Sylvian fissure asymmetries in nonhuman primates revisited: a comparative mri study.
Magnetic resonance images (MRI) were collected in a sample of 28 apes, 16 Old World monkeys and 8 New World monkeys. The length of the sylvian fissure (SF) and the superior temporal sulcus (STS) was traced in each hemisphere from three regions of the cerebral cortex. These three regions were labeled according to their position on the sagittal plane as lateral, medial and insular. It was hypothesized that the length and asymmetry of these fissures would be dependent on the region of measurement and that a leftward asymmetry in the SF and STS would be more robust in the great ape sample than for the monkeys. The results indicated within the ape sample a population-level leftward asymmetry in the medial and insular regions of the SF. Within the Old and New World monkey samples, the SF was leftward in the medial region at the population level, but not at the insular region. Additionally, the Old World monkeys exhibited a population-level rightward lateral SF and a rightward lateral STS. No other families exhibited population-level asymmetries in the lateral region of the SF or in any region of the STS. These results are consistent with findings reported in apes and, to a lesser extent, monkeys. MRI has excellent potential for comparing neuroanatomy across taxonomic families that will help future investigations.


A comparison of muscle activity in concentric and counter movement maximum bench press.
The purpose of this study was to compare the kinematics and muscle activation patterns of regular free-weight bench press (counter movement) with pure concentric lifts in the ascending phase of a successful one repetition maximum (1-RM) attempt in the bench press. Our aim was to evaluate if diminishing potentiation could be the cause of the sticking region. Since diminishing potentiation cannot occur in pure concentric lifts, the occurrence of a sticking region in this type of muscle actions would support the hypothesis that the sticking region is due to a poor mechanical position. Eleven male participants (age 21.9 ± 1.7 yrs, body mass 80.7 ± 10.9 kg, body height 1.79 ± 0.07 m) conducted 1-RM lifts in counter movement and in pure concentric bench presses in which kinematics and EMG activity were measured. In both conditions, a sticking region occurred. However, the start of the sticking region was different between the two bench presses. In addition, in four of six muscles, the muscle activity was higher in the counter movement bench press compared to the concentric one. Considering the findings of the muscle activity of six muscles during the maximal lifts it was concluded that the diminishing effect of force potentiation, which occurs in the counter movement bench press, in combination with a delayed muscle activation unlikely explains the existence of the sticking region in a 1-RM bench press. Most likely, the sticking region is the result of a poor mechanical force position.


Medication error prevention by clinical pharmacists in two children's hospitals.
The purpose of this study was to record prospectively the frequency of and potential harm caused by errant medication orders at two large pediatric hospitals. The objective of the study was to assess the impact of pharmacist intervention in preventing potential harm. The study was conducted during a 6-month period. A total of 281 and 198 errors were detected at the institutions. The overall error rates for the two hospitals were 1.35 and 1.77 per 100-patient days, and 4.9 and 4.5 per 1,000 medication orders, respectively. Pediatric patients aged 2 years and less and pediatric intensive care unit patients received the greatest proportion of errant orders. Neonatal patients received the lowest rate of errant orders. The most common type of error was incorrect dosage, and the most prevalent type of error was overdosage. Antibiotics was the class of drugs for which errant orders were most common. Orders for theophylline, analgesics, and fluid and electrolytes, including hyperalimentation, were also frequently in error. In general, the error rate was greatest among physicians with the least training, but no physician group was error free. Involving pharmacists in reviewing drug orders significantly reduced the potential harm resulting from errant medication orders.


Prevention of thromboembolism in the patient with acute coronary syndrome and atrial fibrillation: the clinical dilemma of triple therapy.
Atrial fibrillation in patients with acute coronary syndrome (ACS) is associated with a high thromboembolic event rate. Combined oral anticoagulant (OAC) and antiplatelet therapy (APT) are often used to reduce thromboembolic risk, recurrent coronary ischemic events, and stent thrombosis, despite the high bleeding risk. This review is timely with the recent introduction of novel OACs (NOACs), more potent antiplatelet agents, and second-generation coronary stents with a lower risk of late stent thrombosis, and considers strategies and new opportunities to reduce both thrombotic events and bleeding. The benefits of NOACs in patients with atrial fibrillation have been shown in recent studies. New evidence indicates that single rather than dual APT may be adequate when an OAC is used in a patient with a recent coronary stent. Limited evidence suggests a NOAC is preferable to warfarin when additional APT is also required. The implications of the new findings are to indicate strategies for more effective antithrombotic therapy, while minimizing the risk of major bleeding in patients with ACS and atrial fibrillation. However, additional research studies are required to further optimize treatment strategies in this high-risk population.


Design and quantitative structure-activity relationship of 3-amidinobenzyl-1H-indole-2-carboxamides as potent, nonchiral, and selective inhibitors of blood coagulation factor Xa.
A series of 138 nonchiral 3-amidinobenzyl-1H-indole-2-carboxamides and analogues as inhibitors of the blood coagulation enzyme factor Xa (fXa) were designed, synthesized, and investigated by X-ray structure analysis and 3D quantitative structure-activity relationship (QSAR) studies (CoMFA, CoMSIA) in order to identify important protein-ligand interactions responsible for biological affinity and selectivity. Several compounds from this series are highly potent and selective inhibitors of this important enzyme linking extrinsic and intrinsic coagulation pathways. To rationalize biological affinity and to provide guidelines for further design, all compounds were docked into the factor Xa binding site. Those docking studies were based on X-ray structures of factor Xa in complex with literature-known inhibitors. It was possible to validate those binding modes by four X-ray crystal structures of representative ligands in factor Xa, while one ligand was additionally crystallized in trypsin to rationalize requirements for selective factor Xa inhibition. The 3D-QSAR models based on a superposition rule derived from these docking studies were validated using conventional and cross-validated r(2) values using the leave-one-out method and repeated analyses using two randomly chosen cross-validation groups plus randomization of biological activities. This led to consistent and highly predictive 3D-QSAR models with good correlation coefficients for both CoMFA and CoMSIA, which were found to correspond to experimentally determined factor Xa binding site topology in terms of steric, electrostatic, and hydrophobic complementarity. Subsets selected as smaller training sets using 2D fingerprints and maximum dissimilarity methods resulted in 3D-QSAR models with remarkable correlation coefficients and a high predictive power. The final quantitative SAR information agrees with all experimental data for the binding topology and thus provides reasonable activity predictions for novel factor Xa inhibitors.


Technique tip: EDL-to-EHL double loop transfer for extensor hallucis longus reconstruction.
Extensor hallucis longus (EHL) tendon injuries often occur in the setting of lacerations to the dorsum of the foot. End-to-end repair is advocated in acute lacerations, or in chronic cases when the tendon edges are suitable for tension free repair. Reconstruction with allograft or autograft is advocated for cases not amenable to a primary direct repair. This is often seen in cases with tendon retraction and more commonly in the chronic setting. In many countries the use of allograft is very limited or unavailable making reconstruction with autograft and tendon transfers the primary choice of treatment. Tendon diameter mismatch and diminished resistance are common issues in other previously described tendon transfers. We present the results of a new technique for reconstruction of non-reparable EHL lacerations in three patients using a dynamic double loop transfer of the extensor digitorum longus (EDL) of the second toe that addresses these issues. At one-year follow up, all patients recovered active/passive hallux extension with good functional (AOFAS Score) and satisfaction results. No reruptures or other complications were reported in this group of patients. No second toe deformities or dysfunction were reported. Second EDL-to-EHL Double Loop Transfer for Extensor Hallucis Longus reconstruction is a safe, reproducible and low-cost technique to address EHL ruptures when primary repair is not possible. IV (Case Series).


High Protective Efficacy of Probiotics and Rice Bran against Human Norovirus Infection and Diarrhea in Gnotobiotic Pigs.
Probiotics have been recognized as vaccine adjuvants and therapeutic agents to treat acute gastroenteritis in children. We previously showed that rice bran (RB) reduced human rotavirus diarrhea in gnotobiotic pigs. Human noroviruses (HuNoVs) are the major pathogens causing non-bacterial acute gastroenteritis worldwide. In this study, Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle 1917 (EcN) were first screened for their ability to bind HuNoV P particles and virions derived from clinical samples containing HuNoV genotype GII.3 and GII.4, then the effects of LGG+EcN and RB on HuNoV infection and diarrhea were investigated using the gnotobiotic pig model. While LGG+EcN colonization inhibited HuNoV shedding, probiotic cocktail regimens in which RB feeding started 7 days prior to or 1 day after viral inoculation in the LGG+EcN colonized gnotobiotic pigs exhibited high protection against HuNoV diarrhea and shedding, characterized by significantly reduced incidence (89 versus 20%) and shorter mean duration of diarrhea (2.2 versus 0.2 days), as well as shorter mean duration of virus shedding (3.2 versus 1.0 days). In both probiotic cocktail groups, the diarrhea reduction rates were 78% compared with the control group, and diarrhea severity was reduced as demonstrated by the significantly lower cumulative fecal scores. The high protective efficacy of the probiotic cocktail regimens was attributed to stimulation of IFN-γ+ T cell responses, increased production of intestinal IgA and IgG, and maintenance of healthy intestinal morphology (manifested as longer villi compared with the control group). Therefore, probiotic cocktail regimens containing LGG+EcN and RB may represent highly efficacious strategies to prevent and treat HuNoV gastroenteritis, and potentially other human enteric pathogens.


