Nutrient intakes of middle-aged men and women in China, Japan, United Kingdom, and United States in the late 1990s: the INTERMAP study.
The purpose of the study was to compare nutrient intakes among Chinese, Japanese, UK, and US INTERMAP samples, and assess possible relationships of dietary patterns to differential patterns of cardiovascular diseases between East Asian and Western countries. Based on a common Protocol and Manuals of Operations, high-quality dietary data were collected by four standardized 24-h dietary recalls and two 24-h urine collections from 17 population samples in China (three samples), Japan (four samples), UK (two samples), and USA (eight samples). There were about 260 men and women aged 40-59 years per sample--total N=4680. Quality of dietary interview and data entry were monitored and enhanced by extensive systematic ongoing quality control procedures at local, country, and international level. Four databases on nutrient composition of foods from the four countries were updated and enhanced (76 nutrients for all four countries) by the Nutrition Coordinating Center, University of Minnesota, in cooperation with Country Nutritionists. The mean body mass index was much higher for Western than East Asian samples. Macronutrient intakes differed markedly across these samples, with Western diet higher in total fat, saturated and trans fatty acids, and Keys dietary lipid score, lower in total carbohydrate and starch, higher in sugars. Based on extensive published data, it is a reasonable inference that this pattern relates to higher average levels of serum total cholesterol and higher mortality from coronary heart disease in Western than East Asian populations. The rural Chinese diet was lower in protein, especially animal protein, in calcium, phosphorus, selenium, and vitamin A. Dietary sodium was higher, potassium lower, hence Na/K ratio was higher in the Asian diet, especially for Chinese samples. This pattern is known to relate to risks of adverse blood pressure level and stroke. At the end of the 20th century, East Asian and Western diets remain significantly different in macro- and micronutrient composition. Both dietary patterns have aspects that can be regarded, respectively, as adverse and protective in relation to the major adult cardiovascular diseases. In both Asian and Western countries, public efforts should be targeted at overcoming adverse aspects and maintaining protective patterns for prevention and control of cardiovascular diseases.


[The preparation of blood samples for the automatic measurement of erythrocyte size].
The following procedure is proposed: fixation for 12 h in low ionic strength solution (4 percent formaldehyde in 50 mM sodium phosphate buffer), drying of the suspension drop on the slide, gallocyanin staining. All red cells were contrast-stained without light central spot. The sizes of different red cell groups on the slide differed by less than 5 percent.


Poly(L-Lactide) microfilaments enhance peripheral nerve regeneration across extended nerve lesions.
After injury, axonal regeneration occurs across short gaps in the peripheral nervous system, but regeneration across larger gaps remains a challenge. To improve regeneration across extended nerve defects, we have fabricated novel microfilaments with the capability for drug release to support cellular migration and guide axonal growth across a lesion. In this study, we examine the nerve repair parameters of non-loaded filaments. To examine the influence of packing density on nerve repair, wet-spun poly(L-Lactide) (PLLA) microfilaments were bundled at densities of 3.75, 7.5, 15, and 30% to bridge a 1.0-cm gap lesion in the rat sciatic nerve. After 10 weeks, nerve cable formation increased significantly in the filament bundled groups when compared to empty-tube controls. At lower packing densities, the number of myelinated axons was more than twice that of controls or the highest packing density. In a consecutive experiment, PLLA bundles with lower filament-packing density were examined for nerve repair across 1.4- and 1.8-cm gaps. After 10 weeks, the number of successful regenerated nerves receiving filaments was more than twice that of controls. In addition, nerve cable areas for control groups were significantly less than those observed for filament groups. Axonal growth across 1.4- and 1.8-cm gaps was more consistent for the filament groups than for controls. These initial results demonstrate that PLLA microfilaments enhance nerve repair and regeneration across large nerve defects, even in the absence of drug release. Ongoing studies are examining nerve regeneration using microfilaments designed to release neurotrophins or cyclic AMP.


Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency.
Inborn errors of DNA repair or replication underlie a variety of clinical phenotypes. We studied 5 patients from 4 kindreds, all of whom displayed intrauterine growth retardation, chronic neutropenia, and NK cell deficiency. Four of the 5 patients also had postnatal growth retardation. The association of neutropenia and NK cell deficiency, which is unusual among primary immunodeficiencies and bone marrow failures, was due to a blockade in the bone marrow and was mildly symptomatic. We discovered compound heterozygous rare mutations in Go-Ichi-Ni-San (GINS) complex subunit 1 (GINS1, also known as PSF1) in the 5 patients. The GINS complex is essential for eukaryotic DNA replication, and homozygous null mutations of GINS component-encoding genes are embryonic lethal in mice. The patients' fibroblasts displayed impaired GINS complex assembly, basal replication stress, impaired checkpoint signaling, defective cell cycle control, and genomic instability, which was rescued by WT GINS1. The residual levels of GINS1 activity reached 3% to 16% in patients' cells, depending on their GINS1 genotype, and correlated with the severity of growth retardation and the in vitro cellular phenotype. The levels of GINS1 activity did not influence the immunological phenotype, which was uniform. Autosomal recessive, partial GINS1 deficiency impairs DNA replication and underlies intra-uterine (and postnatal) growth retardation, chronic neutropenia, and NK cell deficiency.


[Mitochondrial DNA G7444A mutation may influence the phenotypic manifestation of the deafness-associated 12S rRNA A1555G mutation].
Mitochondrial 12S rRNA and tRNASer(UCN) genes are the hot spots for mutations associated with hearing loss. We reported here the clinical, genetic and molecular analysis of a Chinese pedigree with maternally inherited sensorineural hearing loss. Molecular analysis showed that the pedigree carried both mitochondrial DNA (mtDNA) A1555G and G7444A mutations. The penetrance of hearing loss in this pedigree was 58% when aminoglycoside-induced hearing loss was included. When the effect of aminoglycosides was excluded, the penetrance of hearing loss in this pedigree was 25%. The penetrance of hearing loss was significantly higher than other families carrying only A1555G mutation. Sequence analysis of the complete mitochondrial genome in the proband showed that there were 28 mtDNA polymorphisms belonging to East-Asian haplogroup B4c1. In addition to the deafness-associated A1555G and G7444A mutations, there were no other functionally significant variants found in this family. This indicated that mtDNA G7444A mutation may aggravate mitochondrial dysfunction associated with the A1555G mutation. Therefore, the coexistence of both mtDNA mutations may contribute to high penetrance of hearing loss.


Recruitment challenges in stroke rehabilitation randomized controlled trials: a qualitative exploration of trialists' perspectives using Framework analysis.
To explore the underlying reasons for recruitment difficulties to stroke rehabilitation randomized controlled trials from the perspective of trialists. A qualitative study using semi-structured interviews and Framework analysis. Twenty multidisciplinary stroke rehabilitation trialists across 13 countries with a range of clinical and research experience. Twenty semi-structured telephone interviews were carried out. Purposeful sampling ensured a range of opinions were gathered from across the international stroke rehabilitation research community. Using Framework analysis, the analytical framework was formed by three researchers and tested before being applied to the total dataset. Three themes described the trialists' perception of the underlying reasons for recruitment difficulties: (i) decision making, (ii) importance of recruiters and (iii) a broken system. Trialists described frequently disregarding evidence in favour of prior research experiences when planning randomized controlled trial recruitment. All felt that the relationship between the research and clinical teams was vital to ensure recruiters prioritized and found value in recruitment to the trial. Experienced trialists were frustrated by the lack of reporting of the reality of running trials, research governance demands and the feeling that they had to deliberately underestimate recruitment timeframes to secure funding. Stroke rehabilitation trialists described recruitment difficulties which may be related to their experiential based recruitment decision making, a lack of understanding of how best to incentivize and maintain relationships with recruiters and unrealistic bureaucratic expectations both in terms of gaining funding and research governance.


Role of galectin-3 in leukocyte recruitment in a murine model of lung infection by Streptococcus pneumoniae.
Pneumonia can be caused by a variety of pathogens, among which Streptococcus pneumoniae causes one of the most common forms of community-acquired pneumonia. Depending on the invading pathogen, the elements of the immune response triggered will vary. For most pathogens, such as Escherichia coli, neutrophil recruitment involves a well-described family of adhesion molecules, beta(2)-integrins. In the case of streptococcal pneumonia, however, neutrophil recruitment occurs mainly through a beta(2)-integrin-independent pathway. Despite decades of research on this issue, the adhesion molecules involved in neutrophil recruitment during lung infection by S. pneumoniae have not been identified. We have previously shown that galectin-3, a soluble mammalian lectin, can be found in lungs infected by S. pneumoniae, but not by E. coli, and can mediate the adhesion of neutrophils on the endothelial cell layer, implying its role in the recruitment of neutrophils to lungs infected with S. pneumoniae. In this study, using galectin-3 null mice, we report further evidence of the involvement of this soluble lectin in the recruitment of neutrophils to S. pneumonia-infected lungs. Indeed, in the absence of galectin-3, lower numbers of leukocytes, mainly neutrophils, were recruited to the infected lungs during infection by S. pneumoniae. In the case of beta(2)-integrin-dependent recruitment induced by lung infection with E. coli, the number of recruited neutrophils was not reduced. Thus, taken together, our data suggest that galectin-3 plays a role as a soluble adhesion molecule in the recruitment of neutrophils to lungs infected by S. pneumoniae, which induces beta(2)-integrin-independent migration.


Assessment of Evidence About Common Infant Symptoms and Cow's Milk Allergy.
Sales of specialized formula for managing cow's milk allergy (CMA) have increased, triggering concern that attribution of common infant symptoms, such as crying, vomiting, and rashes, to CMA may be leading to overdiagnosis, which could undermine breastfeeding. To understand whether CMA guideline recommendations might promote CMA overdiagnosis or undermine breastfeeding. We reviewed recommendations made in CMA guidelines and critically appraised 2 key recommendations. First, we reviewed relevant literature summarizing whether maternal or infant dietary exclusion of cow's milk is effective for managing common infant symptoms. Second, we reviewed published data on breastmilk composition and thresholds of reactivity in CMA to estimate the probability that cow's milk protein in human breastmilk can trigger symptoms in infants with CMA. We also documented the level of commercial involvement in CMA guidelines. We reviewed 9 CMA guidelines published from 2012 to 2019. Seven suggest considering CMA as a cause of common infant symptoms. Seven recommend strict maternal cow's milk exclusion for managing common symptoms in breastfed infants. We found CMA proven by food challenge affects approximately 1% of infants, while troublesome crying, vomiting, or rashes are each reported in 15% to 20% of infants. We found clinical trials do not provide consistent support for using maternal or infant cow's milk exclusion to manage common symptoms in infants without proven CMA. We estimated that for more than 99% infants with proven CMA, the breastmilk of a cow's milk-consuming woman contains insufficient milk allergen to trigger an allergic reaction. Three CMA guidelines were directly supported by formula manufacturers or marketing consultants, and 81% of all guideline authors reported a conflict of interest with formula manufacturers. Recommendations to manage common infant symptoms as CMA are not evidence based, especially in breastfed infants who are not directly consuming cow's milk. Such recommendations may cause harm by undermining confidence in breastfeeding.


