Bleeding control in endoscopic sinus surgery: a systematic review of the literature.
In the literature various methods are described to reduce bleeding in endoscopic sinus surgery. Scientific evidence and results were gathered and analysed to determine the effectiveness of the various methods used. A total of 20 articles fulfilled the inclusion criteria. Two retrospective articles studied the differences between local and general anaesthesia. Three articles analysed the use of local methods to control bleeding. The majority of the articles analysed the use of different systemic drugs to control intraoperative bleeding. Certain procedures, such as the reverse Trendelenburg position, the use of high doses of epinephrine, the infiltration of phenylephrine and lidocaine into the pterygopalatine fossa, the preoperative use of prednisone, and the control of the heart rate (with dexmedetomidine or remifentanil), appear to reduce the intraoperative blood loss and/or improve the visualisation of the surgical field. However, the evidence supporting these conclusions is poor. The benefits of other procedures, such as the preoperative use of β-blockers, antihypertensive agents, and surgical pledgets with oxymetazoline, phenylephrine, or cocaine, for bleeding control are not evidenced in the literature. In addition, the literature does not present any evidence on the benefits of local anaesthesia compared with general anaesthesia or the use of propofol compared to inhaled analgesics in terms of intraoperative bleeding or complication rates.


Activation of the CheA kinase by asparagine in Bacillus subtilis chemotaxis.
Past experiments have shown that CheA and CheY are required to generate smooth swimming signals in Bacillus subtilis chemotaxis. This study, as anticipated from in vivo experiments, demonstrates in vitro that an attractant-bound chemoreceptor leads to an increase in CheA activity, which in turn leads to an increase in the CheY-P pool that ultimately causes a behavioural change in the bacteria. Asparagine has been found to increase the rate of CheY-P formation in the presence of McpB-containing membranes, CheA, and an excess of CheY. This asparagine effect requires the presence of both CheA and McpB, the latter of which has been shown to be the sole receptor for this attractant. Utilizing membranes from a number of B. subtilis null mutant strains, insight has also been gained into the potential roles of a number of unique chemotaxis proteins in the regulation of CheA activity in the presence and absence of this attractant.


Information space receding horizon control.
In this paper, we present a receding horizon solution to the optimal sensor scheduling problem. The optimal sensor scheduling problem can be posed as a partially observed Markov decision problem whose solution is given by an information space (I-space) dynamic programming (DP) problem. We present a simulation-based stochastic optimization technique that, combined with a receding horizon approach, obviates the need to solve the computationally intractable I-space DP problem. The technique is tested on a sensor scheduling problem, in which a sensor must choose among the measurements of N dynamical systems in a manner that maximizes information regarding the aggregate system over an infinite horizon. While simple, such problems nonetheless lead to very high dimensional DP problems to which the receding horizon approach is well suited.


Myelinated fibres in the human paravertebral sympathetic chain; quantitative studies on white rami communicantes.
Myelinated fibres in the human sympathetic paravertebral chain were examined histologically and in single teased fibre preparations in various age groups in subjects dying from disorders not affecting primarily the autonomic nervous system. An increase in fibre density predominantly due to an increase in the number of small fibres was found in older subjects. A correlation between internodal length and fibre diameter was found but the internodes of sympathetic myelinated fibres are shorter for any given diameter than those found on fibres of comparable size in the sural nerve. A reduction in internodal lengths with advancing years was demonstrated. These observations are interpreted to show that Wallerian degeneration and segmental demyelination occur with increasing frequency in old age and that regeneration does not keep pace with successive degenerative events. The deterioration in function of the autonomic nervous system with advancing years may be attributed in part to the changes found in myelinated fibres in the paravertebral sympathetic chain.


Ghrelin- and GH-induced insulin resistance: no association with retinol-binding protein-4.
Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects. To study GH-independent effects of ghrelin, seven hypopituitary men undergoing replacement therapy with GH and hydrocortisone were given ghrelin (5 pmol/kg per min) and saline infusions for 300 min in a randomized, double-blind, placebo-controlled, crossover design. Circulating RBP4 levels were measured at baseline and during a hyperinsulinemic-euglycemic clamp on both study days. To study the direct effects of GH, nine healthy men were treated with GH (2 mg at 2200 h) and placebo for 8 days in a randomized, double-blind, placebo-controlled, crossover study. Serum RBP4 levels were measured before and after treatment, and insulin sensitivity was measured by the hyperinsulinemic-euglycemic clamp technique. Ghrelin acutely decreased peripheral insulin sensitivity. Serum RBP4 concentrations decreased in response to insulin infusion during the saline experiment (mg/l): 43.2±4.3 (baseline) vs 40.4±4.2 (clamp), P<0.001, but this effect was abrogated during ghrelin infusion (mg/l): 42.4±4.5 (baseline) vs 42.9±4.7 (clamp), P=0.73. In healthy subjects, serum RBP4 levels were not affected by GH administration (mg/l): 41.7±4.1 (GH) vs 43.8±4.6 (saline), P=0.09, although GH induced insulin resistance. i) Serum RBP4 concentrations decrease in response to hyperinsulinemia, ii) ghrelin abrogates the inhibitory effect of insulin on circulating RBP4 concentrations, and iii) ghrelin as well as GH acutely induces insulin resistance in skeletal muscle without significant changes in circulating RBP4 levels.


Usefulness of ultrasound-guided, fine-needle aspiration biopsy for palpable breast tumors.
To investigate whether ultrasound (US) guidance improves the sensitivity of fine-needle aspiration biopsy (FNAB) in patients with palpable breast tumors. A retrospective study. A university hospital. A total of 107 patients with breast tumors (114 lesions) underwent US-guided FNAB and 138 patients (143 lesions) underwent FNAB guided by palpation (standard FNAB). The diagnoses obtained by FNAB were compared with the surgical findings and the diagnostic value of US-guided FNAB was evaluated. The sensitivity of US-guided FNAB was 89.3%, the specificity was 82.9%, and the accuracy was 86.9%. In contrast, the sensitivity of standard FNAB was 61.1%, the specificity was 73.3%, and the accuracy was 65.0%. For breast tumors 2.0 cm or less in diameter, the sensitivity and accuracy of US-guided FNAB were significantly higher than those of standard FNAB. Ultrasound-guided FNAB can improve the preoperative diagnosis of breast cancer, especially in patients with tumors that are 2 cm or less in diameter.


[Determination of glyphosate in heart blood of corpse by ion chromatography].
A method for the determination of glyphosate in human blood by ion chromatography was established. The protein in heart blood from a corpse was precipitated with acetonitrile. The large molecules and Cl(-) in the supernatant were removed by a Dionex OnGuard II RP column and a Dionex OnGuard II Ag column, respectively. The filtrate was separated on an IonPac AS-19 column with KOH solution as eluent produced online by an eluent generator (EG). A suppressor with external water mode and a conductivity detector for the detection were used. The linear range of this method was 10 - 100 mg/L with a correlation coefficient (r2) of 0.9999. The limits of detection (LOD, S/N = 3) and quantification (LOQ, S/N = 10) of glyphosate in blood were 0.12 mg/L and 0.39 mg/L, respectively. The recoveries ranged between 95.2% -109.1% with the relative standard deviations (RSDs, n = 5) of 1.2% - 3.7%. The glyphosate content in a heart blood sample from a corpse in an actual case was 508 mg/L detected by this method. This method is simple, sensitive, accurate, and can rapidly provided reliable clues and evidences for glyphosate poisoning cases. This method can meet the needs of public security work.


Trapping of interstitial defects: filling the gap between the experimental measurements and DFT calculations.
We show that any impurity will slow the diffusion of oxygen in Nb. Using a first-principles plane-wave pseudopotential method and the supercell model, we calculated the interaction energies between substitutional atoms (SA) (X = Ti, V, Ta, Zr, and Hf) and interstitial oxygen in a Nb matrix. All impurities act as traps for oxygen: undersized SA (Ti and V) have strongest binding at the nearest octahedral interstice, while for oversized SA (Zr and Hf), the strongest trapping site is the second-nearest octahedral interstice. We evaluated the diffusion coefficients of O in the Nb-X alloys using kinetic Monte Carlo (KMC) modeling based in the transition state theory, using our calculated oxygen migration energies. From this, the effective (average) X-O interaction energies were extracted using the Oriani model (Oriani 1970 Acta Metall. 18 147-57). The effective X-O interaction energies are close to the strongest interaction energies between X and O obtained from the direct supercell calculations. The phenomenological effective diffusion barrier obtained from the KMC modeling is close to the energy difference between the most stable configuration and the highest saddle point along the diffusion path. Both results demonstrate that the weaker trapping site has negligible influence on the diffusion of O.


Protecting Healthcare Personnel in Outpatient Settings: The Influence of Mandatory Versus Nonmandatory Influenza Vaccination Policies on Workplace Absenteeism During Multiple Respiratory Virus Seasons.
OBJECTIVE To determine the effect of mandatory and nonmandatory influenza vaccination policies on vaccination rates and symptomatic absenteeism among healthcare personnel (HCP). DESIGN Retrospective observational cohort study. SETTING This study took place at 3 university medical centers with mandatory influenza vaccination policies and 4 Veterans Affairs (VA) healthcare systems with nonmandatory influenza vaccination policies. PARTICIPANTS The study included 2,304 outpatient HCP at mandatory vaccination sites and 1,759 outpatient HCP at nonmandatory vaccination sites. METHODS To determine the incidence and duration of absenteeism in outpatient settings, HCP participating in the Respiratory Protection Effectiveness Clinical Trial at both mandatory and nonmandatory vaccination sites over 3 viral respiratory illness (VRI) seasons (2012-2015) reported their influenza vaccination status and symptomatic days absent from work weekly throughout a 12-week period during the peak VRI season each year. The adjusted effects of vaccination and other modulating factors on absenteeism rates were estimated using multivariable regression models. RESULTS The proportion of participants who received influenza vaccination was lower each year at nonmandatory than at mandatory vaccination sites (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.07-0.11). Among HCP who reported at least 1 sick day, vaccinated HCP had lower symptomatic days absent compared to unvaccinated HCP (OR for 2012-2013 and 2013-2014, 0.82; 95% CI, 0.72-0.93; OR for 2014-2015, 0.81; 95% CI, 0.69-0.95). CONCLUSIONS These data suggest that mandatory HCP influenza vaccination policies increase influenza vaccination rates and that HCP symptomatic absenteeism diminishes as rates of influenza vaccination increase. These findings should be considered in formulating HCP influenza vaccination policies. Infect Control Hosp Epidemiol 2018;39:452-461.