Fecal calprotectin levels correlate with main domains of the autism diagnostic interview-revised (ADI-R) in a sample of individuals with autism spectrum disorders from Slovakia.
Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impaired social interaction and communication, as well as repetitive behavior and restricted interests. There is convincing evidence that the intestinal inflammation is involved in etiology of ASD. Increased levels of inflammatory markers were shown to be associated with more aberrant behaviors and communication of subjects with ASD. Calprotectin in the feces is produced by activated neutrophils and epithelial cells of the gut mucosa, and its levels reflect local inflammation of the gastrointestinal tract. Concentration of fecal calprotectin was determined by ELISA method in 87 individuals with ASD and 51 controls, of that 29 siblings of children with ASD and 22 non-related controls. In non-relatives significantly lower values of fecal calprotectin were observed than in both subjects with ASD and their siblings. In the group with ASD significant correlations of fecal calprotectin with all domains of the ADI-R diagnostic tool were found: qualitative abnormalities in reciprocal social interaction and communication, restrictive and repetitive patterns of behavior. Results suggest that low grade intestinal inflammation may be one of factors implicated in the pathophysiology of ASD.


De novo cardiomyocytes from within the activated adult heart after injury.
A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and acute myocardial infarction. A therapeutic ideal--relative to cell transplantation--would be to stimulate a resident source, thus avoiding the caveats of limited graft survival, restricted homing to the site of injury and host immune rejection. Here we demonstrate in mice that the adult heart contains a resident stem or progenitor cell population, which has the potential to contribute bona fide terminally differentiated cardiomyocytes after myocardial infarction. We reveal a novel genetic label of the activated adult progenitors via re-expression of a key embryonic epicardial gene, Wilm's tumour 1 (Wt1), through priming by thymosin β4, a peptide previously shown to restore vascular potential to adult epicardium-derived progenitor cells with injury. Cumulative evidence indicates an epicardial origin of the progenitor population, and embryonic reprogramming results in the mobilization of this population and concomitant differentiation to give rise to de novo cardiomyocytes. Cell transplantation confirmed a progenitor source and chromosome painting of labelled donor cells revealed transdifferentiation to a myocyte fate in the absence of cell fusion. Derived cardiomyocytes are shown here to structurally and functionally integrate with resident muscle; as such, stimulation of this adult progenitor pool represents a significant step towards resident-cell-based therapy in human ischaemic heart disease.


Structural basis for the recognition of C20:2-αGalCer by the invariant natural killer T cell receptor-like antibody L363.
Natural killer T (NKT) cells express a semi-invariant Vα14 T cell receptor (TCR) and recognize structurally diverse antigens presented by the antigen-presenting molecule CD1d that range from phosphoglycerolipids to α- and β-anomeric glycosphingolipids, as well as microbial α-glycosyl diacylglycerolipids. Recently developed antibodies that are specific for the complex of the prototypical invariant NKT (iNKT) cell antigen αGalCer (KRN7000) bound to mouse CD1d have become valuable tools in elucidating the mechanism of antigen loading and presentation. Here, we report the 3.1 Å resolution crystal structure of the Fab of one of these antibodies, L363, bound to mCD1d complexed with the αGalCer analog C20:2, revealing that L363 is an iNKT TCR-like antibody that binds CD1d-presented αGalCer in a manner similar to the TCR. The structure reveals that L363 depends on both the L and H chains for binding to the glycolipid-mCD1d complex, although only the L chain is involved in contacts with the glycolipid antigen. The H chain of L363 features residue Trp-104, which mimics the TCR CDR3α residue Leu-99, which is crucial for CD1d binding. We characterized the antigen-specificity of L363 toward several different glycolipids, demonstrating that whereas the TCR can induce structural changes in both antigen and CD1d to recognize disparate lipid antigens, the antibody L363 can only induce the F' roof formation in CD1d but fails to reorient the glycolipid headgroup necessary for binding. In summary, L363 is a powerful tool to study mechanism of iNKT cell activation for structural analogs of KRN7000, and our study can aid in the design of antibodies with altered antigen specificity.


Exercise training increases arterial compliance in patients with congestive heart failure.
Systemic arterial compliance (SAC) makes an important contribution to cardiac afterload, and thus is a significant determinant of left ventricular work. Previous studies have suggested that arterial compliance may be reduced in patients with congestive heart failure (CHF), and that SAC is increased after a 4-week exercise training programme in healthy, sedentary individuals. The present study aimed to investigate the effects of an 8-week exercise training programme on arterial mechanical properties, left ventricular performance and quality of life in CHF patients. A total of 21 patients with NYHA class II or III CHF (mean+/-S.D. age 55+/-13 years) were randomly allocated to either an 8-week exercise training group or a "usual lifestyle" control group. SAC, as determined non-invasively using applanation tonometry and Doppler aortic velocimetry, increased from 0.57+/-0.11 to 0.77+/-0.14 arbitrary compliance units (mean+/-S.E.M.; P=0.01) in the exercise group, while no change occurred in the control group. Left ventricular structure and function was assessed by echocardiography, and these parameters were unchanged over the 8-week study period. Exercise training significantly increased exercise capacity, measured by a 6-min walking test (474+/-27 to 547+/-34 m; P=0.008). Quality of life, as assessed using the Minnesota Living with Heart Failure Evaluation, demonstrated a decrease in heart failure symptoms from 46+/-7 to 24+/-5 units (P=0.01) following the exercise training programme. These data show that exercise training improves SAC in patients with CHF. The accompanying improvement in exercise capacity may be due, in part, to an improvement in arterial function.


Long-term clinical and radiographic outcomes of the Prestige LP artificial cervical disc replacement at 2 levels: results from a prospective randomized controlled clinical trial.
OBJECTIVE The aim of this study was to assess long-term clinical safety and effectiveness in patients undergoing anterior cervical surgery using the Prestige LP artificial disc replacement (ADR) prosthesis to treat degenerative cervical spine disease at 2 adjacent levels compared with anterior cervical discectomy and fusion (ACDF). METHODS A prospective, randomized, controlled, multicenter FDA-approved clinical trial was conducted at 30 US centers, comparing the low-profile titanium ceramic composite-based Prestige LP ADR (n = 209) at 2 levels with ACDF (n = 188). Clinical and radiographic evaluations were completed preoperatively, intraoperatively, and at regular postoperative intervals to 84 months. The primary end point was overall success, a composite variable that included key safety and efficacy considerations. RESULTS At 84 months, the Prestige LP ADR demonstrated statistical superiority over fusion for overall success (observed rate 78.6% vs 62.7%; posterior probability of superiority [PPS] = 99.8%), Neck Disability Index success (87.0% vs 75.6%; PPS = 99.3%), and neurological success (91.6% vs 82.1%; PPS = 99.0%). All other study effectiveness measures were at least noninferior for ADR compared with ACDF. There was no statistically significant difference in the overall rate of implant-related or implant/surgical procedure-related adverse events up to 84 months (26.6% and 27.7%, respectively). However, the Prestige LP group had fewer serious (Grade 3 or 4) implant- or implant/surgical procedure-related adverse events (3.2% vs 7.2%, log hazard ratio [LHR] and 95% Bayesian credible interval [95% BCI] -1.19 [-2.29 to -0.15]). Patients in the Prestige LP group also underwent statistically significantly fewer second surgical procedures at the index levels (4.2%) than the fusion group (14.7%) (LHR -1.29 [95% BCI -2.12 to -0.46]). Angular range of motion at superior- and inferior-treated levels on average was maintained in the Prestige LP ADR group to 84 months. CONCLUSIONS The low-profile artificial cervical disc in this study, Prestige LP, implanted at 2 adjacent levels, maintains improved clinical outcomes and segmental motion 84 months after surgery and is a safe and effective alternative to fusion. Clinical trial registration no.: NCT00637156 (clinicaltrials.gov).


Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials.
Concern has been raised about the efficacy of antidepressant therapy for major depression in adults. We undertook a systematic review of published and unpublished clinical trial data to determine the effectiveness and acceptability of paroxetine. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, the Cochrane Central Register of Controlled Trials, the GlaxoSmithKline Clinical Trial Register, MEDLINE and EMBASE up to December 2006. Published and unpublished randomized trials comparing paroxetine with placebo in adults with major depression were eligible for inclusion. We selected the proportion of patients who left a study early for any reason as the primary outcome measure because it represents a hard measure of treatment effectiveness and acceptability. We included in our review 29 published and 11 unpublished clinical trials, with a total of 3704 patients who received paroxetine and 2687 who received with placebo. There was no difference between paroxetine and placebo in terms of the proportion of patients who left the study early for any reason (random effect relative risk [RR] 0.99, 99% confidence interval [CI] 0.88-1.11). Paroxetine was more effective than placebo, with fewer patients who did not experience improvement in symptoms of at least 50% (random effect RR 0.83, 99% CI 0.77-0.90). Significantly more patients in the paroxetine group than in the placebo group left their respective studies because of side effects (random effect RR 1.77, 95% CI 1.44-2.18) or experienced suicidal tendencies (odds ratio 2.55, 95% CI 1.17-5.54). Among adults with moderate to severe major depression in the clinical trials we reviewed, paroxetine was not superior to placebo in terms of overall treatment effectiveness and acceptability. These results were not biased by selective inclusion of published studies.