Enhancement of oxidative stress tolerance in transgenic tobacco plants overproducing Fe-superoxide dismutase in chloroplasts.
A chimeric gene consisting of the coding sequence for chloroplastic Fe superoxide dismutase (FeSOD) from Arabidopsis thaliana, coupled to the chloroplast targeting sequence from the pea ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit, was expressed in Nicotiana tabacum cv Petit Havana SR1. Expression of the transgenic FeSOD protected both the plasmalemma and photosystem II against superoxide generated during illumination of leaf discs impregnated with methyl viologen. By contrast, overproduction of a mitochondrial MnSOD from Nicotiana plumbaginifolia in the chloroplasts of cv SR1 protected only the plasmalemma, but not photosystem II, against methyl viologen (L. Slooten, K. Capiau, W. Van Camp, M. Van Montagu, C. Sybesma, D. Inzé [1995] Plant Physiol 107: 737-750). The difference in effectiveness correlates with different membrane affinities of the transgenic FeSOD and MnSOD. Overproduction of FeSOD does not confer tolerance to H2O2, singlet oxygen, chilling-induced photoinhibition in leaf disc assays, or to salt stress at the whole plant level. In nontransgenic plants, salt stress led to a 2- to 3-fold increase in activity, on a protein basis, of FeSOD, cytosolic and chloroplastic Cu/ZnSOD, ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. In FeSOD-overproducing plants under salt stress, the induction of cytosolic and chloroplastic Cu/ZnSOD was suppressed, whereas induction of a water-soluble chloroplastic ascorbate peroxidase isozyme was promoted.


FMR1 CGG Repeats and Stress Influence Self-Reported Cognitive Functioning in Mothers.
Variation in the FMR1 gene may affect aspects of cognition, such as executive function and memory. Environmental factors, such as stress, may also negatively impact cognitive functioning. Participants included 1,053 mothers of children with and without developmental disabilities. Participants completed self-report measures of executive function, memory, and stress (i.e., life events, parenting status), and provided DNA to determine CGG repeat length (ranging from 7 to 192 CGGs). Stress exposure significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems. Cubic CGG effects independently predicted executive function and memory difficulties, suggesting effects of both genetic variation and environmental stress exposure on cognitive functioning.


Electrophysiologic characteristics and catheter ablation results of tachycardia-induced cardiomyopathy in children with structurally normal heart.
The aim of this study is to present electrophysiologic characteristics and catheter ablation results of tachycardia-induced cardiomyopathy (TIC) in children with structurally normal heart. We performed a single-center retrospective review of all pediatric patients with TIC, who underwent an electrophysiology study and ablation procedure in our clinic between November 2013 and January 2019. A total of 26 patients, 24 patients with single tachyarrhythmia substrates and two patients each with two tachyarrhythmia substrates, resulting with a total of 28 tachyarrhythmia substrates, underwent ablation for TIC. The median age was 60 months (2-214 months). Final diagnoses were supraventricular tachycardia (SVT) in 24 patients and ventricular tachycardia (VT) in two patients. The most common SVT mechanisms were focal atrial tachycardia (31%), atrioventricular reentrant tachycardia (27%), and permanent junctional reciprocating tachycardia (15%). Radiofrequency ablation (RFA) was performed in 15 tachyarrhythmia substrates, and cryoablation was performed in 13 tachyarrhythmia substrates, as the initial ablation method. Acute success in ablation was achieved in 24 out of 26 patients (92%). Tachycardia recurrence was observed in two patients (8%) on follow-up, who were treated successfully with repeated RFA later on. Overall success rates were 92% (24 out of 26) in patients and 93% (26 out of 28) in substrates. On echocardiography controls, the median left ventricular recovery time was 3 months (1-24 months), and median reversible remodeling time was 6 months (3-36 months). TIC should be kept in mind during differential diagnosis of dilated cardiomyopathy. Pediatric TIC patients can be treated successfully and safely with RFA or cryoablation. With an early diagnosis of TIC and quick restoration of the normal sinus rythm, left ventricular recovery, and remodeling may be facilitated.


Otitis media with effusion in children.
Up to 80% of children have been affected by otitis media with effusion (OME) by the age of 4 years, but prevalence declines beyond 6 years of age. Non-purulent middle-ear infections can occur in children or adults after upper respiratory tract infection or acute otitis media. Half or more of cases resolve within 3 months and 95% within 1 year, but complications such as tympanic membrane perforation, tympanosclerosis, otorrhoea, and cholesteatoma can occur. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent otitis media with effusion in children? What are the effects of pharmacological, mechanical, and surgical interventions to treat otitis media with effusion in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found one systematic review and one RCT that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: adenoidectomy, antibiotics, antihistamines, autoinflation, bottle feeding, decongestants, exposure to other children, intranasal corticosteroids, mucolytics, oral corticosteroids, passive smoking, and ventilation tubes.


Skin-sparing mastectomy with immediate breast reconstruction.
Skin-sparing mastectomy with immediate reconstruction has become popular with patients because compared to delayed reconstruction it improves the cosmetic result and reduces cost and anesthetic risk. In one stage, it completes most of the surgical treatment the patient will ever require for treatment of her breast cancer. It eliminates the need to live with the deformity caused by mastectomy and thereby contributes to a more positive body image. It does not increase the risk of local or regional recurrence and when properly performed, especially with autogenous tissue, does not interfere with adjuvant therapy. We believe strongly that skin-sparing mastectomy with immediate reconstruction is a significant advance in the treatment of breast cancer: it provides patients an improved cosmetic outcome with less emotional trauma and morbidity. We encourage qualified surgeons to use this method of breast reconstruction whenever possible.


Proline-rich sequences mediate the interaction of the Arg protein tyrosine kinase with Crk.
Arg is a ubiquitously expressed member of the Abelson family of nonreceptor protein-tyrosine kinases. Defining the Arg sequences that mediate its interaction with other proteins is essential to elucidating its role in cellular signaling. In this report we demonstrate that Arg associates with c-Crk, an adaptor protein composed of an SH2 domain and two SH3 domains, and examine the molecular mechanism of the interaction. In vitro experiments revealed that three proline-rich sequences with distinct specificities for SH3 domains are located in the Arg C-terminal domain, just C-terminal to the kinase domain, and that two of these sequences bind to the Crk N-terminal SH3 domain. These two sequences conform to the PxLPxK/R motif that has been observed in other proteins that bind the Crk N-terminal SH3 domain. The interaction of Arg with c-Crk in living cells was confirmed by the detection of coimmunoprecipitation in coinfected Sf9 cells. In addition, increased phosphorylation of c-Crk was observed in cotransfected COS cells, indicating that Crk is an Arg substrate. The site of c-Crk phosphorylation by Arg was identified as tyrosine 221, a residue whose modification has been shown to result in an intramolecular SH2 interaction and a folded conformation. These experiments extend the known Arg protein interacting motifs to include SH3 binding sites and suggest that Arg may function as an effector as well as a regulator of Crk activity.


Radioprotective effect of hypothermia on cells - a multiparametric approach to delineate the mechanisms.
Low temperature (hypothermia) during irradiation of cells has been reported to have a radioprotective effect. The mechanisms are not fully understood. This study further investigates the possible mechanisms behind hypothermia-mediated radioprotection. Human lymphoblastoid TK6 cells were incubated for 20 min at 0.8 or 37°C and subsequently exposed to 1 Gy of γ- or X-rays. The influence of ataxia telangiectasia mutated (ATM)-mediated double-strand break signalling and histone deacetylase-dependent chromatin condensation was investigated using the micronucleus assay. Furthermore, the effect of hypothermia was investigated at the level of phosphorylated histone 2AX (γH2AX) foci, clonogenic cell survival and micronuclei in sequentially-harvested cells. The radioprotective effect of hypothermia (called the temperature effect [TE]) was evident only at the level of micronuclei at a single fixation time, was not influenced by the inhibition of ATM kinase activity and completely abolished by the histone deacetylase inhibition. No TE was seen at the level of γH2AX foci and cell survival. We suggest that low temperature during irradiation can induce a temporary cell cycle shift, which could lead to a reduced micronucleus frequency. Future experiments focused on cell cycle progression are needed to confirm this hypothesis.


Pathogenicity of a QX strain of infectious bronchitis virus in specific pathogen free and commercial broiler chickens, and evaluation of protection induced by a vaccination programme based on the Ma5 and 4/91 serotypes.
The aims of this study were firstly to evaluate the pathogenicity of an Italian isolate of the QX strain of infectious bronchitis (IB) virus using 1-day-old female specific pathogen free chicks (layer type) and 1-day-old female commercial broiler type chickens, and secondly to assess the level of protection induced in these birds by a vaccination programme including the IB Massachusetts and 4/91 serotype live attenuated vaccines. Unvaccinated birds showed clinical signs of varying severity, predominantly affecting the upper respiratory tract. Vaccinated birds appeared healthy, with the exception of a very mild conjunctivitis affecting a limited number of the broilers. Vaccination fully protected specific pathogen free birds, since no histopathological lesions were observed, nor was virus detected following challenge. In broilers, replication of the challenge virus was not prevented but was significantly reduced. This study confirms that vaccination at 1 day old and at 14 days of age using the Ma5 and 4/91 IB vaccines may be instrumental in reducing the economic impact of QX IB virus infections in layer and broiler farms.


