Endovascular repair of popliteal artery aneurysms with Anaconda limbs: technique and early results.
The objective is to report the feasibility and technique of treating popliteal artery aneurysms (PAA) with a stent made of nitinol rings externally supported by thin polyester (Anaconda limbs). PAA are the most common peripheral aneurysms. The main limitations of stents used in these settings are: short lengths, longitudinal and horizontal compliance mismatch; graft failure from angulation and movement at the joint level; and dislodgment. This is a prospective multicenter cohort study of consecutive symptomatic and asymptomatic PAA treated in tertiary vascular centers. Outcomes included patency of the stent and postoperative time-to-independent-ambulation and to-climb-a-flight-of-stairs. Fourteen PAA were treated in 12 men, age 72 +/- 3 years. The median ASA classification was 2.5. The length of artery covered was 147 +/- 41 mm. The PAA diameter was 31 +/- 5 mm, 6 were symptomatic. One stent was used in 6 aneurysms, two in 7, and three in 1. The average stent diameter was 10 +/- 1 mm. The length of the proximal neck was 24 +/- 6 mm with a diameter of 9.8 +/- 1.9, and length of the distal neck 23 +/- 3 mm with a diameter of 8.7 +/- 1.2 mm. In 6 aneurysms, the stent crossed the knee joint. There was no mortality, and one stent occluded (primary patency 93% at 6 +/- 3 months). The median hospital stay was 1.7 days, time to independent ambulation was 3 hr and the time to climbing a flight of stairs was 1 day. The use of Anaconda limbs for endovascular repair of PAA is feasible and safe.


Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs.
To investigate the phenotype of cells in normal and degenerate intervertebral discs by studying the expression of molecules characteristic of chondrocytes in situ. Human intervertebral discs taken at surgery were graded histologically, and classified on this basis as normal or degenerate. Eighteen of each type were selected, and in situ hybridisation was performed for the chondrocytic markers Sox9 and collagen II using (35)S labelled cDNA probes. Aggrecan was located by immunohistochemistry, using the monoclonal antibody HAG7E1, and visualised with an avidin-biotin peroxidase system. In the normal discs, strong signals for Sox9 and collagen II mRNA, and strong staining for the aggrecan protein were seen for the cells of the nucleus pulposus (NP), but reactions were weak or absent over the cells of the annulus fibrosus (AF). In degenerate discs, the Sox9 and collagen II mRNA signals remained visible over the cells of the NP and were again absent in the AF. Aggrecan staining was not visible in the NP cells, and was again absent in the AF. Cells of the normal NP showed expression of all three markers, clearly indicating a chondrocytic phenotype. In degeneration, there was evidence of a loss of aggrecan synthesis, which may contribute to the pathogenesis of disc degeneration. AF cells showed no evidence of a chondrocytic phenotype in either normal or degenerate discs.


Functions and tocopherol content of blood platelets from elderly people after low intake of purified eicosapentaenoic acid.
Elderly people present an increased incidence of atherosclerosis and vascular cerebral damages, associated with blood platelet hyperactivity and a stimulation of arachidonic acid metabolism in vivo. The effects of a low intake of purified eicosapentaenoic acid (EPA) on platelet hyperactivity in old human subjects has been investigated. In a randomized, double blind study, 8 people took during 2 months a daily intake of 100 mg of eicosapentaenoic acid (EPA) given as a triglyceride (1,3-dioctanoyl,2-eicosapentaenoyl-glycerol), and 8 other subjects ingested a placebo. A slight, but significant reduction of platelet-rich plasma aggregation in response to epinephrine and arachidonic acid occurred after EPA intake, as well as a decreased aggregation of washed platelets induced by thrombin, although collagen- and U-46619-induced aggregations were not significantly modified. EPA intake failed to affect arachidonic acid metabolism in thrombin-stimulated platelets or in clotted venous blood. The urinary excretion of thromboxane, 6-keto-PGF1 alpha and their 2,3-dinor-metabolites was also not modified. Similarly, no change in the plasma and platelet lipid fatty acid compositions could be observed. Platelet, but not plasma, alpha- and gamma-tocopherol were enhanced by EPA intake. An increase of platelet vitamin E has been associated with a decrease of aggregation, especially in vitamin E-deficient subjects, like elderly people. Therefore, low intake of EPA might have contributed to inhibit platelet aggregation by increasing cellular vitamin E.


Potential impact of industrial transfer on PM2.5 and economic development under scenarios oriented by different objectives in Guangdong, China.
For sustainable regional development, industrial transfer is an important trend that will potentially change the spatial and temporal pattern of air pollution and economic development. Aiming to better regulate industrial transfer and guide policy-making, this study proposes an assessment framework for industrial transfer that combines precise enterprise data, GIS technology and a 3-D air quality model. Taking Guangdong Province as an example, this study simulates the redistribution of 4015 high-pollution and high-energy-consumption (double-high) enterprises in the Pearl River Delta (PRD) to surrounding areas, and the potential impact on air quality is further evaluated. Three mutually independent transfer scenarios with different objectives are designed-ENV (ENVironment), ENT (ENTerprise), and GOV (GOVernment)-which aim to maximize benefits from the standpoint of the residents of Guangdong, the enterprises themselves, and local governments, respectively. Results show that Western Guangdong (WG), Northern Guangdong (NG), and Eastern Guangdong (EG) would be the primary transfer-in regions under the ENV, ENT, and GOV scenarios due to different resource endowment. Controlled by the different scenarios, the redistribution of enterprises presented different characteristics regarding the transport of pollutant emissions and economic added value between the PRD and surrounding areas. The average concentration of PM2.5 and the related population-weighted concentrations (PWC) showed a slight decrease over the PRD (-0.75 to -0.62 μg/m3 and -0.35 to -0.49 μg/m3 per person) but increased dramatically in surrounding areas under the three scenarios (0.46-7.68 μg/m3 and 0.07-4.44 μg/m3 per person). The transfer of double-high enterprises could potentially decrease the industrial fossil fuel consumption intensity (fossil energy consumption per unit of industrial GDP) of most of the cities while exacerbating pollution intensity (concentration of PM2.5 per unit of industrial GDP), reflecting the huge gap in the regional industrial development pattern in Guangdong Province at this stage, and illustrating the importance of emission control of these enterprises for improvement of regional air quality in the future. The research perspective on industrial transfer proposed in this study could provide a reference for future studies.


RNA release from isolated brain cell nuclei: influence of the postnatal cerebral development.
A method to measure the "in vitro" RNA release from rat brain cell nuclei was described. Nuclear RNA was prelabelled "in vivo" for 30 or 120 min. In the first case the released RNA was heterogeneous and its electrophoretic mobility was similar to that of cytoplasmic messenger RNAs; nuclei prelabelled for 120 min mostly released the two major species of ribosomal RNAs. The release of mRNAs from the nuclei increased during cerebral development while that of the ribosomal RNAs did not. The increased capacity of the nuclei to release "radidly labelled" RNA with age neither determined an increase of the polysomal population, nor seemed to be dependent on cytoplasmic macromolecules.


Bioactivity of Microbacterium barkeri (LMA4) In Vitro and Candidate Gene Annotation In Silico.
Actinomycetes are considered a never-ending treasure trove of biometabolites, which always fascinated researchers. However, to combat with newly emerging bacterial strains, the search for novel or analogs of existing therapeutic agents is recommended. In this context, this research work was carried out to search for a biopotent Actinomycetal strain grown in untapped soil, near the Hirakud dam. This Gram-positive bacteria was subjected to screening for its bioactivity against the medically important bacteria, isolated from local hospital sample using "co-culture" method, following both qualitative and quantitative assays. Further, the 16 s rRNA sequencing, BLASTn analysis, and GC% calculation were carried out. Based upon its bioactivity, a prediction-based genomics work was pursued, considering the gene sequence deposited in public domain. The reverse translation, elution of protein structural file, and the putative protein were predicted. The strain was identified as Microbacterium barkeri, with 54.1% GC content. From Gene Ontology term annotation, it was predicted that the α/β hydrolase fold of hydrolase protein could have been responsible for antibiotic/biometabolite synthesis, in silico. The in vitro-based sequence (from Whole Genome Sequence data) had inferred that there was elution of alpha/beta hydrolase fold, substantiated with conserved domain analysis, ORF finding more over Gene Ontology (GO) terminology annotations. The GO annotations had suggested that the protein had been produced in response to a bacteria, under the influence of external stimuli more so in stress.


Macular edema in Diabetic Retinopathy Study patients. Diabetic Retinopathy Study Report Number 12.
Results from the Diabetic Retinopathy Study (DRS) demonstrate that scatter photocoagulation is associated with some loss of visual acuity soon after treatment. This visual loss is especially prominent in eyes with preexisting macular edema. It is also associated with the intensity of treatment. Reducing macular edema by focal photocoagulation before initiating scatter treatment and dividing scatter treatment into multiple sessions with less intense burns may decrease the risk of the visual loss associated with photocoagulation.


The Simultaneous Presence of Isolated Tumour Cells and Bone Marrow Micrometastases in Stage I and II Colon Cancer-Challenging the Theory of a Chronological Pathway of Tumour Cell Dissemination.
According to the common tenet, tumour progression is a chronological process starting with lymphatic invasion. In this respect, the meaning of bone marrow micrometastases (BMM) in patients with lymph node negative colon cancer (CC) is unclear. This study examines the relationship of isolated tumour cells (ITC) in sentinel lymph nodes (SLN) and BMM in patients in early CC. BM aspirates were taken from both pelvic crests and in vivo SLN mapping was done during open oncologic colon resection in patients with stage I and II CC. Stainings were performed with the pancytokeratin markers A45-B/B3 and AE1/AE3 as well as H&E. The correlation between the occurrence of ITC+ and BMM+ and their effects on survival was examined using Cox regression analysis. In a total of 78 patients with stage I and II CC, 11 patients (14%) were ITC+, 29 patients (37%) BMM+. Of these patients, only two demonstrated simultaneous ITC+ /BMM+. The occurrence of BMM+ was neither associated with ITC+ in standard correlation (kappa = - 0.13 [95% confidence interval [CI] = - 0.4-0.14], p = 0.342) nor univariate (odds ratio [OR] = 0.39, 95%CI:0.07-1.50, p = 0.180) or multivariate (OR = 0.58, 95%CI: 0.09-2.95, p = 0.519) analyses. Combined detection of ITC+ /BMM+ demonstrated the poorest overall (HR = 61.60, 95%CI:17.69-214.52, p = 0.032) and recurrence free survival (HR = 61.60, 95%CI: 17.69-214.5, p = 0.032). These results indicate that simultaneous and not interdependent presence of very early lymphatic and haematologic tumour spread may be considered as a relevant prognostic risk factor for patients with stage I and II CC, thereby suggesting the possible need to reconsider the common assumptions on tumour spread proposed by the prevalent theory of sequential tumour progression.