The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis.
Intestinal dysbiosis is implicated in alcoholic hepatitis (AH). However, changes in the circulating microbiome, its association with the presence and severity of AH, and its functional relevance in AH is unknown. Qualitative and quantitative assessment of changes in the circulating microbiome were performed by sequencing bacterial DNA in subjects with moderate AH (MAH) (n = 18) or severe AH (SAH) (n = 19). These data were compared with heavy drinking controls (HDCs) without obvious liver disease (n = 19) and non-alcohol-consuming controls (NACs, n = 20). The data were related to endotoxin levels and markers of monocyte activation. Linear discriminant analysis effect size (LEfSe) analysis, inferred metagenomics, and predictive functional analysis using PICRUSt were performed. There was a significant increase in 16S copies/ng DNA both in MAH (P < 0.01) and SAH (P < 0.001) subjects. Compared with NACs, the relative abundance of phylum Bacteroidetes was significantly decreased in HDCs, MAH, and SAH (P < 0.001). In contrast, all alcohol-consuming groups had enrichment with Fusobacteria; this was greatest for HDCs and decreased progressively in MAH and SAH. Subjects with SAH had significantly higher endotoxemia (P = 0.01). Compared with alcohol-consuming groups, predictive functional metagenomics indicated an enrichment of bacteria with genes related to methanogenesis and denitrification. Furthermore, both HDCs and SAH showed activation of a type III secretion system that has been linked to gram-negative bacterial virulence. Metagenomics in SAH versus NACs predicted increased isoprenoid synthesis via mevalonate and anthranilate degradation, known modulators of gram-positive bacterial growth and biofilm production, respectively. Heavy alcohol consumption appears to be the primary driver of changes in the circulating microbiome associated with a shift in its inferred metabolic functions. (Hepatology 2018;67:1284-1302).


Computational prediction of optimal metal ions to induce coordinated polymerization of muscle-like [c2]daisy chains.
Recently, a muscle-like organometallic polymer has been successfully synthesized using Fe(2+) as a linker atom. The polymer exhibits acid-base controllable muscle-like expansion and contraction on the micrometer scale. Further development could be facilitated by revealing the polymerization mechanism and by searching for optimal linker atoms. In this work, we have examined possible equilibrium and intermediate polymer structures, which consist of [c2]daisy chains linked by divalent transition metal ions (Sc(2+), Ti(2+), Fe(2+), Co(2+), Ni(2+) or Zn(2+)) with various hexa-coordination arrangements, based on calculations using density functional theory. We find that the metal linkers in polymers are weaker in acid than in base due to excess positive charges on the polymer, leading to their thermodynamical instability or even decomposition. This can explain the experimental difficulty in improving the degree of polymerization for metal-linked polymers. We also find that the polymers with either Fe(2+) or Co(2+) are the most favorable, with the latter extending 1.4% longer than with the former. Since Fe(2+) has been confirmed experimentally to be a successful linker, Co(2+) would function equally well and thus could be used as an alternative choice for polymerization.


Gender and the Publication Output of Graduate Students: A Case Study.
We examine gender differences among the six PhD student cohorts 2004-2009 at the California Institute of Technology using a new dataset that includes information on trainees and their advisors and enables us to construct detailed measures of teams at the advisor level. We focus on the relationship between graduate student publications and: (1) their gender; (2) the gender of the advisor, (3) the gender pairing between the advisor and the student and (4) the gender composition of the team. We find that female graduate students co-author on average 8.5% fewer papers than men; that students writing with female advisors publish 7.7% more. Of particular note is that gender pairing matters: male students working with female advisors publish 10.0% more than male students working with male advisors; women students working with male advisors publish 8.5% less. There is no difference between the publishing patterns of male students working with male advisors and female students working with female advisors. The results persist and are magnified when we focus on the quality of the published articles, as measured by average Impact Factor, instead of number of articles. We find no evidence that the number of publications relates to the gender composition of the team. Although the gender effects are reasonably modest, past research on processes of positive feedback and cumulative advantage suggest that the difference will grow, not shrink, over the careers of these recent cohorts.


Psychosocial outcomes of a randomized controlled trial of outpatient cervical priming for induction of labor.
Induction of labor, an increasingly common intervention, is often preceded by the application of an agent to "prime" or "ripen" the cervix. We conducted a randomized controlled trial to compare clinical, economic, and psychosocial outcomes of inpatient and outpatient cervical priming before induction of labor. In this paper we present the psychosocial outcomes. Women participating in a randomized controlled trial in two Australian metropolitan teaching hospitals completed questionnaires to measure anxiety and depression at enrollment, and to examine satisfaction, experiences, depression, and infant feeding 7 weeks after giving birth. Data analysis was by intention to treat and by having received the intervention as intended (approximately 50% in each group). Of 1,004 eligible women, 85 percent consented (n = 407, outpatient; n = 414 inpatient). No statistically significant or clinically relevant differences were found in immediate anxiety, depression, or infant feeding. Small, statistically significant differences favoring outpatient priming were found in seven of the nine subscales in the 7-week postpartum questionnaire. The direction of the effect was maintained, mostly with a larger effect size in women who received the intervention. Women allocated to outpatient priming were more satisfied with their priming experience than women allocated to inpatient priming. Being informed that they could go home after cervical priming did not increase women's anxiety.


Exploring compassion: implications for contemporary nursing. Part 1.
The origin of compassion is firmly rooted in religious ideologies. In 19th century Great Britain, Christianity was the prominent religion and scripture advocated that followers should always be compassionate in their deeds and actions. Florence Nightingale was a Christian and translated her ideals into the characterization of the professional nurse. The image of the ministering angel, performing the work of God, was perpetuated for some time. However, as the profession of nursing advanced to develop evidence-based practice, some of the ethos of the compassionate nursing character was seemingly lost in favour of technical skills. This is supported by evidence suggesting that nurses have a decreased affinity with the ethos of altruism. Recent reports have highlighted negative patient experiences which reflect a clear lack of compassionate nursing care. This has led to a variety of documents re-endorsing the concept of compassion as a core and fundamental nursing value. This has raised several issues for nursing practice which require due consideration if the profession is to restore the image of the compassionate nurse, technically skilled and clinically effective, equipped with the appropriate skills, knowledge, values and attitudes to fulfil the pledges to respond to patients with humanity and kindness and to deliver high-quality compassionate care.


Brain ferritin iron as a risk factor for age at onset in neurodegenerative diseases.
Tissue iron can promote oxidative damage. Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Higher iron levels in males may contribute to higher risk for younger-onset PD and recent studies have linked the presence of the hemochromatosis gene with a younger age at onset of AD. We examined whether age at onset of PD and AD was associated with increased brain ferritin iron. Ferritin iron can be measured with specificity in vivo with MRI utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in three basal ganglia regions (caudate, putamen, and globus pallidus) and frontal lobe white matter for younger- and older-onset male PD and AD patients and healthy controls. Significant increases in basal ganglia FDRI levels were observed in the younger-onset groups of both diseases compared to their respective control groups, but were absent in the older-onset patients. The results support the suggestion that elevated ferritin iron and its associated toxicity is a risk factor for age at onset of neurodegenerative diseases such as AD and PD. Clinical phenomena such as gender-associated risk of developing neurodegenerative diseases and the age at onset of such diseases may be associated with brain iron levels. In vivo MRI can measure and track brain ferritin iron levels and provides an opportunity to design therapeutic interventions that target high-risk populations early in the course of illness, possibly even before symptoms appear.


Kinetics of 9-aminoacridine block of single Na channels.
The kinetics of 9-aminoacridine (9-AA) block of single Na channels in neuroblastoma N1E-115 cells were studied using the gigohm seal, patch clamp technique, under the condition in which the Na current inactivation had been eliminated by treatment with N-bromoacetamide (NBA). Following NBA treatment, the current flowing through individual Na channels was manifested by square-wave open events lasting from several to tens of milliseconds. When 9-AA was applied to the cytoplasmic face of Na channels at concentrations ranging from 30 to 100 microM, it caused repetitive rapid transitions (flickering) between open and blocked states within single openings of Na channels, without affecting the amplitude of the single channel current. The histograms for the duration of blocked states and the histograms for the duration of open states could be fitted with a single-exponential function. The mean open time (tau o) became shorter as the drug concentration was increased, while the mean blocked time (tau b) was concentration independent. The association (blocking) rate constant, kappa, calculated from the slope of the curve relating the reciprocal mean open time to 9-AA concentration, showed little voltage dependence, the rate constant being on the order of 1 X 10(7) M-1s-1. The dissociation (unblocking) rate constant, l, calculated from the mean blocked time, was strongly voltage dependent, the mean rate constant being 214 s-1 at 0 mV and becoming larger as the membrane being hyperpolarized. The voltage dependence suggests that a first-order blocking site is located at least 63% of the way through the membrane field from the cytoplasmic surface. The equilibrium dissociation constant for 9-AA to block the Na channel, defined by the relation of l/kappa, was calculated to be 21 microM at 0 mV. Both tau -1o and tau -1b had a Q10 of 1.3, which suggests that binding reaction was diffusion controlled. The burst time in the presence of 9-AA, which is the sum of open times and blocked times, was longer than the lifetime of open channels in the absence of drug. All of the features of 9-AA block of single Na channels are compatible with the sequential model in which 9-AA molecules block open Na channels, and the blocked channels could not close until 9-AA molecules had left the blocking site in the channels.


