Adiposity Mediates the Association between the Dietary Inflammatory Index and Markers of Type 2 Diabetes Risk in Middle-Aged Black South African Women.
The dietary inflammatory index (DII®), a validated tool used to measure the inflammatory potential of the diet, has been associated with metabolic disorders in various settings, but not in African populations. The aim of this study was to investigate whether the DII is associated with markers of type 2 diabetes (T2D) risk, and if this association is mediated by adiposity and/or low-grade inflammation, in black South Africa women. Energy-adjusted-DII (E-DII) scores were calculated in 190 women (median age, 53 years) from the Birth-to-Twenty plus cohort using a validated food frequency questionnaire. Fasting glucose, insulin, HbA1c, and inflammatory cytokines were measured, and an oral glucose tolerance test performed. Basic anthropometry and dual-energy x-ray absorptiometry-derived body fat, including estimate of visceral adipose tissue (VAT) area, were measured. E-DII scores were associated with all markers of T2D risk, namely, fasting glucose and insulin, HbA1c, HOMA2-IR, two-hour glucose and Matsuda index (all p < 0.05). After adjusting for age, measures of adiposity, but not inflammatory cytokines, mediated the association between E-DII and markers of T2D risk (p < 0.05). Measures of central obesity had proportionally higher (range: 23.5-100%) mediation effects than total obesity (range: 10-60%). The E-DII is associated with T2D risk through obesity, in particular central obesity, among black middle-aged South African women.


Uncovering Offshore Financial Centers: Conduits and Sinks in the Global Corporate Ownership Network.
Multinational corporations use highly complex structures of parents and subsidiaries to organize their operations and ownership. Offshore Financial Centers (OFCs) facilitate these structures through low taxation and lenient regulation, but are increasingly under scrutiny, for instance for enabling tax avoidance. Therefore, the identification of OFC jurisdictions has become a politicized and contested issue. We introduce a novel data-driven approach for identifying OFCs based on the global corporate ownership network, in which over 98 million firms (nodes) are connected through 71 million ownership relations. This granular firm-level network data uniquely allows identifying both sink-OFCs and conduit-OFCs. Sink-OFCs attract and retain foreign capital while conduit-OFCs are attractive intermediate destinations in the routing of international investments and enable the transfer of capital without taxation. We identify 24 sink-OFCs. In addition, a small set of five countries - the Netherlands, the United Kingdom, Ireland, Singapore and Switzerland - canalize the majority of corporate offshore investment as conduit-OFCs. Each conduit jurisdiction is specialized in a geographical area and there is significant specialization based on industrial sectors. Against the idea of OFCs as exotic small islands that cannot be regulated, we show that many sink and conduit-OFCs are highly developed countries.


Association of Volumetric Epicardial Adipose Tissue Quantification and Cardiac Structure and Function.
Background Epicardial adipose tissue ( EAT ) is in immediate apposition to the underlying myocardium and, therefore, has the potential to influence myocardial systolic and diastolic function or myocardial geometry, through paracrine or compressive mechanical effects. We aimed to review the association between volumetric EAT and markers of myocardial function and geometry. Methods and Results PubMed, Medline, and Embase were searched from inception to May 2018. Studies were included only if complete EAT volume or mass was reported and related to a measure of myocardial function and/or geometry. Meta-analysis and meta-regression were used to evaluate the weighted mean difference of EAT in patients with and without diastolic dysfunction. Heterogeneity of data reporting precluded meta-analysis for systolic and geometric associations. In the 22 studies included in the analysis, there was a significant correlation with increasing EAT and presence of diastolic dysfunction and mean e' (average mitral annular tissue Doppler velocity) and E/e' (early inflow / annular velocity ratio) but not E/A (ratio of peak early (E) and late (A) transmitral inflow velocities), independent of adiposity measures. There was a greater EAT in patients with diastolic dysfunction (weighted mean difference, 24.43 mL; 95% confidence interval, 18.5-30.4 mL; P<0.001), and meta-regression confirmed the association of increasing EAT with diastolic dysfunction ( P=0.001). Reported associations of increasing EAT with increasing left ventricular mass and the inverse correlation of EAT with left ventricular ejection fraction were inconsistent, and not independent from other adiposity measures. Conclusions EAT is associated with diastolic function, independent of other influential variables. EAT is an effect modifier for chamber size but not systolic function.


The identification of an endonuclease that cleaves within an HuR binding site in mRNA.
Messenger RNAs (mRNAs) that contain U-rich elements are targeted for rapid decay. Selective inhibition of this decay results in a rapid increase in steady state level. Thus, this is an important regulatory step in gene expression. Previously, we have found that these mRNAs are selectively stabilized by a specific mRNA binding protein called HuR. The mechanism of action of HuR is not well understood. It has been postulated that HuR stabilizes mRNA by the displacement or inhibition of factors that specifically cleave or deadenyl-ate these mRNAs. In this paper, we report the identification and characterization of a novel endo-nuclease that cleaves within an HuR binding site in p27kip1 mRNA. The specificity of this endonuclease and its inhibition by HuR argue for it playing a role in the postranscriptional regulation of gene expression.


Emergency contraception counseling: an opportunity for pharmacists.
To determine the impact of pharmacist counseling on patients' knowledge of emergency contraception (EC). Single-group, repeated-measures analysis. Academic medical center women's clinic in Little Rock, AR, between January and July 2010. 116 women 18 years or older. 10-minute education session provided by a pharmacist or trained student pharmacist. Change in participants' test scores (range 0 [lowest possible] to 13 [highest possible]) at three assessment periods (pretest, posttest, and follow-up) using 12 knowledge questions. 116 participants with a mean (±SD) age of 25 ± 5.9 years participated in this study. Mean knowledge scores were 5.3 ± 4.1 for the pretest and 10.7 ± 1.4 for the posttest (P < 0.001). The least-squares mean EC knowledge test score (adjusted for demographics) was 5.86 at pretest, 10.75 at posttest, and 10.75 at follow-up. A nonsignificant small change in scores from posttest to follow-up was detected after the Tukey-Kramer adjustment. A higher education level was associated with higher knowledge scores in this population. Brief pharmacist-driven counseling sessions provided in a clinic setting are feasible and have a positive impact on immediate EC knowledge and long-term knowledge retention.


Advanced Spatially Specific Neurofeedback for Symptoms of Depression and Its Electroencephalographic Correlates.
Biofeedback is a type of neurofeedback that delivers a graphical knowledge rich in multimedia for the brain waves and produces a feedback signal on brain activity using the multimedia skills of computers and, thus, teaches self-regulation. It has been examined as potential treatment in recent years. The aim of the present study was to recognize variations in symptoms of depression in terms of electroencephalogram (EEG) neuronal mechanisms underlying quantitative electroencephalography (QEEG) neurofeedback. An analytical study is presented that describes effective results for symptoms of depression corresponding to z-score standardized low-resolution electromagnetic tomography (sLORETA) neurofeeedback training. The pre and post Neurofeedback EEG changes were analyzed for the EEG data corresponding to single subject whose primary complaint was depressive mood. The z score sLORETA neurofeedback was concluded for total of 16 sessions. Where the protocol included surface z score training followed by sLORETA z- score training with identified region of interest. This investigation was focused on examining the changes in brain activities for 16 sessions of neurofeedback using the EEG measures of relative power variations in frequency bands, frontal alpha asymmetry, and QEEG analysis of EEG brain waves. Even though impressive results were observed for neurofeedback in terms of power variations and QEEG analysis, no clear conclusions could be made about frontal alpha variations. Augmented alpha activity and reduced beta activity were observed, which accounts for the relaxation. A clear linear relation is noticeable for changes across the sessions as compared within changes within the sessions. Also, low-resolution electromagnetic tomography (LORETA) showed current sources improved toward a normative range, specifically in the insula and anterior cingulate. However, frontal alpha symmetry variations produced no significant conclusions. This may be due to medication effects, the single case design of research, to unsatisfactory denoising techniques followed in signal processing. This exploratory study in terms of EEG measurements may eventually expand the eminence of neurofeedback as an alternative to treatment of depression. The present report demonstrates the need to further investigate tomographic neurofeedback with a more rigorous randomized controlled trial with a large effect size and using other EEG measures.


Defining coronary artery calcium concordance and repeatability - Implications for development and change: The Dallas Heart Study.
Development and change of coronary artery calcium (CAC) are associated with coronary heart disease. Interpretation of serial CAC measurements will require better understanding of changes in CAC beyond the variability in the test itself. Dallas Heart Study participants (2888) with duplicate CAC scans obtained minutes apart were analyzed to determine interscan concordance and 95% confidence bounds (ie: repeatability limits) for each discrete CAC value. These data derived cutoffs were then used to define change above measurement variation and determine the frequency of CAC development and change among 1779 subjects with follow up CAC scans performed 6.9 years later. Binary concordance (0 vs. >0) was 91%. The value of CAC denoting true development of CAC by exceeding the 95% confidence bounds for a single score of 0 was 2.7 Agatston units (AU). Among those with scores >0, the 95% confidence bounds for CAC change were determined by the following formulas: for CAC≤100AU: 5.6√CAC + 0.3*CAC - 3.1; for CAC>100AU: 12.4√CAC - 67.7. Using these parameters, CAC development occurred in 15.0% and CAC change occurred in 48.9%. Although 225 individuals (24.9%) had a decrease in CAC over follow up, only 1 (0.1%) crossed the lower confidence bound. Compared with prior reported definition of CAC development (ie: >0), the novel threshold of 2.7AU resulted in better measures of model performance. In contrast, for CAC change, no consistent differences in performance metrics were observed compared with previously reported definitions. There is significant interscan variability in CAC measurement, including around scores of 0. Incorporating repeatability estimates may help discern true differences from those due to measurement variability, an approach that may enhance determination of CAC development and change.