What Makes a Quality Health App-Developing a Global Research-Based Health App Quality Assessment Framework for CEN-ISO/TS 82304-2: Delphi Study.
The lack of an international standard for assessing and communicating health app quality and the lack of consensus about what makes a high-quality health app negatively affect the uptake of such apps. At the request of the European Commission, the international Standard Development Organizations (SDOs), European Committee for Standardization, International Organization for Standardization, and International Electrotechnical Commission have joined forces to develop a technical specification (TS) for assessing the quality and reliability of health and wellness apps. This study aimed to create a useful, globally applicable, trustworthy, and usable framework to assess health app quality. A 2-round Delphi technique with 83 experts from 6 continents (predominantly Europe) participating in one (n=42, 51%) or both (n=41, 49%) rounds was used to achieve consensus on a framework for assessing health app quality. Aims included identifying the maximum 100 requirement questions for the uptake of apps that do or do not qualify as medical devices. The draft assessment framework was built on 26 existing frameworks, the principles of stringent legislation, and input from 20 core experts. A follow-up survey with 28 respondents informed a scoring mechanism for the questions. After subsequent alignment with related standards, the quality assessment framework was tested and fine-tuned with manufacturers of 11 COVID-19 symptom apps. National mirror committees from the 52 countries that participated in the SDO technical committees were invited to comment on 4 working drafts and subsequently vote on the TS. The final quality assessment framework includes 81 questions, 67 (83%) of which impact the scores of 4 overarching quality aspects. After testing with people with low health literacy, these aspects were phrased as "Healthy and safe," "Easy to use," "Secure data," and "Robust build." The scoring mechanism enables communication of the quality assessment results in a health app quality score and label, alongside a detailed report. Unstructured interviews with stakeholders revealed that evidence and third-party assessment are needed for health app uptake. The manufacturers considered the time needed to complete the assessment and gather evidence (2-4 days) acceptable. Publication of CEN-ISO/TS 82304-2:2021 Health software - Part 2: Health and wellness apps - Quality and reliability was approved in May 2021 in a nearly unanimous vote by 34 national SDOs, including 6 of the 10 most populous countries worldwide. A useful and usable international standard for health app quality assessment was developed. Its quality, approval rate, and early use provide proof of its potential to become the trusted, commonly used global framework. The framework will help manufacturers enhance and efficiently demonstrate the quality of health apps, consumers, and health care professionals to make informed decisions on health apps. It will also help insurers to make reimbursement decisions on health apps.


L-carnitine therapy in isovaleric acidemia.
Isovaleric acidemia, resulting from isovaleryl-coenzyme A dehydrogenase deficiency, is associated with marked reduction of free carnitine in both plasma and urine. Fast atom bombardment-mass spectrometry, hydrolysis, and gas chromatography/mass spectrometry have unequivocally identified the existence of isovalerylcarnitine, a new metabolite specific for this disorder. Administration of equimolar amounts of glycine or L-carnitine separately with leucine demonstrated that isovaleryl-coenzyme A is removed by supplemental L-carnitine in the form of isovalerylcarnitine as effectively as it is by glycine, in the form of isovalerylglycine. When L-carnitine is given alone, excretion of isovalerylglycine decreases in preference to enhanced excretion of isovalerylcarnitine and hippurate. Treatment with L-carnitine alone has proven effective in preventing further hospitalizations in a patient with this genetic disorder.


Endoscopic Management of Biliary Complications After Orthotopic Liver Transplantation.
After orthotopic liver transplantation (OLT), biliary duct complications can occur in as many as 10% to 35% of patients. In the early medical and surgical literature, surgical therapy was the primary mode of management of biliary tract complications and was the eventual course of operative intervention in up to 70% of cases. However, with recent advances in therapeutic biliary endoscopy, the current endoscopic and transplantation literature suggests that endoscopic management with techniques such as endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy, biliary stenting, and stone removal techniques can be successfully applied for the majority of post-OLT biliary complications. The most common biliary complications after OLT include biliary strictures (anastomotic and nonanastomotic); bile duct leaks, common bile duct stones, and biliary casts; sphincter of Oddi/ampullary muscle dysfunction/spasm; and disease recurrence (eg, primary sclerosing cholangitis). Predisposing factors for biliary complications after OLT include hepatic artery thrombosis, impaired perfusion of the biliary tree, portal vein thrombosis, and preservation or harvesting injuries, which can increase the incidence of complications as much as 40%. Use of immunosuppressive agents such as cyclosporine can lead to cholesterol/bile stasis and stone formation. Outside of endoscopic therapy, there is little medical or dietary management that can be applied for post-OLT biliary complications. Ursodiol (ursodeoxycholic acid) has often been used as a neoadjuvant to ERCP therapy in the setting of common bile duct stones/casts, and low-fat diets may be recommended in this setting, but no large, randomized trials have advocated medical or conservative management alone.


Clinicopathologic Analysis of Chondroblastoma in Adults: A Single-Institution Case Series.
Chondroblastoma is a rare benign tumor of immature cartilage cells that generally occurs in an epiphyseal location of skeletally immature individuals. However, a few studies have reported cases in older patients. The purpose of this study was to evaluate the clinical, radiographic, and pathologic features of chondroblastoma in an adult population. The pathology archives of our institution were searched for cases of chondroblastoma diagnosed in patients ≥25 years of age. Of 14 patients identified, 8 were male and 6 were female with a median age of 34 years (range = 29-54 years). Most lesions occurred in short bones of hands and feet (N = 7, 50%), followed by the long tubular bones (N = 4, 28%). All demonstrated typical histologic features of chondroblastoma, but more extensive calcification, necrosis, and degenerative changes were also seen. At follow-up (median = 73.5 months), 2 patients (17%) had local recurrence. None had metastasis. In summary, chondroblastoma in adults tends to involve the short bones of the hands and feet and demonstrate histologic changes associated with long-standing growth of a benign tumor.


Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection.
Fecal microbiota transfer (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI), but data on procedure-related complications and long-term outcome are scarce. All patients treated with FMT for recurrent CDI at the Academic Medical Center between July 2010 and January 2016 were included. FMT was performed according to the FECAL trial protocol: administration of fresh donor feces (related or unrelated donor) through a duodenal tube after pre-treatment with vancomycin and bowel lavage. We collected information on FMT-related complications, recurrent CDI, and short- and long-term adverse events by telephone interviews using a structured questionnaire at three months after FMT, and at the time of data collection of this study. In total, 39 patients were treated with FMT. The primary cure rate (no recurrence ≤8 weeks after one infusion with donor feces) was 82% (32 of 39 patients). Of the seven patients with recurrent CDI after FMT, four were cured by antibiotic therapy alone (fidaxomicin in three patients, metronidazole in one patient) and three by repeat FMT. Peri-procedural complications occurred in five patients, comprising fecal regurgitation or vomiting. One patient died one week post-FMT due to pneumonia; a causal relation with FMT could not be excluded. The follow-up period ranged between 3 and 68 months. No long-term side effects were reported. Our data underline the efficacy of FMT as treatment for recurrent CDI. Importantly, it is possible to cure post-FMT recurrences with antibiotic therapy alone. Peri-procedural complications do occur and should be closely monitored to help identify high-risk patients. To minimize the risk of complications, all FMT candidates should be evaluated to assess the most ideal delivery method.


Assessment of the effectiveness of genital infection awareness training provided to women based on the IMB model.
Genital infections are one of the most common reasons for a hospital visit in the scope of reproductive health problems. The information-motivation-behavioral skills (IMB), therefore, is an appropriate model to provide women with accurate genital hygiene behaviors and develop effective sexual and reproductive health training programs. This interventional study was conducted to assess the effectiveness of genital infection awareness training provided to women based on the IMB model. Study sample consisted of 62 women (nexperimental= 31, ncontrol= 31) who were chosen based on a nonprobability sampling method from vocational courses of Ankara Keçiören municipality. The data collection form developed by the researchers, knowledge evaluation questions (KEQ), and genital hygiene behavior inventory (GHBI) were used to collect data. Data were obtained at training centers and through phone interviews. Another interview was conducted 1 month later and posttest procedures were completed. The Chi-square test, McNemar's, Mann-Whitney U test, and Wilcoxon Signed-Rank tests were used to calculate mean scores. The mean (SD) age was 39.1 (8.4) years for the women in the experimental group and 37.5 (6.7) for the women in the control group (P = 0.481). Pretest knowledge mean scores M (SD)experimental = 15.7 (2.4); and GHBI mean scores M (SD)experimental= 76.9 (11.1) were calculated. Mean scores showed an increase after the training in the experimental group [M (SD)post-test= 19.1 (1.2); M (SD)GHBI= 94.7 (2.6)] (P < 0.001). Based on these findings, it was concluded that the genital infection awareness training provided to women based on the IMB model, improved knowledge and acted as a positive reinforcer for the hygiene behaviors of the women.