Agitation-free multiphoton microscopy of oblique planes.
The scanning two-photon fluorescence microscope produces optically sectioned images from the focal plane. It is sometimes desirable to acquire images from other planes of the specimen that are inclined with respect to the focal plane. In this Letter, we discuss the issues concerned with acquiring such images together with the effects of the inclination angle on image resolution and sectioning strength. To obtain images from oblique planes at high speed, a two-photon system was built wherein a novel optical system is used to provide aberration-free scanning.


Placental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia.
Preeclampsia and fetal growth restriction (FGR) are major causes of the more than 5 million perinatal and infant deaths occurring globally each year, and both are associated with placental dysfunction. The risk of perinatal and infant death is greater in males, but the mechanisms are unclear. We studied data and biological samples from the Pregnancy Outcome Prediction (POP) study, a prospective cohort study that followed 4,212 women having first pregnancies from their dating ultrasound scan through delivery. We tested the hypothesis that fetal sex would be associated with altered placental function using multiomic and targeted analyses. We found that spermine synthase (SMS) escapes X-chromosome inactivation (XCI) in the placenta and is expressed at lower levels in male primary trophoblast cells, and male cells were more sensitive to polyamine depletion. The spermine metabolite N1,N12-diacetylspermine (DiAcSpm) was higher in the female placenta and in the serum of women pregnant with a female fetus. Higher maternal serum levels of DiAcSpm increased the risk of preeclampsia but decreased the risk of FGR. To our knowledge, DiAcSpm is the first maternal biomarker to demonstrate opposite associations with preeclampsia and FGR, and this is the first evidence to implicate polyamine metabolism in sex-related differences in placentally related complications of human pregnancy.


Transcriptional analysis of late ripening stages of grapevine berry.
The composition of grapevine berry at harvest is a major determinant of wine quality. Optimal oenological maturity of berries is characterized by a high sugar/acidity ratio, high anthocyanin content in the skin, and low astringency. However, harvest time is still mostly determined empirically, based on crude biochemical composition and berry tasting. In this context, it is interesting to identify genes that are expressed/repressed specifically at the late stages of ripening and which may be used as indicators of maturity. Whole bunches and berries sorted by density were collected in vineyard on Chardonnay (white cultivar) grapevines for two consecutive years at three stages of ripening (7-days before harvest (TH-7), harvest (TH), and 10-days after harvest (TH+10)). Microvinification and sensory analysis indicate that the quality of the wines made from the whole bunches collected at TH-7, TH and TH+10 differed, TH providing the highest quality wines.In parallel, gene expression was studied with Qiagen/Operon microarrays using two types of samples, i.e. whole bunches and berries sorted by density. Only 12 genes were consistently up- or down-regulated in whole bunches and density sorted berries for the two years studied in Chardonnay. 52 genes were differentially expressed between the TH-7 and TH samples. In order to determine whether these genes followed a similar pattern of expression during the late stages of berry ripening in a red cultivar, nine genes were selected for RT-PCR analysis with Cabernet Sauvignon grown under two different temperature regimes affecting the precocity of ripening. The expression profiles and their relationship to ripening were confirmed in Cabernet Sauvignon for seven genes, encoding a carotenoid cleavage dioxygenase, a galactinol synthase, a late embryogenesis abundant protein, a dirigent-like protein, a histidine kinase receptor, a valencene synthase and a putative S-adenosyl-L-methionine:salicylic acid carboxyl methyltransferase. This set of up- and down-regulated genes characterize the late stages of berry ripening in the two cultivars studied, and are indirectly linked to wine quality. They might be used directly or indirectly to design immunological, biochemical or molecular tools aimed at the determination of optimal ripening in these cultivars.


An evaluation of the first year of family health nursing practice in Scotland.
Scotland has led enactment of the new World Health Organisation (Europe) Family Health Nurse (FHN) concept. This paper presents research which evaluated the initial operation and impact of the role in remote and rural regions of Scotland. Through use of a multiplex research design informed by ideas from realistic evaluation, fourth generation evaluation and case study research, an initial typology of practice was constructed. The new FHN role typically supplemented, rather than supplanted, pre-existing community nursing services. Implications arising from key findings are discussed in relation to Scottish, UK and European nursing and primary care perspectives.


Effects of peppermint (Mentha piperita L.) extracts on experimental allergic rhinitis in rats.
The present study was carried out to clarify the effects of extracts of the leaves of Mentha piperita L. on experimental allergic rhinitis. The 50% EtOH extract of peppermint inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. The effect was dose-dependent and significant inhibition was observed at a concentration of 3 microg/ml. In addition, the 50% EtOH eluate separated from the 50% EtOH extract of peppermint by column chromatography (DIAION HP-20) was also effective in inhibiting histamine release at a concentration of 1 microg/ml. Nasal symptoms, sneezing and nasal rubbing induced by antigen challenge in actively sensitized rats were inhibited by oral administration of the 50% EtOH eluate. Significant inhibition of sneezing and nasal rubbing was observed at doses of 300 and 1000 mg/kg, p.o., respectively. Furthermore, the 50% EtOH eluate inhibited dye leakage into the nasal cavity of rats induced by antigen in a dose-dependent manner. These results suggested that extracts of Mentha piperita L. may be clinically effective in alleviating the nasal symptoms of allergic rhinitis.


Lower body function and mortality in Mexican American elderly people.
The purpose of this analysis was to examine the differential impact of performance-based and self-reported lower body measures on 2-year mortality in Mexican American elderly persons. Data employed are from the Hispanic Established Population for Epidemiological Studies of the Elderly, a probability survey of 3050 community-dwelling Mexican Americans aged 65 and older from the five Southwestern states interviewed in 1993 and 1994. Of the baseline sample with complete data, 198 persons were confirmed deceased 2 years later. A three-task, performance-based, lower body function measure consisting of a short walk, balance, and repeated chair stands tests was used. Self-reported lower body function was measured by a 4-item Activities of Daily Living (ADL) measure involving the lower body. The three-task, lower body function measure was a significant predictor of 2-year mortality. The short walk alone was as predictive as the summary measure. The predictive ability of both measures was minimally reduced by the inclusion of the self-reported ADL measure and life-threatening medical conditions. Finally, the ADL measure was not a significant predictor of mortality with all the other variables in the analysis. Objective measures of lower body function were significant predicators of mortality in Mexican American elderly persons, as found in the general population. Unlike previous studies, the ADL measure was not an independent predictor of mortality after controlling for the objective measure and other risk factors. Additional research is needed to address why objective measures of function are such strong predictors of death.


Colonization with Helicobacter is concomitant with modified gut microbiota and drastic failure of the immune control of Mycobacterium tuberculosis.
Epidemiological and experimental observations suggest that chronic microbial colonization can impact the immune control of other unrelated pathogens contracted in a concomitant or sequential manner. Possible interactions between Mycobacterium tuberculosis infection and persistence of other bacteria have scarcely been investigated. Here we demonstrated that natural colonization of the digestive tract with Helicobacter hepaticus in mice is concomitant with modification of the gut microbiota, subclinical inflammation, and drastic impairment of immune control of the growth of subsequently administered M. tuberculosis, which results in severe lung tissue injury. Our results provided insights upon the fact that this prior H. hepaticus colonization leads to failures in the mechanisms that could prevent the otherwise balanced cross-talk between M. tuberculosis and the immune system. Such disequilibrium ultimately leads to the inhibition of control of mycobacterial growth, outbreak of inflammation, and lung pathology. Among the dysregulated immune signatures, we noticed a correlation between the detrimental lung injury and the accumulation of activated T-lymphocytes. Our findings suggest that the impact of prior Helicobacter spp. colonization and subsequent M. tuberculosis parasitism might be greater than previously thought, which is a key point given that both species are among the most frequent invasive bacteria in human populations.


Hospital episodes and physician visits: the concordance between self-reports and medicare claims.
Health services use typically is examined using either self-reports or administrative data, but the concordance between the 2 is not well established. We evaluated the concordance of hospital and physician utilization data from self-reports and claims data, and identified factors associated with disagreement. We performed a secondary analysis on linked observational and administrative data. A national sample of 4310 respondents who were 70 years old or older at their baseline interviews was used. Self-reported and Medicare claims-based hospital episodes and physician visits for 12 months before baseline were examined. Kappa statistics were used to evaluate concordance, and multivariable multinomial logistic regression was used to identify factors associated with overreporting (self-reports > claims), underreporting (self-reports < claims), and concordant-reporting (self-reports approximately claims). The concordance of hospital episodes was high (kappa = 0.767 for the 2 x 2 comparison of none vs. some and kappa = 0.671 for the 6 x 6 comparison of none, 1, ..., 4, or 5 or more), but concordance for physician visits was low (kappa = 0.255 for the 2 x 2 comparison of none versus some and kappa = 0.351 for the 14 x 14 comparison of none, 1, ..., 12, and 13 or more). Multivariable multinomial logistic regression indicated that over-, under-, and concordant-reporting of hospital episodes was significantly associated with gender, alcohol consumption, arthritis, cancer, heart disease, psychologic problems, lower body functional limitations, self-rated health, and depressive symptoms. Over-, under-, and concordant-reporting of physician visits were significantly associated with age, gender, race, living alone, veteran status, private health insurance, arthritis, cancer, diabetes, hypertension, heart disease, lower body functional limitations, and poor memory. Concordance between self-reported and claims-based hospital episodes was high, but concordance for physician visits was low. Factors significantly associated with bidirectional (over- and underreporting) and unidirectional (over- or underreporting) error patterns were detected. Therefore, caution is advised when drawing conclusions based on just one physician visit data source.