Development of connections within and between areas V1 and V2 of macaque monkeys.
We have investigated the development of intrinsic and interareal connections in areas V1 and V2 of the macaque monkey using postmortem transport of the lipophilic fluorescent tracer diI, applied to brains fixed at different pre- and postnatal ages. Intrinsic connections in the deep layers of V1 are evident on embryonic day 108 (E108), but are not robust in the superficial layers until around E118, when migration is largely complete. Both intrinsic horizontal projections and extrinsic projections to V2 initially have a continuous distribution. Patchy projections are first evident in V1 around E145, the same age at which cytochrome oxidase blobs appear, presumably signaling the differentiation of the blob-dominated and interblob-dominated streams in the primary visual cortex. The magnocellular-dominated stream becomes distinct at earlier stages (by E122), as judged by connectional and histochemical criteria. In area V2, intrinsic connections initially (at E108) involve only deep layer cells and do not have a clustered organization. By E130, superficial layer cells are involved and the V2 intrinsic connections have a patchy distribution; by E145, an adult-like pattern is present. The projection from V2 to V1 passes through an early stage (up to E133) of originating principally from deep layer cells, and thereafter originating from superficial as well as deep layers. We found evidence for changes in dendritic morphology during development. Most notably, at E118, many neurons in layer 6 which are involved in intrinsic or interareal connections have dendrites that extend well into the superficial layers, even into layer 1, a characteristic not reported in the adult.


Death occurring within one week of cardiac transplantation: findings in eight patients.
Between October 1982 and July 1988, 85 patients underwent orthotopic heart transplantation at Methodist Hospital of Indiana. Excluding perioperative deaths, survival rates at six months, one year, two years and three years were 94%, 80%, 74% and 61%, respectively. However, eight patients (9.4%) died within one week of the transplantation. Causes of death included acute failure of the right side of the heart in four patients; compression of the proximal portions of the coronary arteries in one patient; hyperacute rejection in one patient; acute pneumonia and the adult respiratory distress syndrome in one patient; and sudden death of unknown etiology in one patient. The varied causes of death in this group of patients made it inaccurate to assume a particular cause of death for an individual patient, based on the length of the postoperative period alone. We reviewed these eight deaths in detail to better understand and, therefore, reduce the risk of early postoperative death in future patients.


Congenital microhydranencephalus in cattle.
Hydranencephaly with porencephalic cavitation of the cerebellum was diagnosed, over a 2-year period, in five calves from an 80-cow herd. Affected calves were blind and exhibited fine head tremors and limb rigidity. Bovine virus diarrhea-mucosal disease (BVD-MD) antigens, found in the tissues of two calves, were considered to be the likely cause.


["Hepatitis" following halothane-anesthesia (author's transl)].
"Hepatitis" following halothane-anesthesia is a rare complication, occurring once after about 2500 halothane-anaesthesias. The mortality is estimated to be 20-25%. The disease can be diagnosed by exclusion of other causes only. The differential diagnosis of postoperative jaundice is therefore briefly reviewed. Three hypotheses of possible pathogenic mechanisms are discussed, namely the theory of toxic products of the metabolism of halothane, the theory of delayed hypersensitivity to a metabolite and the theory of coincidence with preexisting unknown liver disease. None of these theories has been proved definitely. The use of halothane is contraindicated if a patient suffered from unexplained pyrexia and jaundice after a previous exposure to halothane. Gamma radiation decomposes halothane to hexachlorofluorobutene, a know hepatotoxin. The repeated use of halothane during irradiation therapy is therefore contraindicated. The risk of "hepatitis" after halothane anaesthesia increases if the patient is exposed to halothane twice within four weeks, especially if he is obese and older than 40 years. The risks and advantages of repeated halothane exposures have to be weighed against the risks of alternative techniques. The increased mortality after repeated anaesthesias within short periods of time, irrespective of the technique used, has to be considered.


Non-cell-autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse.
The OTX2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, which projects to limbic structures controlling complex behaviors. OTX2 is also produced in choroid plexus epithelium, from which it is secreted into cerebrospinal fluid and transferred to limbic structure parvalbumin interneurons. Previously, adult male mice subjected to early-life stress were found susceptible to anxiety-like behaviors, with accompanying OTX2 expression changes in ventral tegmental area or choroid plexus. Here, we investigated the consequences of reduced OTX2 levels in Otx2 heterozygote mice, as well as in Otx2+/AA and scFvOtx2tg/0 mouse models for decreasing OTX2 transfer from choroid plexus to parvalbumin interneurons. Both male and female adult mice show anxiolysis-like phenotypes in all three models. In Otx2 heterozygote mice, we observed no changes in dopaminergic neuron numbers and morphology in ventral tegmental area, nor in their metabolic output and projections to target structures. However, we found reduced expression of parvalbumin in medial prefrontal cortex, which could be rescued in part by adult overexpression of Otx2 specifically in choroid plexus, resulting in increased anxiety-like behavior. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of anxiety-related phenotypes in the mouse.


Set up and run a thrombolysis service for acute stroke.
Intravenous thrombolysis significantly improves the chance of independent recovery from ischaemic stroke but its benefit is strongly time dependent: present evidence supports effectiveness when delivered up to 4.5 h after symptom onset but the chance of recovery is twice as great when it is given within 90 min compared with 3-4.5 h. Delivery of treatment to a high proportion of patients is possible but requires clinicians to optimise systems for patient transfer, clinical and radiological assessment. A high proportion of patients with stroke already present to UK hospitals within the treatment time window even without specific public awareness or prehospital triage. Establishing a service requires dialogue with all those involved in the patient pathway, including ambulance dispatchers, paramedics, emergency department staff, radiology and colleagues in acute medicine. Most acute stroke teams cross traditional medical disciplines. Thrombolysis should ideally be delivered within an integrated service that seamlessly includes acute stroke unit care and rehabilitation.


Clinical and haematological features of haemangiosarcoma in dogs.
Canine haemangiosarcoma was studied retrospectively in 31 cases recorded among 2,871 dogs presented for necropsy (1.08%). The German Shepherd breed was more frequently represented than other breeds. Affected dogs were older than 5 years (mean 9.1 years). Nineteen were males. Presenting signs often included episodic lethargy and weakness, with depression, anorexia and mucosal pallor. Spleen and lungs were the most frequently affected sites. Haematological findings in 9 dogs with splenic or hepatic haemangiosarcoma included a mild to moderate normochromic anaemia, neutrophilia, thrombocytopaenia, poikilocytosis and increased target cells. Acanthocytes occurred in 90% of cases, schizocytes in 80% and keratocytes and metarubyricytes in 70%. Fibrin split products were increased in 2 of the 3 cases in which they were measured. The changes in erythrocyte morphology are considered to be useful diagnostic features of canine haemangiosarcoma.


The effects of heat induction and the siRNA biogenesis pathway on the transgenerational transposition of ONSEN, a copia-like retrotransposon in Arabidopsis thaliana.
Environmental stress influences genetic and epigenetic regulation in plant genomes. We previously reported that heat stress activated a copia-like retrotransposon named ONSEN. To investigate the heat sensitivity and transgenerational activation of ONSEN, we analyzed the stress response by temperature shift and multiple heat stress treatments. ONSEN was activated at 37°C, and the newly inserted ONSEN was transcriptionally active and mobile to the next generation subjected to heat stress, indicating that the regulation of ONSEN is independent of positional effects on the chromosome. Reciprocal crosses with activated ONSEN revealed that the transgenerational transposition was inherited from both sexes, indicating that the transposition is suppressed independently of gametophytic regulation. We showed previously that ONSEN was transposed in mutants deficient in small interfering RNA (siRNA) biogenesis, including nrpd2 and rdr2, but not dcl3. To define the functional redundancy of Dicer-like (DCL) proteins in Arabidopsis, we analyzed ONSEN activation in mutants deficient in DCL proteins, including dcl2, dcl3 and dcl4. ONSEN was nearly immobile in a single Dicer mutant; however, some transgenerational transpositions were observed in dcl2/dcl3/dcl4 triple mutants subjected to heat stress. This indicated that the Dicer family is redundant for ONSEN transposition. To examine the activation of ONSEN in undifferentiated cells, ONSEN transcripts and synthesized DNA were analyzed in heat-stressed callus tissue. In contrast to vegetative tissue, high accumulation of the transcripts and amplified DNA copies of ONSEN were detected in callus. This result indicated that ONSEN activation is controlled by cell-specific regulatory mechanisms.


Differential Serum Cytokine Levels and Risk of Lung Cancer Between African and European Americans.
African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races. Differences in 10 serum cytokine levels, IL1β, IL4, IL5, IL6, IL8, IL10, IL12, granulocyte macrophage colony-stimulating factor, IFNγ, and TNFα, between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the Wayne State University Karmanos Cancer Institute case-control study. Six cytokines, IL4, IL5, IL8, IL10, IFNγ, and TNFα, were significantly higher among European-American as compared with African-American controls. Elevated IL6 and IL8 levels were associated with lung cancer among both races in all three studies. Elevated IL1β, IL10, and TNFα levels were associated with lung cancer only among African Americans. The association between elevated TNFα levels and lung cancer among European Americans was significant after adjustment for additional factors. Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans. Future work examining risk prediction models of lung cancer can measure circulating cytokines to accurately characterize risk within racial groups.


Ghrelin agonist TZP-101/ulimorelin accelerates gastrointestinal recovery independently of opioid use and surgery type: covariate analysis of phase 2 data.
Delayed recovery of gastrointestinal (GI) motility is a common complication following surgery. TZP-101/ulimorelin is a macrocyclic peptidomimetic ghrelin receptor agonist with GI promotility effects that significantly accelerates time to recovery of GI motility compared to placebo following partial colectomy. It is also well tolerated. The objectives of this analysis were to identify predictors of GI motility recovery in patients undergoing partial colectomy and to evaluate whether these factors affect ulimorelin acceleration of GI recovery. Covariate analysis assessed the effect of eight variables-age, sex, body mass index, type of surgery (right colectomy, left colectomy, other), duration of surgery, blood loss, total opioid consumption, country-on recovery of GI motility in 236 patients randomized to ulimorelin (n = 168) or placebo (n = 68). The primary endpoint was the recovery of GI function (time from the end of surgery to first bowel movement). Stepwise regression identified a parsimonious model of the smallest subset of variables best predicting GI recovery. Recovery was shorter for segmental/subtotal colectomies vs. right colectomies (P = 0.016) and longer with increased total opioid use (P = 0.037). The remaining variables had no statistically significant effect on GI recovery. Effects of ulimorelin 480 μg/kg (the most effective dose) on time to GI tract recovery remained statistically and clinically significant (hazard ratio = 1.81, P = 0.014) when adjusted for surgery type and/or total opioid use. Two factors, type of surgery and total opioid use, independently modified times to recovery of GI motility following partial large bowel resection surgery. Acceleration of recovery of GI motility by ulimorelin was independent of these factors.


