Nicorandil stimulates a Na⁺/Ca²⁺ exchanger by activating guanylate cyclase in guinea pig cardiac myocytes.
Nicorandil, a hybrid of an ATP-sensitive K(+) (KATP) channel opener and a nitrate generator, is used clinically for the treatment of angina pectoris. This agent has been reported to exert antiarrhythmic actions by abolishing both triggered activity and spontaneous automaticity in an in vitro study. It is well known that delayed afterdepolarizations (DADs) are caused by the Na(+)/Ca(2+) exchange current (I NCX). In this study, we investigated the effect of nicorandil on the cardiac Na(+)/Ca(2+) exchanger (NCX1). We used the whole-cell patch clamp technique and the Fura-2/AM (Ca(2+) indicator) method to investigate the effect of nicorandil on I NCX in isolated guinea pig ventricular myocytes and CCL39 fibroblast cells transfected with dog heart NCX1. Nicorandil enhanced I NCX in a concentration-dependent manner. The EC50 (half-maximum concentration for enhancement of the drug) values were 15.0 and 8.7 μM for the outward and inward components of I NCX, respectively. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP), a membrane-permeable analog of guanosine 3',5'-cyclic monophosphate (cGMP), enhanced I NCX. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor (10 μM), completely abolished the nicorandil-induced I NCX increase. Nicorandil increased I NCX in CCL39 cells expressing wild-type NCX1 but did not affect mutant NCX1 without a long intracellular loop between transmembrane segments (TMSs) 5 and 6. Nicorandil at 100 μM abolished DADs induced by electrical stimulation with ouabain. Nicorandil enhanced the function of NCX1 via guanylate cyclase and thus may accelerate Ca(2+) exit via NCX1. This may partially contribute to the cardioprotection by nicorandil in addition to shortening action potential duration (APD) by activating KATP channels.


Is the source of domestic water associated with the risk of malaria infection? Spatial variability and a mixed-effects multilevel analysis.
There is a dearth of information on the relationship between domestic water source and malaria infection in malaria-endemic regions such as Tanzania. This study examined the geospatial variability and association between domestic water source and malaria prevalence in Tanzania. We analyzed data from a sample of 6707 children, aged 6-59 months, from the 2017 Tanzania Malaria Indicator Survey. The outcome variable was the result of malaria testing (positive or negative) and the main explanatory variable was domestic water source (piped or non-piped). Random effect variables were administrative region and geographical zone. ArcGIS 10.7 was used to create geospatial distribution maps. A STATA MP 14.0 was used to fit a mixed-effects multilevel logistic regression to examine the factors associated with malaria prevalence. The prevalence of malaria and non-piped domestic water source was respectively 7.3% and 59.6%. The regions and zones with a higher prevalence of malaria also had a higher percentage of non-piped water. There was a statistically significant variation in the risk of malaria across the regions (variance = 1.27; 95% CI, 0.40-4.07) and zones (variance = 4.75; 95% CI, 1.46-15.46). The final fixed-effects model showed that non-piped domestic water was significantly associated with malaria prevalence (adjusted odds ratio (AOR) = 2.18; 95% CI, 1.64-2.89; P < 0.001). A non-piped source of domestic water was independently associated with positive testing for malaria. Moreover, regions with a high percentage of non-piped domestic water had a correspondingly high prevalence of malaria.


Carbohydrate analysis of hemicelluloses by gas chromatography-mass spectrometry of acetylated methyl glycosides.
A method based on gas chromatography-mass spectrometry analysis of acetylated methyl glycosides was developed in order to analyze monosaccharides obtained from various hemicelluloses. The derivatives of monosaccharide standards, arabinose, glucose, and xylose were studied in detail and (13)C-labeled analogues were used for identification and quantitative analysis. Excellent chromatographic separation of the monosaccharide derivatives was found and identification of the anomeric configuration was feasible through a prepared and identified pure methyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside. The electron ionization mass spectrum and fragmentation path was studied for each monosaccharide derivative. Fragment ion pairs of labeled and unlabeled monosaccharides were used for quantification; m/z 243/248 for glucose, 128/132 for xylose, and 217/218 for arabinose. Using the intensity ratios obtained from the extracted ion chromatograms, accurate quantification of monosaccharide constituents of selected hemicelluloses was demonstrated.


Recurrent bleeding following traumatic hyphema due to mild hemophilia B (Christmas disease).
Traumatic hyphemas generally resolve spontaneously. When recurrent bleeding occurs, a coagulopathy should be suspected. We present a unique case of a traumatic hyphema with recurrent bleeding in association with mild hemophilia B (factor IX deficiency).


A venom extract from the sea anemone Bartholomea annulata produces haemolysis and lipid peroxidation in mouse erythrocytes.
The haemolytic and peroxidative effects of crude extracts from Bartholomea annulata, a common Caribbean sea anemone, were investigated in erythrocytes isolated from NIH male albino mice. Significant concentration-dependent effects were found on both haemolysis (evaluated as release of haemoglobin) and lipid peroxidation (as a common index of oxidative damage to membrane lipids) in red blood cells. Moreover, the incubation of erythrocytes in the presence of either a general antioxidant, reduced glutathione (GSH, 50 microM), or an iron chelator, desferrioxamine (DFA, 10 microM), resulted in a significant attenuation of haemolysis in both cases. In light of these findings, the in vitro toxicological characterization of the venom, as well as the involvement of oxygen radical-mediated membrane damage as a potential mechanism of toxicity associated with haemolysis are discussed.


Duration of ovarian stimulation is predictive of in-vitro fertilization outcomes.
The aim of this study is to evaluate the effect of ovarian stimulation duration on oocyte/embryo development and pregnancy outcome in an in-vitro fertilization cycle (IVF). Retrospective cohort study performed at University of South Florida reproductive center between January 2011 and December 2016. A total of 690 sub-fertile women who underwent autologous IVF cycle were included for analysis. The outcomes were compared between patients undergoing ovarian stimulation for ≤8 days and >8 days. Data was further categorized into accelerated stimulation group (≤8 days), normal duration stimulation group (9-12 days), and delayed stimulation group (≥13 days). Primary outcome was live birth rate. Secondary outcomes include oocyte development and embryo characteristics. A total of 69 (10%) and 621 (90%) patients underwent ovarian stimulation for ≤8 and >8 days, respectively. Ovarian stimulation for >8 days had 2.1 times higher odds of live birth (35.7% vs. 20.8%, 95% CI: 1.02-4.44, P=0.04), and 1.9-fold-higher odds of clinical pregnancy (42.6% vs. 27.1%, 95% CI: 1.03-3.87, P=0.05). Number of matured oocytes (P=0.002), normally fertilized embryos (P=0.008), 6-8 cell stage embryos (P=0.003) and blastocysts (P=0.014) were higher in cycles with stimulation >8 days. Further analysis showed that live birth rate was highest in the group of patients with normal duration stimulation group (37.3%) compared to patients with delayed stimulation (25%) and accelerated stimulation (20.8%). In an IVF cycle, optimal ovarian response and pregnancy outcome is associated with stimulation duration of at least 9 days. Both accelerated and delayed follicular recruitment are indicators for suboptimal response.


Nephrogenic adenoma of the urethra: an unusual cause of hematuria in the child.
The authors describe a 9-year-old boy who had an accident with his bicycle. He presented with hematuria a few weeks later, and cystoscopy results showed a polypod lesion near the veru montanum. The lesion was resected, and histologic examination showed a nephrogenic adenoma (NA), which recurred 6 years later with hematuria. NA is a rare lesion in a child's urethra and can be a source of hematuria.


Trypanosomatid Deoxyhypusine Synthase Activity Is Dependent on Shared Active-Site Complementation between Pseudoenzyme Paralogs.
Trypanosoma brucei is a neglected tropical disease endemic to Africa. The polyamine spermidine is essential for post-translational hypusine modification of eukaryotic initiation factor 5A (eIF5A), which is catalyzed by deoxyhypusine synthase (TbDHS). In trypanosomatids, deoxyhypusine synthase (DHS) activity is dependent on heterotetramer formation between two paralogs, DHSc and DHSp, both with minimal activity on their own due to missing catalytic residues. We determined the X-ray structure of TbDHS showing a single functional shared active site is formed at the DHSc/DHSp heterodimer interface, with deficiencies in one subunit complemented by the other. Each heterodimer contains two NAD+ binding sites, one housed in the functional catalytic site and the second bound in a remnant dead site that lacks key catalytic residues. Functional analysis of these sites by site-directed mutagenesis identified long-range contributions to the catalytic site from the dead site. Differences between trypanosomatid and human DHS that could be exploited for drug discovery were identified.


Antenatal tests of fetal wellbeing.
In current obstetric practice, there is frequently a need to assess fetal wellbeing. This is particularly so in those fetuses at risk, including the small-for-gestational-age fetus or the fetus of a mother who presents with reduced fetal movements or who has an obstetric complication such as pre-eclampsia. It is important that the clinician is able to assess fetal wellbeing in such cases, especially in preterm gestations, when inappropriate delivery could have serious adverse consequences. In this paper, we review the current evidence for the use and the limitations of widely used methods of antenatal monitoring including the use of cardiotocography, biophysical profile, and ultrasound-derived parameters including umbilical artery, middle cerebral artery, and ductus venosus Doppler flow.


A randomized, sham-controlled trial of a novel near-infrared phototherapy device on sleep and daytime function.
Near-infrared light exhibits several therapeutic properties, but little is known about the benefits to sleep and daytime function. The purpose of this study was to investigate the effects of red and near-infrared exposure before bed on sleep and next-day function. Thirty adults (30-60 y) with a self-reported sleep complaint but without a sleep disorder participated in a randomized, sham-controlled study for a duration of 5 weeks. After a 2-week baseline period, participants wore either a cervical red light/near-infrared-emitting collar (combined: 660 nm, 740 nm, 810 nm, and 870 nm) or sham device every other night before bed for 3 weeks. Sleep was measured using actigraphy and sleep diaries. Mood and performance were assessed using weekly self-reported surveys and debrief interviews. Objective sleep parameters, as measured by actigraphy, did not differ between the active or sham groups, but improved self-reported sleep, as well as perceived improvements in relaxation and mood, were observed among active but not sham users. Both active and sham users improved in Insomnia Severity Index score by the end of the trial. Red and near-infrared exposure to the head and neck before bed may offer potential therapeutic benefits to sleep and daytime function, but further work needs to be done to determine optimal dose parameters, wavelengths, and milliwatt power level. Registry: ClinicalTrials.gov; Name: Phase II Study-Trial of a Phototherapy Light Device to Improve Sleep Health (PHOTONS); URL: https://clinicaltrials.gov/ct2/show/NCT05116358; Identifier: NCT05116358. Kennedy KER, Wills CCA, Holt C, Grandner MA. A randomized, sham-controlled trial of a novel near-infrared phototherapy device on sleep and daytime function. J Clin Sleep Med. 2023;19(9):1669-1675.