Frequent callers to and users of emergency medical systems: a systematic review.
There appears to be a paucity of studies examining the characteristics and impact of frequent users upon emergency medical services (EMS). To review current primary research on frequent users of EMS and to identify possible gaps in the literature. Ovid, PubMed and CINAHL/Medline were systematically searched for articles that were published in English and either referred to frequent callers to or users of an EMS, or referred to frequent users of other services where admissions were via ambulance. Studies were included regardless of quality. Eighteen studies were included. Ten were emergency department based, seven in EMS and one in a psychiatric emergency service. In emergency department studies, frequent users were more likely to arrive via ambulance than infrequent users. In EMS studies, between 0.2% and 23% of patients using EMS were frequent users accounting for 1.4% to 40% of all ambulance use. No two EMS studies used the same definition of a frequent user. No studies focused on characteristics of callers to EMS. Two studies explored interventions for frequent callers to EMS, with mixed results in reducing ambulance use. It is unknown to what extent frequent callers impact upon EMS resources. Research should identify predictors and characteristics of frequent users of EMS, and a consistent definition of a frequent caller to or user of EMS would provide greater comparability. The lack of studies identified in this review suggests that further research is needed in order to inform policy and practice.


DTI tractography and white matter fiber tract characteristics in euthymic bipolar I patients and healthy control subjects.
With the introduction of diffusion tensor imaging (DTI), structural differences in white matter (WM) architecture between psychiatric populations and healthy controls can be systematically observed and measured. In particular, DTI-tractography can be used to assess WM characteristics over the entire extent of WM tracts and aggregated fiber bundles. Using 64-direction DTI scanning in 27 participants with bipolar disorder (BD) and 26 age-and-gender-matched healthy control subjects, we compared relative length, density, and fractional anisotrophy (FA) of WM tracts involved in emotion regulation or theorized to be important neural components in BD neuropathology. We interactively isolated 22 known white matter tracts using region-of-interest placement (TrackVis software program) and then computed relative tract length, density, and integrity. BD subjects demonstrated significantly shorter WM tracts in the genu, body and splenium of the corpus callosum compared to healthy controls. Additionally, bipolar subjects exhibited reduced fiber density in the genu and body of the corpus callosum, and in the inferior longitudinal fasciculus bilaterally. In the left uncinate fasciculus, however, BD subjects exhibited significantly greater fiber density than healthy controls. There were no significant differences between groups in WM tract FA for those tracts that began and ended in the brain. The significance of differences in tract length and fiber density in BD is discussed.


Clinical implications of electrocardiographic bundle branch block in primary care.
Electrocardiographic bundle branch block (BBB) is common but the prognostic implications in primary care are unclear. We sought to investigate the relationship between electrocardiographic BBB subtypes and the risk of cardiovascular (CV) outcomes in a primary care population free of major CV disease. Retrospective cohort study of primary care patients referred for electrocardiogram (ECG) recording between 2001 and 2011. Cox regression models were used to estimate hazard ratios (HR) as well as absolute risks of CV outcomes based on various BBB subtypes. We included 202 268 individuals with a median follow-up period of 7.8 years (Inter-quartile range [IQR] 4.9-10.6). Left bundle branch block (LBBB) was associated with heart failure (HF) in both men (HR 3.96, 95% CI 3.30 to 4.76) and women (HR 2.51, 95% CI 2.15 to 2.94) and with CV death in men (HR 1.80, 95% CI 1.38 to 2.35). Right bundle branch block (RBBB) was associated with pacemaker implantation in both men (HR 3.26, 95% CI 2.74 to 3.89) and women (HR 3.69, 95% CI 2.91 to 4.67), HF in both sexes and weakly associated with CV death in men. Regarding LBBB, we found an increasing hazard of HF with increasing QRS-interval duration (HR 1.25, 95% CI 1.11 to 1.42 per 10 ms increase in men and HR 1.23, 95% CI 1.08 to 1.40 per 10 ms increase in women). Absolute 10-year risk predictions across age-specific and sex-specific subgroups revealed clinically relevant differences between having various BBB subtypes. Opportunistic findings of BBB subtypes in primary care patients without major CV disease should be considered warnings of future HF and pacemaker implantation.


Improving microbiological safety and quality characteristics of wheat and barley by high voltage atmospheric cold plasma closed processing.
Contamination of cereal grains as a key global food resource with insects or microorganisms is a persistent concern for the grain industry due to irreversible damage to quality and safety characteristics and economic losses. Atmospheric cold plasma presents an alternative to conventional grain decontamination methods owing to the high antimicrobial potential of reactive species generated during the treatment, but effects against product specific microflora are required to understand how to optimally develop this approach for grains. This work investigated the influence of ACP processing parameters for both cereal grain decontamination and grain quality as important criteria for grain or seed use. A high voltage (HV) (80 kV) dielectric barrier discharge (DBD) closed system was used to assess the potential for control of native microflora and pathogenic bacterial and fungal challenge microorganisms, in tandem with effects on grain functional properties. Response surface modelling of experimental data probed the key factors in relation to microbial control and seed germination promotion. The maximal reductions of barley background microbiota were 2.4 and 2.1 log10 CFU/g and of wheat - 1.5 and 2.5 log10 CFU/g for bacteria and fungi, respectively, which required direct treatment for 20 min followed by a 24 h sealed post-treatment retention time. In the case of challenge organisms inoculated on barley grains, the highest resistance was observed for Bacillus atrophaeus endospores, which, regardless of retention time, were maximally reduced by 2.4 log10 CFU/g after 20 min of direct treatment. The efficacy of the plasma treatment against selected microorganisms decreased in the following order: E. coli > P. verrucosum (spores) > B. atrophaeus (vegetative cells) > B. atrophaeus (endospores). The challenge microorganisms were more susceptible to ACP treatment than naturally present background microbiota. No major effect of short term plasma treatment on the retention of quality parameters was observed. Germination percentage measured after 7 days cultivation was similar for samples treated for up to 5 min, but this was decreased after 20 min of direct treatment. Overall, ACP proved effective for cereal grain decontamination, but it is noted that the diverse native micro-flora may pose greater resistance to the closed, surface decontamination approach than the individual fungal or bacterial challenges, which warrants investigation of grain microbiome responses to ACP.


Characterization of rat iodothyronine sulfotransferases.
Sulfation appears to be an important pathway for the reversible inactivation of thyroid hormone during fetal development. The rat is an often used animal model to study the regulation of fetal thyroid hormone status. The present study was done to determine which sulfotransferases (SULTs) are important for iodothyronine sulfation in the rat, using radioactive T4, T3, rT3, and 3,3'-T2 as substrates, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as cofactor, and rat liver, kidney and brain cytosol, and recombinant rat SULT1A1, -1B1, -1C1, -1E1, -2A1, -2A2, and -2A3 as enzymes. Recombinant rat SULT1A1, -1E1, -2A1, -2A2, and -2A3 failed to catalyze iodothyronine sulfation. For all tissue SULTs and for rSULT1B1 and rSULT1C1, 3,3'-T2 was by far the preferred substrate. Apparent Km values for 3,3'-T2 amounted to 1.9 microM in male liver, 4.4 microM in female liver, 0.76 microM in male kidney, 0.23 microM in male brain, 7.7 microM for SULT1B1, and 0.62 microM for SULT1C1, whereas apparent Km values for PAPS showed less variation (2.0-6.9 microM). Sulfation of 3,3'-T2 was inhibited dose dependently by other iodothyronines, with similar structure-activity relationships for most enzymes except for the SULT activity in rat brain. The apparent Km values of 3,3'-T2 in liver cytosol were between those determined for SULT1B1 and -1C1, supporting the importance of these enzymes for the sulfation of iodothyronines in rat liver, with a greater contribution of SULT1C1 in male than in female rat liver. The results further suggest that rSULT1C1 also contributes to iodothyronine sulfation in rat kidney, whereas other, yet-unidentified forms appear more important for the sulfation of thyroid hormone in rat brain.


Multilayered intercalation of 1-octanol into Brodie graphite oxide.
Multilayered intercalation of 1-octanol into the structure of Brodie graphite oxide (B-GO) was studied as a function of temperature and pressure. Reversible phase transition with the addition/removal of one layer of 1-octanol was found at 265 K by means of X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The same transition was observed at ambient temperature upon a pressure increase above 0.6 GPa. This transition was interpreted as an incongruent melting of the low temperature/high pressure B-GO intercalated structure with five layers of 1-octanol parallel to GO sheets (L-solvate), resulting in the formation of a four-layered structure that is stable under ambient conditions (A-solvate). Vacuum heating allows the removal of 1-octanol from the A-solvate layer by layer, while distinct sets of (00l) reflections are observed for three-, two-, and one-layered solvate phases. Step by step removal of the 1-octanol layers results in changes of distance between graphene oxide planes by ∼4.5 Å. This experiment proved that both L- and A-solvates are structures with layers of 1-octanol parallel to GO planes. Unusual intercalation with up to five distinct layers of 1-octanol is remarkably different from the behaviour of small alcohol molecules (methanol and ethanol), which intercalate B-GO structure with only one layer under ambient conditions and a maximum of two layers at lower temperatures or higher pressures. The data presented in this study make it possible to rule out a change in the orientation of alcohol molecules from parallel to perpendicular to the GO planes, as suggested in the 1960s to explain larger expansion of the GO lattice due to swelling with larger alcohols.


