Changes in the organization of actin and myosin in non-muscle cells induced by N-ethylmaleimide.
There is evidence from in vitro studies that the SH reagent N-ethylmaleimide (NEM) causes the formation of ATP-resistant rigor-complexes between actin and myosin, and NEM-modified heavy meromyosin has been used by Cande et al. to study the contractile process during cytokinesis. It is reported here that treatment of tissue-cultured cells with NEM causes an immediate cessation of all motile activities and a simultaneous stabilization of the ultrastructure of the cell visualized on lysis with detergent-containing buffers. After NEM treatment a 5- to 10-fold increase in the amount of myosin was found associated with the detergent-resistant cell residues. As suggested by immunoelectron microscopy, using antibodies to non-muscle myosin together with gold-labelled protein A, increasing amounts of myosin filaments became associated with the microfilament assemblies of the cell with time of NEM treatment. In addition to this there was a slow, progressive reorganization of the cortical wave of microfilaments. The structures interpreted as myosin filaments were visualized at relatively high resolution. The immunoelectron microscopy finally also indicated the presence of a non-filamentous form of myosin in agreement with the results of others.


Critical period of bilirubin-induced cerebellar hypoplasia in a new Sprague-Dawley strain of jaundiced Gunn rats.
Homozygous (j/j) and heterozygous (j/+) newborn Gunn rats of the Sprague-Dawley strain were photoirradiated for 24 h at scheduled postnatal days and the effects of irradiation on the cerebellar development were examined at 30 days of life. Improvement of the survival rate was the most notable effect of photoirradiation. A single 24-h dose of photoirradiation during a period of postnatal days 4-11 effectively prevented hypoplasia in the j/j rat cerebellum. No prevention by light was observed at days 3 and 12. It was found that the most effective day of irradiation on the cerebellar development of j/j rats was centered on postnatal day 7. When plasma bilirubin was assessed during the period of postnatal days 7-10, a distinct diminution of the concentration was observed, restricted to only the period of the light treatment. Although there were some differences in the effective day as well as in the degree of efficacy of phototherapy among cerebellar lobules or sublobules, day 7 was the most critical for cerebellar hypoplasia due to bilirubin.


The binding sites of cytochalasin D. II. Their relationship to hexose transport and to cytochalasin B.
Cytochalasin B (CB) was able to compete with tritiated cytochalasin D (3H-CD) for binding sites in HEp-2 cells. The pattern of inhibition suggested that CB associates with a low affinity class of CD binding sites. Glucose and maltose did not inhibit binding of 3H-CD to isolated HEp-2 plasma membrane. Inhibition of hexose transport by CD was negligible, but CD did not block the potent inhibition of this transport by CB. These results indicate that CD does not bind to the high affinity CB receptor reportedly associated with the hexose transport system, and that this receptor cannot mediate the morphological effects of CD. Both CD and CB induced contraction-zeoisis in HEp-2 cells; CB was less potent than CD, and their effects appeared to be additive. It was concluded that the high affinity binding sites for CD and CB are different, but that these congeners share a low affinity site. Both high and low affinity sites for CD appear to mediate its morphological effects; only the low affinity class appears to be involved for CB. Possible identification of the common low affinity binding site as actomyosin (detailed in Tannenbaum et al., '77) is further discussed.


Clinical studies: evidence for intervention with specific antiplatelet drugs in arterial thromboembolism.
There is conclusive evidence that aspirin is beneficial in patients with unstable angina and that a combination of preoperative dipyridamole with post-operative aspirin is beneficial after coronary artery bypass. The evidence for a beneficial effect of aspirin after myocardial infarction is consistent but inconclusive. The evidence for the use of aspirin alone following coronary bypass is inconclusive. There is convincing evidence that aspirin will reduce the rate of recurrent TIA, stroke, and death in patients with TIA.


A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms.
Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN are asymptomatic at diagnosis although some of them suffer from constitutional symptoms. Thrombosis and bleeding can also be one of the initial manifestations although the reported prevalence varied considerably across the studies. This systematic review and meta-analysis was conducted with the aims to better understand the prevalence and characteristics of thrombosis and bleeding among patients with newly-diagnosed MPN. Using a search strategy that included the terms for myeloproliferative neoplasms, thrombosis, and bleeding, two investigators independently searched for published articles indexed in the MEDLINE and EMBASE databases from inception to August 2018. The pooled prevalence was calculated using the DerSimonian-Laird random-effects model with a double arcsine transformation. A total of 29 cohort studies (8 prospective and 21 retrospective) with 13,436 patients with MPN were included into this meta-analysis. At diagnosis, the pooled prevalence of overall thrombosis among patients with MPN was 20.0% (95% CI, 16.6-23.8%; I2 96%), with the pooled prevalence of arterial thrombosis of 16.2% (95% CI, 13.0-20.0%; I2 95%) and the pooled prevalence of venous thrombosis of 6.2% (95% CI, 4.9-7.8%; I2 89%). Common thrombotic events included cerebrovascular disease/transient ischemic attack, coronary heart disease, and deep venous thrombosis. The pooled prevalence of hemorrhagic complications among patients who were newly diagnosed with MPN patients was 6.2% (95% CI, 5.0-7.8%; I2 85%). Common sites of bleeding included gastrointestinal, mucosal, and cutaneous bleeding. Thrombosis and bleeding are common initial manifestations of MPN. Investigations for MPN should be considered for patients who present with unexplained thrombosis or abnormal bleeding.


Match probabilities for Y-chromosomal profiles: A paradigm shift.
Calculating match probabilities for genetic profiles under the hypothesis that a person of interest (henceforth the 'suspect') is not the donor of a particular forensic trace is challenging because the reference population is usually not clear-defined in such cases. Hence, the concept of 'suspect population' was introduced to allow for the fact that possible alternative trace donors often resemble the suspect in terms of their geographic, ethnic and social affiliation. In fact, they may even be genetically related to the suspect. Although the possibility of relatedness affects the size of the match probability in general, this is not a practically relevant issue for autosomal profiles owing to the stochastic independence of the markers included. The situation is, however, different for Y-chromosomal short tandem repeat (STR) profiles. Here, almost all profile matches are likely to be identical by descent, and profile identity may be common even among distantly related males. The degree of relatedness between suspect and alternative trace donors is thus a critical aspect of the evaluation of Y-chromosomal STR profile matches. All methods hitherto proposed to derive match probabilities for such cases, including our own, were anti-conservative in that they equated the suspect population to a database population (of virtually unrelated individuals). The nature of the true suspect population, however, is usually unknown and hard, if not impossible, to determine so that calculation of proper match probabilities remains a difficult task. Therefore, since lower Y-chromosomal match probabilities would result from higher mutation rates, even for close relatives, future research should rather focus upon the characterization of novel and more mutable Y-chromosomal STRs.


[Local dermatoplastic procedures following the excision of basaliomas of the facial skin under ambulatory condition].
The operative treatment of patients with basal cell carcinomas of the face skin with using local skin plasty can be performed under ambulatory conditions and gives good oncological and cosmetic results.


Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis.
The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19). We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors. A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB. Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.


Isolation and short-term culture of primary keratinocytes, hair follicle populations and dermal cells from newborn mice and keratinocytes from adult mice for in vitro analysis and for grafting to immunodeficient mice.
Protocols for preparing and culturing primary keratinocytes from newborn and adult mouse epidermis have evolved over the past 35 years. This protocol is now routinely applied to mice of various genetic backgrounds for in vitro studies of signaling pathways in differentiation and cell transformation, and for assessing the in vivo phenotype of altered keratinocytes in grafts of cells on immunodeficient mice. Crucial in the development and application of the procedure was the observation that keratinocytes proliferate in media of low calcium concentration, but rapidly commit to differentiation at calcium concentrations >0.07 mM after the initial attachment period. Preparing primary keratinocytes from ten newborn mice requires 2-3 h of hands-on time. Related procedures are also provided: preparing immature hair follicle buds, developing dermal hair follicles and fibroblasts from newborn mice, preparing primary keratinocytes from adult mice and grafting cell mixtures on athymic nude mice.


Managing the pandemic from the radiology department's point of view.
The COVID-19 pandemic is forcing our entire society to adopt numerous changes, at least until an effective treatment and/or vaccine becomes widely available. Because COVID-19 is a new disease that has required us to make complex decisions based on scant evidence, the pandemic is having an enormous impact on our health system. Radiology departments play a fundamental role in the management of COVID-19, both in the diagnosis of the disease and in the posterior management of patients. To ensure the safety of patients and healthcare professionals, it is essential to understand the infection so that safe circuits can be implemented. This article summarizes the pathophysiology of COVID-19 infection and explains the measures that radiology departments need to adopt during the pandemic.


Diagnostic performance of three non-invasive fibrosis scores (Hepamet, FIB-4, NAFLD fibrosis score) in NAFLD patients from a mixed Latin American population.
Several non-invasive scoring systems have been developed and validated worldwide to predict the risk of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). However, information about the performance of these systems in Latin American populations is scarce. Our aim was to evaluate the performance of the Hepamet Fibrosis Score, Fibrosis-4 (FIB-4) and the NAFLD Fibrosis Score (NFS) in a mixed Latin American group of NAFLD patients. Clinical, laboratory and liver biopsy data collected from 379 biopsy-proven NAFLD patients from Latin American tertiary health centers were reviewed. Histological fibrosis stages were classified using the Kleiner score. Accuracy was determined, and new fibrosis score thresholds were calculated to better compare the performances of non-invasive tests and to explore their usefulness in excluding fibrosis. The distribution of fibrosis stages among the sample population was as follows: F0 (45%), F1 (27%), F2 (8%), F3 (16%) and F4 (4%). Using modified thresholds, the areas under the ROC curves (AUROC) for Hepamet and FIB-4 (0.73 and 0.74, respectively) to detect significant fibrosis were higher than that of NFS (0.58). However, the AUROCs of the three scores were not significantly different in advanced fibrosis and cirrhosis. To exclude fibrosis, we calculated lower cutoffs than standard thresholds for Hepamet, FIB-4 and NFS with similar performances. Thresholds of non-invasive fibrosis scores (Hepamet, FIB-4 and NFS) can be modified to maximize diagnostic accuracy in Latin American patients with NAFLD.


