrate here that an aqueous extract prepared from Curcuma longa (ClAqE), a dietary component, promotes the adhesion of peripheral neutrophils to human umbilical vein endothelial cells. To delineate the mechanism of increased adhesion, we investigated the possibility that ClAqE induces the expression of ICAM-1 and E-selectin on endothelial cells. ClAqE increases the steady state transcript levels of ICAM-1, VCAM-1, and E-selectin as determined by RT-PCR. We also show that ClAqE activates nuclear transcription factor NF-kappaB, a major transcription factor involved in the transcription of genes encoding ICAM-1, VCAM-1 and E-selectin. These results have implications for the usage of aqueous preparation of C. longa for upregulation of cell adhesion molecule expression and/or NF-kappaB.


Redox regulation of CD21 shedding involves signaling via PKC and indicates the formation of a juxtamembrane stalk.
Soluble CD21 (sCD21), released from the plasma membrane by proteolytic cleavage (shedding) of its extracellular domain (ectodomain) blocks B cell/follicular dendritic cell interaction and activates monocytes. We show here that both serine- and metalloproteases are involved in CD21 shedding. Using the oxidant pervanadate to mimic B cell receptor activation and thiol antioxidants such as N-acetylcysteine (NAC) and glutathione (GSH) we show that CD21 shedding is a redox-regulated process inducible by oxidation presumably through activation of a tyrosine kinase-mediated signal pathway involving protein kinase C (PKC), and by reducing agents that either directly activate the metalloprotease and/or modify intramolecular disulfide bridges within CD21 and thereby facilitate access to the cleavage site. Lack of short consensus repeat 16 (SCR16) abolishes CD21 shedding, and opening of the disulfide bridge between cys-2 (Cys941) and cys-4 (Cys968) of SCR16 is a prerequisite for CD21 shedding. Replacing these cysteines with selenocysteines (thereby changing the redox potential from -180 to -381 mV) results in a loss of inducible CD21 shedding, and removing this bridge by exchanging these cysteines with methionines increases CD21 shedding.


Honey improves spermatogenesis and hormone secretion in testicular ischaemia-reperfusion-induced injury in rats.
This study was conducted to survey the protective effect of pre-treatment with Persian honey during post-ischaemia reperfusion on ischaemia-reperfusion (IR)-induced testis injury. Animals were divided into four groups of IR, honey + ischaemia- reperfusion (HIR), vitamin C + ischaemia- reperfusion (VIR) and carbohydrates + ischaemia- reperfusion (CIR). The testes were examined for spermatogenesis index. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed. Total serum concentration of FSH, LH and testosterone was measured using ELISA. All data were expressed as mean ± SD in each group, and significance was set at p ≤ .05. Spermatogenesis index was significant in the HIR group (p < .001). Serum levels of FSH and LH were significantly higher in the CIR and HIR groups. Serum levels of testosterone were significantly higher in VIR and HIR groups. Apoptotic cells in IR and CIR groups increased significantly statistically (p < .001), while in HIR and VIR groups, the number of apoptotic cells decreased and the positive cells of TUNEL staining were detected in spermatocytes and spermatid. The present study indicates that honey decreases the cellular damage and apoptosis during testicular I/R injury, with significant protective effects on reproductive hormone production.


Susceptibility of juvenile humpback grouper Cromileptes altivelis to grouper sleepy disease iridovirus (GSDIV).
Susceptibility of juvenile humpback grouper Cromileptes altivelis to the grouper sleepy disease iridovirus (GSDIV) was examined. GSDIV-containing inocula for challenge were obtained using a filtrate of spleen tissues from donor fish (orange-spotted grouper Epinephelus coioides) infected with GSDIV. Groups injected with the primary filtrate showed lower mortalities (30 to 60%) than groups receiving the 10(-4) diluted inoculum (90 to 100% mortality). This result was contrary to the expectation that fish challenged with a higher concentration of virus would show higher mortality. Electron microscopy revealed that moribund fish receiving the 10(-4) diluted inoculum displayed massive formation of typical inclusion body-bearing cells (IBCs) containing an intracytoplasmic inclusion body with many virions in the 180-200 nm size range propagated within a virus assembly site. In contrast, survivors in fish receiving the primary filtrate showed the formation of unusual IBCs containing an abnormal inclusion body that was characterized by the assembly of a small number of deformed virions. This impaired virus assembly appeared to prevent mortality in the challenged fish and was assumed to be due to an interferon-like effect of a previously unknown substance that was passed on to the challenged fish with the tissue filtrate from the donor fish.