Protection of respiratory chain enzymes from ischaemic damage in adult rat brain slices.
The effect of aglycaemic hypoxia (AH) on the activity of the mitochondrial respiratory chain complexes was measured in superfused adult cortical brain slices. After 15 min of AH the activity of complex II-III was significantly reduced (by 45%) with no change in complex I or IV. Following 30 min of reperfusion the activities of complex II-III and IV were significantly reduced (by 45% and 20% respectively). These reductions in enzyme activity were abolished by removing the external calcium or by the addition of N omega-nitro-L-arginine (LNNA) or an analogue of superoxide dismutase (SOD) manganese [III] tetrakis 4-benzoic acid porphyrin (Mn-TBAP). These data suggest that a reactive oxygen species (ROS) such as peroxynitrite is involved in the reduction of mitochondrial complex activities following AH.


Prevention of neonatal group B streptococcal sepsis: is routine antenatal screening appropriate.
Four strategies for prevention of early onset neonatal group B streptococcal (GBS) sepsis were considered: A: routine antenatal screening for GBS vaginal carriage at 26-28 weeks' gestation and intrapartum antibiotic prophylaxis for all carriers; B: screening as above and prophylaxis only for carriers with risk factors for sepsis; C: prophylaxis for all women with risk factors; D: as for C plus screening at 37 weeks' gestation and prophylaxis for carriers. The outcomes considered for each option were: the proportion of women given prophylaxis; the risk of anaphylaxis; cases of neonatal GBS sepsis and deaths prevented; costs of screening, prophylaxis and of acute care of remaining cases. Published local and overseas studies of neonatal GBS sepsis, effectiveness of antenatal screening and prophylaxis and estimated costs were evaluated. Any of the proposed strategies can prevent a significant proportion of cases of neonatal GBS sepsis and a strategy for prevention of neonatal group B streptococcal sepsis should be part of routine obstetric practice. Strategy C is simple, effective, inexpensive and avoids unnecessary antibiotic use; it is recommended particularly when antenatal care is provided mainly in community or private practice. Strategy A (using vaginal and rectal swabs for screening) could prevent more cases, but at greater cost which could be justified only if protocols can be properly implemented and monitored.


Angle-torque relationship of the subtalar pronators and supinators in younger and elderly males and females.
The angle-dependent torque capacity of the subtalar pronators and supinators is important to maintain dynamic ankle stabilisation. Based on the peak torques during maximum voluntary isometric pronation and supination across the subtalar range of motion, the strength curves of younger and elderly males and females were investigated. Maximum voluntary isometric subtalar pronator and supinator strength tests were administered to 30 younger and 30 elderly volunteers (each 15 male and 15 female subjects). Total active subtalar range of motion and peak pronator and supinator torques were measured in five anatomical subtalar joint angles using a custom-built apparatus with two force transducers. Furthermore, relative torques (normalised to the individual peak torque) and pronator-to-supinator strength-ratios were also calculated. Pronator-to-supinator strength ratio, and peak pronator and supinator torques are affected by age and by joint angle x age interactions. All supinator strength curves show a steadily descending characteristic from the pronated to the supinated positions. The pronator strength curve had an inverted U-shaped characteristic, except for younger women of whom 47 % exert highest peak values in the end-range pronation angle. Both relative pronator and supinator strength are dependent on sex (P < 0.05). Relative pronator strength is also affected by joint angle x sex (P < 0.0001) and joint angle x sex x age (P < 0.05) interactions. Beside age effects on all range of motion parameters, pronation range of motion is influenced by a sex x age interaction (P < 0.05). Age- and sex-related differences in both subtalar strength profile and range of motion have to be considered when testing strength across subtalar range of motion. Younger females have higher pronator strength capacity in the most pronated joint angle, which may be due in part to their greater subtalar joint range of motion compared to the other groups. In the most supinated position both pronator and supinator strength capacity is reduced in younger females compared to younger males.


Mechanotransduction is enhanced by the synergistic action of heterotypic cell interactions and TGF-β1.
With the use of planar substrates and collagen gels, the field of mechanotransduction has focused on the role of extracellular matrix stiffness, mechanical tension, and TGF-β1 in generating a more contractile fibroblast. However, little is known about the role of cell-cell interactions in inducing cellular contraction. We used 3-dimensional self-assembled microtissues, in which cell-cell interactions dominate, and a recently developed cell power assay (an assay for mechanotransduction) to quantify the effects of TGF-β1 vs. the heterotypic cell interface on the power exerted by pure normal human fibroblast (NHF) and pure rat hepatocyte 35 (H35) microtissues and their mixes. As a control, we found that TGF-β1 only doubled the power output of pure NHF and pure H35 microtissues, whereas the heterotypic environment resulted in a 5-fold increase in cell power (0.24±0.05 to 1.17±0.13 fJ/h). Seeding TGF-β1-treated NHFs with untreated H35 cells demonstrated that the heterotypic environment and TGF-β1 synergistically increase cell power by 22× by maximizing heterotypic cell interactions. Using a mathematical simulation of stress generation, we showed that tensile forces can be enhanced by heterotypic cell interactions. These data render a new understanding of how heterotypic cell interactions may increase cellular force generation during wound healing.


Multidrug-resistant tuberculosis over 20 years at a referral hospital in South Korea: trends and outcomes.
A referral centre in South Korea. To investigate trends in drug resistance, treatment modalities and outcomes, and adverse events of multidrug-resistant tuberculosis (MDR-TB) over two decades. MDR-TB patients treated at Seoul National Hospital University between 1996 and 2015 were divided into four 5-year cohorts according to the date of initial diagnosis. Changes in demographic characteristics, drug resistance, drugs used, treatment outcomes and adverse events over time were elucidated. Between 1996 and 2015, 418 patients were treated for MDR-TB: 86 patients between 1996 and 2000, 125 between 2001 and 2005, 123 between 2006 and 2010, and 84 between 2011 and 2015. The proportion of patients with positive acid-fast bacilli sputum (60.5-29.7%, P < 0.001) or cavities on chest radiographs (86.0-40.5%, P < 0.001) decreased over time. Resistance to pyrazinamide, fluoroquinolones, cycloserine and p-aminosalicylic acid decreased. Later-generation fluoroquinolones (77.9-90.5%) and linezolid (0-26.2%) became more frequently prescribed. The treatment success rate increased (45.3-88.1%, P < 0.001); neurological adverse events, including peripheral neuropathy also increased (4.7-13.1%, P = 0.027). MDR-TB patients presented with less severe disease and better resistance profiles over time in South Korea, with treatment outcomes improving continuously.


How to improve infection prevention by selective decontamination of the digestive tract (SDD).
From the point of view of prevention, it is useful to divide infections in intensive care into exogenous infections and primary or secondary endogenous infections. Exogenous infections hardly play a role nowadays. With selective decontamination of the digestive tract (SDD) secondary endogenous infections can be effectively prevented, but for primary endogenous infections SDD comes too late. Primary endogenous infection is the major infectious problem in intensive care. A large number of these infections are postoperative infections and are responsible for a high morbidity and mortality in the intensive care unit. Many of these postoperative infections might be prevented if SDD were started before instead of after the operation when the patient is admitted to the ICU. A tentative list of indications for pre-operative SDD is presented with a flow diagram to determine the optimal infection prevention regimen.


The behaviour of infants whose mothers smoke in pregnancy.
The Brazelton Neonatal Behavioural Assessment Scale was used to compare the behaviour patterns of infants of mothers who smoked during pregnancy and those whose mothers did not smoke. Smokers were mothers who had smoked more than 15 cigarettes/day throughout their pregnancy. Over a period of 9 mth, a total of 32 infants (15 of whose mothers smoked and 17 whose mothers did not smoke) between 4 and 6 days of age were examined and the results compared. The two groups were matched for maternal age, social class and parity. All infants were spontaneously delivered at term and of normal birthweight. Sex distribution was equal. Duration of labour and analgesia during labour were similar for smokers and non-smokers. Examinations were carried out in a warm, quiet semi-dark room, the examiner being unaware of which category the infant was in. There was evidence to suggest that the behavioural patterns of infants can be influenced by smoking in pregnancy and that in particular the auditory senses are affected.


Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients.
To measure prevalence, incidence, and mortality of cardiovascular outcomes among persons with chronic obstructive pulmonary disease (COPD) and to assess the extent these outcomes differ from persons without COPD. Retrospective cohort study in longitudinal health care databases maintained by the government of Saskatchewan, Canada. Subjects were persons age 40 years or older who were diagnosed with COPD during 1997-2000 and who received two or more prescriptions for bronchodilators within 6 months of diagnosis. Each subject was matched by age and sex to two controls without COPD or asthma. Of COPD patients (n = 11,493), 54% were male, and 74% were 65 years or older. Prevalence of all cardiovascular diseases was higher in the COPD group than in the comparison group. After adjusting for cardiovascular risk, odds ratios of prevalence were: arrhythmia 1.76 (confidence interval [CI]: 1.64-1.89), angina 1.61 (CI: 1.47-1.76), acute myocardial infarction 1.61 (CI: 1.43-1.81), congestive heart failure 3.84(CI: 3.56-4.14), stroke 1.11 (CI: 1.02-1.21), pulmonary embolism 5.46 (CI: 4.25-7.02). Risk of hospitalization due to each cardiovascular cause was elevated in the COPD group. The risk ratio for cardiovascular mortality was 2.07 (CI: 1.82-2.36) and all cause mortality was 2.82 (CI: 2.61-3.05). Persons with diagnosed and treated COPD are at increased risk for hospitalizations and deaths due to cardiovascular diseases.