Assaying human neutrophil elastase activity by capillary zone electrophoresis combined with laser-induced fluorescence.
Skin aging is a progressive process determining the ultimate skin appearance. Human neutrophil elastase (HNE) has been shown to play an important role in the degradation of the extracellular matrix. In order to assay HNE kinetics, a novel online capillary zone electrophoresis (CZE) assay has been developed in this study for the determination of the maximum velocity (Vmax) and of the Michaelis-Menten constant (Km) of HNE regarding several potential substrates. These assays are based on short-end injection to shorten analysis time, on transverse diffusion of laminar flow profiles (TDLFP) for in-capillary reactant mixing, and on UV or laser-induced fluorescence (LIF) detection. Kinetic constants for a referenced peptidic substrate were determined using not only online assays but also offline (pre-capillary) mode. The results obtained were cross compared and compared to the literature in order to validate the developed assays. The hydrolysis of three new potential fluorogenic substrates by HNE was also monitored. Two new peptidic substrates for HNE were identified through this study. Km values of these novel substrates were successfully determined using online CZE assay (Km ∼0.07mM). This value was in the same order of magnitude of that of the referenced substrate despite the presence of the labeling group 5-carboxyfluorescein (5-FAM). HNE activity has never been assessed using online CZE-based assay, neither with UV nor with LIF detection. The developed assay conducted with the new labeled substrates is particularly sensitive (LOQ of few nM), does not require the presence of micelles in the BGE (which is the case for the reference substrate) and only necessitates few nanoliters of reactants making it particularly adapted for screening studies.


Systolic Sac Pressure Index for the Prediction of Persistent Type II Endoleak for 12 Months After Endovascular Abdominal Aortic Aneurysm Repair.
To assess the relationship between the systolic sac pressure index (SPI) and the presence of endoleaks 12 months after endovascular abdominal aortic aneurysm repair (EVAR). We performed a single-center prospective trial of consecutively treated patients. SPI (calculated as systolic sac pressure/systolic aortic pressure) was measured by catheterization immediately after EVAR. Contrast-enhanced computed tomography was scheduled 12 months after EVAR to detect possible endoleaks. Data were available for 34 patients who underwent EVAR for an AAA. Persisting type II endoleak was found in 8 patients (endoleak-positive group) but not in the other 26 patients (endoleak-negative group). The mean ± standard deviation SPI was significantly greater in the endoleak-positive group than in the endoleak-negative group (0.692 ± 0.048 vs. 0.505 ± 0.081, respectively; P = .001). Receiver-operating characteristic curve analysis revealed that an SPI of 0.638 was the optimum cutoff value for predicting a persistent endoleak at 12 months with high accuracy (0.971; 33/34), sensitivity (1.00), and specificity (0.962) values. The mean change in AAA diameter was -4.28 ± 5.03 mm and 2.22 ± 4.54 mm in patients with SPI of <0.638 or ≥0.638, respectively (P = .002). Patients with an SPI of ≥0.638 immediately after EVAR were more likely to have a persistent type II endoleak at 12 months with an accuracy of 0.971, and showed increases in aneurysm sac diameter compared with patients with an SPI of <0.638.


The effect of maternal educational status, antenatal care and resumption of menses on postpartum contraceptive use in Ethiopia: systematic review and meta-analysis.
The postpartum period is a crucial starting point for the delivery of family planning services. To date, there are numerous primary studies in Ethiopia on postpartum contraceptive use and related factors. However, the results of key variables are inconsistent, making it difficult to use the results to advance the service dimensions of postpartum contraceptive use in the country. Therefore, this systematic review and meta-analysis was required to summarize this inconsistency and compile the best available evidence on the impact of maternal educational status, antenatal care and menstrual resumption on postpartum contraceptive use in Ethiopia. PubMed, Google Scholar, Scopus, Science Direct, and the repositories of online research institutes were searched. Data were extracted with Microsoft Excel and analyzed with the statistical software STATA (version 14). Data on the study area, design, population, sample size, and observed frequency were extracted using the Joanna Briggs Institute tool. To obtain the pooled effect size, a meta-analysis was performed using a weighted inverse variance random effects model. Cochran's Q X2 test, and I2 statistics were used to test for heterogeneity, estimate the total quantity, and measure the variability attributed to heterogeneity. A mixed-effects meta-regression analysis was performed to identify possible sources of heterogeneity. To examine publication bias, the Eggers regression test and the Beggs correlation test were used at a p-value threshold of 0.001. Of the 654 articles reviewed, 18 studies met the inclusion criteria and were included in this meta-analysis. Overall, the final analysis includes 11,263 study participants. In Ethiopia, postpartum contraceptive use correlated significantly with maternal educational status (OR = 3.121:95% CI 2.127-4.115), antenatal care follow-up (OR = 3.286; 95% CI 2.353-4.220), and return of the mother's menses (OR = 3.492; 95% CI 1.843-6.615). A uniform meta-regression was performed based on publication year (p = 0.821), sample size (p = 0.989), and city of residence (p = 0.104), which revealed that none of these factors are significant. The use of postpartum contraceptives was found to be better among mothers who are educated, attended antenatal appointments, and resumed their menstrual cycle. Based on our research, we strongly recommended that antenatal care use and maternal educational accessibility need to improve. For family planning professionals, removing barriers to menstruation resumption should be a key priority.


Thrombin-induced neuropeptide Y secretion from rat platelets.
To study the thrombin-induced secretion of platelet neuropeptide Y (NPY) in rats. The platelet aggregation induced by ADP or thrombin was recorded by an aggregometer. NPY in platelet and plasma was measured by radioimmunoassay. The intracellular free Ca2+ ([Ca2+]i) was measured by Fura-2 fluorescent assay. Thrombin 0.75 or 2.5 kU L-1 increased [Ca2+]i from 119 +/- 8 nmol L-1 to 530 +/- 60 or 1340 +/- 100 nmol L-1, respectively together with the secretion of platelet NPY. Edetic acid 2 mmol L-1 almost abolished the thrombin-induced increases of [Ca2+]i and reduced the NPY secretion by 56% and 30%, respectively. Neither [Ca2+]i increase nor platelet NPY secretion induced by thrombin was affected by verapamil. The thrombin-induced NPY secretion was inhibited by 55%-70% by indometacin or creatine phosphate plus creatine phosphokinase. Thrombin-induced platelet NPY secretion was related to an Ca2+ influx through non-voltage dependent Ca2+ channels and positive feedbacks of arachidonate metabolites or/and released ADP.


Athletic injuries of the lateral abdominal wall: review of anatomy and MR imaging appearance.
The lateral abdominal wall is comprised of three muscles, each with a different function and orientation. The transversus abdominus, internal oblique, and external oblique muscles span the abdominal cavity between the iliocostalis lumborum and quadratus lumborum posteriorly and the rectus abdominis anteriorly. The lateral abdominal wall is bound superiorly by the lower ribs and costal cartilages and inferiorly by the iliac crest and inguinal ligament. The lateral abdominal wall may be acutely or chronically injured in a variety of athletic endeavors, with occasional acute injuries in the setting of high-energy trauma such as motor vehicle collisions. Injuries to the lateral abdominal wall may result in lumbar hernia formation, unique for its high incarceration rate, and also Spigelian hernias. This article will review the anatomy, the magnetic resonance (MR) imaging approach, and the features and complications of lateral abdominal wall injuries.


[The pharmaceutical and biopharmaceutical assessment of acetylaminonitropropoxybenzene (Falimint). 6. Quantitative composition of metabolites].
Substances appearing in the metabolism of Falimint were analyzed quantitatively. The composition of metabolites is remarkable constant in various persons and dosages. The concentration of metabolites in urine accumulates after 2 h. Within 6 h the bulk of metabolites is eliminated.


Microglial expression of GAT-1 in the cerebral cortex.
Microglial cells are the immune cells of the brain that, by sensing the microenvironment, permit a correct brain development and function. They communicate with other glial cells and with neurons, releasing and responding to a number of molecules that exert effects on surrounding cells. Among these, neurotransmitters and, in particular, gamma-aminobutyric acid (GABA) has recently gained interest in this context. We demonstrated the expression of GABA transporter 1 (GAT-1) in microglial cells both in soma and cell processes. We show that microglial cell treatment with 1,2,5,6-tetrahydro-1-[2-[[(diphenylmethylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid hydrochloride (NNC-711), a potent and selective GAT-1 inhibitor, significantly reduced Na+ -dependent GABA uptake. On the other hand, GABA uptake was significantly increased by cell treatment with (S)-1-[2-[tris(4-methoxyphenyl)methoxy]ethyl]-3-piperidinecarboxylic acid (SNAP-5114), a GAT-2/3 inhibitor, and this effect was completely blocked by the botulinum toxin BoNT/C1, that specifically cleaves and inactives syntaxin 1A (STX1A). Overall, these findings show that microglial cells express GAT-1 and indicate that STX1A plays an important role in the regulation of GAT-1-dependent GABA uptake in microglia.


Complete genomic sequence of the goat prion protein gene (PRNP).
Prion protein genetics plays a central role in transmissible spongiform encephalopathies, a disease occurring in human and animals. Here we report a 27-kb genomic sequence containing the goat PRNP gene. It shows, both in structure and content, a remarkable similarity with its sheep ortholog and can serve as a basis for future (comparative) studies with reference to the regulation of PRNP gene expression and the search for genetic tools to prevent/control/eradicate (goat) TSE.