Complex modular cis-acting elements regulate expression of the cardiac specifying homeobox gene Csx/Nkx2.5.
The murine homeobox gene Csx/Nkx2.5 is an evolutionarily highly conserved gene related to the Drosophila tinman gene, which specifies cardiac and visceral mesoderm. Since Csx/Nkx2.5 plays an essential role in heart development, studying its regulation is essential for the better understanding of molecular mechanisms of cardiogenesis and the pathogenesis of congenital heart disease in humans. In this study, we characterized the murine Csx/Nkx2.5 gene and identified two novel untranslated exons, 1a, and 1b, resulting in three different Csx/Nkx2.5 transcripts. To examine the tissue-specific transcriptional regulation in vivo, we analyzed a total of 23 kb of Csx/Nkx2.5 upstream and downstream sequences by generating transgenic embryos carrying lacZ reporter constructs containing various lengths of flanking sequence. With 14 kb of 5' flanking sequence, lacZ expression was observed in the cardiac crescent at E7.5, and in the outflow tract, the interatrial groove, the atrioventricular canal and right and left ventricles, as well as in pharyngeal floor, thyroid primordia, and stomach at E10.5. In adult animals, lacZ expression of the transgene was limited to the atrioventricular junction and the subendocardium of the ventricular septum. Reducing the size of flanking sequence to 3.3 kb of intron 2 restricted lacZ expression to the outflow tract and the basal part of the right ventricle in E10.5 embryos. In contrast, the addition of 6 kb of 3' flanking sequence caused strong expression of the reporter gene in the entire right ventricle. Interestingly, Csx/Nkx2. 5 seems to be negatively regulated by its own gene product, because when lacZ was "knocked-in" to replace the entire coding exons, lacZ expression was much higher in the heart of homozygous embryos than that in the heterozygote. These results indicate that the transcriptional regulatory elements of Csx/Nkx 2.5 seems unexpectedly highly modular, and is temporally regulated in a dynamic manner by different enhancer regions. Since Csx/Nkx2.5-like genes are expressed in all species having a heart, their complex modular organization with multiple enhancers probably reflects progressive addition of regulatory elements during the evolution from a simple heart tube to a complex four-chambered organ.


[Early detection of lung cancer - current status and implementation scenarios].
The prognosis of conventionally diagnosed lung cancer patients is still rather poor. Two large, randomized trials using screening by low dose CT could demonstrate that early detection in persons with smoking as risk factor can improve this prognosis. Early detection of lung cancer can be achieved by structured screening programs using low dose CT for persons at increased risk, but in addition also by consequent management of incidental pulmonary nodules, which are seen on imaging for other reasons. Integral part of these programs should be prevention measures, especially a consequent, repeated, low-threshold offer of a service for smoking cessation. Programs for lung cancer screening for persons at increased risk are only beneficial for the screenees and cost-effective, if the various parts of the program are optimally integrated and coordinated and all necessary disciplines (especially respiratory medicine, radiology, pathology, thoracic surgery, radiotherapy) are included in a multidisciplinary manner. For Germany the certified lung cancer centres in structured cooperation with physicians in private practice (respiratory physicians, radiologists, general practitioners) would be a good option. It is essential that there is a good perception for the need of early detection of lung cancer in politics and the public and that the persons at risk are reached, contacted and motivated by various methods.


Signal function of potassium channels--clinical aspects.
Potassium (K+) channels are the most diverse class of ion channels, and are important for regulating neuronal excitability and signaling activity in a variety of ways. They are major determinants of membrane excitability, influencing the resting potential of membranes, wave forms and frequencies of action potentials, and thresholds of excitation. Voltage-gated K+ cannels exist not as independent units merely responding to changes in transmembrane potential but as macromolecular complexes able to integrate a plethora of cellular signals that fine tune channel activities. There are a wide variety of therapeutic agents that are targeted to non-K+ channels, but result in unintended block of K+ channels. This K+ channel block can result in potentially serious and sometimes even fatal side effects.


The all-or-none phenomenon revisited.
One of the more pervasive tenets of teratology is the "all-or-none" phenomenon, which refers to the concept that embryonic exposure that occurs before organogenesis results in either no adverse embryonic outcome or in embryonic death. This concept has been used extensively in genetic counseling of pregnant women who have inadvertently undergone an exposure in the very early stages of pregnancy, frequently before the pregnancy has been recognized. Herein, we review the data that supports the all-or-none concept and the exceptions to this general rule. In the absence of further human evidence to the contrary, and given the many women exposed to medications or environmental agents before learning of their pregnancies, it would be prudent to continue to counsel pregnant women using the all-or-none hypothesis to avoid needless interruption of pregnancy out of unfounded fear of an adverse pregnancy outcome.


A role for glutathione disulfide as a scavenger of oxygen radicals produced by 2,3-dichloro-1,4-naphthoquinone.
The addition of 2,3-dichloro-1,4-naphthoquinone (CNQ) to isolated mitochondria supplemented with GSSG resulted in a respiratory burst with the production of O2- and H2O2, and a decrease in the level of measurable disulfide. Superoxide generated by the xanthine oxidase system or by CNQ-treated mitochondria caused the reduction of GSSG to GSH. Both disulfide reductions were partially sensitive to exogeneous SOD. GSSG was also shown to interfere with the epinephrine - adrenochrome superoxide assay system. The findings reported herein support the conclusion that GSSG is capable of scavenging O2- and has the potential to scavenge other free radicals by a similar mechanism.


Economic Evaluation of Umeclidinium/Vilanterol versus Umeclidinium or Salmeterol in Symptomatic Non-Exacerbating Patients with COPD from a UK Perspective Using the GALAXY Model.
Dual bronchodilators are recommended as maintenance treatment for patients with symptomatic COPD in the UK; further evidence is needed to evaluate cost-effectiveness versus monotherapy. Cost-effectiveness of umeclidinium/vilanterol versus umeclidinium and salmeterol from a UK healthcare perspective in patients without exacerbations in the previous year was assessed using post hoc EMAX trial data. The validated GALAXY model was populated with baseline characteristics and treatment effects from the non-exacerbating subgroup of the symptomatic EMAX population (COPD assessment test score ≥10) and 2020 UK healthcare and drug costs. Outputs included estimated exacerbation rates, costs, life-years (LYs), and quality-adjusted LYs (QALYs); incremental cost-effectiveness ratio (ICER) was calculated as incremental cost/QALY gained. The base case (probabilistic model) used a 10-year time horizon, assumed no treatment discontinuation, and discounted future costs and QALYs by 3.5% annually. Sensitivity and scenario analyses assessed robustness of model results. Umeclidinium/vilanterol treatment was dominant versus umeclidinium and salmeterol, providing an additional 0.090 LYs (95% range: 0.035, 0.158) and 0.055 QALYs (-0.059, 0.168) with total cost savings of £690 (£231, £1306) versus umeclidinium, and 0.174 LYs (0.076, 0.286) and 0.204 QALYs (0.079, 0.326) with savings of £1336 (£1006, £2032) versus salmeterol. In scenario and sensitivity analyses, umeclidinium/vilanterol was dominant versus umeclidinium except over a 5-year time horizon (more QALYs at higher total cost; ICER=£4/QALY gained) and at the lowest estimate of the St George's Respiratory Questionnaire treatment effect (fewer QALYs at lower total cost; ICER=£12,284/QALY gained); umeclidinium/vilanterol was consistently dominant versus salmeterol. At willingness-to-pay threshold of £20,000/QALY, probability that umeclidinium/vilanterol was cost-effective in this non-exacerbating subgroup was 95% versus umeclidinium and 100% versus salmeterol. Based on model predictions from a UK perspective, symptomatic patients with COPD and no exacerbations in the prior year receiving umeclidinium/vilanterol are expected to have better outcomes at lower costs versus umeclidinium and salmeterol.


The pathogenesis of osteonecrosis and the relationships to corticosteroids.
One of the challenging issues faced by allergists is a risk-benefit analysis on the use of corticosteroids. An uncommon, but serious complication of corticosteroids is the development of avascular necrosis (osteonecrosis). In this review we present the differential diagnosis and pathophysiology of osteonecrosis, with particular emphasis on steroids. Osteonecrosis of the femoral head is a common disorder that may be either naturally occurring or iatrogenic. With the exception of those cases labeled as idiopathic, the majority are the result of some insult to the vascular integrity of the affected hip. The reason for this disruption is manifold and can range from direct trauma to the more subtle or indirect compromise associated with fatty emboli or often an intravascular event such as that seen in sickle cell anemia. Although they are not totally understood, corticosteroids present a special problem because of susceptibility factors that may make some patients more likely to get osteonecrosis than others. The problem may be more complex, in that the association between corticosteroid use and osteonecrosis may be disease-dependent. In any case, any patient receiving long-term corticosteroids should be warned of this potentially debilitating complication.


Neuronal nitric oxide synthase is expressed in rat vascular smooth muscle cells: activation by angiotensin II in hypertension.
The nitric oxide synthase (NOS) inhibitor nitro-L-arginine augmented the contractions to angiotensin (Ang) II in carotid artery rings without endothelium from spontaneously hypertensive rats (SHR) but not normotensive Wistar-Kyoto rats, suggesting the possibility of nonendothelial NOS activity in SHR arteries. In SHR artery without endothelium, the potentiation of Ang II contraction by nitro-L-arginine was prevented by L-arginine, but not by D-arginine, and was observed also in the presence of oxyhemoglobin, monomethyl-L-arginine, and 7-nitroindazole, but not in the presence of aminoguanidine. In further support of NOS activation by Ang II in nonendothelial cells, Ang II but not acetylcholine stimulated cGMP levels by 2-fold in SHR arteries without endothelium; nitro-L-arginine decreased both basal and Ang II-stimulated cGMP levels. When NOS activity in SHR arteries was measured, no calcium-independent L-citrulline formation was detectable, while up to 47% of the total calcium-dependent NOS activity was present in nonendothelial cells. Expression of neuronal NOS was revealed in the media of SHR arteries by immunohistochemistry, Western blot, and reverse transcriptase-polymerase chain reaction. Expression of this NOS isoform was greater in SHR than in Wistar-Kyoto rat preparations. Finally, endothelial NOS was observed in the endothelium, but no detectable levels of inducible NOS were found in these tissues. These results demonstrate the expression of neuronal NOS in rat vascular smooth muscle cells and its activation on stimulation by Ang II in spontaneously hypertensive, but not normotensive, animals.


