Microwave Assisted Conversion of an Amino Acid Into a Fluorescent Solution.
Microwave assisted synthesis is a well established method in organic and inorganic chemistry. It is also used in material science to realize novel carbon nanoparticles exhibiting fluorescence properties. The results presented here are related to a microwave driven solvothermal process used for the conversion of amino acid and 1,2-diaminoethane into fluorescent solutions. Arginine, lysine and glycine were used as amino acids. The process temperatures are set in the range of 80° to 140 °C and the maximum process pressure is 4.5 bar. The process duration is set from 5 to 30 minutes. The fluorescence effect is increased with increasing temperature. The prepared aqueous fluorescent solutions can be used as media to induce fluorescence in textile substrates. The current study can be understood as a first proof-of-concept of a very simple microwave-assisted solvothermal synthesis of fluorescent compounds useful for the modification of different substrates.


Effects of a standard hyperbaric oxygen treatment protocol on pulmonary function.
The prescription of hyperbaric oxygen (HBO) therapy for disorders not related to diving is increasing. Pulmonary oxygen toxicity is well known, but the effect of the cumulative oxygen exposure corresponding to a standard HBO treatment protocol has not been quantified before. Twenty patients (10 male) had 21 HBO treatments at a partial pressure of oxygen of 240 kPa for 90 min daily. None had any previous lung disease and all had normal chest radiography and lung function at the start of the study. Dynamic lung volumes, forced expiratory flows and the transfer factor of the lung for carbon monoxide (TL,CO) were measured before the HBO treatment, on days 7, 14 and 21 during treatment and then 3-4 weeks after treatment. Four patients (one male) reported nonproductive coughing during the last week of treatment. There was a progressive reduction in forced expiratory volume in one second (FEV1) (p<0.001), mean forced mid-expiratory flow rate (FEF25-75%) (p<0.001) and forced expiratory flows at 50 and 75% of forced vital capacity (FVC) expired during HBO treatment. The reduction in FEV1 on day 21 was 4.4+/-1.7% and in FEF25-75% 10.3+/-6.1%. Four weeks after treatment there was a partial normalization. There were no changes in FVC or peak expiratory flow (PEF). TL,CO was slightly reduced on day 21 of treatment only (p<0.01) and fully normalized 1 month later. A reduction in small airways conductance is consistent with other studies where total oxygen exposures have been below the limit causing toxic pulmonary effects traditionally measured as a reduction in vital capacity. This effect is not considered to be of any clinical significance for patients treated with hyperbaric oxygen unless repeated treatment series are to be given.


Influence of thin mucosal tissues on crestal bone stability around implants with platform switching: a 1-year pilot study.
The aim of this pilot study was to determine what effect thin mucosal tissues can have on crestal bone stability around implants with platform switching. Twelve 2-piece implants, consisting of 6 implants with horizontally matching implant-abutment connection (control) and 6 implants with platform switching (test) were placed in 4 patients. The mean age of the patients was 43 years (range, 37 to 56 yrs). Mucosal tissue thickness at implant sites was measured to be 2 mm or less. Implants were restored with 5 splinted crowns and single 3-unit fixed partial denture. Intraoral radiographs were obtained and crestal bone changes were measured at implant placement and after a 1-year follow-up post-treatment. The statistical significance level was set to P less than .05. Bone loss around the test implants was 1.81 +/- 0.39 mm on the mesial site and 1.70 +/- 0.35 mm on the distal aspect. Control implants overcame marginal bone resorption equaling 1.60 +/- 0.46 mm on the mesial site and 1.76 +/- 0.45 mm on distal measurement. No statistically significant difference was found between control and test implants either mesially (F([1,10]) = 0.746; P = .408) or distally (F([1,10]) = 0.080; P = .783). Within the limitations of this pilot study it can be concluded that implants with platform switching did not preserve crestal bone better in comparison with implants with traditional implant-abutment connection if, at the time of implant placement, thin mucosal tissues were present.


Influence of small increments of epinephrine on glucose tolerance in normal humans.
To ascertain whether small elevations of epinephrine alter glucose tolerance, we infused epinephrine or saline into seven healthy volunteers for 5 hours. Two hours after starting the infusions, subjects ingested 100 g of glucose. Plasma epinephrine (basal 23 +/- 4 pg/mL) rose during epinephrine infusion to levels (75 to 80 pg/mL) similar to those observed in nine outpatients presenting with mild viral illnesses (66 +/- 8 pg/mL). Although epinephrine produced only a small (5 mg/dL) increase n plasma glucose before glucose ingestion, after oral glucose the levels of glucose increased by 30 to 60 mg/dL above saline control values (163 +/- 14 mg/dL versus 108 +/- 15 at 2 h, p < 0.005). This diabetogenic effect occurred despite two-fold higher insulin levels and normal suppression of plasma glucagon. We conclude that small physiologic increments of epinephrine, which cause minimal changes in fasting plasma glucose, produce a marked reduction in glucose tolerance. Our data suggest marked sensitivity to the insulin antagonistic effects of epinephrine and may provide a mechanism for stress-induced glucose intolerance.


Short-term effects of crisis response planning on optimism in a U.S. Army sample.
This study examined the short-term effects of a brief crisis intervention on optimism of acutely suicidal soldiers. U.S. Soldiers (N = 97) presenting for an emergency mental health appointment in a military emergency department or behavioural health clinic were randomly assigned to treatment as usual standard crisis response plan, or enhanced crisis response plan (E-CRP). This study is used a subsample of the original clinical trial (n = 64) for those who completed self-report measures of optimism (Life Orientation Test-Revised) prior to receiving any intervention and a secondary self-report assessment one-month following the intervention. Results indicate that individuals with low baseline optimism who received the E-CRP had significant increases in optimism 1 month post-intervention. This provides evidence that discussing a patient's reasons for living during a CRP increases optimism in those high-risk patients with the lowest baseline optimism.


Diet and risk of ischemic heart disease in India.
Ischemic heart disease (IHD) is a leading cause of death in India. Dietary changes could reduce risk, but few studies have addressed the association between diet and IHD risk in India. The goal was to address the association between diet and IHD risk among Indians in New Delhi (northern India) and Bangalore (southern India). We collected data from 350 cases of acute myocardial infarction and 700 controls matched on the basis of age, sex, and hospital as part of a hospital-based case-control study in 8 hospitals. Long-term dietary intake was assessed by using food-frequency questionnaires developed for New Delhi and Bangalore. We used conditional logistic regression to control for the matching factors and other predictors of risk. We observed a significant and dose-dependent inverse association between vegetable intake and IHD risk. The inverse association was stronger for green leafy vegetables; in multivariate analysis, persons consuming a median of 3.5 servings/wk had a 67% lower relative risk (RR: 0.33; 95% CI: 0.17, 0.64; P for trend = 0.0001) than did those consuming 0.5 servings/wk. Controlling for other dietary covariates did not alter the association. Cereal intake was also associated with a lower risk. Use of mustard oil, which is rich in alpha-linolenic acid, was associated with a lower risk than was use of sunflower oil [for use in cooking: RR: 0.49 (95% CI: 0.24, 0.99); for use in frying, RR: 0.29 (95% CI: 0.13, 0.64)]. Diets rich in vegetables and use of mustard oil could contribute to the lower risk of IHD among Indians.


Dual function of rare earth doped nano Bi2O3: white light emission and photocatalytic properties.
Undoped Bi(2)O(3) and single and double doped Bi(2)O(3) : M (where M = Tb(3+) and Eu(3+)) nanophosphors were synthesized through a simple sonochemical process and characterized by using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), EDS, diffuse reflectance (DRS) and photoluminescence (PL) spectrophotometry. The TEM micrographs show that resultant nanoparticles have a rod-like shape. Energy transfer was observed from host to the dopant ions. Characteristic green emissions from Tb(3+) ions and red emissions from Eu(3+) ions were observed. Interestingly, the Commission International de l'Eclairage (CIE) coordinates of the double doped Bi(2)O(3) : Eu(3+)(0.8%) : Tb(3+)(1.2%) nanorods lie in the white light region of the chromaticity diagram and it has a quantum efficiency of 51%. The undoped Bi(2)O(3) showed a band gap of 3.98 eV which is red shifted to 3.81eV in the case of double doped Bi(2)O(3) : Eu(3+)(0.8%) : Tb(3+)(1.2%) nanorods. The photocatalytic activities of undoped nano Bi(2)O(3) and double doped nano Bi(2)O(3) : Eu(3+)(0.8%) : Tb(3+)(1.2%) were evaluated for the degradation of Rhodamine B under UV irradiation of 310 nm. The results showed that Bi(2)O(3) : Eu(3+)(0.8%) : Tb(3+)(1.2%) had better photocatalytic activity compared to undoped nano Bi(2)O(3). The evolution of CO(2) was realized and these results indicated the continuous mineralization of rhodamine B during the photocatalytic process. Thus double doped Bi(2)O(3) : Eu(3+)(0.8%) : Tb(3+)(1.2%) nanorods can be termed as a bifunctional material exhibiting both photocatalytic properties and white light emission.


Inhibition of vascular endothelial growth factor signalling using cediranib (RECENTIN; AZD2171) enhances radiation response and causes substantial physiological changes in lung tumour xenografts.
A number of pre-clinical studies have suggested that blocking vascular endothelial growth factor (VEGF) signalling can be beneficial in combination with radiotherapy. This study investigated the effects of cediranib, a highly potent orally available inhibitor of VEGF receptor tyrosine kinase activity in combination with radiation in Calu-6 lung xenografts. In nude mice, Calu-6 tumours were established and treatments initiated at a volume of 250 mm(3). Tumour-localized radiotherapy was given as three or five daily fractions of 2 Gy. Cediranib (3 mg kg(-1)) was administered 2 h prior to each fraction and continued post radiotherapy (concomitant regimen) or was initiated immediately after the completion of radiotherapy (sequential regimen). The endpoint was the time taken for tumour volume to quadruple (RTV4). Combined treatments resulted in a significantly enhanced growth delay compared with either modality alone. The therapeutic benefit was the same irrespective of the scheduling regimen. Tumour regression was observed post radiotherapy, which was associated with high levels of apoptosis and necrosis, and pronounced antivascular effects in histological samples. The amplified antivascular effect of cediranib when given after radiation suggests that pre-irradiated endothelium is sensitized to cediranib. Concomitant 5-day treatment with both cediranib and radiation reduced vessel density, perfusion and increased in tumour hypoxia. This was not associated with an acquired radioresistance suggesting that the maintenance of cediranib treatment post radiotherapy prevents the contribution of hypoxic cells to tumour regrowth. Collectively, these data support the contention that VEGFR inhibition can enhance radiation response in pre-clinical models and provide a rationale to develop cediranib in combination with radiotherapy in the clinical setting.