Feasibility, Safety and Accuracy of Echocardiography-Fluoroscopy Imaging Fusion During Percutaneous Atrial Septal Defect Closure in Children.
Imaging fusion between echocardiography and fluoroscopy was recently developed. The aim of this study was to assess its feasibility and accuracy during pediatric cardiac catheterization. Thirty-one patients (median weight, 26 kg; interquartile range [IQR], 21-37 kg) who underwent percutaneous atrial septal defect closure were prospectively included. The feasibility and accuracy of various imaging fusion modalities (live two-dimensional, live color two-dimensional, live three-dimensional and markers) with EchoNavigator software were assessed. To assess the accuracy of spatial registration of the echocardiogram on the fluoroscopic image, the occluder screw, an object that appeared on each image, was used as a reference tool, and the distance between the two when fused was measured. A distance was measured on the fusion screen between a marker positioned on the screw from the echocardiography screen and from the fluoroscopy screen (distance 1). Another distance was measured on the fusion screen between the screw visualized by three-dimensional echocardiography and by fluoroscopy (distance 2). The two distances were measured on four C-arm orientations in end-systolic and end-diastolic frames. Fusion and marker positioning were feasible in real time in all cases. On the fusion screen, median systolic and diastolic distance 1 were 0.5 mm (IQR, 0.3-1 mm) and 2 mm (IQR, 1.5-2.5 mm; P < .0001), respectively. The marker positioned from the echocardiography screen was fixed on the fusion screen and did not follow the movement of the screw. Median systolic and diastolic distance 2 were 0.5 mm (IQR, 0-0.5 mm) and 2 mm (IQR, 1.5-2.5 mm; P < .0001), respectively. Echocardiographic fluoroscopic imaging fusion is feasible, safe, and accurate in children weighting >20 kg. This technique offers a new method of imaging guidance in the catheterization laboratory for complex procedures and training.


Development and preliminary evaluation of the psychometric properties of the psychological flexibility in epilepsy questionnaire (PFEQ).
The present study describes the development and preliminary psychometric evaluation of the Psychological Flexibility in Epilepsy Questionnaire (PFEQ), which was developed to measure the construct referred to as Psychological Flexibility (PF) in epilepsy. Results from 81 participants with epilepsy support a one-factor solution, consisting of 12 items, indicating a satisfactory structure and reliability with an alpha coefficient of 0.92. Criterion validity of the instrument was supported by moderate correlations with outcomes predicting quality of life, PF in the general population, depressive symptoms, and anxiety symptoms. Number of seizures in the past three and 12 months was positively correlated with scores on the PFEQ. These findings are consistent with the instrument's underlying theory. Further development and investigation of the PFEQ is recommended, as the preliminary results of the questionnaire suggest that the scale has the potential to be a valuable contribution to the future exploration of the role of PF in epilepsy.


Aquaporin-4-autoimmunity in patients with systemic lupus erythematosus: A predominantly population-based study.
Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE. The study included a predominantly population-based cohort with clinical and serological investigations of 208 patients with SLE, followed prospectively since 1995. All patients received immunosuppressive treatment. NMOSD was evaluated retrospectively based on the 2015 International Panel for NMOSD Diagnosis (IPND) criteria. Polymorphisms in programmed cell death protein 1 (PDCD-1) PD-1.3 G/A were genotyped. AGP4-IgG and other autoantibodies, including myelin oligodendrocyte glycoprotein (MOG), was determined blinded to clinical diagnosis. Of 208 patients with SLE, 45(22%) had neuropsychiatric (NP) SLE, and CNS involvement predominated in 30 of 45 (67%) patients. Serum AQP4-IgG was detected in 2 of 30 (6.7%) neuropsychiatric SLE (NPSLE) patients both of whom had myelitis and antiphospholipid syndrome; one patient also had myasthenia gravis. None had MOG-IgG. PD-1.3A allele was not associated with SLE nor with NPSLE. AQP4-IgG autoimmune syndrome may rarely co-exist with SLE, and such patients have other NMOSD-typical syndromes such as myelitis.


Duration of labor and risk of cerebral white-matter damage in very preterm infants who are delivered with intrauterine infection.
The purpose of this study was to assess whether the duration of labor has any effect on the occurrence of cerebral white-matter damage in very preterm infants who are delivered in the presence of intrauterine infection. From a cohort of infants who were born spontaneously at <32 weeks of gestation for whom placental information was available and who survived 7 days from birth, 126 infants had clinical, laboratory, or histologic evidence of intrauterine infection. Among them, variables were compared between those infants with white-matter damage (defined as intraventricular hemorrhage grade 3 plus, periventricular leukomalacia, or ventriculomegaly not associated with hydrocephaly [n = 13]) and those infants without it (n = 113). Comparisons were made with t test, chi-squared test, and survival analysis; a probability value of <.05 was considered significant. There were no differences between the 2 groups in gestational age at delivery and rates of labor or cesarean delivery. Duration of active labor (66 +/- 45 minutes vs 88 +/- 75 minutes; P =.49) and of clinical chorioamnionitis (310 +/- 186 minutes vs 529 +/- 544 minutes; P =.44) were similar in cases with and without neonatal white-matter damage. In 126 infants who were born at <32 weeks of gestation with intrauterine infection, we found no correlation between the duration of labor or clinical chorioamnionitis and neonatal white-matter damage.


Treatment efficacy and safety of adalimumab versus tocilizumab in patients with active and severe Takayasu arteritis: an open-label study.
This study aimed to compare the efficacy and safety of adalimumab (ADA) versus tocilizumab (TCZ) in patients with Takayasu arteritis (TAK). This was a randomized, controlled, open-label study. Forty patients with active and severe TAK were enrolled. They were treated with ADA (n = 21) combined with glucocorticoids (GCs) and methotrexate (MTX) or TCZ (n = 19) combined with GCs and MTX. The planned follow-up duration was 12 months. The primary end point was the efficacy rate (ER) at 6 months. The secondary endpoints included ER at 9 and 12 months, relapse rate, GC tapering, adverse effects, and life quality changes during treatment. In the intention-to-treat (ITT) population, the ER at 6 months was higher in the ADA group (85.71% vs 52.63%, P= 0.02). A similar direction of effect was noted in the per-protocol set (89.47% vs 62.50%, P= 0.06). The percentages of patients who achieved a GC dose of ≤ 10 mg/day at 6 months were similar between the ADA and TCZ groups (47.37% vs 43.75%, P= 0.83). The ERs at 9 and 12 months were similar between the two groups (P> 0.05). During the first 12 months of treatment, the relapse rate and adverse event incidence were comparable between the two groups (ADA vs TCZ: 9.52% vs 10.53%, P= 0.96; 38.10% vs 47.37%, P= 0.55, respectively). ADA combined with GCs and MTX may be more efficacious than TCZ combined with GCs and MTX among patients with active and severe TAK. Clinicaltrials.gov; NCT04300686.


Molecular implications of the human glutathione transferase A-4 gene (hGSTA4) polymorphisms in neurodegenerative diseases.
Several lines of evidence, including an increased level of lipid peroxidation and the depletion of antioxidant molecules like as glutathione (GSH), indicate that oxidative stress plays an important role in the pathogenesis of several neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD). We previously observed a significant increased level of DNA oxidative damage in peripheral blood cells of PD patients, with respect to controls, moreover, the activity of glutathione transferases (GSTs) measured in circulating plasma was higher in controls than in PD patients, suggesting a lower enzymatic protection in PD individuals. Among human GSTs, glutathione transferase A4-4 displays a high catalitic activity towards 4-hydroxy-2-nonenal (HNE), a marker of lipid peroxidation whose levels have been found significantly increased in the substantia nigra of Parkinson's disease patients, in respect to controls. We performed this study to determine the presence of allelic variants of functional interest in the coding region of the hGSTA4 gene on 60 PD patients and 60 healthy controls. By the combined effort of polymerase chain reaction/single-strand conformation polymorphisms (PCR/SSCP) techniques, we observed a single nucleotide polymorphism (SNP) G351A leading to the silent mutation Gln117Gln. No significant difference was observed in the distribution of this polymorphism between PD individuals and controls, moreover, we did not observe any other polymorphism in the hGSTA4 gene in our population. Further studies are required to test the role played by both factors regulating the level of the expression of the hGSTA4 gene and any possible post-translational modification of the protein, in the protection against oxidative damage in neuronal cells.


The relationship between mercury concentration in human organs and different predictor variables.
Samples from different tissues were collected from autopsies of individuals of the general population of the Stockholm area, Sweden. The samples were analysed for total mercury content using radiochemical neutron activation analysis. Average concentrations of mercury in occipital cortex, abdominal muscle, pituitary gland and kidney cortex were, 10.6 (2.4-28.7), 3.3 (0.9-5.4), 25.0 (6.3-77) and 229 (21.1-810) micrograms/kg wet weight, respectively. Possible predictor variables for mercury concentrations were tested in multiple linear regression models. An effect of a number of tooth surfaces with amalgam was seen in occipital lobe cortex, abdominal muscle and pituitary gland, but not in kidney cortex. In occipital lobe cortex and abdominal muscle, concentrations of mercury increased with age. Explanations discussed include: that a significant fraction of the mercury retained from amalgam fillings has a very long biological half-life; a decreasing capacity of mercury excretion with age; or higher fish consumption in the older individuals. In kidney cortex mercury concentrations decreased with age. The reason for this remains unclear, but it might indicate a decreasing capacity of mercury excretion with age. Chronic alcohol abuse was associated with decreased concentrations of mercury in occipital cortex.


Diagnosis and surgical correction of the pediatric varicocele.
We reviewed our experience with the diagnosis and management of varicoceles in 40 patients 9 to 18 years old. Of the patients 29 underwent varicocelectomy and 11 are being managed conservatively with periodic followup. The results of therapy and criteria for surgical intervention are discussed.


Cord Blood 25-hydroxyvitamin D and Fetal Growth in the China-Anhui Birth Cohort Study.
We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: -110.5, -26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration.


Agreement of implantable collamer lens sizes using parameters from different devices.
To assess agreement and repeatability of white-to-white (WTW) and anterior chamber depth (ACD), and agreement of implantable collamer lens (ICL) size using these measurements from different devices. A retrospective review of 83 eyes with ICL implantation (42 patients) was conducted. The agreement of WTW (measured with WaveLight Topolyzer and Orbscan IIz) and ACD (measured with WaveLight Oculyzer and Orbscan IIz) was analysed. Correlation of ICL sizes and difference of eyes with unacceptable vaults between two data sets (WaveLight platform; Topolyzer and Oculyzer and Orbscan IIz) were assessed. Average WTW measured by Orbscan IIz and Topolyzer demonstrated good agreement (Ρ 0.884) with low systematic bias (-0.03±0.1 mm) and narrow 95% limits of agreement (LoA) of -0.28 to 0.22. Average ACD measured by Orbscan IIz and Oculyzer also showed good agreement (Ρ 0.903) with low systematic bias (-0.04±0.1 mm) and relatively narrow 95% LoA (0.2 to 0.12). ICL size selected according to two data sets showed moderate to strong level of agreement (Kappa=0.81). There was a statistically significant difference (p<0.001) in the proportion of eyes with unacceptable postoperative vaults when using the Wavelight platform data set (five eyes, 6.02%) and the Orbscan IIz data set (12 eyes, 14.46%). Although the agreement of WTW and ACD between devices was good, there was a significant difference in proportion of eyes with unacceptable postoperative vaults when using two data sets. Therefore, Topolyzer and Oculyzer might not be suitable for operating interchangeably with Orbscan IIz for ICL size selection.


