Anterior Chest Wall Reconstruction After Separation of Thoraco-Omphalopagus Conjoined Twins With Cadaveric Rib Grafts and Omental Flap.
Anterior chest wall defects have a wide range of etiologies in the pediatric population, ranging from infection, tumor, and trauma to congenital diseases. The reconstructive goals include restoring skeletal stability, obliterating dead space, preserving cardiopulmonary mechanics, and protecting vital underlying mediastinal organs. Although various reconstructive methods have been described in the literature, selecting the optimal method is challenging for the growing pediatric skeleton. Here, we report a case of previously thoraco-omphalopagus twins who underwent successful separation and reconstruction and presented for definitive anterior chest wall reconstruction. A pair of previously thoraco-omphalopagus conjoined twins underwent definitive anterior chest wall defect reconstruction using cadaveric ribs and omental flap. Twin A received 2 cadaveric ribs, whereas twin B had a much larger sternal defect that required 3 cadaveric ribs combined with an omental flap for soft tissue chest coverage. Both twins were followed up for 8 months. Twin A's postoperative course was uneventful, and she was discharged on postoperative day 6. Twin B's course was complicated, and she was discharged on supported ventilation on postoperative day 10. At 8 months postoperatively, both twins healed well, and chest radiographs confirmed the stability of the chest reconstructions. The rib grafts in the twin with a tracheostomy were not mobile, and the patient had a solid sternum with adequate pulmonary expansion. The construct initially did not facilitate pulmonary functioning, but after a healing process, it eventually allowed for the twin with the tracheostomy who required pulmonary assistance to no longer need this device. Cryopreserved cadaveric ribs and omental flaps offer safe and reliable reconstructive methods to successfully reconstruct congenital anterior chest wall skeletal defects in the growing pediatric population. The involvement of multidisciplinary team care is key to optimizing the outcomes.


Deciphering the Nature of X(3872) in Heavy Ion Collisions.
Exploring the nature of exotic multiquark candidates such as the X(3872) plays a pivotal role in understanding quantum chromodynamics (QCD). Despite significant efforts, consensus on their internal structures is still lacking. As a prime example, it remains a pressing open question to decipher the X(3872) state between two popular exotic configurations: a loose hadronic molecule or a compact tetraquark. We demonstrate a novel approach to help address this problem by studying the X(3872) production in heavy ion collisions, where a hot fireball with ample light as well as charm (anti-)quarks is available for producing the exotics. Adopting a multiphase transport model (AMPT) for describing such collisions and implementing appropriate production mechanism of either molecule or tetraquark picture, we compute and compare a series of observables for X(3872) in Pb-Pb collisions at the Large Hadron Collider. We find the fireball volume plays a crucial role, leading to a 2-order-of-magnitude difference in the X(3872) yield and a markedly different centrality dependence between hadronic molecules and compact tetraquarks, thus offering a unique opportunity for distinguishing the two scenarios. We also make the first prediction of X(3872) elliptic flow coefficient to be tested by future experimental measurements.


The invertebrate odorant-binding protein LUSH is required for normal olfactory behavior in Drosophila.
The invertebrate odorant-binding proteins consist of a large family of low-molecular-weight, highly divergent proteins expressed exclusively in the chemosensory sensilla of insects. Each member of this family studied to date is secreted into the sensillum lymph of a small subset of sensilla by non-neuronal support cells. These expression patterns suggests an odor-specific function for these proteins as opposed to a general role in sensillum biology. Consistent with this notion, mutants defective for LUSH, a Drosophila member of this family, have odor-specific defects in olfactory behavior. The Drosophila genome contains at least 32 members of this gene family, rivaling the number of odorant receptors in this species. The relationship between these two protein families and how they act to determine odor specificity of olfactory neurons will be the topic of future studies.


Proteomic characterization of the whole secretome of Legionella pneumophila and functional analysis of outer membrane vesicles.
Secretion of effector molecules is one of the major mechanisms by which the intracellular human pathogen Legionella pneumophila interacts with host cells during infection. Specific secretion machineries which are responsible for the subfraction of secreted proteins (soluble supernatant proteins [SSPs]) and the production of bacterial outer membrane vesicles (OMVs) both contribute to the protein composition of the extracellular milieu of this lung pathogen. Here we present comprehensive proteome reference maps for both SSPs and OMVs. Protein identification and assignment analyses revealed a total of 181 supernatant proteins, 107 of which were specific to the SSP fraction and 33 of which were specific to OMVs. A functional classification showed that a large proportion of the identified OMV proteins are involved in the pathogenesis of Legionnaires' disease. Zymography and enzyme assays demonstrated that the SSP and OMV fractions possess proteolytic and lipolytic enzyme activities which may contribute to the destruction of the alveolar lining during infection. Furthermore, it was shown that OMVs do not kill host cells but specifically modulate their cytokine response. Binding of immunofluorescently stained OMVs to alveolar epithelial cells, as visualized by confocal laser scanning microscopy, suggested that there is delivery of a large and complex group of proteins and lipids in the infected tissue in association with OMVs. On the basis of these new findings, we discuss the relevance of protein sorting and compartmentalization of virulence factors, as well as environmental aspects of the vesicle-mediated secretion.


Prospective randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams.
To examine whether early enteral iron supplementation (EI) would improve serum ferritin as a measure of nutritional iron status at 2 months of age and would prevent definite iron deficiency (ID) in infants with a birth weight of <1301 g. Infants were randomly assigned to receive enteral iron supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of >100 mL/kg/day were tolerated (EI) or at 61 days of life (late enteral iron supplementation [LI]). Nutritional iron status was assessed: 1) at birth, 2) at 61 days of life, 3) when the infants reached a weight of 1.6 times birth weight, and 4) before blood was transfused at a hematocrit of <.25. ID was defined by any one of the following criteria: ferritin, <12 microg/L; transferrin saturation, <17%; or increase of absolute reticulocyte counts by >50% one week after the onset of enteral iron supplementation. Restrictive red cell transfusion guidelines were followed and all transfusions were documented. Erythropoietin was not administered. The primary outcome variables were: 1) ferritin at 61 days and 2) the number of infants with ID. Ferritin at 61 days was not different between the groups. Infants in the LI group were more often iron-deficient (26/65 vs 10/68) and received more blood transfusions after day 14 of life. No adverse effects of EI were noted. EI is feasible and probably safe in infants with birth weight <1301 g. EI may reduce the incidence of ID and the number of late blood transfusions. ID may occur in very low birth weight infants despite early supplementation with iron and should be considered in the case of progressive anemia.preterm infant, iron supplementation, iron deficiency, blood transfusion.


Ransomware: Analysing the Impact on Windows Active Directory Domain Services.
Ransomware has become an increasingly popular type of malware across the past decade and continues to rise in popularity due to its high profitability. Organisations and enterprises have become prime targets for ransomware as they are more likely to succumb to ransom demands as part of operating expenses to counter the cost incurred from downtime. Despite the prevalence of ransomware as a threat towards organisations, there is very little information outlining how ransomware affects Windows Server environments, and particularly its proprietary domain services such as Active Directory. Hence, we aim to increase the cyber situational awareness of organisations and corporations that utilise these environments. Dynamic analysis was performed using three ransomware variants to uncover how crypto-ransomware affects Windows Server-specific services and processes. Our work outlines the practical investigation undertaken as WannaCry, TeslaCrypt, and Jigsaw were acquired and tested against several domain services. The findings showed that none of the three variants stopped the processes and decidedly left all domain services untouched. However, although the services remained operational, they became uniquely dysfunctional as ransomware encrypted the files pertaining to those services.


Précising definitions as a way to combat overdiagnosis.
Roughly, overdiagnosis (ODx) occurs when people are harmed by receiving diagnoses (often accompanied by interventions) that do not benefit them, usually because the diagnosed conditions do not pose a threat to their health. ODx is a theoretical as well as a practical problem as it relates to definitions of disease. Elsewhere, it has been argued that disease is a vague concept and that this vagueness may contribute to ODx. In response, we develop a stipulative or précising definition of disease, for the specific purpose of decreasing or preventing ODx. We call this diseaseODx , aimed at distinguishing cases where it would be beneficial to identify (and treat the condition) from those where diagnosis is more likely to harm than benefit. A preliminary definition of diseaseODx is that X is a diseaseODx iff there is dysfunction that has a significant risk of causing severe harm. This paper examines the 3 concepts in this definition, using a naturalistic account of function, a Feinbergian account of comparative harm, and a probabilistic understanding of risk. We then test the utility of this approach using examples of clinical conditions that are currently overdiagnosed.


Microwave ablation for hepatic malignancies: a multiinstitutional analysis.
This study hypothesized that tumor size, number of tumors, surgical approach, and tumor histology significantly affected microwave ablation (MWA) success and recurrence-free survival. Although many hepatobiliary centers have adopted MWA, the factors that influence local control are not well described. Consecutive patients with hepatic malignancy treated by MWA were included from 4 high-volume institutions (2003-2011) and grouped by histology: hepatocellular carcinoma (HCC), colorectal liver metastases, neuroendocrine liver metastases, and other cancers. Independent significance of outcome variables was established with logistic regression and Cox proportional hazards models. Four hundred fifty patients were treated with 473 procedures (139 HCC, 198 colorectal liver metastases, 61 neuroendocrine liver metastases, and 75 other) for a total of 875 tumors. Median follow-up was 18 months. Concurrent hepatectomy was performed in 178 patients (38%), and when performed was associated with greater morbidity. Complete ablation was confirmed for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (10 were unevaluable). A surgical approach (open, laparoscopic, or percutaneous) had no significant impact on complication rates, recurrence, or survival. The local recurrence rate was 6.0% overall and was highest for HCC (10.1%, P = 0.045) and percutaneously treated lesions (14.1%, P = 0.014). In adjusted models, tumor size 3 cm or more predicted poorer recurrence-free survival (hazard ratio: 1.60, 95% CI: 1.02-2.50, P = 0.039). In this large data set, patients with 3 cm or more tumors showed a propensity for early recurrence, regardless of histology. Higher rates of local recurrence were noted in HCC patients, which may reflect underlying liver disease. There were no significant differences in morbidity or survival based on the surgical approach; however, local recurrence rates were highest for percutaneously ablated tumors.