An application of association rule mining to extract risk pattern for type 2 diabetes using tehran lipid and glucose study database.
Type 2 diabetes, common and serious global health concern, had an estimated worldwide prevalence of 366 million in 2011, which is expected to rise to 552 million people, by 2030, unless urgent action is taken. The aim of this study was to identify risk patterns for type 2 diabetes incidence using association rule mining (ARM). A population of 6647 individuals without diabetes, aged ≥ 20 years at inclusion, was followed for 10-12 years, to analyze risk patterns for diabetes occurrence. Study variables included demographic and anthropometric characteristics, smoking status, medical and drug history and laboratory measures. In the case of women, the results showed that impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), in combination with body mass index (BMI) ≥ 30 kg/m(2), family history of diabetes, wrist circumference > 16.5 cm and waist to height ≥ 0.5 can increase the risk for developing diabetes. For men, a combination of IGT, IFG, length of stay in the city (> 40 years), central obesity, total cholesterol to high density lipoprotein ratio ≥ 5.3, low physical activity, chronic kidney disease and wrist circumference > 18.5 cm were identified as risk patterns for diabetes occurrence. Our study showed that ARM is a useful approach in determining which combinations of variables or predictors occur together frequently, in people who will develop diabetes. The ARM focuses on joint exposure to different combinations of risk factors, and not the predictors alone.


Baseless assumptions: activation of TLR9 by DNA.
The Toll-like receptor 9 (TLR9) is activated by DNA presented in acidified, intracellular compartments. Previous studies suggested that signaling required unmethylated CpG dinucleotides, but in this issue of Immunity, Haas et al. (2008) challenge this view, showing that DNA can activate TLR9 in a sequence-independent manner.


A multiple-dose pharmacodynamic, safety, and pharmacokinetic comparison of extended- and immediate-release formulations of lovastatin.
Because lovastatin is efficiently extracted by the liver and because its administration in divided doses is associated with increased efficacy, an extended-release (ER) formulation may have the potential for a dose-sparing advantage relative to the immediate-release (IR) formulation in the treatment of hypercholesterolemia. This study compared the short-term pharmacodynamics, safety, and pharmacokinetics of multiple doses of lovastatin ER with those of lovastatin IR in patients with fasting low-density lipoprotein cholesterol (LDL-C) levels between 130 and 250 mg/dL and fasting triglyceride levels < 350 mg/dL. The study had a randomized, single-blind, positive-controlled, 2-way crossover design, with a 4-week diet/placebo run-in period and two 4-week active-treatment periods. During period 1, patients received either lovastatin ER or lovastatin IR (both 40 mg OD). After 4 weeks of the initial study treatment and a 2-week washout period, patients were switched to the alternate treatment (period 2). Pharmacodynamic parameters (LDL-C, high-density lipoprotein cholesterol, total cholesterol, and triglyceride levels) were evaluated by combining data from weeks 3 and 4 of treatment. In a pharmacokinetic substudy, maximum plasma concentrations (C(max)) and area under the plasma concentration-time curve from zero to 24 hours (AUC(024)) were determined for lovastatin, lovastatin acid, and total and active inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on days 1 and 28 of active treatment. The geometric mean ratio of AUC(0-24) (lovastatin ER/lovastatin IR) was also calculated for each of these substances. Of 76 patients who entered the run-in period, 26 (12 men, 14 women; mean age, 56.2 years) were randomized to receive active treatment and 24 were included in the efficacy analysis; 13 patients were included in the pharmacokinetic substudy, 12 of whom had complete pharmacokinetic data. Compared with lovastatin IR, lovastatin ER produced a 3.9% greater reduction in LDL-C (P = 0.044). Changes in other lipid parameters were not statistically significant. In the pharmacokinetic substudy, C(max) values for lovastatin, lovastatin acid, and in hibitors of HMG-CoA reductase were lower at day 28 with lovastatin ER than with lovastatin IR. The AUC(0-24) ratio for lovastatin was 1.91 (90% CI, 1.77 - 3.35), reflecting higher bioavailability of the prodrug with lovastatin ER; in contrast, the ratios for lovastatin acid and active and total inhibitors of HMG-CoA reductase were < 1. In this short-term study in a small number of patients, lovastatin ER 40 mg produced significantly greater LDL-C lowering than did an equal dose of lovastatin IR, with a relatively low C(max) and comparable systemic exposure to lovastatin acid and active and total inhibitors of HMG-CoA reductase. Lovastatin ER was well tolerated, with no discontinuations due to adverse events.


Propagation of the prion phenomenon: beyond the seeding principle.
The deposition of misfolded proteins is the hallmark of the late-onset, rapidly progressive and devastating neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. These diseases are caused by a gain of toxic properties associated with the propensity of otherwise soluble proteins to misfold. What governs the deposition of the disease-causing proteins in aged neurons is unclear, but recent evidence suggests that once misfolded, the diverse proteins associated with the neurodegenerative diseases can induce aggregation of their soluble counterpart, thereby sharing one of the defining properties of prions. In addition to the seeded polymerization, prions have the ability to replicate their aberrant conformation indefinitely and are transmissible. Are these properties also shared by diverse misfolded proteins?


Hg and As pollution in the soil-plant system evaluated by combining multispectral UAV-RS, geochemical survey and machine learning.
The combination of a low-density geochemical survey, multispectral data obtained with Unmanned Aerial Vehicle-Remote Sensing (UAV-RS), and a machine learning technique was tested in the search for a statistically robust prediction of contaminant distribution in soil and vegetation, for zones with a highly variable pollutant load. To this end, a novel methodology was devised by means of a limited geochemical study of topsoil and vegetation combined with multispectral data obtained by UAV-RS. The methodology was verified in an area affected by Hg and As contamination that typifies abandoned mining-metallurgy sites in recent decades. A broad selection of spectral indices were calculated to evaluate soil-plant system response, and four machine learning techniques (Multiple Linear Regression, Random Forest, Generalized Boosted Models, and Multivariate Adaptive Regression Spline) were tested to obtain robust statistical models. Random Forest (RF) provided the best non-biased models for As and Hg concentration in soil and vegetation, with R2 and rRMSE (%) ranging from 0.501 to 0.630 and from 180.72 to 46.31, respectively, and with acceptable values for RPD and RPIQ statistics. The prediction and mapping of contaminant content and distribution in the study area were well enough adjusted to the geochemical data and revealed superior accuracy for As than Hg, and for vegetation than topsoil. The results were more precise than those obtained in comparable studies that applied satellite or spectrometry data. In conclusion, the methodology presented emerges as a powerful tool for studies addressing soil and vegetation pollution and an alternative approach to classical geochemical studies, which are time-consuming and expensive.


Immobilization of yeast cells in acrylamide gel matrix.
Entrapment of yeast cells in a three-dimensional polymer matrix was achieved, and various properties of the polymer matrix as well as the invertase activity of the yeast cells were studied. When the matrix was highly cross-linked or synthesized from concentrated polymer solutions, its swelling ratio decreased. Invertase activity was found to increase with water content of the matrix. Cell content of the gel was found to affect adversely enzyme activity. The enzyme was found to retain its activity after seven runs with the same sample.


Characterization of H2 influenza virus hemagglutinin with monoclonal antibodies: influence of receptor specificity.
Antigenic analysis of human and avian H2 influenza viruses were done with monoclonal antibodies to the HA molecules in hemagglutination inhibition (HI) assays. These studies revealed that the receptor-binding specificity of the hemagglutinin can markedly influence the antigenic analysis obtained with monoclonal antibodies in HI tests. Influenza viruses that are sensitive or resistant to inhibition by horse serum inhibitors showed marked differences in their reactivity with monoclonal antibodies to the hemagglutinin. This was apparent with the A/RI/5+/57 and A/RI/5-/57 strains of H2N2 viruses isolated by Choppin and Tamm (1960a), half of the panel of different monoclonal antibodies failed to inhibit hemagglutination of the RI/5- variant, whereas all of the 18 monoclonal antibodies inhibited RI/5+. These findings have important implications in the antigenic analysis of influenza viruses where HI assays are conventionally used to determine the extent of antigenic drift in nature. Antigenic differences were detectable between different human H2 influenza virus isolates from 1957 that were sensitive to inhibition by horse serum, indicating that minor antigenic variation occurs within the first year of appearance of the new subtype. Minor antigenic variation continued in the H2 viruses until 1961, but by 1962 antigenically distinguishable variants that could be discriminated with both monoclonal antibodies and postinfection ferret antisera predominated. Analysis of avian H2 influenza viruses with a panel of monoclonal antibodies indicated that antigenic variation occurs and that multiple different variants cocirculate in the population. There was no progressive antigenic change in the avian H2 influenza viruses with time, as was found with the human H2N2 strains. Topographical mapping of the H2 hemagglutinin by selection of antigenic variants with monoclonal antibodies and analysis of their reactivity patterns by HI showed overlap between the epitopes examined. These results may reflect restriction in the antibody repertoire of the mice used in preparation of the monoclonal antibodies or that the H2 hemagglutinin does not have such discrete nonoverlapping antigenic regions found in the early H3 influenza virus.