A tetravalent peptide that binds to the RANK-binding region of TRAF6 via a multivalent interaction efficiently inhibits osteoclast differentiation.
Inhibition of osteoclast differentiation is a promising approach for the treatment of osteoporosis and rheumatoid arthritis. Receptor activator of nuclear factor kappa B (NF-κB) (RANK), which is an essential molecule for osteoclast differentiation, interacts with tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) to transduce downstream signals. Both RANK and TRAF6 have homo-trimeric structures, forming a multivalent interaction between the Pro-X-Glu-X-X-(aromatic/acidic) motif of RANK and the C-terminal domain of TRAF6 (TRAF-C), that markedly increases the binding affinity. Here, we designed a tetravalent peptide, RANK-tet, containing the TRAF-C-binding motif of RANK and found that RANK-tet binds to TRAF-C with high affinity. In contrast, a monomeric form of RANK-tet (RANK-mono) with the same TRAF-C-binding motif did not bind to TRAF-C, clearly indicating the multivalent interaction is strictly required for the high-affinity binding to TRAF-C. RANK-tet did not bind to a series of TRAF-C-mutants with an amino acid substitution in the RANK-binding region, indicating that RANK-tet specifically targets the RANK-binding region of TRAF-C. A cell-permeable form of RANK-tet that has poly-Arg residues at each C-terminal of the TRAF-C-binding motif efficiently inhibited the RANK ligand (RANKL)-induced differentiation of bone marrow cells to osteoclasts. Thus, this compound can be an effective anti-osteoclastogenic agent.


Phase 1/2 Trial of Pembrolizumab and Concurrent Chemoradiation Therapy for Limited-Stage SCLC.
Few advancements in treating limited-stage SCLC (LS-SCLC) have been made in decades. We report here a phase 1/2 trial of concurrent chemoradiotherapy (CRT) and pembrolizumab. This single-center, open-label phase 1/2 study recruited adults with LS-SCLC or other neuroendocrine tumors and good performance status (Eastern Cooperative Oncology Group ≤ 2). The primary end point was safety, as assessed by dose-limiting toxicities. Concurrent CRT consisted of etoposide and a platin with 45 Gy radiotherapy (30 twice daily). Prophylactic cranial irradiation (25 Gy, 10 fractions) was given at the physician's discretion. Pembrolizumab was started concurrently with CRT and continued for up to 16 cycles. The phase 1 portion consisted of a 3 + 3 design. Toxicity was assessed with Common Terminology Criteria for Adverse Events version 4.0. Secondary outcomes were progression-free survival, overall survival, and tumor response as measured by the immune-related response criteria. A total of 45 patients were screened, and 40 were enrolled. All completed radiation therapy and received greater than or equal to one cycle of pembrolizumab. A total of 27 (61%) received percutaneous coronary intervention. One dose-limiting toxicity was observed in the phase 1 portion. There were no grade 5 toxicities, but there were three grade 4 events (two neutropenia, one respiratory failure). Pneumonitis rate was 15% (three grade 2 and three grade 3). All 17 esophagitis events (42.5%) were grades 1 to 2. At median follow-up time of 23.1 months, the median progression-free survival time was 19.7 months (95% confidence interval: 8.8‒30.5) and the median overall survival time was 39.5 months (95% confidence interval: 8.0‒71.0). Concurrent CRT and pembrolizumab for LS-SCLC was well tolerated and yielded favorable outcomes, providing a basis for randomized studies.


The flame-not the ashes: achievements and heritage of a passionate analytical chemist.
On December 28, 2018, Carl Remigius Fresenius would have celebrated his 200th birthday. Called a father, nestor, or pioneer and forerunner of analytical chemistry, he left behind a remarkable heritage which lives on today. This journal and several others have published various articles commemorating him and more comprehensive monographies are available. The present feature article pays tribute to an outstanding representative of analytical chemistry in the nineteenth century, lets him have his say, and highlights his lasting achievements, including the foundation of one of this journal's ancestors.


The upper limit of the cardiorespiratory training zone (40-84%HRR) is overestimated for postmenopausal women.
The purpose of this study was to examine the heart rate reserve (HRR) at first and second ventilatory thresholds (VT's) in postmenopausal women and compare it with optimal intensity range recommended by the ACSM (40-84%HRR). An additional aim was to evaluate whether a higher aerobic power level corresponded to a higher HRR at VT's. Fifty-eight postmenopausal women participated in this study (aged 48-69). A graded 25 Wmin(-2) cycle ergometer (Monark E839) exercise protocol was performed in order to assess aerobic power. The heart rate and gas-exchange variables were measured continuously using a portable gas analyzer system (Cosmed K4b). The first (VT1) and the second (VT2) VT's were determined by the time course curves of ventilation and O2 and CO2 ventilatory equivalents. A K-means clustering analysis was used in order to identify VO2max groups (cut-off of 30.5 mlkg(-1)min(-1)) and differences were evaluated by an independent sample t-test. Bland-Altman plots were performed to illustrate the agreement between methods. The women's HRR values at VT1 were similar to 40% HRR in both VO2max groups. At VT2 both VO2max groups exhibited negative differences (P<0.01) for the predicted 84%HRR intensity (-14.46% in the lower VO2max group and -16.32% in the higher VO2max group). An upper limit of 84% overestimates the %HRR value for the second ventilatory threshold, suggesting that the cardiorespiratory target zone for this population should be lower and narrower (40-70%HRR).


Clinicopathological and prognostic significance of octamer-binding transcription factor 4 in patients with gastric cancer: a systematic review and meta-analysis.
The role of octamer-binding transcription factor 4 (Oct4) in gastric cancer (GC) progression is still under debate and reported results are inconsistent. Therefore, we conducted a meta-analysis to evaluate the clinicopathological and prognostic significance of Oct4 expression in patients with GC. Relevant articles were retrieved from a diverse number of databases, and meta-analysis was completed using STATA software 12.0. Total of 21 studies were included in this analysis (3209 samples). Expression of Oct4 was associated with incidence, tumor size, lymph node metastasis, histological differentiation, pTNM stage, tumor depth of infiltration, vascular invasion and distal metastasis. Additionally, Oct4 expression was correlated with poor overall survival rate. The Oct4 overexpression suggested aggressive biological behaviors and imply that Oct4 may be a useful prognostic biomarker in gastric cancers.


Do financial barriers to access to primary health care increase the risk of poor health? Longitudinal evidence from New Zealand.
Primary health care policies in New Zealand, as in many countries, have focused on reducing barriers to access. Financial barriers to obtaining timely health care, while not the only important barriers, are amongst the most important, and are amenable to policy reforms. There is little robust empirical evidence about the extent to which cost related barriers are associated with adverse health outcomes. Past evidence is limited to cross-sectional studies of selected groups, selected primary health care services, and to cross-sectional studies that are susceptible to unmeasured confounding bias. Using fixed effects regression modelling and data from 17,363 participants with at least two observations in three waves (2004-05, 2006-07, 2008-09) of the SoFIE-Health panel data, this study examines the impact of financial barriers to access to primary health care (general practitioner and dentist) on health status using a longitudinal national panel study of adult New Zealanders. Self-rated health (SRH), physical health (PCS) and mental health summary scores (MCS) were the health measures. The two exposures were: not seeing 1) the doctor and 2) the dentist because of cost at least once during the preceding 12 months. We also tested for interactions between the exposure (deferral of care) and age, gender, ethnicity and three health outcomes. For all outcomes, after adjusting for time-varying confounders, health deteriorated as the number of waves increased in which a non-visit was reported. Moreover, the effect size for any health deterioration was greater for deferring a dentist visit than for deferring a physician visit. Except gender and age (for MCS and doctor visits), and gender and ethnicity (for SRH and dentist visits) we did not find any evidence of interactions. These results support policy responses focussed on decreasing financial barriers to access. In the New Zealand context this finding is particularly important for dental care.


Fast Mapping Across Time: Memory Processes Support Children's Retention of Learned Words.
Children's remarkable ability to map linguistic labels to referents in the world is commonly called fast mapping. The current study examined children's (N = 216) and adults' (N = 54) retention of fast-mapped words over time (immediately, after a 1-week delay, and after a 1-month delay). The fast mapping literature often characterizes children's retention of words as consistently high across timescales. However, the current study demonstrates that learners forget word mappings at a rapid rate. Moreover, these patterns of forgetting parallel forgetting functions of domain-general memory processes. Memory processes are critical to children's word learning and the role of one such process, forgetting, is discussed in detail - forgetting supports extended mapping by promoting the memory and generalization of words and categories.


The causal effect on firm performance of China's financing-pollution emission reduction policy: Firm-level evidence.
The relationship between pollution emissions and economic development matters greatly to sustainable growth goals. China has experienced rapid growth in pollution emissions, energy consumption, and the effects of climate change. To achieve pollution reduction and energy savings targets, China's green loan policy implements a financing-pollution emissions reduction strategy for Chinese firms. Employing a difference-in-difference estimation method, we use Jiangsu Province manufacturing firm data for the period 2005 to 2013 to evaluate the effect of financing-pollution emission reduction policy tools on firm performance. Our analysis yields the following results. First, the financing-emission reduction policy has a "punishment" effect on highly polluting firm performance, including total factor productivity, profitability, and sales growth. Second, we find that these negative effects are weakened in dynamic processes. Further, pollution emissions are significantly reduced. Third, financial constraints act as the mechanism through which firm performance is punished, via the financial-emission reduction policy. Short-term and long-term bank financing decrease, while working capital and trade credit are increased to finance investment. Finally, with regard to ownership structure, state-owned firm performance is more likely to be penalized than other forms of ownership.