Adherence to a Mediterranean diet and prediction of incident stroke.
There are limited data on the potential association of adherence to Mediterranean diet (MeD) with incident stroke. We sought to assess the longitudinal association between greater adherence to MeD and risk of incident stroke. We prospectively evaluated a population-based cohort of 30 239 individuals enrolled in REasons for Geographic and Racial Differences in Stroke (REGARDS) study, after excluding participants with stroke history, missing demographic data or food frequency questionnaires, and unavailable follow-up information. Adherence to MeD was categorized using MeD score. Incident stroke was adjudicated by expert panel review of medical records during a mean follow-up period of 6.5 years. Incident stroke was identified in 565 participants (2.8%; 497 and 68 cases of ischemic stroke [IS] and hemorrhagic stroke, respectively) of 20 197 individuals fulfilling the inclusion criteria. High adherence to MeD (MeD score, 5-9) was associated with lower risk of incident IS in unadjusted analyses (hazard ratio, 0.83; 95% confidence interval, 0.70-1.00; P=0.046). The former association retained its significance (hazard ratio, 0.79; 95% confidence interval, 0.65-0.96; P=0.016) after adjustment for demographics, vascular risk factors, blood pressure levels, and antihypertensive medications. When MeD was evaluated as a continuous variable, a 1-point increase in MeD score was independently associated with a 5% reduction in the risk of incident IS (95% confidence interval, 0-11%). We documented no association of adherence to MeD with incident hemorrhagic stroke. There was no interaction of race (P=0.37) on the association of adherence to MeD with incident IS. High adherence to MeD seems to be associated with a lower risk of incident IS independent of potential confounders. Adherence to MeD is not related to the risk of incident hemorrhagic stroke.


Chronic allergic contact dermatitis promotes skin cancer.
Allergic contact dermatitis (ACD) is well recognized as an adverse event associated with implantable medical devices that contain allergenic materials like nickel; however, other cutaneous consequences of chronic exposure to allergens in implanted devices are not well understood. Here, we present a clinical case of Marjolin's ulcer, an invasive squamous cell carcinoma (SCC) that developed in response to chronic ACD caused by an orthopedic implant. We used a standard murine model of contact hypersensitivity to determine whether chronic ACD promotes skin carcinogenesis. Chronic application of 1-fluoro-2,4-dinitrobenzene (DNFB) to carcinogen-treated skin led to the development of papillomas and aggressive SCC. DNFB-driven chronic ACD was marked by type 2 inflammation, which mediated skin carcinogenesis, as mice unable to mount an inflammatory response were less likely to develop skin tumors. Importantly, we found similar tumor-promoting inflammation surrounding the SCC in our patient. Our findings demonstrate that chronic ACD caused by constant exposure to an allergen can promote tumorigenesis at skin sites with preexisting cancer-initiated cells. Moreover, our results suggest that patients with implantable devices placed in close proximity to the skin should be monitored for ACD and highlight the importance of patch testing prior to the placement of such devices.


American Society of Clinical Oncology Summit on Addressing Obesity Through Multidisciplinary Provider Collaboration: Key Findings and Recommendations for Action.
Given the increasing evidence that obesity increases the risk of developing and dying from malignancy, the American Society of Clinical Oncology (ASCO) launched an Obesity Initiative in 2013 that was designed to increase awareness among oncology providers and the general public of the relationship between obesity and cancer and to promote research in this area. Recognizing that the type of societal change required to impact the obesity epidemic will require a broad-based effort, ASCO hosted the "Summit on Addressing Obesity through Multidisciplinary Collaboration" in 2016. This meeting was held to review current challenges in addressing obesity within the respective health care provider communities and to identify priorities that would most benefit from a collective and cross-disciplinary approach. Efforts focused on four key areas: provider education and training; public education and activation; research; and policy and advocacy. Summit attendees discussed current challenges in addressing obesity within their provider communities and identified priorities that would most benefit from multidisciplinary collaboration. A synopsis of recommendations to facilitate future collaboration, as well as examples of ongoing cooperative efforts, provides a blueprint for multidisciplinary provider collaboration focused on obesity prevention and treatment.


Measurement of vertebral rotation in standing versus supine position in adolescent idiopathic scoliosis.
Thirty-three structural curves of 25 patients with adolescent idiopathic scoliosis were evaluated using computed tomography (CT) scans and plain radiography. The average Cobb angle on standing radiographs was 55.72 degrees and was observed to be corrected spontaneously to 39.42 degrees while the patients were in supine position (29.78% correction). Average apical rotation according to Perdriolle was 22.75 degrees on standing radiographs and 16.78 degrees on supine scanograms. The average rotation according to Aaro and Dahlborn on CT scans was 16.48 degrees. Radiographic measurements were significantly different from axial CT slice or scanogram measurements (p = 0.000), but the two latter measurements, both obtained in the supine position, did not appear to be different (p = 0.495). Deformities on the transverse plane as well as on the coronal plane are influenced by patient positioning. If the patient lies supine, the scoliosis curve corrects spontaneously to some degree on both planes. Measurements obtained from the scanograms by the Perdriolle method in the supine position are very similar to those obtained by CT. Perdriolle's is a simple, convenient, and reliable method to measure rotation on standing radiograms.


Pearls and Pitfalls of an Orthopaedic Mission Trip.
Many physicians chose to pursue years of rigorous medical training because of an innate desire to care for others, which often translates into volunteering in their local communities. Some physicians take this a step further by contributing their time and skills to global health delivery through medical mission trips. The need is apparent: a 40-year discrepancy in average life span, 36 deaths versus 4 deaths per 1,000 births in low-income versus high-income countries, and over 70% of preventable pediatric deaths occurring in solely 15 countries. In addition, a remarkable gap exists in the access of care and resources, with the world's poorest countries receiving only 4% of surgical services. Orthopaedic missions are seldom because the cost and complexity of these trips supersede many other specialties. However, the care that orthopaedic surgery can provide restores an individual's function, allowing them to increase productivity in their personal lives and in their community. Addressing this disparity in health care is a great first step, but studies have shown that mission trips may have some serious downfalls. We aim to discuss these downfalls and provide recommendations to mitigate them.


Surgical Management of Traumatic Peripheral Osteoma of the Mandible.
Osteomas are benign osteogenic lesions that result from the proliferation of mature bone. Three variants are known: central, peripheral, and extraskeletal. The peripheral variant is the most common and it most frequently affects the paranasal sinuses, rarely occurring in the jaws. This article describes the case of a 33-year-old white male patient who was referred complaining of facial asymmetry. Clinical examination revealed an increase in volume at the base of the right side of the mandible, hard bony consistency and well delimited, painless to the touch, without signs of infection or intraoral alterations. Radiographic examination revealed an oval lobulated, radiopaque sessile lesion adhered to the mandibular base near the insertion of the masseter muscle. The patient reported practicing martial arts many years ago. Owing to the limited access, it was decided to perform the complete lesion removal through an extraoral surgical approach, by using a skin crease in the upper neck region below the lesion. The patient recovered well and the histopathological analysis confirmed the diagnosis of osteoma. The etiopathogenesis of osteoma is not completely elucidated, and 3 theories are more accepted: developmental defect, neoplastic nature, and reactive lesion owing to trauma or local infection. The clinicopathological correlation in the present case supports a traumatic origin. Traumatic peripheral osteoma should be considered in the differential diagnosis of nodular bone-forming lesions affecting the mandible.


Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum.
Controversy exists over whether or not Ureaplasma urealyticum colonization or infection of the respiratory tract contributes to the severity of chronic lung disease (CLD), a major cause of morbidity and mortality in preterm infants. To evaluate the efficacy and safety of prophylactic or therapeutic erythromycin in preventing chronic lung disease in intubated preterm infants with unknown U. urealyticum status or proven positivity. Searches were done of MEDLINE (1966-June 9, 2003), EMBASE (1980-May 5, 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), previous reviews including cross-references, and abstracts of conference proceedings (Pediatric Academic Societies 2000-2003, American Thoracic Society 2001-2003). There were no language restrictions. Expert informants were contacted. Randomized or quasi-randomized studies comparing either prophylactic or therapeutic administration of oral or intravenous erythromycin (regardless of dose and duration) versus no treatment or placebo among intubated preterm infants <37 weeks and <2500 grams with either unknown U. urealyticum status or proven positivity by culture or polymerase chain reaction. Data were extracted by all of the authors independently and differences were resolved by consensus. Treatment effects for categorical outcomes were expressed as relative risk, with 95% confidence intervals. Two small controlled studies, both involving intubated babies <30 weeks gestation, were eligible for inclusion. Lyon 1998 tested prophylactic erythromycin in babies whose U. urealyticum status was unknown at the time of initiation of treatment. Jonsson 1998 tested erythromycin in babies known to be culture positive for U. urealyticum. Neither trial showed a statistically significant effect of erythromycin on CLD, death or the combined outcome CLD or death. Because the two studies differed importantly in their design, the results were not combined in meta-analyses. No adverse effects of a 7-10 day course of erythromycin were reported in either study. Current evidence does not demonstrate a reduction in CLD/death when intubated preterm infants are treated with erythromycin prophylactically before U. urealyticum culture/PCR results are known or when Ureaplasma colonized, intubated preterm infants are treated with erythromycin. However, a true benefit could easily have been missed with the small sample sizes in the two eligible studies. The studies were greatly underpowered to detect uncommon adverse effects such as pyloric stenosis. Additional controlled trials are required to determine whether antibiotic therapy of Ureaplasma reduces CLD and/or death in intubated preterm infants.