Management of arthropathy in inflammatory bowel diseases.
The most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) is articular involvement, with a prevalence ranging between 17% and 39%. It is frequently characterized by an involvement of the axial joints but may also be associated with peripheral arthritis. The target of therapy in the management of arthritis associated with IBD is to reduce the inflammation and prevent any disability and/or deformity. This requires active cooperation between gastroenterologist and rheumatologist. The treatment of axial involvement has focused on the combination of exercise with nonsteroidal anti-inflammatory drugs. Immunomodulators have been efficacious in patients with peripheral arthritis and other extra-intestinal manifestations, but they are not effective for the treatment of axial symptoms of spondylitis. Tumor necrosis factor (TNF) α inhibitors have been proven to be highly effective in the treatment of IBD patients which are steroid-dependent or refractory to conventional therapy and in patients with associated articular manifestations. The treatment of peripheral involvement and/or enthesitis and/or dactylitis is based on local steroid injections, while sulfasalazine and/or low doses of systemic steroids may be useful in case of inadequate response to intra-articular steroids. Sulfasalazine induces only a little improvement in peripheral arthritis. Immunomodulators such as methotrexate, azathioprine, cyclosporine and leflunomide show their efficacy in some patients with peripheral arthritis and other extra-intestinal components. TNF-α inhibitors should be considered the first-line therapeutic approach when moderate-to-severe luminal Crohn's disease or ulcerative colitis is associated with polyarthritis. The aim of this review is to provide a fair summary of current treatment options for the arthritis associated with IBD.


Loss of (2'-5')oligoadenylate synthetase activity by production of antisense RNA results in lack of protection by interferon from viral infections.
An expression vector was constructed that carries part of the human BK papovavirus with 0.5 kilobases of (2'-5')oligoadenylate (2-5A) synthetase cDNA inserted in inverted orientation downstream from the virion proteins (VP) promoter and the neomycin-resistance gene neo under the control of a simian virus 40 promoter. Cells transfected with this vector and selected for resistance to the neomycin derivative G418 synthesized RNA complementary to 2-5A synthetase mRNA. These cells lacked 2-5A synthetase activity, and the enzyme was not inducible by interferon. In contrast, 2-5A synthetase was induced in cells transfected with a control vector without the cDNA insert. Such cells were protected by interferon from RNA viruses, whereas cells lacking 2-5A synthetase were not protected from encephalomyocarditis virus, vesicular stomatitis virus, and Sindbis virus but were fully protected from influenza virus. These findings show that a high level of 2-5A synthetase is required for interferon-induced protection from the cytoplasmic RNA viruses tested.


A comparison of the efficacy of long-acting beta 2-agonists: eformoterol via Turbohaler and salmeterol via pressurized metered dose inhaler or Accuhaler, in mild to moderate asthmatics. Force Research Group.
Four hundred and sixty nine patients were randomized to receive either 12 micrograms bd of eformoterol (Oxis, Astra Pharmaceuticals Ltd., Kings Langley, U.K.) delivered via Turbohaler or 50 micrograms bd salmeterol (Serevent, Glaxo-Wellcome Ltd., Uxbridge, U.K.) via either the Accuhaler (Glaxo-Wellcome Ltd.) or pressurized metered dose inhaler (pMDI, Glaxo-Wellcome Ltd.) for 8 weeks. This was followed by a 4-week cross-over period when patients who had received salmeterol in the previous 8 weeks were given eformoterol and patients who had received eformoterol were given either salmeterol via the Accuhaler or pMDI to assess patient device and treatment preference. For the primary efficacy variable, the increase in peak expiratory flow (PEF) rate from run-in to 8 weeks, similar significant improvements were seen in all three treatment groups. Eformoterol Turbohaler (FT) achieved a greater increase in morning PEF than salmeterol Accuhaler (SA) from randomisation to 4 weeks; the increase shown in the eformoterol Turbohaler group was 28.9 l min-1 compared to 19.9 l min-1 for the salmeterol Accuhaler group. The addition of eformoterol Turbohaler 12 micrograms bd, to patients' existing asthma therapy was found to have a significantly more beneficial effect on the severity of patients' daytime asthma symptoms than had salmeterol Accuhaler 50 micrograms bd (P = 0.014). Eformoterol Turbohaler reduced the severity of daytime asthma symptoms by 42% after only 4 weeks of treatment. The patients in the eformoterol Turbohaler treated group experienced a higher percentage of days when they were symptom-free and did not use their short-acting bronchodilator to relieve symptoms (32.8, 24.1 and 28.0% in the FT, SA and SM groups, respectively). At 8 weeks there were no significant differences in any of these variables between the three groups. Patients in all the treatment groups gained an additional 1-1.5 nights undisturbed by asthma per week. The changes in sleep disturbance were not significantly different between the three treatment groups. In addition to the therapeutic benefits provided by eformoterol Turbohaler the device (Turbohaler) was the significant preference of patients given both Turbohaler and pMDI (P = 0.0168) and was also considered to be significantly more convenient to carry around than the Accuhaler (P < 0.0001). No other differences were found between the three devices. The results of this study demonstrate that the addition of a long-acting B2-agonist is an effective tool for achieving the goals of asthma treatment. Eformoterol via the Turbohaler is at least as effective as salmeterol via either the Accuhaler or the pMDI in achieving these goals.


Improving Agreement About Intervention Plans in Probation by Decision Support.
Reliability in decision making about intervention plans is a necessary condition for evidence-based probation work and equal treatment of offenders. Structuring decision making can improve agreement between clinical decision makers. In a former study however, we found that in Dutch probation practice structured risk and needs assessment did not result in acceptable agreement about intervention plans. The Dutch probation services subsequently introduced a tool for support in decision making on intervention plans. This article addresses the question whether the use of this tool results in better agreement between probation officers. A significant and meaningful improvement in agreement was found on all domains of the intervention plan. Implications for probation practice are discussed.


Adult rhabdomyosarcoma: cross-sectional imaging findings including histopathologic correlation.
The purpose of our study was to present the MRI and CT features of adult rhabdomyosarcomas with histopathologic correlation. Forty-nine sequential cases were incorporated over a 5-year period from the sarcoma unit database. Twenty-six patients had adequate imaging (16 MRI, 10 CT) and histopathology available for retrospective review. The alveolar subtype was present in 13 patients, embryonal subtype in four patients, and pleomorphic subtype in nine patients. On both CT and T1-weighted MRI, all tumors were isodense to skeletal muscle, although enhancement was variable after the administration of IV contrast material. Pleomorphic tumors were very high signal on T2-weighted/STIR imaging, and both pleomorphic and alveolar subtypes were extremely heterogeneous. Embryonal tumors were more homogeneous. Although adult rhabdomyosarcomas have certain imaging appearances in common with other soft-tissue sarcomas, features at presentation such as tumor heterogeneity, site, regional lymphadenopathy, and pulmonary metastasis should make the radiologist consider this important diagnosis.


Asymptomatic carotid artery stenosis treated with medical therapy alone: temporal trends and implications for risk assessment and the design of future studies.
The rate of adverse clinical outcomes among patients with asymptomatic carotid stenosis receiving medical therapy alone can be used to guide clinical decision-making and to inform future research. We aimed to investigate temporal changes in the incidence rate of clinical outcomes among patients with asymptomatic carotid stenosis receiving medical therapy alone and to explore the implications of these changes for the design of future comparative studies. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, US Food and Drug Administration documents, and reference lists of included studies (last search: December 31, 2012). We selected prospective cohort studies of medical therapy for asymptomatic carotid artery stenosis and we extracted information on study characteristics, risk of bias, and outcomes. We performed meta-analyses to estimate summary incidence rates, meta-regressions to assess trends over time, and simulations to explore sample size requirements for the design of future studies comparing new treatments against medical therapy. The main outcomes of interest were ipsilateral stroke, any stroke, cardiovascular death, death, and myocardial infarction. We identified 41 studies of medical therapy for patients with asymptomatic carotid stenosis (last recruitment year: 1978-2009). The summary incidence rate of ipsilateral carotid territory stroke (25 studies) was 1.7 per 100 person-years. This incidence rate was significantly lower in recent studies (last recruitment year from 2000 onwards) as compared to studies that ended recruitment earlier (1.0 vs. 2.3 events per 100 person-years; p < 0.001). The incidence rates of any territory stroke (17 studies), cardiovascular death (6 studies), death (13 studies), and myocardial infarction (5 studies) were 2.7, 4.1, 4.6, and 1.8 per 100 person-years, respectively. Simulations showed that future studies would need to enroll large numbers of patients with a relatively high incidence rate under medical therapy, and evaluate interventions with large effect sizes, to have adequate power to reliably detect treatment effects. Improved prognosis under medical therapy alone has narrowed the potential range of risk reduction attainable with new treatments for asymptomatic carotid stenosis. Future comparative studies will need to enroll large numbers of patients to assess treatment effectiveness.


Validation of a multi-sensor activity monitor for assessing sleep in children and adolescents.
To assess the validity of a multi-sensor activity monitor in estimating sleep and wake compared to polysomnography in children and adolescents. A total of 43 children and adolescents (29 boys, 14 girls), aged 7-17years (mean age [SD] = 11.0 [2.4] years) participated in the study. Participants wore the SenseWear Pro(3) Armband™ (SWA) body monitor (BodyMedia Inc) during an overnight polysomnographic assessment in a paediatric sleep laboratory. Sleep measures included sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE). No systematic bias of the SWA was noted for any of the sleep measures assessed, but limits of agreement were wide and amounted to -76 to +58min for SOL, -75 to 102min for WASO, -109 to +99min for TST and -22 to +20% for SE. In addition, no effect of gender, age group (children versus adolescents) or overweight on the accuracy of the SWA was found. The SenseWear Armband™ showed good agreement with polysomnography at the group level, while at the individual level rather, poor agreement between the two methods was observed. Consequently, at this point the use of the SWA in the clinical evaluation of sleep cannot be advocated.