Impaired motor coordination in mice lacking prion protein.
1. Prion protein (PrPC) is a host-encoded glycoprotein constitutively expressed on the neuronal cell surface. Accumulation of its protease-resistant isoform is closely related to pathologic changes and prion propagation in the brain tissue of a series of prion diseases. However, the physiological role of PrPC remains to be elucidated. 2. After long-term observation, we noted impaired motor coordination and loss of cerebellar Purkinje cells in the aged mice homozygous for a disrupted PrP gene, a finding which strongly suggests that PrPC plays a role in the long-term survival of Purkinje cells. 3. We also describe the resistance of the PrP null mice to the prion, indicating the requirement of PrPC for both the development of prion diseases and the prion propagation.


Insights into the genetic basis for natural phenotypic resistance of human rhinoviruses to pleconaril.
Recent phylogenetic analyses of the deduced amino acid sequence of the major viral capsid protein (VP1) of all human rhinovirus (HRV) serotypes revealed two distinct species within the genus: species A (75 serotypes) and species B (25 serotypes). Pleconaril is a novel capsid inhibitor of HRVs. All 75 species A serotypes and 18 of the 25 species B serotypes are susceptible to inhibition by pleconaril in cell culture. The seven resistant serotypes are HRV-4, -5, -42, -84, -93, -97 and -99. We were interested in understanding the genetic basis for phenotypic resistance to pleconaril among these naturally occurring viruses. We compared the 25 amino acids of VP1 that comprise the drug-binding pocket of susceptible and resistant species B viruses. A consistent difference was observed at two positions: the vast majority of susceptible viruses had tyrosine and valine at VP1 residues 152 and 191, respectively (Y(152) and V(191)); all resistant viruses had phenylalanine and leucine at these positions (F(152) and L(191)). HRV-14, a pleconaril susceptible virus, has a drug-binding pocket amino acid composition that differs from the naturally resistant HRV-5 and HRV-42 only at these two positions. To gain further insight into the role of these specific residues in natural resistance to pleconaril, we substituted the amino acids at these two positions individually and in combination in an infectious clone of HRV-14 and tested the rescued virus for susceptibility to pleconaril and virion stability. The results indicate that substitution of V(191) to Leu in HRV-14 has a profound negative impact on drug susceptibility but that full resistance to pleconaril is only seen when combined with Phe at position 152 in a HRV-14 double variant (F(152), L(191)). These data identify L(191) in species B HRV as a potentially key residue in conferring significantly reduced susceptibility to pleconaril. These results may be useful in distinguishing naturally occurring viral resistance to pleconaril from treatment-emergent resistance.


Baseline erectile function alters the cavernous nerve quantity and distribution around the prostate.
We clarified the distribution of neuronal nitric oxide synthase positive nerve fibers around the prostate and factors contributing to fiber quantity. We investigated 46 hemispheres of 23 nonnerve sparing radical prostatectomy specimens from patients with available preoperative International Index of Erectile Function and maximum penile circumferential change data. We performed immunohistochemical staining with neuronal nitric oxide synthase antibody, and divided the prostatic hemisphere into 6 zones to assess the distribution of neuronal nitric oxide synthase positive nerve fibers at the apex, midportion and base of the prostate. Multivariate analysis of the quantity of overall neuronal nitric oxide synthase positive nerve fibers used the variables of specimen weight, patient age, body mass index, International Index of Erectile Function and maximum penile circumferential change. A maximum penile circumferential change of 20 mm or less was considered objective erectile dysfunction. Median patient age was 68 years (range 57 to 74). Median International Index of Erectile Function-erectile function domain score was 12 (range 0 to 24) and median maximum penile circumferential change was 25.0 mm (range 2.70 to 38.3). Of the neuronal nitric oxide synthase positive nerve fibers 65% were distributed in a 3 to 5 o'clock sextant (p <0.001). Logistic regression analysis revealed that maximum penile circumferential change was the single significant variable (p = 0.019). The fiber count was greater in the objective erectile dysfunction group (median 1,500, range 382 to 2,760) than in the nonerectile dysfunction group (median 649, range 156 to 2,916) (p = 0.009). The fiber count was significantly different between the 2 groups in the 3 to 6 o'clock area, especially at the apex. Baseline erectile function greatly impacts cavernous nerve quantity and distribution. Cavernous nerve preservation in the neurovascular bundle, especially at the apex, is still essential for patients with erectile dysfunction.


An involvement of SR-B1 mediated p38 MAPK signaling pathway in serum amyloid A-induced angiogenesis in rheumatoid arthritis.
Serum amyloid A (SAA) has been reported high expression in autoimmune diseases, such as rheumatoid arthritis (RA). However, detailed molecular mechanisms induced by SAA in the pathogenesis of RA are still unclear. Herein, we focused on the role of SAA-SR-B1 mediated p38 MAPK signaling pathway in the process of RA angiogenesis. Our results showed that both SAA and SR-B1 predominantly localized to vascular endothelial cells, lining and sublining layers in RA synovium. In a series of in vitro experiments with human umbilical vein endothelial cells (HUVECs), SAA induced the endothelial cells (ECs) proliferation, migration and tube formation. However, blockage of SR-B1 and p38 MAPK inhibited SAA-induced cells proliferation, migration and tube formation. In conclusion, our data showed a possible molecular mechanism for SAA-SR-B1 induced angiogenesis events via p38 MAPK signaling pathway.


ERS International Congress 2018: highlights from best-abstract awardees.
A summary of the ERS International Congress 2018 from the best-abstract awardees for each ERS Assembly and their views on the evolving field of research of their respective Assemblies http://ow.ly/c0eq30ntKuw.


Socioeconomic factors and autism among 16- to 30-month-old children: Evidence from a national survey of China.
Does being born in a family of high socioeconomic status mean a higher risk of being diagnosed with autism? The evidence from the Asian area is lacking. This research was conducted among 6049 toddlers who went through an evaluation-diagnose procedure of autism and whose parents were surveyed during the national survey of China, 2016-2017. Parents reported their education levels, occupations, family income, and ethnic background. We recruited the toddlers and parents from kindergartens, communities, and hospitals in five geographically representative areas of China. On average, these toddlers were 23 months of age. We found toddlers whose mothers had less than 9 years of education (junior middle school or below) had 2.46 times the chance to get a diagnosis of autism, compared with toddlers whose mothers had more than 15 years of education (college or above). We also found that 1.17 toddlers could be diagnosed with autism in each 100 Chinese toddlers. These findings have important implications for providing support to families that have low socioeconomic status, especially families with a mother who did not complete 9 years of education. Early detection programs focused on children from low socioeconomic backgrounds should be promoted.


Evaluation of AID-COM, a communication-focused program for family carers of people with early-stage Alzheimer's disease: A pilot study (innovative practice).
Families providing care to relatives with Alzheimer's disease are quickly destabilized by changes that disrupt communication. This pilot mixed-design study aimed to provide a quantitative and qualitative evaluation of a communication-based training program for carers of people with early-stage Alzheimer's disease. Five participants received three training sessions. The use of communication strategies by participants and their effectiveness were evaluated before and after the training, and a focus group was conducted to gather participants' impressions about the impacts of the training on communication with the person they cared for. The AID-COM (AID for COMmunication) program appears to have met expectations.


Pyrrolidinyl peptide nucleic acid homologues: effect of ring size on hybridization properties.
The effect of ring size of four- to six-membered cyclic β-amino acid on the hybridization properties of pyrrolidinyl peptide nucleic acid with an alternating α/β peptide backbone is reported. The cyclobutane derivatives (acbcPNA) show the highest T(m) and excellent specificity with cDNA and RNA.


Antiviral activities of flavonoids and organic acid from Trollius chinensis Bunge.
The flower of Trollius chinensis Bunge is used for treating upper respiratory infections, pharyngitis, tonsillitis, and bronchitis in Chinese folk medicine. The antiviral activities of the crude extract, total flavonoids, orientin, vitexin and proglobeflowery acid isolated from the flowers of T. chinensis against parainfluenza type 3 (Para 3) virus were investigated. The results showed that the crude extract and total flavonoids exhibited a weak antiviral activity against Para 3. Orientin and vitexin demonstrated potent or moderate antiviral activity against Para 3. Proglobeflowery acid showed weak antiviral activity against Para 3.


The effect of deinstitutionalization on the longitudinal continuity of mental health care in the Netherlands.
Deinstitutionalization has been accompanied by a decreasing continuity of care in a number of countries. This study evaluates the effects of the Dutch model for deinstitutionalizing mental health care. Details of users and their use of community- and hospital-based services between 1990 and 1999 were retrieved from the Groningen case register. The time between discharge from the hospital and the first subsequent community-based contact was the primary indicator for changes in continuity of care. The total proportion of discharges from hospital-based mental health care followed within 6 months by community-based care increased by 11% due to the improved availability of day treatment and home treatment. In terms of median survival time, aftercare in the years 1998/1999 was delivered more than twice as fast as in the years 1990/1991. Study results supported the hypothesis in Dutch deinstitutionalization policy that the continuity of mental health care would benefit as to its longitudinal dimension.


Chiral-layered metal phosphonate formed via spontaneous resolution showing dehydration-induced antiferromagnetic to ferromagnetic transformation.
Metal phosphonates M (II){(2-C 5H 4N)CH 2NHCH 2PO 3} (H 2O) [M = Mn ( 1), Cd ( 2)] with chiral-layered structures are obtained by spontaneous resolution using achiral starting materials. The magnetic behavior of 1 is transformed from antiferromagnetic to ferromagnetic upon dehydration.


[Evaluation of macroamputations of the upper extremity in the management of primary malignant bone and soft-tissue tumours using the DASH score].
The purpose of this retrospective analysis was to identify patients with macroamputations of the upper extremity due to malignant bone or soft-tissue tumours at a single institution. The German DASH score (Disability of Arm, Shoulder, Hand) was obtained in order to measure how patients manage their daily activities. Between 1998 and 2005, 1652 patients were operated due to a bone or soft-tissue tumour, 370 of these due to a malignant one (22 %). The tumour was localised in the lower extremity or in the pelvis in 246 cases, in the trunk in 38 and in the upper extremity in 86 cases. These 86 primary malignant tumours comprised 22 bone and 64 soft tissue tumours. Amputations had to be performed in the lower extremity in 14 % (35/246) and in the upper extremity in 7 % (6/86). Six patients with macroamputations of the upper extremity were identified and in five of these the DASH score was obtained. The mean DASH score for the module 1 (disability/symptom) was 75.1 points ([sum of responses - 30]/1.2), for module 2 (work) 92.4 ([sum of responses - 4]/0.16), and for module 3 (sports/performing arts) 90 points ([sum of responses - 4]/0.16). Only two patients worked again and only one played an instrument. Despite neo-/adjuvant therapeutic options and modified reconstructive procedures 7 % of patients with malignant bone or soft tissue tumours of the upper extremity had to undergo an amputation. The DASH score is an appropriate instrument to measure the disability after upper limb amputation due to tumour.