Rotational dynamics of water molecules near biological surfaces with implications for nuclear quadrupole relaxation.
Based on Molecular Dynamics simulations of two different systems, the protein ubiquitin dissolved in water and an AOT reverse micelle, we present a broad analysis of the single particle rotational dynamics of water. A comprehensive connection to NQR, which is a prominent experimental method in this field, is developed, based on a reformulation of its theoretical framework. Interpretation of experimental NQR results requires a model which usually assumes that the NQR experiences retardation only in the first hydration shell. Indeed, the present study shows that this first-shell model is correct. Moreover, previous experimental retardation factors are quantitatively reproduced. All of this is seemingly contradicted by results of other methods, e.g., dielectric spectroscopy, responsible for a long-standing debate in this field. Our detailed analysis shows that NQR omits important information contained in overall water dynamics, most notably, the retardation of the water dipole axis in the electric field exerted by a biological surface.


Developmental origin and functional specialization of mast cell subsets.
Mast cells (MCs) are constitutively present in most tissues and a distinct subset of MCs can also be induced upon host responses to inflammation. The hematopoietic lineage development of tissue MCs is unique compared to other myeloid-derived cells because it is early lineage progenitors, undetectable by histochemistry, that leave the bone marrow to enter the circulation. These immature lineage MCs immediately undergo transendothelial recruitment into peripheral tissues wherein the appearance of secretory granules with a particular protease phenotype is regulated by the peripheral tissue. In this Perspective, we discuss our current understanding of how these unique immunocytes arise, traffic to various sites, and may or may not mature into tissue-directed granulated phenotypes and query whether a granulated end stage is their only intended role.


Effectiveness of extended-duration transdermal nicotine therapy: a randomized trial.
Tobacco dependence is a chronic, relapsing condition that may require extended treatment. To assess whether extended-duration transdermal nicotine therapy increases abstinence from tobacco more than standard-duration therapy in adult smokers. Parallel randomized, placebo-controlled trial from September 2004 to February 2008. Participants and all research personnel except the database manager were blinded to randomization. (ClinicalTrials.gov registration number: NCT00364156) Academic center. 568 adult smokers. In an unstratified small block-randomization scheme, participants were randomly assigned to standard therapy (Nicoderm CQ [GlaxoSmithKline, Research Triangle Park, North Carolina], 21 mg, for 8 weeks and placebo for 16 weeks) or extended therapy (Nicoderm CQ, 21 mg, for 24 weeks). The primary outcome was biochemically confirmed point-prevalence abstinence at weeks 24 and 52. Secondary outcomes were continuous and prolonged abstinence, lapse and recovery events, cost per additional quitter, and side effects and adherence. At week 24, extended therapy produced higher rates of point-prevalence abstinence (31.6% vs. 20.3%; odds ratio, 1.81 [95% CI, 1.23 to 2.66]; P = 0.002), prolonged abstinence (41.5% vs. 26.9%; odds ratio, 1.97 [CI, 1.38 to 2.82]; P = 0.001), and continuous abstinence (19.2% vs. 12.6%; odds ratio, 1.64 [CI, 1.04 to 2.60]; P = 0.032) versus standard therapy. Extended therapy reduced the risk for lapse (hazard ratio, 0.77 [CI, 0.63 to 0.95]; P = 0.013) and increased the chances of recovery from lapses (hazard ratio, 1.47 [CI, 1.17 to 1.84]; P = 0.001). Time to relapse was slower with extended versus standard therapy (hazard ratio, 0.50 [CI, 0.35 to 0.73]; P < 0.001). At week 52, extended therapy produced higher quit rates for prolonged abstinence only (P = 0.027). No differences in side effects and adverse events between groups were found at the extended-treatment assessment. The generalizability of the findings may be limited because participants were smokers without medical comorbid conditions who were seeking treatment, and differences in adherence across treatment groups were detected. Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy. National Institutes of Health.


Effect of Adolescent Bariatric Surgery on the Brain and Cognition: A Pilot Study.
Neurocognitive deficits in pediatric obesity relate to poor developmental outcomes. We sought preliminary evidence for changes in brain and cognitive functioning relevant to obesogenic behavior following vertical sleeve gastrectomy (VSG) in adolescents relative to wait-listed (WL) and healthy controls (HC). Thirty-six adolescents underwent fMRI twice 4 months apart, during executive, reward, and episodic memory encoding, in addition to behavioral testing for reward-related decision making. VSG adolescents lost weight, while WL gained weight and HC did not change between time points. Gains in executive and reward-related performance were larger in VSG than control groups. Group × Time interaction (P < 0.05 corrected) in left prefrontal cortex during N-back showed greater presurgical activation and postsurgical reduction comparable to HC levels but increased in WL between time points. Similarly, left striatal parametric response to reward value reduced after surgery to HC levels; WL did not change. Memory-related medial temporal activation did not change in any group. Results provide pilot evidence for functional brain changes induced by VSG in adolescents with severe obesity. Weight loss and gain were paralleled by reduced and increased prefrontal activation, respectively, suggesting neural plasticity related to metabolic change.


Impact of Obesity and Alanine Aminotransferase Levels on the Diagnostic Accuracy for Advanced Liver Fibrosis of Noninvasive Tools in Patients With Nonalcoholic Fatty Liver Disease.
Some evidence suggests an interference of obesity and alanine aminotransferase (ALT) levels on the diagnostic accuracy for advanced fibrosis of noninvasive tools such as liver stiffness measurement (LSM) by FibroScan, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). We assessed whether the diagnostic accuracy of LSM, Fibrosis-4 (FIB-4), and NFS and strategies based on the combination of these tools is affected by obesity and/or ALT levels. We analyzed data from 968 patients with a histological diagnosis of nonalcoholic fatty liver disease. FIB-4, NFS, and LSM by FibroScan were measured. LSM was better than both FIB-4 and NFS for staging F3-F4 fibrosis area under the receiver operating characteristic curve test (AUC) 0.863, 0.777, and 0.765, respectively; P < 0.001 for both), showing higher accuracy and higher negative predictive value (NPV), but lower positive predictive value (PPV). LSM worked less well in high ALT (>100 IU) (AUC 0.811 vs 0.877, P = 0.04; PPV 57.5% vs 62.4%; NPV 90.7% vs 94%) or obese patients (AUC 0.786 vs 0.902, P < 0.001; PPV 58.7% vs 64.8%; NPV 88.3% vs 95.2%), the latter not being affected by the M or XL probe. Consistently, LSM worked better in terms of AUC and accuracy compared with both FIB-4 and NFS only in nonobese or high ALT patients, even with always keeping a slightly lower PPV. A serial combination of FIB-4 or NFS with LSM as the second test in patients in the gray area of the first test retained-in most scenarios-similar PPV and NPV compared with LSM alone. These strategies also increased the diagnostic accuracy of about 20% in all groups of patients, even if with a lower overall accuracy in obese patients (71.3% and 67.1% for FIB-4 and NFS as the first test, respectively) compared to nonobese patients (81.9% and 82.4% for FIB-4 and NFS as the first test, respectively). All tested noninvasive tools have overall better NPV than PPV. LSM has a better diagnostic accuracy for advanced fibrosis than both FIB-4 and NFS only in nonobese and/or low ALT patients. Serial combination strategies are better than a single tool strategy, regardless of obesity and ALT levels, although the accuracy is lower in obese patients.


Complement Component C1q as Serum Biomarker to Detect Active Tuberculosis.
Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI. Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls. Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection. Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB.


Relationship of patient safety culture with factors influencing working environment such as working hours, the number of night shifts, and the number of days off among healthcare workers in Japan: a cross-sectional study.
Patient safety culture is defined as a product of individual and group values, attitudes, perceptions, competencies, and patterns of behavior that determine the commitment to, and the style and proficiency of, an organization's health and safety management. Factors influencing healthcare workers' working environment such as working hours, the number of night shifts, and the number of days off may be associated with patient safety culture, and the association pattern may differ by profession. This study aimed to examine the relationship between patient safety culture and working environment. Questionnaire surveys were conducted in 2015 and 2016. The first survey was conducted in hospitals in Japan to investigate their patient safety management system and activities and intention to participate in the second survey. The second survey was conducted in 40 hospitals; 100 healthcare workers from each hospital answered a questionnaire that was the Japanese version of the Hospital Survey on Patient Safety Culture for measuring patient safety culture. The relationship of patient safety culture with working hours in a week, the number of night shifts in a month, and the number of days off in a month was analyzed. Response rates for the first and second surveys were 22.4% (731/3270) and 94.2% (3768/4000), respectively. Long working hours, numerous night shifts, and few days off were associated with low patient safety culture. Despite adjusting the working hours, the number of event reports increased with an increase in the number of night shifts. Physicians worked longer and had fewer days off than nurses. However, physicians had fewer composites of patient safety culture score related to working hours, the number of night shifts, and the number of days off than nurses. This study suggested a possibility of improving the patient safety culture by managing the working environment of healthcare workers. High number of night shifts may lead to high number of event reports. Working hours, the number of night shifts, and the number of days off may differently influence patient safety culture in physicians and nurses.


Operations that are Questionable for Control of Obesity.
At the last review of the literature, there were 43 different operations or modifications thereof used for the control of obesity. An effective operation for obesity control should produce a significant weight loss (>/= 25% excess weight loss) to ameliorate the associated medico-sociopsycho-economic ramifications of the obesity. The operative and postoperative significant morbidity should be less than 20% and mortality less than 1%. The weight lost should be maintained for a long period (>/= 5 years). The effects of the operation should be reproducible and documentable by more than two authors working independently. For the purpose of this paper, operations which do not meet these criteria are considered questionable and not recommended for general use. Based on these criteria, questionable operations for treatment of obesity include: tooth wiring, acupuncture, hypothalamic center manipulation, liposuction, balloon insertion, unbanded gastric partitioning, vagotomy, gastrogastrostomy, horizontal gastroplasty, gastric wrap, gastroclip, and any variety of gastroplasty without a reinforced stoma, intestinal bypass, duodenal bypass and biliointestinal bypass. Data to substantiate this classification will be presented and discussed. Since the surgical treatment of obesity is evolving, there is need to collect data from and make modifications to improve the effects of all operations. There is not enough data at this time to prohibit the use of any operation, but the data presented will justify limiting the use of certain operations to institutions dedicated to meticulous follow-up and research.