Efficacy and Safety of Agents in IgA Nephropathy: An Update Network Meta-Analysis.
The present network meta-analysis of randomized controlled trials (RCTs) was to explore the efficacy and safety of different pharmacologic interventions in IgA nephropathy with proteinuria more than 0.75 g/d. We systematically searched the Cochrane Library, Embase, and PubMed database for studies compared the rate of clinical remission and/or serious adverse events in IgA nephropathy patients with proteinuria (> 0.75 g/d) up to August 1, 2018. We ranked the comparative effects of all drugs against placebo on the surface under the cumulative ranking area (SUCRA) probabilities. There were 29 RCTs comprising 2517 participants included for the comparisons of 9 interventions. The rank of the most effective treatments for inducing clinical remission was renin-angiotensin system inhibitors (RASi) in combination with steroid, tonsillectomy combined with steroid pulse therapy, and azathioprine plus RASi with SUCRA of 82.9%, 80.5%, and 67.6%, respectively. RASi in combination with steroid (SUCRA 3.9%) was the most effective in prevention of end-stage renal disease or doubling serum creatinine, followed by RASi monotherapy (SUCRA 38.4%) and azathioprine combined with steroid (SUCRA 49.0%). As for the occurrence of serious adverse events, azathioprine combined with RASi (SUCRA 88.0%) and steroid plus RASi (SUCRA 74.6%) showed the first and second highest incidence of adverse events, respectively. RASi combined with steroid demonstrated the most effective therapeutic approach for IgA nephropathy patients in terms of reducing proteinuria and stabilizing renal function.


Building global change resilience: Concrete has the potential to ameliorate the negative effects of climate-driven ocean change on a newly-settled calcifying invertebrate.
Global climate change is driving sea level rise and increasingly frequent storm events, which are negatively impacting rapidly-growing coastal communities. To mitigate these impacts, coastal infrastructure must be further protected by upgrading hard defences. We propose that incorporating pH-buffering materials into these upgrades could safeguard marine organisms from the adverse effects of ocean acidification and ocean warming during the vulnerable transition from planktonic larvae to benthic juveniles. To test this, we examined the effects of ocean warming (24 or 27 °C), ocean acidification (pH 8.1, 7.9, 7.7), and substratum (concrete, greywacke, granite) in all combinations on the settlement success of an ecologically and commercially important sea urchin, Tripneustes gratilla. Low pH (7.9, 7.7) generally reduced the quantity and size of juveniles four weeks post-settlement, although this was partially ameliorated by increased temperature (24 vs. 27 °C). In the warmed and acidified treatments, settlement rates were lower on concrete than granite or greywacke, but two weeks post-settlement, juveniles on concrete were larger, and had longer spines and higher survival rates than on greywacke or granite, respectively. The benefits provided by concrete to newly-settled juveniles may be related to alkali chemicals leaching from concrete buffering low pH conditions in surrounding seawater and/or increased availability of bicarbonate in the boundary layers around its surface. Our results highlight the potential for pH-buffering materials to assist marine organisms in coping with the effects of changing ocean conditions, but further research is required to understand the generality and mechanism(s) driving the beneficial effects of concrete and to test pH-buffering materials in the field.


Juvenile rheumatoid arthritis: physical therapy and rehabilitation.
Juvenile arthritis is one of the most prevalent chronic diseases in the childhood period (ages 0 to 16 years). This disease was first defined in the first half of the 16th century. In the course of time, its differential diagnosis and characteristics have been determined, and it has been classified. Incidence and prevalence values are 10 to 20 in 100,000 and 56 to 113 in 100,000, respectively. Various factors are suggested for its underlying cause. Its denomination is also in dispute. Treatment of juvenile arthritis includes education, medical treatment, physical therapy, and occupational therapy. This article summarizes the objectives and methods of physical therapy and rehabilitation that are important parts of treatment.


Risk factors for idiopathic frozen shoulder.
Idiopathic frozen shoulder is a self-limiting regional skeletal problem of unknown etiology. Clinically, patients first experience a phase of pain, progressing to a freezing stage when glenohumeral motion is lost, followed by a thawing phase when pain gradually subsides and most of the lost motion returns. To identify possible specific and non-specific risk factors for idiopathic frozen shoulder. We compared the medical histories, drug treatment, previous hospital as well as health management organization blood tests of 126 new consecutive frozen shoulder patients from a shoulder clinic to those of an age-matched control group of 98 consecutive patients from an orthopedic foot and ankle clinic and to the regional population disease prevalence registry. Frozen shoulder was classified as idiopathic only if there was no history of trauma and no evidence of a rotator cuff tear. Among the frozen shoulder patients 29.4% had diabetes and 13.5% had thyroid disorders. The risk ratio for diabetes in the frozen shoulder group was 5.9 for males (95% confidence interval 4.1-8.4, P< 0.001) and 5.0 for females (95% CI 3.3-7.5, P< 0.001). The risk ratio for thyroid disorders among females with frozen shoulder was 7.3 (95% CI 4.8-11.1, P= 0.001). No significant difference was found in the prevalence of thyroid disorders between frozen shoulder and the control group, but there was a significantly higher prevalence of diabetes in males and a trend for higher prevalence in females in the frozen shoulder group. Physicians should be aware that diabetes is a specific risk factor for idiopathic frozen shoulder in both males and females and thyroid disorders are a non-specific risk factor in females only.


Current Considerations in the Diagnosis and Treatment of Circadian Rhythm Sleep-Wake Disorders in Children.
Circadian Rhythm Sleep-Wake Disorders (CRSWDs) are important sleep disorders whose unifying feature is a mismatch between the preferred or required times for sleep and wakefulness and the endogenous circadian drives for these. Their etiology, presentation, and treatment can be different in pediatric patients as compared to adults. Evaluation of these disorders must be performed while viewed through the lens of a patient's comorbid conditions. Newer methods of assessment promise to provide greater diagnostic clarity and critical insights into how circadian physiology affects overall health and disease states. Effective clinical management of CRSWDs is multimodal, requiring an integrated approach across disciplines. Therapeutic success depends upon appropriately timed nonpharmacologic and pharmacologic interventions. A better understanding of the genetic predispositions for and causes of CRSWDs has led to novel clinical opportunities for diagnosis and improved therapeutics.


Impact of Sodium Bicarbonate-Buffered Lidocaine on Patient Pain During Image-Guided Breast Biopsy.
This randomized, double-blind controlled study evaluated the effectiveness of sodium bicarbonate-buffered lidocaine on reducing pain during imaging-guided breast biopsies. This prospective, HIPAA-compliant study randomly assigned 85 women undergoing ultrasound- or stereotactic-guided core-needle breast biopsies to receive intradermally and intraparenchymally either 1% lidocaine buffered with sodium bicarbonate (9:1 ratio) (bicarbonate study group) or 1% lidocaine alone (control group). Pain was evaluated using a 0-to-10 Likert pain scale during both intradermal and intraparenchymal anesthesia injections and during tissue sampling. Prebiopsy breast pain, anxiety, medical history, demographics, biopsy type, radiologist level of training, breast density, and lesion histology were recorded. Data were analyzed using analysis of variance and analysis of covariance. Unadjusted mean pain scores were 1.47 and 2.07 (study and control groups, respectively; P = .15) during intradermal injections, and 1.84 and 2.98 (study and control groups, respectively; P = .03) during intraparenchymal injections. Tissue sampling mean pain scores were .81 and 1.71 (study and control groups, respectively; P = .07). Moderator analyses found (1) among patients with preprocedural pain, those in the bicarbonate group experienced less intradermal injection pain (0.85 ± 1.23) than patients in the control group (2.50 ± 2.09); (2) among patients with fatty or scattered fibroglandular tissue, those in the bicarbonate group (1.35 ± 1.95) experienced less intraparenchymal injection pain than the control group (3.52 ± 3.13); and (3) during ultrasound-guided biopsies, patients in the bicarbonate group experienced less tissue-sampling pain (0.23 ± 0.63) than the control group (1.79 ± 3.05). Overall, buffering lidocaine with sodium bicarbonate significantly reduced pain during intraparenchymal injections, and additional pain reduction was found in certain patient subgroups during intradermal injections, intraparenchymal injections, and tissue sampling.


[A nonplanar condenser model for calculating electric fields in membrane proteins].
A method for calculating the transmembrane electric fields in surface and integral proteins of plasma membrane is suggested. It is shown that the function of distribution of electrostatic potential along the length of the membrane channel in protein differs essentially from the linear function. A nonuniform distribution of the electric field in the hydrophobic moiety of the lipid bilayer around the protein was found and the electrostatic interaction of proteins in a bilayer was analyzed. The effect of electric polarization on proteins and lipids was estimated. The mechanisms of formation of "lipid rings" around the proteins was explained. The shape and size of the membrane protein are predicted that is able to perform unilateral transfer across the membrane of neutral molecules possessing the dipole moment.


Acetyl-CoA:benzylalcohol acetyltransferase--an enzyme involved in floral scent production in Clarkia breweri.
Volatile esters impart distinct characteristics to the floral scent of many plants, and are important in attracting insect pollinators. They are also important flavor compounds in fruits. The ester benzylacetate is a major constituent of the floral scent of Clarkia breweri, an annual plant native to California. The enzyme acetyl-CoA:benzylalcohol acetyltransferase (BEAT), which catalyzes the formation of benzylacetate, has been purified from C. breweri petals, and a cDNA encoding this enzyme has been isolated and characterized. The sequence of the 433-residue BEAT protein does not show high similarity to any previously characterized protein, but a 35-residue region from position 135-163 has significant similarity (42-56% identity) to several proteins known or suspected to use an acyl-CoA substrate. E. coli cells expressing C. breweri BEAT produced enzymatically active protein, and also synthesized benzylacetate and secreted it into the medium. Of the different parts of the C. breweri flower, petals contained the majority of BEAT transcripts, and no BEAT mRNA was detected in leaves. The levels of BEAT mRNA in the petals increased as the bud matured, and peaked at anthesis, paralleling changes in BEAT activity. However, three days after anthesis, mRNA levels began a steep decline, whereas BEAT activity remained high for the next two days, suggesting that the BEAT protein is relatively stable.


Elimination of 7-aminoflunitrazepam and flunitrazepam in urine after a single dose of Rohypnol.
The hypnotic benzodiazepine flunitrazepam (Rohypnol) has been identified as the drug of choice for the purposes of "drugging" unsuspecting victims and raping them while they are under the influence of this substance. The objective of this paper was to study elimination of flunitrazepam and 7-aminoflunitrazepam in urine collected from ten healthy volunteers who received a single 2 mg oral dose of Rohypnol, to determine how long after drug administration 7-aminoflunitrazepam can be detected. A highly sensitive NCI-GC-MS method for the simultaneous quantitation of flunitrazepam (LOQ 100 pg/mL) and 7-aminoflunitrazepam (LOQ 10 pg/mL) in urine was developed. All samples were screened for benzodiazepines using optimized micro-plate enzyme immunoassay. The highest concentrations of 7-aminoflunitrazepam (70-518 ng/mL) and flunitrazepam (0.7-2.8 ng/mL) in urine were observed 6 h after drug administration in nine subjects and after 24 h in one subject. In six subjects 7-aminoflunitrazepam was detected up to 14 days after flunitrazepam administration, in one subject up to 21 days and in three subjects up to 28 days. In urine samples collected from six volunteers, flunitrazepam was detected three days after Rohypnol intake, in three subjects 24 h, and in one subject 5 days later. Benzodiazepine micro-plate enzyme immunoassay kit allowed the detection of flunitrazepam and metabolities 5 to 21 days after drug administration.