Income and Insurance Status Impact Access to Health Care for Hip Osteoarthritis.
To explore differences in the affordability of and accessibility to health care among adults with hip osteoarthritis with respect to race/ethnicity, income, and insurance status. This cross-sectional retrospective study was conducted using 2016 National Health Interview Survey (NHIS) data. NHIS data collection occurred continuously from January to December 2016. Individuals belonging to households and noninstitutionalized groups were included in the study. Because NHIS randomized surveys are conducted face-to-face on an annual basis, follow-up data are not collected. Answers from 38,158,634 weighted respondents with a mean age of 58.33 ± 0.33 years were assessed. Among adults with hip osteoarthritis, those with public insurance had increased odds of delaying care owing to lack of transportation and had decreased odds of delaying care and follow-up care owing to cost. Individuals who were uninsured or who belonged to lower income brackets were associated with increased odds of being unable to afford or utilize health care. In this study, we found that income bracket and insurance status affect the accessibility to health care among adults with hip osteoarthritis in the United States. Level IV, prognostic case series.


Effects of awareness and nociception on heart rate variability during general anaesthesia.
During anaesthesia awareness and nociception are serious complications that may further lead to haemodynamic instability. Specific monitoring of depth of hypnosis and depth of analgesia based on heart rate variability (HRV) analysis is eligible to improve patient safety and reduce efforts in post-operative care. Consequently, in this analysis we assess the applicability of HRV parameters during surgical interventions with standardized intravenous propofol-remifentanil-anaesthesia. Peri-operative electrocardiograms were recorded from cardiovascular stable patients (ASA Score I/II, N = 32, age: 36.4 ± 11.23 a, BMI: 25.2 ± 3.16) scheduled for trauma and dentofacial surgery. HRV time- and frequency-domain parameters, measures of complexity and nonlinear dynamics were compared by analysing longitudinally distributed 300 s intervals preceding/following induction of anaesthesia (BL-I1), intubation (I1-I2) and extubation (E1-E2). Mean value (meanNN) and standard deviation (sdNN) of the heart rate are influenced in BL-I1 (p < 0.001), I1-I2 (p < 0.05) and E1-E2 (p < 0.001). The number of forbidden words of symbolic dynamics changes significantly for BL-I1 (p < 0.001) and not for I1-I2 and E1-E2 (p > 0.05). Probability of low-variability POLVAR10 is significantly altered in all comparisons (BL-I1: Δ = 0.032, p < 0.01, I1-I2: Δ = 0.12, p < 0.05, E1-E2: Δ = 0.169, p < 0.01) but especially during nociception. While standard time-domain parameters lacked selectivity, parameters of symbolic dynamics appear to be specifically influenced by changes in depth of hypnosis and nociception, respectively. However, the lack of steady-state ventilation/breathing in this study needs to be considered in future research. To be used for clinical anaesthesia monitoring our results have to be prospectively validated in clinical studies.


Relationships between adipose tissue and cytokine responses to a randomized controlled exercise training intervention.
Adipose-derived cytokines play a prominent role in mediating the metabolic consequences of obesity and excess body fat. Given this, we hypothesized that alterations in adipose tissue stores incurred with exercise training would be reflected in changes in systemic cytokine concentrations. The Studies of Targeted Risk Reduction Intervention through Defined Exercise, where pronounced changes in adipose tissue stores were observed in the absence of significant changes in dietary intake, provided an ideal setting in which to test this hypothesis. Participants were randomized to 6 months of inactivity or one of 3 types of aerobic exercise training regimens: low-amount-moderate-intensity, low-amount-vigorous-intensity, and high-amount-vigorous-intensity. Plasma samples were collected at baseline and 2 weeks after cessation of 6 months of exercise training or inactivity. In 189 participants, concentrations of 17 cytokines were measured using Bio-Plex Cytokine Assays (Bio-Rad, Hercules, CA); 10 additional cytokines were measured in 60 of these subjects. Of all cytokines tested, the only concentration changes that approached statistical significance were those for granulocyte monocyte-colony stimulating factor and vascular endothelial growth factor, which appeared to increase with training in the low-amount-high-intensity group only (P < .05 for both cytokines). No response to exercise training was noted for any additional cytokine in any of the groups. No relationships were observed between changes in cytokine concentrations and changes in fat mass or other measures of body habitus. In contradiction to our hypothesis, despite significant alterations in body composition, exercise training produced limited cytokine responses.


Determination of biomarkers of exposure to boscalid, captan, folpel, mancozeb and tebuconazole in urine and hair samples.
In order to develop a tiered approach to identify relevant biomarkers and matrices for assessing pesticide exposure in residents living close to vineyards, five priority pesticides (boscalid, captan, folpel, mancozeb and tebuconazole) and their metabolites were analyzed in urine and hair samples from the biobank of a French national prevalence study conducted between 2014 and 2016. To do this, several analytical methods based on gas chromatography coupled with tandem mass spectrometry (GC/MS/MS) were developed by relying on the expertise of the laboratory and the scientific literature, in particular on a paper describing the use of gas chromatography-mass spectrometry for the determination in human urine samples of ethylene thiourea (ETU), a metabolite of mancozeb, after a supported liquid extraction followed by a derivatization step [1]. The main adaptations carried out as part of this study concerned:•the determination of ethylene urea (EU), another metabolite of mancozeb, at the same time as ETU in urine samples•the determination of all substances of interest including boscalid, EU and ETU, folpel and one of its metabolite (phthalimide), tebuconazole and one of its metabolite (hydroxytebuconazole), and tetrahydrophthalimide (metabolite of captan) in organic hair extracts by GC/MS/MS after a derivatization step.


Anatomical variability of the frontal sinuses and their application in forensic identification.
The uniqueness of anatomical structures and their variations provides the basis for forensic identification of unknown deceased persons. Similar to fingerprints, each frontal sinus is so distinctive and unique that the chances of two individuals having the same morphology of the frontal sinuses is extremely remote. Radiographs, especially the occipitomental view commonly used in the assessment of paranasal pathology, provide excellent records of these sinuses. The case illustrated here is an application of the frontal sinus identification of a victim in a mass disaster.


[Fluorescence studies of changes in methemoglobin structure during interaction with liposomes].
Using fluorescence quenching technique the influence of phospholipids on methemoglobin conformation was investigated. The interaction of methemoglobin with model phospholipid membranes was shown to be followed by changes of protein structure-dynamic organization.


Two novel brain proteins, CaBP33 and CaBP37, are calcium-dependent phospholipid- and membrane-binding proteins.
Two acidic Ca2(+)-binding proteins (CaBP33 and CaBP37) purified from bovine brain have been characterized in terms of immunological properties, heat-sensitivity, electrophoretic mobility, and Ca2(+)-dependent binding to negatively charged phospholipids and to brain membranes. They were induced to bind to membranes by homogenization of brain tissue in the presence of CaCl2. The membrane-bound CaBP33/CaBP37 mixture resisted extraction with detergents and was solubilized with high concentrations of EGTA/KCl. However, apparent Ca2(+)-independent binding of the two proteins to membranes seemed to occur as well. This latter fraction of membrane-bound CaBP33 and CaBP37 could be solubilized with Triton X-100, indicating that brain membranes normally contain the two proteins as intrinsic components.


Spatial regulation of resource allocation in response to nutritional availability.
It is critical for a living organism to appropriately allocate resources among its organs, or within a specific organ, because available resources are generally limited. For example, in response to the nutritional environment of their soil, plants regulate resource allocation in their roots in order to plastically change their root system architecture (RSA) for efficiently absorbing nutrients. However, it is still not understood why and how RSA is adaptively controlled. Therefore, we modeled and investigated the spatial regulation of resource allocation, focusing on RSA in response to nutrient availability, and provided analytical solutions to the optimal strategy in the case of simple fitness functions. We first showed that our model could explain the experimental evidence where root growth is maximized at the optimal nutrient concentration under the homogeneous condition. Next, we extended our model to incorporate the spatial heterogeneity of nutrient availability. This extended model revealed that growth suppression by systemic control is required for adapting to high nutrient conditions, whereas growth promotion by local control is sufficient for adaptation to low-nutrient environments. This evidence predicts that systemic control can be evolved in the presence of excessive amounts of nutrition, consistent with the 'N-supply' systemic signal that is observed experimentally. Furthermore, our model can also explain various experimental results using nitrogen nutrition. Our model provides a theoretical basis for understanding the spatial regulation of adaptive resource allocation in response to nutritional environment.


Towards the international interoperability of clinical research networks for rare diseases: recommendations from the IRDiRC Task Force.
Many patients with rare diseases are still lacking a timely diagnosis and approved therapies for their condition despite the tremendous efforts of the research community, biopharmaceutical, medical device industries, and patient support groups. The development of clinical research networks for rare diseases offers a tremendous opportunity for patients and multi-disciplinary teams to collaborate, share expertise, gain better understanding on specific rare diseases, and accelerate clinical research and innovation. Clinical Research Networks have been developed at a national or continental level, but global collaborative efforts to connect them are still lacking. The International Rare Diseases Research Consortium set a Task Force on Clinical Research Networks for Rare Diseases with the objective to analyse the structure and attributes of these networks and to identify the barriers and needs preventing their international collaboration. The Task Force created a survey and sent it to pre-identified clinical research networks located worldwide. A total of 34 responses were received. The survey analysis demonstrated that clinical research networks are diverse in their membership composition and emphasize community partnerships including patient groups, health care providers and researchers. The sustainability of the networks is mostly supported by public funding. Activities and research carried out at the networks span the research continuum from basic to clinical to translational research studies. Key elements and infrastructures conducive to collaboration are well adopted by the networks, but barriers to international interoperability are clearly identified. These hurdles can be grouped into five categories: funding limitation; lack of harmonization in regulatory and contracting process; need for common tools and data standards; need for a governance framework and coordination structures; and lack of awareness and robust interactions between networks. Through this analysis, the Task Force identified key elements that should support both developing and established clinical research networks for rare diseases in implementing the appropriate structures to achieve international interoperability worldwide. A global roadmap of actions and a specific research agenda, as suggested by this group, provides a platform to identify common goals between these networks.