Do cardiometabolic, behavioural and socioeconomic factors explain the 'healthy migrant effect' in the UK? Linked mortality follow-up of South Asians compared with white Europeans in the Newcastle Heart Project.
Immigrants are sometimes found to have better health than locally born populations. We examined the mortality experience of South Asian origin and white European origin individuals living in Newcastle upon Tyne, UK. A linked 17-21 year mortality follow-up of a cross-sectional study of European (n=825) and South Asian (n=709) men and women, aged 25-74 years, recruited between 1993 and 1997. Poisson regression was used to estimate mortality rate ratios (MRRs) for all-cause mortality. Sensitivity analysis explored the possible effect of differences between ethnic groups in loss to follow-up. The impact of adjustment for established risk factors on MRRs was studied. South Asians had lower all-cause age-adjusted and sex-adjusted mortality than Europeans (MRR 0.70; 95% CI 0.58 to 0.85). There was higher loss to follow-up in South Asians. Sensitivity analyses demonstrated that this did not account for the observed lower mortality. Adjustment for cardiometabolic, behavioural and socioeconomic characteristics attenuated but did not eliminate the mortality differences between South Asians and Europeans, although CIs now cross 1 (MRR 0.79; 95% CI 0.55 to 1.13). South Asians had lower all-cause mortality compared with European origin individuals living in Newcastle upon Tyne that were not accounted for by incomplete mortality data. It is possible that such migrants to the UK have the resources and motivation to move in search of better opportunities and may be healthier and wealthier than those who remain in their country of origin. These findings challenge us to better understand and measure the factors contributing to their survival advantage.


Clinical safety and effectiveness evaluation of a new antimicrobial wound dressing designed to manage exudate, infection and biofilm.
The objective of this work was to evaluate the safety and effectiveness of a next-generation antimicrobial wound dressing (NGAD; AQUACEL® Ag+ Extra™ dressing) designed to manage exudate, infection and biofilm. Clinicians were requested to evaluate the NGAD within their standard protocol of care for up to 4 weeks, or as long as deemed clinically appropriate, in challenging wounds that were considered to be impeded by suspected biofilm or infection. Baseline information and post-evaluation dressing safety and effectiveness data were recorded using standardised evaluation forms. This data included wound exudate levels, wound bed appearance including suspected biofilm, wound progression, skin health and dressing usage. A total of 112 wounds from 111 patients were included in the evaluations, with a median duration of 12 months, and biofilm was suspected in over half of all wounds (54%). After the introduction of the NGAD, exudate levels had shifted from predominantly high or moderate to low or moderate levels, while biofilm suspicion fell from 54% to 27% of wounds. Wound bed coverage by tissue type was generally shifted from sloughy or suspected biofilm towards predominantly granulation tissue after the inclusion of the NGAD. Stagnant (65%) and deteriorating wounds (27%) were shifted to improved (65%) or healed wounds (13%), while skin health was also reported to have improved in 63% of wounds. High levels of clinician satisfaction with the dressing effectiveness and change frequency were accompanied by a low number of dressing-related adverse events (n = 3; 2·7%) and other negative observations or comments. This clinical user evaluation supports the growing body of evidence that the anti-biofilm technology in the NGAD results in a safe and effective dressing for the management of a variety of challenging wound types.


Sub-angstrom noninvasive imaging of atomic arrangement in 2D hybrid perovskites.
Noninvasive imaging of the atomic arrangement in two-dimensional (2D) Ruddlesden-Popper hybrid perovskites (RPPs) is challenging because of the insulating nature and softness of the organic layers. Here, we demonstrate a sub-angstrom resolution imaging of both soft organic layers and inorganic framework in a prototypical 2D lead-halide RPP crystal via combined tip-functionalized scanning tunneling microscopy (STM) and noncontact atomic force microscopy (ncAFM) corroborated by theoretical simulations. STM measurements unveil the atomic reconstruction of the inorganic lead-halide lattice and overall twin-domain composition of the RPP crystal, while ncAFM measurements with a CO-tip enable nonperturbative visualization of the cooperative reordering of surface organic cations driven by their hydrogen bonding interactions with the inorganic lattice. Moreover, such a joint technique also allows for the atomic-scale imaging of the electrostatic potential variation across the twin-domain walls, revealing alternating quasi-1D electron and hole channels at neighboring twin boundaries, which may influence in-plane exciton transport and dissociation.


Subtyping primary insomnia: is sleep state misperception a distinct clinical entity?
Among the range of primary insomnia subtypes, those assigned such labels as subjective insomnia or sleep state misperception historically have been among the most intriguing yet challenging to understand and manage clinically. Such patients who produce seemingly normal polysomnograms often present rather compelling and, at times, dramatic sleep complaints. Our earliest formal sleep nosology included a separate diagnostic category for such individuals, but little research has been devoted to this insomnia subtype in the 20 years since this classification scheme was proposed. As a result, use of diagnoses such as subjective insomnia or sleep state misperception have remained controversial. The current article reviews this controversy and highlights the major criticisms forged against subdividing primary insomnia into objective and subjective subtypes. Subsequently, the relative merits of these criticisms are considered in view of early and recent findings vis-à-vis the subjective/objective insomnia dichotomy. Although available data are not conclusive, there appears to be sufficient evidence to suggest subjective and objective insomnia subtypes may suffer from distinctive forms of sleep-related pathophysiology. We conclude by advocating continued study of the subjective insomnia phenomenon and by providing specific directions for relevant future research.


Amikacin once daily: a new dosing regimen based on drug pharmacokinetics.
Once-daily dosing of amikacin is a novel therapy regimen which seems pharmacokinetically appropriate for the primary group of patients considered for aminoglycoside therapy. In this study of 29 elderly patients with serious infections, amikacin 11 mg/kg or 15 mg/kg bw was administered as a short-term (30 min) intravenous infusion. The amikacin serum concentration-time profile was best described by a bi-exponential equation with a half-life of about 4.8 h. A triexponential equation was not applicable because the slow terminal elimination phase was not detected during the 24 h dosing interval. In practice, a uni-exponential equation is often used, and this may lead to incorrect conclusions about the elimination rate of amikacin. Amikacin clearance provides more direct information about elimination of amikacin than does serum half-life. Thus, there was a better correlation between the individual amikacin clearances and creatinine clearances (r = 0.89), than between the serum half-lives of amikacin and the creatinine clearances (r = 0.71). For elderly patients a smaller dose of amikacin than the regular daily dose of 15 mg/kg bw, i.e. about 11 mg/kg bw, seems recommendable, when it is given once daily. From the data obtained it is also obvious that once-daily dosing of amikacin does not eliminate the need for checking serum concentrations of the drug.


Improving access to psychological therapies in voice disorders: a cognitive behavioural therapy model.
The improving access to psychological therapies initiative has highlighted the importance of managing mental health problems effectively, and research has shown excellent outcomes from cognitive behavioural therapy (CBT) interventions. Patients presenting with functional dysphonia will often also describe psychological distress including anxiety, depression and reduced general well-being, and it is felt that effective voice therapy needs to include the management of psychological well-being. The evidence for the use of CBT enhanced voice therapy is limited to date. Recent research has only started to identify the benefits of this approach and questions regarding how to achieve and maintain competence are essential. Voice therapy outcomes are positive and patients receiving CBT with voice therapy have shown more improvement in their general well-being and distress. CBT is a very well evidenced therapy and recommended by The National Institute for Health and Care Excellence (NICE) as the treatment of choice for mental health difficulties and medically unexplained symptoms. Allied health professionals are increasingly being trained to use CBT skills in the management of a number of symptoms/illnesses, and this should be considered for the management of functional dysphonia. However, there is a need for more research and detailed consideration of how therapists should be trained and supervised and how cost-effective this approach may be.


Antibiotic use and resistance in emerging economies: a situation analysis for Viet Nam.
Antimicrobial resistance is a major contemporary public health threat. Strategies to contain antimicrobial resistance have been comprehensively set forth, however in developing countries where the need for effective antimicrobials is greatest implementation has proved problematic. A better understanding of patterns and determinants of antibiotic use and resistance in emerging economies may permit more appropriately targeted interventions.Viet Nam, with a large population, high burden of infectious disease and relatively unrestricted access to medication, is an excellent case study of the difficulties faced by emerging economies in controlling antimicrobial resistance. Our working group conducted a situation analysis of the current patterns and determinants of antibiotic use and resistance in Viet Nam. International publications and local reports published between 1-1-1990 and 31-8-2012 were reviewed. All stakeholders analyzed the findings at a policy workshop and feasible recommendations were suggested to improve antibiotic use in Viet Nam.Here we report the results of our situation analysis focusing on: the healthcare system, drug regulation and supply; antibiotic resistance and infection control; and agricultural antibiotic use. Market reforms have improved healthcare access in Viet Nam and contributed to better health outcomes. However, increased accessibility has been accompanied by injudicious antibiotic use in hospitals and the community, with predictable escalation in bacterial resistance. Prescribing practices are poor and self-medication is common - often being the most affordable way to access healthcare. Many policies exist to regulate antibiotic use but enforcement is insufficient or lacking.Pneumococcal penicillin-resistance rates are the highest in Asia and carbapenem-resistant bacteria (notably NDM-1) have recently emerged. Hospital acquired infections, predominantly with multi-drug resistant Gram-negative organisms, place additional strain on limited resources. Widespread agricultural antibiotic use further propagates antimicrobial resistance. Future legislation regarding antibiotic access must alter incentives for purchasers and providers and ensure effective enforcement. The Ministry of Health recently initiated a national action plan and approved a multicenter health improvement project to strengthen national capacity for antimicrobial stewardship in Viet Nam. This analysis provided important input to these initiatives. Our methodologies and findings may be of use to others across the world tackling the growing threat of antibiotic resistance.


Enacting narrative pedagogy. The lived experiences of students and teachers.
Reforming nursing education to meet contemporary challenges in educational and clinical environments is needed through the development and implementation of new pedagogies. Nancy Diekelmann is advancing the science of nursing education by describing a new phenomenological pedagogy, Narrative Pedagogy, identified through interpretive research in nursing education. Narrative Pedagogy is an approach to reforming nursing education that is always site specific and not generalizable from school to school. However, the processes of Narrative Pedagogy are transferable and can be enacted in many contexts. This study describes the common experiences and shared meanings of teachers and students engaging in or enacting Narrative Pedagogy. Diekelmann gathered seven teachers and students in five schools of nursing in four midwestern states to share their experiences. Interpretive phenomenology was used to analyze the group interview. One of the findings identified during this analysis, Enacting Narrative Pedagogy, is explicated, and two themes, Decentering Skill Acquisition and Content and Attending to the Practices of Thinking, are described.