Sustained protection against distilled water provocation by a single dose of salmeterol in patients with asthma.
The long-acting beta2-agonist salmeterol inhibits in vitro the release of inflammatory mediators up to 20 h. These mediators are involved in ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction. We investigated whether salmeterol provides prolonged protection against UNDW provocation and whether this effect was paralleled by its bronchodilator effects. Nineteen asthmatic patients (mean forced expiratory volume in one second (FEV1) 84.8% predicted, mean provocative concentration of histamine producing a 20% decrease in FEV1 0.65 mg x mL(-1)) participated in this randomized, double-blind, placebo-controlled crossover trial. After measuring baseline FEV1, patients inhaled 50 microg salmeterol or placebo by metered-dose inhaler. FEV1 was measured after 20 and 40 min, and UNDW provocations and FEV1 measurements were performed after 10, 20 and 34 h. Compared to placebo, salmeterol caused marked bronchodilatation from 20 min up to 20 h after inhalation. Salmeterol also provided more than 20 h of protection against UNDW provocation (still more than one doubling dose). Protection beyond the period of bronchodilatation did not occur. Eleven subjects had a significant reduction in provocative dose of UNDW causing a 20% fall in FEV1 (PD20,UNDW) values between 10 and 20 h, at a time when there was still persistent bronchodilation. No correlation existed between changes in FEV1 and changes in PD20,UNDW. From the equations of regression lines between FEV1 and corresponding PD20,UNDW values, it was calculated that only approximately 25% of the afforded protection was explained by bronchodilatation. In conclusion, a single dose of salmeterol induces both bronchodilatation and protection independently of this bronchodilation against a physiological bronchoconstrictor stimulus for more than 20 h.


Improved method for preparing anaerobic bacteroid suspensions of Rhizobium leguminosarum for the acetylene reduction assay.
A method using ethylenediaminetetraacetate (EDTA) and toluene-treated pea bacteroid suspensions for the acetylene reduction assay is described. The high level of acetylene reduction by these bacteroids is comparable to that of intact plants. Reproducibility of the EDTA-toluene treatment is, on the average, within 5%. Preliminary experiments with soybeans indicate that the EDTA-toluene method might be applicable to other legumes as well.


The structure and activity of a monomeric interferon-gamma:alpha-chain receptor signaling complex.
Interferon-gamma (IFN-gamma) is a homodimeric cytokine that exerts its various activities by inducing the aggregation of two different receptors. The alpha chain receptor (IFN-gammaRalpha) is a high affinity receptor that binds to IFN-gamma in a symmetric bivalent manner to form a stable, intermediate 1:2 complex. This intermediate forms a binding template for the subsequent binding of two copies of the second receptor, beta chain receptor (IFN-gammaRbeta), producing the active 1:2:2 signaling complex. A single chain monovalent variant of IFN-gamma (scIFN-gamma) was constructed and complexed to one copy of the extracellular domain (ECD) of IFN-gammaRalpha. The structure of this 1:1 complex was determined and the hormone-receptor interface shown to be characterized by a number of hydrophilic interactions mediated by several highly ordered water networks. The scIFN-gamma interface consists of segments from each of the monomer chains of the homodimer. The principal hydrophobic contact of the receptor involves a tripeptide segment of the receptor having an unusual and high energy conformation. Despite containing only one binding site for IFN-gammaRalpha, the monovalent scIFN-gamma molecule has significant activity in antiviral biological assays. ScIFN-gamma binds the ECD of IFN-gammaRalpha through a highly hydrated interface with an important set of hormone-receptor contacts mediated through structured waters. Although the interface is highly hydrated, it supports tight binding and has a considerable degree of specificity. The biological activity of scIFN-gamma confirms that the scIFN-gamma:IFN-gammaRalpha complex represents a productive intermediate and that it can effectively recruit the other required component, IFN-gammaRbeta, to signal based on the 1:1:1 complex.


Force-Based Algorithm for Motion Planning of Large Agent.
This article presents a distributed, efficient, scalable, and real-time motion planning algorithm for a large group of agents moving in 2-D or 3-D spaces. This algorithm enables autonomous agents to generate individual trajectories independently with only the relative position information of neighboring agents. Each agent applies a force-based control that contains two main terms: 1) collision avoidance and 2) navigational feedback. The first term keeps two agents separate with a certain distance, while the second term attracts each agent toward its goal location. Compared with existing collision-avoidance algorithms, the proposed force-based motion planning (FMP) algorithm can find collision-free motions with lower transition time, free from velocity state information of neighboring agents. It leads to less computational overhead. The performance of proposed FMP is examined over several dense and complex 2-D and 3-D benchmark simulation scenarios, with results outperforming existing methods.


[Evaluation the effectiveness of radiation therapy high-grade gliomas based on the model of TDF (time-dose fractionation)].
There were showed the possibility of using the model of TDF, through which it was possible to take into account the selection of fractionation of radiation for high-grade gliomas and to judge the effectiveness of treatment. Currently, the basis of adjuvant radiation therapy in patients with primary high-grade gliomas is the use of the traditional mode of fractionation dose of radiation from a single focal dose of 2 Gy up to a total focal dose of 60 Gy to the tumor (bed of the removed residual tumor) in Grade 4 and Grade 3 - 54 Gy. In patients who underwent radiotherapy using a single focal dose of 3 Gy, overall survival rate was higher as compared to the group of patients, which was carried out using radiotherapy small dose fractionation.


Attention deficit hyperactivity disorder symptoms in adults with autism spectrum disorders.
Features of attention deficit hyperactivity disorder (ADHD) and impairments on neuropsychological, tests of attention have been documented in children with autism spectrum disorders (ASDs). To date, there has been a lack of research comparing attention in adults with ASD and adults with ADHD. In study 1, 31 adults with ASD and average intellectual function completed self-report measures of ADHD symptoms. These were compared with self-report measures of ADHD symptoms in 38 adults with ADHD and 29 general population controls. In study 2, 28 adults with a diagnosis of ASD were compared with an age- and intelligence quotient-matched sample of 28 adults with ADHD across a range of measures of attention. Study 1 showed that 36.7% of adults with ASD met Diagnostic and Statistical Manual-IV criteria for current ADHD "caseness" (Barkley Current self-report scores questionnaire). Those with a diagnosis of pervasive developmental disorder-not otherwise specified were most likely to describe ADHD symptoms. The ASD group differed significantly from both the ADHD and control groups on total and individual symptom self-report scores. On neuropsychological testing, adults with ASD and ADHD showed comparable performance on tests of selective attention. Significant group differences were seen on measures of attentional switching; adults with ADHD were significantly faster and more inaccurate, and individuals with Asperger's syndrome showed a significantly slower and more accurate response style. Self-reported rates of ADHD among adults with ASD are significantly higher than in the general adult population and may be underdiagnosed. Adults with ASD have attentional difficulties on some neuropsychological measures.


Redefining Outcome Measurement: A Model for Brief Psychotherapy.
The zeitgeist for short-term psychotherapy efficacy has fundamentally shifted away from evidence-based practices to include evidence-informed practices, resulting in an equally important paradigm shift in outcome measurement designed to reflect change in this short-term modality. The present article delineates a short-term psychotherapy structure which defines four fundamental stages that all brief therapies may have in common, and are represented through Cognitive Behavioral Therapy, Solution-Focused Brief Therapy, Narrative Therapy, and Emotion-Focused Therapy. These four theoretical approaches were analyzed via a selected literature review through comparing and contrasting specific and common tasks as they relate to the process of psychotherapy and change. Once commonalities were identified within session, they were categorized or grouped into themes or general stages of change within the parameters of a four to six session model of short-term therapy. Commonalities in therapeutic stages of change may more accurately and uniformly measure outcome in short-term work, unlike the symptom-specific psychometric instruments of longer-term psychotherapy. A systematic framework for evaluating the client and clinician adherence to 20 specific tasks for these four short-term therapies is presented through the newly proposed, Brief Task Acquisition Scale (BTAS). It is further proposed that the client-clinicians' adherence to these tasks will track and ultimately increase treatment integrity. Thus, when the client-clinician relationship tracks and evaluates the three pillars of (1) stage/process change, (2) task acquisition, and (3) treatment integrity, the culmination of these efforts presents a new way of more sensitively measuring outcome in short-term psychotherapy. Data collection is suggested as a first step to empirically evaluate the testable hypotheses suggested within this current model. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Message The clinician practitioner will note that the proposed Brief Services model removes the subjectivity of client satisfaction as a reliable outcome measure, and relies upon client and therapist adherence to specific tasks and stages of change within and across short-term psychotherapy. The clinical significance of the BTAS for the practitioner is three fold. The psychometric instrument (1) tracks stage or process change, (2) guides task acquisition, and (3) incorporates greater treatment integrity unlike other outcome measures. The BTAS present a new way of conceptualizing change in short-term psychotherapy regardless of modality or presenting issue, making it a more flexible and usable instrument for the clinician. The BTAS may measure outcome more sensitively and accurately, thus offering the client, therapist and client-therapist more information regarding change at each stage and at the end of short-term psychotherapy.


A robust methodology for in vivo T1 mapping.
In this article, a robust methodology for in vivo T(1) mapping is presented. The approach combines a gold standard scanning procedure with a novel fitting procedure. Fitting complex data to a five-parameter model ensures accuracy and precision of the T(1) estimation. A reduced-dimension nonlinear least squares method is proposed. This method turns the complicated multi-parameter minimization into a straightforward one-dimensional search. As the range of possible T(1) values is known, a global grid search can be used, ensuring that a global optimal solution is found. When only magnitude data are available, the algorithm is adapted to concurrently restore polarity. The performance of the new algorithm is demonstrated in simulations and phantom experiments. The new algorithm is as accurate and precise as the conventionally used Levenberg-Marquardt algorithm but much faster. This gain in speed makes the use of the five-parameter model viable. In addition, the new algorithm does not require initialization of the search parameters. Finally, the methodology is applied in vivo to conventional brain imaging and to skin imaging. T(1) values are estimated for white matter and gray matter at 1.5 T and for dermis, hypodermis, and muscle at 1.5 T, 3 T, and 7 T.