Cu (II) binded chitosan/Fe3O4 nanocomomposite as a new biosorbent for efficient and selective removal of phosphate.
The aim of this study was to develop a chitosan-based magnetic adsorbent for selective and effective removal of phosphate from aqueous solutions. For this purpose, Cu-chitosan/Fe3O4 nanocomposite was prepared using a facile method and characterized. The prepared adsorbent exhibited more porous surface with higher specific area compared to neat chitosan based on SEM and BET studies. The FTIR and EDX studies indicated the presence of Cu(II) bonded to the adsorbent surface. Crystalline properties of the adsorbent were also studied using XRD. Experimental isotherm data were fitted to nonlinear forms of Langmuir and Freunlich models. The maximum capacity for the modified adsorbent was calculated to be 88mg P2O5/g, much higher than that for neat chitosan and chitosan/Fe3O4 according to the Langmuir isotherm. The adsorption by the modified adsorbent had fast kinetics and obeyed pseudo-second-order kinetic model. Interestingly, the maximum removal efficiency for the modified adsorbent was observed in neutral pH values, pHs of natural waters. A high selectivity against natural waters common anions as well as good regeneration ability was obtained for the introduced adsorbent.


Vaccinations in adults with chronic inflammatory joint disease: Immunization schedule and recommendations for patients taking synthetic or biological disease-modifying antirheumatic drugs.
The risk of infection associated with autoimmune diseases is further increased by the use of biotherapies. Recommendations to minimize this risk include administering the full complement of vaccines on the standard immunization schedule, as well as the pneumococcal and influenza vaccines. Adults with chronic inflammatory joint disease (IJD) may receive a 13-valent pneumococcal conjugate vaccine, as well as a live attenuated vaccine against recurrent herpes zoster, recently licensed by European regulatory authorities. Live attenuated vaccines can be given only after an interval without immunosuppressant and/or glucocorticoid therapy. The effectiveness of vaccines, as assessed based on titers of protective antibodies, varies across vaccine types and disease-modifying antirheumatic drugs (DMARDs). Thus, methotrexate and rituximab are usually associated with decreased vaccine responses. The risks associated with vaccines are often considerably exaggerated by the media, which serve lobbies opposed to immunizations and make some patients reluctant to accept immunizations. Increasing immunization coverage may diminish the risk of treatment-related infections. A physician visit dedicated specifically to detecting comorbidities in patients with chronic IJD may result in improved immunization coverage. In this review, we discuss immunizations for adults with chronic IJD based on the treatments used, as well as immunization coverage. Many questions remain unanswered and warrant investigation by studies coordinated by the French networks IREIVAC (Innovative clinical research network in vaccinology) and IMIDIATE (Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research).


Anxiety increased among children and adolescents during pandemic-related school closures in Europe: a systematic review and meta-analysis.
Considering the heterogenous evidence, a systematic review of the change in anxiety in European children and adolescents associated with the COVID-19 pandemic is lacking. We therefore assessed the change compared with pre-pandemic baselines stratified by gender and age as well as evaluated the impact of country-specific restriction policies. A registration on the 'International Prospective Register of Systematic Reviews' (PROSPERO) occurred and an a priori protocol was published. We searched six databases (PubMed, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, WHO COVID-19) using a peer-reviewed search string with citation tracking and grey literature screening. Primary outcomes were: (1) general anxiety symptoms; and (2) clinically relevant anxiety rates. We used the Oxford COVID-19 Stringency Index as an indicator of pandemic-related restrictions. Screening of title/abstract and full text as well as assessing risk of bias (using the 'Risk of Bias in Non-randomized Studies of Exposure' [ROBINS-E]) and certainty of evidence (using the 'Grading of Recommendations Assessment, Development and Evaluation' [GRADE]) was done in duplicate. We pooled data using a random effects model. Reporting is in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement. Of 7,422 non-duplicate records, 18 studies with data from 752,532 pre-pandemic and 763,582 pandemic participants met full inclusion criteria. For general anxiety symptoms the total change effect estimate yielded a standardised mean difference (SMD) of 0.34 (95% confidence interval [CI], 0.17-0.51) and for clinically relevant anxiety rates we observed an odds ratio of 1.08 (95%-CI, 0.98-1.19). Increase in general anxiety symptoms was highest in the 11-15 years age group. Effect estimates were higher when pandemic-related restrictions were more stringent (Oxford Stringency Index > 60: SMD, 0.52 [95%-CI, 0.30-0.73]) and when school closures (School Closure Index ≥ 2: SMD, 0.44 [95%-CI, 0.23-0.65]) occurred. General anxiety symptoms among children and adolescents in Europe increased in a pre/during comparison of the COVID-19 pandemic; particularly for males aged 11-15 years. In periods of stringent pandemic-related restrictions and/or school closures a considerable increase in general anxiety symptoms could be documented. PROSPERO registration: CRD42022303714.


Rogue cell-like chromosomal aberrations in peripheral blood lymphocytes of interventional radiologists: A case study.
We report two cases of interventional radiologists who had been exposed to radiation while performing fluoroscopically-guided interventional procedures (FGIPs), mainly transcatheter arterial chemoembolization, percutaneous catheter drainage, and percutaneous transhepatic biliary drainage procedures, for over 10 years. They had a unique multi-aberrant cell type with not only high numbers of dicentrics and/or centric rings but also excess acentric double minutes, similar to a rogue cell. As revealed in a self-administered questionnaire, they wore personal dosimeters and protective equipment at all times and used shielding devices during interventional fluoroscopy procedures. However, the exposed dose levels derived from cytogenetic dosimetry were much higher than the doses recorded on their personal dosimeters. A large number of unstable and stable chromosomal aberrations that were found in the peripheral blood lymphocytes of these interventional radiologists might be due to repeated and long-term exposure to ionizing radiation while performing FGIPs. Further investigations of chromosomal aberrations in interventional radiologists may improve the understanding of the long-term effects of radiation exposure on medical personnel.


Angiomatoid change in polyps of the nasal and paranasal regions: an underrecognized and commonly misdiagnosed lesion--report of 45 cases.
We present 45 patients with angiomatoid polyps of the nasal and paranasal regions (APNPRs), which are underrecognized lesions which may cause considerable diagnostic difficulties. There were 32 men and 13 women in our series. The average age at diagnosis was 49 years in men and 54.3 years in women. Locations were known in 41 cases and included the nasal septum (14), maxillary sinus (12), ethmoid sinuses (5), lateral wall of the nasal cavity (5), sphenoid sinus (1), and nasal cavity, not otherwise specified (4). X-ray or computed tomography was performed in 19 cases and revealed bone erosions/deviations in four cases. Initial misdiagnoses submitted by referring pathologists were reported in 20/32 of the consultation cases. Our study confirms that APNPRs are benign lesions which often recur and sometimes multiple recurrences are seen. APNPRs sometimes cause severe changes of the skeletal bones especially in recurrent lesions. Awareness of the above described features and familiarity with the clinical presentation of APNPRs is the best way to avoid a misdiagnosis.


Longitudinal analysis of local government spending on adult social care and carers' subjective well-being in England.
Reform of England's social care system is repeatedly discussed in the context of increasing demand, rising costs and austere policies that have decreased service provision. This study investigates the association between unpaid carers' subjective well-being and local government spending on adult social care (ASC). Our sample consists of 110 188 observations on 29 174 adults in England from the 2004-2007 British Household Panel Survey and the 2009-2018 UK Household Longitudinal Study. The data on local authorities' spending on ASC where participants live is derived from the publications Personal Social Care Expenditure and Unit Costs (2004-2016); and ASC Activity and Finance Report England (2016-2018). Subjective well-being is measured by the 12-item version of the General Health Questionnaire (GHQ-12) and 12-item version of the Mental Component Summary (MCS-12). We applied fixed-effects linear models to investigate the moderating effect of ASC spending on the association between subjective well-being and caring, controlling for a range of socioeconomic and demographic variables. Carers have a lower level of subjective well-being compared with non-carers, evident in their higher average GHQ-12 Likert score (β=2.7277 95% CI 0.2547 to 5.2008). Differences in the subjective well-being of carers and non-carers decrease with local government spending on ASC. Subjective well-being for carers was at a similar level to that of non-carers in high ASC spending local authorities (GHQ-12: -0.0123 95% CI -0.2185 to 0.1938, MCS-12: 0.0347 95% CI -0.3403 to 0.4098) and lower in other areas (GHQ-12: 0.1893 95% CI 0.0680 to 0.3107, MCS-12: -0.2906 95% CI -0.5107 to -0.0705). The moderating effect of ASC spending is found among people who care for 35+ hours per week. Government spending on ASC protects unpaid carers' well-being, and people providing more than 35 weekly hours of unpaid care are more likely to benefit from the current social care system.


Trained innate immunity and resistance to Mycobacterium tuberculosis infection.
Some individuals, even when heavily exposed to an infectious tuberculosis patient, develop neither active nor latent tuberculosis infection (LTBI). This 'early clearance' of Mycobacterium tuberculosis is associated with a history of bacillus Calmette-Guérin (BCG) vaccination. As BCG vaccination can boost innate immune responses through a process termed 'trained immunity', we hypothesize that BCG-induced trained innate immunity contributes to early clearance of M. tuberculosis. We describe the epidemiological evidence and biological concepts of early clearance and trained immunity, and the possible relation between these two processes through BCG vaccination. Relevant data from published reports up to November 2018 were examined in the conduct of this review. Several observational studies and one recent randomized trial support the concept that boosting innate immunity contributes to protection against M. tuberculosis infection, with BCG vaccination providing approximately 50% protection. The molecular mechanisms mediating early clearance remain largely unknown, but we propose that trained immunity, characterized by epigenetic and metabolic reprogramming of innate immune cells such as monocytes or macrophages, is at least partially responsible for eliminating the mycobacteria and inducing early clearance. Future studies should examine if BCG revaccination increases early clearance of M. tuberculosis through induction of trained immunity. Epigenetic or metabolic modulation may further boost BCG-induced trained innate immunity to promote tuberculosis prevention. New tuberculosis vaccine candidates should also be examined for their capacity to improve protection against M. tuberculosis infection and induce trained immunity.