Ulcerative tracheobronchitis after lung transplantation. A new form of invasive aspergillosis.
Invasive aspergillosis is frequently a fatal disease in the setting of immunosuppression, including organ transplant recipients. The fungus usually affects lung parenchyma and may disseminate from there. We have recently noted tracheobronchitis in six patients with heart-lung and lung transplants, three of whom had deep mucosal ulceration and histologic evidence of invasive aspergillosis. This apparently new form of invasive disease is initially limited to the anastomosis site and large airways. Ulceration, necrosis, cartilage invasion, and formation of a pseudomembrane are the pathologic features. In two patients subsequent disseminated aspergillosis occurred with a fatal outcome. In the two single-lung recipients, disease was limited to the transplanted side emphasizing the importance of abnormal local defense mechanisms in the airways of lung transplant recipients. Routine bronchoscopic examination of the airways is important in early detection of this complication. Oral therapy with the new, antifungal agent itraconazole was successful in five of the six patients, with fatal relapse in one. A classification of the various forms of saprophytic, allergic, and invasive forms of aspergillus tracheobronchitis, to include this new entity, is proposed.


A simplified method of protein electroblotting after isoelectric focusing on an ultrathin polyacrylamide gel layer fixed on a cellophane support.
A method is described for isoelectric focusing of proteins, using an ultrathin-layer polyacrylamide gel on cellophane, followed by electrophoretic transfer of separated proteins onto a nitrocellulose membrane. The polyacrylamide gel is firmly attached to the cellophane and thus protected from mechanical damage; such gels are easily manipulated. Cellophane is permeable to ions and application of this gel support overcomes difficulties resulting from the removal of ultrathin gels from a plastic support on electroblotting. Proteins separated under nondenaturing conditions were transferred onto a nitrocellulose membrane and detected by the concanavalin A-peroxidase technique. The proposed approach makes it possible to analyze the variability of nondenatured proteins and glycoproteins of different origin.


Relationships in nurse prescribing in district nursing practice in England: a preliminary investigation.
Nurse prescribing is a significant change in the working lives of district nurses in the United Kingdom. It has been achieved as the result of a 13-year sociopolitical struggle, eventually culminating in an Act of Parliament, which enabled selected nurses to prescribe from a limited formulary. This research attempts to discover the nature of its impact on the relationships between prescribers, nurses, doctors, pharmacists, patients and carers. Using a qualitative approach, guided interviews were carried out with nurses, doctors, pharmacists, patients and carers. Initial findings indicate that far from producing an independent prescribing workforce, some prescribers are reverting to their preprescribing behaviour. For these prescribers, there is a suggestion that old hierarchies are being reinforced, which might be detrimental to nurse prescribing.


Assessing the Contribution of Songbirds to the Movement of Ticks and Borrelia burgdorferi in the Midwestern United States During Fall Migration.
The geographic distributions of Ixodes scapularis (black-legged tick) and the bacterium Borrelia burgdorferi (the causative agent of Lyme disease) are expanding in the USA. To assess the role of migratory songbirds in the spread of this tick and pathogen, we captured passerines in central Illinois during the fall of 2012. We compared forested sites in regions where I. scapularis populations were either previously or not yet established. Ticks were removed from birds and blood samples were taken from select avian species. Ticks were identified by morphology and molecular techniques were used to detect B. burgdorferi and other tick-borne pathogens in ticks and avian blood samples. Ixodes spp. were detected on 10 of 196 migrants (5.1%), with I. scapularis larvae found on 2 individuals. Borrelia burgdorferi sensu stricto was detected in the blood of 9 of 29 birds sampled (31%), yet only 1 infected bird was infested by ticks. The ticks were mostly Haemaphysalis leporispalustris and I. dentatus larvae, and none tested positive for B. burgdorferi. Infestation of birds by Ixodes spp. differed significantly by region, while B. burgdorferi infection did not. These data suggest that migratory birds may play a larger role in the dispersal of B. burgdorferi than previously realized.


Mental Health Diagnoses among Children and Adolescents with Chronic Medical Conditions in a Large Urban Cohort.
We analyzed data for 6,458 children with chronic conditions. The most prevalent diagnoses were mood disorders (8.6%), attention deficit hyperactivity disorder (ADHD; 7.4%), conduct disorders (6.1%), and anxiety disorders (4.8%). Adjusted odds of having a mental health diagnosis increased with age for mood disorders and anxiety disorders and decreased with age for ADHD and conduct disorders. When compared with females, males had lower odds of being diagnosed with mood and anxiety disorders and higher odds of being diagnosed with ADHD and conduct disorders. Blacks had lower odds of being diagnosed with anxiety, mood disorders, and ADHD than children in the other racial category. Hispanics had lower odds of being diagnosed with ADHD than children in the other racial category. Racial/ethnic minorities were less likely to have a mental health diagnosis than children in the other race/ethnicity category, which suggests under identification of mental health needs particularly in minority children.


Circumcision and complications in patients with haemophilia in southern part of Turkey: Çukurova experience.
Circumcision is the oldest and most frequent surgical procedure in the world and especially in Turkey as is seen in the other Islamic countries because of religious and traditional pressures. In this study, we aim to report the experience of circumcision at Çukurova University in a total of 76 patients with haemophilia between 1990 and 2011. We retrospectively reviewed medical records of 69 haemophilia patients without inhibitors and seven haemophilia patients with inhibitors who had been circumcised. Before the year 2000, factor concentrates were given before and after circumcision for 6-7 days. After 2000, we used fibrin glue together with factor concentrates for only 3 days. By-passing agents were used for circumcision in haemophilia patients with inhibitors. Twelve of 69 patients without inhibitors were referred to our centre with bleeding after the circumcision before diagnosis of haemophilia. Nine of these twelve patients had severe life threatening bleeding and three of them had moderate bleeding. Sixty-four patients with haemophilia were circumcised in our centre under general anaesthesia except for three patients who were given local anaesthesia. Thirteen of 57 haemophilia patients (22.8%) without inhibitors had seven mild and six moderate bleeding complications. A few patients had significant bleeding, despite adequate factor replacement. Five of seven haemophilia patients with inhibitors had two moderate and three mild bleeding complications. Our experience showed that circumcision for patients with haemophilia should be carefully performed by surgeons together with paediatric haematologist, under appropriate conditions in haemophilia centres which has comprehensive coagulation lab.


Clusters of corneal epithelial cells reside ectopically in human conjunctival epithelium.
The ocular surface is covered by two biologically distinct epithelia: corneal and conjunctival. The expression of keratin12 (K12) is currently considered a hallmark of cornea-type differentiation. In the current study, the biological features of K12-positive cells in human bulbar conjunctival epithelium were examined. Human conjunctival tissues were subjected to investigate the K12-positive cells in conjunctiva by immunostaining, in situ hybridization, Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR), and fluorescence-activated cell sorting (FACS). Gene expression profiling of these cells was performed with introduced amplified-fragment length polymorphism (iAFLP). To determine the presence of stem- or progenitor cells, immunostaining and colony-forming assays were performed. Western blot analysis, RT-PCR revealed that K12 was expressed in conjunctival epithelium. Immunostaining analysis showed that K12-positive cells reside mainly in clusters in conjunctival epithelium. FACS analysis showed that 0.2% to 1.7% of conjunctival epithelial cells collected from the inferior bulbar conjunctiva were K12 positive. iAFLP analysis revealed that the gene expression patterns of these cells were highly similar to that of corneal epithelial cells. p63 and ABCG2 were expressed beneath the K12-positive cells. Some colony-forming cells expressed K12. The K12-positive cells appear to be ectopically residing, self-maintaining corneal epithelial cells in the conjunctival epithelium.


Shifts in morphology and diet of non-native sticklebacks introduced into Japanese crater lakes.
An increasing number of exotic animals are causing ecological problems. Therefore, for better ecosystem management, it is important to understand how exotic species colonize and adapt to novel environments. The threespine sticklebacks (Gasterosteus aculeatus) can be a good vertebrate model system to explore the ecological and genetic mechanisms of adaptation not only in natural populations, but also in non-native populations. Although morphological changes have been documented in several introduced populations of stickleback, little is known about the dietary changes during colonization into novel environments. Here, we investigated the morphological and dietary changes of exotic threespine stickleback populations introduced into three Japanese crater lakes (Lake Towada, Lake Kussharo, and Lake Shikotsu). Sticklebacks were introduced into the crater lakes likely along with salmonids transplanted for aquaculture. The stickleback population in Lake Kussharo had multiple mitochondrial haplotypes and had larger phenotypic variances than other crater lake stickleback populations that had only one mitochondrial haplotype. Compilation of historical data on the morphology and stomach contents of the Lake Towada stickleback population showed that substantial shifts in body size and stomach contents occurred after colonization. Some of these changes may be related to an outbreak of the Schistocephalus parasite. These results suggest that sticklebacks can change their morphology and trophic ecology when they colonize novel environments. Therefore, extreme care should be taken when salmonids are transported between watersheds for aquaculture and that long-term monitoring of exotic species is essential for ecosystem management. In addition, further genetic studies on phenotypic changes in crater lake sticklebacks would help elucidate the genetic mechanisms underlying the adaptation of exotic fishes to novel environments.