Proximity of public elementary schools to major roads in Canadian urban areas.
Epidemiologic studies have linked exposure to traffic-generated air and noise pollution with a wide range of adverse health effects in children. Children spend a large portion of time at school, and both air pollution and noise are elevated in close proximity to roads, so school location may be an important determinant of exposure. No studies have yet examined the proximity of schools to major roads in Canadian cities. Data on public elementary schools in Canada's 10 most populous cities were obtained from online databases. School addresses were geocoded and proximity to the nearest major road, defined using a standardized national road classification scheme, was calculated for each school. Based on measurements of nitrogen oxide concentrations, ultrafine particle counts, and noise levels in three Canadian cities we conservatively defined distances < 75 m from major roads as the zone of primary interest. Census data at the city and neighborhood levels were used to evaluate relationships between school proximity to major roads, urban density, and indicators of socioeconomic status. Addresses were obtained for 1,556 public elementary schools, 95% of which were successfully geocoded. Across all 10 cities, 16.3% of schools were located within 75 m of a major road, with wide variability between cities. Schools in neighborhoods with higher median income were less likely to be near major roads (OR per $20,000 increase: 0.81; 95% CI: 0.65, 1.00), while schools in densely populated neighborhoods were more frequently close to major roads (OR per 1,000 dwellings/km²: 1.07; 95% CI: 1.00, 1.16). Over 22% of schools in the lowest neighborhood income quintile were close to major roads, compared to 13% of schools in the highest income quintile. A substantial fraction of students at public elementary schools in Canada, particularly students attending schools in low income neighborhoods, may be exposed to elevated levels of air pollution and noise while at school. As a result, the locations of schools may negatively impact the healthy development and academic performance of a large number of Canadian children.


Natriuretic Peptides as a Prognostic Marker for Delirium in Cardiac Surgery-A Pilot Study.
Background and Objectives: Delirium is a common and major complication subsequent to cardiac surgery. Despite scientific efforts, there are no parameters which reliably predict postoperative delirium. In delirium pathology, natriuretic peptides (NPs) interfere with the blood-brain barrier and thus promote delirium. Therefore, we aimed to assess whether NPs may predict postoperative delirium and long-term outcomes. Materials and Methods: To evaluate the predictive value of NPs for delirium we retrospectively analyzed data from a prospective, randomized study for serum levels of atrial natriuretic peptide (ANP) and the precursor of C-type natriuretic peptide (NT-proCNP) in patients undergoing coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (off-pump coronary bypass grafting; OPCAB). Delirium was assessed by a validated chart-based method. Long-term outcomes were assessed 10 years after surgery by a telephone interview. Results: The overall incidence of delirium in the total cohort was 48% regardless of the surgical approach (CABG vs. OPCAB). Serum ANP levels >64.6 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 100% (75.3-100) and specificity of 42.9% (17.7-71.1). Serum NT-proCNP levels >1.7 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 92.3% (64.0-99.8) and specificity of 42.9% (17.7-71.1). Both NPs could not predict postoperative survival or long-term cognitive decline. Conclusions: We found a positive correlation between delirium and preoperative plasma levels of ANP and NT-proCNP. A well-powered and prospective study might identify NPs as biomarkers indicating the risk of delirium and postoperative cognitive decline in patients at risk for postoperative delirium.


Comparative study of diagnostic procedures for congenital cytomegalovirus infection.
In a prospective study the incidence of congenital cytomegalovirus (CMV) infection was 2.2% (31 OF 1,412) as evidenced by viruria during the first week of life. Among immunoserologic methods used to screen these neonates, the rheumatoid factor test, although non-specific, proved to be the most convenient; its sensitivity for identifying infants with CMV infection was 35% to 45% with no false-positives. The rates for correct and incorrect identification of neonates at risk was, respectively, 33% and 3.1% when testing for increased levels of IgM; 5% and 10% when testing for increased levels of IgA; 76% and 21% when testing for IgM anti-CMV (IgM immunofluorescent test) antibody, and 0% when testing for IgA anti-CMV antibody. Rapid virologic diagnosis was achieved by assessing urine specimens. Confirmation by electron microscopy was possible in less than one hour in 92% of cases. The detection of early induced CMV-specific nuclear antigens by anticomplement immunofluorescence was diagnostic in 91% of cases within one day of inoculation of specimens in tissue culture. Infectivity of CMV in urine was well preserved for a least seven days at 4 C. Thus, in order to achieve a rapid diagnosis of congenital CMV infection, in sick as well as asymptomatic neonates, urine specimens may, if necessary, be transported at 4 C to distant laboratories.


The role of TNF-alpha in patients with chronic low back pain-a prospective comparative longitudinal study.
In this prospective longitudinal clinical study with a matched-pair design, we evaluated the role of tumor necrosis factor-alpha (TNF-alpha) and its clinical relevance in patients with chronic low back pain. One hundred twenty patients with chronic low back pain were matched to a healthy control group. Patients and controls were prospectively followed for 6 months. At 4 fixed time points (day 0, day 10, day 20, and 6 mo) blood samples were taken and TNF-alpha levels compared in the 2 groups, and correlations with pain level and clinical function were analyzed. At the beginning and at all other time points, there was a significantly higher proportion of TNF-alpha positive participants in the patients group than in the control group. The proportion of TNF-alpha positive patients decreased during the first 10 days of a multidisciplinary therapy in the patient group, but after this initial period, TNF-alpha levels remained constantly high with no further change until the final follow-up. In the healthy control group, the proportion of participants with positive TNF-alpha levels remained constant throughout the entire period. No significant correlation between TNF-alpha levels and pain or clinical function was detected. TNF-alpha seems to have a significant role in patients with chronic low back pain. However, the pathophysiology of this process, the clinical relevance of TNF-alpha and, especially, its part in a potential therapy regimen in these patients need to be more closely examined and defined in additional studies.


Beliefs about voices and schemas about self and others in psychosis.
In people who experience auditory verbal hallucinations, beliefs the person holds about their voices appear to be clinically important as mediators of associated distress and disability. Whilst such beliefs are thought to be influenced by broader schematic representations the person holds about themselves and other people, there has been little empirical examination of this, in particular in relation to beliefs about voice intent and the personal meaning of the voice experience. Thirty-four voice hearers with a diagnosis of schizophrenia or schizoaffective disorder completed the Psychotic Symptom Rating Scales and measures of beliefs about voices (Revised Beliefs About Voices Questionnaire, Interpretation of Voices Inventory) and schemas (Brief Core Schema Scales). Beliefs about voices were correlated with both negative voice content and schemas. After controlling for negative voice content, schemas were estimated to predict between 9% and 35% of variance in the six beliefs about voices that were measured. Negative-self schemas were the strongest predictors, and positive-self and negative-other schemas also showed potential relationships with beliefs about voices. Schemas, particularly those regarding the self, are potentially important in the formation of a range of clinically-relevant beliefs about voices.


Ultrasound for central venous cannulation: economic evaluation of cost-effectiveness.
We compared the economics of using two-dimensional ultrasound locating devices and more traditional landmark methods for central venous cannulation in the National Health Service (NHS). The evaluation consisted of a systematic review of randomised controlled trials and an economic evaluation using decision analytic cost-effectiveness modelling. Incremental costs per complication avoided associated with landmark and ultrasound central venous cannulation were modelled for patients scheduled for central venous cannulation. The marginal economic cost of using ultrasound for central venous cannulation was less than 10 pounds sterling per procedure, assuming that a machine is used for 15 procedures each week. The base case scenario implied that 2000 pounds sterling worth of resource savings result for every 1000 procedures undertaken and 90 avoided complications. Sensitivity analysis indicated that the results of modelling appear robust to the central assumptions used. Ultrasound guidance used in central venous cannulation procedures saves NHS resources even with conservative modelling assumptions.


Solid-phase synthesis of bleomycin group antibiotics. Elaboration of deglycobleomycin A(5).
The solid-phase syntheses of two deglycobleomycin A(5) analogues were achieved using a commercially available polystyrene resin containing triphenylmethyl-linked spermidine. The final products were deblocked and released from the resin, analyzed, and purified by C(18) reversed phase HPLC and characterized by high-field (1)H NMR spectroscopy and mass spectrometry. The purified products relaxed supercoiled plasmid DNA in a concentration-dependent fashion and to the same extent as authentic material derived from natural BLM A(5).


Synergy between Cu and Co in a Layered Double Hydroxide Enables Close to 100% Nitrate-to-Ammonia Selectivity.
Nitrate electroreduction (NO3RR) holds promise as an energy-efficient strategy for the removal of toxic nitrate to restore the natural nitrogen cycle and mitigate the adverse impacts caused by overfertilization from suboptimal agricultural practices. However, existing catalysts suffer from limited electrocatalytic activity, poor selectivity, inadequate durability, and low scalability. To address this quadrilemma, in this study, we developed a cost-effective layered double hydroxide (LDH) electrocatalyst with a lamellar structure that presents trimetallic CuCoAl active sites on the nanomaterial surface. This codoping design enabled electrochemical upcycling of nitrate into ammonia exclusively and efficiently with an onset potential at 0 V vs RHE, where the electrocatalytic process is less energy intensive and has a lower carbon footprint than conventional practices. The synergistic interaction among Cu, Co, and Al further afforded a 99.5% Faradic efficiency (FE) and a yield rate of 0.22 mol h-1 g-1 for nitrate-to-ammonia electroreduction, surpassing the performance of state-of-the-art nonprecious metal NO3RR electrocatalysts over an extended operation period. To gain insights into the origin of the catalytic performance observed on LDH, control materials were employed to elucidate the roles of Cu and Co. Cu was found to improve the NO3RR onset potential despite displaying limited FE for ammonia synthesis, while Co was discovered to suppress the formation of nitrite byproduct though requiring large overpotential. Simulated wastewater containing phosphate and sulfate, which are typically present in industrial effluents, was used to further investigate the effect of electrolytes on NO3RR. Intriguingly, the use of phosphate buffer resulted in a superior yield rate and FE for ammonia production while simultaneously inhibiting nitrite byproduct formation compared with the sulfate case. These experimental findings were supported by density functional theory (DFT) calculations, which explored the adsorption strength of nitrate adducts adjacent to coadsorbed electrolytes on the LDH surface. Additionally, the relative free energies of NO3RR species were also computed to examine the proton-coupled electron transfer (PCET) mechanism on CuCoAl LDH, shedding light on the potential-dependent step (PDS) and the exclusive selectivity for nitrate-to-ammonia conversion. The CuCoAl LDH developed here offers scalability by eliminating the need for precious metals, rendering this earth-abundant catalyst particularly appealing for sustainable nitrate electrovalorization technology.