Back to normal: A retrospective, cross-sectional study of the multi-factorial determinants of normal birth in Queensland, Australia.
currently, care providers and policy-makers internationally are working to promote normal birth. In Australia, such initiatives are being implemented without any evidence of the prevalence or determinants of normal birth as a multidimensional construct. This study aimed to better understand the determinants of normal birth (defined as without induction of labour, epidural/spinal/general anaesthesia, forceps/vacuum, caesarean birth, or episiotomy) using secondary analyses of data from a population survey of women in Queensland, Australia. women who birthed in Queensland during a two-week period in 2009 were mailed a survey approximately three months after birth. Women (n=772) provided retrospective data on their pregnancy, labour and birth preferences and experiences, socio-demographic characteristics, and reproductive history. A series of logistic regressions were conducted to determine factors associated with having labour, having a vaginal birth, and having a normal birth. overall, 81.9% of women had labour, 66.4% had a vaginal birth, and 29.6% had a normal birth. After adjusting for other significant factors, women had significantly higher odds of having labour if they birthed in a public hospital and had a pre-existing preference for a vaginal birth. Of women who had labour, 80.8% had a vaginal birth. Women who had labour had significantly higher odds of having a vaginal birth if they attended antenatal classes, did not have continuous fetal monitoring, felt able to 'take their time' in labour, and had a pre-existing preference for a vaginal birth. Of women who had a vaginal birth, 44.7% had a normal birth. Women who had a vaginal birth had significantly higher odds of having a normal birth if they birthed in a public hospital, birthed outside regular business hours, had mobility in labour, did not have continuous fetal monitoring, and were non-supine during birth. these findings provide a strong foundation on which to base resources aimed at increasing informed decision-making for maternity care consumers, providers, and policy-makers alike. Research to evaluate the impact of modifying key clinical practices (e.g., supporting women׳s mobility during labour, facilitating non-supine positioning during birth) on the likelihood of a normal birth is an important next step.


Push-out bond strength and SEM evaluation of a new bonding approach into the root canal.
This study evaluated the performance of different adhesive systems in fiber post placement aiming to clarify the influence of different hydrophobic experimental blend adhesives, and of one commercially available adhesive on the frictional retention during a luting procedure. One luting agent (70 Wt% BisGMA, 28.5% TEGDMA; 1.5% p-tolyldiethanolamine) to cement fiber posts into root canals was applied with 4 different adhesive combinations: group 1: The etched roots were rinsed with water for 30 s to remove the phosphoric acid, then rinsed with 99.6% ethanol for 30 s, and blotdried. A trial adhesive (base to catalyst on a 1:1 ratio) was used with an experimental luting agent (35% Bis-GMA, 14.37% TeGDMA, 0.5% eDMAB, 0.13% CQ); group 2: A trial adhesive (base to catalyst on a 1:2 ratio) was luted as in group 1; group 3: One-Step Plus (OSP, Bisco Inc.) following the ethanol bonding technique in combination with the luting agent as in group 1; group 4: OSP strictly following the manufacturer's instructions using the luting agent as in group 1. The groups were challenged with push-out tests. Posted root slices were loaded until post segment extrusion in the apical-coronal direction. Failure modes were analyzed under scanning electron microscopy. Push-out strength was not significantly influenced by the luting agent (p>0.05). No statistically significant differences among the tested groups were found as group 1 (exp 1--ethanol-wet bonding technique)=group 2 (exp 2--ethanol-wet bonding technique)=Group 3 (OSP--ethanol-wet bonding technique)=group 4 (control, OSP--water-wet bonding technique) (p>0.05). The dominating failure modes in all the groups were cohesive/adhesive failures, which were predominantly observed on the post/luting agent interface. The results of this study support the hypothesis that the proposal to replace water with ethanol to bond fiber posts to the root canal using highly hydrophobic resin is plausible, but this seems to be more the proof of a concept than a clinically applicable procedure.


Biotyping of aerobic actinomycetes by modified killer system.
Forty-four yeasts belonging to the genera Pichia, Candida, Saccharomyces and Kluyveromyces were tested for their potential killer effect on 13 aerobic actinomycetes (6 Nocardia asteroides, 1 N. brasiliensis, 1 N. caviae and 5 Actinomadura madurae). Only a few yeast strains did not display any killer activity against the aerobic actinomycetes studied, thus confirming that the killer phenomenon is widespread among microorganisms. For epidemiological purposes, a killer system was developed. According to their susceptibility to the 9 killer yeasts chosen, it was possible to differentiate the Nocardia and Actinomadura isolates into biotypes. Fitting conditions of the killer system to potential sensitive microorganisms with different characteristics of growth are also discussed.


Traditional uses of some medicinal plants in Malatya (Turkey).
This study has identified not only the wild plants collected for medical purposes by local people of Malatya Province in the Eastern Anatolia Region, but also the uses and local names of these plants. It tried to provide a source for researchers studying in ethnobotany, pharmacology and chemistry by comparing the information obtained from traditionally used herbs with previous laboratory studies. In Turkey, use of plants for medical purposes has been a tradition. This study aims to identify wild plants collected for medical purposes by the local people of Malatya Province, located in the Eastern Anatolia Region of Turkey, and to establish the uses and local names of these plants. A field study had been carried out for a period of approximately 2 years (2010-2011). A questionnaire was administered to the local people, through face-to-face interviews. During this period, 330 vascular plant specimens were collected. Demographic characteristics of participants, names of the local plants, their utilized parts and preparation methods were investigated and recorded. The plant species were collected within the scope of the study; herbarium materials were prepared; and the specimens were entitled. In addition, the relative importance value of the species was determined and informant consensus factor (FIC) was calculated for the medicinal plants included in the study. In the area of research, 132 individuals who had knowledge about plants were interviewed. Mean age of the respondents was 44 years (in 35-73 years range). 108 plants were found to be used for medical purposes before in the literature analysis of the plants used in our study, while 15 plants were found to have no literature records. The most common families are: Asteraceae (21 plants), Lamiaceae (14 plants), and Rosaceae (12 plants). Local people were recorded to use the aerial parts, branches, flowers, fruits, latex, leaves, matured fruits, peduncle, resin, rhizomes, root bark, roots, seeds and style of the plants. Besides, it was observed that they dried and stored plants in unfavorable seasons in order to use them later. The medicinal uses of Heracleum antasiaticum Manden., Pimpinella olivieroides Boiss. & Hausskn., Scandix iberica Bieb., Taraxacum hybernum Stev., Tripleurospermum transcaucasicum (Manden.) Pobed., Cerastium chlorifolium Fisch. & Mey., Andrachne telephioides L., Euphorbia denticulata Lam., Astragalus cephalotes Banks. & Sol. var. brevicalyx Eig., Geranium ibericum Cav., Cyclotrichium nivenum (Boiss.) Manden. & Scheng., Salvia syriaca L., Papaver arenarium Bieb., Dactylis glomerata L., Polygonum arenarium Waldst. & Kit. that we found were used in our study area and recorded for the first time. No information could be obtained regarding the names of eight wild plants that are being used in Malatya. In Turkey, local plant names display differences especially due to ethnographic reasons. The plants used in Malatya are known by the same or different local names in various parts of Anatolia. Our research area also includes people with Kurdish and Zaza ethnic origins. The respondents of the questionnaire are Turkish citizens. These plants are used in the treatment of many diseases. Comparison of the data obtained in this study from derived the plants growing in Malatya with the experimental data obtained in previous laboratory studies proved ethnobotanical usages to a great extent. Literature review indicated that curative plants that grow in Malatya are used in different parts of the world for the treatment of the same or similar diseases. These plants, used for the treatment of many varying diseases, are abundantly found in this region. Drying enabled local people to use medicinal plants in every seasons of the year. The plant flora of Malatya is threatened by such factors as grazing, expansion of new agricultural lands, and unsustainable picking of plants to generate income. Steps should be taken immediately to ensure the inclusion of relevant flora within conservation designations.


[Epidemiology of and risk factors for invasive aspergillosis in nonneutropenic patients].
Invasive aspergillosis is a major cause of mortality among patients with hematological malignancies and undergoing bone marrow transplantation. Whereas diagnosis and therapeutic strategies are evaluated for neutropenic patients, only limited data among nonneutropenic patients are available. Beside classical chronic pulmonary aspergillosis, an increased incidence of acute invasive aspergillosis is reported for nonneutropenic patients, such as patients suffering from chronic respiratory diseases or systemic diseases treated with corticosteroid therapy, and solid organ transplant recipients. A better knowledge of pathophysiology and epidemiology of invasive aspergillosis is needed to adapt the disease classification for nonneutropenic patients. Beside, the performance of diagnostic tools must be evaluated specifically in this population. Invasive aspergillosis is underdiagnosed in nonneutropenic patients which may simultaneously be colonized by Aspergillus and receive immunosuppressive therapy. It remains a life-threatening disease as severe as in neutropenic patients, at least partially related to a delayed diagnostic.


Pharmacy benefit managers and their obligations during serious prescription drug shortages.
Pharmacy benefit managers are connected to some 215 million Americans and to every prescribing physician and retail pharmacy in the United States. Many of them have their own large and sophisticated dispensing operations. These capabilities could be put to use when drug shortages threaten life. Indeed, these capabilities are such that they confer obligations on pharmacy benefit managers to address such shortages--not only on behalf of their clients but for society in general.