Sport Specialization, Club Sport Participation, Quality of Life, and Injury History Among High School Athletes.
Many factors can affect the injury risk and quality of life among high school athletes. Early sport specialization and club sport participation may be components to consider when assessing the injury risk and quality of life. To investigate patient-reported quality-of-life and injury-history measures among adolescent athletes at different sport-specialization levels and to compare these measures between those who did and those who did not report participating in club sports. Cross-sectional study. High school athletic facility. High school student athletes 13 to 18 years of age were recruited and tested during their annual preseason athletic physical examinations. Our primary grouping variables were sport-specialization level (classified as low, moderate, or high) and club sport participation (organized sport outside of traditional school athletics). Our outcome variables were the Patient-Reported Outcome Measurement Information System Pediatric Profile-37 rating, Severity Measure for Depression-Child score, and injury history. A total of 97 individuals participated (mean age = 15.2 ± 1.1 years; 38% female). Relatively similar proportions of individuals reported participating at each level of sport specialization (low = 34%, moderate = 40%, high = 26%). Forty-six (48%) participants stated they participated in club sports. No differences were evident in quality of life (P values = .15-.92 across domains), depression (P = .60), or injury history (P > .70) among the specialization groups. Those who described participating in club sports had a higher proportion of time-loss musculoskeletal injuries (63% versus 29%; P = .002) and of injuries requiring imaging, injection, a cast, a brace, or crutches (72% versus 46%; P = .013) than those who did not. Although no injury-history differences were found among the sport-specialization groups, a higher proportion of club sport athletes than nonclub sport athletes reported a history of injury. Club sports are generally seen as more competitive, and the higher number of injuries seen in this setting could be related to a higher level of play among club sport athletes.


Activated Signaling Pathways and Targeted Therapies in Desmoid-Type Fibromatosis: A Literature Review.
Desmoid-type fibromatosis (DTF) is a rare, soft tissue tumor of mesenchymal origin which is characterized by local infiltrative growth behavior. Besides "wait and see," surgery and radiotherapy, several systemic treatments are available for symptomatic patients. Recently, targeted therapies are being explored in DTF. Unfortunately, effective treatment is still hampered by the limited knowledge of the molecular mechanisms that prompt DTF tumorigenesis. Many studies focus on Wnt/β-catenin signaling, since the vast majority of DTF tumors harbor a mutation in the CTNNB1 gene or the APC gene. The established role of the Wnt/β-catenin pathway in DTF forms an attractive therapeutic target, however, drugs targeting this pathway are still in an experimental stage and not yet available in the clinic. Only few studies address other signaling pathways which can drive uncontrolled growth in DTF such as: JAK/STAT, Notch, PI3 kinase/AKT, mTOR, Hedgehog, and the estrogen growth regulatory pathways. Evidence for involvement of these pathways in DTF tumorigenesis is limited and predominantly based on the expression levels of key pathway genes, or on observed clinical responses after targeted treatment. No clear driver role for these pathways in DTF has been identified, and a rationale for clinical studies is often lacking. In this review, we highlight common signaling pathways active in DTF and provide an up-to-date overview of their therapeutic potential.


Prednisolone elimination in human saliva.
The elimination of prednisolone in saliva was studied following administration of intravenous doses of 16, 32, 48 and 64 mg to 7 healthy human subjects. While there was an approximate relationship between salivary and plasma concentrations of prednisolone a wide inter- and intraindividual variation in the ratio of the concentration in these two body fluids was observed. Salivary estimations of prednisolone concentration cannot replace plasma concentrations in biopharmaceutical studies.


Defective potassium currents in ataxia telangiectasia fibroblasts.
Similarities exist between the progressive cerebellar ataxia in ataxia telangiectasia (AT) patients and a number of neurodegenerative diseases in both mouse and man involving specific mutations in ion channels and/or ion channel activity. These relationships led us to investigate the possibility of defective ion channel activity in AT cells. We examined changes in the membrane potential of AT fibroblasts in response to extracellular cation addition and found that the ability of AT fibroblasts to depolarize in response to increasing concentrations of extracellular K+ is significantly reduced when compared with control fibroblasts. Electrophysiological measurements performed with a number of AT cell lines, as well as two matched sets of primary AT fibroblast cultures, reveal that outward rectifier K+ currents are largely absent in AT fibroblasts in comparison with control cells. These K+ current defects can be corrected in AT fibroblasts transfected with the full-length ATM cDNA. These data implicate, for the first time, a role for ATM in the regulation of K+ channel activity and membrane potential.


[Coordinated organization of symptoms management and support in all the stages of cancer disease: putting in place pluridisciplinary structures of supportive oncological care].
The organization of the management of pain and other symptoms all along the cancer disease, of psychological support and palliative care is a complex question that does not correspond to any perfectly established model, both in France and abroad. Different structures are implied in there care and coexist with an insufficient coordination: cancerology structures, structures of chronic pain management, structures of psycho-oncology, structures of palliative care. Some other assistances are more or less isolated inside the hospital: nutritional support, social assistance, action against tobacco and other addictions, volunteer work. Because of the evolution of practices and mentalities over the last ten years, the highlights of evident interfaces and complementary activities, the notions of "continuous care" and "integrated care" inside conventional departments, the budgetary and organizational restraints, it is now possible to propose a model of hospital structure adapted to the problem of supportive care. The creation is proposed from preexisting structures, consultations, units, departments of supportive oncological care according to the size of the institution. The structure should comply with some specifications, sometimes regulations, and to coordinate at best different competencies in the interest of the patients and medical teams : pain and symptoms management (of which palliative care is an important part), psycho-oncology, rehabilitation (functional rehabilitation, nutrition, social work, fights against addictions). A pooling of technology settings is one of its interest. The model can be applied in other domains than cancerology and in most health institutions.


Immunocytochemical identification of type I collagen in acid-etched dentin.
The hypothesis tested in this study is that the application of phosphoric acid prevents collagen fibrils (CF) from maintaining their structural morphology, as assessed by their immunochemical antigenicity. Dentin was conditioned with EDTA and with 35% H3PO4 for 15, 30, and 60 s. For a control there was no treatment. A pre-embedding immunohistochemical procedure was evaluated under high-resolution SEM and a postembedding immunolocalization technique was performed on ultrathin sections at TEM level. Conditioning with EDTA resulted in a weaker labeling signal than for dentin conditioned with H3PO4. The most intense labeling was observed after dentin had been etched with H3PO4 for 15 s. The least intensive labeling was evident when the acid was applied for 30 s or for 60 s. A very weak signal was detected on the untreated dentin surface. These results provide evidence that a 15-s application of 35% H3PO4 causes mineral dissolution of the crystals enveloping the superficial CF without damaging the ultrastructure of the CF while longer applications of 35% H3PO4 cause alterations in the CF that decrease their antigenicity.


A new mermithid species (Nematoda) from chironomid imagos eclosing from Lake Ozawindib in northern Minnesota.
Hydromermis biesboeri n. sp. (Nematoda: Mermithidae) is described from the hemocoel of imagos of chironomid host species eclosing from Lake Ozawindib in northern Minnesota in July and August 2008 and 2009. The new species is distinguished from the other 28 described species in the genus by terminal mouth, wide oval (male) and long oval (female) amphids with a dorsal commissure, tapered and rounded posterior ends, split base of the spicule, short protractor muscles in males, and by females having an S-shaped vagina with equal-length terminal limbs. The new species represents the 10th Hydromermis mermithid species described, or reported, from the region and the second from Lake Ozawindib.


[Weight loss, joint pain and abdominal lymphadenopathy as signs of sarcoidosis, but also of Whipple's disease].
Two patients, a woman aged 66 and a man aged 56 years, with an inflammatory syndrome, weight loss, joint pain and abdominal lymphadenopathy received long-term treatment with corticosteroids for alleged sarcoidosis. No long-term remission was induced and the patients were referred for a second opinion. Eventually the diagnosis of Whipple's disease was established 5 years after the appearance of the first symptoms in the case of the female patient and 4 years after in the case of the male patient. Both patients showed a marked clinical improvement after treatment with trimethoprim-sulfamethoxazole. An atypical presentation of alleged sarcoidosis should suggest the possibility of Whipple's disease, especially in the case of gastrointestinal symptoms and the failure to respond to corticosteroids, and warrants duodenal biopsy. The presence of granulomas with an elevated angiotensin-converting enzyme level is not pathognomonic for sarcoidosis. It is vitally important to distinguish the two disorders, as Whipple's disease is an infectious disorder that requires antibiotic therapy to prevent a fatal outcome.


Efficiency Loss Caused by Linearity Condition in Dimension Reduction.
Linearity, sometimes jointly with constant variance, is routinely assumed in the context of sufficient dimension reduction. It is well understood that, when these conditions do not hold, blindly using them may lead to inconsistency in estimating the central subspace and the central mean subspace. Surprisingly, we discover that even if these conditions do hold, using them will bring efficiency loss. This paradoxical phenomenon is illustrated through sliced inverse regression and principal Hessian directions. The efficiency loss also applies to other dimension reduction procedures. We explain this empirical discovery by theoretical investigation.


Zenker's diverticulum treated by the endoscopic stapling technique.
The objective of the present study is to determine whether the endoscopic stapling technique for the treatment of Zenker's diverticulum provides a relief of symptoms and an acceptably low number of complications. Previous studies have indicated that endoscopic stapling of the common wall between the oesophagus and the diverticulum is a safe and effective method that has a low complication rate and only necessitates a few days of hospitalization. To the present only a few investigations including a limited number of patients have reported the clinical outcome with regard to relief of symptoms and degree of satisfaction in a group of patients treated with this new approach. Twenty-three consecutive patients with Zenker's diverticulum treated with endoscopic staple-assisted oesophagodiverticulotomy were investigated. The median age was 70 years and the median observation time was 12 months. All patients but one (96%), reported significant relief of symptoms and 76% had no symptoms at all at the time of follow-up. In one patient, a postoperative episode of uncomplicated fever occurred, which was managed successfully with gastric tube and antibiotics. Most patients resumed oral intake of fluids and foods within the first postoperative day. The high degree of patient satisfaction, the low rate of complications and the few recurrences of symptoms reported in the present study indicate that the endoscopic stapling technique is an efficient and reliable treatment for Zenker's diverticulum.