125Iodine decay in DNA: a discussion of its effectiveness for the breaking of DNA strands.
125I incorporated in DNA is known to be exceptionally toxic. Values of D0 range from about 40 to about 90 decays for survival of mammalian cells. The effectiveness of 125I in DNA with respect to the induction of breaks of the DNA strands, however, appears to be comparatively low. The numbers of strand breaks per energy deposited in subnuclear cellular structures such as DNA is smaller for a disintegration of 125I than for gamma-rays. The difference in effectiveness diminishes with increasing mass of the considered sensitive volume. The apparent inefficiency of 125I-decay may, on one hand, result from a waste of local energy deposition. On the other hand, it may be caused by a multitude of local strand breaks (clusters) induced by 125I-decay which are measured as one break only by the conventionally applied techniques of strand break measurement. The apparent inefficiency of 125I may be evidence furthermore for the importance of considering not only the DNA as the sensitive target but with equal pertinence the gross sensitive volume, i.e. the whole cell nucleus. Further, for drawing meaningful comparisons, it may be necessary to take into consideration the microdosimetric event size distributions for the critical targets.


Discovery of sclareol and sclareolide as filovirus entry inhibitors.
Filoviruses cause severe hemorrhagic fever in humans. Ebola virus (EBOV) is the most contagious filovirus. Although compassionate treatments have been used during the latest Ebola outbreak, novel anti-EBOV agents are still urgently needed. In this study, sclareol and sclareolide, two natural products in Salvia sclarea, were identified as EBOV entry inhibitors with EC50s of 2.4 μmol/L and 8.0 μmol/L, respectively, through blocking the viral fusion process. Moreover, both compounds exhibited inhibitory effects on all tested filoviruses' entry, indicating their wide-spectrum activities against filoviruses. This study provides insights into the two natural products and their applications against filovirus infectious diseases.


"Eating" epilepsy revisited- an electro-clinico-radiological study.
This study aimed to evaluate the clinical, video electroencephalographic and MRI attributes of patients with eating epilepsy (EE). Consecutive patients who were diagnosed with EE and underwent potential pre-surgical work-up from 2003 to 2012 formed the study cohort. Their electro-clinico-radiological and seizure outcome data were obtained from our prospectively maintained medical records. Out of 7094 patients who underwent evaluation for refractory seizures, 47 patients satisfied the criteria for EE. Twenty-three (48.9%) had exclusive EE; the remainder had a combination of predominantly eating-induced and unprovoked seizures with no differences noted in timing of seizures in relation to meals. Lesional epilepsy was seen in 34% of patients, with posterior cortex (PC; posterior temporo-parieto-occipital) predominance. In MRI negative patients, PC interictal epileptiform discharges were present in 34.4% of patients and multifocal in 20.6% of patients compared to the MRI positive group with 12.5% and 6.5%, respectively (p=0.003). Among 24 patients (51.1%) with co-existent unprovoked seizures, developmental delay and PC ictal onset was more prevalent (p=0.013 and 0.029) as compared to exclusive EE. The seizure frequency and outcome did not significantly differ between patients with or without MRI abnormality. Two patients underwent anterior temporal lobectomy, with persistence of their eating seizures postoperatively. EE is a complex reflex epilepsy of cryptogenic and symptomatic etiology. As opposed to the traditionally implied temporo-limbic mechanisms behind epileptogenesis, a multilobar network originating from the PC receiving sensory and visual inputs linked to the limbic-opercular pathways represents a plausible mechanism. Surgical selection should be diligent and cautious in this group of patients.


Prevalence of cytomegalovirus antiviral drug resistance in transplant recipients.
Cytomegalovirus (CMV) is a significant human pathogen, especially for immunocompromised patients, often treated with one or more antiviral drugs. Although the prevalence of resistance is low, the impact of drug resistant CMV infections on patient outcomes is high and genotypic testing is recommended when resistance is suspected. To assess the prevalence of CMV drug resistance mutations among samples submitted for genotypic testing, 2750 patient sample results were analyzed. Testing was performed by sequencing for ganciclovir (GCV), cidofovir (CDV), foscarnet (FOS), maribavir (MBV) and/or letermovir (LMV) resistance conferring mutations. Of the 2750 patient samples, 826 (30.04%) had resistance to one or more anti-CMV drug. Resistance mutations were most common in UL97, with 27.64% and 9.96% of samples having GCV and MBV mutations, respectively. Resistance mutations in UL54 were less common, with 6.11%, 5.98% and 1.76% of samples having GCV, CDV and FOS mutations, respectively. For LMV, resistance mutations in UL56 were present in 7.17% of samples, with mutations at codon 325 representing 80.95% of the observed LMV resistance mutations. Resistance to two drugs was identified in 215 samples and to 3 or more drugs in 35 samples. While a high prevalence of CMV resistance mutations was identified, this must be taken in the context of healthcare providers submitting samples from patients with suspected resistant CMV strains. For these patients, rapid monitoring for resistance allows treatment modifications based on objective results rather than empiric drug selection, which is particularly relevant given the presence of mutations conferring resistance to more than one drug.


Text Messaging (SMS) Helping Cancer Care in Patients Undergoing Chemotherapy Treatment: a Pilot Study.
Cancer treatment is an extremely stressful life experience that is accompanied by a range of psychological, social, physical, and practical difficulties. Cancer patients need to receive information that helps them to better understand the disease, assists them in decision-making, and helps them deal with treatment. Patients are interested in receiving such information. The degree of satisfaction with the information received has been associated with positive health outcomes, specifically regarding quality of life, severity of side effects, and psychological well-being. This study investigates a method of guiding cancer patients, in relation to outpatient chemotherapy treatment, using SMS (short message service) text messaging. A smartphone application called cHEmotHErApp was developed, and its primary function is to send out SMS text messages with guidance for self-care and emotional support for oncology patients undergoing chemotherapy. Thus, the main objective of this study is to evaluate the acceptance and perception of patients of the receipt of these SMS messages, as well as to evaluate the possible benefits reported by the participants. Adult patients diagnosed with cancer, who started the first outpatient chemotherapy treatment scheme between August and November 2016 at the School Hospital (HE) of the Federal University of Pelotas (UFPel), were invited to participate in this pilot study. In total, 14 cancer patients were adherent to this study. Each of these patients received a daily text message on their cell phone with some guidance on encouraging self-care and emotional support. Patients reported that, because of the SMS text messages they received, they felt more confident in their treatment, felt more supported and encouraged, and that the text messages facilitated self-care. In addition, patients reported that the SMS text messages they received helped them to take better care of themselves and to continue further treatment.


Effect of surface topography on removal of cortical bone screws in a novel sheep model.
Difficulty in removing implants used in trauma patients can be a complication, and increased bone-implant adhesion likely is a major contributing factor. In vitro studies have shown that surface morphology of implant materials has the ability to influence cellular responses, with polished surfaces decreasing the potential for mineralization. This study examined the effect of polishing commercially pure titanium (cpTi) and the titanium alloy TAN on the removal torque and percentage bone-implant contact in cortical and cancellous bone of sheep. Polishing had a significant effect on both removal torque and percentage bone-implant contact, with the polished implants demonstrating a lower removal torque in both cortical and cancellous bone. Polished cpTi and stainless steel were similar in terms of surface roughness and removal torque. However, polished TAN, which was not as smooth as polished cpTi, did not show the same low level for reducing removal torque. Improved polishing of TAN should reduce the removal torque further. The results of the study show that polishing is promising in improving the ease of implant removal after fracture fixation and repair.


Nitrosatable amines and nitrosamide formation in natural stimulants: Cola acuminata, C. nitida and Garcinia cola.
Three varieties of kola nut, Cola acuminata, C. nitida and Garcinia cola, of Nigerian origin, were analysed for their content of primary and secondary amines, and assessed for their relative methylating potential due to nitrosamide formation. Primary and secondary amines were determined as benzene sulfonamides by gas chromatography/thermal energy analysis (GC/TEA). Dimethylamine, methylamine, ethylamine and isopentylamine were detected in all kola nut varieties, while pyrrolidine, piperidine and isobutylamine were detected in one or more varieties. Estimated average total daily intake of aliphatic amines by a typical kola nut chewer varied from 260 to 1040 micrograms/day for secondary amines and from 2430 to 9710 micrograms/day for primary amines. Methylating activity of the nitrosated kola nuts, expressed as N-nitroso-N-methylurea equivalents, was also determined by GC/TEA. Methylating activity was significantly higher in kola nuts (170-490 micrograms/kg) than has ever been reported for a fresh plant product. These data suggest that the possible role of kola nut chewing in human cancer aetiology should be explored in countries where kola nuts are widely consumed as stimulants.


Parenting While Incarcerated: Tailoring the Strengthening Families Program for Use with Jailed Mothers.
Most incarcerated women are mothers. Parenting programs may benefit women, children and families, yet effectively intervening in correctional settings is a challenge. An evidence-based parenting intervention (the Strengthening Families Program) was tailored and implemented with women in a jail setting. Goals were to assess mothers' needs and interests regarding parenting while they were incarcerated, adapt the program to address those needs, and establish intervention delivery and evaluation methods in collaboration with a community-based agency. Women reported wanting to know more about effective communication; how children manage stress; finances; drug and alcohol use; self-care; and stress reduction. They reported high program satisfaction and reported reduced endorsement of corporal punishment after the intervention. Barriers to implementation included unpredictable attendance from session to session due to changing release dates, transfer to other facilities, and jail policies (e.g., lock-down; commissary hours). Implications for sustainable implementation of parenting programs in jail settings are discussed.


(1S,3R)-N-{(3S,10S,12S,13R,17R)-12-Hy-droxy-17-[(R)-5-hy-droxy-pentan-2-yl]-10,13-di-methyl-hexa-deca-hydro-1H-cyclo-penta-[a]phenanthren-3-yl}adamantane-1-carboxamide 0.25-hydrate.
The title compound, C35H57NO3·0.25H2O, was synthesized from de-oxy-cholic acid followed by a protection, a Mitsonobu substitution, a Staudinger reduction, formation of an amide and final reduction in the lateral chain. The compound crystallizes in the P1 space group with four steroid mol-ecules and one water mol-ecule in the triclinic cell unit. The crystal structure features O-H⋯O hydrogen bonding. The crystal studied was refined as a non-merohedral twin.