Work-related exhaustion and telomere length: a population-based study.
Psychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells. We used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30-64. Work-related exhaustion was assessed using the Maslach Burnout Inventory--General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR) -based method. After adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016) than those with no exhaustion (p = 0.009). The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008). These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.


Is there a risk for interaction between mobile phones and single lead VDD pacemakers?
Mobile phones may cause pacemaker interference. Patients with a single lead VDD pacemaker might be at special risk, since the atrial sensitivity is often programmed to low (high sensitivity) threshold values and the majority of patients are pacemaker dependent due to the underlying high degree AV block. We evaluated 31 patients with three types of single lead VDD pacemakers: 12 Unity, 292-07 (Intermedics, Inc.); 10 Thera VDD, 8948 or 8968i (Medtronic, Inc.); and 9 Saphir 600 (Vitatron, Inc.) for interference from a cellular mobile phone with a power of 2 W (D-net). For this purpose, atrial and ventricular sensitivity settings were programmed to their most sensitive values (A: 0.1-0.25 mV; V: 1.0 mV) and ventricular sensing was programmed to unipolar. With the ECG continuously monitored, the phone's extendable antenna was brought in direct contact with the patient's skin at the right sternal border, with the tip of the antenna in skin contact just below the clavicle, within 5 cm of the pacemaker connector. Then multiple phases of phone calls were performed, and the effects on the pacemakers recorded. In our group of patients with three different types of single lead VDD pacemakers, no interference could be detected using a 2-W mobile phone in the digital D-net. The programmed values remained unchanged after the interference test. Therefore, the risk of interference seems to be low for the VDD pacemakers tested, although our study design does not allow to entirely exclude the possibility of interference from a mobile phone.


Human papillomavirus genotypes in human immunodeficiency virus-positive patients with anal pathology in Madrid, Spain.
We studied anal specimens to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain). We studied a total of 82 anal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid. These included 4 specimens with benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion, 24 specimens with high-grade anal squamous intraepithelial lesions and 2 specimens with invasive anal carcinoma. HPV genotyping was performed with PCR amplification and reverse dot blot hybridization. We detected 33 different HPV genotypes, including 16 HPVs associated with a high risk of carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and 14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an uncharacterized HPV genotype was detected. The most frequent HPV genotypes found were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV-43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 83.9% of all types of lesions. The majority of cases (90.2%) were concomitantly infected with the human immunodeficiency virus (HIV). The prevalence of high-risk carcinogenic genotypes in anal pathological samples was remarkable. Therefore, further studies that include a greater number of samples, particularly invasive carcinoma cases are needed to evaluate the potential influence of these HPV genotypes in the appearance of anal carcinomas. Also, the influence of other accompanying infections should be evaluated clarify the appearance of this type of carcinoma. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2075238024106058.


Integrating Clinical Decision Support into EMR and PHR: a Case Study Using Anticoagulation.
Clinical decision support (CDS) for atrial fibrillation is expected to ease the implementation of often-complex guidelines for atrial fibrillation and anticoagulation. Most clinical decision support systems (CDSS) for anticoagulation are stand-alone systems that do not integrate with electronic medical records (EMR). We have developed an architecture that consists of a computerized CDS that can integrate with multiple EMRs and multiple patient health records (PHRs). The design process revealed some significant issues that were resolved through systematic business/clinical analysis and creative clinical design in the diagnostic and treatment domains. Key issues identified and resolved include: 1) how to correctly allocate existing patients into various CDSS states (e.g., MAINTENANCE, HOLD, DISCONTINUE, etc), 2) identify when a patient becomes eligible for CDSS guidance over time, 3) how the CDSS maintains information about the patient's anticoagulation state and 4) how to transform vague human-readable concepts to explicit computable concepts. The management of anticoagulation for atrial fibrillation is no easy task and we believe our architecture will improve patient care at all levels and ultimately better balance the reduction of stroke risk while minimizing harms from major bleeding. In addition, the architecture presented is scalable to other treatment guidelines and is scalable to multiple EMRs and PHRs, making it suitable for use in a platform approach.


Evaluation of specific stabilizing exercise in the treatment of chronic low back pain with radiologic diagnosis of spondylolysis or spondylolisthesis.
A randomized, controlled trial, test--retest design, with a 3-, 6-, and 30-month postal questionnaire follow-up. To determine the efficacy of a specific exercise intervention in the treatment of patients with chronic low back pain and a radiologic diagnosis of spondylolysis or spondylolisthesis. A recent focus in the physiotherapy management of patients with back pain has been the specific training of muscles surrounding the spine (deep abdominal muscles and lumbar multifidus), considered to provide dynamic stability and fine control to the lumbar spine. In no study have researchers evaluated the efficacy of this intervention in a population with chronic low back pain where the anatomic stability of the spine was compromised. Forty-four patients with this condition were assigned randomly to two treatment groups. The first group underwent a 10-week specific exercise treatment program involving the specific training of the deep abdominal muscles, with co-activation of the lumbar multifidus proximal to the pars defects. The activation of these muscles was incorporated into previously aggravating static postures and functional tasks. The control group underwent treatment as directed by their treating practitioner. After intervention, the specific exercise group showed a statistically significant reduction in pain intensity and functional disability levels, which was maintained at a 30-month follow-up. The control group showed no significant change in these parameters after intervention or at follow-up. A "specific exercise" treatment approach appears more effective than other commonly prescribed conservative treatment programs in patients with chronically symptomatic spondylolysis or spondylolisthesis.


Breastfeeding and feminism: a focus on reproductive health, rights and justice.
The annual Breastfeeding and Feminism Symposia aim to reposition breastfeeding as a valued part of women's (re)productive lives and rights. The symposia are designed to raise the profile of breastfeeding within the women's advocacy and feminist studies' communities, and to increase recognition among breastfeeding supporters that breastfeeding promotion could receive more socio-political support by partnering with those concerned with women's reproductive health, rights and justice, women's economic advancement, and the elimination of social, economic and health inequities. The third symposium (2007) sought to build dialogue and increase communications between and among these diverse communities. The nine articles presented in this thematic series were selected by the journal editors, and represent the core discussions at the symposium. This editorial presents the areas of synergy and strategies for action that emerged from the discussions. These strategies and this thematic issue are intended to reassert the momentum that evolved among participants, and to stimulate involvement among individuals and organizations not in attendance in promoting breastfeeding as a women's reproductive health, rights and justice concern.


A selective membrane-targeting repurposed antibiotic with activity against persistent methicillin-resistant Staphylococcus aureus.
Treatment of Staphylococcus aureus infections is complicated by the development of antibiotic tolerance, a consequence of the ability of S. aureus to enter into a nongrowing, dormant state in which the organisms are referred to as persisters. We report that the clinically approved anthelmintic agent bithionol kills methicillin-resistant S. aureus (MRSA) persister cells, which correlates with its ability to disrupt the integrity of Gram-positive bacterial membranes. Critically, bithionol exhibits significant selectivity for bacterial compared with mammalian cell membranes. All-atom molecular dynamics (MD) simulations demonstrate that the selectivity of bithionol for bacterial membranes correlates with its ability to penetrate and embed in bacterial-mimic lipid bilayers, but not in cholesterol-rich mammalian-mimic lipid bilayers. In addition to causing rapid membrane permeabilization, the insertion of bithionol increases membrane fluidity. By using bithionol and nTZDpa (another membrane-active antimicrobial agent), as well as analogs of these compounds, we show that the activity of membrane-active compounds against MRSA persisters positively correlates with their ability to increase membrane fluidity, thereby establishing an accurate biophysical indicator for estimating antipersister potency. Finally, we demonstrate that, in combination with gentamicin, bithionol effectively reduces bacterial burdens in a mouse model of chronic deep-seated MRSA infection. This work highlights the potential repurposing of bithionol as an antipersister therapeutic agent.


Organ donation education initiatives: A report of the Donor Management Task Force.
It is essential that hospitals and health professionals establish systems to facilitate patients' organ donation wishes. Donation education has been neither standardized nor systematic, and resources related to donation processes have not been widely accessible. This report describes 2 free, publicly available educational resources about the organ donation process created to advance the mission of basic education and improve donation processes within hospitals and health care systems. Members of the Donor Management Task Force of the Organ Donation and Transplantation Alliance (the Alliance) and the Health Resources and Services Administration of the US Department of Health and Human Services convened annually in person and by teleconferencing during the year to develop 2 educational vehicles on organ donation. Two educational products were developed: the Organ Donation Toolbox, an online repository of documents and resources covering all aspects of the donation process, and the Educational Training Video that reviews the basic foundations of a successful hospital donation system. There is a need for more research and education about the process of organ donation as it relates to the medical and psychosocial care of patients and families before the end of life. The educational products described can help fill this critical need.