High Survivorship and Few Complications With Cementless Total Wrist Arthroplasty at a Mean Followup of 9 Years.
Total wrist arthroplasty (TWA) has been described as traditionally being performed with fixation in the radius and carpus with cement. The TWA implant used in our series has been associated with promising results in studies with up to 6 years followup; however, studies evaluating survivorship, pain, and function with this implant are limited. QUESTION/PURPOSE: (1) To report ROM and pain scores after wrist reconstruction with cementless fourth-generation TWA at a mean followup of 9 years (range, 4.8-14.7 years). (2) To report complications of a cementless fourth-generation TWA and the cumulative probability of not undergoing a revision at a mean followup of 9 years. This is a retrospective case series of 69 patients who were treated for pancarpal wrist arthritis between 2002 and 2014. Of those, 31 had inflammatory arthritis (rheumatoid arthritis [n = 29], juvenile rheumatoid arthritis [n = 1], and psoriatic arthritis [n = 1]); all of these patients received TWA with the cementless implant studied in this investigation. Another 38 patients had osteoarthritis or posttraumatic arthritis; in this subgroup, 28 patients were 65 years or younger, and all underwent wrist fusion (none were offered TWA). Ten patients with osteoarthritis were older than 65 years and all were offered TWA; of those, eight underwent TWA, and two declined the procedure and instead preferred and underwent total wrist arthrodesis. The mean age of the 39 patients who had TWA was 56 ± 8.9 years (range, 31-78 years) at the time of surgery; 36 were women and three were men. The patients who underwent TWA were seen at a minimum of 4 years (mean, 9 years; range, 4-15 years), and all had been examined in 2016 as part of this study except for one patient who died 9 years after surgery. The dominant wrist was involved in 60% (25) of the patients. All patients were immobilized for 4 weeks postoperatively and then underwent hand therapy for 4 to 6 weeks. Pain and ROM were gathered before surgery as part of clinical care, and were measured again at latest followup; at latest followup, radiographs were analyzed (by the senior author) for evidence of loosening, defined as any implant migration compared with any previous radiograph with evidence of periimplant osteolysis and bone resorption. Subjective pain score was assessed by a verbal pain scale (0-10) and ROM was measured with a goniometer. Complications were determined by chart review and final examination. Kaplan Meier survival analysis was performed to estimate the cumulative probability of not undergoing a revision. The mean preoperative active ROM was 34o ± 18° flexion and 36° ± 18° extension. Postoperatively, the mean active ROM was 37° ± 14° flexion and 29° ± 13° extension. The mean difference between the preoperative pain score (8.6 ± 1.2) and postoperative pain score (0.4 ± 0.8) was 8.1 ± 1.9 (p < 0.001). Implant loosening occurred in three (7.7%) patients. No other complications occurred in this series. Kaplan-Meier survivorship analysis estimated the cumulative probability of remaining free from revision as 78% (95% CI, 62%-91%) at 15 years. Cementless fourth-generation TWA improves pain while generally preserving the preoperative arc of motion. The cumulative probability of remaining free from revision at 14.7 years after the index procedure is 77.7% (95% CI, 62.0%-91.4%). Future studies should compare alternative approaches for patients with endstage wrist arthritis; such evaluations-which might compare TWA implants, or TWAs with arthrodesis-will almost certainly need to be multicenter, as the problem is relatively uncommon. Level IV, therapeutic study.


Cell receptors for the mammalian reovirus. II. Monoclonal anti-idiotypic antibody blocks viral binding to cells.
A monoclonal anti-idiotypic antibody directed against an idiotypic determinant on a monoclonal anti-reovirus type 3 hemagglutinin antibody with viral neutralization activity is capable of binding to the surface of lymphoid cells (BW5147, R.1.1, and R1.E) and of inhibiting viral binding to cell surface receptors. The inhibition of viral binding was specific for the anti-idiotype antibody; viral binding was not inhibited by antibodies bound to the H-2k and Thy-1.2 antigens on the surface. Viral binding to idiotype-negative cells (P-815, EL-4) was not inhibited by the anti-idiotypic antibody, although these cells are susceptible to type 3 reovirus infection. These data suggest that there are at least two structural classes of type 3 reovirus receptors on murine cells. It is probable that anti-idiotypic antibodies of this type will be useful in studying the structure and regulation of viral receptors on cell surfaces and for the purification of these receptors, and may provide a way to block viral infection.


Prevalence of hypogonadism in males aged at least 45 years: the HIM study.
The Hypogonadism in Males study estimated the prevalence of hypogonadism [total testosterone (TT) < 300 ng/dl] in men aged > or = 45 years visiting primary care practices in the United States. A blood sample was obtained between 8 am and noon and assayed for TT, free testosterone (FT) and bioavailable testosterone (BAT). Common symptoms of hypogonadism, comorbid conditions, demographics and reason for visit were recorded. Of 2162 patients, 836 were hypogonadal, with 80 receiving testosterone. Crude prevalence rate of hypogonadism was 38.7%. Similar trends were observed for FT and BAT. Among men not receiving testosterone, 756 (36.3%) were hypogonadal; odds ratios for having hypogonadism were significantly higher in men with hypertension (1.84), hyperlipidaemia (1.47), diabetes (2.09), obesity (2.38), prostate disease (1.29) and asthma or chronic obstructive pulmonary disease (1.40) than in men without these conditions. The prevalence of hypogonadism was 38.7% in men aged > or = 45 years presenting to primary care offices.


[UV-light-tested protein--DNA interactions in the nuclei during the cell cycle in Physarum polycephalum].
The release of DNAs from nuclear preparations isolated at different steps of the cell cycle of the synchronous culture of Physarum polycephalum and irradiated with UV-light for 5 min (lambda 253.7 A, i = 1.8 . 10(2) j . m-2 . min-1) into 1% Na-DS - 1.5 M NaCl solution was studied. The value obtained correlated well with the degree of binding of interacting proteins with DNA in chromatin and was identical for all the preparations tested with the only exception of the nuclei isolated at the end of the S-phase, when a slight but significant (15 +/- 10%) increase in DNA release was observed. The results obtained are discussed in terms of structural transitions and function of chromatin during the cell cycle of the myxomycete Physarum polycephalum.


Clinical utility of dual-energy vertebral assessment (DVA).
The current study was undertaken to evaluate the clinical utility of DVA, a system for imaging the lateral spine on the Lunar Prodigy densitometer. DVA images were obtained and bone density of the lumbar spine and proximal femur measured in 297 subjects (272 women), aged 64+/-13 years. The images were classified as: normal (N) if no fractures were detected and all vertebrae between T6 and L4 were visualized, fracture (F) if any vertebra had a fracture (defined as 25% or more reduction in the vertebral height) even if some of the other vertebrae could not be visualized, and un-interpretable (U) if at least one of the vertebra between T6 and L4 could not be classified and no fractures were detected in the visualized vertebrae. A subset of 66 patients also had standard radiographs of the thoracic and lumbar spine. Compared to radiographs, DVA had a 95% sensitivity to detect fractures and 82% specificity (to exclude them). Among all 297 subjects studied, DVAs were interpretable in 87%. They were classified as N in 204 (68%), F in 55 (19%) and U in 38 (13%). The reasons for un-interpretability were: scoliosis, scapular or rib shadow, severe arthritic changes and multiple vertebral compression fracture with severe spinal deformities. Only 11% of F subjects gave a history of a vertebral fracture, and only 56% of F subjects met the BMD criteria for osteoporosis (T score <-2.5). These results indicate that adding DVA, a low radiation and relatively low cost "point of service" procedure, to BMD measurement provides the clinician with a more comprehensive fracture risk assessment than that afforded by clinical evaluation and BMD measurement alone.


Patient perception of anticoagulant treatment for stroke prevention (RE-SONANCE study).
We evaluated atrial fibrillation (AF) patients' perceptions of anticoagulation treatment with dabigatran or a vitamin K antagonist (VKA) for stroke prevention, according to accepted indications. The RE-SONANCE observational, prospective, multicentre, international study used the validated Perception on Anticoagulant Treatment Questionnaire (PACT-Q) to assess patients with AF already taking a VKA who were switched to dabigatran (cohort A), and newly diagnosed patients initiated on either dabigatran or a VKA (cohort B). Visit 1 (V1) was at baseline, and visit 2 (V2) and visit 3 (V3) were at 30-45 and 150-210 days after baseline, respectively. Primary outcomes were treatment satisfaction and convenience in cohort A at V2 and V3 versus baseline, and in cohort B for dabigatran and a VKA at V2 and V3. The main analysis set comprised 4100 patients in cohort A and 5365 in cohort B (dabigatran: 3179; VKA: 2186). In cohort A, PACT-Q2 improved significantly (p<0.001 for all) for treatment convenience (mean change V1 vs V2=20.72; SD=21.50; V1 vs V3=24.54; SD=22.85) and treatment satisfaction (mean change V1 vs V2=17.60; SD=18.76; V1 vs V3=21.04; SD=20.24). In cohort B, mean PACT-Q2 scores at V2 and V3 were significantly higher (p<0.001 for all) for dabigatran versus a VKA for treatment convenience (V2=18.38; SE =0.51; V3=23.34; SE=0.51) and satisfaction (V2=15.88; SE=0.39; V3=19.01; SE=0.41). Switching to dabigatran from long-term VKA therapy or newly initiated dabigatran is associated with improved patient treatment convenience and satisfaction compared with VKA therapy.


In vitro studies on the mechanism of action of hepsulfam in chronic myelogenous leukemia patients.
In the present study we have characterized the cytotoxicity and DNA damage induced by hepsulfam and busulfan in cells isolated from both chronic myelogenous leukemia (CML) patients and normal donors. hepsulfam inhibited colony-forming units-granulocyte, macrophage to a greater extent than busulfan in peripheral blood cells (PBCs) isolated from CML patients. Normal PBCs were equally sensitive to both agents and were more sensitive than the cells isolated from CML patients. Hepsulfam induced DNA interstrand cross-links in PBCs and bone marrow from both CML and normal volunteers, whereas busulfan produced few or no DNA interstrand cross-links. In addition, hepsulfam induced higher levels of DNA interstrand cross-linking than busulfam in three samples isolated from CML patients in blast crisis. Busulfan did however cause a small number of DNA strand breaks to be formed in human cells. Both agents produced similar levels of DNA-protein cross-links in PBCs from CML patients. These results suggest that the mechanism of DNA reactivity of hepsulfam and busulfan differ and that hepsulfam may prove useful in the treatment of CML.