13C-urea breath test, referral patterns, and results in children.
The family is the core unit for Helicobacter pylori (Hp) infection. In most instances, Hp colonization occurs in early childhood, and correlates with socioeconomic parameters. Helicobacter pylori infection is highly prevalent in many countries, and may cause chronic gastritis and peptic ulcer in adults and in children. Gastritis induced by Hp may be associated with recurrent abdominal pain in children, and eradication of the bacterium may improve the clinical symptoms. AIM The primary aim of this study is to characterize the group of pediatric patients according to the referral patterns and results of 13C-urea breath test (13C -UBT) in our laboratory. The secondary aim is to investigate the result of different treatment combinations for Hp eradication. The 13C-UBT was performed with 75 mg urea labeled with 13C in 200 mL orange juice. Breath samples were collected at 0 and 30 minutes, and the results expressed as the change in the 13C/12C ratio at T30' minus T0' The cutoff for Hp eradication was 3.5. The physicians who ordered the test completed a questionnaire covering demographic data (age, gender, and origin), indication for the test was use of a proton pump inhibitor (PPI), and type of combination eradication therapy. The study sample consisted of 1655 children, aged 1 to 18 years, 992 (59.9%) boys and 663 (40.1%) girls, from all parts of the country. The 13C-UBT was positive in 763 (46.1%). The prevalence of positive results was directly correlated with age. History of peptic disease was the main indication for the test, in 1346 (81.4%) cases. Details on eradication therapy were available for 435 children of whom 42.5% had a positive 13C-UBT, indicating a successful eradication rate of 57.5%. Compared with Israeli and American-European origin, children of Asian-African origin had a higher rate of referrals for reason of validation of successful Hp eradication, greater long-term PPI use, and a higher rate of 13C-UBT positivity. No significant difference was demonstrated between the triple therapy regimens used. 13C-UBT may be performed in children of all age groups. The main indication is a history of peptic ulcer disease. The prevalence of Hp infection increased with age and the only factor associated with increased Hp infection was Asian-African origin. The most frequent eradication therapy used in children is a combination of omeprazole, amoxicillin, and clarithromycin.


High-Density Lipoprotein Proteomic Composition, and not Efflux Capacity, Reflects Differential Modulation of Reverse Cholesterol Transport by Saturated and Monounsaturated Fat Diets.
Acute inflammation impairs reverse cholesterol transport (RCT) and reduces high-density lipoprotein (HDL) function in vivo. This study hypothesized that obesity-induced inflammation impedes RCT and alters HDL composition, and investigated if dietary replacement of saturated (SFA) for monounsaturated (MUFA) fatty acids modulates RCT. Macrophage-to-feces RCT, HDL efflux capacity, and HDL proteomic profiling was determined in C57BL/6j mice following 24 weeks on SFA- or MUFA-enriched high-fat diets (HFDs) or low-fat diet. The impact of dietary SFA consumption and insulin resistance on HDL efflux function was also assessed in humans. Both HFDs increased plasma (3)H-cholesterol counts during RCT in vivo and ATP-binding cassette, subfamily A, member 1-independent efflux to plasma ex vivo, effects that were attributable to elevated HDL cholesterol. By contrast, ATP-binding cassette, subfamily A, member 1-dependent efflux was reduced after both HFDs, an effect that was also observed with insulin resistance and high SFA consumption in humans. SFA-HFD impaired liver-to-feces RCT, increased hepatic inflammation, and reduced ABC subfamily G member 5/8 and ABC subfamily B member 11 transporter expression in comparison with low-fat diet, whereas liver-to-feces RCT was preserved after MUFA-HFD. HDL particles were enriched with acute-phase proteins (serum amyloid A, haptoglobin, and hemopexin) and depleted of paraoxonase-1 after SFA-HFD in comparison with MUFA-HFD. Ex vivo efflux assays validated increased macrophage-to-plasma RCT in vivo after both HFDs but failed to capture differential modulation of hepatic cholesterol trafficking. By contrast, proteomics revealed the association of hepatic-derived inflammatory proteins on HDL after SFA-HFD in comparison with MUFA-HFD, which reflected differential hepatic cholesterol trafficking between groups. Acute-phase protein levels on HDL may serve as novel biomarkers of impaired liver-to-feces RCT in vivo.


Theoretical Study on Hydrogenolytic Cleavage of Intermonomer Linkages in Lignin.
Hydrogenolysis is an important approach for depolymerization of lignin, which provides attractive new sustainable platforms of fuels, chemicals, and materials. The theory of lignin hydrogenolysis is, however, still unsound, which limits the development of this approach and causes inconsistencies among experimental studies. In this paper, density functional theory is employed to investigate the initial hydrogenolytic cleavages of recognized five different types of interaromatic unit linkages of lignin, assuming the presence of hydrogen free radicals. The relative free energies of reactant complexes, reaction free energy changes, and rate constants for candidate reactions are calculated comprehensively at 298-538 K. On the basis of the results of calculation and a rapid equilibrium hypothesis, the major reaction channel is decided for each linkage, and its kinetics is assessed. It is concluded that the hydrogenolysis occurs at β-O-4 ether, diphenyl ether 4-O-5', and β-1' diphenylmethane linkages instantaneously if these are accessible to hydrogen free radicals, while β-5 phenylcoumaran and β-β' pinoresinol linkages are virtually inert to hydrogenolysis.


Cruciate ligament integrity in osteoarthritis of the knee.
To evaluate, using magnetic resonance imaging (MRI), the prevalence of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) rupture in knees with symptomatic osteoarthritis (OA) compared with those without OA, and the relationship to pain and recalled injury. MRI and plain radiography of the knee were performed in a group of 360 subjects with painful knee OA (cases; 66.7% male, mean age 67.1 years) and 73 without knee pain (controls; 57.5% male, mean age 66.1 years). MRIs were read for the presence or absence of complete or partial ACL or PCL tear. Subjects with knee pain were asked to quantify severity of pain on a visual analog scale and to report whether they could recall a significant knee injury (requiring use of a cane or crutches). We compared the prevalence of ACL and PCL rupture in those with and those without knee pain and also evaluated whether, in cases, there was any association with recalled knee injury. The proportion of cases who had complete ACL rupture was 22.8%, compared with 2.7% of controls (P = 0.0004). PCL rupture was rare both in cases (0.6%) and in controls (0%). Cases with ACL rupture had more severe radiologic OA (P < 0.0001) and were more likely to have medial joint space narrowing (P < 0.0001) than cases with intact ACLs, but did not have higher pain scores. Among cases, only 47.9% of those with complete ACL tears reported a previous knee injury, compared with 25.9% of those without complete ACL tears (P = 0.003). ACL rupture is more common among those with symptomatic knee OA compared with those without knee OA. Fewer than half of subjects with ACL rupture recall a knee injury, suggesting that this risk factor for knee OA is underrecognized.


Nutritional, physical, and sensory evaluation of hydroponic carrots (Daucus carota L.) from different nutrient delivery systems.
Carrot (Daucus carota L.) has the highest carotenoid content among foods and is consumed in large quantities worldwide, while at the same time its market demand continues to increase. Carotenoids have also been associated with protective effects against cancer and other chronic diseases. The most predominant carotenoids in carrots are beta- and alpha-carotenes. Moisture, ash, fat, texture, color, carotene content, and consumer acceptance of carrots grown in a hydroponic system with nutrient film technique (NFT) and microporous tube membrane system (MTMS) were evaluated. The moisture contents of the NFT- and MTMS-grown carrots ranged from 86.8 +/- 0.13% to 92.2 +/- 2.25% and 80.9 +/- 0.31% to 91.6 +/- 1.01%, respectively. Fat and ash contents of the carrots were negligible. NFT-grown Oxheart had the most beta-carotene (9900 +/- 20 microg/100 g) while Juwaroot had the least (248 +/- 10 microg/100 g). However, the beta-carotene content of Juwaroot from the NFT batch II carrots was 3842 +/- 6 microg/100 g. MTMS-grown carrots had less variation in the total beta-carotene contents (2434 +/- 89 to 10488 +/- 8 microg/100 g) than those from NFT. Overall, Nantes Touchan (4.8 +/- 2.3) and Nevis-F (7 +/- 1.4) from NFT were the least and most preferred by consumers. Mignon was also acceptable to consumers, and significantly (P < 0.05) more preferred than the other carrots in that NFT batch. MTMS-grown Kinko and Paramex, which were significantly (P < 0.05) more preferred than Nandrin-F and the commercial field-grown carrot, were equally liked by consumers. Nevis-F, Mignon (NFT), Paramex, and Kinko (MTMS) are potentially good cultivars to be included in NASA's food system.


Keeping it in the family: when Mexican American older adults choose not to use home healthcare services.
Mexican American elders are more functionally impaired and chronically ill than Anglo elders, yet use home care services less. The purpose of this study was to describe the cultural norms that influence Mexican American elders and their caregivers not to use home care services. A secondary analysis using descriptive ethnography was conducted. Thematic analysis was used to analyze Mexican American elders' (N = 4) and family caregivers' (N = 3) individual interviews. The overall finding was the category, "We Take Care of our Own!" This finding represented how Mexican American families faced increasing needs of elders at home in the context of their cultural norm of familism. The cultural findings, "Taking Care of Our Own!" were similar to those by elders who had chosen to use home care services in a previous study. Recognizing the importance of this norm, which is central to the culture, may shape interdisciplinary interventions that support traditional Mexican American family values, yet bring skilled or supportive help into the home. Interventions to increase the use of home care services by Latino families can contribute solutions to the national agenda to reduce healthcare disparities.


Acute Effects of Stretching on Leg and Vertical Stiffness During Treadmill Running.
Pappas, PT, Paradisis, GP, Exell, TA, Smirniotou, AS, Tsolakis, CK, and Arampatzis, A. Acute effects of stretching on leg and vertical stiffness during treadmill running. J Strength Cond Res 31(12): 3417-3424, 2017-The implementation of static (SS) and dynamic (DS) stretching during warm-up routines produces significant changes in biological and functional properties of the human musculoskeletal system. These properties could affect the leg and vertical stiffness characteristics that are considered important factors for the success of athletic activities. The aim of this study was to investigate the influence of SS and DS on selected kinematic variables, and leg and vertical stiffness during treadmill running. Fourteen men (age: 22.58 ± 1.05 years, height: 1.77 ± 0.05 m, body mass: 72.74 ± 10.04 kg) performed 30-second running bouts at 4.44 m·s, under 3 different stretching conditions (SS, DS, and no stretching). The total duration in each stretching condition was 6 minutes, and each of the 4 muscle groups was stretched for 40 seconds. Leg and vertical stiffness values were calculated using the "sine wave" method, with no significant differences in stiffness found between stretching conditions. After DS, vertical ground reaction force increased by 1.7% (p < 0.05), which resulted in significant (p < 0.05) increases in flight time (5.8%), step length (2.2%), and vertical displacement of the center of mass (4.5%) and a decrease in step rate (2.2%). Practical durations of SS and DS stretching did not influence leg or vertical stiffness during treadmill running. However, DS seems to result in a small increase in lower-limb force production which may influence running mechanics.