A bandage contact lens prevents extrusion of ocular contents.
A 76 year old male presents with a corneal perforation in a phthisical eye. Definitive treatment in the form of an evisceration was delayed by 38 days. During this period a bandage contact lens prevented extrusion of ocular contents through an enlarging corneal perforation. This case demonstrates that a bandage contact lens can be effective in the immediate management of large corneal perforations whilst awaiting urgent definitive treatment.


Lever pressing and active avoidance conditioning after electrolytic lesions of the entopeduncular nucleus in cats.
Several authors have shown that CN participates in the acquisition of motor conditioned responses (MCR), probably as the integrating structure. Most of CN's efferent fibers in the cat end in the entopeduncular nucleus (EPN), therefore the command for the motor pattern could be exerted through EPN, representing part of the efferent link of the neuronal circuitry involved in MCR. Thirty-two cats were trained to avoid actively an electrical stimulus when a series of flashes appeared, and to press a lever to obtain 0.5 ml of milk. After the cats reached the learning criterion for both responses, electrolytic lesions of the entopeduncular nucleus or internal capsule (IC) were made bilaterally. When the cats recovered their normal motor behavior, the conditioned sessions were resumed once a day, for 45-50 days. Both learning responses disappeared (p less than 0.01) in those animals with the largest EPN lesions. In contrast, for small EPN lesions, learned responses were absent only during the first 3 or 4 sessions, and then the level of responses increased each day. However, it never reached that of sham lesioned cats. On the other hand, IC lesioned cats showed no statistical differences with respect to sham lesioned animals. These data support the participation of EPN in the motor circuitry responsible for MCR.


A radical relationist solution to the problem of intentional inexistence.
The problem of intentional inexistence arises because the following (alleged) intuitions are mutually conflicting: it seems that sometimes we think about things that do not exist; it seems that intentionality is a relation between a thinker and what such a thinker thinks about; it seems that relations entail the existence of what they relate. In this paper, I argue for what I call a radical relationist solution. First, I contend that the extant arguments for the view that relations entail the existence of their relata are wanting. In this regard, I defend a kind of pluralism about relations according to which more than one kind of relation involves non-existents. Second, I contend that there are reasons to maintain that all thoughts are relations between thinkers and the things they are about. More accurately, I contend that the radical relationist solution is to be preferred to both the intentional content solution (as developed by Crane) and the adverbial property solution (as developed by Kriegel). Finally, I argue that once the distinction between thinking "X" and thinking about X has been drawn, the radical relationist solution can handle issues like ontological commitment, substitutivity failure, scrutability, and non-specificity.


Prenatal and Infancy Nurse Home Visiting Effects on Mothers: 18-Year Follow-up of a Randomized Trial.
Prenatal and infancy home-visiting by nurses is promoted as a means of improving maternal life-course, but evidence of long-term effects is limited. We hypothesized that nurse-visitation would lead to long-term reductions in public-benefit costs, maternal substance abuse and depression, and that cost-savings would be greater for mothers with initially higher psychological resources. We conducted an 18-year follow-up of 618 out of 742 low-income, primarily African-American mothers with no previous live births enrolled in an randomized clinical trial of prenatal and infancy home visiting by nurses. We compared nurse-visited and control-group women for public-benefit costs, rates of substance abuse and depression, and examined possible mediators of intervention effects. Nurse-visited women, compared with controls, incurred $17 310 less in public benefit costs (P = .03), an effect more pronounced for women with higher psychological resources ($28 847, P = .01). These savings compare with program costs of $12 578. There were no program effects on substance abuseor depression. Nurse-visited women were more likely to be married from child age 2 through 18 (19.2% vs 14.8%, P = .04), and those with higher psychological resources had 4.64 fewer cumulative years rearing subsequent children after the birth of the first child (P = .03). Pregnancy planning was a significant mediator of program effects on public benefit costs. Through child age 18, the program reduced public-benefit costs, an effect more pronounced for mothers with higher psychological resources and mediated by subsequent pregnancy planning. There were no effects on maternal substance abuse and depression.


Classification and treatment of postburn proximal interphalangeal joint flexion contractures in children.
Two hundred and sixty-four surgically treated proximal interphalangeal joint flexion contractures in children were reviewed. A classification system on the basis of contracture severity was devised to assess the efficacy of treatment. Contracture severity was determined from preoperative radiographs and physical examination. Eighty-eight percent of the digits were successfully treated (postoperative contracture less than 20 degrees). Unsatisfactory results (12% of digits) were directly proportional to the severity of the contracture and tended to occur in older children with large total body surface burns. The time interval between burn and contracture release did not correlate with contracture severity or therapeutic failure. The most common cause of an unsatisfactory result was failure to fully release the contracture.


Inflammation-induced CD69+ Kupffer cell feedback inhibits T cell proliferation via membrane-bound TGF-β1.
Kupffer cells, tissue-resident macrophage lineage cell, are enriched in vertebrate liver. The mouse F4/80+ Kupffer cells have been subclassified into two subpopulations according to their phenotype and function: CD68+ subpopulation with potent reactive oxygen species (ROS) production and phagocytic capacities, and CD11b+ subpopulation with a potent capacity to produce T helper 1 cytokines. In addition, CD11b+ Kupffer cells/macrophages may be migrated from the bone marrow or spleen, especially in inflammatory conditions of the liver. For analyzing diverse Kupffer cell subsets, we infected mice with Listeria monocytogenes and analyzed the phenotype variations of hepatic Kupffer cells. During L. monocytogenes infection, hepatic CD69+ Kupffer cells were significantly induced and expanded, and CD69+ Kupffer cells expressed higher level of CD11b, and particularly high level of membrane-bound TGF-β1 (mTGF-β1) but lower level of F4/80. We also found that clodronate liposome administration did not eliminate hepatic CD69+ Kupffer cell subset. We consider the hepatic CD69+ Kupffer cell population corresponds to CD11b+ Kupffer cells, the bone marrow-derived population. Hepatic CD69+ Kupffer cells suppressed Ag-nonspecific and OVA-specific CD4 T cell proliferation through mTGF-β1 both in vitro and in vivo, meanwhile, they did not interfere with activation of CD4 T cells. Thus, we have identified a new subset of inflammation-induced CD69+ Kupffer cells which can feedback inhibit CD4 T cell response via cell surface TGF-β1 at the late stage of immune response against infection. CD69+ Kupffer cells may contribute to protect host from pathological injure by preventing overactivation of immune response.


Liquid marbles as a micro-reactor for efficient radical alternating copolymerization of diene monomer and oxygen.
Liquid marbles have been shown to be a novel micro-reactor to synthesize polyperoxides by the radical alternating copolymerization of the 1,3-diene monomer with oxygen in a good yield. Oxygen gas is effectively absorbed as a comonomer by the large and permeable gas-liquid interface of the liquid marbles.


Uptake and photo-toxicity of Foscan®, Foslip® and Fospeg® in multicellular tumor spheroids.
In cancer photodynamic therapy (PDT), an efficient and homogeneous intratumoral accumulation of the photosensitizer (PS) is required to induce cell damages in the entire tumor mass after light activation. Thus, in this study we investigated penetration ability and photodynamic efficiency of meta-tetra(hydroxyphenyl)chlorin (m-THPC) in standard formulation (Foscan®) and in its non PEGylated and PEGylated liposomal formulations, Foslip® and Fospeg®, in HeLa multicellular spheroids, as in vitro avascular models of solid tumors. Confocal microscopy studies demonstrated that m-THPC fluorescence was confined in the external cell layers of spheroids with a slightly higher accumulation of Foslip® and Fospeg® with respect to Foscan®. Irradiation with red light, following 24h incubation of spheroids with the m-THPC formulations, caused however photodamages also in cells located in the central part of spheroids, as documented by transmission electron microscopy analyses. Overall, the photodynamic effects of the three m-THPC formulations on HeLa cell spheroids were comparable in terms of cell viability measured with the MTS assay. It is however worth noting that the delivery of m-THPC by liposomes significantly abolished its cytotoxicity in the dark, slightly improved the cellular uptake and, following PDT, promoted cell loss and spheroid disassembling to a higher extent when compared to Foscan®.


Quality validation of platelets obtained from the Haemonetics and Trima Accel automated blood-collection systems.
Platelet transfusion is required to treat haemo-oncology or trauma patients. Platelet apheresis (PA) performed with apheresis equipment has increased rapidly in recent years. Leucocyte-reduced platelet apheresis (LRPA) can reduce the risk of platelet refractoriness and febrile nonhemolytic transfusion reactions (FNHTRs) for transfusion. Accordingly, this study aimed to investigate and compare the platelet metabolic and functional responses between PA performed with Haemonetics and LRPA performed with Trima Accel cell separator. The qualities of platelets collected through PA and LRPA were evaluated in terms of visual appearance, morphology, platelet-aggregation changes, metabolic activities, and bacterium-screening test during 5-day storage. Statistical analyses included two-sample t-test and generalised estimating equation(GEE) method. During 5-day storage in LRPA, residual leucocytes were all <1.0×106, and the parameters of platelet function were as follows: platelet aggregated to agonists such as adenosine 5'-diphosphate (ADP) and collagen, and the extent of shape change and pO2 showed no statistically significant difference between PA and LRPA. The hypotonic shock reaction (HSR) on days 0, 1, and 3 were significantly higher in LRPA than in PA (71.78±6.92 vs. 64.10±7.42; P=0.002; 71.53±8.98 vs. 62.96±9.84; P=0.007; 68.05±7.28 vs. 57.76±6.80; P<0.0001, respectively). Values of mean platelet volume (MPV) were statistically larger in PA than in LRPA on days 0, 1, and 3. On day 5, the swirling score was higher in LRPA than in PA. The mean lactate levels had no statistically significant difference between PA and LRPA. Moreover, no growth was observed through bacterium-screening test conducted on 40 samples. Comparison of LRPA and PA products collected from the Trima Accel and Haemonetics automated blood-collection systems, respectively, revealed that both products possessed good platelet qualities even though additional processes are needed to reduce leucocytes. Furthermore, investigating the outcomes of other apheresis instruments with focus on the safety of donors, products, and recipients is necessary.