Influenza in the older adult. Indications for the use of vaccine and antiviral therapy.
Each year, the influenza virus is responsible for 20,000 to 40,000 deaths and up to 300,000 hospitalizations in the United States. Although children and younger adults experience more cases of influenza, older individuals who are infected with the virus experience greater morbidity and mortality. The most effective means of influenza prevention for older adults is the influenza vaccine. Antivirals are used as adjuvant therapy, but they are not intended as primary prevention except for at-risk patients who are allergic to the vaccine. The neuroaminidase inhibitors may cause fewer side effects than the older antivirals and therefore may be a useful alternative in the treatment of influenza symptoms in older adults.


The effect of arrestin conformation on the recruitment of c-Raf1, MEK1, and ERK1/2 activation.
Arrestins are multifunctional signaling adaptors originally discovered as proteins that "arrest" G protein activation by G protein-coupled receptors (GPCRs). Recently GPCR complexes with arrestins have been proposed to activate G protein-independent signaling pathways. In particular, arrestin-dependent activation of extracellular signal-regulated kinase 1/2 (ERK1/2) has been demonstrated. Here we have performed in vitro binding assays with pure proteins to demonstrate for the first time that ERK2 directly binds free arrestin-2 and -3, as well as receptor-associated arrestins-1, -2, and -3. In addition, we showed that in COS-7 cells arrestin-2 and -3 association with β(2)-adrenergic receptor (β2AR) significantly enhanced ERK2 binding, but showed little effect on arrestin interactions with the upstream kinases c-Raf1 and MEK1. Arrestins exist in three conformational states: free, receptor-bound, and microtubule-associated. Using conformationally biased arrestin mutants we found that ERK2 preferentially binds two of these: the "constitutively inactive" arrestin-Δ7 mimicking microtubule-bound state and arrestin-3A, a mimic of the receptor-bound conformation. Both rescue arrestin-mediated ERK1/2/activation in arrestin-2/3 double knockout fibroblasts. We also found that arrestin-2-c-Raf1 interaction is enhanced by receptor binding, whereas arrestin-3-c-Raf1 interaction is not.


Relations of behavioral inhibition and activation system sensitivities with vaccination outcomes: Investigating the mediating role of vaccine hesitancy in older adults.
The study of behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivities has produced a multitude of models and frameworks to better understand decision-making and behavior. We extend this research to the study of a vaccination by exploring the relation of BIS and BAS sensitivities with vaccination willingness, receipt, and word-of-mouth. We also assess whether dimensions of vaccine hesitancy mediate these relations, testing whether they are viable explanatory mechanisms. By conducting a multi-wave survey study, our results support that BIS sensitivity does not meaningfully relate to vaccine hesitancy or vaccination outcomes. On the other hand, BAS sensitivity related to detrimental vaccination outcomes, and these effects were mediated by vaccine hesitancy dimensions associated with perceptions that vaccines cause health risks and are not needed for healthy individuals. Based on extant BIS and BAS theory, these results suggest that certain people may see refraining from vaccination as a nonpunishment.


Bioavailability of a natural lead-contaminated invertebrate diet to zebrafish.
Dietary metals are increasingly recognized as key determinants of total metal burdens in fish, yet their ecotoxicological significance remains unclear. In this study, a pairwise experimental design was used to assess reproductive performance of zebrafish (Danio rerio) fed diets supplemented with a natural Pb-enriched polychaete, Nereis diversicolor. Zebrafish were fed 1% flake food (dry wt diet/wet wt fish/d), 1% brine shrimp, and 1% N. diversicolor collected from either Gannel estuary, Cornwall, United Kingdom (UK), an estuary with legacy Pb contamination, or Blackwater estuary, Essex, UK, a reference site with low background metal concentrations, for 63 d. Mean daily dietary doses of Pb were 0.417 and 0.1 mg/kg/d (dry wt feed:wet wt fish) for fish fed N. diversicolor from Gannel and Blackwater estuaries, respectively. With the exception of Ag, which was higher for fish fed N. diversicolor from Gannel estuary, there were no differences in daily dietary exposures to other metals (As, Cd, Cu, Fe, and Zn) between treatment groups. Fish fed Pb-enriched Gannel N. diversicolor exhibited no significant impairment to incidence of spawning, numbers of eggs per breeding pair or hatch rate of embryos compared with pre-exposure levels, when N. diversicolor was omitted from the dietary regimen. Nevertheless, metal analysis revealed significant increases in whole-body Pb burdens of male fish fed polychaetes from Gannel estuary, Ag in female fish fed Gannel worms, and Ag and Cd in male fish fed the Blackwater worms. These data demonstrate that Pb naturally incorporated in N. diversicolor is bioavailable to fish, and fish exhibit sex-dependent dietary metal accumulation patterns, but after 63 d of the experimental feeding regimen, reproductive performance was unaffected.


A polyoxyethylene sorbitan oleate modified hollow gold nanoparticle system to escape macrophage phagocytosis designed for triple combination lung cancer therapy via LDL-R mediated endocytosis.
Presently, a combination of chemotherapy, radiotherapy, thermotherapy, and other treatments has become a hot topic of research for the treatment of cancer, especially lung cancer. In this study, novel hollow gold nanoparticles (HGNPs) were used as drug carriers, and in order to improve the targeting ability of HGNPs to a lung tumor site, polyoxyethylene sorbitol oleate (PSO) was chosen here as a target ligand since it can be specifically recognized by the low-density lipoprotein (LDL) receptor which is usually over expressed on A549 lung cancer cells. In this way, a PSO-modified doxorubicin-loaded HGNP drug delivery system (PSO-HGNPs-DOX) was constructed and its physicochemical properties, photothermal conversion ability, and drug release of PSO-HGNPs-DOX was investigated. Further, the effects of triple combination therapy, the intracellular uptake, and the ability to escape macrophage phagocytosis of PSO-HGNPs-DOX were also studied using A549 cells in vitro. In addition, an in vivo mouse model was also used to study the targeting of PSO-HGNPs-DOX to lung cancer. PSO-HGNPs-DOX demonstrated a good triple therapeutic effect for lung cancer (A549 cell viability was only 10% at 500 μM) by LDL receptor mediated endocytosis and was able to escape macrophage phagocytosis to enhance its accumulation at the target site. Therefore, PSO-HGNPs-DOX is a novel, safe, promising, and targeted drug carrier designed for triple combination lung cancer therapy which should be further studied for such applications.


Expression of the tuberous sclerosis 2 gene product, tuberin, in adult and developing nervous system tissues.
Tuberous sclerosis (TS) is an autosomal dominant disorder in which affected individuals manifest mental retardation, seizures, and a variety of benign and malignant tumors. The TSC2 tumor suppressor gene was recently identified by positional cloning and its protein product, tuberin, shown to represent one member of the rap GTPase activating protein (rapGAP) family. In order to determine the contribution of tuberin to the development of mental retardation and seizures in patients with TS, we examined the expression of tuberin in adult and developing nervous system tissues. Since tuberin is the second rapGAP found in the nervous system, the expression of tuberin was compared to the expression of rapGAP, rap1, and rap2. In this study, we demonstrate that tuberin is expressed at greatest levels in the spinal cord and cerebellum as opposed to rapGAP, which is not enriched in these tissues. Tuberin expression in the adult CNS is restricted to the olfactory bulb, several CNS neuronal populations, brainstem nuclei, cerebellar Purkinje cells, and motor neurons in the ventral spinal cord. In contrast, rapGAP is expressed in many different cell types in the adult CNS, but not in cerebellar Purkinje cells or motor neurons in the ventral spinal cord. However, there is significant expression of rapGAP in astrocytes. The restricted distribution of tuberin expression relative to rap1 and rapGAP suggests that tuberin may be the primary rap1 regulator in a subpopulation of CNS neurons.


Influence of Point Mutations on PR65 Conformational Adaptability: Insights from Nanoaperture Optical Tweezer Experiments and Molecular Simulations.
PR65 is the HEAT-repeat scaffold subunit of the heterotrimeric protein phosphatase 2A (PP2A) and an archetypal tandem-repeat protein, forming a spring-like architecture. PR65 conformational mechanics play a crucial role in PP2A function by opening/closing the substrate-binding/catalysis interface. Using in-silico saturation mutagenesis we identified "hinge" residues of PR65, whose substitutions are predicted to restrict its conformational adaptability and thereby disrupt PP2A function. Molecular simulations revealed that a subset of hinge mutations stabilized the extended/open conformation, whereas another had the opposite effect. By trapping in nanoaperture optical tweezer, we characterized PR65 motion and showed that the former mutants exhibited higher corner frequencies and lower translational scattering, indicating a shift towards extended conformations, whereas the latter showed the opposite behavior. Thus, experiments confirm the conformations predicted computationally. The study highlights the utility of nanoaperture-based tweezers for exploring structure and dynamics, and the power of integrating this single-molecule method with in silico approaches.


Diverticulitis Diagnosed in the Emergency Room: Is It Safe to Discharge Home?
Inpatient treatment of patients with colon diverticulitis represents a significant financial and clinical burden to the health care system and patients. The aim of this study was to compare patients with diverticulitis in the emergency department (ED), who were discharged to home vs admitted to the hospital. We reviewed all patients evaluated in the ED of a metropolitan health system, with the primary diagnosis of diverticulitis (ICD-9 562.11), from 2010 through 2012. Only patients diagnosed with CT and those with follow-up were included. We identified 240 patients; 132 (55%) were women and mean age was 59.1 years (SD 16.1 years). Imaging findings included extraluminal air (21%), pericolic or pelvic abscess (12%), free fluid (16%), and pneumoperitoneum (6%). One hundred forty-four (60%) were admitted to the hospital and 96 (40%) were discharged to home on oral antibiotics. Patients admitted to the hospital were more likely to be older than 65 years (p = 0.0007), have a Charlson comorbidity score ≥ 2 (p = 0.0025), to be on steroids or immunosuppression (p = 0.0019), and have extraluminal air (p < 0.0001) or diverticular abscess (p < 0.0001) on imaging. Median follow-up for all patients was 36.5 months (interquartile range 25.2 to 43 months). Among patients discharged from the ED, 12.5% returned to the ED or were readmitted within 30 days, with only 1 patient (1%) requiring emergency surgery, but not until 20 months later. Patients admitted to the hospital had similar rates of readmission (15%; p = 0.65). Patients diagnosed with uncomplicated diverticulitis in the emergency room can be safely discharged home on oral antibiotics, as long as CT findings are included in the decision-making process. Patients with complicated diverticulitis on CT scan should be admitted to the hospital with surgical consultation.