Gene expression and miR profiles of human corneal fibroblasts in response to dexamethasone.
Dexamethasone (DEX) is commonly used as a therapeutic agent for various ocular inflammatory diseases; however, its effect on resident naive cells is unknown. In this study, genome microarray and microRNA (miR) analyses were used to evaluate the global gene and miR expression of human corneal fibroblasts (HKFs) in response to treatment with DEX. Primary HKFs from three donors were treated with DEX for 16 hours. Treated and untreated cells were snap frozen for microarray and miR array analyses. Genes with a more than threefold change were classified into gene families using the DAVID web-based classification database, and six of these genes were validated using quantitative real-time PCR. Five miRs were also validated using miR-detection assays. Of the 41,093 genes examined, 261 were upregulated and 123 were downregulated greater than threefold after DEX treatment. Real-time PCR confirmed upregulation of six genes, including oculocutaneous albinism II (OCA2), angiopoietin-like 7 (ANGPTL7), neuron navigator 2 (NAV2), neurofilament light chain polypeptide (NEFL), solute carrier family 16/member 12 (SLC16A12), and serum amyloid A1 (SAA1). Expression of several miR including miR-16, -21, and -29C were upregulated, whereas miR-100 was downregulated in fibroblasts by DEX. DEX can greatly change the global gene and miR profile of HKFs. DEX not only downregulates inflammatory genes, but can also induce expression of angiogenic and inflammatory genes. In addition, DEX may exert posttranscriptional gene regulation through miRs. These data support a complex role for DEX-induced changes in resident cells that may have implications in the clinical management of corneal inflammation with topical glucocorticoids.


The experience of financial stress among emerging adult cancer survivors.
Objective: The experience of cancer-related financial stress was examined within the developmental context of emerging adulthood.Methodological approach: This study is a secondary analysis of data drawn from two samples of testicular or hematologic cancer survivors. In-depth interviews from 52 emerging adult (EA) cancer survivors, ages 18-29, were coded by combining thematic analysis with an abductive approach.Findings: Emergent themes included some common to most age groups, including worries about medical costs and availability of health insurance, as well as specific age-related concerns, such as fertility preservation. Financial stress appeared to interrupt developmental tasks of emerging adulthood, including completing an education, establishing independence, and managing relationships. Surprisingly, financial stress was experienced as a benefit for some participants.Conclusion: Financial stress affects EA cancer survivors in unique ways. To provide support, health professionals should consider survivors' developmental life stage to understand their financial stress, and ultimately, to improve quality of life.


Ultrasonic contrast agent shell rupture detected by inertial cavitation and rebound signals.
Determining the rupture pressure threshold of ultrasound contrast agent microbubbles has significant applications for contrast imaging, development of therapeutic agents, and evaluation of potential bioeffects. Using a passive cavitation detector, this work evaluates rupture based on acoustic emissions from single, encapsulated, gas-filled microbubbles. Sinusoidal ultrasound pulses were transmitted into weak solutions of Optison at different center frequencies (0.9, 2.8, and 4.6 MHz), pulse durations (three, five, and seven cycles of the center frequencies), and peak rarefactional pressures (0.07 to 5.39 MPa). Pulse repetition frequency was 10 Hz. Signals detected with a 13-MHz, center-frequency transducer revealed postexcitation acoustic emissions (between 1 and 5 micros after excitation) with broadband spectral content. The observed acoustic emissions were consistent with the acoustic signature that would be anticipated from inertial collapse followed by "rebounds" when a microbubble ruptures and thus generates daughter/free bubbles that grow and collapse. The peak rarefactional pressure threshold for detection of these emissions increased with frequency (e.g., 0.53, 0.87, and 0.99 MPa for 0.9, 2.8, and 4.6 MHz, respectively; five-cycle pulse duration) and decreased with pulse duration. The emissions identified in this work were separated from the excitation in time and spectral content, and provide a novel determination of microbubble shell rupture.


Acupuncture for neck disorders.
Neck pain is one of the three most frequently reported complaints of the musculoskeletal system. Treatments for neck pain are varied, as are the perceptions of benefits. Acupuncture has been used as an alternative to more traditional treatments for musculoskeletal pain. This review summarizes the most current scientific evidence on the effectiveness of acupuncture for acute, subacute and chronic neck pain. To determine the effects of acupuncture for individuals with neck pain. We searched CENTRAL (2006, issue 1) and MEDLINE, EMBASE, MANTIS, CINAHL from their beginning to February 2006. We searched reference lists and the acupuncture database TCMLARS in China. Any published trial using randomized (RCT) or quasi-randomized (quasi-RCT) assignment to the intervention groups, either in full text or abstract form, were included. Two reviewers made independent decisions for each step of the review: article inclusion, data abstraction and assessment of trial methodological quality. Study quality was assessed using the Jadad criteria. Consensus was used to resolve disagreements. When clinical heterogeneity was absent, we combined studies using random-effects meta-analysis models. We did not find any trials that examined the effects of acupuncture for acute or subacute pain, but we found 10 trials that examined acupuncture treatments for chronic neck pain. Overall, methodological quality had a mean of 2.3/5 on the Jadad Scale. For chronic mechanical neck disorders, there was moderate evidence that acupuncture was more effective for pain relief than some types of sham controls, measured immediately post-treatment. There was moderate evidence that acupuncture was more effective than inactive, sham treatments measured immediately post-treatment and at short-term follow-up (pooled standardized mean difference (SMD) -0.37, 95% confidence interval (CI) -0.61 to -0.12). There was limited evidence that acupuncture was more effective than massage at short-term follow-up. For chronic neck disorders with radicular symptoms, there was moderate evidence that acupuncture was more effective than a wait-list control at short-term follow-up. There is moderate evidence that acupuncture relieves pain better than some sham treatments, measured at the end of the treatment. There is moderate evidence that those who received acupuncture reported less pain at short term follow-up than those on a waiting list. There is also moderate evidence that acupuncture is more effective than inactive treatments for relieving pain post-treatment and this is maintained at short-term follow-up.