Prevalence, antimicrobial resistance, and virulence characteristics of mecA-encoding coagulase-negative staphylococci isolated from soft cheese in Brazil.
Coagulase-negative staphylococci (CoNS), which are generally neglected as foodborne bacteria, are emerging as significant opportunistic pathogens that may be highly resistant to available antimicrobial drugs. In this study, antimicrobial susceptibility patterns, mecA gene occurrence, and virulence-associated characteristics were evaluated in CoNS isolated from soft cheese in Brazil. A total of 227 bacterial isolates were recovered from 35 cheese samples belonging to 5 batches with 7 different trademarks. The CoNS counts ranged from 10(6) to 10(7) CFU/g. High antimicrobial resistance percentages were observed for oxacillin (76.2%), penicillin (78.5%), erythromycin (67.8%), gentamicin (47.2%), clindamycin (35.7%), rifampicin (26.8%), azithromycin (14.7%), tetracycline (14.7%), levofloxacin (14.2%), and sulfamethoxazole-trimethoprim (11.9%). A low antimicrobial resistance percentage was observed for chloramphenicol (2.3%), and all of the tested bacteria were susceptible to vancomycin and linezolid. In total, a multiple antibiotic resistance (MAR) index of >0.2 was observed for 80.6% of the isolated CoNS. However, the MAR index ranged from 50% to 92.6% when only bacterial cheese isolates belonging to the same trademark were considered. Regarding to the prevalence of CoNS carrying mecA gene, 81.5% of the isolated strains were mecA(+) , and 76.2% of these were phenotypically resistant to oxacillin. Three isolates carried the enterotoxin A gene (sea), 29.5% produced biofilm in a laboratory test, and α- or ß-hemolysis were observed for 3% and 5.2%, respectively. This study highlights the extent of the antimicrobial resistance phenomenon in neglected foodborne microorganisms and the potential public health risks that are related to the consumption of CoNS-contaminated soft cheese.


Knowledge, perceptions and use of generic drugs: a cross sectional study.
To assess the level of knowledge, perceptions and usage profile for generic drugs among laypersons. A cross-sectional study was conducted with 278 volunteers (180 women and 98 men, aged 37.1±15.8 years). A questionnaire was drawn up with questions on their use, perceptions and knowledge of generic drugs. Most respondents (99.6%) knew that generic drugs exist, but only 48.6% were able to define them correctly, while 78.8% of the respondents had some information about generics. This information was obtained mainly through television (49.3%). In terms of generic drug characteristics, 79.1% stated that they were confident about their efficacy, 74.8% believed that generic drugs have the same effect as branded medications, 88.8% said that generics were priced lower than branded medications, and 80.2% stated that they bought generic drugs because of price. With regard to drugs prescribed by medical practitioners, 17.6% of the participants said that their doctors never prescribed generics and only 7.5% confirmed that their doctors always prescribed generics. For the lay public, the sample in this study has sufficient knowledge of generic drugs in terms of definition, efficacy and cost. Consequently, the volunteers interviewed are very likely to use generics. Furthermore, the results of this study indicate that programs should be implemented in order to boost generic drug prescriptions by medical practitioners.


Hemocyte morphology and phagocytic activity in the common cuttlefish (Sepia officinalis).
Little is known about the immune system of cephalopods, in spite of their many highly derived characters within the molluscan clade, including a vertebrate-like high-pressure closed circulatory system. Further the economic importance of cephalopod fisheries, potential for aquaculture, and use as ecotoxicology models demand a thorough understanding of their immune system. In this study, we present a comprehensive characterization of hemocytes in the common cuttlefish Sepia officinalis. Cytological stainings, electron microscopy- and flow cytometry-observations highlight a single granulocyte population with various densities of eosinophilic granules and unstained vesicles. These hemocytes contain acid phosphatase-, lysozyme- and proPO system enzymes, and have high activity in bead phagocytosis assays. Interestingly, bead pre-incubation in plasma results in time-dependent aggregation perhaps resulting from hemocyanin-coating, and decrease in phagocytosis. This study provides the basis for understanding hemocyte-mediated immunity in the common cuttlefish, and essential background for future studies on cephalopod immunity.


Extracellular vesicles derived from bone marrow mesenchymal stem cells repair functional and structural rat adrenal gland damage induced by fluoride.
The adrenal glands have striking morpho-biochemical features that render them vulnerable to the effects of toxins. This study was conducted to explore the therapeutic utility of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) against fluoride-induced adrenal toxicity. The work included isolation and further identification of BMSC-EVs by transmission electron microscopy and flow cytometric analysis. Adrenal toxicity in rats was induced by oral administration of 300 ppm of sodium fluoride (NaF) in drinking water for 60 days followed by a single dose injection of BMSC-EVs. The effects of BMSC-EVs against NaF was evaluated by adrenal oxidant/antioxidant biomarkers, hormonal assay of plasma adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) and mRNA gene expression quantitation for adrenal cortical steroidogenic pathway-encoding genes. Histopathological examination of the adrenal tissue was performed. BMSC-EVs were effectively isolated and characterized. NaF exposure decreased adrenal superoxide dismutase and catalase activities, increased adrenal malondialdehyde levels, elevated plasma ACTH, diminished CORT concentrations and downregulated the adrenal cortical steroidogenic pathway-encoding genes. In addition, NaF-induced marked adrenal histopathological lesions. BMSC-EVs treatment repaired damaged adrenal tissue and recovered its function greatly following NaF consumption. BMSC-EVs reversed the toxic effects of NaF and reprogramed injured adrenal cells by activating regenerative processes.


Regulation of macropinocytosis by p21-activated kinase-1.
The process of macropinocytosis is an essential aspect of normal cell function, contributing to both growth and motile processes of cells. p21-activated kinases (PAKs) are targets for activated Rac and Cdc42 guanosine 5'-triphosphatases and have been shown to regulate the actin-myosin cytoskeleton. In fibroblasts PAK1 localizes to areas of membrane ruffling, as well as to amiloride-sensitive pinocytic vesicles. Expression of a PAK1 kinase autoinhibitory domain blocked both platelet-derived growth factor- and RacQ61L-stimulated uptake of 70-kDa dextran particles, whereas an inactive version of this domain did not, indicating that PAK kinase activity is required for normal growth factor-induced macropinocytosis. The mechanisms by which PAK modulate macropinocytosis were examined in NIH3T3 cell lines expressing various PAK1 constructs under the control of a tetracycline-responsive transactivator. Cells expressing PAK1 (H83,86L), a mutant that dramatically stimulates formation of dorsal membrane ruffles, exhibited increased macropinocytic uptake of 70-kDa dextran particles in the absence of additional stimulation. This effect was not antagonized by coexpression of dominant-negative Rac1-T17N. In the presence of platelet-derived growth factor, both PAK1 (H83,86L) and a highly kinase active PAK1 (T423E) mutant dramatically enhanced the uptake of 70-kDa dextran. Neither wild-type PAK1 nor vector controls exhibited enhanced macropinocytosis, nor did PAK1 (H83,86L) affect clathrin-dependent endocytic mechanisms. Active versions of PAK1 enhanced both growth factor-stimulated 70-kDa dextran uptake and efflux, suggesting that PAK1 activity modulated pinocytic vesicle cycling. These data indicate that PAK1 plays an important regulatory role in the process of macropinocytosis, perhaps related to the requirement for PAK in directed cell motility.


Drug evaluation of clevidipine for acute hypertension.
Clevidipine is an investigational agent undergoing late-stage clinical development to evaluate its potential as a novel short-acting intravenous agent for treating acute hypertension, either in hypertensive emergencies encountered in the emergency department and intensive care units, or in the perioperative period. Clevidipine has been evaluated in four Phase I studies, nine Phase II studies and six Phase III clinical studies. The patient populations studied include healthy volunteers, patients with essential hypertension, patients undergoing cardiac surgery, and patients presenting to the emergency department with hypertensive emergencies. Studies providing comparative data of clevidipine versus nitroglycerin, nicardipine or sodium nitroprusside are also available. This article reviews the results of clinical studies evaluating the pharmacological properties, clinical effects and safety profiles of clevidipine in various patient populations. Clevidipine is an effective agent for reducing acute elevation in blood pressure in various settings, including hypertensive emergencies and perioperative hypertension with a good safety profile.


The VEGF family in cancer and antibody-based strategies for their inhibition.
Angiogenesis is required in normal physiological processes, but is also involved in tumor growth, progression and metastasis. Vascular endothelial growth factor (VEGF), a primary mediator of angiogenesis in normal physiology and in disease, and other VEGF family members and their receptors provide targets that have been explored extensively for cancer therapy. Small molecule inhibitors and antibody/protein-based strategies that target the VEGF pathway have been studied in multiple types of cancer. This review will focus on VEGF pathway targeting antibodies that are currently being evaluated in pre-clinical and clinical studies.


Self-efficacy and health-related quality of life in family carers of people with dementia: a systematic review.
This review aims to explore the role of self-efficacy (SE) in the health-related quality of life (QoL) of family carers of people with dementia. A systematic review of literature identified a range of qualitative and quantitative studies. Search terms related to caring, SE, and dementia. Narrative synthesis was adopted to synthesise the findings. Twenty-two studies met the full inclusion criteria, these included 17 quantitative, four qualitative, and one mixed-method study. A model describing the role of task/domain-specific SE beliefs in family carer health-related QoL was constructed. This model was informed by review findings and discussed in the context of existing conceptual models of carer adaptation and empirical research. Review findings offer support for the application of the SE theory to caring and for the two-factor view of carer appraisals and well-being. Findings do not support the independence of the negative and positive pathways. The review was valuable in highlighting methodological challenges confronting this area of research, particularly the conceptualisation and measurement issues surrounding both SE and health-related QoL. The model might have theoretical implications in guiding future research and advancing theoretical models of caring. It might also have clinical implications in facilitating the development of carer support services aimed at improving SE. The review highlights the need for future research, particularly longitudinal research, and further exploration of domain/task-specific SE beliefs, the influence of carer characteristics, and other mediating/moderating variables.