The methylation and telomere landscape in two families of marsupials with different rates of chromosome evolution.
Two marsupial families exemplify divergent rates of karyotypic change. The Dasyurid family has an extremely conserved karyotype. In contrast, there is significant chromosomal variation within the Macropodidae family, best exemplified by members of the genus Petrogale (rock-wallabies). Both families are also distinguished by their telomere landscape (length and epigenetics), with the dasyurids having a unique telomere length dimorphism not observed in other marsupials and hypothesised to be regulated in a parent-of-origin fashion. Previous work has shown that proximal ends of chromosomes are enriched in cytosine methylation in dasyurids, but that the chromosomes of a macropod, the tammar wallaby, have DNA methylation enrichment of pericentric regions. Using a combination of telomere and 5-methylcytosine immunofluorescence staining, we investigated the telomere landscape of four dasyurid and three Petrogale species. As part of this study, we also further examined the parent-of-origin hypothesis for the regulation of telomere length dimorphism in dasyurids, using epigenetic modifications known to differentiate the active maternal X chromosome, including 5-methylcytosine methylation and histone modifications H3K4me2, H3K9ac and H4Kac. Our results give further support to the parent-of-origin hypothesis for the regulation of telomere length dimorphism in dasyurids, where the paternally derived X chromosome in females was associated with long telomeres and the maternally derived with short telomeres. In contrast to the tammar wallaby, rock-wallabies demonstrated a similar 5-methylcytosine staining pattern across all chromosomes to that of dasyurids, suggesting that DNA methylation of telomeric regions is not responsible for differences in the rates of chromosome evolution between these two families.


Pleural effusions. 2. Definitive evaluation of the exudate.
Based on the current literature, the following steps seem reasonable in evaluating a pleural effusion: document the presence, location, and approximate volume of pleural fluid; decide clinically on the likelihood of an exudative effusion; if clinical evaluation suggests an exudative effusion, perform a thoracentesis and obtain fluid for diagnostic evaluation; perform the necessary tests to characterize the effusion as a transudate or an exudate; if a transudate exists, normally do not perform further tests on the effusion; if an exudate exists, perform selected tests to narrow the differential diagnosis; if this evaluation is undiagnostic, consider closed pleural biopsy; if the diagnosis remains unclear after two closed biopsies, consider pleuroscopy with biopsy or open pleural biopsy at the time of a thoracotomy.


Nonpharmacologic complementary therapies in symptom management for breast cancer survivors.
The request and use of nonpharmacologic interventions and complementary and alternative medicine (CAM) in cancer survivors is increasing. Given the large number of breast cancer survivors and the multiple treatment-related symptoms they endure, it is important for physicians to be aware of the evidence supporting nonpharmacologic therapies. Several studies evaluating such interventions have demonstrated improved overall quality of life (QOL). For other symptoms, the literature is limited but growing. We summarize the evidence to support complementary and alternative therapies for the major symptoms in breast cancer survivors.


Description of Kordiimonas aquimaris sp. nov., isolated from seawater, and emended descriptions of the genus Kordiimonas Kwon et al. 2005 emend. Xu et al. 2011 and of its existing species.
A Gram-negative, aerobic, rod-shaped (0.6-0.9 × 0.7-1.2 µm), motile marine bacterium, designated MEBiC06554(T), was isolated from seawater collected from the East Sea, Korea (also known as the Sea of Japan). 16S rRNA gene sequence analysis revealed that strain MEBiC06554(T) was affiliated to the order Kordiimonadales and showed high similarity to Kordiimonas gwangyangensis GW14-5(T) (95.4 %), but formed a distinct phyletic line. Growth was observed at 10.5-35.0 °C (optimum 20 °C), at pH 5.0-8.0 (optimum pH 7.0) and with 0-13 % (w/v) NaCl (optimum 3.0-3.5 %). The predominant cellular fatty acids were iso-C(15 : 0) (14.9 %), iso-C(17 : 1)ω9c (44.6 %), iso-C(17 : 0) (6.3 %) and summed feature 3 (comprising iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c; 13.9 %). The DNA G+C content was 50.3 mol%. The major respiratory quinone was Q-10. Phosphatidylethanolamine, two unidentified glycolipids, six unidentified aminolipids, three unidentified lipids and one unidentified aminophospholipid were detected as major polar lipids. On the basis of the data from our polyphasic taxonomic study, strain MEBiC06554(T) should be classified within a novel species of the genus Kordiimonas, as Kordiimonas aquimaris sp. nov. The type strain is MEBiC06554(T) (= KCCM 42940(T) = JCM 16665(T)). Emended descriptions of the genus Kordiimonas and of its species Kordiimonas gwangyangensis and Kordiimonas lacus are also proposed.


Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on epidemiology and phenotype of osteoarthritis.
Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.


1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline increases extracellular serotonin and stimulates hydroxyl radical production in rats.
1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), a neurotoxin structurally similar to the dopaminergic neurotoxin MPTP, may be formed in humans treated with chloral hydrate or exposed to trichloroethylene, a widely used industrial solvent. Systemically administered TaClo (0.4 mg/kg, i.p.) induced an immediate and transient release of dopamine (DA) and serotonin (5-HT) measured using microdialysis. However, only 5-HT was increased significantly (area under the curve, AUC, for the 1-2 h-period following TaClo administration: 400% compared with the respective control value; 2-3 h-period: 326%). This was followed by a progressive increase in hydroxyl radical formation reflected by higher extracellular concentrations of the hydroxylate product of salicylic acid, 2,3-dihydroxybenzoic acid (AUC for the 1-2 h period following TaClo administration: 182% compared with the respective control value; 2-3 h period: 190%). In contrast, extracellular glutamate and GABA were increased 2-3 h post-injection by 64 and 51%, respectively. These data suggest that TaClo stimulates the generation of hydroxyl free radicals via an acute release of 5-HT and perhaps DA.


Violent and Nonviolent Crimes Against Sex Workers: The Influence of the Sex Market on Reporting Practices in the United Kingdom.
Previous research has shown that sex workers experience extremely high rates of victimization but are often reluctant to report their experiences to the police. This article explores how the markets in which sex workers operate in the United Kingdom impact upon the violent and nonviolent crimes they report to a national support organization and their willingness to report victimization to the police. We use a secondary quantitative data analysis of 2,056 crime reports submitted to the U.K. National Ugly Mugs (NUM) scheme between 2012 and 2016. The findings indicate that although violence is the most common crime type reported to NUM, sex workers operating in different markets report varying relative proportions of different types of victimization. We also argue that there is some variation in the level of willingness to share reports with the police across the different sex markets, even when the types of crime, presence of violence, and other variables are taken into account. Our finding that street sex workers are most likely to report victimization directly to the police challenges previously held assumptions that criminalization is the key factor preventing sex workers from engaging with the police.


Blood viscosity responses to maximal exercise in endurance-trained and sedentary female subjects.
To assess whether the rheological properties of blood might be altered by exercise, we measured whole blood viscosity, plasma viscosity, and its components in healthy female subjects before, immediately after, and 1 h after maximal upright exercise using the Bruce graded exercise protocol. Forty-seven female subjects (15 sedentary, 14 who ran 5-15 miles/wk, and 18 who ran greater than 50 miles/wk), ages 18-43 yr, were evaluated. Whole blood viscosity, measured with a cone and plate viscometer, increased an average of 12.6% with exercise. The increase was greater than can be attributed to the observed 8.9% increase in hematocrit alone due to a coincident increase in plasma protein concentration. However, plasma viscosity did not rise to the degree expected, likely due to a disproportionate observed loss of fibrinogen from the protein pool. These changes were independent of conditioning level or aerobic capacity. In this cross-sectional study, there appears to be no adaptive adjustment in females to physical conditioning that results in changes in blood viscosity.


An experimental test of the role of postsynaptic calcium levels in determining synaptic strength using perirhinal cortex of rat.
1. We have investigated the prediction of a relationship between the magnitude of activity-dependent increases in postsynaptic calcium and both the magnitude and direction of synaptic plastic change in the central nervous system. 2. Activity-dependent increases in calcium were buffered to differing degrees using a range of concentrations of EGTA and the effects on synaptic plasticity were assessed. Activity-dependent synaptic plasticity was induced during whole-cell recording in rat perirhinal cortex in vitro. In control conditions (0.5 mM EGTA) low frequency stimulation (LFS; 200 stimuli) delivered to neurones held at -40 or -70 mV induced long-term depression (LTD) or, at -10 mV, induced long-term potentiation (LTP). 3. The relationship between EGTA concentration (0.2 to 10 mM) and the magnitude of LTD was examined. This relationship described a U-shaped curve, as predicted by models of synaptic plasticity. This provides strong evidence that the magnitude of LTD is determined by the magnitude of the increase in intracellular calcium concentration. 4. LFS paired with depolarisation to -10 mV induced LTD, no change or LTP as activity-dependent postsynaptic calcium levels were allowed to increase progressively by the use of progressively lower concentrations of buffer (10 to 0.2 mM EGTA). 5. We investigated if the lack of plasticity that occurs at the transition between LTD and LTP is due to induction of both of these processes with zero net change, or is due to neither LTD nor LTP being induced. These experiments were possible as LTP but not LTD was blocked by the protein kinase inhibitor staurosporine while LTD but not LTP was blocked by the mGlu receptor antagonist MCPG. At the transition between LTD and LTP, blocking LTP mechanisms did not uncover LTD whilst blocking LTD mechanisms did not uncover LTP. This suggests that the transition between LTD and LTP is due to the lack of induction of both of these processes and also suggests that these two processes are induced independently of one another.