Rotator cuff injuries and factors associated with reoperation.
To evaluate the prevalence of rotator cuff tears and describe the profile of reoperated patients, causes of repeated tendon tears, tear evolution and range of times between surgical procedures. This was a cross-sectional study involving 604 surgical procedures performed at two regional referral hospitals between January 2006 and December 2012. After approval by the ethics committee, data describing the patients' epidemiological profile were gathered at a single time, using Cofield's classification to measure the extent of the tears, all of which underwent arthroscopic surgery. The data were entered into Epi Info 3.5.3 and were analyzed using SPSS version 18.0. Among the 604 surgical procedures, females were affected in more cases (351; 58.1%). When the dominant limb was the right limb, it was affected in 90% of the cases (p < 0.05). The supraspinatus tendon was affected in 574 cases (95%) and the tears were of medium size in 300 cases (49.7%). Eighteen reoperations were performed (2.98%) and the upper right limb was the most affected (66.6%). The cause was non-traumatic in 12 patients. The repeated tears were mostly smaller (44%), and the length of time between the two surgical procedures ranged from 6 to 298 weeks. Female gender, smaller extent in the second procedure and non-traumatic cause were found in most of the cases analyzed.


Functional external anal sphincter reconstruction for treatment of anal incontinence using muscle progenitor cell auto grafting.
This study aimed to investigate the feasibility of autologous muscle progenitor cell transplantation for anal sphincter regeneration in a rabbit model of anal incontinence. We examined the serial changes in structure, with particular emphasis on histology and functional properties of the anal sphincter. External anal sphincterotomy was performed in 21 rabbits; these rabbits were randomly assigned to 2 groups. In group I (n = 9), autologous muscle progenitor cells were isolated from quadriceps myofiber explants, labeled with PKH-26, and injected into sphincter 3 weeks after sphincterotomy. In group II (n = 12), saline buffer was injected at the site of damage. Sphincter electromyography and manometry were performed immediately before sphincterotomy and 14, 28, and 60 days after injection in 3 animals in each group at every interval and the findings were correlated with histomorphological studies. In addition, electromyography and manometry were performed in the remaining 3 rabbits in group II after 6 months. In group II, a flaccid sphincter persisted during the 6 months of follow-up. In group I, muscle progenitor autografting accelerated sphincter myofiber repair and improvement in functional capacity of the damaged sphincter. Fluorescently labeled cells were detected in all of the grafted sphincters; regenerated myotubes were detectable at the injection site as evidenced by the presence of desmin. We also observed a significant decrease in interstitial fibrosis in the 4th week and strikingly higher amounts of Ki-67-positive cells in group I. Manometry and electromyography showed a significant improvement in the mean resting anal canal pressure and sphincteric electrical activity 4 weeks after cell injection, respectively. Transplanting muscle progenitor cells showed the potential for recapitulation of a myogenic program when injected into deficient rabbit anal sphincter. Objective anal measures of resting and stimulated pressures and electromyographic profile improved. Stem cell-mediated anal myoplasty warrants additional investigation as a new method to treat anal incontinence before attempting this modality in the clinical setting.


Augmented expression of daintain/allograft inflammatory factor-1 is associated with clinical disease: dynamics of daintain/allograft inflammatory factor-1 expression in spleen, peripheral nerves and sera during experimental autoimmune neuritis.
Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome, characterized by inflammation and demyelination of the peripheral nervous system (PNS). Daintain/allograft inflammatory factor-1 (daintain/AIF-1) is a novel interferon-gamma-inducible protein expressed by macrophages during organ specific autoimmune diseases. To study the involvement of daintain/AIF-1 in EAN we induced EAN in Lewis rats by immunizing with bovine PNS myelin (BPM) and complete Freund's adjuvant (CFA). The expression of daintain/AIF-1 was examined in the spleen, peripheral nerves and sera during the course of EAN by immunohistochemistry and radioimunoassay (RIA). The expression of daintain/AIF-1 in the spleen and in the sciatic nerves peaked at the preclinical stage (day 7 post immunization (p.i.)) and at the height (day 15 p.i.) of clinical EAN, consistent with a disease promoting role for daintain/AIF-1. Daintain/AIF-1 expressing cells represented a subset of ED1+ or CD11b/c+ mononuclear cells. A significant increase of daintain/AIF-1-like immunoreactivity in sera occurred at the preclinical stage of EAN. Taken together, these data indicate that daintain/AIF-1 may play a proinflammatory role in the pathogenesis of EAN.


Dietary alpha-ketoglutarate enhances intestinal immunity by Th17/Treg immune response in piglets after lipopolysaccharide challenge.
Alpha-ketoglutarate (AKG) is important for improving intestinal and systemic immune function. This study aimed to explore whether AKG enhances gut immunity in lipopolysaccharide (LPS)-challenged piglets by modulating the immune-related helper T cells 17 (Th17)/regulatory T cells (Treg) balance pathway. A 2 × 2 factor design was used on 24 pigs, with the major factors being diet (basal diet or 1% AKG diet) and immunological challenge (saline or LPS). Piglets were fed with a basal or AKG diet for 21 d and then received intraperitoneal injection of LPS or saline. The results demonstrated that AKG supplementation enhanced growth performance compared with the control group (P < 0.05). AKG improved the ileal morphological structure (P < 0.01). Finally, AKG supplementation increased interleukin (IL)-10, transforming growth factor beta-1, forkhead box P3, and signal transducer and activator of transcription 5 genes expression whereas decreasing IL-6, IL-8, IL-1β, tumor necrosis factor-α, IL-17, IL-21, signal transducer and activator of transcription 3 and rar-related orphan receptor c genes expression (P < 0.05). These findings suggested that dietary AKG can improve the growth performance of piglets. Meanwhile, dietary AKG can alleviate LPS-induced intestinal inflammation through Th17/Treg immune response signaling pathway.


Attitudes and impact among people with abnormal premarital screening test results in Muscat governorate's primary healthcare centers in 2018.
Hereditary hemoglobin disorders are among the most common inherited diseases globally. In Oman, the burden of hereditary hemoglobin disorders has long been recognized as a major public health problem. In Oman, the prevalence of SCD ranges between 0.2 and 0.3% and of homozygous B-thalassemia was 0.07-0.08% while the prevalence of sickle cell trait and B-thalassemia trait reached up to 4.8-6% and 2-2.6% respectively. Glucose-6-phosphate dehydrogenase (G6PD) had a high prevalence in Oman, being 25% in males and 10% in females. The premarital screening and counseling (PMSC) program is an important preventative service for the most common hereditary hemoglobin disorders in Oman. The aim of this research is to study the attitude of those with abnormal premarital screening results and the impact of these results. This cross-sectional study was carried out in all primary healthcare centers in the Muscat governorate in 2018 to analyze abnormal premarital screening (PMS) tests results which mainly include sickle cell disease, thalassemia, and G6PD deficiency. Data were collected through telephone questionnaires with those with abnormal PMS test results. The questionnaire consisted of 3 parts investigating sociodemographic characteristics, attitudes toward PMS, and impact of the screening on participants. Of the 159 participants, 72.3% were between 20 and 29 years of age. Over two-thirds (71.5%) took PMS test while engaged. Consanguineous marriage was reported in 38.4% of married participants. The majority (94.3%) of participants believed PMSC to be important and (90%) agreed PMS should be obligatory before marriage. Half took the test as a personal decision while 17% complied with their spouse. Healthcare worker advice accounted for 21.4% of participants' decisions. Participant response to positive PMS results showed that 23% canceled their engagement, while 13.8% continued with marriage. Overall, 57.9% believed that PMS affected their lives positively. There is a relatively high favorable attitude toward PMSC. More effort is needed to raise public awareness regarding early PMS. Additionally, further genetic counseling before and after PMS testing is essential for the program's success.


Preventing drug-related morbidity--the development of quality indicators.
To describe the process that has been undertaken to (i) validate further UK indicators for preventable drug-related morbidity (PDRM) generated by a previous study and (ii) develop additional new indicators derived from UK clinical practice. A two-round Delphi questionnaire survey. A UK study based in primary care. A purposively selected sample of primary care pharmacists (n = 9) and general practitioners (n = 8). The establishment of consensus among the panel as to whether an indicator represented a PDRM. The pre-defined level of consensus was achieved for 24 indicators (59%; 24 of 41). We have identified that although mechanisms exist for identifying 'the outcome' component of PDRM indicators, identifying the 'pattern of care' that is needed to prevent their occurrence is far more challenging. Nonetheless, we have taken considerable steps along the path of validating such indicators. Future operationalization in a general practice setting should help to facilitate improvements in medicine management in primary care and ultimately benefit patients.


Plant sphingolipids promote extracellular vesicle release and alleviate amyloid-β pathologies in a mouse model of Alzheimer's disease.
The accumulation of amyloid-β protein (Aβ) in brain is linked to the early pathogenesis of Alzheimer's disease (AD). We previously reported that neuron-derived exosomes promote Aβ clearance in the brains of amyloid precursor protein transgenic mice and that exosome production is modulated by ceramide metabolism. Here, we demonstrate that plant ceramides derived from Amorphophallus konjac, as well as animal-derived ceramides, enhanced production of extracellular vesicles (EVs) in neuronal cultures. Oral administration of plant glucosylceramide (GlcCer) to APP overexpressing mice markedly reduced Aβ levels and plaque burdens and improved cognition in a Y-maze learning task. Moreover, there were substantial increases in the neuronal marker NCAM-1, L1CAM, and Aβ in EVs isolated from serum and brain tissues of the GlcCer-treated AD model mice. Our data showing that plant ceramides prevent Aβ accumulation by promoting EVs-dependent Aβ clearance in vitro and in vivo provide evidence for a protective role of plant ceramides in AD. Plant ceramides might thus be used as functional food materials to ameliorate AD pathology.