Inhibitory effect of melatonin on 7, 12-dimethylbenz[a]anthracene-induced carcinogenesis of the uterine cervix and vagina in mice and mutagenesis in vitro.
Forty female CBA mice aged 3-4 months were exposed twice a week during 2 months to intravaginal applications of polyurethane sponges impregnated with 0.1% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in triethyleneglycol. Three hours after each application the sponges were taken out. Starting from the day of the 1st DMBA application a part of mice was exposed five times a week during 4 months with melatonin in tap water (20 mg/l) given at night time (from 18:00 to 09:00 h). Additional 20 female CBA mice were intact and served as a control. All mice were sacrificed in 6 months after start of the experiment. Seven of 20 mice exposed to DMBA alone developed malignancies in the vagina and cervix uteri and two mice developed benign cervical tumors. No malignancies in vagina and uterine cervix and three vaginal papillomas were observed in mice exposed to DMBA+melatonin. There were no any tumors in intact controls. Two in vitro tests were used for mutagenicity studies: the Ames test (strains TA 97 and TA 98 of Salmonella typhimurium) and the single cell gel electrophoresis assay (SCGE assay or COMET assay) performed on CHOK1 cells. In tested strains melatonin significantly reduced the mutagenicity of DMBA. In the SCGE assay preincubation with melatonin led to a strong inhibition of clastogenic activities of DMBA. Thus, our data indicate that pineal indole hormone melatonin inhibits cervical and vaginal carcinogenesis induced by DMBA in mice and possess antimutagenic and anticlastogenic effect in vitro.


[Entomological monitoring of an area to assess Dirofilaria transmission risk].
As the basis for entomological monitoring, the authors first propose to investigate the structure of a season of D. repens invasion transmission in the carrier in relation to the ambient temperature, such as onset of a transmission season, terminaton of mosquito infection, the number of invasion circulations. A calculating procedure has been developed. It is shown that there is a need for entomological monitoring of each specific area irrespective of the latitude to study a risk for local dirofilariasis cases.


Estimating utility value for female genital mutilation.
Female genital mutilation/cutting (FGM/C) is a clear violation of women's rights and can have adverse and irreversible health effects as well. Worldwide, more than 200 million women and girls have undergone FGM/C. Utility value of FGM/C has not been estimated yet, so we designed this study to extract the health utility value of FGM/C for the first time in the world. In a cross-sectional study in Iran, 125 girls and women who underwent FGM/C procedure were examined by the trained midwives in order to determine its type. In addition, a questionnaire was completed for identifying the socio-demographic factors and extracting the health utility of these individuals. Health utility was measured using Time Trade-off method and also to determine the effects of the socio-demographic factors on the health utility a two-limit censored regression model was applied. The mean and median of the health utility of women with FGM/C were 0.971 (SE: 0.003) and 0.968 (IQR: 1-0.95), respectively. Number of non-traders was 58 (46.4%) who reported perfect health utility. However, the mean of health utility among traders was 0.946 (SE: 0.002). Only type 1 (Clitoridectomy) and type 2 (Excision) FGM/C were seen in this study. Women with Type 1 FGM/C had significantly lower health utility value (Mean: 0.968, Median: 0.957) than their type 2 counterparts (Mean: 0.987, Median: 1.00). Moreover, women in the age group of 31-45 years (Mean: 0.962, Median: 0.956), single (Mean: 0.950, Median: 0.954), divorced (Mean: 0.951, Median: 0.950), employed (Mean: 0.959, Median: 0.956), and with supplementary insurance (Mean: 0.962, Median: 0.950) had significantly lower health utility than their counterparts. FGM/C affects physical and psychological well-being of these individuals, resulting in a lack of personal and marital satisfaction, which ultimately leads to a 3% reduction in their health related quality of life. Therefore, preventing from this practice is very important and should be considered by health system policy makers more than before.


Nitrogen metabolism and hormonal responses of steers fed wheat silage and infused with amino acids or casein.
Four Holstein steers (159 kg) surgically fitted with abomasal-infusion cannulas were used in a 4 x 4 Latin square study to test amino acid (AA) and casein (CAS) infusions on nitrogen balance and hormonal status of steers consuming vegetative wheat (Triticum aestivum L.) silage (12.3% CP). Treatments were 5-d infusions of 1) water (CONT), 2) arginine (ARG; 13.69 g/d), 3) limiting amino acids (LAA, 13.69 g/d arginine + 10.92 g/d histidine + 28.97 g/d lysine + 10.88 g/d methionine + 16.96 g/d threonine, and 4) Na-CAS (300 g/d). Whole blood was collected for plasma AA, growth hormone (GH), insulin, and IGF-I concentrations. Data were analyzed by ANOVA, and the following orthogonal contrasts were used to separate treatment means: CONT vs ARG; ARG vs LAA; and LAA vs CAS. Urinary N increased (P < .02) for CAS vs LAA. Arginine increased N retention, as did CAS, compared to LAA. Total plasma essential AA were decreased by arginine. Mean plasma insulin concentrations were increased by CAS (P < .034). Arginine increased mean plasma GH levels, but not IGF-I. The CAS treatment increased (P < .015) IGF-I levels, but not GH. These data suggest that performance of steers fed wheat silage was limited by duodenal AA flow and that arginine was the first-limiting AA. Casein infusion increased plasma insulin and IGF-I, which would explain the improved growth noted in calves and lambs fed forages supplemented with ruminally undegraded protein.


Effects of acupuncture as a treatment for hyperventilation syndrome: a pilot, randomized crossover trial.
Sustained and subtle hyperventilation can result in a wide variety of symptoms, leading to a chronic condition that has been termed hyperventilation syndrome (HVS). Treatment options include physiotherapy, in the form of breathing retraining (BR), but additional approaches aim to reduce the anxiety that is recognized as being a frequent component of this condition. The aim of this study was to evaluate whether acupuncture is an appropriate treatment for HVS to reduce anxiety, and whether a crossover trial is an appropriate study design to evaluate acupuncture in this condition. A single-blind crossover trial was carried out comparing the effects of 4 weeks (30 minutes twice weekly) acupuncture and BR on patients with HVS. Ten (10) patients diagnosed with HVS were recruited to the trial and randomized into two groups. Both groups received acupuncture and BR with a washout period of 1 week. The primary outcome measure used was the Hospital Anxiety and Depression (HAD) Scale. Other outcome measures used were the Nijmegen questionnaire and Medical Research Council Dyspnea scale. The results showed statistically significant treatment differences between acupuncture and breathing retraining, in favor of acupuncture. Reductions were found in the HAD A (anxiety) (p = 0.02) and Nijmegen (symptoms) (p = 0.03) scores. There was no statistical evidence of any carryover effects. However, when graphically examining individual anxiety scores, in those who received acupuncture first, there was a reduction in anxiety levels which persisted through the washout period, suggesting that there may have been some carryover effect from this treatment. This study suggests that acupuncture may be beneficial in the management of HVS in terms of reducing anxiety levels and symptom severity. However, there may be some carryover effect, after acupuncture treatment, which went undetected because the small sample size. This preliminary study provides the basis for a larger, sufficiently powered and methodologically sound trial.


Achieving a patient-centred consultation by giving feedback in its early phases.
The traditional medical consultation comprises history, examination, and investigations, followed by explanation to the patient of diagnosis and management. In the course of studying a series of tape-recorded consultations in a specialist medical clinic for chronic fatigue, we have observed a different structure. In some consultations, those categorized as more 'patient-centred', doctors introduced explanation and education into the early history-taking stage. This strategy is contrasted with the traditional approach, where the doctor only elicits information during the history, and gives an explanation later. The 'early feedback' strategy may result in patients with chronic illnesses achieving greater understanding of their symptoms. We discuss the implication of these findings for medical training.


Crystallization and preliminary X-ray crystallographic analysis of zebrafish prototype galectin Drgal1-L2.
Zebrafish (Danio rerio) are an important developmental and embryological model given the optical clarity of the embryos and larvae, which permits real-time viewing of developing pathologies. More recently, a broader scope for these vertebrates to model a range of human diseases, including some cancers, has been indicated. Zebrafish Drgal1-L2 has been identified as an orthologue of mammalian galectin-1, which is is a carbohydrate-binding protein that exhibits β-galactoside-binding specificity and which is overexpressed by many aggressive human cancers. This study describes the cloning, expression in Escherichia coli, purification and crystallization of recombinant Drgal1-L2 protein in the presence of lactose (ligand). X-ray diffraction data from these novel crystals of zebrafish Drgal1-L2 were collected to a resolution of 1.5 Å using a synchrotron-radiation source, enabling their characterization.


Allelic imbalance on 12q22-23 in serum circulating DNA of melanoma patients predicts disease outcome.
Allelic imbalance (AI) encompassing the apoptotic protease-activating factor 1 (APAF-1) locus (12q22-23) is found frequently in metastatic melanoma. Circulating DNA with AI on 12q22-23 in serum was evaluated as a surrogate marker to predict biochemotherapy (BC) treatment response in melanoma patients. Sera were collected from 49 American Joint Committee on Cancer stage IV melanoma patients treated with BC. Serum AI of the 12q22-23 region was demonstrated to be present before and/or after BC. BC responders showed a significantly lower frequency of AI (5 of 24, 21%) compared with nonresponders (11 of 20, 55%; Fisher's exact test, P < 0.029). Serum AI on 12q22-23 was associated with worse prognosis (log-rank test, P < 0.046). These findings indicate that serial serum genetic analysis of tumor-related AI on 12q22-23 may have clinical use in predicting tumor response to therapy.


Stochastic power processing through logic operation of power packets.
This article presents an application of the recently proposed logic operation of power based on power packetization. In a power packet despatching system, the power supply can be considered as a sequence of power pulses, where the occurrence of pulses follows a probability that corresponds to the capacity of the power sources or power lines. In this study, we propose a processing scheme to reshape a stream of power packets from such stochastic sequences to satisfy the load demand. The proposed scheme is realized by extending the concept of stochastic computing to the power domain. We demonstrate the operation of the proposed scheme through experiments and numerical simulations by implementing it as a function of a power packet router, which forms a power packet despatching network. The stochastic framework proposed in this study provides a new design foundation for low-power distribution networks as an embodiment of the close connection between the cyber and physical components.