Revascularization-associated Intracanal Calcification: Assessment of Prevalence and Contributing Factors.
Intracanal calcifications have been reported in endodontic cases after revascularization. The purpose of the current study was to determine the incidence of intracanal calcification and potential contributing factors in retrospective revascularization cases. Among 37 patients who had undergone revascularization between 2010 and 2014, 29 cases were assessed with average follow-up period of 24.9 months. Clinical and radiographic examinations were performed to evaluate the treatment outcomes, eg, resolution of apical periodontitis (AP), root development, and occurrence of intracanal calcification. Radiographic assessment revealed varied calcification patterns, which were classified into calcific barrier or canal obliteration, collectively referred to as revascularization-associated intracanal calcification (RAIC). All 29 cases demonstrated resolution of AP, whereas continued root development with apical closure occurred in 23 of 29 cases (79.3%). RAIC was noted in 18 of 29 cases (62.1%), among which 5 of 18 cases (27.8%) were classified as calcific barrier and 13 of 18 cases as canal obliteration (72.2%). Higher frequency of RAIC was noted in the cases with induced bleeding (16 of 23 cases, 69.6%), whereas the 6 cases without induced bleeding showed RAIC at 33.4%. Also, RAIC occurred more frequently in cases medicated with Ca(OH)2 (10 of 13 cases, 76.9%) than in those medicated with antibiotic pastes (6 of 13 cases, 46.2%). This study indicated that RAIC is common (62.1%) among cases treated with revascularization. Multiple contributing factors may include the type of medicaments and induction of intracanal bleeding. Although RAIC does not interfere with resolution of AP, some cases may progress to complete obliteration of root canals and would impede normal function of dental pulp tissues.


The R527H mutation in LMNA gene causes an increased sensitivity to ionizing radiation.
Mandibuloacral dysplasia type A (MADA; OMIM # 248370) is a premature ageing disease caused by the homozygous R527H mutation in the LMNA gene. At the cellular level, MADA is characterized by unprocessed prelamin A accumulation, nuclear architecture alterations, chromatin defects and increased incidence of apoptosis. In some progeroid laminopathies (e.g., HGPS) it has been demonstrated that such biochemical and morphological alterations are strongly linked with genomic instability. To test this also in MADA fibroblasts, their response to the ionising radiation-induced damage was analysed. We observed that their ability to repair the damage was significantly impaired, as demonstrated by the increased chromosome damage and the higher percentage of residual gamma-H2AX foci, corresponding to unrepaired DNA-damage sites. Moreover, MADA fibroblasts showed a markedly reduced phosphorylation of p53 at Ser15(S15) and a lower induction of p53 and CDKN1A proteins after irradiation, compared to the control cell line. Upon irradiation, we also detected differences in the expression of some p53 downstream target genes. In addition, MADA cells showed partial defects in the checkpoint response, particularly in G(1)/S transition. Our results indicate that accumulation of the lamin A precursor protein determines a defect in DNA damage response after X-ray exposure, supporting a crucial role of lamin A in regulating DNA repair process and cell cycle control.


Heparin surface modified intraocular lenses in uveitis.
A retrospective analysis of the results of cataract surgery using heparin surface modified intraocular lenses (HSM-IOL) performed on patients with uveitis between August 1989 and July 1993 was undertaken. In total, 32 eyes of 28 patients with various types of uveitis underwent extracapsular cataract extraction and implantation of a posterior chamber HSM-IOL. In four patients, cataract extraction was combined with trabeculectomy. The post-operative follow-up period ranged from two to 51 months (average 16 months). The visual acuity improved in 31 of 32 eyes (96.8%) with 28 eyes (87.5%) seeing 6/18 or better. In four eyes (12.5%), the visual acuity was only 6/60 due to longstanding, pre-operative cystoid macular oedema. Posterior synechiae developed in eight eyes (25%), inflammatory deposits were noticed on the IOL surface in five eyes (15.6%), and three eyes (9.3%) required YAG laser posterior capsulotomy. These results suggest that HSM lenses are associated with minimal post-operative complications and appear safe to be used in human uveitic eyes.


Dissemination of relevant information on hypertension.
The timely dissemination of new medical information to the practicing physician has been identified as a problem. To examine the magnitude of this problem and useful strategies for correction, we surveyed primary care physicians to determine their knowledge of the Hypertension Detection and Follow-up Program, a recent clinical trial with important treatment implications. Forty percent of family physicians (44/110) were aware of the study within two months of publication, and 63% of internists (114/182) learned of it within six months. Eighty percent of the family physicians and 50% of the internists listed medicine journals as the source of their knowledge, while 40% of the internists learned of it from continuing medical education (CME) courses. These findings indicate that rapid dissemination of new information can occur when relevant journals are used and that CME courses also provide a timely and effective means of dissemination.


Evolutionary Analysis of the Mammalian Tuftelin Sequence Reveals Features of Functional Importance.
Tuftelin (TUFT1) is an acidic, phosphorylated glycoprotein, initially discovered in developing enamel matrix. TUFT1 is expressed in many mineralized and non-mineralized tissues. We performed an evolutionary analysis of 82 mammalian TUFT1 sequences to identify residues and motifs that were conserved during 220 million years (Ma) of evolution. We showed that 168 residues (out of the 390 residues composing the human TUFT1 sequence) are under purifying selection. Our analyses identified several, new, putatively functional domains and confirmed previously described functional domains, such as the TIP39 interaction domain, which correlates with nuclear localization of the TUFT1 protein, that was demonstrated in several tissues. We also identified several sites under positive selection, which could indicate evolutionary changes possibly related to the functional diversification of TUFT1 during evolution in some lineages. We discovered that TUFT1 and MYZAP (myocardial zonula adherens protein) share a common ancestor that was duplicated circa 500 million years ago. Taken together, these findings expand our knowledge of TUFT1 evolution and provide new information that will be useful for further investigation of TUFT1 functions.


[The changes in vascular reactivity during aging].
Adult and old rats and rabbits revealed age-related changes of the reactivity of isolated vessels to catecholamines, vasopressin and acetylcholine. Changes that occurred in the sensitivity of various vascular areas during ageing were irregular. The increase in sensitivity of coronary vessels to vasopressin and rise of concentration of hormones in the blood promoted the development of coronary insufficiency. Stress, catecholamines sharply increased the sensitivity of coronary vessels of old rats to vasopressin. In adult and old rabbits the dyslipoproteinemia altered the sensitivity of aortal smooth muscles to epinephrine, while in old animals it enhanced the contractile effect. The shifts in vascular endothelium were shown to play certain role in the changes of vascular reactivity during ageing. The vasopressin-induced rise of cGMP in the vascular smooth muscles was more obvious in old vs. adult rats.


Altered mechanisms of endothelium-dependent dilation in skeletal muscle arterioles with genetic hypercholesterolemia.
With most cardiovascular disease risk factors, endothelium-dependent dilation of skeletal muscle resistance arterioles is compromised, although with hypercholesterolemia, impairments to reactivity are not consistently observed. Using apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) gene deletion male mouse models of hypercholesterolemia at 20 wk of age, we tested the hypothesis that arteriolar dilation would be maintained due to an increased stimulus-induced production of dilator metabolites via cyclooxygenase and cytochrome P-450 epoxygenase pathways. Arterioles from both strains demonstrated mild reductions in dilation to hypoxia and acetylcholine versus responses in C57/Bl/6J (C57) controls. However, although inhibition of nitric oxide synthase (NOS) attenuated dilation in arterioles from C57 controls, this effect was absent in ApoE or LDLR strains. In contrast, cyclooxygenase-dependent portions of dilator reactivity were maintained across the three strains. Notably, although combined NOS and cyclooxygenase inhibition abolished arteriolar responses to hypoxia and acetylcholine in C57 controls, significant reactivity remained in ApoE and LDLR strains. Whereas inhibition of cytochrome P-450 omega-hydroxylase and epoxygenases had no effect on this residual reactivity in ApoE and LDLR strains, inhibition of 12/15-lipoxygenase with nordihydroguaiaretic acid abolished the residual reactivity. With both hypoxic and methacholine challenges, arteries from ApoE and LDLR strains demonstrated an increased production of both 12(S)- and 15(S)-hydroxyeicosatetraenoic acid, end products of arachidonic acid metabolism via 12/15-lipoxygenase, a response that was not present in C57 controls. These results suggest that with development of hypercholesterolemia, mechanisms contributing to dilator reactivity in skeletal muscle arterioles are modified such that net reactivity to endothelium-dependent stimuli is largely intact.