Wine yeast strains engineered for glycogen overproduction display enhanced viability under glucose deprivation conditions.
We used metabolic engineering to produce wine yeasts with enhanced resistance to glucose deprivation conditions. Glycogen metabolism was genetically modified to overproduce glycogen by increasing the glycogen synthase activity and eliminating glycogen phosphorylase activity. All of the modified strains had a higher glycogen content at the stationary phase, but accumulation was still regulated during growth. Strains lacking GPH1, which encodes glycogen phosphorylase, are unable to mobilize glycogen. Enhanced viability under glucose deprivation conditions occurs when glycogen accumulates in the strain that overexpresses GSY2, which encodes glycogen synthase and maintains normal glycogen phosphorylase activity. This enhanced viability is observed under laboratory growth conditions and under vinification conditions in synthetic and natural musts. Wines obtained from this modified strain and from the parental wild-type strain don't differ significantly in the analyzed enological parameters. The engineered strain might better resist some stages of nutrient depletion during industrial use.


Molecular classification of high grade endometrioid and clear cell ovarian cancer using TCGA gene expression signatures.
It is unclear whether the transcriptional subtypes of high grade serous ovarian cancer (HGSOC) apply to high grade clear cell (HGCCOC) or high grade endometrioid ovarian cancer (HGEOC). We aim to delineate transcriptional profiles of HGCCOCs and HGEOCs. We used Agilent microarrays to determine gene expression profiles of 276 well annotated ovarian cancers (OCs) including 37 HGCCOCs and 66 HGEOCs. We excluded low grade OCs as these are known to be distinct molecular entities. We applied the prespecified TCGA and CLOVAR gene signatures using consensus non-negative matrix factorization (NMF). We confirm the presence of four TCGA transcriptional subtypes and their significant prognostic relevance (p<0.001) across all three histological subtypes (HGSOC, HGCCOC and HGEOCs). However, we also demonstrate that 22/37 (59%) HGCCOCs and 30/67 (45%) HGEOCs form 2 additional separate clusters with distinct gene signatures. Importantly, of the HGCCOC and HGEOCs that clustered separately 62% and 65% were early stage (FIGO I/II), respectively. These finding were confirmed using the reduced CLOVAR gene set for classification where most early stage HGCCOCs and HGEOCs formed a distinct cluster of their own. When restricting the analysis to the four TCGA signatures (ssGSEA or NMF with CLOVAR genes) most early stage HGCCOCs and HGEOC were assigned to the differentiated subtype. Using transcriptional profiling the current study suggests that HGCCOCs and HGEOCs of advanced stage group together with HGSOCs. However, HGCCOCs and HGEOCs of early disease stages may have distinct transcriptional signatures similar to those seen in their low grade counterparts.


Neuromuscular blockade for critical patients in the emergency department.
This retrospective study examines the indications and the effects of 119 doses of succinylcholine or pancuronium given in the emergency department during a 24-month period to patients considered to have immediately life-threatening emergencies. The most common indication for succinylcholine was to accomplish tracheal intubation (20 of 25 patients). Indications for pancuronium included computerized tomography of the head (60 of 94), control of agitation (40 of 94), facilitation of tracheal intubation (20 of 94), control of ventilation (12 of 94), and control of seizure unresponsive to anticonvulsants (4 of 94). Deterioration following succinylcholine occurred in three cases. These included two involving bradycardia and one involving ventricular tachycardia. Major complications following pancuronium included four incidences of ventricular arrhythmias. Intubation failure requiring surgical airway occurred in one patient given succinylcholine, two patients given pancuronium, and one patient who received both succinylcholine and pancuronium. Inadequate documentation of neurological examination prior to blockade was noted in six of 25 succinylcholine and nine of 94 pancuronium cases. Failure to sedate patients who might be aware of paralysis occurred in three of 25 succinylcholine and eight of 94 pancuronium uses. Neuromuscular blocking agents facilitate expeditious management of selected critical patients in the ED. Their prudent use requires anticipation of potential complications, preparation for surgical airway should intubation fail, documentation of physical examination before paralysis, and prior sedation when the patient responds to pain.


Transplantation of parathyroid, adrenal cortex and adrenal medulla using procedures which successfully prolonged islet allograft survival.
Life-long hormone replacement therapy is today the only form of therapy for several endocrine insufficiencies. Transplantation of endocrine tissues could represent a more physiological approach to the treatment of different syndromes such as adrenal insufficiency, diabetes or hypoparathyroidism. Successful experimental islet transplantation across major histocompatibility barriers using cultural pretreatment of the insulin producing tissue in conjunction with temporary immunosuppression of the recipients, encouraged us to attempt similar approaches with parathyroids, adrenal cortex and adrenal medulla. Either bilateral parathyroidectomy or bilateral adrenalectomy were performed on the recipient rats before transplantation, followed by the implantation of parathyroid, adrenal cortical or adrenal medullary tissue beneath the renal capsule. The tissue was transplanted either immediately after its dissection or after pretreatment with 1 week culture. Some of the recipients received a short term cyclosporine treatment. The results indicated that parathyroid and adrenal medulla transplants were often infiltrated by mononuclear cells 30 days after transplantation. In contrast, adrenal cortical tissue was well preserved 4 weeks after transplantation, without showing any sign of rejection when a combination of pre-transplant culture of the adrenal tissue and temporary cyclosporine treatment of the recipients was used.


Validating the European Health Literacy Survey Questionnaire in people with type 2 diabetes: Latent trait analyses applying multidimensional Rasch modelling and confirmatory factor analysis.
To validate the European Health Literacy Survey Questionnaire (HLS-EU-Q47) in people with type 2 diabetes mellitus. The HLS-EU-Q47 latent variable is outlined in a framework with four cognitive domains integrated in three health domains, implying 12 theoretically defined subscales. Valid and reliable health literacy measurers are crucial to effectively adapt health communication and education to individuals and groups of patients. Cross-sectional study applying confirmatory latent trait analyses. Using a paper-and-pencil self-administered approach, 388 adults responded in March 2015. The data were analysed using the Rasch methodology and confirmatory factor analysis. Response violation (response dependency) and trait violation (multidimensionality) of local independence were identified. Fitting the "multidimensional random coefficients multinomial logit" model, 1-, 3- and 12-dimensional Rasch models were applied and compared. Poor model fit and differential item functioning were present in some items, and several subscales suffered from poor targeting and low reliability. Despite multidimensional data, we did not observe any unordered response categories. Interpreting the domains as distinct but related latent dimensions, the data fit a 12-dimensional Rasch model and a 12-factor confirmatory factor model best. Therefore, the analyses did not support the estimation of one overall "health literacy score." To support the plausibility of claims based on the HLS-EU score(s), we suggest: removing the health care aspect to reduce the magnitude of multidimensionality; rejecting redundant items to avoid response dependency; adding "harder" items and applying a six-point rating scale to improve subscale targeting and reliability; and revising items to improve model fit and avoid bias owing to person factors.


Class I KNOX genes are associated with organogenesis during bulbil formation in Agave tequilana.
Bulbil formation in Agave tequilana was analysed with the objective of understanding this phenomenon at the molecular and cellular levels. Bulbils formed 14-45 d after induction and were associated with rearrangements in tissue structure and accelerated cell multiplication. Changes at the cellular level during bulbil development were documented by histological analysis. In addition, several cDNA libraries produced from different stages of bulbil development were generated and partially sequenced. Sequence analysis led to the identification of candidate genes potentially involved in the initiation and development of bulbils in Agave, including two putative class I KNOX genes. Real-time reverse transcription-PCR and in situ hybridization revealed that expression of the putative Agave KNOXI genes occurs at bulbil initiation and specifically in tissue where meristems will develop. Functional analysis of Agave KNOXI genes in Arabidopsis thaliana showed the characteristic lobed phenotype of KNOXI ectopic expression in leaves, although a slightly different phenotype was observed for each of the two Agave genes. An Arabidopsis KNOXI (knat1) mutant line (CS30) was successfully complemented with one of the Agave KNOX genes and partially complemented by the other. Analysis of the expression of the endogenous Arabidopsis genes KNAT1, KNAT6, and AS1 in the transformed lines ectopically expressing or complemented by the Agave KNOX genes again showed different regulatory patterns for each Agave gene. These results show that Agave KNOX genes are functionally similar to class I KNOX genes and suggest that spatial and temporal control of their expression is essential during bulbil formation in A. tequilana.


Cognitive function after electroconvulsive therapy for depression: relationship to clinical response.
As uncertainty remains about whether clinical response influences cognitive function after electroconvulsive therapy (ECT) for depression, we examined the effect of remission status on cognitive function in depressed patients 4 months after a course of ECT. A secondary analysis was undertaken on participants completing a randomised controlled trial of ketamine augmentation of ECT for depression who were categorised by remission status (MADRS ⩽10 v. >10) 4 months after ECT. Cognition was assessed with self-rated memory and neuropsychological tests of anterograde verbal and visual memory, autobiographical memory, verbal fluency and working memory. Patients were assessed through the study, healthy controls on a single occasion, and compared using analysis of variance. At 4-month follow-up, remitted patients (N = 18) had a mean MADRS depression score of 3.8 (95% CI 2.2-5.4) compared with 27.2 (23.0-31.5) in non-remitted patients (N = 19), with no significant baseline differences between the two groups. Patients were impaired on all cognitive measures at baseline. There was no deterioration, with some measures improving, 4-months after ECT, at which time remitted patients had significantly improved self-rated memory, anterograde verbal memory and category verbal fluency compared with those remaining depressed. Self-rated memory correlated with category fluency and autobiographical memory at follow-up. We found no evidence of persistent impairment of cognition after ECT. Achieving remission improved subjective memory and verbal memory recall, but other aspects of cognitive function were not influenced by remission status. Self-rated memory may be useful to monitor the effects of ECT on longer-term memory.


Racial Differences in Elevated C-Reactive Protein Among US Older Adults.
To investigate racial differences in elevated C-reactive protein (CRP) and the potential factors contributing to these differences in US older men and women. Nationally representative cohort study. Health and Retirement Study, 2006 to 2014. Noninstitutionalized non-Hispanic black and white older adults living in the United States (n = 13 517). CRP was categorized as elevated (>3.0 mg/L) and nonelevated (≤3.0 mg/L) as the primary outcome. Measures for demographic background, socioeconomic status, psychosocial factors, health behaviors, and physiological health were examined as potential factors contributing to race differences in elevated CRP. Median CRP levels (interquartile range) were 1.67 (3.03) mg/L in whites and 2.62 (4.95) mg/L in blacks. Results from random effects logistic regression models showed that blacks had significantly greater odds of elevated CRP than whites (odds ratio = 2.58; 95% confidence interval [CI] = 2.20-3.02). Results also showed that racial difference in elevated CRP varied significantly by sex (predicted probability [PP] [white men] = 0.28 [95% CI = 0.27-0.30]; PP [black men] = 0.38 [95% CI = 0.35-0.41]; PP [white women] = 0.35 [95% CI = 0.34-0.36]; PP [black women] = 0.49 [95% CI = 0.47-0.52]) and remained significant after risk adjustment. In men, the racial differences in elevated CRP were attributable to a combination of socioeconomic (12.3%) and behavioral (16.5%) factors. In women, the racial differences in elevated CRP were primarily attributable to physiological factors (40.0%). In the US older adult population, blacks were significantly more likely to have elevated CRP than whites; and the factors contributing to these differences varied in men and women. J Am Geriatr Soc 68:362-369, 2020.