PDID: database of molecular-level putative protein-drug interactions in the structural human proteome.
Many drugs interact with numerous proteins besides their intended therapeutic targets and a substantial portion of these interactions is yet to be elucidated. Protein-Drug Interaction Database (PDID) addresses incompleteness of these data by providing access to putative protein-drug interactions that cover the entire structural human proteome. PDID covers 9652 structures from 3746 proteins and houses 16 800 putative interactions generated from close to 1.1 million accurate, all-atom structure-based predictions for several dozens of popular drugs. The predictions were generated with three modern methods: ILbind, SMAP and eFindSite. They are accompanied by propensity scores that quantify likelihood of interactions and coordinates of the putative location of the binding drugs in the corresponding protein structures. PDID complements the current databases that focus on the curated interactions and the BioDrugScreen database that relies on docking to find putative interactions. Moreover, we also include experimentally curated interactions which are linked to their sources: DrugBank, BindingDB and Protein Data Bank. Our database can be used to facilitate studies related to polypharmacology of drugs including repurposing and explaining side effects of drugs. PDID database is freely available at http://biomine.ece.ualberta.ca/PDID/.


Sources of Stress and Psychological Health Outcomes Among U.S. Air Force Total Force Distributed Common Ground System Operators.
U.S. Air Force Distributed Common Ground Station (DCGS) intelligence (Intel) operators sustain 24/7 battlefield situational awareness and facilitate precision-strike operations. DCGS operations are global, synergistic, Total Force (TF) endeavors by active duty, Air National Guard (ANG) and Reserve units, providing combatant commanders with critical real-time intelligence and shaping operational and tactical decisions. Continual surveillance of this community's psychological health is important to its military leaders. This study re-examines the most frequently reported occupational stressors, as well as the prevalence of occupational burnout (i.e., high-emotional exhaustion and cynicism, and low professional efficacy), and psychological distress within this population. Active duty (n = 1717), ANG (n = 139), and Reserve (n = 173) Intel operators participated in a comprehensive, online, occupational health assessment. Results reveal that occupational stressors contributing to elevated rates of distress, regardless of TF status (i.e., low manning, long work hours, excessive workload, and organizational communication concerns) are consistent with previous research. The prevalence of high-emotional exhaustion (AD: 29%/ANG: 25%/RES: 14%) and psychological distress (AD: 19%/ANG: 17%/RES: 5%) are above estimates for other military communities. These findings combined with demographic and occupational risk factors lay the foundation for improving psychological health within this Total Force community.


Examining overweight and obesity as risk factors for common mental disorders using fat mass and obesity-associated (FTO) genotype-instrumented analysis: The Whitehall II Study, 1985-2004.
The Mendelian randomization approach exploits genetic variants to improve causal inference when using observational data. The authors examined the relation between long-term obesity and common mental disorders (CMD) by utilizing the known relation between fat mass and obesity-associated (FTO) genotype and body mass index (BMI; weight (kg)/height (m)(2)). Data collection in 2,981 men and 1,164 women (mean age at baseline = 44 years) from the Whitehall II Study (London, United Kingdom) included 4 repeated examinations of BMI and CMD over a 19-year follow-up period (1985-2004), plus an assessment of FTO polymorphism rs1421085. In men, there was an association of FTO genotype with all measures of adiposity (mean BMI, number of times obese, and, in nonobese persons, number of times overweight). FTO was also associated with CMD in men. This was independent of adiposity, thus potentially violating the exclusion restriction assumption. According to both conventional and FTO-instrumented regression analysis, measurement of obesity was associated with an increased occurrence of CMD. In the FTO-instrumented analysis only, higher BMI and overweight were also associated with CMD. In women, there was no link between FTO and adiposity. Mendelian randomization analyses supported the status of long-term obesity as a risk factor for CMD in men-a finding that should be interpreted cautiously because the function of the FTO gene is unknown.


Intravitreal injection of bevacizumab in a case of occlusive retinal vasculitis accompanied by syphilitic intraocular inflammation.
We report a rare case of syphilitic intraocular inflammation with occlusive retinal vasculitis treated with intravitreal injection of bevacizumab (IVB) in addition to conventional therapy for syphilis. A 24-year-old woman who complained floaters in both her eyes showed occlusive retinal vasculitis OU. According to the high titer of the Treponema antigen and characteristic cutaneous eruption, she was diagnosed as secondary syphilis. She was treated with oral amoxicillin and retinal photocoagulation OU. Then, administration of prednisolone was required to the intraocular inflammations considered as Jarisch-Herxheimer reactions. IVB was also performed toward exacerbated retinal neovascularization and showed transient effects. We experienced a rare case of occlusive retinal vasculitis accompanied by syphilis intraocular inflammation. IVB was considered to be effective as an adjunctive therapy for inflammatory neovascularizations.