Comparison of the Hepatitis C Continua of Care Between Hepatitis C Virus/HIV Coinfected and Hepatitis C Virus Mono-Infected Patients in Two Treatment Eras During 2008-2015.
Treatment of chronic hepatitis C virus (HCV) infection included use of pegylated interferon-based regimens before 2014 and direct-acting agents (DAA) since 2014 at the VA Medical Center in Washington, DC. We compared the continua of care between our HCV/HIV coinfected and HCV mono-infected patients during 2008-2015. A review of summary data from our local HCV Clinical Case Registry was conducted for the interferon treatment era (2008-2013) and the DAA era (2014-2015). Data were analyzed on a modified HCV Continuum of Care based on these stages: HCV diagnosis, engagement in medical care, HCV treatment, and HCV sustained virologic response (SVR) for differences between HCV/HIV coinfected and HCV mono-infected patients. All patients had 88% engagement in primary care during 2008-2013. HCV mono-infected and HCV/HIV coinfected patients had similar treatment (6% vs. 5%, p = .6622) and HCV SVR (1% vs. 0.5%, p = .1737) rates in the interferon era. However, more HCV/HIV coinfected patients were engaged in care (93% vs. 87%, p = .0044), accessed HCV treatment (36% vs. 23%, p < .0001), and achieved HCV SVR (31% vs. 21% p = .0002) compared to mono-infected patients in the DAA era. Both HCV/HIV coinfected and HCV mono-infected patients achieved higher SVR of ≥86% after DAA treatment. Although improvements were seen for treatment and SVR among HCV mono-infected patients, better rates for care engagement, HCV treatment, and SVR were realized for HCV/HIV coinfected patients in the DAA era.


Microlymphaticovenous anastomosis in the treatment of lower limb obstructive lymphedema: analysis of 91 cases.
Since 1980, 110 cases of lymphedema have been treated by microlymphaticovenous anastomosis. Of these 110 patients, 91 with obstructive lymphedema of lower limbs were reviewed. The immediate and long-term results have been very satisfactory. Excellent and good results were obtained in 79.1 percent. An average reduction in circumference of the affected limb of 6.4 cm and an average reduction of excess volume of 59.2 +/- 29.5 percent (representing 703 +/- 850 ml) were obtained. Subjective symptoms and objective signs were improved. Four patients (4.4 percent) showed poor results owing to severe fibrosis of neighboring tissue; no lymphatics could be located for anastomosis. As the authors gained experience with the operation over the last 3 years, they modified the operative procedure, the anastomotic technique, and the selection of collective lymphatics. The data obtained suggest that the quality of results is proportional to the number of anastomoses. In order to obtain the best results, the criteria for selection of patients and avoidance of postoperative relapse are discussed. Finally, a test for determination of the indications for microlymphatic surgery is described.


OspA, a lipoprotein antigen of the obligate intracellular bacterial pathogen Piscirickettsia salmonis.
No effective recombinant vaccines are currently available for any rickettsial diseases. In this regard the first non-ribosomal DNA sequences from the obligate intracellular pathogen Piscirickettsia salmonis are presented. Genomic DNA isolated from Percoll density gradient purified P. salmonis, was used to construct an expression library in lambda ZAP II. In the absence of preexisting DNA sequence, rabbit polyclonal antiserum raised against P. salmonis, with a bias toward P. salmonis surface antigens, was used to identify immunoreactive clones. Catabolite repression of the lac promoter was required to obtain a stable clone of a 4,983 bp insert in Escherichia coli due to insert toxicity exerted by the accompanying radA open reading frame (ORF). DNA sequence analysis of the insert revealed 1 partial and 4 intact predicted ORF's. A 486 bp ORF, ospA, encoded a 17 kDa antigenic outer surface protein (OspA) with 62% amino acid sequence homology to the genus common 17 kDa outer membrane lipoprotein of Rickettsia prowazekii, previously thought confined to members of the genus Rickettsia. Palmitate incorporation demonstrated that OspA is posttranslationally lipidated in E. coli, albeit poorly expressed as a lipoprotein even after replacement of the signal sequence with the signal sequence from lpp (Braun lipoprotein) or the rickettsial 17 kDa homologue. To enhance expression, ospA was optimized for codon usage in E. coli by PCR synthesis. Expression of ospA was ultimately improved (approximately 13% of total protein) with a truncated variant lacking a signal sequence. High level expression (approximately 42% tot. prot.) was attained as an N-terminal fusion protein with the fusion product recovered as inclusion bodies in E. coli BL21. Expression of OspA in P. salmonis was confirmed by immunoblot analysis using polyclonal antibodies generated against a synthetic peptide of OspA (110-129) and a strong antibody response against OspA was detected in convalescent sera from coho salmon (Oncorhynchus kisutch).


Late onset familial dystonia: could mitochondrial deficits induce a diffuse lesioning process of the whole basal ganglia system?
Striatal necrosis has been related to various clinical syndromes, with acute or chronic progression, and juvenile or late occurrence, but the most common type is Leigh's encephalopathy. Between 1967 and 1995, six out of seven related patients with chronic familial dystonia were examined. MRIs were performed in four, between 1992-1994. The seven members, affected over three generations, were the father, three daughters (one surviving), and three surviving grandsons. The leading symptoms were gait disorders and dystonia in all, dysarthria in six, verbal and motor stereotypies in two, and parkinsonian and cerebellar signs in three. Optic neuropathy was found in three. A frontal lobe syndrome without amnesia occurred in two. Symptoms occurred between the second and the fifth decade, with progressive deterioration. Magnetic resonance imaging, performed in four, showed in the two patients with severe neurological signs diffuse striatopallidal abnormal hyposignal (comparable with CSF signal) in T1 weighted images, suggesting extensive necrosis of the striatum and pallidum, associated with thalamo-subthalamo-rubro-dentato-nigral and substantia innominata hypersignals in T2 weighted images suggesting gliosis in these respective areas. The same images were described to a lesser extent in a third patient. Concentrations of lactate in CSF and serum were normal in three. Muscle biopsy, performed in four, was shown to be normal. Enzyme histochemistry showed complex I, III, and IV deficiency in surviving patients. This familial dystonia of chronic progression may be related to basal ganglia necrosis or gliosis, associated with alterations in the respiratory chain. These metabolic alterations probably play a part in the pathophysiology of these unusual brain lesions.


First Report on the Occurrence of Tetrodotoxins in Bivalve Mollusks in The Netherlands.
Tetrodotoxin (TTX) is traditionally associated with seafood from tropical regions, but recently TTX was detected in bivalve mollusks in more temperate European waters. In The Netherlands it was therefore decided to monitor TTX in shellfish harvested from Dutch production areas. All shellfish production areas were monitored in 2015, 2016 and 2017. Samples were analyzed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In total 1063 samples were investigated, and the highest concentrations were observed in 2016, i.e., 253 µg TTX/kg in oysters and 101 µg TTX/kg in mussels. No TTX analogues, with the exception of 4-epi-TTX in one single sample, were found and contaminated samples also showed positive results in the neuro-2a bioassay. The occurrence of TTX seems to be consistent over the last three years with the highest concentrations observed annually in late June. The causative organism and the reasons why specific Dutch production areas are affected while others are not, are still unclear. Initially in The Netherlands an action limit of 20 µg TTX/kg was used to ensure the safety of consumers (2016), but recently The European Food Safety Authority (EFSA) established an acute reference dose, and based on a high portion size of consuming 400 g mussels, this dose was translated into a safe concentration of 44 µg TTX per kg for shellfish. This concentration is now used as an action limit and TTX is formally included in the Dutch shellfish monitoring program.


Perceived barriers to healthy lifestyle activities in midlife and older Australian women with type 2 diabetes.
Type 2 diabetes is a leading cause of morbidity and mortality in midlife and older Australian women with known modifiable risk factors for type 2 diabetes including smoking, nutrition, physical activity and obesity. In Australia little research has been done to investigate the perceived barriers to healthy lifestyle activities in midlife and older women with type 2 diabetes. The primary aim of this study was to explore the level and type of perceived barriers to health promotion activities. The secondary aim was to explore the relationship of perceived barriers to smoking behaviour, fruit and vegetable intake, physical activity, and body mass index. The study was a cross sectional survey of women, aged over 45 with type 2 diabetes, recruited from four metropolitan community health clinics (n = 41). Data were collected from self-report questionnaires and analysed using quantitative methods. Women in the study had average total barriers scores similar to those reported in the literature for women with a range of physical disabilities and illnesses. The leading barriers for this group of women were: lack of interest, concern about safety, too tired, lack of money and feeling what they do does not help. There was no association between total barriers scores and body mass index, physical activity, fruit and vegetable intake or socio-demographic variables. This study contributes to understanding the perceptions of midlife and older women with type 2 diabetes about the level and type of barriers to healthy lifestyle activities that they experience. The participants reported a high level perceived barriers with a range of personal, social and environmental issues identified and described. This study suggests that health promo- tion education and interventions for risk factor reduction in women with type 2 diabetes may be enhanced by explicitly addressing perceived barriers to healthy lifestyle activities.


The role of p21-activated kinase in the initiation of atherosclerosis.
p21-activated kinase (PAK) has been implicated in the inflammatory activation of endothelial cells by disturbed fluid shear stress, which is the initiating stimulus in atherosclerosis. The study addresses whether PAK1 contributes to inflammatory marker expression in endothelial cells at atherosclerosis-susceptible regions of arteries in vivo. Aortas from WT and PAK1-/- C57BL/6J mice on a normal chow diet were fixed, dissected and processed for immunohistochemistry using a panel of inflammatory markers. We visualized and quantified staining in the endothelium at the greater and lesser curvatures of the arch of aorta, as atherosclerosis-resistant and susceptible regions, respectively. Fibronectin, VCAM-1 and the activated RelA NF-κB subunit were localized to the lesser curvature and decreased in PAK1-/- mice. The activated RelB NF-κB subunit was also localized to the lesser curvature but was increased in PAK1-/- mice. Low levels of staining for ICAM-1 and the monocyte/macrophage marker Mac2 indicated that overall inflammation in this tissue was minimal. These data show that PAK1 has a significant pro-inflammatory function at atherosclerosis-prone sites in vivo. These effects are seen in young mice with very low levels of inflammation, suggesting that inflammatory activation of the endothelium is primarily biomechanical. Activation involves NF-κB, expression of leukocyte recruitment receptors and fibronectin deposition. These results support and extend in vitro studies demonstrating that PAK contributes to activation of inflammatory pathways in endothelial cells by fluid shear stress.