Burnout and stress amongst interns in Irish hospitals: contributing factors and potential solutions.
The transition from medical school to internship can be daunting for newly qualified doctors. High rates of stress and burnout have been reported, with negative impacts on patient care and physician wellbeing. We surveyed interns in our hospital group to evaluate rates of stress and burnout, as well as identify the causative factors and propose potential solutions to these. A hundred and one interns working in four different hospitals over a 2-year period were invited to participate in an anonymous survey. The survey collected basic demographic details and surveyed aspects of mental health using the burnout scale, Maslach Burnout Inventory (MBI) and the stress scale and 12-item General Health Questionnaire (GHQ-12). Interns were also asked to rate a variety of workplace factors on a Likert scale based on the degree of stress caused. Finally, they were surveyed on their awareness of support services available to them. Our results showed that 37% of interns met the criteria for psychological distress, high levels of emotional exhaustion, high depersonalisation and a low sense of personal accomplishment were reported in 55.4, 51.5 and 41.6%, respectively. Inadequate preparation for practice, financial worries, poor role definition and sleep deprivation were reported as significant stressors. Most were unaware of available support services and expressed interest in leaving Ireland after internship. Burnout and stress are significant problems amongst doctors in Irish hospitals. Ensuring better preparation for clinical practice and awareness of support services is vital to tackle this issue.


Behavioral analyses of killifish exposed to weightlessness in the Apollo-Soyuz test project.
Two groups of killifish, Fundulus heteroclitus, which were flown aboard Apollo-Soyuz, were subjected to postflight behavioral testing. The first group examined consisted of a graded series of embryos representing key developmental stages at orbital insertion (32-h, 66-h, and 128-h stages; pre-liftoff fertilization times). The tests revealed that the young adults from the flight 32-h stage had a significantly decreased positive geotaxis and increased negative phototaxis when compared with ground controls. These findings suggested a greater sensitization of the least-developed flight stage to post-hatching environmental influences. The second group consisted of 21-d old juveniles which were subjected to light orientation tests soon after recovery. No significant differences were detected.


The efficacy of adjuvant chemotherapy on the survival of early stage endometrial cancer.
No consensus exists on the adjuvant chemotherapy for the International Federation of Gynecology and Obstetrics (FIGO) Stage I-II endometrial cancer with risk factors for recurrence. This study evaluated adjuvant chemotherapy's efficacy in improving these patients' survival. We conducted a retrospective chart review of patients with FIGO Stage I-II endometrial cancer with recurrence risk factors. The patients received no adjuvant therapy at the National Cancer Center Hospital (NCCH) but received platinum-based chemotherapy at Shiga University of Medical Science (SUMS). Six hundred thirty-eight patients with endometrial cancer were identified. Of these, 118 met the inclusion criteria, 321 were excluded from NCCH, while 49 met the inclusion criteria, and 150 were excluded from SUMS. Multivariate analyses of age, surgery, para-aortic lymphadenectomy, omentectomy, histological type, myometrial invasion, cervical stromal invasion, and adjuvant therapy revealed that in patients aged > 60 years with type II histology, the outer half of myometrial invasion, cervical stromal invasion, and positive peritoneal cytology had significantly worse recurrence-free survival (RFS) rates, and patients aged > 60 years with type II histology, outer half of myometrial invasion, and positive peritoneal cytology had significantly worse overall survival (OS) rates. Patients that received adjuvant chemotherapy showed equivalent effects on RFS (hazard ratio [HR] = 2.13; 95% confidence interval [CI] = 0.82-5.53) and worse on OS ([HR = 5.20; 95 %CI = 1.26-21.50) than patients who did not. This study did not show that adjuvant chemotherapy for FIGO Stages I-II endometrial cancer with recurrence risk factors has survival benefit. Further large-scale studies are necessary to validate our findings.


The role of vasopressin in experimental and clinical hypertension.
The vasoconstrictor and vasopressor actions of vasopressin have been revealed in recent research through the use of highly specific and sensitive radioimmunoassays, employment of peptide antagonists, and comparison with an animal model which has hereditary absence of this hormone, the Brattleboro rat. Factors now known to modify the pressor effect of vasopressin are the baroreflexes, local vascular prostaglandin production, and a specific interaction with angiotensin II. In experimental models the volume retaining, but not the vasoconstrictor effect of vasopressin is necessary for mineralocorticoid-salt hypertension. Vasopressin contributes directly to the increase in arterial pressure of glycerol induced acute renal failure. In nephrectomized rats, plasma vasopressin is elevated and contributes directly to maintenance of pressure. Vasopressin antagonism may reduce arterial pressure in Goldblatt 1 and 2 kidney hypertension and in one genetic model, spontaneously hypertensive rat (SHR), but the peptide is not necessary for hypertension in these models. Plasma vasopressin is reduced in primary aldosteronism, but may be elevated in malignant hypertension. In essential hypertension, there is considerable disagreement among various studies in which plasma vasopressin, urine vasopressin excretion, platelet associated vasopressin, or vasopressin-neurophysin were measured as to whether there is evidence for increased secretion of vasopressin. Only preliminary studies of vasopressin antagonism in clinical hypertension have been reported. At present, there is no conclusive evidence that elevated vasopressin secretion occurs or is necessary for any form of clinical hypertension.


Palaeobiology: Born and Gone in Global Warming.
Why ichthyosaurs - marine Mesozoic reptiles - disappeared before the dinosaur extinction has remained a mystery. New research suggests they may have gone extinct stepwise, during one of the most extreme greenhouse periods in the history of complex life-forms.


THE ROLE OF HETEROPLASMY IN THE DIAGNOSIS AND MANAGEMENT OF MATERNALLY INHERITED DIABETES AND DEAFNESS.
Objective: Maternally inherited diabetes and deafness (MIDD) is a rare diabetic syndrome mainly caused by a point mutation in the mitochondrial DNA (mtDNA), mt3243 adenine to guanine (A>G). The objective of this paper is to review the genetic inheritance, clinical manifestations, and treatment of patients with MIDD. Methods: The current review used a literature search of scientific papers on this rare syndrome. Results: mtDNA is primarily inherited through the maternal oocyte; therefore, the genetic abnormalities in MIDD are associated with maternal inheritance. Mitochondria contain circular mtDNA, which codes for various mitochondrial genes. The mtDNA can be heteroplasmic, containing more than one type of mtDNA sequence; if one of the mtDNAs contains the mt3243 A>G mutation, a patient may develop MIDD. Patients can inherit different amounts of mutated mtDNA and normal mtDNA that affect the severity of the clinical manifestations of MIDD. The most common clinical manifestations include diabetes mellitus, deafness, ophthalmic disease, cardiac disease, renal disease, gastrointestinal disease, short stature, and myopathies. In order to effectively treat patients with MIDD, it is important to recognize the underlying pathophysiology of this specific form of diabetes and the pathophysiology associated with the organ-specific complications present in this disease. Conclusion: The heteroplasmic inheritance of mutated mtDNA plays an important role in the clinical manifestations of various mitochondrial diseases, specifically MIDD. This review will alert endocrinologists of the signs and symptoms of MIDD and important clinical considerations when managing this disease. Abbreviations: ATP = adenosine triphosphate; CoQ10 = coenzyme Q10; MELAS = mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MIDD = maternally inherited diabetes and deafness; mtDNA = mitochondrial DNA; tRNA = transfer ribonucleic acid; ROS = reactive oxygen species; T2DM = type 2 diabetes mellitus.


Are psychosocial factors of aetiological importance in functional dyspepsia?
The causes of functional dyspepsia remain unclear. Research has linked other functional gastrointestinal disorders, particularly irritable bowel syndrome, to a history of physical or sexual abuse, psychosocial distress and certain psychiatric disorders. In functional dyspepsia, there is a possibility of certain psychiatric disorders, particularly alcohol abuse and eating disorders, indirectly influencing the development of functional dyspepsia-like symptoms. However, the literature on possible psychosocial correlates in functional dyspepsia is not as mature as the literature on irritable bowel syndrome. This paper critically reviews the psychosocial dimensions and implications for the psychotherapeutic treatment of functional dyspepsia.


Association between mixed exposure of polycyclic aromatic hydrocarbons and telomere length in general population: NHANES 2001-2002.
Although an association between single polycyclic aromatic hydrocarbons (PAHs) adult exposure and telomere length has been reported, the evidence of mixed PAHs (1-napthol, 2-napthol, 3-fluorene, 2-fluorene, 3-phenanthrene, 1-phenanthrene, 2-phenanthrene, and 1-pyrene) exposure and telomere length in the adult general population is still not clear. A total of 1460 adults over the age of 20 years provided urine information on 8 PAHs and selected covariates from the 2001-2002 National Health and Nutrition Examination Survey (NHANES). Bayesian nuclear machine regression (BKMR) was conducted to analyze these associations of telomere length in multiple PAH-exposed environments. Linear regression is mainly used for correlation analysis of PAHs with selected covariate adjustments. Restricted cubic spline (RCS) is used to estimate the correlation between selected PAHs and telomere length. After adjusting for potential covariates, PAHs mixed exposure was negatively associated with telomere length. The linear regression results showed that 2-napthol and 2-fluorene were negatively correlated with telomere length. Telomere length decreased by 1.0% in the fully adjusted model per increment of one unit in the base-10-logarithm-transformed 2-napthol and 2-fluorene concentrations (P = 0.030 and 0.049, respectively). However, the other 6 PAH metabolites were not significantly different. In addition, RCS results showed that 2-napthol has a marginal dose effect relationship with telomere length. Our present study suggested that PAHs are negatively associated with telomere length in the general population of the USA. Considering that the low level of PAHs exposure in the general population can also induce reduced telomere length and potential health risks, future research is needed to explore potential mechanisms.