Experimental population genetics of meiotic drive systems. I. Pseudo-Y chromosomal drive as a means of eliminating cage populations of Drosophila melanogaster.
The experimental population genetics of Y-chromosome drive in Drosophila melanogaster is approximated by studying the behavior of T(Y;2),SD lines. These exhibit "pseudo-Y" drive through the effective coupling of the Y chromosome to the second chromosome meiotic drive locus, Segregation distorter (SD). T(Y;2),SD males consequently produce only male offspring. When such lines are allowed to compete against structurally normal SD(+) flies in population cages, T(Y;2),SD males increase in frequency according to the dynamics of a simple haploid selection model until the cage population is eliminated as a result of a deficiency in the number of adult females. Cage population extinction generally occurs within about seven generations.-Several conclusions can be drawn from these competition cage studies:(1) Fitness estimates for the T(Y;2),SD lines (relative to SD(+ )) are generally in the range of 2-4, and these values are corroborated by independent estimates derived from studies of migration-selection equilibrium. (2) Fitness estimates are unaffected by cage replication, sample time, or the starting frequency of T(Y;2),SD males, indicating that data from diverse cages can be legitimately pooled to give an overall fitness estimate. (3) Partitioning of the T(Y;2),SD fitnesses into components of viability, fertility, and frequency of alternate segregation (Y + SD from X + SD(+)) suggests that most of the T(Y;2),SD advantage derives from the latter two components. Improvements in the system might involve increasing both the viability and the alternate segregation to increase the total fitness. While pseudo-Y drive operates quite effectively against laboratory stocks, it is less successful in eliminating wild-type populations which are already segregating for suppressors of SD action. This observation suggests that further studies into the origin and rate of accumulation of suppressors of meiotic drive are needed before an overall assessment can be made of the potential of Y-chromosome drive as a tool for population control.


The relationship of alanine aminotransferase to metabolic syndrome in a Korean population.
Although associations between serum alanine aminotransferase and metabolic syndrome are well-recognized in Western countries, only a limited number of prospective studies have been performed in Asian populations. The aim of the study was to cross-sectionally and longitudinally examine whether serum alanine aminotransferase levels are associated with metabolic syndrome and its associated components in a Korean population. A total of 31,832 subjects who received health screenings were included in cross-sectional analyses; a subgroup of 4.070 subjects without metabolic syndrome at baseline was included in the longitudinal analyses. The metabolic syndrome definition was based on the National Cholesterol Education Program Third Adult Treatment Panel criteria with modification on waist circumference cut-off to be more appropriate for an Asian population. In the cross-sectional analyses, serum alanine aminotransferase is positively associated with metabolic syndrome and its components. In the longitudinal analyses, the prevalence of metabolic syndrome increased across serum alanine aminotransferase quartiles in a dose-dependent manner after extensive adjustments (hazard ratios were 1.000, 1.609, 2.601, and 3.015 for quartiles, 1 through quartile 4; P for trend<0.001). Our study confirmed a positive association between components of metabolic syndrome and elevated serum alanine aminotransferase in a Korean population.


The role of xenobiotic transporters in ophthalmic drug delivery.
The eye is a very complex sensory organ consisting of numerous structures to coordinate the function of sight. It has a series of physical and chemical barriers to help maintain its homeostasis, and mediate environmental exposures. Transporters in the eye play a very important role in maintaining homeostasis by facilitating the movement of ions, nutrients and xenobiotics to various tissues in the eye, especially to non-vascular tissues like the lens and cornea. They also ensure proper cell signaling by shuttling neurotransmitters within the retina. Thus, they are expected to play an important role in determining the ocular exposure of drugs and other pharmacotherapeutics. However, the role of ocular transporters in ophthalmic drug delivery and their clinical relevance has not been well characterized. The purpose of the present review is to summarize the current evidence in the literature on ocular drug transporters and their role in ocular drug delivery, with the emphasis predominantly on their role in ocular pharmacokinetics.


Differential interaction of cisplatin with the HIV-1 long terminal repeat in a resistant ovarian carcinoma cell line.
We constructed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) sequences of HIV-1 linked to the reporter chloramphenicol acetyl transferase (CAT) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV1 in a human ovarian cancer cell line A2780 and in a cisplatin resistant variant 2780CP, and obtained stable geneticin resistant A27HIV1-1 and 27CPHIV1-1 cells, respectively. Both transfectant cells expressed CAT activity from the HIV LTR promoter. The response to the anti-neoplastic drug cisplatin was studied on the LTR regulated CAT activity in both cell lines. It was found that cisplatin at 2.5 x 10(-5) M concentration stimulates the expression of CAT by 26-fold from the HIV LTR in A27HIV1-1, but requires a concentration of 5 x 10(-5) M to enhance expression by 4.1-fold in the cisplatin resistant 27CPHIV1-1 cells. Carboplatin, over a range of concentrations (1 x 10(-6) to 1 x 10(-4) M), does not stimulate expression of CAT from the HIV-1 LTR in either of the transfected cells.


Clinical decision-making and therapeutic approaches in osteopathy - a qualitative grounded theory study.
There is limited understanding of how osteopaths make decisions in relation to clinical practice. The aim of this research was to construct an explanatory theory of the clinical decision-making and therapeutic approaches of experienced osteopaths in the UK. Twelve UK registered osteopaths participated in this constructivist grounded theory qualitative study. Purposive and theoretical sampling was used to select participants. Data was collected using semi-structured interviews which were audio-recorded and transcribed. As the study approached theoretical sufficiency, participants were observed and video-recorded during a patient appointment, which was followed by a video-prompted interview. Constant comparative analysis was used to analyse and code data. Data analysis resulted in the construction of three qualitatively different therapeutic approaches which characterised participants and their clinical practice, termed; Treater, Communicator and Educator. Participants' therapeutic approach influenced their approach to clinical decision-making, the level of patient involvement, their interaction with patients, and therapeutic goals. Participants' overall conception of practice lay on a continuum ranging from technical rationality to professional artistry, and contributed to their therapeutic approach. A range of factors were identified which influenced participants' conception of practice. The findings indicate that there is variation in osteopaths' therapeutic approaches to practice and clinical decision-making, which are influenced by their overall conception of practice. This study provides the first explanatory theory of the clinical decision-making and therapeutic approaches of osteopaths.


A mutualism with a native membracid facilitates pollinator displacement by Argentine ants.
The loss of biodiversity and associated ecosystem services are major threats posed by the spread of alien invasive species. Invasive ants are frequently associated with declines in the diversity of ground-dwelling arthropods but also may affect plants through their attraction to floral nectar and tending of hemipterans. Protea nitida is a tree native to the South African fynbos that hosts a native membracid, Beaufortiana sp., which is tended by ants. Here I compare Argentine ants (Linepithema humile) to native ants in their attraction to P. nitida inflorescences in the presence and absence of the membracid, and their effects on other floral arthropod visitors, seed set, and ovule predation. Argentine ant discovery of inflorescences increased at least 13-fold when membracids were present on the branch, whereas native ant discovery of inflorescences was only doubled by membracid presence at one site in one study year and was unaffected in the other three site-years. Excluding Argentine ants from inflorescences resulted in an increase in several arthropod taxa and potential pollinators; native ant exclusion had no positive effects. Thus the mutualism between Argentine ants and the membracid is facilitating pollinator deterrence by the ants. Though Argentine ants were not associated with a decline in P. nitida seed set or ovule predation, declines in generalist insect pollinators may have ramifications for the 83% of fynbos plants that are insect pollinated. Pitfall traps showed that Argentine ants were not more abundant than native ants in non-invaded sites. Focusing only on abundance on the ground and displacement of ground-dwelling arthropod fauna may lead to an underestimate of the effects of invasive ants on their adopted communities.


"The Journey I Have Been Through": The Role of Religion and Spirituality in Aging Well Among HIV-Positive Older Adults.
The National Institutes of Health human immunodeficiency virus (HIV) and Aging Working Group identified spirituality as a research emphasis. This qualitative study examines the importance of religion and spirituality among 30 HIV-positive older adults. Using modified grounded theory, adults 50+ were recruited in Ontario, Canada, through AIDS service organizations, clinics, and community agencies. Descriptions of religion and spirituality encapsulated the idea of a journey, which had two components: the long-term HIV survivor profile combined with the experience of aging itself. A final category of HIV as a spiritual journey was finalized through consensus and included the properties of (1) being rejected by as well as rejection of formalized religion, (2) differentiating spirituality from religion, (3) having a connection, (4) feeling grateful, and (5) mindfulness and learning new skills. Interventions fostering resilience and strengths in HIV-positive older adults using spirituality should be considered, including the promotion of person-centered spirituality and interventions that include mindfulness and skill building.


Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7.
Recognition of viruses by pattern recognition receptors (PRRs) causes interferon-β (IFN-β) induction, a key event in the anti-viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV) protein C6 is identified as an inhibitor of PRR-induced IFN-β expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-κB and IFN regulatory factors (IRFs) to activate the IFN-β promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-κB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1) and IκB kinase-ε (IKKε), which phosphorylate and activate these IRFs. However, C6 does not inhibit TBK1- and IKKε-independent IRF7 activation or the induction of promoters by constitutively active forms of IRF3 or IRF7, indicating that C6 acts at the level of the TBK1/IKKε complex. Consistent with this notion, C6 immunoprecipitated with the TBK1 complex scaffold proteins TANK, SINTBAD and NAP1. C6 is expressed early during infection and is present in both nucleus and cytoplasm. Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7.


Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.
Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.