Action of linezolid or vancomycin on biofilms in ventriculoperitoneal shunts in vitro.
Cerebrospinal fluid (CSF) shunts used to treat hydrocephalus have an overall infection rate of about 10% of operations. The commonest causative bacteria are Staphylococcus epidermidis, followed by Staphylococcus aureus and enterococci. Major difficulties are encountered with nonsurgical treatment due to biofilm development in the shunt tubing and inability to achieve sufficiently high CSF drug levels by intravenous administration. Recently, three cases of S. epidermidis CSF shunt infection have been treated by intravenous linezolid without surgical shunt removal, and we therefore investigated vancomycin and linezolid against biofilms of these bacteria in vitro. A continuous-perfusion model of shunt catheter biofilms was used to establish mature (1-week) biofilms of Staphylococcus aureus, Staphylococcus epidermidis (both methicillin resistant [MRSA and MRSE]), Enterococcus faecalis, and Enterococcus faecium. They were then "treated" with either vancomycin or linezolid in concentrations achievable in CSF for 14 days. The biofilms were then monitored for 1 week for eradication and for regrowth. Enterococcal biofilms were not eradicated by either vancomycin or linezolid. Staphylococcal biofilms were eradicated by both antibiotics after 2 days and did not regrow. No resistance was seen. Linezolid at concentrations achievable by intravenous or oral administration was able to eradicate biofilms of both S. epidermidis (MRSE) and S. aureus (MRSA). Neither vancomycin at concentrations achievable by intrathecal administration nor linezolid was able to eradicate enterococcal biofilms. It is hoped that these in vitro results will stimulate further clinical trials with linezolid, avoiding surgical shunt removal.


Cryptosporidiosis in immunocompromised patients in the Islamic Republic of Iran.
Cryptosporidiosis is a parasitic zoonosis, which is prevalent all over the world. The manifestation of the disease is either self-limiting acute diarrhea in immunocompetent individuals, or potentially fatal chronic diarrhea in immunocompromised patients. In this study, which was conducted in Tehran, 214 patients from ten health centers were investigated. Stool samples were collected, fixed and examined by three methods: acid-fast staining, auramin phenol fluorescence and direct fluorescence using monoclonal antibody. Overall, 1.4% of all patients and 6.3% of diarrheal patients were infected by Cryptosporidium. The results revealed three cases of cryptosporidiosis, including two cases of acquired immunodeficiency syndrome (AIDS) and one of acute myeloid leukemia (AML). The prevalence of infection in subjects with AIDS or AML who were suffering from diarrhea was 33.4% and 11.1%, respectively. The duration of disease in infected patients lasted for weeks, and was terminated by death in two AIDS patients. In the patient with AML, diarrhea lasted for 18 days, and stopped after discontinuation of immunosuppressive therapy. Immunosuppressed people are at a significant risk of severe or even fatal Cryptosporidium infections.


Array comparative genomic hybridization analysis of Trichoderma reesei strains with enhanced cellulase production properties.
Trichoderma reesei is the main industrial producer of cellulases and hemicellulases that are used to depolymerize biomass in a variety of biotechnical applications. Many of the production strains currently in use have been generated by classical mutagenesis. In this study we characterized genomic alterations in high-producing mutants of T. reesei by high-resolution array comparative genomic hybridization (aCGH). Our aim was to obtain genome-wide information which could be utilized for better understanding of the mechanisms underlying efficient cellulase production, and would enable targeted genetic engineering for improved production of proteins in general. We carried out an aCGH analysis of four high-producing strains (QM9123, QM9414, NG14 and Rut-C30) using the natural isolate QM6a as a reference. In QM9123 and QM9414 we detected a total of 44 previously undocumented mutation sites including deletions, chromosomal translocation breakpoints and single nucleotide mutations. In NG14 and Rut-C30 we detected 126 mutations of which 17 were new mutations not documented previously. Among these new mutations are the first chromosomal translocation breakpoints identified in NG14 and Rut-C30. We studied the effects of two deletions identified in Rut-C30 (a deletion of 85 kb in the scaffold 15 and a deletion in a gene encoding a transcription factor) on cellulase production by constructing knock-out strains in the QM6a background. Neither the 85 kb deletion nor the deletion of the transcription factor affected cellulase production. aCGH analysis identified dozens of mutations in each strain analyzed. The resolution was at the level of single nucleotide mutation. High-density aCGH is a powerful tool for genome-wide analysis of organisms with small genomes e.g. fungi, especially in studies where a large set of interesting strains is analyzed.