Regioselective competitive adsorption of water and organic vapor mixtures on pristine single-walled carbon nanotube bundles.
Sequential adsorption of water and organic vapor mixtures onto single-walled carbon nanotube (SWNT) bundles is studied experimentally and by grand canonical Monte Carlo (GCMC) simulation to elucidate the distinct interactions between select adsorbates and the nanoporous structure of SWNTs. Experimental adsorption isotherms on SWNT bundles for hexane, methyl ethyl ketone, cyclohexane, and toluene individually mixed in carrier gases that were nearly saturated with water vapor are compared with the GCMC-simulated isotherms for hexane, as a representative organic, on the external surface of the heterogeneous SWNT bundles. From the nearly perfect overlap between the experimental and simulated isotherms, it is concluded that until near saturation only the internal pore volume of pristine SWNT bundles fills with water. The adsorption of water vapor on the peripheral surface of the bundles remains insignificant, if not negligible, in comparison to the adsorption of water in the internal volume of the bundles. This is in contrast with the adsorption of pure hexane, which exhibits appreciable adsorption both inside the bundles and on their external surface. It is also suggested that during competitive adsorption, water molecules take precedence over small nonpolar and polar organic molecules for adsorption inside SWNTs and leave unoccupied the hydrophobic external surface of the bundles for other more compatible adsorbates.


The causation-prevention chain in infrastructure safety measures: A consideration of four types of policy lock-ins.
Safety policies typically follow Lasswell's linear decision cycle paradigm: diagnostics, prescription, application, monitoring, and appraisal. Contemporary policy research highlights the existence of complexities in policy-making, which trigger policy lock-ins. We consider four cases in which the complex nature of the causation-prevention discourse leads to decision-making lock-ins, which deter safety progress. The four cases are conflicting narratives, missing causation inferences, prevention and mobility mismatch, and a tension between policy transfer and existing policy environments. The cases are demonstrated on recent examples of infrastructure measures that were observed in Israeli practice, which are, respectively: adding a motorway illumination, setting bus priority routes, safety improvements of multi-lane urban roads, and establishing traffic calming areas. While the four case-studies are region-specific, the discussion is relevant to other road safety measures and countries with similar policy-making problems. The consideration highlights the importance of policy-making dynamics to increase the resilience of the Safe System approach.


[Clinical, biomedical , neurological and molecular study of 11 patients with new mutations in PAH gene].
PKU is an autosomal recessive disorder. There is a broad spectrum phenotype which depends mainly on residual enzymatic activity and also on other factors such as modifying genes and non-genetic factors. This fact makes us consider that a multidisciplinary study of these patients is necessary to improve knowledge of the condition. To establish phenotype-genotype correlation and classify nine new mutations according to severity. We evaluated the clinical data obtained from a multidisciplinary trial of 11 patients with PKU/HPA who presented with nine new mutations (P275S, P279fsdelC, V388delTG, N61/I62/T63fsdel5bp, P281S, P362T, H1OOR, I164V and Y168H) identified during a molecular study of the PAH gene done in Catalonia (Spain). In our patients the genotype is correlated with the biochemical phenotype whereas the cognitive phenotype depends on determining factors such as early diagnosis and diet. Therefore, although PKU may be considered to be a complex characteristic, the mutations in the PAH gene are the main determining factor of the metabolic phenotype of PKU. A multidisciplinary study is the best way to understand and control these patients.


Regional versus systemic analgesia in video-assisted thoracoscopic lobectomy: a retrospective analysis.
The optimal perioperative analgesic strategy in video-assisted thoracic surgery (VATS) for anatomic lung resections remains an open issue. Regional analgesic concepts as thoracic paravertebral or epidural analgesia were used as systemic opioid application. We hypothesized that regional anesthesia would provide improved analgesia compared to systemic analgesia with parenteral opioids in VATS lobectomy and would be associated with a lower incidence of pulmonary complications. The study was approved by the local ethics committee (AZ 99/15) and registered (germanctr.de; DRKS00007529, 10th June 2015). A retrospective analysis of anesthetic and surgical records between July 2014 und February 2016 in a single university hospital with 103 who underwent VATS lobectomy. Comparison of regional anesthesia (i.e. thoracic paravertebral blockade (group TPVB) or thoracic epidural anesthesia (group TEA)) with a systemic opioid application (i.e. patient controlled analgesia (group PCA)). The primary endpoint was the postoperative pain level measured by Visual Analog Scale (VAS) at rest and during coughing during 120 h. Secondary endpoints were postoperative pulmonary complications (i.e. atelectasis, pneumonia), hemodynamic variables and postoperative nausea and vomiting (PONV). Mean VAS values in rest or during coughing were measured below 3.5 in all groups showing effective analgesic therapy throughout the observation period. The VAS values at rest were comparable between all groups, VAS level during coughing in patients with PCA was higher but comparable except after 8-16 h postoperatively (PCA vs. TEA; p < 0.004). There were no significant differences on secondary endpoints. Intraoperative Sufentanil consumption was significantly higher for patients without regional anesthesia (p < 0.0001 vs. TPVB and vs. TEA). The morphine equivalence postoperatively applicated until POD 5 was comparable in all groups (mean ± SD in mg: 32 ± 29 (TPVB), 30 ± 27 (TEA), 36 ± 30 (PCA); p = 0.6046). Analgesia with TEA, TPVB and PCA provided a comparable and effective pain relief after VATS anatomic resection without side effects. Our results indicate that PCA for VATS lobectomy may be a sufficient alternative compared to regional analgesia. The study was registered (germanctr.de; DRKS00007529 ; 10th June, 2015).


Effect of Resistant Starch on the Gut Microbiota and Its Metabolites in Patients with Coronary Artery Disease.
Bacteroides vulgatus and B. dorei have a protective effect against atherosclerosis, suggesting that expansion of these species in the gut microbiota could help patients with coronary artery disease (CAD). This study aimed to investigate the effect of resistant starch (RS) on the gut microbiota and its metabolites in fecal sample cultures from patients with CAD and individuals without CAD, using a single-batch fermentation system. Fecal samples from 11 patients with CAD and 10 individuals without CAD were fermented for 30 h with or without RS in the Kobe University Human Intestinal Microbiota Model (KUHIMM). Gut microbiota and the abundance of B. vulgatus and B. dorei were analyzed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing and the quantitative polymerase chain reaction. Short-chain fatty acids were analyzed using high-performance liquid chromatography. Gut microbial analysis showed significantly lower levels of B. vulgatus and B. dorei in the original fecal samples from patients with CAD, which was simulated after 30 h of fermentation in the KUHIMM. Although RS significantly increased the absolute numbers of B. vulgatus and B. dorei, and butyrate levels in CAD fecal sample cultures, the numbers varied among each patient. The effect of RS on gut microbiota and its metabolites in the KUHIMM varied between CAD and non-CAD fecal sample cultures. The KUHIMM may be useful for preclinical evaluations of the effects of RS on the gut microbiota and its metabolites.


Inflammasomes in stroke: a triggering role for acid-sensing ion channels.
Stroke is devastating and a major cause of morbidity and mortality around the world. The innate immune response plays an important role in various brain injuries, including stroke, and targeting it for therapeutic interventions would likely prove beneficial. The panoply of inflammatory cells, which induce various cellular, hormonal, and biochemical alterations, mediates the rapid progression of injury in stroke. The inflammasome, a multiprotein oligomer and a key component of specific innate immune responses, contributes toward the worsening of stroke outcomes by activating inflammatory cytokines. Acidotoxicity, mediated by acid-sensing ion channels (ASICs), also contributes toward exacerbating the condition. A role for ASICs in stroke, through the activation of the inflammasome, is emerging, which opens new avenues for understanding and intervening in stroke. In this review, we describe the various types of inflammasomes and their mechanisms of activation in stroke. Furthermore, therapeutic approaches targeting the inflammasome and that may be helpful in improving stroke outcome are discussed.


BoneJ2 - refactoring established research software.
Research software is often developed with expedience as a core development objective because experimental results, but not the software, are specified and resourced as a project output. While such code can help find answers to specific research questions, it may lack longevity and flexibility to make it reusable. We reimplemented BoneJ, our software for skeletal biology image analysis, to address design limitations that put it at risk of becoming unusable. We improved the quality of BoneJ code by following contemporary best programming practices. These include separation of concerns, dependency management, thorough testing, continuous integration and deployment, source code management, code reviews, issue and task ticketing, and user and developer documentation. The resulting BoneJ2 represents a generational shift in development technology and integrates with the ImageJ2 plugin ecosystem.


Regimes of wave type patterning driven by refractory actin feedback: transition from static polarization to dynamic wave behaviour.
Patterns of waves, patches, and peaks of actin are observed experimentally in many living cells. Models of this phenomenon have been based on the interplay between filamentous actin (F-actin) and its nucleation promoting factors (NPFs) that activate the Arp2/3 complex. Here we present an alternative biologically-motivated model for F-actin-NPF interaction based on properties of GTPases acting as NPFs. GTPases (such as Cdc42, Rac) are known to promote actin nucleation, and to have active membrane-bound and inactive cytosolic forms. The model is a natural extension of a previous mathematical mini-model of small GTPases that generates static cell polarization. Like other modellers, we assume that F-actin negative feedback shapes the observed patterns by suppressing the trailing edge of NPF-generated wave-fronts, hence localizing the activity spatially. We find that our NPF-actin model generates a rich set of behaviours, spanning a transition from static polarization to single pulses, reflecting waves, wave trains, and oscillations localized at the cell edge. The model is developed with simplicity in mind to investigate the interaction between nucleation promoting factor kinetics and negative feedback. It explains distinct types of pattern initiation mechanisms, and identifies parameter regimes corresponding to distinct behaviours. We show that weak actin feedback yields static patterning, moderate feedback yields dynamical behaviour such as travelling waves, and strong feedback can lead to wave trains or total suppression of patterning. We use a recently introduced nonlinear bifurcation analysis to explore the parameter space of this model and predict its behaviour with simulations validating those results.