Physical activity intervention (Movi-Kids) on improving academic achievement and adiposity in preschoolers with or without attention deficit hyperactivity disorder: study protocol for a randomized controlled trial.
The prevention of obesity and improvement of academic achievement in children are concerns of industrialized societies. Obesity has been associated with psychological disorders, including attention deficit hyperactivity disorder, whose prevalence has been estimated at 6.8 % in Spanish children and adolescents. It is known that physical activity is positively related to academic achievement and negatively related to the risk of obesity in children. However, studies to test the effectiveness of physical activity interventions in improving academic achievement in preschool children are scarce and have some weaknesses that threaten their validity. Moreover, very few studies have examined their effectiveness in improving symptoms of attention deficit hyperactivity disorder. This paper outlines a two-year multidimensional preschool intervention (Movi-Kids) aimed at preventing obesity and improving academic achievement in children with or without attention deficit hyperactivity disorder. Twenty-one schools from Ciudad Real and Cuenca, Spain, were randomized to intervention and control groups. In the first academic year, children in the third grade of preschool and the first grade of primary school in the intervention group received the Movi-Kids intervention. In the second academic year, schools were crossed over to the other group. The intervention included children, parents and teachers, and the school environment, and consisted of: (i) three hour-long sessions of recreational non-competitive physical activity after school, weekly, (ii) educational materials for parents and teachers addressing sedentary lifestyle risks and (iii) playground modifications to promote physical activity during breaks. Primary outcome measures of this study were academic achievement (intelligence, cognition, memory, attention and perception), assessed by the Battery of General and Differential Aptitudes, and adiposity measures (body mass index, waist circumference, triceps skinfold thickness and body fat percentage). Secondary outcome measures were: attention deficit hyperactivity disorder risk, motor skills, health-related quality of life and sleep quality. These variables will all be measured in both groups at baseline and at the end of the first and second academic years. It seems reasonable that an intervention to promote physical activity based on playground games will be useful for simultaneously improving academic achievement and controlling obesity. ClinicalTrials.gov NCT01971827 .


Fat necrosis of the breast--a review.
Fat necrosis of the breast is a benign condition that most frequently affects peri-menopausal women. It can mimic breast cancer clinically or radiologically. In other cases it can obscure malignant lesions. The core of this review is derived from a MEDLINE database literature search from 1966-2004. Further references were from lateral search. In this paper, we review the pathogenesis and pathology clinical and radiological features of fat necrosis of the breast. The implication of fat necrosis in the management of patients with breast lump is also discussed. Fat necrosis of breast is a complex process. Therefore, a systematic review of this condition will enable surgeons, radiologists and oncologists working in the field of breast disease to understand it better and improve its management.


Current status on researches of Meniere's disease: a review.
Background: Meniere's disease (MD) is a complex and multifactorial inner ear disease. The etiology of MD is unclear. Significant progress had been made in diagnosis and treatment. Complete cure for this disease is still impossible.Objectives: This review covers the updated research results in MD in the past decades.Material and methods: Recent publications were critically reviewed.Results: The relationship between Endolymphatic hydrops and Meniere symptoms requires further study. Direct visualization of EH is achieved by special sequences of inner ear MRI. Appearance of EH could be observed in MD patients both in symptomatic and asymptomatic ears. Visualization of EH in vivo might make a great substantial improvement in diagnose of MD. The first goal of the management of MD is to reduce the attack frequency. Several safe and effective medical and surgical therapies are practiced to help patients to control vertigo and preserve hearing.Conclusions and significance: There has been no major breakthrough in the pathogenesis research of MD in recent years. Visualization of EH in vivo might make a great substantial improvement in diagnose of MD. Clinicians still have few effective ways to alleviate the progress of the disease.


Prevalence and processing of child sexual abuse: a multi-data-set analysis of urban and rural counties.
This study investigated how contextual factors affect the processing of child sexual abuse cases, from reporting to sentencing. We analyzed three types of data: (a) data compiled by the Pennsylvania Coalition Against Rape from monthly reports by all rape crisis centers in the state; (b) data from the Pennsylvania Office of Children, Youth, and Families; and (c) sentencing data from the Pennsylvania Commission on Sentencing. Results indicated that aggregate rates of reporting, substantiation, and sentencing were affected by county levels of expenditure. In addition, reporting and substantiation were affected by county-level factors, such that rural counties, counties with a higher percentage of individuals living below the poverty level, counties with higher expenditures, and counties with a higher percentage of stranger assaults had higher rates of child sexual abuse reporting.


Growth, tolerance, and enzyme activities of Trichoderma strains in culture media added with a pyrethroids-based insecticide.
The application of pyrethroids and carbamates represents an environmental risk and may exert adverse effects on beneficial microorganisms such as Trichoderma, which contribute to the biocontrol of several fungal phytopathogens. This research evaluated the tolerance of several strains of Trichoderma to a selected culture medium contaminated with a commercial insecticide (H24®) composed of pyrethroids, permethrin and prallethrin, and carbamate propoxur, and determined the influence of this insecticide on the release of enzymes such as chitinases, peroxidases, and endoglucanases by a consortium of selected Trichoderma strains grown in liquid culture medium. Four out of 10 Trichoderma strains showed tolerance to 200ppm (∼48.3% of growth) of the commercial insecticide after 96h of exposure to a contaminated solid medium. After eight days of growth in liquid culture, the insecticide enhanced extracellular protein content and peroxidase activities in the Trichoderma consortium but decreased both chitinase and glucanase activities. These fungal responses should be considered when implementing strategies that combine alternative pesticides and fungal biocontrollers for managing fungal phytopathogens.


Growing bioengineered teeth from single cells: potential for dental regenerative medicine.
The ultimate goal of regenerative therapy is to develop fully functioning bioengineered organs that can replace organs lost or damaged due to disease, injury or aging. Dental regenerative medicine has made the most progress and is the most useful model for the consideration of strategies in future organ replacement therapies. This review describes strategies that have been pursued to date and experiments currently being conducted to bioengineer teeth in anticipation of the production of fully functional organs. To realize the practical application of 'bioengineered tooth' transplantation therapy, four major hurdles must be overcome. The present status of the hurdles to this therapy are described and discussed in this review. The bioengineering techniques developed for tooth regeneration will in the future make substantial contributions to the ability to grow primordial organs in vitro and also to grow fully functioning organs, such as the liver, kidney and heart.


Increased hypercholesterolemia and atherosclerosis in mice lacking both ApoE and leptin receptor.
Diabetes mellitus is one of the major risk factors associated with atherosclerosis and coronary heart disease but the mechanistic links between the disease and atherosclerosis are not well understood. In this study, we investigated the effect of the deletion of the long-form leptin receptor on the progression of atherosclerosis in ApoE-/- mouse. ApoE-/-;db/db double knockout mice as well as ApoE-/-;db/+ and ApoE-/- littermates were generated by crossing ApoE-/- and db/+ mice. On a regular chow diet, ApoE-/-;db/db mice at 20 weeks of age exhibited features typical of type 2 diabetes: obesity, hyperglycemia, hyperinsulinemia and dyslipidemia and had significantly accelerated atherosclerosis compared with their age-matched ApoE-/- littermates as assessed by either the percentage of the aorta bearing lesion (5.3+/-0.9% for ApoE-/-;db/db versus 1.5+/-0.5% for ApoE-/-) or by aortic lipid content ( approximately 1.5-2-fold increase in free cholesterol and approximately 3-4-fold increase in cholesteryl ester). The atherosclerosis in these ApoE-/-;db/db mice was further accelerated by feeding mice with a Western diet and markedly inhibited by fenofibrate with a 2.5- and 5.3-fold reduction of the lesion in male and female mice, respectively. The results from this study demonstrate that type 2 diabetes can accelerate atherogenesis in mice. This mouse model may provide insight into the mechanistic link between type 2 diabetes and atherosclerosis as well as serve as a valuable tool for evaluating therapeutics.


Pediatric presence at cesarean section: justified or not?
This study was undertaken to determine the incidence and type of resuscitation required for infants delivered by both elective and emergency cesarean section relative to spontaneous vaginal delivery. A hospital-based cohort study from 1990 to 2002. Information was extracted from a prospectively collected database on term (>/=37 weeks) singleton infants delivered by cesarean section and spontaneous vaginal delivery. Analysis was performed on type of cesarean section, type of anesthetic, fetal presentation, and evidence of fetal distress. Outcomes assessed were resuscitation and Apgar scores. There were 44,938 eligible deliveries. There was no significant difference in need for resuscitation between infants born by elective cesarean section under regional anesthetic compared with spontaneous vaginal delivery (chi(2)=0.998; df=1; P=.318). General anesthesia, fetal distress, and noncephalic presentation increase the need for resuscitation. An advanced skills practitioner does not need to be present at elective cesarean sections under regional anesthesia provided there are no additional risk factors.


Galactose Supplementation in Patients With TMEM165-CDG Rescues the Glycosylation Defects.
TMEM165 deficiency is a severe multisystem disease that manifests with metabolic, endocrine, and skeletal involvement. It leads to one type of congenital disorders of glycosylation (CDG), a rapidly growing group of inherited diseases in which the glycosylation process is altered. Patients have decreased galactosylation by serum glycan analysis. There are >100 CDGs, but only specific types are treatable. Galactose has been shown to be beneficial in other CDG types with abnormal galactosylation. The aim of this study was to characterize the effects of galactose supplementation on Golgi glycosylation in TMEM165-depleted HEK293 cells, as well as in 2 patients with TMEM165-CDG and in their cultured skin fibroblast cells. Glycosylation was assessed by mass spectrometry, western blot analysis, and transferrin isoelectrofocusing. Both unrelated patients with TMEM165-CDG with the same deep intronic homozygous mutation (c.792+182G>A) were allocated to receive d-galactose in a daily dose of 1 g/kg. We analyzed N-linked glycans and glycolipids in knockout TMEM165 HEK293 cells, revealing severe hypogalactosylation and GalNAc transfer defects. Although these defects were completely corrected by the addition of Mn2+, we demonstrated that the observed N-glycosylation defect could also be overcome by galactose supplementation. We then demonstrated that oral galactose supplementation in patients with TMEM165-deficient CDG improved biochemical and clinical parameters, including a substantial increase in the negatively charged transferrin isoforms, and a decrease in hypogalactosylated total N-glycan structures, endocrine function, and coagulation parameters. To our knowledge, this is the first description of abnormal glycosylation of lipids in the TMEM165 defect and the first report of successful dietary treatment in TMEM165 deficiency. We recommend the use of oral d-galactose therapy in TMEM165-CDG.