[Effect of incomplete starvation on development of compensatory testicular hypertrophy during postnatal ontogenesis of rats].
The incomplete starvation of rats during the first month of life resulted in the inhibition of development of the spermatogenic epithelium cells in 80% of seminiferous tubules, preserved the increased permeability of hematotesticular barrier with respect to rivanol and the ability of rats to react by the increase of testis volume in response to unilateral castration. The data obtained confirm our hypothesis according to which there is a definite correlation between the degree of spermatogenesis completion, the function of hematotesticular barrier and the ability of animals for compensatory hypertrophy of testis.


Mapping psoralen cross-links at the nucleotide level in mammalian cells: suppression of cross-linking at transcription factor- or nucleosome-binding sites.
We have developed a new genomic sequencing method for detecting, with resolution at the nucleotide level, the interstrand DNA cross-links induced by 4,5',8-trimethylpsoralen along single-copy genes in mammalian cells. The cross-links (diadducts) initially formed are converted into monoadducts by alkali reversal prior to the use of terminal transferase-dependent PCR (TD-PCR). After alkali reversal, but not before, the DNA strands can be separated and used as templates for gene-specific primer extension, which is the first step in the TD-PCR procedure. The converted psoralen adducts block primer extension, and the prematurely terminated single-stranded products are then amplified by TD-PCR and visualized on a sequencing gel. Adducts formed by angelicin, a psoralen derivative that forms only monoadducts, were also investigated by use of TD-PCR. Comparison of the adduct distribution patterns of in vivo-treated DNA with those of in vitro-treated DNA revealed that the binding of transcription factors inhibited both psoralen cross-linking and angelicin monoadduct formation in the c-JUN and c-FOS promoters in living human cells. Adduct formation was also inhibited in the region of a putative positioned nucleosome in the c-FOS promoter. These methods should be of general use for study of in vivo protein-DNA interactions and DNA repair.


Proteinopathy and Longitudinal Cognitive Decline in Parkinson Disease.
People with Parkinson disease (PD) commonly experience cognitive decline, which may relate to increased α-synuclein, tau, and β-amyloid accumulation. This study examines whether the different proteins predict longitudinal cognitive decline in PD. All participants (PD n = 152, controls n = 52) were part of a longitudinal study and completed a lumbar puncture for CSF protein analysis (α-synuclein, total tau [tau], and β-amyloid42 [β-amyloid]), a β-amyloid PET scan, and/or provided a blood sample for APOE genotype (ε4+, ε4-), which is a risk factor for β-amyloid accumulation. Participants also had comprehensive, longitudinal clinical assessments of overall cognitive function and dementia status, as well as cognitive testing of attention, language, memory, and visuospatial and executive function. We used hierarchical linear growth models to examine whether the different protein metrics predict cognitive change and multivariate Cox proportional hazard models to predict time to dementia conversion. Akaike information criterion was used to compare models for best fit. Baseline measures of CSF β-amyloid predicted decline for memory (p = 0.04) and overall cognitive function (p = 0.01). APOE genotypes showed a significant group (ε4+, ε4-) effect such that ε4+ individuals declined faster than ε4- individuals in visuospatial function (p = 0.03). Baseline β-amyloid PET significantly predicted decline in all cognitive measures (all p ≤ 0.004). Neither baseline CSF α-synuclein nor tau predicted cognitive decline. All 3 β-amyloid--related metrics (CSF, PET, APOE) also predicted time to dementia. Models with β-amyloid PET as a predictor fit the data the best. Presence or risk of β-amyloid accumulation consistently predicted cognitive decline and time to dementia in PD. This suggests that β-amyloid has high potential as a prognostic indicator and biomarker for cognitive changes in PD.


[Study on the transgenic tobacco expressing truncated wheat cold shock protein gene TA3-13 and analysis of disease resistance].
TA3-13 is a truncated gene coding for the fragment of wheat (Triticum aestivum L.) cold shock protein WCP1. It has been shown previously that the procaryotically expressed TA3-13 can induce resistance to Tobacco mosaic virus (TMV) when sprayed onto plant leaves. In this study, we constructed an expression vector pB-3-13 by cloning TA3-13 into the bionary vector pBI121 and transformed it into Agrobacterium tumefaciense strain EHA105 via freeze-thaw method. Tobacco (Nicotiana tobacum cv. Xanthi nc.) transformation was performed using the leaf disc infection method. After screening on MS medium containing kanamycin and PCR analysis, 33 T0 plantlets were identified as transgenic. Seeds from twenty T0 plants were collected and planted as T1 lines. Two T1 lines were selected for further characterization. PCR and GUS staining analysis showed that TA3-13 was integrated into the T1 tobacco genome and expressed. When inoculated on leaves, the transgenic tobacco showed significant resistance against TMV and rot pathogen Pectobactrium carotovorum subsp. carotovorum. These results suggest that the expression of TA3-13 in tobacco can induce defense responses to pathogen infection.


A novel retinoid-related molecule inhibits pancreatic cancer cell proliferation by a retinoid receptor independent mechanism via suppression of cell cycle regulatory protein function and induction of caspase-associated apoptosis.
Retinoid-related molecules are important potential agents for the treatment of cancer. In the present study, we test the effect of a novel retinoid-related ligand, AGN193198 (4-[3-(1-heptyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-oxo-prophenyl] benzoic acid), on pancreatic cancer cell proliferation and survival. AGN193198 treatment reduces BxPC-3 cell proliferation more efficiently than high-affinity retinoid acid receptor (RAR)- or retinoid X receptor (RXR)-selective retinoids. Moreover, AGN193198 does not activate transcription from RAR or RXR response elements and its effects on cell survival are not reversed by treatment with RAR- or RXR receptor-selective antagonists. These results suggest that the AGN193198-dependent inhibition of BxPC-3 cell function is not mediated via activation of the classical retinoid receptors. Cell cycle analysis of AGN193198-treated BxPC-3 cells indicates that AGN193198 causes accumulation of cells in G2/M. This change is associated with a marked reduction in regulators of S (cyclin A, cyclin-dependent kinase (cdk)2), G2/M (cyclin B1, cdk1, cdc25c) and G1 (cyclin D1, cyclin E, cdk2, cdk4) phase, and an increase in p21 and p27 level. Kinases assays reveal that cdk1, cdk2 and cdk4 activity are suppressed in AGN193198-treated cells. In addition, reduced cell proliferation is associated with enhanced procaspase (3, 8 and 9) and PARP cleavage. Z-VAD-FMK, a pancaspase inhibitor, inhibits AGN193198-dependent caspase activation and attenuates cell death. Z-VAD-FMK inhibits PARP cleavage, but does not alter the AGN193198-dependent reduction in cell cycle regulatory protein expression and activity, suggesting that caspase activation and suppression of cell cycle regulatory protein levels are independent processes. AGN193198 produces similar responses in other pancreatic cancer cell lines including AsPC-1 and MIA PaCa-2. These studies suggest that AGN193198 may be useful for the treatment of pancreatic cancer.


Effects of bacterial lipopolysaccharide on the induction and expression of cell-mediated immunity. II. Stimulation of the efferent arc.
The delayed-type hypersensitivity (DTH) produced by subcutaneous or intravenous immunization of mice with sheep red blood cells (SRBC) is mediated by T cells in cooperation with accessory cells (monocytes). Different effects of bacterial lipopolysaccharide (LPS) on this T cell activity were found at different stages of the immune response. a) T cell activity was enhanced by LPS given 1 to 3 days after sensitization. Enhancement, which was most marked when treatment was given on the 2nd day of the immune response, did not occur unless LPS was introduced into a site that drains to the responding lymph node. This stimulatory effect was dose dependent. b) A similar effect on the response to intravenous immunization caused DTH to appear transiently in mice given a T cell-blocking dose (10-9) of SRBC. c) DTH was suppressed by LPS given at the height of the T cell response (day 4). This effect, which was short lived and reversible, was due to the action of LPS on the accessor cells needed for the expression of DTH. Treatment of recipients with LPS completely blocked the adoptive transfer of DTH to both normal and spenectomized mice. The ability to react was regained slowly, but it returned promptly to splenectomized recipients. LPS has clearly more than one effect on the expression of cell-mediated immunity because it affects specific and non-specific mediator cells in different ways.


Clear cell papillary renal cell carcinoma with angiomyomatous stroma: a histological, immunohistochemical, and fluorescence in situ hybridization study.
Clear cell papillary renal cell carcinoma (CCPRCC) is a novel tumor entity that was recently recognized as a new distinct epithelial tumor within the current classification system. Nonclassic morphologic variants have rarely been reported. We present six challenging cases of CCPRCC with prominent (>75 %) tubular, acinar, and/or solid component and angioleiomyomatous stroma. The tumors lacked well-organized papillary architecture. All tumors had a variously thick capsule formed by a layer of bands of smooth muscle. The leiomyomatous tissue often entirely encased patches of tubular structures, or it formed only small leiomyomatous islands within the epithelial component. There was a remarkable relationship between the vascular network and the epithelial component in the sense that every single tubule or acinus was associated with a fine capillary network, with the capillaries intimately surrounding the tubular or acinar circumference. CCPRCC with variant morphology expressed carbonic anhydrase IX (CA-IX) in cup-shaped distribution. In addition, the tumor cells stained positive for cytokeratin 34betaE12, CK7, and vimentin. Renal cell carcinoma (RCC), P504s/AMACR, Melan A, and HMB45 were negative in tumor cells in all cases examined. Fluorescence in situ hybridization studies showed the presence of a normal copy number for chromosomes 7, 17, 3q, and 3p. CCPRCC with variant morphology seems to have a favorable prognosis. In the current series, tumor stage was low at presentation, and none of the patients had local recurrence or metastatic disease. The distinction between CCPRCC with variant morphology and clear cell RCC is critical because no case of CCPRCC has behaved aggressively.