A novel use of inertial sensors to measure the craniocervical flexion range of motion associated to the craniocervical flexion test: an observational study.
The craniocervical flexion test (CCFT) is recommended when examining patients with neck pain related conditions and as a deep cervical retraining exercise option. During the execution of the CCFT the examiner should visually assess that the amount of craniocervical flexion range of motion (ROM) progressively increases. However, this task is very subjective. The use of inertial wearable sensors may be a user-friendly option to measure and objectively monitor the ROM. The objectives of our study were (1) to measure craniocervical flexion range of motion (ROM) associated with each stage of the CCFT using a wearable inertial sensor and to determine the reliability of the measurements and (2) to determine craniocervical flexion ROM targets associated with each stage of the CCFT to standardize their use for assessment and training of the deep cervical flexor (DCF) muscles. Adults from a university community able to successfully perform the CCFT participated in this study. Two independent examiners evaluated the CCFT in two separate sessions. During the CCFT, a small wireless inertial sensor was adhered to the centre of the forehead to provide real-time monitoring and to record craniocervical flexion ROM. The intra- and inter-rater reliability of the assessment of craniocervical ROM was calculated. This study was approved by the Research Ethics Committee of CEU San Pablo University (236/17/08). Fifty-six participants (18 males, 23 females; mean [SD] age, 21.8 [3.45] years) were included in the study and successfully completed the study protocol. All interclass correlation coefficient (ICC) values indicated good or excellent reliability of the assessment of craniocervical ROM using a wearable inertial sensor. There was high variability between subjects on the amount of craniocervical ROM necessary to achieve each stage of the CCFT. The use of inertial sensors is a reliable method to measure the craniocervical flexion ROM associated with the CCFT. The great variability in the ROM limits the possibility to standardize a set of targets of craniocervical flexion ROM equivalent to each of the pressure targets of the pressure biofeedback unit.


Biological activity and metabolic clearance of recombinant human follicle stimulating hormone produced in Sp2/0 myeloma cells.
Human follicle stimulating hormone is a pituitary glycoprotein that is essential for the maintenance of ovarian follicle development and testicular spermatogenesis. Like other members of the glycoprotein hormone family, it contains a common a subunit and a hormone specificβ subunit. Each subunit contains two glycosylation sites. The specific structures of the oligosaccharides of human follicle stimulating hormone have been shown to influence both thein vitro andin vivo bioactivity. Since the carbohydrate structure of a protein reflects the glycosylation apparatus of the host cells in which the protein is expressed, we examined the isoform profiles,in vitro bioactivity and metabolic clearance of a preparation of purified recombinant human follicle stimulating hormone derived from a stable, transfected Sp2/0 myeloma cell line, and pituitary human follicle stimulating hormone. Isoelectric focussing and chromatofocussing studies of human follicle stimulating hormone preparations both showed a more basic isoform profile for the recombinant human follicle stimulating hormone compared to that of pituitary human follicle stimulating hormone. The recombinant human follicle stimulating hormone had a significantly higher radioreceptor activity compared to that of pituitary human follicle stimulating hormone, consistent with a greaterin vitro potency. Pharmacokinetic studies in rats indicated a similar terminal half life (124 min) to that of the pituitary human follicle stimulating hormone (119 min). Preliminary carbohydrate analysis showed recombinant human follicle stimulating hormone to contain high mannose and/or hybrid type, in addition to complex type carbohydrate chains, terminating with bothα2,3 andα2,6 linked sialic acids. These results demonstrate that recombinant human follicle stimulating hormone made in the Sp2/0 myeloma cells is sialylated, has a more basic isoform profile, and has a greaterin vitro biological potency compared to those of the pituitary human follicle stimulating hormone.


Monitoring consumption of methadone and heroin in major Chinese cities by wastewater-based epidemiology.
Methadone maintenance treatment (MMT) services have been used in China for treatment of heroin dependence. But no study has been conducted to assess the appropriateness of MMT distribution and the potential abuse of methadone in China. This study aims to do that through a nationwide estimation of methadone consumption in China via wastewater-based epidemiology and subsequently compare it with MMT data and level of heroin abuse. Wastewater samples were collected from 53 wastewater treatment plants in 27 major cities that cover all geographic regions of China. Methadone and pure heroin consumptions were estimated based on influent concentrations of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), morphine and codeine. Drug residues were detected in most samples. The ratio of EDDP/methadone was around 2 in influents and methadone and EDDP loads were strongly correlated, indicating that they originated from human consumption. Both influent methadone and EDDP loads in Southwest and Northwest China were significantly higher than those in other regions. The highest estimated consumptions of methadone and heroin in China were 22.0 ± 2.1 mg/1000 in./d and 263.9 ± 115.9 mg/1000 in./d, respectively. There was a significant positive correlation between methadone and heroin consumptions. Consumption of methadone in China was primarily from MMT services. The use of methadone and heroin displayed a clear geographical pattern: it is higher in the western inland regions than in the eastern regions. This study has shown that the distribution of MMT services is reflective of the level of heroin abuse in different regions of China.


Keeping puberty on time: novel signals and mechanisms involved.
Puberty is the culmination of a complex series of maturational events that lead to the completion of sexual and somatic maturation and the acquisition of reproductive competence. This key developmental transition, which defines the boundary between immaturity and adulthood, is under the control of sophisticated regulatory networks that impinge upon the brain centers governing the reproductive axis. These networks are sensitive to earlier maturational events, such as brain sex differentiation, and dynamically regulated by a plethora of hormonal factors and environmental signals, which are essential for the fine-tuning of the tempo of puberty. While much knowledge on mammalian puberty had been gleaned during the last decades, important recent developments have substantially expanded our understanding of the neuroendocrine and molecular mechanisms governing puberty onset. We will provide here a synoptic account of some of these important advancements, including the identification of the essential roles of hypothalamic kisspeptin signaling, and some of its putative partners, in pubertal maturation, the characterization of novel mechanisms involved in the metabolic regulation of puberty, and the recognition of the potential roles of epigenetics and miRNA-related pathways in the central control of puberty. It is expected that further progress in these and related areas will follow in the coming years. This will permit a better understanding of the physiological mechanisms responsible for pubertal timing and will help to decipher the pathophysiological basis for pubertal alterations in humans and wildlife species.


Six percent hetastarch versus lactated Ringer's solution - for preloading before spinal anesthesia for cesarean section.
Regional anesthesia has been the choice of preference for elective cesarean sections. This study was designed to determine whether preoperative administration of 6% hetastarch decreases the incidence of hypotension. This study was conducted on 50 nonlaboring American Society of Anesthesiologists class I and II women undergoing elective cesarean section. Patients were randomly divided into two groups and were preloaded either with 1000 ml Ringer's lactate (RL) or 500 ml of 6% hetastarch 30 min prior to the surgery. Spinal anesthesia was performed with patients in the left lateral position and 2 cc (10 mg) of 0.5% of bupivacaine injected into subarachnoid space. Hemodynamic variables (heart rate, noninvasive blood pressure, and SpO2) were recorded from prior to preloading until the recovery from the subarachnoid blockade. Our study showed the incidence of hypotension to be 28% in the hetastarch group and 80% in the RL group. Rescue ephedrine requirements for the treatment of hypotension were significantly less in patients who were preloaded with 6% hetastarch prior to cesarean section. The neonatal outcome, as determined by Apgar scores was good and similar in both groups. Hence, we conclude that 6% hydroxyl ethyl starch is more effective than lactated Ringers solution and that its routine use for preloading prior to spinal anesthesia should be considered.


Dynamics and Power Balance of Near Unity Target Gain Inertial Confinement Fusion Implosions.
The change in the power balance, temporal dynamics, emission weighted size, temperature, mass, and areal density of inertially confined fusion plasmas have been quantified for experiments that reach target gains up to 0.72. It is observed that as the target gain rises, increased rates of self-heating initially overcome expansion power losses. This leads to reacting plasmas that reach peak fusion production at later times with increased size, temperature, mass and with lower emission weighted areal densities. Analytic models are consistent with the observations and inferences for how these quantities evolve as the rate of fusion self-heating, fusion yield, and target gain increase. At peak fusion production, it is found that as temperatures and target gains rise, the expansion power loss increases to a near constant ratio of the fusion self-heating power. This is consistent with models that indicate that the expansion losses dominate the dynamics in this regime.


Isomorphic skin reaction with DNCB in SLE and DLE.
DNCB sensitization was studied in 76 cases of systemic and 44 of discoid lupus erythematosus and in 101 immunosuppressed and tumor patients as controls, as well as in 40 contact-sensitized eczematous and 115 unselected patients. Sensitization of patients with discoid LE and that of mixed patients are of the same order, while it is lower in the systemic LE group. The highest incidence was found in the polysensitized positive control group; the lowest in the immunosuppressed and tumor patients. DNCB sensitization showed clear age dependency in the different groups. At the site of the DNCB exposure, isomorphic reactions were found in 43% of discoid and 25% of systemic LE patients. Histological and immunofluorescence studies supported the findings of the clinical picture, i. e. the appearance of isomorphic reactions at the site of the exposure cannot be related either to the intensity of the early reaction or with the developing intensity.


BAY 41-2272 inhibits human T lymphocyte functions.
BAY 41-2272 increases guanosine 3', 5'-cyclic monophosphate (cGMP) levels by stimulating soluble guanylate cyclase (sGC). In this study, we evaluated the effect of BAY 41-2272 on human T lymphocyte functions. Pretreating T cells for 24 h with BAY 41-2272 at 3 μM and 30 μM, followed by activation with 90 nM phorbol myristate acetate (PMA), inhibited interferon-gamma (IFN-γ) production, with 3 μM and 30 μM BAY causing 16.5-fold and 12.1-fold inhibition, respectively, compared to PMA alone (p < 0.05, one-way ANOVA followed by Tukey's test). We also observed suppressive effects on the expression of CD69, with 30 μM BAY causing 3.55-fold lower expression than PMA/ionomycin (p < 0.001 one-way ANOVA followed by Tukey's test), and T-bet, with 30 μM BAY causing 1.47-fold lower expression than PMA/ionomycin (p < 0.05, one-way ANOVA test followed by Tukey's test). Additionally, T lymphocyte proliferation was reduced 2.13-fold and 4.3-fold, respectively, by 3 μM BAY and 30 μM BAY compared to PMA/ionomycin (p < 0.01, p < 0.001, one-way ANOVA followed by Tukey's test). BAY 41-2272 inhibits human T lymphocyte function and may be explored as an immunomodulatory drug in patients with autoimmune/inflammatory diseases and lymphoproliferative syndromes.