Multiple Tools Are Needed for the Detection of Prenatal Alcohol Exposure: Findings From a Community Antenatal Setting.
Although the toxic effects of prenatal alcohol exposure (PAE) on children are well established, there is emerging evidence about the dynamics and associated demographics of drinking patterns across pregnancy, with risky drinking more likely to take place in the period before pregnancy awareness. This study investigated the use of complementary measurement tools in the understanding of alcohol use across pregnancy and reports on the rates and patterns of alcohol use in a community antenatal setting. Data on alcohol consumption before and after awareness of pregnancy were collected via multiple measurement tools: anonymous lifestyle questionnaire, TWEAK (Tolerance, Worried, Eye-opener, Amnesia, K/Cut down) screener questionnaire, and Substance Use Inventory interviews across multiple pregnancy timepoints. Additionally, phosphatidylethanol (PEth), a direct biomarker of alcohol metabolism, collected from newborns' dried blood spot cards, was analyzed. The TWEAK screener was more likely to identify risky drinking behavior than the lifestyle questionnaire. When pregnancy was unplanned, women were more likely to find out they are pregnant significantly later (p < 0.001) and consume alcohol at moderate-heavy levels (p = 0.03), prolonging the risk to the fetus. There was an association between maternal self-reported alcohol use on the lifestyle questionnaire and Substance Use Inventory interviews, but no association between maternal reports of alcohol use and PEth results (p = 0.72). Women self-reported moderate-heavy alcohol use in early pregnancy only and a positive PEth screen indicated PAE in late pregnancy, suggesting that these methods may identify different groups of women. Multiple measurement tools and methods are needed to identify PAE at different points across pregnancy. Prospective sensitive interviewing is better suited to detecting PAE in early pregnancy, but not later when social desirability bias is stronger, and the use of an objective biomarker, such a PEth, may be useful for identifying the risk of PAE in late pregnancy.


Luminal endocytosis and intracellular targeting by acinar cells during early biliary pancreatitis in the opossum.
Cell necrosis in acute experimental pancreatitis is preceded by a redistribution of digestive enzymes into a lysosomal subcellular compartment. We have investigated whether endocytosis from the acinar cell lumen might contribute to this disturbance of intracellular compartmentation. In an animal model of pancreatitis involving pancreatic bile duct ligation in opossums, we have studied in vivo endocytosis of dextran 40 and [14C]dextran 70, cationized ferritin, and horseradish peroxidase from the apical surface of acinar cells before the onset of necrosis. Marker solutions were instilled into the pancreatic duct of anesthetized animals at physiological pressure. Tissue samples obtained at intervals of up to 60 min after instillation of markers were studied by electron microscopy and electron microscope autoradiography. All markers were taken up by acinar cells in control animals and in animals with obstructed pancreatic bile ducts. Markers for membrane-mediated endocytosis (cationated ferritin and horseradish peroxidase) were transported to lysosomes in both groups. In contrast, the fluid-phase tracer dextran was transported to the secretory pathway in controls but to lysosomes after duct ligation. Since dextran and luminally present secretory proteins can be expected to follow the same route after endocytosis, our findings suggest that altered intracellular targeting of endocytosed proteases might be one mechanism by which digestive zymogens reach an intracellular compartment in which premature activation can occur. This phenomenon may be a critical and early event in the pathogenesis of biliary pancreatitis.


Regional Royal College of Physicians conference. Nottingham, September 1994.
The September 1994 Regional Royal College of Physicians Conference was held in the newly refurbished Postgraduate Medical Education Centre at the Nottingham City Hospital. Over 100 participants enjoyed a broadly based programme where topical issues in many of the specialty areas of general medicine were discussed and posters of local research were displayed. The presentations were given by both local and national experts and were of a uniformly high standard.


Reliability of a combined biomechanical and surface electromyographical analysis system during dynamic barbell squat exercise.
An analysis system for barbell weightlifting exercises is proposed to record reliable performance and neuromuscular responses. The system consists of surface electromyography (sEMG) synchronized with electrogoniometry and a barbell position transducer. The purpose of this study was to establish the reliability of the three components of the system. Nine males (age 28.9 ± 4.8 years, mass 85.7 ± 15.1 kg) performed squat exercise at three loads on three separate trial days. A data acquisition and software system processed maximal knee angle (flexion), mean power for the concentric phase of squat exercise, and normalized root mean square of the vastus lateralis. Inter-trial coefficients of variation for each variable were calculated as 5.3%, 7.8%, and 7.5% respectively. In addition, knee joint motion and barbell displacement were significantly related to each other (bar displacement (m) = 1.39-0.0057 × knee angle (degress), with goodness-of-fit value, r² = 0.817), suggesting knee goniometry alone can represent the kinematics of a multi-joint squat exercise. The proven reliability of the three components of this system allows for real-time monitoring of resistance exercise using the preferred training methods of athletes, which could be valuable in the understanding of the neuromuscular response of elite strength training methods.


The slow component of O2 uptake kinetics during heavy exercise.
During constant-load exercise of moderate intensity, pulmonary O2 uptake (VO2) is characterized by two temporal response components. The first occurs during the transit delay from the exercising limbs and is mediated predominantly by increased pulmonary blood flow. Thereafter, this response is supplemented by the influence of increased O2 extraction, causing VO2 to increase monoexponentially to its steady state, with a time constant that does not vary appreciably with work rate, at this intensity. At work rates that engender a lactic acidosis, however, an additional slow phase of VO2 is superimposed upon the underlying kinetics: this is of delayed onset and prolongs the time to steady state over the range within which the increases in blood lactate and [H+] stabilize or even decrease (heavy exercise). At higher work rates (severe exercise) a steady state is unattainable, with the VO2 trajectory resulting in VO2max progressively earlier the higher the work rate: it is therefore a fundamental determinant of exercise tolerance. Although the kinetic features of this slow VO2 component (other than its delay) remain to be determined, current evidence suggests that it is manifest predominantly in the exercising limbs, with the recruitment profile and metabolic features of fast-twitch fiber activation being the major contributor.


Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension.
We show that 1 of the type II bone morphogenetic protein (BMP) receptor ligands, BMP4, is widely expressed in the adult mouse lung and is upregulated in hypoxia-induced pulmonary hypertension (PH). Furthermore, heterozygous null Bmp4(lacZ/+) mice are protected from the development of hypoxia-induced PH, vascular smooth muscle cell proliferation, and vascular remodeling. This is associated with a reduction in hypoxia-induced Smad1/5/8 phosphorylation and Id1 expression in the pulmonary vasculature. In addition, pulmonary microvascular endothelial cells secrete BMP4 in response to hypoxia and promote proliferation and migration of vascular smooth muscle cells in a BMP4-dependent fashion. These findings indicate that BMP4 plays a dominant role in regulating BMP signaling in the hypoxic pulmonary vasculature and suggest that endothelium-derived BMP4 plays a direct, paracrine role in promoting smooth muscle proliferation and remodeling in hypoxic PH.


Low-grade albuminuria and the risks of hypertension and blood pressure progression.
It has been postulated that glomerular hyperfiltration and endothelial dysfunction are early features of essential hypertension that may antedate blood pressure elevation. Microalbuminuria, a marker of glomerular hyperfiltration and endothelial dysfunction, has been described in individuals with established hypertension, but its role as a biomarker of preclinical stages of this disease has not been investigated prospectively. We examined the association between urinary albumin excretion and the risks of hypertension and blood pressure progression in 1499 nonhypertensive individuals (58% women) without diabetes. During a mean follow-up of 2.9 years, 230 participants (15%) developed hypertension and 499 (33%) progressed to a higher blood pressure category (defined by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). In multivariable logistic regressions that adjusted for known risk factors, the urine albumin-creatinine ratio (UACR) was a significant predictor of incident hypertension (adjusted OR 1.20, 95% CI 1.01 to 1.44, per 1-SD increment in log UACR). Compared with those in the lowest UACR quartile, participants in the highest quartile (men: >6.66 mg/g; women: >15.24 mg/g) had an approximately 2-fold risk of developing hypertension (adjusted OR 1.93, P=0.006) and 1.5-fold risk of blood pressure progression (adjusted OR 1.45, P=0.03). Urinary albumin excretion predicts blood pressure progression in nondiabetic, nonhypertensive individuals incrementally over established risk factors and at levels well below the conventional threshold for microalbuminuria. UACR may be a useful biomarker for identifying individuals most likely to develop hypertension.


From 2R to 3R: evidence for a fish-specific genome duplication (FSGD).
An important mechanism for the evolution of phenotypic complexity, diversity and innovation, and the origin of novel gene functions is the duplication of genes and entire genomes. Recent phylogenomic studies suggest that, during the evolution of vertebrates, the entire genome was duplicated in two rounds (2R) of duplication. Later, approximately 350 mya, in the stem lineage of ray-finned (actinopterygian) fishes, but not in that of the land vertebrates, a third genome duplication occurred-the fish-specific genome duplication (FSGD or 3R), leading, at least initially, to up to eight copies of the ancestral deuterostome genome. Therefore, the sarcopterygian (lobe-finned fishes and tetrapods) genome possessed originally only half as many genes compared to the derived fishes, just like the most-basal and species-poor lineages of extant fishes that diverged from the fish stem lineage before the 3R duplication. Most duplicated genes were secondarily lost, yet some evolved new functions. The genomic complexity of the teleosts might be the reason for their evolutionary success and astounding biological diversity.


Professional appraisal of online information about children's footwear measurement and fit: readability, usability and quality.
Parents increasingly use the internet to seek health information, share information and for purchasing textiles and footwear. This shift in footwear purchasing habits raises concern about how (and if) parents are getting their children's feet measured, and what support strategies are in place to support the fit of footwear. In response to this, some companies and healthcare organisations have developed resources to support home measurement of foot size, and link these measures to footwear selection, measurement and fitting. The aim of this research was to undertake an appraisal of web-based resources about measurement and fit of children's footwear, focussing specifically on readability, usability and quality. Search terms relating to children's foot measurement were compiled and online searching was undertaken. Search results were saved and screened for relevance. Existing resources were categorised based on their source e.g. a footwear company or a health website. The 15 most commonly identified resources were reviewed by a professional panel for readability, content, usability and validity. One researcher also assessed the accessibility and reading ease of the resources. Online resources were predominantly from commercial footwear companies (54%). Health information sources from professional bodies made up 4.2% of the resources identified. The top 15 resources had appropriate reading ease scores for parents (SMOG Index 4.3-8.2). Accessibility scores (the product of the number of times it appeared in search results and its ranking in the results) were highest for commercial footwear companies. The panel scores for readability ranged from 2.7 to 9 out of 10, with a similar range for content, usability and validity. Information for parents seeking to purchase footwear for their children is readily available online but this was largely dominated by commercial footwear companies. The quality and usability of this information is of a moderate standard; notable improvements could be made to the validity of the task the child is asked to undertake and the measures being taken. Improvements in these resources would improve the data input to the selection of footwear and therefore have a beneficial impact on footwear fit in children.