Potassium inhibition during sludge and biopulp co-digestion; experimental and model-based approaches.
Process instability with consecutive low methane production are common challenges of the anaerobic digestion (AD) of municipal wastes. In the present study, the co-digestion of sewage sludge and municipal biopulp was investigated at batch and continuously fed digesters. At batch tests, the highest methane yield for co-digestion (467 ± 17 mLCH4/gVS) was achieved when biopulp contributed to 80% of organic matter content and sludge the remaining 20%. At continuous mode operation, co-digestion achieved 0.91 ± 0.11 L/(L·d) methane productivity, while mono-digestion of sludge achieved 0.62 ± 0.05 L/(L·d). Potassium inhibition was investigated at the most efficient co-digestion scenario and was found that the half maximal inhibitory concentration (IC50) occurred at 8 g-K+/L. Subsequently, the effect of K+ was investigated at different scenarios at continuous operation. Simulations based on BioModel described the inhibitory effect of K+ by introducing non-competitive inhibition of methanogens. Simulation results confirmed the strongly inhibitory effect of potassium to the AD process.


OSNA Total Tumor Load for the Prediction of Axillary Involvement in Breast Cancer Patients: Should We use Different Thresholds According to the Intrinsic Molecular Subtype? MOTTO Study.
To assess the impact of the molecular subtype (MS) on the total number of CK19 mRNA copies in all positive SLN (TTL) threshold, to predict non-SLN affectation, and to compare 5 years progression-free survival (PFS) according to the risk of recurrence (ROR) group by PAM50. Cohort with infiltrating breast cancer with intra-operative metastatic SLN detected by one-step nucleic acid amplification (OSNA) assay who underwent subsequent ALND. Logistic regression was used to assess a possible interaction between TTL and MS(Triple Negative, Her-2-Enriched, Luminal A, or Luminal B), or hormone receptors (HR: positive or negative) by immunohistochemistry (IMH). Cox regression was used to compare PFS and OS in the 3 ROR groups (high, medium, or low). TTL was predictive of non-SLN affectation in both univariate (OR [95% CI]: 1.72 [1.43, 2.05], P < .001) and multivariate (1.55 [95% CI: 1.04, 2.32], P = .030) models, but MS-IMH or HR-IMH, and their interactions with TTL were not (best multivariate model: HR + main effect OR 1.16 [95% CI: 0.18, 7.64], P = .874; interaction OR: 1.04 [0.7, 1.55], P = .835; univariate model: HR + main effect OR: 1.44 [95% CI: 0.85, 2.44], P = .180). PFS was lower in the high-risk ROR group (81.1%) than in the low-risk group (93.9%) (HR: 3.68 [95 CI: 1.70, 7.94], P < .001). our results do not provide evidence to support the utilization of subtype-specific thresholds for TTL values to make therapeutic decisions on the axilla. The ROR group was predictive of 5 years-PFS.


Multicenter retrospective database evaluation of Takotsubo syndrome in subjects undergoing catheter ablation for atrial fibrillation.
Intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation may result in Takotsubo syndrome (TS), but the frequency, predisposing factors (age, sex, mental health disorders), and outcomes are currently unknown. This study sought to assess the frequency, predisposing factors, and outcomes of subjects who underwent intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation and were diagnosed with TS. This was a retrospective observational cohort study utilizing TriNetX® electronic health record (EHR) data. We included subjects aged older than 18 years who underwent intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation. The study population was divided into two groups (no TS diagnostic code presence and TS diagnostic code presence). We analyzed the distributions of age, sex, race, diagnostic codes, common terminology procedures (CPT), and vasoactive medication codes and examined mortality rate within 30 days. We included 69,116 subjects. Of these, 27 (0.04%) had a TS diagnostic code, the cohort was comprised mostly of females [17 (63.0%)], and 1 (3.7%) death within 30 days was reported. There were no significant differences in age and frequency of mental health disorders between those patients in TS and non-TS cohorts. Adjusting for age, sex, race, ethnicity, patient regionality, and mental health disorder diagnostic code, those patients who developed TS had a significantly higher odds of dying in 30 days after catheter ablation compared to those without TS (OR = 15.97, 95% CI: 2.10-121.55, p = .007). Approximately 0.04% of subjects who underwent intracardiac catheter ablation of atrial fibrillation by pulmonary vein isolation had a subsequent diagnostic code of TS. Further study is needed to determine whether there are predisposing factors associated with the development of TS in subjects who undergo catheter ablation of atrial fibrillation by pulmonary vein isolation.


Sucrose Gradient Analysis of Human Mitochondrial Ribosomes and RNA.
Faithful expression of the mitochondrial genome is required for the synthesis of the oxidative phosphorylation complexes and cell fitness. In humans, mitochondrial DNA (mtDNA) encodes 13 essential subunits of four oxidative phosphorylation complexes along with tRNAs and rRNAs needed for the translation of these proteins. Protein synthesis occurs on unique ribosomes within the organelle. Over the last decade, the revolution in genetic diagnostics has identified disruptions to the faithful synthesis of these 13 mitochondrial proteins as the largest group of inherited human mitochondrial pathologies. All of the molecular steps required for mitochondrial protein synthesis can be affected, from the genome to protein, including cotranslational quality control. Here, we describe methodologies for the biochemical separation of mitochondrial ribosomes from cultured human cells for RNA and protein analysis. Our method has been optimized to facilitate analysis for low-level sample material and thus does not require prior organelle enrichment.


A Novel, Efficient, Unit Circle-Based, Method for Positioning and Operating Cryo-Surgical Probes in Convex Target Areas.
A novel method for positioning and operating needle-like cryo-surgical probes in 2D convex target areas is presented. The method is based on the recorded dynamic performance of a single probe, termed "unit circle," (UC) embedded in a semi-infinite, tissue-like medium. Up to 15 cryo-probes, inserted into the same depth, are operated uniformly for 2-5 min. A predetermined number of probes are rearranged inside the target area until a "tight configuration" is obtained. The probes are initially arranged inside the target area such that the "lethal temperature" circles produced by them are tangent to its contour and to both adjacent lethal temperature circles. Subsequently, all probes are repositioned inwardly, each at a specific distance that depends on the local radius of curvature of the target area. Resulting total "defect areas"-internal and external-for a number of demonstrated cases, amounted to between 2.5% and 7.6% of the target area. The lower values of the defect areas were obtained with increasing numbers of inserted probes coupled with shorter operating times. Possible freezing damages to regions beyond the target area were reduced by up to about 30% for these cases. Similar results were obtained for a case of combined convex-concave target area, treated with additional, externally inserted, heating probes.


Hypoxic ventilatory response of cats at high altitude: an interpretation of 'blunting'.
Cats acclimatized to a simulated altitude of 5500 m developed attenuated ventilatory response in the hypoxic test range of PAO2 = 60-45 torr, but their CO2 response remained normal, although the curve was shifted to a lower PACO2 range. The acclimatized cats a high respiratory frequency and maintained hyperventilation under normoxia. Cats from 3100 m altitude had hypoxic reponses which were, on the average, slightly below sea level standards, but the difference was not statistically significant. Two cats raised at 4640 m had a normal hypoxic ventilatory response even though the frequency response was 'blunted'. These data suggest the possibility of hypoxic 'threshold' near 5500 m to produce an attenuation effect. Another series of cats acclimatized to 5500 m were tested with more severe hypoxia, and they exhibited brisk ventilatory response in range PAO2, 40-25 torr, although they showed typical 'blunting' in the range PAO2, 60-45 torr. These results suggested that the phenomenon of attenuated hypoxic response at high altitude was a reflection of shift of hypoxic set point to a lower PAO2. Finally, it was shown that the hypoxic responses of 'blunted' animals were restored to normal after mid-collicular decerebration; and that decortication resulted in a typical hyperexcitability of the hypoxic response. These results are discussed in terms of hypothesized suprapontine modulating influences on the control of breathing, and possiblities for a contribution of these mechanisms in pathogenesis of hypoxic 'blunting' are raised.


Draft Genome Sequence of Campylobacter ureolyticus Strain CIT007, the First Whole-Genome Sequence of a Clinical Isolate.
Herein, we present the draft genome sequence of Campylobacter ureolyticus. Strain CIT007 was isolated from a stool sample from an elderly female presenting with diarrheal illness and end-stage chronic renal disease.


Monitoring for intraoperative awareness.
Despite advances in anesthetic technique and technology, intraoperative awareness continues to occur with alarming regularity. The psychological effects on patients and the medicolegal consequences to providers have created the need for a reliable monitor of the hypnotic component of anesthesia. A new technology known as bispectral analysis (BIS) has the potential to put an end to the devastating occurrence of intraoperative awareness, as well as improve the overall effectiveness of anesthetic delivery and the surgical experience. Applicable to almost any situation requiring sedation or general anesthesia, BIS's reliability is a real-time measure of hypnosis levels.


Adjuvant arthritic (AA) rats exhibit enhanced endotoxin-induced plasma TNF (EIPT) levels.
Adjuvant arthritis (AA) was induced in male Lewis rats by a single FCA (M. butyricum) injection into the tail. At various time periods post FCA injection, AA and control rats were anesthetized and administered E. coli endotoxin (30 mg/kg, i.v.). Plasma samples were obtained at 30, 60, 90, 120 and 150 min following endotoxin administration and assayed for TNF alpha levels by ELISA. Compared to control rats, AA rats exhibited enhanced EIPT levels (706% of control, p < 0.05) which was associated with the onset of inflammatory lesions on days 12-14 post FCA, and remained significantly elevated (> 300% of control, p > 0.05) for at least 30 days post FCA. There were no significant correlations between EIPT levels and hindpaw volumes or body weights. The results of this study support previous observations that AA is associated with macrophage activation and suggest that EIPT levels in AA rats may be a useful parameter for the evaluation of novel antiarthritic agents.


Evaluation of a newly developed direct agglutination test (DAT) for serodiagnosis and sero-epidemiological studies of visceral leishmaniasis: comparison with IFAT and ELISA.
A newly developed direct agglutination test (DAT) for visceral leishmaniasis, IFAT and ELISA were applied to sera of patients with visceral leishmaniasis, African and American trypanosomiasis, other parasitic infections and healthy controls. The sensitivities of the 3 tests were comparable (96.3% to 100%); excluding patients with African and American trypanosomiasis, the specificities of DAT and IFAT were 100% and ELISA 87.3%. When trypanosomiasis sera were included, the specificities were 72.6%, 94.3% and 79.4% in DAT, IFAT and ELISA respectively. In 273 sera from a leishmaniasis endemic area (Baringo District, Kenya), the sensitivity was 80% in DAT and IFAT and 60% in ELISA, specificities being 99.6% (DAT), 98.5% (IFAT) and 62.5% (ELISA). As the new DAT is economical and easy to perform, it is recommended for sero-epidemiological field work on visceral leishmaniasis.