A simplified approach for computed tomography with an X-ray grating interferometer.
We present a simplified acquisition and processing method for X-ray grating interferometry computed tomography (CT). The proposed approach eliminates the need to scan the gratings, thus allowing for a faster CT acquisition compared to methods presently in use. The contrast in the reconstructed images can be expressed as a linear combination of the absorption and refraction within the sample. Experimental images of a test phantom made of known materials and a human bone-cartilage sample prove the correctness of the method and show very good agreement with the theory. The here proposed approach might be highly interesting in many fields where a reduced imaging acquisition time is requested and/or where the radiation dose delivered to the sample has to be kept low, such as, for example, in in-vivo imaging.


A novel crystallization pathway for SiGe alloy rapid cooling.
Understanding the structural evolution of covalent systems under rapid cooling is very important to establish a comprehensive solidification theory. Herein, we conducted molecular dynamics simulations to investigate the crystallization of silicon-germanium (SiGe) alloys. It was found that during crystallization, the saturation and orientation of covalent bonds are satisfied in order, resulting in three phase transitions. The saturation is satisfied during a continuous phase transition that occurs in the super-cooled liquid state. When the orientation was satisfied at the local scale, a novel state, the critical-nuclei crystalline (CNC) phase was obtained, where the local diamond structures increase in number with time and ultimately stabilize at an average size at the critical value. Finally with a coordinated rearrangement of atoms, the orientation is satisfied globally and a stable diamond crystal is produced. For SiGe alloys this CNC phase is universal and rather stable, and the stable temperature range has a certain relationship with the cooling rate and number fraction of atoms. This novel pathway is believed to be universal for such materials including carbon. The CNC state can explain the observation that diamond can be obtained without high pressure. These findings will significantly advance the understanding of the mechanism of phase transition, particularly for covalently bonded materials.


Comprehension and acceptability of on-board traffic information: Beliefs and driving behaviour.
Co-Drive on-board traffic information system is a complementary tool providing a dynamic management of transportation infrastructure and traffic as well as the diffusion of accurate real-time information about the road environment and motorists' driving behaviour. The aim of this study was to examine drivers' acceptability of Co-Drive by investigating the impact of traffic information provided via on-board display devices on motorists' beliefs and behaviour. 116 drivers (Men=46.6%), between 22 and 62 years, participated to a driving simulator experiment. They were randomly divided into two experimental groups according to the type of display device (Blackberry vs. iPhone) and a control group. The experimental groups were exposed to fourteen on-board traffic messages: warning (e.g., road crash), recommendation (e.g., the use of seat-belt) and comfort messages (e.g., the location of a gas station). They had to validate each message by pushing the headlight flashing button as soon as they understood it. At the end, all participants had to fill in a questionnaire. Drivers evaluated positively the on-board messages, expressed a high level of confidence in the on-board information and estimated having received it sufficiently in advance for them to adjust their behaviour. Regardless of the type of display device, they took more time to read warning and recommendation messages as compared to comfort messages and complied with them. Finally, those exposed to the messages adapted their behaviour easier to the road events than those who did not receive them. Practical implications of the results are discussed.


Lithium carbonate in cluster headache: assessment of its short- and long-term therapeutic efficacy.
The short- and long-term effects of administration of lithium carbonate in cluster headache (CH) have been investigated. Of the 90 patients treated (78 males and 12 females), 68 had episodic CH and 22 had the chronic form of the disease. The doses used were almost always 900 mg/day. Eleven of the 22 patients with chronic CH showed a definite, constant improvement both short and long term. In 7 of the 22 patients, lithium treatment provided excellent results initially but was later followed by some transient worsening; in the remaining 4 only partial benefits were observed initially and treatment proved still less effective after a few months. The effects of cessation of lithium administration after at least five months of continuous treatment were studied in 9 cases. In 6 of them the attacks re-appeared immediately, whereas in 3 the attacks occurred again only after free intervals of four to six months. Of the 68 patients with episodic CH, 26 proved highly responsive to treatment, 26 only partially responsive, and 16 refractory. In 3 cases, after one to three years of continuous treatment, euthyroid goitre developed, which disappeared after the drug was discontinued.


Preoperative brain MRI features and occurrence of postoperative delirium.
Delirium is a frequent complication after surgery with important negative outcomes for affected patients and society. However, it is still largely unknown why some patients have a predisposition for delirium and others not. To increase our understanding of the neural substrate of postoperative delirium, we studied the association between preoperative brain MRI features and the occurrence of delirium after major surgery. A group of 413 patients without dementia (Mean 72 years, SD: 5) was included in a prospective observational two-center study design. The study was conducted at Charité Universitätsmedizin (Berlin, Germany) and the University Medical Center Utrecht (Utrecht, The Netherlands). We measured preoperative brain volumes (total brain, gray matter, white matter), white matter hyperintensity volume and shape, brain infarcts and cerebral perfusion, and used logistic regression analysis adjusted for age, sex, intracranial volume, study center and type of surgery. Postoperative delirium was present in a total of 70 patients (17%). Preoperative cortical brain infarcts increased the risk of postoperative delirium, although this did not reach statistical significance (OR (95%CI): 1.63 (0.84-3.18). Furthermore, we found a trend for an association of a more complex shape of white matter hyperintensities with occurrence of postoperative delirium (OR (95%CI): 0.97 (0.95-1.00)). Preoperative brain volumes, white matter hyperintensity volume, and cerebral perfusion were not associated with occurrence of postoperative delirium. Our study suggests that patients with preoperative cortical brain infarcts and those with a more complex white matter hyperintensity shape may have a predisposition for developing delirium after major surgery.


Characterization and expression of human bifunctional 3'-phosphoadenosine 5'-phosphosulphate synthase isoforms.
Sulphonation, a fundamental process essential for normal growth and development, requires the sulphonate donor molecule 3'-phosphoadenosine 5'-phosphosulphate (PAPS), which is produced from ATP and inorganic sulphate by the bifunctional enzyme PAPS synthase. In humans, two genes encode isoenzymes that are 77% identical at the amino acid level, and alternative splicing creates two subtypes of PAPS synthase 2. The question as to whether distinctions in amino acid composition are reflected in differences in activity has been examined. The specific activity of the PAPS synthase 2 subtypes is 10- to 15-fold higher than that for PAPS synthase 1. The greater catalytic efficiency of the PAPS synthase 2 subtypes is demonstrated further by the 3- to 6-fold higher k(cat)/K(m) ratios for ATP and inorganic sulphate as compared with the ratios for PAPS synthase 1. In humans, PAPS synthase 1 is expressed ubiquitously, and is the dominant isoform in most tissues, whereas expression of the PAPS synthase 2 subtypes is variable and tissue-specific. It is noteworthy that, similar to other human tissues, PAPS synthase 1 also appears to be the dominant isoform expressed in cartilage. The latter finding initially created a conundrum, since there is a specific human dwarfing disorder that is known to be caused by a mutation in the PAPS synthase 2 gene. This apparent enigma would seem to be resolved by examination of cartilage from guinea-pigs as an animal model. Similar to humans, cartilage from mature animals predominantly expresses PAPS synthase 1. In contrast, expression of PAPS synthase 1 is relatively low in the cartilage of immature guinea-pigs, including the growth plate of long bones, whereas PAPS synthase 2 is the highly expressed isoenzyme.


Brain dynamic neurochemical changes in dystonic patients: a magnetic resonance spectroscopy study.
Measurements of the concentrations of γ-aminobutyric acid (GABA) and glutamate in the motor cortices and lentiform nuclei of dystonic patients using single-voxel (1)H magnetic resonance spectroscopy (MRS) have yielded conflicting results so far. This study aimed to investigate dynamic changes in metabolite concentrations after stimulation of the motor cortices in patients with upper limb dystonia. Using single-voxel MRS at 3 T, the concentrations of GABA, glutamate plus glutamine, and N-acetylaspartate were measured bilaterally in the primary sensorimotor cortex, lentiform nucleus, and occipital region before and after 5-Hz transcranial magnetic stimulation (TMS) over the dominant motor cortex. Data obtained from 15 patients with upper limb primary dystonia were compared with data obtained from 14 healthy volunteers. At baseline, there was no group difference in concentration of metabolites in any region. rTMS induced a local (in the stimulated motor cortex) decrease of N-acetylaspartate (P < .006) to the same extent in healthy volunteers and patients. GABA concentrations were modulated differently, however, decreasing mildly in patients and increasing mildly in healthy volunteers (P = .05). There were no remote effects in the lentiform nucleus in either group. The stimulation-induced changes in metabolite concentrations have been interpreted in view of the increased energy demand induced by rTMS. The dynamics of the GABA concentration were specifically impaired in dystonic patients. Whether these changes reflect changes in the extrasynaptic or synaptic GABA component is discussed.


Current status of clinical trials for small cell lung cancer.
SCLC represents 13% of all lung cancer cases and is the most aggressive form of lung cancer with an overall 5-year survival less than 5%. The combination of cisplatin or carboplatin with etoposide remains the standard treatment for SCLC. Despite a good initial response to therapy, most SCLC patients suffer from the development of chemotherapy resistance and relapse. Second-line chemotherapy should then be applied, which however frequently results in only a low survival increase. To improve the outcome of SCLC, new drugs such as topotecan, irinotecan, amrubicin, paclitaxel or gemcitabin have recently been added to chemotherapeutic regimens. In combination with etoposide or platinum-based agents, some of these drugs could be able to offer a significant survival benefit. Moreover, recent progress in the understanding of SCLC biology has led to the identification of critical signaling pathways, which allowed the development of specific targeted therapies for the disease. A number of new molecules are currently under clinical evaluation in SCLC. These inhibitors target the proteasome, receptors tyrosine kinases, farnesyltransferase, Bcl-2, or angiogenic pathways. Some studies have demonstrated that these new strategies can be associated with chemotherapy and show positive results. This review summarizes recent clinical trials performed with new chemotherapeutic regimens and the current status of specific targeted approaches in SCLC patients.