Comparison of cauliflower mosaic virus 35S and nopaline synthase promoters in transgenic plants.
We have compared the level of expression of the Cauliflower Mosaic Virus 35S promoter and the nopaline synthase promoter when fused to a common reporter gene. A cassette containing the neomycin phosphotransferase (type II) coding sequence followed by the nopaline synthase 3' nontranslated region was used for transcriptional and translational evaluation of the two different promoters. These chimeric genes were introduced into petunia plants and the copy number of the gene, the steady state level of NPTII transcript and the levels of NPTII enzyme activity were determined. In this paper, we report that the NPT II transcript levels are on the average 30 fold higher in plants containing CaMV 35S promoter and leader sequences than in plants containing the same reporter gene but nopaline synthase promoter and leader sequences. Similarly, plants containing the CaMV 35S promoter had an average of 110 fold higher levels of NPTII enzyme activity than those containing the nopaline synthase promoter. The significance of these results for expression of foreign genes in plants is discussed. In addition, we describe the construction of a convenient plant expression cassette vector (pMON316) which utilizes the CaMV 35S promoter.


Effectiveness of mindfulness-based stress reduction in mood, breast- and endocrine-related quality of life, and well-being in stage 0 to III breast cancer: a randomized, controlled trial.
To assess the effectiveness of mindfulness-based stress reduction (MBSR) for mood, breast- and endocrine-specific quality of life, and well-being after hospital treatment in women with stage 0 to III breast cancer. A randomized, wait-listed, controlled trial was carried out in 229 women after surgery, chemotherapy, and radiotherapy for breast cancer. Patients were randomly assigned to the 8-week MBSR program or standard care. Profile of Mood States (POMS; primary outcome), Functional Assessment of Cancer Therapy-Breast (FACT-B), Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) scales and the WHO five-item well-being questionnaire (WHO-5) evaluated mood, quality of life, and well-being at weeks 0, 8, and 12. For each outcome measure, a repeated-measures analysis of variance model, which incorporated week 0 measurements as a covariate, was used to compare treatment groups at 8 and 12 weeks. There were statistically significant improvements in outcome in the experimental group compared with control group at both 8 and 12 weeks (except as indicated) for POMS total mood disturbance (and its subscales of anxiety, depression [8 weeks only], anger [12 weeks only], vigor, fatigue, and confusion [8 weeks only]), FACT-B, FACT-ES, (and Functional Assessment of Cancer Therapy subscales of physical, social [8 weeks only], emotional, and functional well-being), and WHO-5. MSBR improved mood, breast- and endocrine-related quality of life, and well-being more effectively than standard care in women with stage 0 to III breast cancer, and these results persisted at three months. To our knowledge, this study provided novel evidence that MBSR can help alleviate long-term emotional and physical adverse effects of medical treatments, including endocrine treatments. MBSR is recommended to support survivors of breast cancer.


Viral membrane glycoproteins: comparison of the amino terminal amino acid sequences of the precursor and mature glycoproteins of three serotypes of vesicular stomatitis virus.
The NH2-terminal amino acid sequences of the envelope glycoproteins and the in vitro synthesized, nonglycosylated precursors of the glycoproteins of three serotypes, namely Indiana (Toronto), Cocal, and New Jersey (Concan) of vesicular stomatitis virus were determined. A comparison of the sequences showed little homology in the signal peptides present in the nonglycosylated precursors except for their high hydrophobic amino acid content. In contrast, the NH2-terminal amino acid sequences of the mature envelope glycoproteins revealed extensive homology suggesting that this region is conserved and may be involved in essential biological function(s) of the rhabdovirus.


Anxiety, Depression, and Pain Symptoms: Associations With the Course of Marijuana Use and Drug Use Consequences Among Urban Primary Care Patients.
This exploratory study aims to investigate whether anxiety, depression, and pain are associated with changes in marijuana use and drug use consequences among primary care patients. In all, 331 adult primary care patients with marijuana as the only drug used were followed prospectively to investigate associations between anxiety/depression symptoms (no/minimal symptoms; anxiety or depression symptoms; symptoms of both) and pain (1-10 scale: none [0]; low [1-3]; medium [4-6]; high [7-10]) (independent variables) and substance use outcomes in regression models. These outcomes were changes (over 6 months) in primary outcomes: marijuana use days (past 30); and drug use consequences (Short Inventory of Problems-Drugs [SIP-D]); secondary outcomes-drug use risk (Alcohol, Smoking, and Substance Involvement Screening Test [ASSIST] score for drugs). At baseline, 67% reported no/minimal anxiety/depression symptoms, 16% anxiety or depression symptoms, 17% both; 14% reported no pain, 16% low, 23% medium, 47% high pain level. Mean (SD) number of marijuana use days was 16.4 (11.6), mean SIP-D 5.9 (9.0), mean ASSIST 12.5 (7.8); no significant association was found between anxiety/depression and marijuana use changes. Given the same baseline status for SIP-D and ASSIST, respectively, those with anxiety or depression had greater increases in SIP-D (adjusted mean difference [95% confidence interval] +3.26 [1.20; 5.32], P = 0.004) and borderline significant increases in ASSIST (+3.27 [-0.12; 6.65], P = 0.06) compared with those without anxiety or depression; those with both anxiety and depression had greater increases in ASSIST (+5.42 [2.05; 8.79], P = 0.003), but not SIP-D (+1.80 [-0.46; 4.06], P = 0.12). There was no significant association between pain and marijuana use and SIP-D changes. Given the same baseline ASSIST level, those with high pain level had greater increases in ASSIST (+4.89 [1.05; 8.72], P = 0.04) compared with those with no pain. In these exploratory analyses, anxiety, depression, and high pain level appear to be associated with increases in drug-related harm among primary care patients using marijuana.


Impact of cross-linking of polymers on transport of salt and water in polyelectrolyte membranes: A mesoscopic simulation study.
Our recent atomistic simulation studies demonstrated that the transport properties of salt ions and water in non-crosslinked polymer electrolyte membrane exhibit an intriguing dependence on salt concentration that is opposite to that seen in electrolyte solutions. Here, we extend our study to probe the influence of the degree of cross-linking of the polymer on the transport properties of salt and water in polymer electrolyte membranes. Towards this objective, we use a coarse-grained model embedded within dissipative particle dynamics (DPD) mesoscale simulations, which allows us to access time scales necessary for studying crosslinked polymer systems. Our DPD simulations on non-crosslinked membranes reproduce results that are in qualitative agreement with our atomistic simulations. For the case of crosslinked membranes, our results demonstrate that the diffusion of salt ions and water is reduced significantly relative to crosslinked systems. However, the trends exhibited by the salt concentration dependence of diffusivities and the coordination of the cations with anions and with the polymer backbone remain qualitatively similar to those observed in non-crosslinked membranes.


Closed-loop decoder adaptation shapes neural plasticity for skillful neuroprosthetic control.
Neuroplasticity may play a critical role in developing robust, naturally controlled neuroprostheses. This learning, however, is sensitive to system changes such as the neural activity used for control. The ultimate utility of neuroplasticity in real-world neuroprostheses is thus unclear. Adaptive decoding methods hold promise for improving neuroprosthetic performance in nonstationary systems. Here, we explore the use of decoder adaptation to shape neuroplasticity in two scenarios relevant for real-world neuroprostheses: nonstationary recordings of neural activity and changes in control context. Nonhuman primates learned to control a cursor to perform a reaching task using semistationary neural activity in two contexts: with and without simultaneous arm movements. Decoder adaptation was used to improve initial performance and compensate for changes in neural recordings. We show that beneficial neuroplasticity can occur alongside decoder adaptation, yielding performance improvements, skill retention, and resistance to interference from native motor networks. These results highlight the utility of neuroplasticity for real-world neuroprostheses.


Observed mechanism for the breakup of small bundles of cellulose Iα and Iβ in ionic liquids from molecular dynamics simulations.
Explicit, all-atom molecular dynamics simulations are used to study the breakup of small bundles of cellulose Iα and Iβ in the ionic liquids [BMIM]Cl, [EMIM]Ac, and [DMIM]DMP. In all cases, significant breakup of the bundles is observed with the initial breakup following a common underlying mechanism. Anions bind strongly to the hydroxyl groups of the exterior strands of the bundle, forming negatively charged complexes. Binding also weakens the intrastrand hydrogen bonds present in the cellulose strands, providing greater strand flexibility. Cations then intercalate between the individual strands, likely due to charge imbalances, providing the bulk to push the individual moieties apart and initiating the separation. The peeling of an individual strand from the main bundle is observed in [EMIM]Ac with an analysis of its hydrogen bonds with other strands showing that the chain detaches glucan by glucan from the main bundle in discrete, rapid events. Further analysis shows that the intrastrand hydrogen bonds of each glucan tend to break for a sustained period of time before the interstrand hydrogen bonds break and strand detachment occurs. Examination of similar nonpeeling strands shows that, without this intrastrand hydrogen bond breakage, the structural rigidity of the individual unit can hinder its peeling despite interstrand hydrogen bond breakage.


Atomistic simulation studies of ionic cyanine dyes: self-assembly and aggregate formation in aqueous solution.
Cyanine dyes are known to form large-scale aggregates of various morphologies via spontaneous self-assembly in aqueous solution, akin to chromonic liquid crystals. Atomistic molecular dynamics simulations have been performed on four cyanine dyes: pseudoisocyanine chloride (PIC), pinacyanol chloride (PCYN), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine chloride (TTBC) and 1,1'-disulfopropyl-3,3'-diethyl-5,5',6,6'-tetrachloro-benzimidazolylcarbocyanine sodium salt (BIC). Simulations employed an optimised general AMBER force field and demonstrate the organisation of the dyes into stacked structures at dilute concentrations. The thermodynamics of self-assembly was studied by calculating potentials of mean force for n-mers (n = 2, 3 or 4), from which the free energies of association are determined. We report binding free energies in the range of 8 to 15kBT for dimerisation, concordant with typical values for ionic chromonics (7 to 14kBT), and examine the enthalpic and entropic contributions to the aggregation process. The self-assembly of these dyes yields two distinct classes of structures. We observe the formation of H-aggregate stacks for PCYN, with further complexity in these assemblies for PIC; where the aggregates contain shift and Y junction defects. TTBC and BIC associate into a J-aggregate sheet structure of unimolecular thickness, and is composed of a brickwork arrangement between molecules. These sheet structures are characteristic of the smectic chromonic mesophase, and such assemblies provide a route to the emergence of nanoscale tubular architectures.