Replication Stress Drives Constitutive Activation of the DNA Damage Response and Radioresistance in Glioblastoma Stem-like Cells.
Glioblastoma (GBM) is a lethal primary brain tumor characterized by treatment resistance and inevitable tumor recurrence, both of which are driven by a subpopulation of GBM cancer stem-like cells (GSC) with tumorigenic and self-renewal properties. Despite having broad implications for understanding GSC phenotype, the determinants of upregulated DNA-damage response (DDR) and subsequent radiation resistance in GSC are unknown and represent a significant barrier to developing effective GBM treatments. In this study, we show that constitutive DDR activation and radiation resistance are driven by high levels of DNA replication stress (RS). CD133+ GSC exhibited reduced DNA replication velocity and a higher frequency of stalled replication forks than CD133- non-GSC in vitro; immunofluorescence studies confirmed these observations in a panel of orthotopic xenografts and human GBM specimens. Exposure of non-GSC to low-level exogenous RS generated radiation resistance in vitro, confirming RS as a novel determinant of radiation resistance in tumor cells. GSC exhibited DNA double-strand breaks, which colocalized with "replication factories" and RNA: DNA hybrids. GSC also demonstrated increased expression of long neural genes (>1 Mbp) containing common fragile sites, supporting the hypothesis that replication/transcription collisions are the likely cause of RS in GSC. Targeting RS by combined inhibition of ATR and PARP (CAiPi) provided GSC-specific cytotoxicity and complete abrogation of GSC radiation resistance in vitro These data identify RS as a cancer stem cell-specific target with significant clinical potential.Significance: These findings shed new light on cancer stem cell biology and reveal novel therapeutics with the potential to improve clinical outcomes by overcoming inherent radioresistance in GBM. Cancer Res; 78(17); 5060-71. ©2018 AACR.


Extracellular microRNAs are dynamic non-vesicular biomarkers of muscle turnover.
Extracellular microRNAs (miRNAs) are promising biomarkers of the inherited muscle wasting condition Duchenne muscular dystrophy, as they allow non-invasive monitoring of either disease progression or response to therapy. In this study, serum miRNA profiling reveals a distinct extracellular miRNA signature in dystrophin-deficient mdx mice, which shows profound dose-responsive restoration following dystrophin rescue. Extracellular dystrophy-associated miRNAs (dystromiRs) show dynamic patterns of expression that mirror the progression of muscle pathology in mdx mice. Expression of the myogenic miRNA, miR-206 and the myogenic transcription factor myogenin in the tibialis anterior muscle were found to positively correlate with serum dystromiR levels, suggesting that extracellular miRNAs are indicators of the regenerative status of the musculature. Similarly, extracellular dystromiRs were elevated following experimentally-induced skeletal muscle injury and regeneration in non-dystrophic mice. Only a minority of serum dystromiRs were found in extracellular vesicles, whereas the majority were protected from serum nucleases by association with protein/lipoprotein complexes. In conclusion, extracellular miRNAs are dynamic indices of pathophysiological processes in skeletal muscle.


Lysosomal Ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases.
Disrupted cellular Ca(2+) signaling is believed to play a role in a number of human diseases including lysosomal storage diseases (LSD). LSDs are a group of ∼50 diseases caused predominantly by mutations in lysosomal proteins that result in accumulation of macromolecules within the lysosome. We recently reported that Niemann-Pick type C (NPC) is the first human disease to be associated with defective lysosomal Ca(2+) uptake and defective NAADP-mediated lysosomal Ca(2+) release. These defects in NPC cells leads to the disruption in endocytosis and subsequent lipid storage that is a feature of this disease. In contrast, Chediak-Higashi Syndrome cells have been reported to have enhanced lysosomal Ca(2+) uptake whilst the TRPML1 protein defective in mucolipidosis type IV is believed to function as a Ca(2+) channel. In this review we provide a summary of the current knowledge on the role of lysosomal Ca(2+) signaling in the pathogenesis of this group of diseases.


Factors Affecting Food Allergy-Related Quality of Life From Parents' Perception in Turkish Children.
Food allergy (FA) affects the daily lives of children and parents in varying degrees. The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a valid and reliable instrument to assess the quality of life (QoL) of children from parents' perception. The aim of this study was to validate and determine the reliability of the Turkish FAQLQ-PF and to assess QoL in food-allergic children. Children aged between 0 and 12 years and diagnosed with immunoglobulin E (IgE)-mediated FA for at least 1 month were enrolled. The English FAQLQ-PF was translated into Turkish according to the World Health Organization guidelines. The Food Allergy Independent Measure and the Turkish Child Health Questionnaire-Parent Form 50 were used for construct validity. One hundred and fifty-seven patients participated. The median age of patients and FA duration were 2.4 years (1.2-5.2 years, interquartile-ranges) and 2 years (0.8-5.1), respectively. Ninety-six (61.1%) patients had anaphylaxis. The Cronbach's alpha coefficient and intra-class correlation coefficient for test-retest reliability was good for all age groups of children (<4, 4-6, and 7-12 years). Patients with either asthma or anaphylaxis had worse scores than others. Total scores of FAQLQ-PF tended to increase with age. Patients aged 7-12 had the highest total scores among all patients (2.2±0.1, 3.0±0.2, and 3.3±0.3 for <4, 4-6, and 7-12 years, respectively, P<0.001, P for trend <0.001). Other factors causing the poor QoL were cow's milk allergy, sibling allergy, mother's age over 30 years, mother's high education level and lower number of persons in household. The Turkish FAQLQ-PF is a valid and reliable scale. FA-related QoL was significantly worse with age. Coexistent asthma, anaphylaxis regardless of its severity, cow's milk allergy, sibling allergy and the older and educated mothers seem to poorly affect QoL.


Evolution of the treatment of cerebral vasospasm.
Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a disease process for which the lack of effective treatments has plagued neurosurgeons for decades. Historically, successful treatment after SAH in the acute setting was often followed by a rapid, uncontrollable deterioration in the subacute interval. Little was known regarding the nature and progression of this condition until the mid-1800s, when the disease was first described by Gull. Insight into the origin and natural history of cerebral vasospasm came slowly over the next 100 years, until the 1950s. Over the past five decades our understanding of cerebral vasospasm has expanded exponentially. This newly discovered information has been used by neurosurgeons worldwide for successful treatment of complications associated with vasospasm. Nevertheless, although great strides have been made toward elucidating the causes of cerebral vasospasm, a lasting cure continues to elude experts and the disease continues to wreak havoc on patients after aneurysmal SAH.


Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation.
To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a population that is at risk for post-transplant complications. Cancer 2017;123:1828-1838. © 2017 American Cancer Society.


Detection of metallothionein 1G as a methylated tumor suppressor gene in human hepatocellular carcinoma using a novel method of double combination array analysis.
Gene expression profiling or karyotyping analysis has made it possible to identify novel genes with altered expressions or copy numbers that have not been previously reported in liver cancer. On the same HCC sample, we performed double array analysis, both expression profiling and karyotyping analysis using a single nucleotide polymorphism (SNP) array in an attempt to find a novel tumor suppressor gene for its prognostic marker. We conducted expression array and SNP chip array using tumor and corresponding non-tumor tissues from the resected liver specimen of a 68-year-old woman who had chronic hepatitis type C. Additionally, we performed quantitative real-time reverse transcription polymerase chain reaction (PCR) and methylation-specific PCR (MSP) for gene detection using specimens from 48 patients with HCC, and investigated their correlation with the prognosis. Metallothionein (MT) 1G gene located on 16q13 showed a decreased expression in tumor tissue. The copy number by SNP chip array revealed no loss of heterozygosity since no deletions were detected in 16q13, and HCC tissue showed AB call in both SNPs next to MT1G. In quantitative real-time PCR using 48 HCC clinical samples, mRNA expression of MT1G decreased significantly compared with that in corresponding non-cancerous liver tissues (p<0.0323). Twenty-nine (60.4%) of 48 HCCs gave a positive result in MSP, indicating a poorer prognosis than the negative group, although the difference was not significant (p<0.0978). Our results indicated that MT1G acts as a tumor suppressor gene in HCC. Moreover, findings suggested that the mechanisms of MT1G silencing are related to promoter hypermethylation.


Pigmented villonodular synovitis (giant-cell tumor of the tendon sheath and synovial membrane). A review of eighty-one cases.
We reviewed the cases of eighty-one patients with pigmented villonodular synovitis and giant-cell tumor of the tendon sheath. The average duration of symptoms prior to consulting a physician was twenty-seven months. The lesion was slow-growing, was located in one joint or tendon sheath, and usually was asymptomatic in a finger or thumb but painful in a knee or toe. Twenty-nine per cent of the finger or thumb lesions and 21 per cent of the knee lesions that were followed recurred. Approximately 70 per cent of the radiographs showed abnormalities that ranged from soft-tissue swelling to bone erosion. Six lesions were incidental findings during arthrotomy for some other lesion. The histological characteristics of the solitary nodular, multiple nodular, and diffuse lesions suggested that they have a common histogenesis that is characterized by proliferation of fibroblastic or histiocytic mesenchymal cells, or both, beneath the synovial or tenosynovial lining cells, and by collagen production. Foam cells and iron deposits appear to be secondary changes and are usually seen in the periphery of the expanding nodules. The centrifugal growth pattern and the distinct differences between the lesional tissue and the adjacent hyperplastic synovial tissue suggest that pigmented villonodular synovitis is a true neoplastic process.