[Gastrointestinal hemorrhage secondary to a pancreatic pseudoaneurysm].
Acute hemorrhage from pancreatic pseudoaneurysm is the most rapidly fatal complication of pancreatitis, with a reported mortality rate of > 90% in untreated patients. The diagnosis of pancreatic pseudoaneurysm requires a high index of suspicion and the abdominal angiography is the gold standard. Transcatheter embolization is an alternative to surgery for treatment in selected patients. Early diagnosis and treatment decrease the mortality dramatically. We describe a patient with a gastrointestinal bleeding from a ruptured pancreatic pseudoaneurysm, with an angiography diagnosis and transcatheter embolization. We treated the pseudocyst with an endoscopic drainage. A review of literature is presented.


Low-pathogenicity H7N2 avian influenza outbreak in Virgnia during 2002.
An outbreak of low-pathogenicity H7N2 avian influenza virus (AIV) in the Shenandoah Valley of Virginia during the spring and summer of 2002 affected 197 farms and resulted in the destruction of over 4.7 million birds. The outbreak affected primarily turkey farms (28 breeders, 125 grow out) with some spillover into chicken farms (29 breeders, 13 grow out, 2 table-egg layers). Although no direct link was established, the strain of H7N2 AIV in this outbreak had a molecular fingerprint that was essentially identical to the H7N2 AIV strain that has circulated in the live bird markets of the northeastern United States for the last 8 yr. After an initial delay caused by lack of viable disposal options, depopulation and disposal, primarily in sanitary landfills, was carried out within 24 hr of detection of a positive flock. Increased surveillance efforts included once-a-week testing of the daily mortality of all poultry farms in the region, testing of all breeder farms every 2 wk, and testing of all flocks prior to movement for any reason. A statistical sampling of backyard flocks and wild birds found no evidence of the virus. The successful eradication of this outbreak was the result of the efforts of a highly effective task force of industry, state, and federal personnel.


Automated Annotation and Evaluation of In-Source Mass Spectra in GC/Atmospheric Pressure Chemical Ionization-MS-Based Metabolomics.
Gas chromatography using atmospheric pressure chemical ionization coupled to mass spectrometry (GC/APCI-MS) is an emerging metabolomics platform, providing much-enhanced capabilities for structural mass spectrometry as compared to traditional electron ionization (EI)-based techniques. To exploit the potential of GC/APCI-MS for more comprehensive metabolite annotation, a major bottleneck in metabolomics, we here present the novel R-based tool InterpretMSSpectrum assisting in the common task of annotating and evaluating in-source mass spectra as obtained from typical full-scan experiments. After passing a list of mass-intensity pairs, InterpretMSSpectrum locates the molecular ion (M0), fragment, and adduct peaks, calculates their most likely sum formula combination, and graphically summarizes results as an annotated mass spectrum. Using (modifiable) filter rules for the commonly used methoximated-trimethylsilylated (MeOx-TMS) derivatives, covering elemental composition, typical substructures, neutral losses, and adducts, InterpretMSSpectrum significantly reduces the number of sum formula candidates, minimizing manual effort for postprocessing candidate lists. We demonstrate the utility of InterpretMSSpectrum for 86 in-source spectra of derivatized standard compounds, in which rank-1 sum formula assignments were achieved in 84% of the cases, compared to only 63% when using mass and isotope information on the M0 alone. We further use, for the first time, automated annotation to evaluate the purity of pseudospectra generated by different metabolomics preprocessing tools, showing that automated annotation can serve as an integrative quality measure for peak picking/deconvolution methods. As an R package, InterpretMSSpectrum integrates flexibly into existing metabolomics pipelines and is freely available from CRAN ( https://cran.r-project.org/ ).


Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness.
Type beta transforming growth factor (TGF-beta) is a unique polypeptide that has been isolated from a number of different tissues and can induce the phenotypic transformation of non-neoplastic fibroblasts as measured by the stimulation of their growth in soft agar. Recently, TGF-beta has been demonstrated to exert profound inhibitory effects on T and B lymphocyte proliferation. In this study, the effects of TGF-beta on natural killer (NK) cell function were investigated. After 20 hr of culture in the presence of TGF-beta, the NK activity of peripheral blood lymphocytes (PBL) was significantly reduced compared with PBL cultured in medium alone. Similarly, TGF-beta produced a significant depression in the cytolytic activity of highly enriched large granular lymphocytes (LGL). This effect of TGF-beta appeared to be mediated directly on the effector cells, because cultivation of the K562 target cells in TGF-beta did not affect target cell susceptibility to lysis. Binding studies with 125I-TGF-beta indicated that LGL possess approximately 1400 high-affinity (Kd = 1PM) receptors/cell, which represents a considerably higher affinity receptor for TGF-beta than that found on fibroblasts. Culturing of PBL and LGL in TGF-beta resulted in a marked blunting of the boosting of NK cytolysis by interferon-alpha but not by interleukin 2, which suggested that TGF-beta may down-regulate interferon-alpha receptors on NK cells. These results, indicate that in addition to inhibitory effects on T and B cells, TGF-beta also inhibits NK cell function. Although the in vivo role of TGF-beta is presently undefined, it may be an important immunoregulatory protein that has a negative influence on lymphocyte activation.


Targeting and structuring information resource use: a path toward informed clinical decisions.
A core skill for all physicians to master is that of information manager. Despite a rapidly expanding set of electronic and print-based information resources, clinicians continue to answer their clinical queries predominantly through informal or formal consultation. Even as new tools are brought to market, the majority of them present information in a rigid fashion, presenting cumbersome user interfaces and inflexible data presentation. The need to rethink the structure of electronic information is paramount to improving the use of evidence at the bedside. As new tools are developed and educators teach clinicians to use them, the context for use of information resources must be considered, with special attention to physician work-flow, following the three paths outlined in this article. The process will be facilitated greatly by promoting evidence-based practice for the care of patients in the hospital and clinic setting.


Comparative Raman and HRTEM study of nanostructured GaN nucleation layers and device layers on sapphire (0001).
Raman spectroscopy in conjunction with high-resolution transmission electron microscopy (HRTEM) has been used to study structural characteristics and strain distribution of the nanostructured GaN nucleation layer (NL) and the GaN device layer on (0001) sapphire substrates used for light-emitting diodes and lasers. Raman peaks corresponding to the cubic and the hexagonal phase of GaN are observed in the Raman spectrum from 15 nm and 45 nm NLs. A comparison of the peak intensities for the cubic and hexagonal phases of GaN in the NLs suggests that the cubic phase is dominant in the 15 nm NL and the hexagonal phase in the 45 nm NL. An increase in the density of stacking faults in the metastable cubic GaN (c-GaN) phase with increasing growth time lowers the system energy as well as locally converts c-GaN phase into hexagonal GaN (h-GaN). It also explains the observation of the more intense peaks of h-GaN in the 45 nm NL compared to c-GaN peaks. For the sample wherein an h-GaN device layer was grown at higher temperatures on the NL, narrow Raman peaks corresponding to only h-GaN were observed, confirming the high-quality of the films. The peak shift of the E2(H)(LO) mode of h-GaN in the NLs and the h-GaN film suggests the presence of a tensile stress in the NL which is attributed to defects such as stacking faults and twins, and a compressive stress in high-temperature grown h-GaN film which is attributed to the thermal-expansion mismatch between the film and the substrate. The peak shifts of the substrate also reveal that during the low temperature growth of the NL the substrate is under a compressive stress which is attributed to defects in the NL and during the high temperature growth of the device layer, there is a tensile strain in the substrate as expected from differences in coefficients of thermal expansion of the film and the substrate during the cooling cycle.


Evaluation of the introduction of the national Down syndrome screening program in the Netherlands: age-related uptake of prenatal screening and invasive diagnostic testing.
To study the effect of different government prenatal screening (PNS) policies on the uptake of PNS and prenatal diagnostic testing (PND) over the periods 2001-2003 (PNS on request), 2004-2006 (permission to offer the first-trimester combined test (FCT) to women of advanced maternal age (AMA), with women aged <36 years informed on explicit request) and 2007-2010 (introduction of population screening) and to evaluate whether trends in uptake are related to maternal age. The indication AMA for PND is still warranted, and the costs for FCT are only reimbursed for AMA women. Analysis of data on the first- and second-trimester screening program (n=41,600) for Down syndrome (DS) and on PND (n=10,795) performed from 2001 to 2010 in the region North-Holland of the Netherlands. To evaluate the actual participation in PNS and PND in different maternal age groups, estimation of the age distribution of women who underwent a fetal anomaly scan in 2009 (n=14,481) was used as a reference population (participation of 85.2%). The overall uptake of FCT was 35.2% in 2010. Over the years the number of FCT in all age groups increased significantly (P<0.001). Overall the number of PND decreased significantly; the number of PND for AMA decreased and the number of PND for increased risk at FCT (in women <36 and ≥36 years) increased (P<0.05). Since 2004 significantly more DS cases were detected with FCT in AMA women and fewer with PND for AMA, and since 2007 more DS cases were detected with FCT in women <36 years (P<0.001). The effect of the national screening program is limited. Significantly more women opt for PNS but the overall uptake remains low, especially in younger women. A significant number of AMA women still opt for PND for AMA. The choice for FCT and PND for AMA seems dependent on background risk. To accomplish a more effective screening policy, reimbursement of the cost of the test should apply to all women and the indication for PND for AMA should be abolished.


Meta-analysis of the effect of natural frequencies on Bayesian reasoning.
The natural frequency facilitation effect describes the finding that people are better able to solve descriptive Bayesian inference tasks when represented as joint frequencies obtained through natural sampling, known as natural frequencies, than as conditional probabilities. The present meta-analysis reviews 20 years of research seeking to address when, why, and for whom natural frequency formats are most effective. We review contributions from research associated with the 2 dominant theoretical perspectives, the ecological rationality framework and nested-sets theory, and test potential moderators of the effect. A systematic review of relevant literature yielded 35 articles representing 226 performance estimates. These estimates were statistically integrated using a bivariate mixed-effects model that yields summary estimates of average performances across the 2 formats and estimates of the effects of different study characteristics on performance. These study characteristics range from moderators representing individual characteristics (e.g., numeracy, expertise), to methodological differences (e.g., use of incentives, scoring criteria) and features of problem representation (e.g., short menu format, visual aid). Short menu formats (less computationally complex representations showing joint-events) and visual aids demonstrated some of the strongest moderation effects, improving performance for both conditional probability and natural frequency formats. A number of methodological factors (e.g., exposure to both problem formats) were also found to affect performance rates, emphasizing the importance of a systematic approach. We suggest how research on Bayesian reasoning can be strengthened by broadening the definition of successful Bayesian reasoning to incorporate choice and process and by applying different research methodologies. (PsycINFO Database Record