Experimental schistosomiasis, protective aspects of granulomatous reaction in the mouse liver.
We show two mechanisms of liver protection by the granulomatous reaction against Schistosoma mansoni eggs entrapped in the organ. First, eosinophil peroxidase and its substrate H(2)O(2) are released by inflammatory cells in the immediate vicinity of the parasite eggs. The efficiency of this process was demonstrated by administration of antioxidants to infected mice. The treatment, which reduces H(2)O(2) production, significantly improved the ability of parasite eggs to hatch after collection from the liver. Secondly, we labeled the released egg antigens in liver histological sections and we found that the lattice of collagen fibers which is built around eggs appears to create a barrier preventing released compounds from diffusing freely in surrounding tissues. Together, oxidative processes and antigen containment allow the parasitized liver to cope with the dual threat posed by parasite eggs, i.e. a highly resistant chitinous eggshell and the release of toxic substances.


Biopterin in Parkinson's disease.
Tetrahydrobiopterin is an essential co-factor in the natural synthesis of dopamine. Oral tetrahydrobiopterin was given in small doses to four patients with early Parkinson's disease but had no discernible effect.


DNA clone of avian Fujinami sarcoma virus with temperature-sensitive transforming function in mammalian cells.
We have molecularly cloned an integrated proviral DNA of Fujinami sarcoma virus (FSV) into a lambda phage vector and further subcloned it into plasmid pBR322. The source of provirus was a quail nonproducer cell clone transformed by FSV. The FSV strain used is temperature sensitive in the maintenance of transformation of avian cells. The recombinant plasmid was shown to contain an entire FSV genome by fingerprinting the hybrids formed with 32P-labeled FSV RNA. This analysis also revealed a previously undetected env-related sequence in FSV which represents the 3' end of the gp85 env gene. A physical map of cloned FSV DNA identifying sites of several restriction enzymes is described. Upon transfection, FSV DNA cloned in pBR322 transformed mouse NIH-3T3 cells, which proved to be temperature sensitive in maintaining transformation. Phosphorylation but not synthesis of p140, the only known gene product of FSV, was also temperature sensitive in these cells. The correlation between transformation and phosphorylation of p140 suggests that phosphorylation of p140 is necessary for transformation of mouse cells, as was shown previously for avian cells. These results provide direct genetic evidence that the mechanisms for maintaining transformation of mammalian and avian cells involve the same FSV gene product, p140. Homology was detected by hybridization between transformation-specific sequences of FSV DNA and certain restriction endonuclease-resistant fragments of cellular DNA of two avian species, chicken and quail. Under the same conditions homology was also detected with DNA of non-avian species, although apparently to a lower degree than with avian cells.


There and (slowly) back again: entropy-driven hysteresis in a model of DNA overstretching.
When pulled along its axis, double-stranded DNA elongates abruptly at a force of approximately 65 pN. Two physical pictures have been developed to describe this overstretched state. The first proposes that strong forces induce a phase transition to a molten state consisting of unhybridized single strands. The second picture introduces an elongated hybridized phase called S-DNA. Little thermodynamic evidence exists to discriminate directly between these competing pictures. Here we show that within a microscopic model of DNA we can distinguish between the dynamics associated with each. In experiment, considerable hysteresis in a cycle of stretching and shortening develops as temperature is increased. Since there are few possible causes of hysteresis in a system whose extent is appreciable in only one dimension, such behavior offers a discriminating test of the two pictures of overstretching. Most experiments are performed upon nicked DNA, permitting the detachment (unpeeling) of strands. We show that the long-wavelength progression of the unpeeled front generates hysteresis, the character of which agrees with experiment only if we assume the existence of S-DNA. We also show that internal melting can generate hysteresis, the degree of which depends upon the nonextensive loop entropy of single-stranded DNA.


Efficacy of buprenorphine and clonidine in opioid detoxification: A hospital- based study.
The need for effective and accepted method for opioid detoxification is ever increasing. Sublingual buprenorphine and oral clonidine have been effective in opioid detoxification. As often, there is a great variation in the dosage of buprenorphine and clonidine prescribed by the clinicians; hence, there is a felt need to find an effective dosage for a favorable outcome of opioid detoxification. The objective of this study was to compare the effectiveness of different doses of sublingual buprenorphine and clonidine in opioid detoxification. A total of 100 patients with the diagnosis of opioid dependence as per the international classification of diseases-10 criteria were recruited for this study. Participants were assigned randomly into four groups - low-dose clonidine, high-dose clonidine, low-dose sublingual buprenorphine, and high sublingual dose buprenorphine using a computer-generated random number table, resulting in 25, 26, 23, and 26 patients in each group, respectively. The four groups had comparable scores on all the items of "stages of change readiness and treatment eagerness scale" for the assessment of motivation at baseline. Progressive decrease in withdrawal score was seen in all the groups on "clinical opiate withdrawal scale" and "subjective opiate withdrawal scale." From the current study, we can infer that both low and high doses of buprenorphine and clonidine are comparable regarding controlling withdrawal.


Association between genotypes of rs34436714 of NLRP12 and serum tumor necrosis factor-alpha in inflammatory bowel disease: A case-control study.
We aimed to investigate the impact of the single nucleotide polymorphisms of rs34436714 of the NOD-like receptor protein 12 gene on the production of tumor necrosis factor-alpha (TNFα) in patients with inflammatory bowel disease (IBD)In a matched case-control study 90 patients with IBD, 56 with Crohn disease (CD) and 34 with ulcerative colitis, were genotyped and compared to 98 healthy comparators matched for age and gender. Expression level of TNFα, interleukin (IL)-6, IL-12, and soluble triggering receptor expressed on myeloid cells were measured in patients' sera. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated for TNFα production.Serum TNFα was greater among carriers of GT/TT genotypes than GG genotypes of rs34436714. Stimulated TNFα production was also higher in carriers of GT/TT genotypes. The frequency of CD with fistulizing behavior and with CD involving the small intestine was greater among carriers of GT/TT genotypes than of the GG genotype. Distribution of the GG, GT, and TT genotypes of rs34436714 were in Hardy-Weinberg equilibrium in both groups. The genotype distribution was the same in both groups.Carriage of minor frequency alleles of rs34436714 was accompanied by greater circulating levels of TNFα and by greater capacity for stimulated TNFα production by PBMCs. These alleles had an impact on the phenotype of patients with CD.


[Growth and oxidation of sulfur compounds by Thiocapsa roseopersicina in darkness].
The purple sulphur bacterium Thiocapsa roseopersicina, strain BBS, grown in the darkness in aerobic autotrophic conditions, oxidized sulphides to free sulphur and then to sulphates. This was accompanied with the fixation of carbon dioxide by the cells. Addition of glucose to the mineral medium increased the biomass yield; the cells oxidized thiosulphate still at a high rate. These results prove the possibility of switching T. roseopersicina from photosynthesis to a dark chemolithautotrophic way of life.


Genome Sequence Analysis of Vibrio cholerae clinical isolates from 2013 in Mexico reveals the presence of the strain responsible for the 2010 Haiti outbreak.
The first week of September 2013, the National Epidemiological Surveillance System identified two cases of cholera in Mexico City. The cultures of both samples were confirmed as Vibrio cholerae serogroup O1, serotype Ogawa, biotype El Tor. Initial analyses by pulsed-field gel electrophoresis and by polymerase chain reaction-amplification of the virulence genes, suggested that both strains were similar, but different from those previously reported in Mexico. The following week, four more cases were identified in a community in the state of Hidalgo, located 121 km northeast of Mexico City. Thereafter a cholera outbreak started in the region of La Huasteca. Genomic analyses of the strains obtained in this study confirmed the presence of pathogenicity islands VPI-1 and VPI-2, VSP-1 and VSP-2, and of the integrative element SXT. The genomic structure of the 4 isolates was similar to that of V. cholerae strain 2010 EL-1786, identified during the epidemic in Haiti in 2010. This study shows that molecular epidemiology is a very powerful tool to monitor, prevent and control diseases of public health importance in Mexico.


Electromyographic assessment of neuromuscular blockade induced by atracurium.
The effects of atracurium besylate 0.3 mg kg-1 or 0.6 mg kg-1 on neuromuscular function were assessed by electromyography in 11 normal subjects, using successive trains of four supramaximal stimuli. After the induction of anaesthesia, the relation between the reduction in the amplitude of the compound muscle action potential and decrement was studied during the onset and recovery of nondepolarizing blockade. During induction, the decrease in the amplitude of the initial compound muscle action potential was usually greater than decrement, and resembled the pattern observed with pancuronium. In contrast, during recovery from myoneural blockade, decrement was invariably greater than the reduction in the amplitude of the action potential. It was considered that these effects were consistent with the action of atracurium on more than one group of receptors at the neuromuscular junction. The effects of atracurium were rapidly antagonized by neostigmine, and supplementary doses of the drug showed no evidence of cumulation.


Three-dimensional phase contrast imaging by an annular illumination microscope.
A method of observing 3-D phase structures through a microscope incorporating computer reconstruction is discussed. This microscope is equipped with an annular pupil in illumination optics, but no phase shifter is included in the imaging optics. The sample stage is longitudinally (z-axial) scanned to collect a focus image series. The 3-D phase transfer function is derived and computer-plotted based on Streibl's 3-D image transfer theory under the first-order Born approximation and the mutual intensity propagation theorem. Experimental results of 3-D phase reconstruction are shown with cultured tobacco cells by Helstrom's inverse filtering of the transfer function to a series of focused images.