Gold Nanocage-Based Multifunctional Nanosensitizers for Programmed Photothermal /Radiation/Chemical Coordinated Therapy Guided by FL/MR/PA Multimodal Imaging.
Radiotherapy is one of the main clinical methods for the treatment of malignant tumors at present. However, its application is limited by the radiation resistance of some tumor cells and the irradiation damage to the surrounding normal tissues, and the limitation of radiotherapy dose also affects the therapeutic effect. Therefore, developing diagnostic and therapeutic agents with imaging and radiosensitizing functions is urgently needed to improve the accuracy and efficacy of radiotherapy. Herein, we synthesized multifunctional nanotheranostic FRNPs nanoparticles based on gold nanocages (GNCs) and MnO2 for magnetic resonance (MR)/photoacoustic (PA) imaging and combined photothermal, radiosensitive and chemical therapy. A programmed therapy strategy based on FRNPs is proposed. First, photothermal therapy is applied to ablate large tumors and increase the sensitivity of the tumor tissue to radiotherapy, then X-ray radiation is performed to further reduce the tumor size, and finally chemotherapeutic agents are used to eliminate smaller residual tumors and distant metastases. As revealed by fluorescence, MR and PA imaging, FRNPs achieved efficient aggregation and retention at tumor sites of mice after intravenous injection. In vivo studies have shown that the programmed treatment of FRNPs-injected nude mice which were exposed to X-ray after 808 laser irradiation achieved the greatest inhibition of tumor growth compared with other treatment groups. Moreover, no obvious systemic toxicity was observed in all groups of mice, indicating the good biocompatibility of FRNPs and the safety of the treatment scheme. To sum up, our work not only showed a new radiosensitizer, but also provided a promising theranostic strategy for cancer treatment.


High resolution gamma ray tomography scanner for flow measurement and non-destructive testing applications.
We report on the development of a high resolution gamma ray tomography scanner that is operated with a Cs-137 isotopic source at 662 keV gamma photon energy and achieves a spatial image resolution of 0.2 line pairs/ mm at 10% modulation transfer function for noncollimated detectors. It is primarily intended for the scientific study of flow regimes and phase fraction distributions in fuel element assemblies, chemical reactors, pipelines, and hydrodynamic machines. Furthermore, it is applicable to nondestructive testing of larger radiologically dense objects. The radiation detector is based on advanced avalanche photodiode technology in conjunction with lutetium yttrium orthosilicate scintillation crystals. The detector arc comprises 320 single detector elements which are operated in pulse counting mode. For measurements at fixed vessels or plant components, we built a computed tomography scanner gantry that comprises rotational and translational stages, power supply via slip rings, and data communication to the measurement personal computer via wireless local area network.


Charged anesthetics selectively alter plasma membrane order.
Although indirect evidence supporting differential lipid fluidity in the two monolayers of plasma membranes has accumulated, unambiguous demonstration of this difference has been difficult to obtain. In the present study, the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), selective quenching of fluorescence by trinitrophenyl groups, and differential polarized phase fluorescence techniques were used to directly examine the static (order) and dynamic (rotational rate) components of lipid motion in the exofacial and cytofacial leaflets of LM fibroblast plasma membranes. The limiting anisotropy (0.137), the order parameter (0.590), and the rotational relaxation time (1.20 ns) of DPH in the plasma membranes (inner plus outer leaflet) indicated rapid but restricted probe motion in the lipid environment. However, the statics and dynamics of DPH motion in the individual monolayers were significantly (p less than 0.025) different. The limiting anisotropy, order parameter, and rotational relaxation time of DPH in the cytofacial monolayer were 0.036, 0.08, and 0.16 ns, respectively, greater than calculated for the exofacial monolayer of the LM plasma membrane. At appropriate concentrations, phenobarbital and, to a lesser degree, pentobarbital preferentially reduced the limiting anisotropy of DPH calculated for the exofacial leaflet while prilocaine reduced the limiting anisotropy of DPH in the cytofacial leaflet of LM fibroblast plasma membranes. In contrast, the putative cytofacial anesthetic procaine failed to show any preference for either leaflet. Arrhenius plots of DPH fluorescence in LM plasma membranes showed a prominent characteristic break point near 30-32 degrees C. Phenobarbital, pentobarbital, and procaine did not affect this break point while prilocaine selectively abolished it. The break point was therefore assigned to the inner monolayer of the LM plasma membrane.


Computerized survelliance of adverse drug reactions in hospital: pilot study.
To develop and assess the use of computerized laboratory data as a detection support tool of adverse drug reactions (ADRs) in hospital. This was a retrospective observational study of 153 sequential medical admissions during a 2-month period to the 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. Measurements made were 1) Retrospective chart review for recognized and unrecognized adverse drug reactions (ADRs) and 2) Analysis of computerizied laboratory data according to defined automatic laboratory signals (ALS) for adverse reactions. Forty ADRs have been detected in 38 out of the 153 hospital admissions (24.8%). Nine reactions were considered severe. Altogether 212 ALS were generated involving 86 admissions. In 25 (65.8%) of the ADR-positive admissions ADRs were detected through automatic signals generated from the laboratory data. ALS were detected in 56 out of the 115 (48.7%) ADR-negative admissions. Twenty-four (60%) of the ADRs were not recognized as such by the attending physicians. Two of these reactions were severe. ALS could have generated an alert for 19 (79.2%) of the unrecognized reactions. Application of automatic laboratory signals can increase the rate of recognition of the ADRs and thereby improve medical care. The sensitivity and specificity of the method might be increased by refinement and redefinition of the signals.


Topological Analysis and Gaussian Decision Tree: Effective Representation and Classification of Biosignals of Small Sample Size.
Bucking the trend of big data, in microdevice engineering, small sample size is common, especially when the device is still at the proof-of-concept stage. The small sample size, small interclass variation, and large intraclass variation, have brought biosignal analysis new challenges. Novel representation and classification approaches need to be developed to effectively recognize targets of interests with the absence of a large training set. Moving away from the traditional signal analysis in the spatiotemporal domain, we exploit the biosignal representation in the topological domain that would reveal the intrinsic structure of point clouds generated from the biosignal. Additionally, we propose a Gaussian-based decision tree (GDT), which can efficiently classify the biosignals even when the sample size is extremely small. This study is motivated by the application of mastitis detection using low-voltage alternating current electrokinetics (ACEK) where five categories of bisignals need to be recognized with only two samples in each class. Experimental results demonstrate the robustness of the topological features as well as the advantage of GDT over some conventional classifiers in handling small dataset. Our method reduces the voltage of ACEK to a safe level and still yields high-fidelity results with a short assay time. This paper makes two distinctive contributions to the field of biosignal analysis, including performing signal processing in the topological domain and handling extremely small dataset. Currently, there have been no related works that can efficiently tackle the dilemma between avoiding electrochemical reaction and accelerating assay process using ACEK.


Robust Fetal Heart Rate Tracking through Fetal Electrocardiography (ECG) and Photoplethysmography (PPG) Fusion.
Fetal electrocardiogram (fECG) or photoplethysmogram (fPPG) devices are being developed for fetal heart rate (FHR) monitoring. However, deep tissue sensing is challenged by low fetal signal-to-noise ratio (SNR). Data quality is easily degraded by motion, or interference from maternal tissues and data losses can happen due to communication faults. In this paper, we propose to combine fECG and fPPG measurements in order to increase robustness against such dynamic challenges and increase FHR estimation accuracy. To the author's knowledge the fusion of two sensory data types (fECG, fPPG) has not been investigated for FHR tracking purposes in the literature. The proposed methods are evaluated on real-world data captured from gold-standard large pregnant animal experiments. A particle filtering algorithm with sensor fusion in the measurement likelihood, called KUBAI, is used to estimate FHR. Fusion of PPG&ECG data resulted in 36.6% improvement in root-mean-square-error (RMSE) and 20.3% improvement in R2 correlation between estimated and reference FHR values compared to single sensor-type (PPG-only or ECG-only) data. We demonstrate that using different types of sensory data improves the robustness and accuracy of FHR tracking.


The Different Roles of The Channel-Kinases TRPM6 and TRPM7.
Melastatin-related Transient Receptor Potential 6 and 7 (TRPM6 and TRPM7) are cation channels with the almost unique trait of each possessing a kinase domain in its C terminus. Both the transmembrane pore and kinase are functional, and have been characterized experimentally, but whether one domain regulates the function of the other, or vice versa has remained largely unsettled. These proteins play important physiological roles in magnesium homeostasis and other cellular processes such as cell death, proliferation, differentiation and migration, and are consequently associated with several types of pathologies. Recently, studies performed in mice expressing a TRPM7 kinase-dead mutant suggest that the enzyme may function as part of a Mg(2+) sensor and transducer of signaling pathways during stressful environmental conditions. Additionally, it has been shown that TRPM7's kinase can act on its own in chromatin remodeling processes. Thus, the recent work in this field has provided new insights into the function of these interesting proteins and how they might be involved in human disease.


Biodiversity's big wet secret: the global distribution of marine biological records reveals chronic under-exploration of the deep pelagic ocean.
Understanding the distribution of marine biodiversity is a crucial first step towards the effective and sustainable management of marine ecosystems. Recent efforts to collate location records from marine surveys enable us to assemble a global picture of recorded marine biodiversity. They also effectively highlight gaps in our knowledge of particular marine regions. In particular, the deep pelagic ocean--the largest biome on Earth--is chronically under-represented in global databases of marine biodiversity. We use data from the Ocean Biogeographic Information System to plot the position in the water column of ca 7 million records of marine species occurrences. Records from relatively shallow waters dominate this global picture of recorded marine biodiversity. In addition, standardising the number of records from regions of the ocean differing in depth reveals that regardless of ocean depth, most records come either from surface waters or the sea bed. Midwater biodiversity is drastically under-represented. The deep pelagic ocean is the largest habitat by volume on Earth, yet it remains biodiversity's big wet secret, as it is hugely under-represented in global databases of marine biological records. Given both its value in the provision of a range of ecosystem services, and its vulnerability to threats including overfishing and climate change, there is a pressing need to increase our knowledge of Earth's largest ecosystem.