Direct costs of blood drawings with pre-analytical errors in tertiary paediatric hospital care.
Blood drawings is a common hospital procedure involving laboratory and clinical disciplines that is important for the diagnosis and management of illnesses in children. Blood drawings with pre-analytical error (PAE) can lead to increased costs for hospitals and healthcare organisations. The direct cost of blood drawings after a PAE is not fully understood in paediatric hospital care. The aim of this study was to estimate the average direct cost of PAE per year and per 10,000 blood drawings in tertiary paediatric care. A cost analysis using a bottom-up approach was conducted on the basis of combined information from the hospital's laboratory register for the period 2013-2014 and clinical in-ward observations at a tertiary children's referral hospital in Sweden, the Astrid Lindgren Children's Hospital. For the analysis, we hypothesised the re-collection of all blood drawings with PAE and included the average costs of the sampling materials, the time of the healthcare personnel, the laboratory analyses, and in-ward premises based on the time spent on the blood sampling procedure. The annual cost of PAE was estimated to be 74,267 euros per 54,040 blood drawings, which corresponds to 13,756 euros per 10,000 blood drawings or 1.5 euros per draw. The personnel cost represented 60.1% (45,261 euros per year) of the cost due to PAE, followed by costs for hospitalisation (25.2%), laboratory analyses (8.1%), and materials (5.7%). PAEs lead to substantial increases in the costs in tertiary paediatric hospital care. If these PAEs can be avoided, costs related to the re-collection of blood drawings with PAE may be re-allocated to other health-promoting activities for children visiting hospital institutions.


Paraneoplastic syndromes of the CNS.
Major advances in the management of paraneoplastic neurologic disorders (PND) include the detection of new antineuronal antibodies, the improved characterisation of known syndromes, the discovery of new syndromes, and the use of CT and PET to reveal the associated tumours at an early stage. In addition, the definition of useful clinical criteria has facilitated the early recognition and treatment of these disorders. In this article, we review some classic concepts about PND and recent clinical and immunological developments, focusing on paraneoplastic cerebellar degeneration, opsoclonus-myoclonus, and encephalitides affecting the limbic system.


Large uterine neurofibroma.
Herein we report a rare case of a large uterine neurofibroma. The patient reported infertility and nonspecific pelvic symptoms. Physical examination and ultrasonography revealed a mass of uterine origin with echo texture similar to that of a myoma. With a provisional diagnosis of a myomatous uterus, laparoscopic myomectomy was attempted. The mass, which measured 13 × 9 × 8 cm, was noted to be arising from the uterine fundus and extending into the left broad ligament. Histopathologic examination revealed a neurofibroma, which was confirmed at immunohistochemical analysis of the specimen. Most neurofibromas arise as subcutaneous swellings, and large neurofibromas arising from the myometrium are rare. Deep-tissue neurofibromas are known to recur and are associated with a higher probability of becoming malignant.


Salvage of infected vascular graft via 'perivascular venous banding' technique coupled with rectus abdominis myocutaneous muscle flap transposition.
This is the case of a severe Pseudomonas aeruginosa biological vascular graft infection, completely involving the perianastomotic tract of a femoro - femoral crossover bypass and resulting in repeated bleeding from the offended vessel wall. After the failure of a sartorious rotational muscle flap transposition into the infected groin wound, this 'high-grade' vascular graft infection was finally treated successfully by wrapping a great saphenous vein patch reinforcement circumferentially around the damaged biological vascular conduit and filling the infected wound with a rectus abdominis myocutaneous muscle flap transposition. The aim of this report is to illustrate this novel, to our knowledge, 'perivascular venous banding' technique and to evaluate the prospective of future testing of this surgical procedure. Starting from this singular case, we will also review the role of the rotational muscle flaps in the conservative management of major vascular graft infections.


Childhood adversity and depressive symptoms among young adults: Examining the roles of individuation difficulties and perceived social support.
While childhood adversity is a known risk for depressive symptoms, little is known about the contributing role of individuation difficulties among young adults. The present study examined individuation difficulties and perceived social support-and their interaction-as moderators of the relationship between childhood adversity exposure and depressive symptoms. Young adults (N = 119; M = 20.8 years) completed self-report assessments of childhood adversity, depressive symptoms, individuation difficulties, and perceived social support. Regression analyses were used to examine interaction effects regarding depressive symptom severity. A significant moderated moderation effect was found whereby individuation difficulties interacted with adversity exposure as perceived social support was reduced. Thus, at high levels of individuation difficulties, young adults with exposure to childhood adversity reported elevated depressive symptoms. This effect was buffered by social support such that when individuation difficulties were high, the association between adversity and depressive symptoms decreased from low to moderate and high support. Individuation difficulties and social support are important factors in the development of depressive symptoms from exposure to childhood adversity among young adults.


Video-based self-assessment enhances laparoscopic skills on a virtual reality simulator: a randomized controlled trial.
Hysterectomy rates are decreasing in many countries, and virtual reality (VR) simulators bring new training opportunities for residents. As coaching interventions while training on a simulated complex procedure represents a resource challenge, alternative strategies to improve surgical skills must be investigated. We sought to determine whether self-guided learning using a video-based self-assessment (SA) leads to improved surgical skills in laparoscopic hysterectomy (LH) on a VR simulator. Twenty-four gynecology residents from two university hospitals were randomized into an SA group (n = 12) and a Control group (n = 12). Each participant's baseline performance on a validated VR basic task was assessed. Both groups then performed three virtually simulated LHs during which the participants received no guidance nor feedback. Following each LH, the SA group participants rated the video of their own performance using a generic and a procedure-specific rating scale, while the Control group participants watched an LH video demonstration. The LH videos of both groups' participants were blindly reviewed and rated by expert surgeons, using modified Objective Structured Assessment of Technical Skills scores (OSATS). Objective metrics recorded by the VR simulator were also compared. There was no difference between the groups' baseline performances on the VR basic task. For the first LH, the OSATS-derived scores did not differ between SA and Control groups (9 [7-13] versus 9 [8-14]; p = 0.728). For the third LH, the OSATS-derived scores were higher for the SA group than for the Control group (17 [15-21] versus 15 [11-17], p = 0.039). Between the two groups, the objective metrics did not differ from the first to the third LH. The use of a structured video-based SA leads to improved procedural skills in LH on a VR simulator compared to watching benchmark expert performance, in a population of residents with moderate experience in the operating room.


All eyes on relevance: strategic allocation of attention as a result of feature-based task demands in multiple object tracking.
Multiple object tracking (MOT) plays a fundamental role in processing and interpreting dynamic environments. Regarding the type of information utilized by the observer, recent studies reported evidence for the use of object features in an automatic, low- level manner. By introducing a novel paradigm that allowed us to combine tracking with a noninterfering top-down task, we tested whether a voluntary component can regulate the deployment of attention to task-relevant features in a selective manner. In four experiments we found conclusive evidence for a task-driven selection mechanism that guides attention during tracking: The observers were able to ignore or prioritize distinct objects. They marked the distinct (cued) object (target/distractor) more or less often than other objects of the same type (targets /distractors)-but only when they had received an identification task that required them to actively process object features (cues) during tracking. These effects are discussed with regard to existing theoretical approaches to attentive tracking, gaze-cue usability as well as attentional readiness, a term that originally stems from research on attention capture and visual search. Our findings indicate that existing theories of MOT need to be adjusted to allow for flexible top-down, voluntary processing during tracking.


Monosodium glutamate in the chick embryo: lack of obvious toxic or teratogenic effects when administered at 24 hours incubation.
The administration of monosodium glutamate (MSC) to chick embryos at 24 hours did neither produce gross developmental defects nor influence growth by 72 hours total incubation. The concentrations of MSG administered ranged from 0.3 to 46.6%, the volumes injected being 0.05, 0.1, or 0.2 ml. Several injection methods were evaluated. It is suggested that injection into the centre of the yolk is the most effective way to give water-soluble treatments during this period of development.


Costs and benefits of "insect friendly" artificial lights are taxon specific.
The expansion of human activity into natural habitats often results in the introduction of artificial light at night, which can disrupt local ecosystems. Recent advances in LED technology have enabled spectral tuning of artificial light sources, which could in theory limit their impact on vulnerable taxa. To date, however, experimental comparisons of ecologically friendly candidate colors have often considered only one type of behavioral impact, sometimes on only single species. Resulting recommendations cannot be broadly implemented if their consequences for other local taxa are unknown. Working at a popular firefly ecotourism site, we exposed the insect community to artificial illumination of three colors (blue, broad-spectrum amber, red) and measured flight-to-light behavior as well as the courtship flash behavior of male Photinus carolinus fireflies. Firefly courtship activity was greatest under blue and red lights, while the most flying insects were attracted to blue and broad-spectrum amber lights. Thus, while impacts of spectrally tuned artificial light varied across taxa, our results suggest that red light, rather than amber light, is least disruptive to insects overall, and therefore more generally insect friendly.


The performance of a postinduction fentanyl test in identifying severe obstructive sleep apnea syndrome.
Children with severe obstructive sleep apnea syndrome (OSAS) are more sensitive to opioids. Identifying such children and reducing or even eliminating opioids are necessary but difficult. We have previously shown that patients sensitive to intraoperative fentanyl require less opioids postoperatively. The objective of this study was to evaluate the performance of a postinduction fentanyl test in identifying severe obstructive sleep apnea syndrome. A prospective, observational, assessor-blinded study was carried out with 104 sleep study assessed children undergoing elective adenotonsillectomy. Intravenous fentanyl (1 µg/kg) was administered as a test in nonpremedicated, spontaneously breathing, sevoflurane-induced patients before endotracheal intubation. The respiratory rates before and after fentanyl administration were studied. The primary outcome was the sensitivity and specificity of the postinduction fentanyl test in identifying severe OSAS compared with polysomnography. A postinduction fentanyl test had a likelihood ratio of 7.2 (95% CI: 3.6-14.6) and an area under the curve value of 0.896 (95% CI: 0.821-0.947) to identify severe obstructive sleep apnea syndrome. The pragmatic cut-off value for the postinduction fentanyl test was found to be 50%. Using a reduction in respiratory rate of >50%, the postinduction fentanyl test detected severe OSAS with a sensitivity of 87%, a specificity of 88%, a positive predictive value of 85%, and a negative predictive value of 89%. Our study showed that a postinduction fentanyl test had good predictive value in identifying severe obstructive sleep apnea syndrome and early postoperative adverse respiratory events and could provide a reference for postoperative analgesia in children undergoing adenotonsillectomy.