Supramolecular Competitive Host-Guest Interaction Induced Reversible Macromolecular Metamorphosis.
In this work, a rational strategy of competitive host-guest complexation between dioxynaphthalene (Naph) and tetrathiafulvalene (TTF) subunits as guests and cyclophane cyclobis(paraquat-p-phenylene) (CBPQT4+ ) module as host is exploited to modify the macromolecular architecture, so-called supramolecular metamorphosis, in aqueous media. The architectures of the polymers can be reversibly transformed from a linear diblock copolymer AB to a linear AC block copolymer or from a linear block copolymer to a comb copolymer by redox switching. Interestingly, as TTF- and Naph-based complexes feature different characteristic colors, it offers a great opportunity to directly observe nanoscaled macromolecular metamorphosis of materials with the naked eye.


Functional Movement Screening and Injury Rates in High School and Collegiate Runners: A Retrospective Analysis of 3 Prospective Observational Studies.
Determine if the Functional Movement Screening (FMS) can be used to predict injury in high school and collegiate cross-country and track runners. Prospective Observational, Cohort Study, Level of Evidence, 2. High schools and colleges in the Central Ohio area. Inclusion: (1) cross-country or track runners at participating schools; (2) full participation without restrictions; and (3) signed informed assent or consent. Exclusion: (1) Any injury or lower extremity surgery within 30 days; (2) planned limited participation in the upcoming season; or (3) other participation restrictions. Functional Movement Screening was completed before the start of each season. Injuries were tracked during the regular season. No interventions were made based on FMS score. Functional Movement Screening scores, including overall, lower extremity, and specific exercises were compared between runners who did and did not sustain an injury using 2 sample t tests. A cutoff FMS score of ≤14 (most common in previous studies), and ≤15 (determined by a receiver operating characteristic curve), were compared using χ tests. One hundred eighty-three runners were enrolled in the study. Overall, 32 (17.5%) runners sustained an injury. Functional Movement Screening score was not accurate in predicting injury for ≤14 (sensitivity: 65.6%; specificity: 39.7%; and area under the curve = 0.501) or ≤15 (sensitivity: 84.4% and specificity: 23.8%). There was no difference in risk of injury for runners with a FMS score of ≤14 (15.5%) and >14 (18.8%) (P = 0.572) or with a FMS score of ≤15 (17.5%) and >15 (17.4%) (P = 0.988). Functional Movement Screening composite score may not be useful for injury prediction in populations of high school and collegiate runners.


Naked chancelloriids from the lower Cambrian of China show evidence for sponge-type growth.
Chancelloriids are an extinct group of spiny Cambrian animals of uncertain phylogenetic position. Despite their sponge-like body plan, their spines are unlike modern sponge spicules, but share several features with the sclerites of certain Cambrian bilaterians, notably halkieriids. However, a proposed homology of these 'coelosclerites' implies complex transitions in body plan evolution. A new species of chancelloriid, Allonnia nuda, from the lower Cambrian (Stage 3) Chengjiang Lagerstätte is distinguished by its large size and sparse spination, with modified apical sclerites surrounding an opening into the body cavity. The sclerite arrangement in A. nuda and certain other chancelloriids indicates that growth involved sclerite addition in a subapical region, thus maintaining distinct zones of body sclerites and apical sclerites. This pattern is not seen in halkieriids, but occurs in some modern calcarean sponges. With scleritome assembly consistent with a sponge affinity, and in the absence of cnidarian- or bilaterian-grade features, it is possible to interpret chancelloriids as sponges with an unusually robust outer epithelium, strict developmental control of body axis formation, distinctive spicule-like structures and, by implication, minute ostia too small to be resolved in fossils. In this light, chancelloriids may contribute to the emerging picture of high disparity among early sponges.


Patient Reported Experiences and Delays During the Diagnostic Pathway for Pulmonary Fibrosis: A Multinational European Survey.
Introduction: Pulmonary fibrosis includes a spectrum of diseases and is incurable. There is a variation in disease course, but it is often progressive leading to increased breathlessness, impaired quality of life, and decreased life expectancy. Detection of pulmonary fibrosis is challenging, which contributes to considerable delays in diagnosis and treatment. More knowledge about the diagnostic journey from patients' perspective is needed to improve the diagnostic pathway. The aims of this study were to evaluate the time to diagnosis of pulmonary fibrosis, identify potential reasons for delays, and document patients emotions. Methods: Members of European patient organisations, with a self-reported diagnosis of pulmonary fibrosis, were invited to participate in an online survey. The survey assessed the diagnostic pathway retrospectively, focusing on four stages: (1) time from initial symptoms to first appointment in primary care; (2) time to hospital referral; (3) time to first hospital appointment; (4) time to final diagnosis. It comprised open-ended and closed questions focusing on time to diagnosis, factors contributing to delays, diagnostic tests, patient emotions, and information provision. Results: Two hundred and seventy three participants (214 idiopathic pulmonary fibrosis, 28 sarcoidosis, 31 other) from 13 countries responded. Forty percent of individuals took ≥1 year to receive a final diagnosis. Greatest delays were reported in stage 1, with only 50.2% making an appointment within 3 months. For stage 2, 73.3% reported a hospital referral within three primary care visits. However, 9.9% reported six or more visits. After referral, 76.9% of patients were assessed by a specialist within 3 months (stage 3) and 62.6% received a final diagnosis within 3 months of their first hospital visit (stage 4). Emotions during the journey were overall negative. A major need for more information and support during and after the diagnostic process was identified. Conclusion: The time to diagnose pulmonary fibrosis varies widely across Europe. Delays occur at each stage of the diagnostic pathway. Raising awareness about pulmonary fibrosis amongst the general population and healthcare workers is essential to shorten the time to diagnosis. Furthermore, there remains a need to provide patients with sufficient information and support at all stages of their diagnostic journey.


Genetic selection for mutations that reduce or abolish ribosomal recognition of the HIS4 translational initiator region.
A unique genetic selection was devised at the HIS4 locus to address the mechanism of translation initiation in Saccharomyces cerevisiae and to probe sequence requirements at the normal translational initiator region that might participate in ribosomal recognition of the AUG start codon. The first AUG codon at the 5' end of the HIS4 message serves as the start site for translation, and the -3 and +4 nucleotide positions flanking this AUG (AXXAUGG) correspond to a eucaryotic consensus start region. Despite this similarity, direct selection for mutations that reduce or abolish ribosomal recognition of this region does not provide any insight into the functional nature of flanking nucleotides. The only mutations identified that affected recognition of this region were alterations in the AUG start codon. Among 150 spontaneous isolates, 26 were shown to contain mutations in the AUG start codon, including all +1 changes (CUG, GUG, and UUG), all +3 changes (AUA, AUC, and AUU), and one +2 change (ACG). These seven mutations of the AUG start codon, as well as AAG and AGG constructed in vitro, were assayed for their ability to support HIS4 expression. No codon other than AUG is physiologically relevant to translation initiation at HIS4 as determined by growth tests and quantitated in his4-lacZ fusion strains. These data and analysis of other his4 alleles are consistent with a mechanism of initiation at HIS4 as proposed in the scanning model whereby the first AUG codon nearest the 5' end of the message serves as the start site for translation and points to the AUG codon in S. cerevisiae as an important component for ribosomal recognition of the initiator region.


Aldehydes and ketones in pyrolysis oil: analytical determination and their role in the aging process.
Aldehydes and ketones are known to play a role in the aging process of pyrolysis oil and generally, aldehydes are known for their high reactivity. In order to discern in pyrolysis oil the total aldehyde concentration from that of the ketones, a procedure for the quantification of aldehydes by 1H-NMR was developed. Its capability is demonstrated with a hardwood pyrolysis oil at different stages of the aging process. It was treated by the Accelerated Aging Test at 80 °C for durations of up to 48 h. The aldehyde concentration was complemented by the total concentration of carbonyls, quantified by carbonyl titration. The measurements show, that the examined hardwood pyrolysis oil contained 0.31-0.40 mmol g-1 aldehydes and 4.36-4.45 mmol g-1 ketones. During the first 24 h, the aldehyde concentration declined by 23-39% and the ketone concentration by 9%. The rate of decline of aldehyde concentration slows down within 24 h but is still measureable. In contrast, the total carbonyl content does not change significantly after an initial decline within the first 4 h. Changes for vinylic, acetalic, phenolic and hydroxyl protons and for protons in the α-position to hydroxy, ether, acetalic and ester groups were detected, by 1H-NMR. In the context of characterizing pyrolysis oil and monitoring the aging process, 1H-NMR is a reliable tool to assess the total concentration of aldehydes. It confirms the reactivity of aldehydes and ketones and indicates their contribution to the instability of pyrolysis oil.


Molecular Mechanisms Associated with Aging Kidneys and Future Perspectives.
The rapid growth of the elderly population is making the need for extensive and advanced information about age-related organ dysfunction a crucial research area. The kidney is one of the organs most affected by aging. Aged kidneys undergo functional decline, characterized by a reduction in kidney size, decreased glomerular filtration rate, alterations in renal blood flow, and increased inflammation and fibrosis. This review offers a foundation for understanding the functional and molecular mechanisms of aging kidneys and for selecting identifying appropriate targets for future treatments of age-related kidney issues.


[Carotid stenosis--is arteriography necessary in investigation and treatment].
The present study was undertaken in order to evaluate whether arteriography changed the planned treatment (carotid endarterectomy) of patients with symptomatic carotid artery disease, who had been investigated primarily by ultrasound Duplex scanning. The material was comprised of 50 consecutive patients admitted for arteriography. All patients were symptomatic and were by ultrasound examination found to have lesions of the relevant internal carotid artery (ICA). In three cases arteriography was performed because ultrasound examination was inconclusive. Of the remaining 47 cases, arteriography only changed the planned treatment in three. In one case, arteriography showed a long stenosis continuing into the intracranial part of the ICA, which was not observed by ultrasound. In two cases of minor disease ultrasound overestimated the degree of stenosis. The study concludes that carotid endarterectomy may be performed based on ultrasound duplex scanning, without prior arteriography, if the degree of stenosis is 70% or greater and if the distal end of the stenosis is clearly extracranial.