Nelumbo nucifera synthesized selenium nanoparticles modulate the immune-antioxidants, biochemical indices, and pro/anti-inflammatory cytokines pathways in Oreochromis niloticus infected with Aeromonas veronii.
Bacterial infection is considered one of the major issues in fish culturing that results in economic losses. Metal nanoparticles are a cutting-edge and effective disease management and preventive strategy because of their antibacterial ability. In this investigation, the selenium nanoparticles were prepared by a biological method using Nelumbo nucifera leaves extract. The in-vitro antibacterial activity of N. nucifera synthesized selenium nanoparticles (NN-SeNPs) was tested against Aeromonas veronii. A treatment assay was conducted on 210 Oreochromis niloticus (average body weight: 27 ± 2.00 g). A preliminary approach was conducted on 90 fish for determination of the therapeutic concentration of NN-SeNPs which was found to be 4 mg/L. Fish (n = 120) were categorized into four groups for 10 days; G1 (control) and G2 (NN-SeNPs) were non-challenged and treated with 0 and 4 mg/L NN-SeNPs, respectively. While, G3 and G4 were infected with 2 × 106 CFU/mL of A. veronii and treated with 0 and 4 mg/L NN-SeNPs, respectively. NN-SeNPs exhibited an inhibition zone against A. veronii with a diameter of 16 ± 1.25 mm. The A. veronii infection increased the hepato-renal biomarkers (alanine and aspartate aminotransferases and creatinine) than the control group. An oxidative stress was the consequence of A. veronii infection (higher malondialdehyde and hydrogen peroxide levels with lower glutathione peroxidase superoxide, dismutase, and catalase activity). A. veronii infection resulted in lower immunological biomarker values (immunoglobulin M, lysozyme, and complement 3) with higher expression of the inflammatory cytokines (interleukin-1β and tumor necrosis factor-ɑ) as well as lower expression of the anti-inflammatory cytokines (interleukin-10 and transforming growth factor-β). Therapeutic application with 4 mg/L NN-SeNPs prevented the disease progression; and modulated the hepato-renal function disruptions, oxidant-immune dysfunction, as well as the pro/anti-inflammatory cytokines pathway in the A. veronii-infected fish. These findings suggest that NN-SeNPs, employed as a water therapy, can safeguard fish from the harmful effects of A. veronii and serve as a promising antibacterial agent for sustainable aquaculture.


Effects of a Milk-Based Meal Replacement Program on Weight and Metabolic Characteristics in Adults with Severe Obesity.
Low energy meal replacement regimens can induce short-term weight loss in patients with severe obesity, but usually require specially formulated dietary supplements. We sought to determine the effects of a milk-based meal replacement program on anthropometric and metabolic characteristics in adults with severe obesity. We conducted a retrospective cohort study of patients attending our hospital-based bariatric medicine service who completed a 24-week program consisting of eight weeks of milk-based meal replacement followed by weight stabilisation and maintenance phases. Patients were seen fortnightly by the bariatric physician, nurse and dietitian. We assessed changes in anthropometric and metabolic outcomes in completers at 0, 8, 16 and 24 weeks. Of 105 program completers available for follow-up, 53.3% were female. Mean age was 51.1±11.2 years. Body weight decreased from 144.0±27.6 kg at baseline to 121.1±25.0 kg at 24 weeks (P<0.001), a mean total body weight loss of 15.9±6.0%, with a reduction in body mass index from 50.6±8.0 to 42.6±7.6 kg m-2 (P<0.001). In patients with diabetes, haemoglobin A1c decreased from 66.3±13.0 to 48.3±13.5 mmol/mol (P<0.001) and diabetes medication use decreased significantly. There were significant improvements also in lipid profiles and reductions in antihypertensive medication use. These preliminary findings suggest that completion of a 24-week milk-based meal replacement program has large effects on important outcomes in adults with severe obesity. However, attrition was high. Prospective assessment of the efficacy, safety, durability and cost-effectiveness of this intervention seems warranted.


Eighteen Years' Retrospective Review of Colorectal Cancer Cases in Eastern Population.
We aimed to determine the demographic characteristics of colorectal cases and changes in cancer localization according to years in our region. In the present study, 752 patients diagnosed with colorectal cancer between January 1992 and December 2010 were included. Of all the patients, 427 (56.8%) were males and 325 (43.2%) were females, with a male/female ratio of 1.3/1. The mean age was 56.2±14.9 years. The most commonly encountered complaint at the first application was rectal bleeding (38.4%). The most commonly encountered tumor localizations were in the rectum (55%) and sigmoid colon (18%). In general, tumors were observed to be localized in the right colon at 16.1% and in the left colon at 83.9%. When tumor localizations were compared in the first 10 years of the study with the second 10 years in the present study, it was observed that tumor numbers in the right colon were increased. Cases in our study were diagnosed as Stage IV according to the tumor, node, metastasis (TNM) classification, and liver metastasis was encountered most commonly. Although colorectal cancer cases have been most commonly encountered in the rectum, it has been recently determined that right colon tumor percentages were increased. It was defined that they were generally diagnosed at later stages. Therefore, colorectal cancer incidence may be decreased by the widespread use of endoscopic techniques in the determination of precancerous lesions.


He Pikinga Waiora Kimi Ora lifestyle programme: case study of a successful community-based Indigenous diabetes intervention.
To co-design and implement a whānau-centred, community-based lifestyle programme (Kimi Ora) intended to ensure no worsening of HbA1c and to improve wellbeing for Māori whānau and communities with diabetes or pre-diabetes. Māori healthcare providers, community members, research advisors and wider stakeholders used a co-design process underpinned by He Pikinga Waiora to collaboratively develop and implement Kimi Ora Control group comparisons and participants were recruited from Te Kōhao Health. Multi-method monitoring and collection captured individual, whānau and community data. Kimi Ora was run in two communities in Aotearoa New Zealand. In total, there were 35 participants who took part in an eight-week programme offered five times alongside a comparison group comprising 21 participants. Kimi Ora resulted in significant improvements on all biomedical measures compared to baseline, and participants had gains relative to the comparison group for variables including weight, BMI, blood pressure and waist measurement. Of particular note was the 100% retention rate and sustained community support for Kimi Ora. Outcomes from Kimi Ora demonstrate this programme, which was actively tailored for and worked with Māori communities in a responsive and flexible manner, resulted in successful biomedical outcomes, high engagement and high retention.


Wogonin, a flavonoid isolated from Scutellaria baicalensis, has anti-viral activities against influenza infection via modulation of AMPK pathways.
Wogonin, a flavonoid isolated from Scutellaria baicalensis, has attracted increasing scientific attention in recent years because of its potent anti-tumor activity. Its role during viral infection has largely been unexplored. Wogonin treatment effectively suppressed both influenza A and B virus replication in Madin-Darby Canine Kidney (MDCK) cells and human lung epithelial (A549) cells. In contrast, wogonin treatment following influenza A virus infection led to up-regulation of interferon (IFN)-induced antiviral signaling. Additionally, influenza A virus infection in A549 cells induced 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and activation in a time-dependent manner and wogonin treatment led to the suppression of AMPK phosphorylation. Furthermore, the treatment with AMPK-specific inhibitor (compound C; CC) attenuated influenza A virus replication. These data suggest that wogonin possesses a potent anti-influenza activity mediated by regulation of AMPK activation, suggesting that wogonin has the potential to be developed as an anti-influenza drug.


Overexpression of autotaxin, a lysophosphatidic acid-producing enzyme, enhances cardia bifida induced by hypo-sphingosine-1-phosphate signaling in zebrafish embryo.
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are second-generation lysophospholipid mediators that exert multiple biological functions through their own cognate receptors. They are both present in the blood stream, activate receptors with similar structures (endothelial differentiation gene receptors), have similar roles in the vasculature and are vasoactive. However, it is unclear whether these lysophospholipid mediators cross-talk downstream of each receptor. Here, we provide in vivo evidence that LPA signaling counteracted S1P signaling. When autotaxin (Atx), an LPA-producing enzyme, was overexpressed in zebrafish embryos by injecting atx mRNA, the embryos showed cardia bifida, a phenotype induced by down-regulation of S1P signaling. A similar cardiac phenotype was not induced when catalytically inactive Atx was introduced. The cardiac phenotype was synergistically enhanced when antisense morpholino oligonucleotides (MO) against S1P receptor (s1pr2/mil) or S1P transporter (spns2) was introduced together with atx mRNA. The Atx-induced cardia bifida was prominently suppressed when embryos were treated with an lpar1 receptor antagonist, Ki16425, or with MO against lpar1. These results provide the first in vivo evidence of cross-talk between LPA and S1P signaling.


Surgical timing of the subependymal giant cell astrocytoma (SEGA) with the patients of tuberous sclerosis complex.
Tuberous sclerosis complex has shown a wide variety of clinical, pathologic and radiologic manifestations. Many tumor types are found in tuberous sclerosis, which includes subependimal giant cell astrositoma. The aim of this study is to focus on surgical timing of the tumor. This study included 37 children with tuberous sclerosis presenting to Erciyes Univercity Medical School, whose hospital record were retrospectively evaluated between 1995 and 2010. Of the 5 patients had diagnosed with the subependymal giant cell astrocytoma and three patients were opereted on. In the 27 of the patients had subependimal nodules (73%), cortical tubers were in the 19 patients (51,4%), giant cell astrositoma (SEGA) were in the 5 patients (13,5%). Mental retardation in different level was detected in the 18 patients (48.6%). The other clinical findings of the patients were angiomyolipomas (37.8%), hypomelanotic macules (91.9%), Convulsion (54.1%), adenoma sebaceum (32.4%) , West syndrome (16.22%), shagreeen patch (16.2%), intracardiac tumor (37.8%), subungual fibroma (2.7%), fibroadenom in the neck (2.7%). A multidisciplinary approach is essential for an early, accurate diagnosis and proper management of affected individuals. The early surgical menagement for subependimal giant cell astrocytoma are recommended, and also periodic monitoring even for asymptomatic patients with subependymal nodules.


Clinical detection and movement recognition of neuro signals.
Neuro signal has many more advantages than myoelectricity in providing information for prosthesis control, and can be an ideal source for developing new prosthesis. In this work, by implanting intrafascicular electrode clinically in the amputee's upper extremity, collective signals from fascicules of three main nerves (radial nerve, ulnar nerve and medium nerve) were successfully detected with sufficient fidelity and without infection. Initial analysis of features under different actions was performed and movement recognition of detected samples was attempted. Singular value decomposition features (SVD) extracted from wavelet coefficients were used as inputs for neural network classifier to predict amputee's movement intentions. The whole training rate was up to 80.94% and the test rate was 56.87% without over-training. This result gives inspiring prospect that collective signals from fascicules of the three main nerves are feasible sources for controlling prosthesis. Ways for improving accuracy in developing prosthesis controlled by neuro signals are discussed in the end.