Does Pallidal Physiology Determine the Success of Unilateral Deep Brain Stimulation in Cervical Dystonia?
Pallidal deep brain stimulation is a well-known surgical treatment for cervical dystonia. The resolution of dystonia typically requires bilateral pallidal stimulation, but in some instances, unilateral stimulation has been successful. In such instances, generally, the stimulated hemisphere was contralateral to the dystonic sternocleidomastoid, but rarely it was ipsilateral. We sought for the physiological features that determine the basis for success and laterality of deep brain stimulation for cervical dystonia with prominent torticollis. We found that pallidal physiology such as high burst to tonic ratio and significant interhemispheric differences in the neuronal firing rate and regularity are critical determinants of successful treatment with unilateral deep brain stimulation. We also found that higher lateralized differences in pallidal physiological parameters predict more robust improvement. In three out of four patients, the stimulation of the hemisphere ipsilateral to the dystonic sternocleidomastoid muscle was effective. These patients did not have any structural brain abnormalities on clinically available imaging studies. One patient responded to the unilateral deep brain stimulation in the hemisphere contralateral to the dystonic sternocleidomastoid. This patient had a structural putamen lesion on brain MRI. These results provide objective parameters determining the success of pallidal deep brain stimulation for treatment of cervical dystonia. The results also depict differences in the pallidal physiology in patients where ipsilateral versus contralateral deep brain stimulation was effective.


Job satisfaction among mental health professionals in Rome, Italy.
Although various surveys on job satisfaction have been performed in mental health care settings, no studies have investigated in-depth the level of satisfaction with the various aspects of work in Italian mental health services. In the present study, all clinical mental health staff working in a large psychiatric catchment area in Rome were invited to anonymously complete a previously validated questionnaire designed to measure job satisfaction among mental health professionals. Of the total 236 health professionals, 196 (83%) agreed to participate. Most participants were not completely satisfied with many aspects of their job, and many were not even moderately satisfied. The level of satisfaction increased with age, and it was significantly lower among hospital-ward staff compared to the staff of outpatient clinics or residential facilities, even after adjusting for age, gender, profession, work setting, and time in current job, using a multiple logistic regression model. Our findings suggest that interventions aimed at increasing job satisfaction among Italian mental health professionals might be warranted, particularly among hospital-ward staff.


Conducting Polymer Dough for Deformable Electronics.
A simple strategy for changing a brittle conducting polymer ( PSS) into a solution-processed highly deformable viscoelastic polymer is presented. Rapid self-healing of conductivity, customer-designed LEDs with complex micro-patterns, and foldable stretchable LEDs are demonstrated.


Influence of long-term metoprolol treatment on early and late exercise test performance after acute myocardial infarction.
The effect of therapy on exercise performance during a 3-year follow-up after acute myocardial infarction (AMI) was evaluated in a double-blind randomized comparison between 154 patients given metoprolol (100 mg twice daily) and 147 patients given placebo. Exercise tests were performed 1.5, 6, 12, 24 and 36 months after AMI. Maximal accomplished workloads were similar in the 2 groups throughout follow-up. Maximal heart rate was significantly higher in the placebo-treated group throughout the study (p less than 0.001). At the 6-week test more patients in the placebo group terminated exercise due to angina pectoris (40 vs 25%, p less than 0.05) and showed exercise-induced ST-depressions (38 vs 27%, p = 0.05) compared with the metoprolol group. Exercise-induced ventricular arrhythmias were significantly more common in the placebo group during the initial 6 months. Death, another AMI or both were significantly reduced by metoprolol treatment in patients with exercise-induced ST depression greater than or equal to 1 mm at the 6-week test. In a multiple logistic regression analysis maximal accomplished workload at 6 weeks (p less than 0.026), male sex (relative risk [rr] = 3.57, p = 0.016), previous AMI (rr = 3.07, p = 0.001), therapy with placebo (rr = 2.14, p = 0.007) and left ventricular failure (rr = 2.04, p = 0.023) were shown to carry independent prognostic information as well as exercise-induced ST-depression (greater than or equal to 1 mm) in placebo-treated patients (rr = 2.70, p = 0.01).


An early gastric cancer concurrent with a hyperplastic polyp in a patient confirmed negative for Helicobacter pylori.
A 58-year-old man was suspected of having a gastric polyp based on an upper gastrointestinal series. Esophagogastroduodenoscopy showed a gastric polyp, approximately 7mm in diameter, located at the greater curvature of the upper gastric body. Helicobacter pylori testing yielded negative results, and there was no atrophy of the gastric mucosa. Biopsy revealed a well differentiated tubular adenocarcinoma (Group 5). Endoscopic submucosal biopsies were performed, and histopathology revealed a well differentiated tubular adenocarcinoma coexisting with a hyperplastic polyp. Complete en bloc resection was performed, in accordance with the current Japanese guidelines.


Polyamine/salt-assembled microspheres coated with hyaluronic acid for targeting and pH sensing.
The poly(allylamine hydrochloride)/trisodium citrate aggregates were fabricated and further covalently crosslinked via the coupling reaction of carboxylic sites on trisodium citrate with the amine groups on polyamine, onto which poly-L-lysine and hyaluronic acid were sequentially assembled, forming stable microspheres. The pH sensitive dye and pH insensitive dye were further labeled to enable the microspheres with pH sensing property. Moreover, these microspheres could be specifically targeted to HeLa tumor cells, since hyaluronic acid can specifically recognize and bind to CD44, a receptor overexpressed on many tumor cells. Quantitative pH measurement by confocal laser scanning microscopy demonstrated that the microspheres were internalized into HeLa cells, and accumulated in acidic compartments. By contrast, only a few microspheres were adhered on the NIH 3T3 cells surface. The microspheres with combined pH sensing property and targeting ability can enhance the insight understanding of the targeted drug vehicles trafficking after cellular internalization.


Unexpected neurotoxicity in chronic toxicity studies with a HBV viral expression inhibitor.
The non-clinical safety profile of the small molecule hepatitis B virus viral expression inhibitor RG7834 was studied in a package consisting of safety pharmacology, genotoxicity, repeat dose toxicity and reproductive toxicity studies. The chronic monkey toxicity study identified dose- and time-dependent symptoms of polyneuropathy, with correlating nerve conduction velocity reductions and axonal degeneration in peripheral nerves and spinal cord, in all compound treatment groups with no evidence of reversibility after approximately 3 months of treatment cessation. Similar histopathological findings were observed in the chronic rat toxicity study. Subsequent in vitro neurotoxicity investigations and ion channel electrophysiology did not elucidate a potential mechanism for the late toxicity. However, based on similar findings observed with a structurally different molecule, an inhibition of their common pharmacological targets, PAPD5 & PAPD 7, was considered as a possible mechanism of toxicity. In conclusion, the marked neuropathies, only observed after chronic dosing, did not support further clinical development of RG7834 because of its foreseen clinical treatment duration of up to 48 weeks in chronic HBV patients.


Serum amino acids quantification by plasmonic colloidosome-coupled MALDI-TOF MS for triple-negative breast cancer diagnosis.
Triple-negative breast cancer (TNBC) is characterized with high diffusion, metastasis and recurrence. The early treatment and early diagnosis of TNBC are highly important for the survival of TNBC patients. Nevertheless, traditional methods for TNBC diagnosis, i.e. imaging examinations and tissue biopsy, cannot achieve early diagnosis, are invasive and associated with the risk of arousing tumor spreading. Herein, we developed colloidosomes-coupled matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantify free serum amino acids for the diagnosis of TNBC. Gold nanoparticles (AuNPs) were used to form water-in-oil colloidosomes and to encapsulate deproteinated serum for MALDI-TOF MS analysis. With small sample spot size (200-300 μm) and densely packed AuNPs monolayer, the dried sample spot from colloidosomes can facilitate MALDI-TOF MS analysis of small molecule metabolites with high sensitivity, high reproducibility and good quantification performance. We used the method to quantify free amino acids in human serum. A cohort of 30 TNBC patients, 30 breast lump patients and 30 healthy controls were recruited for the study. It was found that the concentrations of free amino acids in TNBC patients were significantly lower than that of heathy controls, and the concentrations were also significantly different from that of breast lump patients. Based on the quantities of serum free amino acids, we have built a machine learning-based classification model to differentiate TNBC patients from the controls, including healthy controls and breast lump patients, and the sensitivity, specificity and accuracy were 95%, 100% and 97%, respectively. The assay consumes less than 1 μL serum per analysis, and takes only minutes to analyze a sample. With the advantages of low cost, low sample consumption, high throughput in analysis and high accuracy in identification, the non-invasive liquid biopsy method is promising to be applied to clinical diagnosis of TNBC.


CSF flow patterns in the brain in patients with neuro-Behçet disease and Behçet disease.
In the etiopathogenesis of Behcet disease (BD) and Neuro-Behcet disease (NBD), vascular eclipse occurs in both the arteries and veins. The disease affects all vascular structures. The present study evaluates the use of Phase Contrast (PC) Cerebral Spinal Fluid (CSF) Flow Magnetic Resonance Imaging (MRI), a non-invasive technique for measuring CSF dynamics, for determining the level of aqueducts that are influenced in BD and NBD. The quantitative evaluation of CSF flow in BD and NBD was performed using images obtained at the level of the cerebral aqueduct on the semi-axial plane. The PC-MRI angiography technique was used. There is no distinctive difference between BD and NBD that can be distinguished by the aqueduct diameters of both conditions. A clear increase in aqueduct diameter occurred BD and NBD group when compared to the control group. While there were no differences found between the BD group and the control group regarding peak velocity, average velocity, forward flow, reverse flow, net forward flow, and flow, there were distinctive increases in these various factors in the NBD group. Using the non-invasive PC-MRI technique, this study found that in BD and NBD patients, changes occurred in CSF flow figures. Increases in CSF parameters were also observed in NBD patients, a finding which may be helpful for future distinction between BD and NBD during diagnosis.