Nitrofurantoin-Induced Granulomatous Interstitial Pneumonia.
Nitrofurantoin-induced lung toxicity is relatively common, but rare histologic patterns sometimes occur that may make diagnosis difficult. We present the case of a 69-year-old woman taking prophylactic nitrofurantoin for urinary tract infections, who developed granulomatous interstitial pneumonia. She improved with cessation of nitrofurantoin, without other therapy. To our knowledge, this is the fourth reported case of granulomatous interstitial pneumonia associated with nitrofurantoin, and the first to show complete resolution with cessation of the drug alone, without steroids. It is important to recognize that idiosyncratic reactions to nitrofurantoin can produce a wide spectrum of histologic patterns. Of these patterns, granulomatous interstitial pneumonia is a rarely evidenced manifestation (possibly because few cases undergo a confirmatory lung biopsy). Recognition of granulomatous interstitial pneumonia as a manifestation of nitrofurantoin toxicity can aid in early identification of the reaction and prompt withdrawal of the drug, both of which are essential to prevent long-term complications.


Myocardial cell damage during experimental infective endocarditis.
Infective endocarditis was induced in 15 catheterized rabbits by a single intravenous injection of Streptococcus viridans and the papillary muscles from the left ventricle were examined for histologic and ultrastructural changes at 3 and 6 days of infection. Papillary muscles from 10 normal and 12 catheterized uninfected animals were used for comparison. Catheterized animals, infected and uninfected, had cardiac hypertrophy and papillary muscles which showed an increase in myofiber size and some interstitial edema. The muscle from infected hearts had areas of focal necrosis, diffuse monocytic infiltration, and loss of normal myocardial architecture. The papillary muscles from catheterized uninfected animals showed some degree of mitochondrial and sarcotubular swelling as well as contracture of myofibrils; the infected myocardium exhibited dramatic changes in ultrastructure such as mitochondrial swelling and destruction, sarcotubular swelling, separation of the intercalated disc, and myofibrillar contracture and disruption. These histopathologic and ultrastructural changes in papillary muscles from rabbits with bacterial endocarditis are indicative of the presence of myocardial cell damage.


An effective electrochemical biosensing platform for the detection of reduced glutathione.
A biosensor was developed using glutathione peroxidase (GSH-Px) as the enzyme. Firstly, platinum (Pt) nanoparticles were deposited onto a glassy carbon paste electrode (GCPE), and then GSH-Px was immobilized by means of gelatin that was then crosslinked with glutaraldehyde. The measurement was based on the electrochemical oxidation of GSH to its disulfide form in the presence of hydrogen peroxide. The linear range was found to be between 10 and 250 μM, with a correlation coefficient of R(2) = 0.9968. The R.S.D value for 25 μM GSH (n = 6) was calculated as 2.92%. Finally, the proposed biosensor was used to analyze GSH in a synthetically prepared plasma sample, and a promising recovery value was obtained.


Antidiabetic potential of active fraction obtained from methanolic extract of Ichnocarpus frutescens: A possible herbal remedy.
Ichnocarpus frutescens is a common plant used by tribal people and in Ayurveda for its high medicinal value. The purpose of the study was to investigate whether I. frutescens has any persuasive medicinal property to manage diabetes mellitus. Initially, male albino Wistar rats were given intraperitoneal injection of streptozotocin-nicotinamide to induce diabetes, followed with the administration of active fraction obtained from the methanolic extract of I. frutescens for the next 28 consecutive days. Glibenclamide (25 mg/kg) was used as positive control. According to the results obtained, active fraction at a dose of 50 mg/kg body weight exhibited significant antihyperglycemic activity, which was evident with reduced blood glucose level up to 58.84%. The active fraction also showed improvement in serum lipid profile as well as regeneration of pancreatic β-cells in diabetic rats. Concurrent histopathological studies reinforce the effect of active fraction in healing pancreas, thus justifying the possible mechanism of its antidiabetic activity. The results of the present investigation lead credence to the use of I. frutescens in ameliorating the diabetic condition.


U.S. Air Force aeromedical evacuation of obstetric patients in Europe.
U.S. Air Force (USAF) regulations do not recommend the routine movement of obstetrical patients greater than 34 weeks gestation. However, U.S. Department of Defense and embassy physicians throughout Europe continually request aeromedical movement of obstetrical patients greater than 34 weeks gestation. Therefore, a year-long prospective review of obstetric patient movement within the military aeromedical system in Europe was undertaken to evaluate the need for and safety of transporting pregnant women over 34 weeks gestation. Civilian studies demonstrate the safety of transporting these patients, but these studies generally address short-range transport by helicopter. By contrast, the USAF operates a high-volume, long-range aeromedical evacuation system with large fixed-wing aircraft. Of the 13,095 patients reported for military aeromedical movement within the study time frame, 329 patients were uneventfully airlifted for obstetrical reasons. This study suggests that long distance movement by fixed-wing aircraft of obstetric patients at any gestational age can be done safely in the USAF military aeromedical system.


Annexin A2 is required for the early steps of cytokinesis.
Cytokinesis requires the formation of an actomyosin contractile ring between the two sets of sister chromatids. Annexin A2 is a calcium- and phospholipid-binding protein implicated in cortical actin remodeling. We report that annexin A2 accumulates at the equatorial cortex at the onset of cytokinesis and depletion of annexin A2 results in cytokinetic failure, due to a defective cleavage furrow assembly. In the absence of annexin A2, the small GTPase RhoA-which regulates cortical cytoskeletal rearrangement-fails to form a compact ring at the equatorial plane. Furthermore, annexin A2 is required for cortical localization of the RhoGEF Ect2 and to maintain the association between the equatorial cortex and the central spindle. Our results demonstrate that annexin A2 is necessary in the early phase of cytokinesis. We propose that annexin A2 participates in central spindle-equatorial plasma membrane communication.


Effects of i.v. anaesthetic agents and halothane on [3H]tetracaine binding to rat cerebrocortical membranes.
In an attempt to determine if there is any overlap in local and general anaesthetic binding sites, we have examined the effects of thiopental, phenobarbital, pentobarbital, propofol, ketamine (racemic and R(+)/S(-)), alfaxalone, etomidate and halothane on [3H]tetracaine binding to rat cerebrocortical membranes. Membranes were prepared in Tris HCI 50 mmol litre-1, pH 7.4, by homogenization and centrifugation. Binding assays were performed in 1-ml volumes of Tris HCI buffer at room temperature or 37 degrees C for halothane. Binding of [3H]tetracaine was displaced dose-dependently by unlabelled tetracaine with a mean pIC50 value of 6.91 (SEM 0.07) (123 nmol litre-1). With the exception of propofol (at high concentrations), all i.v. anaesthetic agents failed to displace the binding of [3H]tetracaine. In contrast, halothane produced a dose-dependent and statistically significant reduction in total [3H]tetracaine binding at clinically achievable concentrations (0.289, 0.885 and 1.484 mmol litre-1 equivalent to 1.0, 3.1 and 5.1 rat MAC) without markedly affecting the pIC50. Collectively these data may suggest some overlap in the binding sites for [3H]tetracaine and volatile but not i.v. general anaesthetic agents.


Seizure-related outcome after corticoamygdalohippocampectomy in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis evaluated by magnetic resonance imaging alone.
The authors conducted a study to assess the efficacy of surgery in patients who underwent magnetic resonance (MR) imaging alone for localization of foci in temporal lobe epilepsy (TLE). One hundred patients (43 men, 57 women) with a clinical diagnosis of TLE were prospectively studied (mean age 28 +/- 9 years [+/- standard deviation {SD}]). All patients underwent high-resolution MR imaging, and in all unilateral mesial temporal sclerosis (MTS) was diagnosed by visual inspection. All patients underwent interictal preoperative electroencephalography (EEG) and in 87 patients pre- and 1-year postoperative neuropsychological testing was performed. Both EEG and neuropsychological examinations were conducted in a blinded fashion, and these data were not taken into account during the surgery-related decision-making process. All patients underwent a corticoamygdalohippocampectomy at the side of the MTS. Surgery-related outcome was rated as Class I (seizure free or simple partial seizures only) or Class II (> or = 90% improvement). The follow-up period ranged from 18 to 48 months (mean 24 +/- 5 months [+/-SD]). No patient underwent prolonged video-EEG monitoring, Wada testing, positron emission tomography, or single-photon emission computerized tomography. In eighty-nine patients Class I results were achieved, and 11 Class II results were achieved postoperatively. There was no mortality in this series. Except for in two patients who underwent surgery in the dominant temporal lobe, there was no postoperatively cognitive decline. In these two patients verbal memory decline occurred, which was associated with posterior temporal cortical damage, demonstrated postoperatively on MR imaging. Twenty-five percent of the patients experienced improved memory function related to the nonoperated side, and 54% experienced a 10% gain in general intelligence quotient status. In patients with clinically suspected TLE, MR imaging alone is able to localize temporal lobe foci correctly. Ruling out pseudoseizures remains the only indication for prolonged video-EEG recordings in this group of patients.


Expression of p21 predicts PSA failure in locally advanced prostate cancer treated by prostatectomy.
The management of prostate cancer is based on several clinicopathological criteria. The ability to determine the tumor's biological potential is one goal of tumor markers in order to identify patients who may require more intensive treatment strategies. The purpose of our study was to determine if p21/(WAF1/CIP1) expression can predict biochemical failure in patients with locally advanced prostate cancer treated by radical retropubic prostatectomy (RRP). We used immunohistochemistry to analyze patterns of p21 expression in a population of 296 patients with locally advanced (pT3) prostate cancer treated by RRP. Results were correlated with clinicopathological parameters and time to PSA failure. For the entire cohort of 296 patients, after adjustment for prognostic factors, p21 expression was associated with an increased risk of PSA failure (relative risk [RR] = 1.48) of statistical significance at a median follow-up of 54.5 months. Other parameters that independently predicted the risk of PSA failure included lymph node metastasis and seminal vesicle involvement. Because neoadjuvant hormonal therapy (NHT) is known to lead to involutional changes in prostatic carcinoma, we performed multivariate analyses after stratifying for NHT prior to surgery. Among the 172 patients treated by RRP alone, p21 expression was an independent predictor of PSA failure (RR = 2.30), as were lymph node metastases (RR = 3.19) and pathological grade 5-7 and 8-10 (RR = 2.87 and 3.50, respectively). p21 over-expression is an independent predictor of PSA failure in pT3 patients treated by radical prostatectomy, especially if they did not receive NHT. This tumor marker may help clinicians identify patients who may require adjuvant treatment strategies following radical prostatectomy.