Prescribing DOACs with specific patient populations in mind.
What prescribing considerations should be top of mind when obesity, renal disease, cancer, or thrombophilia are at play?


Chryseomonas luteola bloodstream infection in a pediatric patient with pulmonary arterial hypertension receiving intravenous treprostinil therapy.
Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension (PAH). It is commonly administered through a central venous catheter (CVC). Treprostinil is associated with the incidence of Gram-negative bacterial bloodstream infections (BSI), a susceptibility that has been associated with a diluent used for treprostinil. We report the case of a 14-year-old boy with idiopathic PAH on continuous intravenous treprostinil therapy who presented with fever and fatigue. A blood culture drawn from his CVC was positive for the rare Gram-negative organism Chryseomonas luteola. The patient made a complete recovery with antibacterial treatment. This is the only documented case of a C. luteola BSI in a PAH patient receiving continuous intravenous treprostinil. We recommend maintaining a high index of suspicion for both common and rare Gram-negative pathogens and the early administration of appropriate antibiotic therapy in this population. The use of an alternate diluent solution, such as Sterile Diluent for Flolan, further decreases the infection risk.


High-Curie-temperature ferromagnetism in self-organized Ge1-xMnx nanocolumns.
The emerging field of spintronics would be dramatically boosted if room-temperature ferromagnetism could be added to semiconductor nanostructures that are compatible with silicon technology. Here, we report a high-TC (>400K) ferromagnetic phase of (Ge,Mn) epitaxial layer. The manganese content is 6%, and careful structural and chemical analyses show that the Mn distribution is strongly inhomogeneous: we observe eutectoid growth of well-defined Mn-rich nanocolumns surrounded by a Mn-poor matrix. The average diameter of these nanocolumns is 3nm and their spacing is 10nm. Their composition is close to Ge(2)Mn, which corresponds to an unknown germanium-rich phase, and they have a uniaxially elongated diamond structure. Their Curie temperature is higher than 400K. Magnetotransport reveals a pronounced anomalous Hall effect up to room temperature. A giant positive magnetoresistance is measured from 7,000% at 30K to 200% at 300K and 9T, with no evidence of saturation.


Diminished TLR2-TLR9 mediated CD4+ T cell responses are associated with increased inflammation in intraocular tuberculosis.
Intraocular tuberculosis (IOTB) is amongst the leading causes of uveitis in tropical countries. Despite reports on involvement of proinflammatory cytokines, studies on innate immune responses in disease pathogenesis are lacking. Reports from animal models and patients with pulmonary tuberculosis indicate that defects in toll like receptor (TLR)2 and TLR9 signalling predispose them to tuberculosis. In this context, we investigated the role of TLR2, TLR4 and TLR9 in generation of CD4+ T effector (Teff) cell responses during IOTB. Firstly, the cells in vitreous fluids showed lower expression of TLR2 and TLR9 in IOTB as compared to non-uveitis and non-TB uveitis groups. Next, peripheral CD4+ Teff cells of subjects with IOTB showed decreased proliferative responses and lower induction of Tregs following TLR2 and TLR9 stimulation. Further, TLR9 ligation resulted in increased IFN-γ and IL-17a but decreased expression of IL-10 and TGF-β. Lastly, lower expression of genes involved in TLR9 signalling after direct TLR9 ligation was observed in IOTB. Collectively, our results show that a subdued response to direct TLR2 and TLR9 stimulation in CD4+ T cells is associated with increased proinflammatory responses in IOTB. These findings reveal an important link between innate immune signalling and ensuing adaptive immune responses in IOTB with implications in other forms of extrapulmonary tuberculosis.


Industrial functional safety assessment for WSN using QoS metrics.
Wireless Sensor Networks are increasingly getting deployed for the safety use cases in industrial applications. While several research papers discuss about the Quality & Reliability improvement techniques in WSN systems to achieve minimal delay, higher node life, optimal routing etc., very limited work is witnessed on assessment of safety integrity levels of WSN systems. In this paper we tried to bridge this gap by bringing out a QoS metric-based safety integrity assessment for the end-to-end industrial Wireless Sensor Network (WSN) system. To identify relevant QoS metrics for monitoring the safety integrity levels, we also bring out a 4-step mapping methodology to link the QoS metrics and communication defenses/safety mechanisms. This mapping approach is expected to serve the network safety design engineers. Finally, a simulation case example is discussed to illustrate safety integrity assessment and we conclude by bringing out future research opportunities to improve safety integrity levels of industrial WSN systems.


Association of blood donor characteristics and in vitro haemolysis of packed red blood cell concentrates during storage.
Blood donor variability can affect the storage properties of packed red blood cells (PRBCs). This study aimed to determine the association of donor characteristics with in vitro storage haemolysis of PRBCs. In the prospective observational study, a total of 109 whole blood donors were enrolled using the purposive sampling method. A pre-donation sample was collected for haemoglobin (Hb) and serum uric acid (UA) levels. PRBC aliquots were tested for potassium, lactate dehydrogenase (LDH), Hb, haematocrit, plasma Hb and haemolysis on days 1, 21 and 35 of storage. The association of these parameters with donor age, sex, donation status, dietary pattern and body mass index was determined. Mean haemolysis was significantly higher in PRBCs from donors with UA levels ≤6 mg/dL than donors with UA levels >6 mg/dL on day 35 of storage (0.22 ± 0.11 vs. 0.18 ± 0.07, p = 0.03). Median plasma Hb (mg/L) was significantly higher in PRBCs from first-time donors on day 21 (586 vs. 509, p = 0.05) and day 35 (1507 vs. 1358, p = 0.02) of storage in comparison to frequent donors. Significantly higher mean potassium (p = 0.04 day 1; p = 0.02 day 21) and median LDH values (p = 0.02 day 1, p = 0.05 day 21) were observed in PRBCs from male donors. A statistically significant positive association was observed between donor UA and LDH levels of PRBCs on day 35 of storage (β coefficient: 715.52, p-value: 0.003) on multiple regression analysis. In vitro haemolysis of PRBCs is affected by blood donor characteristics.


Levels and distribution of the calcium-modulated proteins S100 and calmodulin in rat C6 glioma cells.
To understand better the mechanisms involved in the transduction of a calcium signal into an intracellular response via multiple calcium-modulated proteins, we have examined the calcium-modulated proteins, S100 and calmodulin, and their intracellular targets in rat C6 glioma cells. Subconfluent, confluent, and postconfluent C6 cells contain predominantly, if not exclusively, the S100 beta polypeptide. The level of S100 beta in C6 cells increases approximately 20-fold from subconfluency to postconfluency whereas the level of calmodulin increases only about two-fold. The subcellular distribution of S100 beta and calmodulin in mitotic cells is similar. However, the subcellular distribution of these proteins in interphase cells is different and appears to change with cell density. Gel overlay analysis demonstrated that the S100- and calmodulin-binding protein profiles are significantly different and that some of the binding proteins appear to change in intensity with cell density. These data demonstrate that S100 beta is the predominant S100 polypeptide in C6 cells and suggest that changes in S100 beta and S100 beta-binding proteins may be involved in regulating S100-mediated intracellular processes in C6 cells. Our studies also suggest that the levels of S100 and calmodulin may be differentially regulated in C6 cells.


Task-related variations in the surface EMG of the human first dorsal interosseous muscle.
Evidence from human and animal studies suggests that motor neuron pool organization is not uniform for all motor tasks. Groupings of motor units within a muscle may be recruited differentially for a given task based on principles beyond anatomical or architectural features of the muscle alone. This study aimed to determine whether: (1) there was differential activation across locations of the first dorsal interosseous (FDI) muscle during a given task, (2) the differential activation was related to directional requirements and/or end goal of the task, and (3) there was an anatomical pattern to the differential activation. Twenty-six healthy right-handed participants carried out isometric finger/hand contractions in sitting while surface EMG was collected from 4 bipolar sites on the FDI muscle simultaneously. The tasks included: abduction, flexion, diagonal, 30% abduction + 30% flexion, 30% flexion + 30% abduction, key pinch, and power grasp. Mean peak integrated EMG for each task was normalized to site and task specific mean M waves. Differential activation was evident across FDI sites based on movement direction, order of directional components within a combination condition, and end goal of the task. There was greatest activation in the distal ulnar site for all tasks. Additionally there was a trend toward an ordering effect in the amount of activation at each site: distal ulnar > distal radial > proximal radial > proximal ulnar.


Site-directed mutagenesis in human tissue-plasminogen activator. Distinguishing sites in the amino-terminal region required for full fibrinolytic activity and rapid clearance from the circulation.
Recombinant variants of tissue plasminogen activator (t-PA) containing either substitutions or deletions of amino acids within the fibronectin finger-like domain (residues 6-50) were found to exhibit widely varying in vivo clearance profiles in rats and fibrinolytic activity in 125I-fibrin clot lysis assays. Clearance was not significantly affected by changes in the densely charged region of amino acid residues 7-10. Deletions or substitutions of amino acids in the region 14-32 decreased both fibrinolytic activity and the clearance of the enzyme. Modifications within the predicted omega loop of residues 37-41 affected clearance only to a small degree, whereas amino acid alterations in the region of residues 42-49 resulted in as much as a 6-fold decrease in the rate of clearance with only relatively minor decreases in the fibrinolytic activity of the variants. The cumulative results distinguish discrete sections of the NH2-terminal region of the enzyme as determinants of in vivo clearance and fibrinolytic activity of t-PA. In addition, the fibrinolytic activity of a variant containing the substitutions Gln42----Asn, His44----Glu, and Asn117----Gln, when compared with wild-type t-PA in an in vivo rabbit venous clot lysis model, was found to have similar lytic efficacy at approximately one-fourth the dose. We conclude that decreases in the in vivo clearance of t-PA can result in more potent thrombolytic agents in vivo, even though the in vitro fibrinolytic activity of the enzyme may be somewhat impaired.