Job strain and ischaemic disease: does the inclusion of older employees in the cohort dilute the association? The WOLF Stockholm Study.
Evidence on the association between job strain and ischaemic disease is mixed. This study examined whether including older age individuals in a cohort used to assess job strain attenuates findings towards the null. A prospective cohort study with baseline screening in 1992-5. A follow-up for ischaemic disease until 2003 was based on linkages to national registries. Ischaemic disease was corroborated by objective criteria (hospitalisation as a result of acute myocardial infarction, unstable angina or ischaemic stroke; or death from ischaemic heart disease, cardiac arrest or ischaemic stroke). 3160 male employees aged 19-65 years without pre-existing or current ischaemic disease. 93 cases of incident ischaemic disease were recorded. In the 19-55 year age group, the participants with job strain had a 1.76 (95% CI 1.05 to 2.95) times higher age-adjusted risk of incident ischaemic disease than those free of strain. Further adjustment for conventional cardiovascular risk factors had little effect on this association, but the impact of job strain was reduced by 70% to non-significant after the inclusion of employees older than 55 years in the cohort (hazard ratio 1.22, 95% CI 0.75 to 1.96). Including older employees in a cohort may dilute the effect of job strain on cardiovascular disease and is a potential reason for inconsistent findings in previous studies.


Procedural pain and brain development in premature newborns.
Preterm infants are exposed to multiple painful procedures in the neonatal intensive care unit (NICU) during a period of rapid brain development. Our aim was to examine relationships between procedural pain in the NICU and early brain development in very preterm infants. Infants born very preterm (N=86; 24-32 weeks gestational age) were followed prospectively from birth, and studied with magnetic resonance imaging, 3-dimensional magnetic resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks). We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to choline ratios, average diffusivity, and white matter fractional anisotropy (FA) from up to 7 white and 4 subcortical gray matter regions of interest. Procedural pain was quantified as the number of skin-breaking events from birth to term or scan 2. Data were analyzed using generalized estimating equation modeling adjusting for clinical confounders such as illness severity, morphine exposure, brain injury, and surgery. After comprehensively adjusting for multiple clinical factors, greater neonatal procedural pain was associated with reduced white matter FA (β=-0.0002, p=0.028) and reduced subcortical gray matter NAA/choline (β=-0.0006, p=0.004). Reduced FA was predicted by early pain (before scan 1), whereas lower NAA/choline was predicted by pain exposure throughout the neonatal course, suggesting a primary and early effect on subcortical structures with secondary white matter changes. Early procedural pain in very preterm infants may contribute to impaired brain development.


Twelve-month comparative multicenter study of the TCu 380A and ML 250 intrauterine devices in Bangkok, Thailand.
The long-term effectiveness of the copper-bearing intrauterine device (IUD) has been documented. This paper reports 12-month results from a multiyear comparative study of the Copper T (TCu) 380A and Multiload (ML) 250 IUD in Bangkok, Thailand, among 1396 women. Continuation of the assigned IUD was relatively high after 12 months of use, with continuation rates of 90.17 and 87.54 per 100 women, respectively. Whereas the accidental pregnancy rate was higher for the ML 250 IUD than for the TCu 380A IUD (1.0 and 0.2 per 100 women, respectively), this difference was not considered statistically significant (p < 0.69). The rate of IUD expulsion was significantly higher among women using the ML 250 IUD than for women using the TCu 380A IUD (4.61 and 2.40 per 100 women, respectively, p = 0.05).


Intensity of mental health treatment of cancer-related psychopathology: the predictive role of Early Maladaptive Schemas.
With the limited availability of mental healthcare, it is of utmost importance to provide care that matches the needs of patients: short if possible, but also more intense when necessary. This study explored whether Early Maladaptive Schemas (EMSs) play a predictive role in the intensity of needed mental health treatment of cancer-related psychopathology. EMSs were assessed before mental health treatment in 256 patients who sought help at a specialized mental health care centre for those affected by cancer in the Netherlands. Data about treatment indication and intensity of mental health treatment were collected. Univariate and multivariate logistic regression analysis were used to assess the predictive value of the EMSs total score and specific domains on treatment indication and treatment intensity. The presence of more severe EMSs predicted an indication for a more intense mental health treatment before start of the treatment, and actual more intense mental health treatment. The domain Impaired Autonomy and Performance appeared to be conceptually close to the domain Disconnection and Rejection, we left the latter out in our multivariate analysis and then found that Impaired Autonomy was the best predictor of intensity of mental health treatment. Our findings imply that assessing EMSs could help to identify patients who will receive more treatment time.


Utilizing Angled O-Ball Narrow-Diameter Implants to Solve the Restorative Challenge Posed by Alveolar Resorption: A Case Report.
An angled narrow-diameter implant has been introduced for use in cases where the atrophic edentulous ridge is wide enough to accommodate narrow-diameter implants but the necessary implant angulations would make it impossible to fabricate an esthetically acceptable overdenture. A case is described in which such implants were placed and restored.


A disposable laser print-cut-laminate polyester microchip for multiplexed PCR via infra-red-mediated thermal control.
Infrared (IR)-mediated thermal cycling system, a method proven to be a effective for sub-μL scale polymerase chain reaction (PCR) on microchips, has been integrated with DNA extraction and separation on a glass microchip in a fully integrated micro Total Analysis System by Easley et al., in 2006. IR-PCR has been demonstrated on both glass and PMMA microdevices where the fabrication (bonding) is not trivial. Polyester-toner (PeT) microfluidic devices have significant potential as cost-effective, disposable microdevices as a result of the ease of fabrication (∼$0.25 USD and <10 min per device) and availability of commercial substrates. For the first time, we demonstrate here the thermal cycling in PeT microchips on the IR-PCR system. Undesirable IR absorption by the black-toner bonding layer was eliminated with a spatial filter in the form of an aluminum foil mask. The solution heating rate for a black PeT microchip using a tungsten lamp was 10.1 ± 0.7 °C s(-1) with a cooling rate of roughly -12 ± 0.9 °C s(-1) assisted by forced air cooling. Dynamic surface passivation strategies allowed the successful amplification of a 520 bp fragment of the λ-phage genome (in 11 min) and a 1500 bp region of Azospirillum brasilense. Using a centrosymmetric chamber configuration in a multichamber PeT microchip, homogenous temperature distribution over all chambers was achieved with inter-chamber temperature differences at annealing, extension and denaturing steps of less than ±2 °C. The effectiveness of the multichamber system was demonstrated with the simultaneous amplification of a 390 bp amplicon of human β-globin gene in five PeT PCR microchambers. The relative PCR amplification efficiency with a human β-globin DNA fragment ranged from 70% to 90%, in comparison to conventional thermal cyclers, with an inter-chamber standard deviation of ∼10%. Development of PeT microchips for IR-PCR has the potential to provide rapid, low-volume amplification while also integrating PCR with extraction upstream and separation/detection downstream.


Parity violation and the origins of biomolecular handedness.
The violation of parity by the weak interactions ensures that enantiomeric chiral molecules have inequivalent energies, one being inherently stabilized with respect to the other. These parity-violating energy differences have been calculated for a number of fundamental biomolecules including a series of alpha-amino acids, polypeptide structures, and a representative of the sugar series together with its variation over a possible prebiotic reaction path leading to alpha-amino acids. In each case the natural enantiomer found in terrestrial biochemistry was shown to be intrinsically stabilized and preferred over its unnatural enantiomer. The significance of these results in accounting for the prebiotic origins of the terrestrial biomolecular homochirality is discussed and the possible consequences of parity-violating energy differences in mineral catalysts during the prebiotic era considered.


Development and validation of a survey designed to measure patient experience of and preference for surgical wound care discharge education: A pilot study.
To develop and undertake validation testing of a survey designed to measure patients' experiences of and preferences for surgical wound care discharge education. A literature review and content analysis was undertaken on patients' experiences of and preferences for surgical wound care discharge education. Four themes were uncovered in the literature (wound care discharge education, preferences for discharge education delivery, participation in wound care decisions and patient ability to manage their surgical wound to prevent wound complications), which guided item generation. Three types of validity testing occurred including: 1) face validity testing by the research team; 2) content validity testing (using Delphi study) with an international panel of experts including patients, clinicians and researchers; and 3) content validity (using pilot-testing) of the survey with seven patients from the target population. Initially 106 items were generated from the literature, and of these, 55 items were subjected to content validity testing by an international panel of 41 experts. After two Delphi rounds, 18 items were retained. Most patients provided limited and very minor feedback during pilot-testing. However, pilot-testing resulted in a revised survey administration plan to deliver the survey via telephone, including adding prompts and preambles to items. An 18-item survey comprised of three groups of items and an individual item was rigorously developed. The survey requires further testing among a larger sample of patients to confirm the items reflect important aspects of patients' experiences of and preferences for surgical wound care discharge education.


Clinical trial of a lyophilized inactivated hepatitis A candidate vaccine in healthy adult volunteers.
The safety and immunogenicity of a lyophilized inactivated hepatitis A vaccine was tested in healthy adult male volunteers. Thirty-six volunteers, all of whom were negative for antibody to HAV (anti-HAV), were divided into three dosage groups, 1.0, 0.5 and 0.25 micrograms of viral protein, respectively. Each group received a total course of three intramuscular injections at months 0, 1 and 6. Slight side effects were noted after 16 of 99 injections and the occurrence and degree were almost identical to those of other commercial vaccines. On the other hand, all subjects had measurable titres of serum anti-HAV neutralizing antibodies as early as 2 months after the first injection. The mean values of serum anti-HAV neutralizing antibodies at 7 months in the 1.0, 0.5 and 0.25 micrograms dose groups were 64-, 12-, and 9-fold higher, respectively, than those observed at 5 days in five recipients given 7.5 mg kg-1 body weight of immune serum globulin (ISG).


Studies on the retention of passively transferred antibodies in man. II. Antibody activity in the blood after intravenous or intramuscular administration of anti-HBs human immunoglobulin.
Catabolism of intravenously or intramuscularly administered human immunoglobulin in man was studied by the administration of HBs antibodies at a high titer and analysis with a highly sensitive radioimmunoassay technique. The half-life in the blood of the antibodies in the aggregate-reduced antibody preparation administered intravenously was found to be 17.7 days and of those in the antibody preparation administered intramuscularly to be 23.8 days.