Measurement and control of dissolved carbon dioxide in mammalian cell culture processes using an in situ fiber optic chemical sensor.
At high viable cell concentrations in large-scale mammalian cell culture processes, the accumulation of dissolved carbon dioxide (dCO(2), typically quantified as an equilibrium gas-phase concentration) becomes problematic as a result of low CO(2) removal rates at reduced surface-to-volume ratios. High dCO(2) concentrations have previously been shown to inhibit cell growth and product formation in mammalian cells and to alter the glycosylation pattern of recombinant proteins. Therefore, reliable monitoring and control of dCO(2) are important for successful large-scale operation. Off-line measurements by instruments such as blood gas analyzers (BGA) are constrained by the low frequency of data collection and cannot be used for on-line control. In a preliminary evaluation of the YSI 8500 in situ sensor, a response time (t(90%)) of 6 min, sensitivity of 0.5% CO(2) (3.6 mmHg), and linearity of measurement (R(2) = 0.9997) between the equivalent gas-phase partial pressure of 0-180 mmHg (0% and 25% CO(2)) were established. Measurements were found to be unaffected by culture pH and typical mammalian cell culture concentrations of glucose, glutamine, glutamate, lactate, and ammonium. The sensor withstood repeated sterilization and cleaning cycles. The reliability of this sensor was demonstrated in microcarrier-based Chinese hamster ovary (CHO) cell perfusion cultures at reactor scales of 30, 40, 340, and 2000 L and was successfully implemented in a dCO(2) control strategy using N(2) sparging.


Electronic Structure Investigation of the Bulk Properties of Uranium-Plutonium Mixed Oxides (U, Pu)O2.
We present electronic structure calculations of bulk properties of (U, Pu)O2, in the whole Pu content range for which only very few experimental data are available. We use DFT+U and the vdW-DF functional in order to take into account the strong 5f electron correlations and nonlocal correlations. We investigate structural, elastic, electronic, and energetic properties of (U, Pu)O2 in the approximation of the ideal solid solution as described by the special quasirandom structures (SQS) method. The results on electronic properties highlight the narrowing of the band gap due to the mixing of UO2 and PuO2. Results on the mixing enthalpy are used to describe the phase stability of (U, Pu)O2 solid solutions, using both SQS configurations and a parametric method. In particular, the issue of an ideal solid solution on a limited supercell size is discussed.


[Methodology of choosing priority parameters of water body pollution with oil-containing waste waters].
The article deals with possibility to optimize control over water pollution with waste waters. The optimization covers definition of priority parameters by using a system of 15-17 hygienic criteria of danger resulting from industrial waste presence in water bodies. The authors recommend lists of parameters to control inflow of waste waters from oil-processing and oil-extracting enterprises into water objects, to evaluate water state after unexpected leakage of oil at the output enterprises and pipelines.


Proximal, Distal, and Contralateral Effects of Blood Flow Restriction Training on the Lower Extremities: A Randomized Controlled Trial.
Blood flow restriction (BFR) training involves low-weight exercises performed under vascular occlusion via an inflatable cuff. For patients who cannot tolerate high-load exercises, BFR training reportedly provides the benefits of high-load regimens, with the advantage of less tissue and joint stress. Low-load BFR training is safe and efficacious for strengthening muscle groups proximal, distal, and contralateral to tourniquet placement in the lower extremities. Randomized controlled trial. Level 1. This was a randomized controlled trial of healthy participants completing a standardized 6-week course of BFR training. Patients were randomized to BFR training on 1 extremity or to a control group. Patients were excluded for cardiac, pulmonary, or hematologic disease; pregnancy; or previous surgery in the extremity. Data collected at baseline and completion included limb circumferences and strength testing. The protocol was completed by 26 patients, providing 16 BFR and 10 control patients (mean patient age, 27 years; 62% female). A statistically greater increase in strength was seen proximal and distal to the BFR tourniquet when compared with both the nontourniquet extremity and the control group ( P < 0.05). Approximately twice the improvement was seen in the BFR group compared with controls. Isokinetic testing showed greater increases in knee extension peak torque (3% vs 11%), total work (6% vs 15%), and average power (4% vs 12%) for the BFR group ( P < 0.04). Limb circumference significantly increased in both the thigh (0.8% vs 3.5%) and the leg (0.4% vs 2.8%) compared with the control group ( P < 0.01). Additionally, a significant increase occurred in thigh girth (0.8% vs 2.3%) and knee extension strength (3% vs 8%) in the nontourniquet BFR extremity compared with the control group ( P < 0.05). There were no reported adverse events. Low-load BFR training led to a greater increase in muscle strength and limb circumference. BFR training had similar strengthening effects on both proximal and distal muscle groups. Gains in the contralateral extremity may corroborate a systemic or crossover effect. BFR training strengthens muscle groups proximal, distal, and contralateral to cuff placement. Patients undergoing therapy for various orthopaedic conditions may benefit from low-load BFR training with the advantage of less tissue stress.


Exposure to Trihalomethanes and Bone Mineral Density in US Adolescents: A Cross-Sectional Study (NHANES).
Animal and human studies have suggested that trihalomethane (THM) has toxicity to bone. In this study, we included adolescents from the National Health and Nutrition Examination Survey who had quantified blood and tap water THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and lumbar spine or total body less head (TBLH) bone mineral density (BMD). A 2.7-fold increase in concentrations of blood TCM, DBCM, chlorinated THMs (the sum of TCM, BDCM, and DBCM), and total THMs (the sum of 4 THMs) was associated with lower lumbar spine BMD z-scores by -0.06 [95% confidence interval (CI): -0.12, -0.01], -0.06 (95% CI: -0.11, -0.003), -0.08 (95% CI: -0.14, -0.02), and -0.07 (95% CI: -0.13, -0.003), respectively, in adjusted models. Similarly, a 2.7-fold increase in blood BDCM, DBCM, and chlorinated THM concentrations was associated with lower TBLH BMD z-scores by -0.10 (95% CI: -0.17, -0.02), -0.10 (95% CI: -0.17, -0.03), and -0.11 (95% CI: -0.20, -0.01), respectively. Low-to-moderate predictive power was attained when tap water THM concentrations were used to predict blood THM measurements. Notably, the inverse associations for blood THMs persisted exclusively between water concentrations of DBCM and Br-THMs and the TBLH BMD z-scores. Our findings suggest that exposure to THMs may adversely affect the adolescent BMD.


4'-Methyl-14',19'-dioxa-4'-aza-spiro-[acenaphthyl-ene-1,5'-tetra-cyclo-[18.104.22.168(2,6).0(8,13)]tetra-cosa-ne]-1'(24'),8',10',12',20',22'-hexa-ene-2,7'(1H)-dione.
In the title compound, C33H29NO4, the acenaphthyl-ene ring system is essentially planar (r.m.s. deviation = 0.0290 Å). The pyrrolidine ring adopts a C-envelope conformation with a C atom displaced by 0.671 (2) Å from the mean-plane formed by the remaining ring atoms. The pyrrolidine ring is fused to acenaphthyl-ene ring system making a dihedral angle of 88.0 (7)°. In the crystal, mol-ecules are linked into R(2)2(9) dimers via C-H⋯N and C-H⋯O hydrogen bonds. Two C atoms act as donors to the same O atom acceptor, resulting in the formation of R(2)1(7) ring motifs. These two motifs combine to form hydrogen-bonded sheets running along the a- and b-axis directions.


Structural adaptation of the plant protease Deg1 to repair photosystem II during light exposure.
Deg1 is a chloroplastic protease involved in maintaining the photosynthetic machinery. Structural and biochemical analyses reveal that the inactive Deg1 monomer is transformed into the proteolytically active hexamer at acidic pH. The change in pH is sensed by His244, which upon protonation, repositions a specific helix to trigger oligomerization. This system ensures selective activation of Deg1 during daylight, when acidification of the thylakoid lumen occurs and photosynthetic proteins are damaged.


Efficacy of Novel Aminooxyacetic Acid Prodrugs in Colon Cancer Models: Towards Clinical Translation of the Cystathionine β-Synthase Inhibition Concept.
Upregulation of hydrogen sulfide (H2S) biosynthesis, at least in part related to the upregulation of cystathionine β-synthetase (CBS) in cancer cells, serves as a tumor-promoting factor and has emerged as a possible molecular target for antitumor drug development. To facilitate future clinical translation, we have synthesized a variety of novel CBS-targeting, esterase-cleavable prodrugs based on the structure of the prototypical CBS inhibitor aminooxyacetic acid (AOAA). The pharmacological properties of these compounds were evaluated in cell-free assays with recombinant human CBS protein, the human colon cancer cell line HCT116, and in vivo using various tumor-bearing mice models. The prodrug YD0251 (the isopropyl ester derivative of AOAA) was selected for detailed characterization. YD0251 exhibits improved antiproliferative efficacy in cell culture models when compared to AOAA. It is up to 18 times more potent than AOAA at suppressing HCT116 tumor growth in vivo and is effective when administered to tumor-bearing mice either via subcutaneous injection or oral gavage. Patient-derived xenografts (PDTXs) with higher levels of CBS protein grew significantly larger than tumors with lower levels, and YD0251 treatment inhibited the growth of PDTXs with elevated CBS, whereas it had no significant effect on PDTXs with low CBS protein levels. The toxicity of YD0251 was assessed in mice subjected to subchronic administration of supratherapeutic doses the inhibitor; no significant alteration in circulating markers of organ injury or histopathological alterations were noted, up to 60 mg/kg/day × 5 days. In preparation to a future theranostic concept (to match CBS inhibitor therapy to high-CBS expressors), we identified a potential plasma marker of CBS-expressing tumors. Colon cancer cells produced significant levels of lanthionine, a rare metabolic intermediate of CBS-mediated H2S biosynthesis; forced expression of CBS into non-transformed epithelial cells increased lanthionine biogenesis in vitro and in vivo (measured in the urine of tumor-bearing mice). These current results may be useful to facilitate the translation of a CBS inhibition-based antitumor concept into the clinical space.