Differential expression of miR-145 in children with Kawasaki disease.
Kawasaki disease is an acute, self-limited vasculitis of childhood that can result in structural damage to the coronary arteries. Previous studies have implicated the TGF-β pathway in disease pathogenesis and generation of myofibroblasts in the arterial wall. microRNAs are small non-coding RNAs that modulate gene expression at the post-transcriptional level and can be transported between cells in extracellular vesicles. To understand the role that microRNAs play in modifying gene expression in Kawasaki disease, we studied microRNAs from whole blood during the acute and convalescent stages of the illness. RNA isolated from the matched whole blood of 12 patients with acute and convalescent Kawasaki disease were analyzed by sequencing of small RNA. This analysis revealed six microRNAs (miRs-143, -199b-5p, -618, -223, -145 and -145* (complementary strand)) whose levels were significantly elevated during the acute phase of Kawasaki disease. The result was validated using targeted qRT-PCR using an independent cohort (n = 16). miR-145, which plays a critical role in the differentiation of neutrophils and vascular smooth muscle cells, was expressed at high levels in blood samples from acute Kawasaki disease but not adenovirus-infected control patients (p = 0.005). miR-145 was also detected in small extracellular vesicles isolated from acute Kawasaki disease plasma samples. Pathway analysis of the predicted targets of the 6 differentially expressed microRNAs identified the TGF-β pathway as the top pathway regulated by microRNAs in Kawasaki disease. Sequencing of small RNA species allowed discovery of microRNAs that may participate in Kawasaki disease pathogenesis. miR-145 may participate, along with other differentially expressed microRNAs, in regulating expression of genes in the TGF-β pathway during the acute illness. If the predicted target genes are confirmed, our findings suggest a model of Kawasaki disease pathogenesis whereby miR-145 modulates TGF-β signaling in the arterial wall.


Hessian-based norm regularization for image restoration with biomedical applications.
We present nonquadratic Hessian-based regularization methods that can be effectively used for image restoration problems in a variational framework. Motivated by the great success of the total-variation (TV) functional, we extend it to also include second-order differential operators. Specifically, we derive second-order regularizers that involve matrix norms of the Hessian operator. The definition of these functionals is based on an alternative interpretation of TV that relies on mixed norms of directional derivatives. We show that the resulting regularizers retain some of the most favorable properties of TV, i.e., convexity, homogeneity, rotation, and translation invariance, while dealing effectively with the staircase effect. We further develop an efficient minimization scheme for the corresponding objective functions. The proposed algorithm is of the iteratively reweighted least-square type and results from a majorization-minimization approach. It relies on a problem-specific preconditioned conjugate gradient method, which makes the overall minimization scheme very attractive since it can be applied effectively to large images in a reasonable computational time. We validate the overall proposed regularization framework through deblurring experiments under additive Gaussian noise on standard and biomedical images.


Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement.
As vitamins and dietary supplements are obtainable without prescription, treating physicians often ignore their intake by patients with multiple sclerosis (MS) and may therefore miss potential adverse effects and interactions. We aimed to assess the spectrum and intake frequency of supplementary medication in a cohort of MS patients and to analyse the effect of biotin intake on measurement of serum neurofilament light chain (sNfL), an emerging marker of disease activity. MS patients visiting our neurology outpatient clinic completed a questionnaire on their past or present use of vitamins or dietary supplements. In addition, the impact of two different doses of biotin (10 and 300 mg/day) on sNfL was studied in healthy volunteers. Of 186 patients, 72.6% reported taking over-the-counter vitamins or dietary supplements currently or previously. Most frequently used was vitamin D (60.0%), followed by biotin. Female patients and patients with primary progressive MS tended to use supplements more frequently. Biotin intake did not interfere with sNfL measurement by single molecule array (Simoa). The use of vitamins and dietary supplements is frequent among patients with MS. Thus, treating physicians should be aware of the pitfalls of supplementary treatment and educate their patients accordingly.


[Effectivity of early psychosocial counselling for family caregivers in general practioner based dementia care].
Psychoeducation and professional support of family caregivers are regarded as important aspects in dementia care. In the context of a general practitioner's (GP) based dementia care project we investigated if professional counselling after making a diagnosis of dementia can reduce the development of depression in family caregivers. 42 patients with dementia and their family caregivers took part in the prospective, randomized study with a follow-up after 18 months. 29 families received psychosocial counselling, the control group was provided an information brochure about dementia including helpful contact addresses. Counselling included education about the illness. Additionally, the current individual needs were identified and assistance was administered if necessary. The counseling was rated as "very helpful" or "helpful" by most of the caregivers as well as by the partaking GPs. While depression rate between counseling and control group did not differ significantly at baseline, the depression rate was significantly increased in the control group after 18 month as compared to the intervention group. Despite the small study size we provide first strong evidence that early psychosocial counselling can reduce the development of depression in family caregivers. Early, professional counselling improves the quality of dementia care within a GP-based dementia care setting and it might stabilize and extend the home care duration of dementia patients.