Identifying Qualitative Between-Subject and Within-Subject Variability: A Method for Clustering Regime-Switching Dynamics.
Technological advancement provides an unprecedented amount of high-frequency data of human dynamic processes. In this paper, we introduce an approach for characterizing qualitative between and within-subject variability from quantitative changes in the multi-subject time-series data. We present the statistical model and examine the strengths and limitations of the approach in potential applications using Monte Carlo simulations. We illustrate its usage in characterizing clusters of dynamics with phase transitions with real-time hand movement data collected on an embodied learning platform designed to foster mathematical learning.


Emergency department text messaging for adolescent violence and depression prevention: A pilot randomized controlled trial.
This study's purpose was to evaluate feasibility and acceptability, obtain preliminary efficacy data, and evaluate predictors of improvement with iDOVE, a technology-augmented violence and depression prevention intervention for high-risk adolescents seen in the emergency department (ED). We conducted a pilot randomized controlled trial (RCT) with 116 English-speaking adolescents (ages 13-17 years), presenting to the ED for any reason, who reported past-year physical peer violence and current depressive symptoms. The cognitive-behavioral therapy- and motivational interviewing-based intervention consisted of a brief in-ED intervention session and 8 weeks of automated text-message daily mood queries and tailored responses. The control was a brief in-ED presentation and twice-weekly text messages on healthy behaviors. Follow-up was conducted at 8 and 16 weeks. Descriptive statistics, bivariate comparisons, mixed-effects longitudinal regression models, and latent class models (LCMs) were calculated. iDOVE had high acceptability and feasibility, with 86% of eligible youth consenting (n = 116), 95% completing 8-week follow-up, and 91% completing 16-week follow-up. High quantitative and qualitative satisfaction were reported by intervention and control participants. Comparing intervention to control, improved depressive symptoms (p = .07) and physical peer violence (p = .01) were observed among the more symptomatic youth in the intervention group (but no difference in symptoms between full intervention and control groups). LCMs showed that intervention responsiveness correlated with lower mood (measured through daily text messages) at Day 7 of the intervention. This RCT of a technology-augmented intervention shows high feasibility and acceptability and a promising signal of reduced violence among the highest-risk participants. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Language Growth in Young Children with Autism: Interactions Between Language Production and Social Communication.
Young children with autism spectrum disorder (ASD) present with a broad range of spoken language abilities, as well as delays in precursor skills such as gesture production and joint attention skills. While standardized assessments describe language strengths, the Communication and Symbolic Behavior Scales (CSBS-DP) is a particularly robust measure as it additionally characterizes precise aspects of social communication. This study provides a unique contribution by assessing the interactional effects of CSBS-DP Social Composite performance with early language samples on later language outcomes. Our results indicate that multiple social communication elements significantly interact with early spoken language to predict later language. Our findings also highlight the transactional relationship between early spoken vocabulary and social communication skills that bolster language development growth.


Outcomes in adult Fontan patients with atrial tachyarrhythmias.
The optimal management strategy for atrial tachyarrhythmia in the Fontan population is unknown. Retrospective review of 264 adult Fontan patients with atrial tachyarrhythmia evaluating 3 clinically adopted scenarios: antiarrhythmic drug (AAD) therapy, catheter ablation (CA), and Fontan conversion (FC). These patients were followed up at Mayo Clinic from 1994 to 2014. The study objective was to compare freedom from atrial tachyarrhythmia recurrence (AR) and occurrence of composite adverse events (stroke, heart failure hospitalization, death, or heart transplant) between treatment groups. The age of atrial tachyarrhythmia onset was 25 ± 4 years, time from Fontan operation was 13 ± 6 years, follow-up was 74 ± 18 months, atriopulmonary Fontan was 215 (81%), and atrial flutter/intra-atrial reentry tachycardia was 173 (65%). In those managed with AAD (n = 110), freedom from AR was 7% at 60 months. Catheter ablation (n = 31) was associated with an acute procedural success of 94%, and freedom from AR was 41% at 60 months. Fontan conversion (n = 33) resulted in a perioperative mortality of 3%, and freedom from AR was 51% at 60 months. Fontan conversion and CA were similar with regard to AR (P = .14) and significantly better compared with AAD (P < .0001). Adverse events were found to occur more frequently in the patients with AR (P < .0001) and the patients treated with AAD only (P < .0001). Catheter ablation and FC operations are associated with less recurrence of atrial tachyarrhythmia compared with AAD. Atrial tachyarrhythmias are more likely to recur in patients with a longer history of the arrhythmia and are associated with more adverse events. Early referral to a specialty center for these interventions should be considered.


State-dependent modulation of positive and negative affective valences by a parabrachial nucleus-to-ventral tegmental area pathway in mice.
Appropriately responding to various sensory signals in the environment is essential for animal survival. Accordingly, animal behaviors are closely related to external and internal states, which include the positive and negative emotional values of sensory signals triggered by environmental factors. While the lateral parabrachial nucleus (LPB) plays a key role in nociception and supports negative valences, it also transmits signals including positive valences. However, the downstream neuronal mechanisms of positive and negative valences have not been fully explored. In the present study, we investigated the ventral tegmental area (VTA) as a projection target for LPB neurons. Optogenetic activation of LPB-VTA terminals in male mice elicits positive reinforcement in an operant task and induces both avoidance and attraction in a place-conditioning task. Inhibition of glutamic acid decarboxylase (GAD) 65-expressing cells in the VTA promotes avoidance behavior induced by photoactivation of the LPB-VTA pathway. These findings indicate that the LPB-VTA pathway is one of the LPB outputs for the transmission of positive and negative valence signals, at least in part, with GABAergic modification in VTA.


Angiopoietin-1 Mimetic Peptide Promotes Neuroprotection after Stroke in Type 1 Diabetic Rats.
Angiopoietin-1 (Ang1) mediates vascular maturation and immune response. Diabetes decreases Ang1 expression and disrupts Ang1/Tie2 signaling activity. Vasculotide is an Ang1 mimetic peptide, and has anti-inflammatory effects. In this study, we test the hypothesis that vasculotide treatment induces neuroprotection and decreases inflammation after stroke in type 1 diabetic (T1DM) rats. T1DM rats were subjected to embolic middle cerebral artery occlusion (MCAo) and treated with: 1) phosphate buffered saline (PBS); 2) vasculotide (3µg/kg, i.p. injection) administered half an hour prior to MCAo and at 8 and 24 hours after MCAo. Rats were sacrificed at 48 h after MCAo. Neurological function, infarct volume, hemorrhage, blood brain barrier (BBB) permeability and neuroinflammation were measured. Vasculotide treatment of T1DM-MCAo rats significantly improves functional outcome, decreases infarct volume and BBB permeability, but does not decrease brain hemorrhagic transformation compared with PBS-treated T1DM-MCAo rats. In the ischemic brain, Vasculotide treatment significantly decreases apoptosis, number of cleaved-caspase-3 positive cells, the expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor (TNF-α). Western blot analysis shows that vasculotide significantly decreases expression of receptor for advanced glycation end products (RAGE), MCP-1 and TNF-α in the ischemic brain compared with T1DM-MCAo rats. Vasculotide treatment in cultured primary cortical neurons (PCN) significantly decreases TLR4 expression compared with control. Decreased neuroinflammation and reduced BBB leakage may contribute, at least in part, to vasculotide-induced neuroprotective effects after stroke in T1DM rats.


[The patient as expert--introduction to evidence-based orthopedics].
The surgical act is based on the laws of causality from Newton and Galilei and it is determined by the principle of cause and effect. Therefore, the healing process must be interpreted as a turning back of pathogenesis or the linear chain of casualities. Scientific knowledge of this century demonstrates that biological healing processes are connected with the laws of cybernetics and the principles of semiotics. There are functional relations between the level of the organ (impairments) of the individual (disabilities) and of the society (handicaps). This International Classification of Impairments, Disabilities and Handicaps (ICIDH) serves as the key for the management of chronic diseases. An independent and a separate classification of the severity in each level is necessary to identify the consequences of the disease to the patient. Surgical interventions occur on the organ level, benefit and evidence are reflected especially on the individual level (gain of abilities). The assessment and the integration of the so-called "sensory impairment", influenced by the biographical events of the patient and the evaluation of the psychosocial resistance are important factors to recognize unfavourable conformity between the degree of impairment and the degree of disability. With this classification, a more patient-oriented discussion of the indications regarding operative procedures can be realised. The MARA model (mean age-related ability) serves as a pragmatic basis for the description of the benefits of carried out and omitted interventions as changes of abilities by using the MARA curve as an ethical guideline. This model, which is on ICIDH, the hierarchy of needs and the salutogenesis (semiotics, cybernetics), facilitate the introduction of evidence-based surgery. It helps to estimate the several predictive values and correlation factors influencing the manifestation of the disease. In this way astonishing results in evidence can be expected. Finally, many misunderstandings in health care discussions are explained by the fact that the differences between pathology and illness are not clearly interpreted.


High-Resolution Magnetic Resonance Imaging of Aging Upper Face Fat Compartments.
Age-related changes in fat compartments have yet to be fully characterized. Uncertainty remains in terms of volume gains/losses or shape fluctuations over time. The authors' aim was to determine the evolution of subcutaneous fat in the aging upper face, focusing on shifts in volume and dimension. Over the course of 4.5 years, 100 faces of living female Caucasian patients were prospectively studied using high-resolution magnetic resonance imaging. Subjects were stratified by age as follows: group 1, 18 to 30 years; group 2, 30 to 60 years; and group 3, older than 60 years. Superficial temporal and central forehead compartments were delimited, analyzing respective volumes and dimensions by group. In 85 patients studied, superficial temporal fat (mean volume, 5.14 cm) increased 35.48 percent in total volume between youth and old age (p = 0.046). Overall height and magnitude of the lower one-third also increased with aging. Central forehead fat (mean volume, 2.56 cm), studied in 83 patients, showed a 209.75 percent volume gain in group 2 (versus group 1) and a 17.59 percent volume loss in group 3 (versus group 2) (p = 0.001). Subcutaneous facial fat fluctuates with aging, increasing in the upper face and promoting ptosis through basal compartmental expansion.