Electrochemically induced morphology and volume changes in surface-grafted poly(ferrocenyldimethylsilane) monolayers.
Poly(ferrocenyldimethylsilanes), composed of alternating ferrocene and dimethylsilane units in their main chain and featuring a thiol end group, were self-assembled to redox-active monolayers on gold. Electrochemical atomic force microscopy was employed to study the morphology of the monolayers as a function of the applied potential in situ. Surface plasmon resonance spectroscopy and spectroscopic ellipsometry measurements, performed under electrochemical control, indicated thickness changes of up to 15% upon oxidizing and reducing the surface-grafted polymers. X-ray reflectivity measurements unambiguously showed a thickness increase upon electrochemical oxidation of the monolayers. The reversible thickness change was attributed to stretching of the polymer chains upon oxidation due to an increase in charge density and to the attraction of counterions and associated solvent molecules, which are released when the polymer film is reduced to its neutral state.


Assessing the performance of single-copy genes for recovering robust phylogenies.
Phylogenies involving nonmodel species are based on a few genes, mostly chosen following historical or practical criteria. Because gene trees are sometimes incongruent with species trees, the resulting phylogenies may not accurately reflect the evolutionary relationships among species. The increase in availability of genome sequences now provides large numbers of genes that could be used for building phylogenies. However, for practical reasons only a few genes can be sequenced for a wide range of species. Here we asked whether we can identify a few genes, among the single-copy genes common to most fungal genomes, that are sufficient for recovering accurate and well-supported phylogenies. Fungi represent a model group for phylogenomics because many complete fungal genomes are available. An automated procedure was developed to extract single-copy orthologous genes from complete fungal genomes using a Markov Clustering Algorithm (Tribe-MCL). Using 21 complete, publicly available fungal genomes with reliable protein predictions, 246 single-copy orthologous gene clusters were identified. We inferred the maximum likelihood trees using the individual orthologous sequences and constructed a reference tree from concatenated protein alignments. The topologies of the individual gene trees were compared to that of the reference tree using three different methods. The performance of individual genes in recovering the reference tree was highly variable. Gene size and the number of variable sites were highly correlated and significantly affected the performance of the genes, but the average substitution rate did not. Two genes recovered exactly the same topology as the reference tree, and when concatenated provided high bootstrap values. The genes typically used for fungal phylogenies did not perform well, which suggests that current fungal phylogenies based on these genes may not accurately reflect the evolutionary relationships among species. Analyses on subsets of species showed that the phylogenetic performance did not seem to depend strongly on the sample. We expect that the best-performing genes identified here will be very useful for phylogenetic studies of fungi, at least at a large taxonomic scale. Furthermore, we compare the method developed here for finding genes for building robust phylogenies with previous ones and we advocate that our method could be applied to other groups of organisms when more complete genomes are available.


High Expression of CHST11 Correlates with Poor Prognosis and Tumor Immune Infiltration of Pancreatic Cancer.
Pancreatic cancer (PC) is the seventh leading cause of cancer death worldwide, and its prognosis is poor. It has been reported that carbohydrate sulfotransferase 11 (CHST11) is associated with tumor progression in various cancers but rarely reported in PC. The aim of this study was to comprehensively investigate the clinical value of CHST11 in PC. CHST11 gene expression analysis was conducted by The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases. Survival analysis and receiver operating characteristic (ROC) curves were performed to evaluate the prognostic significance of CHST11 based on TCGA and International Cancer Genome Consortium (ICGC) databases. Additionally, functional enrichment analysis was also performed. Moreover, single-sample Gene Set Enrichment Analysis (ssGSEA) and ESTIMATE algorithm were used to assess immune infiltration. Finally, the relationship between CHST11 expression and immune checkpoint gene levels was estimated by Spearman's correlation analysis. CHST11 was highly expressed in PC tissues compared with normal tissues, and the expression of CHST11 was related to T stage, N stage, and histological grade. The survival time of PC patients with CHST11 low-expression was significantly better than those with CHST11 high-expression. The areas under the ROC curve corresponding to 1-, 3-, and 5-year survival in the TCGA dataset were 0.573, 0.671, and 0.740, respectively, and those in the ICGC dataset were 0.588, 0.602, and 0.626, respectively. Functional enrichment analysis showed that CHST11 may be involved in the regulation of immune function. Finally, the level of CHST11 was significantly correlated with 22 types of tumor-infiltrating immune cells, immune and stromal scores, and 7 immune checkpoint genes. High-expression of CHST11 was correlated with poor prognosis and tumor immune infiltration in PC. Moreover, CHST11 may act as a novel prognostic marker and potential therapeutic target of PC.


Global public awareness of venous thromboembolism.
Data on public awareness about thrombosis in general and venous thromboembolism (VTE) in particular are limited. We aimed to measure the global awareness of thrombosis to address this gap. With Ipsos-Reid, from 22 July to 5 August 2014, we surveyed 800 respondents in their native language from each of Argentina, Australia, Canada, Germany, Japan, Thailand, the Netherlands, the United Kingdom and the United States to measure general awareness about thrombosis, including deep vein thrombosis (DVT) and pulmonary embolism (PE). In each country, respondents were distributed among three age groups: 18-39 years, 40-64 years, and over 65 years of age. Proportions and 95% confidence intervals (CIs) were calculated. Overall, the proportion of respondents that were aware of thrombosis, DVT and PE (68%, 44% and 54%, respectively) was lower than the proportion that was aware of other thrombotic disorders, such as heart attack and stroke (88% and 85%, respectively), and health conditions such as hypertension, breast cancer, prostate cancer and AIDS (90%, 85%, 82% and 87%, respectively). Although there was variation across countries, lower awareness was associated with younger age and being male. Only 45% (95% CI, 43.9-46.5) of respondents were aware that blood clots were preventable, and awareness of cancer, hospitalization and surgery as risk factors was low (16%, 25%, and 36%, respectively). On a global level, public awareness about thrombosis overall, and VTE in particular, is low. Campaigns to increase public awareness about VTE are needed to reduce the burden from this largely preventable thrombotic disorder.


Update on acne.
In summary, the therapy of acne has to be individualized according to the nature of the lesions. Noninflammatory acne requires a different therapeutic approach from that for inflammatory acne, and even among those with inflammatory acne, there can be a difference in the therapeutic approach, depending upon the extent of involvement. Attention to the principles of therapy will be a great aid in the success of the therapeutic program for acne.


Prevalence of intestinal parasite infections on a national scale among primary schoolchildren in Laos.
In order to investigate the epidemiological situation of intestinal parasite infections in Laos, parasitological surveys were carried out on a national scale including 17 provinces and the Vientiane Municipality. A total of 29,846 stool specimens were collected from primary schoolchildren from May 2000 to June 2002 and examined once with the cellophane thick smear technique. The cumulative egg positive rate for intestinal helminths was 61.9%. By species, the rate for Ascaris lumbricoides was 34.9%, hookworm 19.1%, Trichuris trichiura 25.8%, Opisthorchis viverrini 10.9%, Taenia spp. 0.6% and Hymenolepis spp. 0.2%. The northern mountainous regions such as Phongsaly, Huaphan or Saysomboune Province showed a higher prevalence (over 70%) of soil- transmitted helminths. The regions along the Mekong River such as Khammuane, Saravane or Savannakhet Province showed a higher prevalence (over 20%) of fish-borne parasites. On the other hand, Schistosoma mansoni eggs were detected in 1.7% of schoolchildren only in Champassak Province, a previously endemic area. The highest prevalence was noted in Phongsaly Province (96.0%) and the lowest in Bolikhamxay Province (27.5%). An additional small-scale survey by cellophane anal swab detected Enterobius vermicularis eggs in 35.7% of 451 schoolchildren aged 6-8 years in Khammuane, Vientiane, Champassak Province and the Vientiane Municipality. Meanwhile, the mean blood haemoglobin level of hookworm-infected children was not lower than that of children not infected with hookworm, suggesting that nutritional factors are more important than parasite infection per se. Nevertheless, the above results indicate that a nationwide parasite control project is necessary to reduce possible morbidity due to parasitic diseases in the country.


Supramolecular helices from helical building blocks via head-to-tail intermolecular interactions.
Supramolecular helices from helical building blocks represent an emerging analogue of the α-helix. In cases where the helicity of the helical building block is well propagated, the head-to-tail intermolecular interactions that lead to the helix could be enhanced to promote the formation and the stability of the supramolecular helix, wherein homochiral elongation dominates and functional helical channel structures could also be generated. This feature article outlines the supramolecular helices built from helical building blocks, i.e., helical aromatic foldamers and helical short peptides that are held together by intermolecular π-π stacking, hydrogen/halogen/chalcogen bonding, metal coordination, dynamic covalent bonding and solvophobic interactions, with emphasis on the influence of efficient propagation of helicity during assembly, favouring homochirality and channel functions.


Definitive reconstruction of circumferential, fusiform intracranial aneurysms with the pipeline embolization device.
The Pipeline embolization device (PED; Chestnut Medical, Menlo Park, CA) is a new endovascular construct designed to exclude aneurysms from the parent cerebrovasculature. We report the results of the first two human implantations of this device in North America. Two patients presenting with large, symptomatic, circumferential, fusiform intracranial vertebral artery aneurysms were treated with the PED. In both cases, more traditional open microneurosurgical and neuroendovascular treatment strategies had either failed or were associated with unacceptably high risk. Three PEDs were placed across the aneurysms in each of the patients to achieve reconstruction of a new parent vessel through the center of a circumferential aneurysm. In the first patient, who had previously been treated with stent-supported coil embolization, the PED construct alone was sufficient to achieve parent vessel reconstruction and exclusion of the recurrent aneurysm. In the second patient, a microcatheter was jailed within the saccular portion of the aneurysm and the parent vessel was reconstructed with three telescoped PEDs. Although the PED construct dramatically reduced flow into the aneurysm, the lesion remained patent. Coiling of the saccular portion of the aneurysm was subsequently performed via the jailed microcatheter. Follow-up angiography performed 72 hours after the procedure demonstrated occlusion of the aneurysm with cylindrical reconstruction of the affected vascular segment. Neither patient has experienced any complication in the periprocedural period (30 d) or during subsequent long-term (>1 year) follow-up. The PED represents an important advance in the endovascular therapy of cerebral aneurysms, targeting primary parent vessel reconstruction rather than endosaccular occlusion as a means by which to achieve exclusion of the aneurysm and definitive anatomic reconstruction of the parent artery.