[Sonographic artifacts in nephrology].
The huge spreading of sonography in the field of nephrology led to the use of more performant equipment with construction of better quality images, but with an unfavorable signal/noise ratio, that bring to the generation of artifacts: false signals which creates images not corresponding to reality. Interaction between ultrasounds and biological structures generates a lot of physical phenomena: reflection, dispersion, absorption and diffraction; these elements create not only the images but also the artifacts. The artifacts, which don't correspond to anatomic reality, could be related to the extreme difference of acoustic impedance between the biological structures, or to an error in the settings of B-Mode and color-doppler functions. Sometimes they can be dangerous and make a diagnosis hard, but most of the time they are useful and pathognomonic of a lesion or physiologic structure. It's fundamental for the sonographer being able to discern between real to artifact; the rule is that everything that is repeated in all scans with different insonation angles is true, while what is not repeated in all scans can be an artifact.


Polymorphisms of the HDL receptor gene associated with HDL cholesterol levels in diabetic kindred from three populations.
We examined polymorphisms in the HDL receptor, SR-BI, for association with plasma HDL cholesterol levels. Study subjects, including 847 women and 725 men, were from families originally ascertained for type 2 diabetes from Finland, Sweden and Israel. Four common polymorphisms were examined in linear regression analysis: an exon 1 missense (EX1), exon 8 silent (EX8), intron 5 (IVS5) and intron 10 (IVS10) variants. Genotype combinations for the three polymorphisms in linkage disequilibrium (IVS5, EX8 and IVS10) were found to be associated with HDL-C among women from the Israeli (p = 0.01) and Swedish (p = 0.06) populations. In Finnish women, the association was only apparent after taking into account effect modification by triglyceride levels (p = 0.04). One specific pattern of genotypes, denoted by presence of the IVS5_T and EX8_C alleles, and absence of the IVS10_G allele, was consistently associated with the lowest mean levels of HDL-C in women from all three populations. These same associations were not found in men. Polymorphic variation of the SR-BI gene may influence HDL-C levels and act in a sex-dependent manner.


Specialization effect and its influence on memory and problem solving in expert chess players.
Expert chess players, specialized in different openings, recalled positions and solved problems within and outside their area of specialization. While their general expertise was at a similar level, players performed better with stimuli from their area of specialization. The effect of specialization on both recall and problem solving was strong enough to override general expertise-players remembering positions and solving problems from their area of specialization performed at around the level of players 1 standard deviation (SD) above them in general skill. Their problem-solving strategy also changed depending on whether the problem was within their area of specialization. When it was, they searched more in depth and less in breadth; with problems outside their area of specialization, the reverse. The knowledge that comes from familiarity with a problem area is more important than general purpose strategies in determining how an expert will tackle it. These results demonstrate the link in experts between problem solving and memory of specific experiences and indicate that the search for context-independent general purpose problem-solving strategies to teach to future experts is unlikely to be successful.


Advances in the Science, Treatment, and Prevention of the Disease of Obesity: Reflections From a Diabetes Care Editors' Expert Forum.
As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors' Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease.


Outcomes after minimally invasive lumbar decompression: a biomechanical comparison of unilateral and bilateral laminotomies.
The unilateral approach for bilateral decompression was developed as an alternative to laminectomy. Unilateral laminotomy has been rated technically considerably more demanding and associated with more perioperative complications than bilateral laminotomy. Several studies have indicated that bilateral laminotomy are associated with a substantial benefit in most outcome parameters and thus constituted a promising treatment alternative. However, no complete kinematic data and relative biomechanical analysis for evaluating spinal instability treated with unilateral and bilateral laminotomy are available. Therefore, the purpose of this study was to compare the stability of various decompression methods. Ten porcine lumbar spines were biomechanically evaluated regarding their strain and range of motion, and the results were compared following unilateral or bilateral laminotomies and laminectomy. The experimental protocol included flexion and extension in the following procedures: intact, unilateral or bilateral laminotomies (L2-L5), and full laminectomy (L2-L5). The spinal segment kinematics was captured using a motion tracking system, and the strain was measured using a strain gauge. No significant differences were observed during flexion and extension between the unilateral and bilateral laminotomies, whereas laminectomy yielded statistically significant findings. Regarding strain, significant differences were observed between the laminectomy and other groups. These results suggest that laminotomy entails higher spinal stability than laminectomy, with no significant differences between bilateral and unilateral laminotomies. The laminectomy group exhibited more instability, including the index of the range of motion and strain. However, bilateral laminotomy seems to have led to stability similar to that of unilateral laminotomy according to our short-term follow-up. In addition, performing bilateral laminotomies is easier for surgeons than adopting a unilateral approach for bilateral decompression. The results provide recommendations for surgeons regarding final decision making. Future studies conducting long-term evaluation are required.


Detection by action: neuropsychological evidence for action-defined templates in search.
How do we detect a target in a cluttered environment? Here we present neuropsychological evidence that detection can be based on the action afforded by a target. A patient showing symptoms of unilateral neglect following damage to the right fronto-temporal-parietal region was slow and sometimes unable to find targets when they were defined by their name or even by a salient visual property (such as their color). In contrast, he was relatively efficient at finding a target defined by the action it afforded. Two other patients with neglect showed an opposite pattern; they were better at finding a target defined by its name. The data suggest that affordances can be effective even when a brain lesion limits the use of other properties in search tasks. The findings give evidence for a direct pragmatic route from vision to action in the brain.