Seminal Plasma Triggers the Differential Expression of the Glucocorticoid Receptor (NR3C1/GR) in the Rabbit Reproductive Tract.
Rabbits are interesting as research animal models for reproduction, due to their condition of species of induced ovulation, with the release of endogenous gonadotropin-releasing hormone (GnRH) due to coitus. Glucocorticoid (GC) signaling, crucial for physiological homeostasis, is mediated through a yet unclear mechanism, by the GC receptor (NR3C1/GR). After mating, the female reproductive tract undergoes dynamic modifications, triggered by gene transcription, a pre-amble for fertilization and pregnancy. This study tested the hypothesis that when ovulation is induced, the expression of NR3C1 is influenced by sperm-free seminal plasma (SP), similarly to after mating (whole semen), along the different segments of the internal reproductive tract of female rabbits. Semen (mating) was compared to vaginal infusion of sperm-free SP (Experiment 1), and changes over time were also evaluated, i.e., 10, 24, 36, 68, and 72 h post-mating, corresponding to specific stages, i.e., ovulation, fertilization, and the interval of early embryo development up to the morula stage (Experiment 2). All does were treated with GnRH to induce ovulation. Samples were retrieved from seven segments of the reproductive tract (from the cervix to infundibulum), at 20 h post-mating or sperm-free SP infusion (Experiment 1) or at 10, 24, 36, 68, and 72 h post-mating (Experiment 2). Gene expression of NR3C1 was analyzed by qPCR. Results showed an increase in NR3C1 expression in the infundibulum compared to the other anatomical regions in the absence of spermatozoa when sperm-free SP infusion was performed (Experiment 1). Moreover, during the embryo transport through the oviduct, the distal isthmus was time-course upregulated, especially at 72 h, when morulae are retained in this anatomical region, while it was downregulated in the distal uterus at 68 h (Experiment 2). The overall results suggest that NR3C1, the GC receptor gene, assessed in the reproductive tract of does for the first time, shows differential expression changes during the interval of oviductal and uterine embryo transport that may imply a relevant role of the GC action, not only close to the site of ovulation and fertilization, but also in the endometrium.


Does a causal relation exist between the functional hemispheric asymmetries of visual processing subsystems?
Past research indicates that specific shape recognition and spatial-relations encoding rely on subsystems that exhibit right-hemisphere advantages, whereas abstract shape recognition and spatial-relations encoding rely on subsystems that exhibit left-hemisphere advantages. Given these apparent regularities, we tested whether asymmetries in shape processing are causally related to asymmetries in spatial-relations processing. We examined performance in four tasks using the same stimuli with divided-visual-field presentations. Importantly, the asymmetry observed in any one task did not correlate with the asymmetries observed in the other tasks in ways predicted by extant theories. Asymmetries in shape processing and spatial-relations encoding may not be due to a common causal force influencing multiple subsystems.


GLAST (GLutamate and ASpartate Transporter) in human prefrontal cortex; interactome in healthy brains and the expression of GLAST in brains of chronic alcoholics.
We have analysed post-mortem samples of prefrontal cortex from control and alcoholic human brains by the technique of Western blotting to estimate and compare the expressions of glutamate transporter GLAST (Excitatory Amino Acid Transporter One; EAAT1). Furthermore, using the non-alcoholic prefrontal cortex and custom-made GLAST (EAAT1) antibody we determined GLAST (EAAT1) "interactome" i.e. the set of proteins selectively bound by GLAST (EAAT1). We found that GLAST (EAAT1) was significantly more abundant (about 1.6-fold) in the cortical tissue from alcoholic brains compared to that from non-alcoholic controls. The greatest increase in the level of GLAST (EAAT1) was found in plasma membrane fraction (2.2-fold). Additionally, using the prefrontal cortical tissue from control brains, we identified 38 proteins specifically interacting with GLAST (EAAT1). These can be classified as contributing to the cell structure (6 proteins; 16%), energy and general metabolism (18 proteins; 47%), neurotransmitter metabolism (three proteins; 8%), signalling (6 proteins: 16%), neurotransmitter storage/release at synapses (three proteins; 8%) and calcium buffering (two proteins; 5%). We discuss possible consequences of the increased expression of GLAST (EAAT1) in alcoholic brain tissue and whether or how this could disturb the function of the proteins potentially interacting with GLAST (EAAT1) in vivo. The data represent an extension of our previous proteomic and metabolomic studies of human alcoholism revealing another aspect of the complexity of changes imposed on brain by chronic long-term consumption of ethanol.


Positron emission tomography in pediatric epilepsy.
PET is an additional tool in the armamentarium to provide improved care to children and infants with epilepsy. It provides important lateralizing information noninvasively, thus avoiding the need for depth or subdural electrodes in most instances. It can be invaluable when CT and MR imaging do not show a structural lesion. When it corresponds to an EEG focus of epileptogenicity, intraoperative electrocorticography may be used to delineate further the extent of surgical resection, often with impressive reduction in the seizure frequency postoperatively. As PET technology continues to improve, the clinical role of PET in the future will undoubtedly continue to grow.


[5,10,15,20-Tetra-kis-(penta-fluoro-phen-yl)porphyrin-ato]zinc(II) benzene disolvate.
Single crystals of the title zinc porphyrinato complex, [Zn(C44H8F20N4)]·2C6H6, were obtained by the solvent evaporation method. The molecular complex exhibits point group symmetry with the central ZnII atom located on an inversion centre. The porphyrinato core is approximately planar, and the cation has no other ligating atoms than the four porphyrinato N atoms. π-π inter-actions between benzene solvent mol-ecules and [Zn(TFPP)] units lead to multilayer packing structures. In addition, inter-molecular C-H⋯F hydrogen bonding is observed between [Zn(TFPP)] mol-ecules.


The Antinociceptive Effect of Sympathetic Block is Mediated by Transforming Growth Factor β in a Mouse Model of Radiculopathy.
Although sympathetic blockade is clinically used to treat pain, the underlying mechanisms remain unclear. We developed a localized microsympathectomy (mSYMPX), by cutting the grey rami entering the spinal nerves near the rodent lumbar dorsal root ganglia (DRG). In a chemotherapy-induced peripheral neuropathy model, mSYMPX attenuated pain behaviors via DRG macrophages and the anti-inflammatory actions of transforming growth factor-β (TGF-β) and its receptor TGF-βR1. Here, we examined the role of TGF-β in sympathetic-mediated radiculopathy produced by local inflammation of the DRG (LID). Mice showed mechanical hypersensitivity and transcriptional and protein upregulation of TGF-β1 and TGF-βR1 three days after LID. Microsympathectomy prevented mechanical hypersensitivity and further upregulated Tgfb1 and Tgfbr1. Intrathecal delivery of TGF-β1 rapidly relieved the LID-induced mechanical hypersensitivity, and TGF-βR1 antagonists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX. In situ hybridization showed that Tgfb1 was largely expressed in DRG macrophages, and Tgfbr1 in neurons. We suggest that TGF-β signaling is a general underlying mechanism of local sympathetic blockade.


[STRATEGY AND METHODS FOR THE RISK ASSESSMENT OF THERMAL COMFORT IN THE WORKPLACE].
This paper examines the problem of assessing thermal conditions in moderate working environments. We reviewed all the laws and technical standards on the focus to propose a method of evaluation by steps including a subjective assessment and technical measurements.


Impact and appropriateness of the emergency ultrasonography in a tertiary care hospital.
To quantify the notion of the impact of ultrasonography (US) on and the appropriateness of its use in, the diagnosis and treatment of emergency conditions. A prospective study was conducted between September 2006 andApri 2007 at a tertiary care hospital. US was performed or supervised by experienced staff radiologists during the working hours and by final year radiology residents during the off-hours. Data collection forms were filled by radiology residents. The final discharge diagnoses were obtained from medical charts and computerized records. Data collected included age, gender provisional diagnosis, ultrasound findings, the discharge diagnosis, time of ultrasound examination, other radiologic investigations and therapeutic interventions. Outcomes included the impact, appropriateness, and diagnostic accuracy of US. Six hundred eighteen patients underwent 702 emergency ultrasound examinations. The median age was 51 years. Approximately 50% were male. The anatomical region most commonly examined was the abdomen (80%). US had an impact on clinical management in 85% of all examinations. Appropriate use of US was seen in 64% of all examinations. The overall accuracy of US was 90%. Factors associated with higher impact included suspected urological, vascular and musculoskeletal conditions, while vague abdominal conditions were associated with less impact. The impact of US on the management of emergency conditions was high and most requests for US were appropriate. However a more efficient use of emergency US is still possible, especially for abdominal conditions.


Factors associated with attrition in a longitudinal rheumatoid arthritis registry.
Loss of participants in longitudinal data collection can affect the validity of outcomes in rheumatoid arthritis (RA) registries. Prior research indicates that demographics and socioeconomic and psychosocial factors contribute to attrition. This study analyzed the characteristics of an RA registry that may contribute to attrition in a hospital-based population. Subjects consisted of RA patients enrolled in the Brigham and Women's Rheumatoid Arthritis Sequential Study. Demographics and clinical and psychological factors were evaluated in univariate analyses to determine differences between participants who dropped out and those who completed 5 years of followup. Univariate factors with a P value <0.1 were used in a survival analysis to determine significant factors associated with attrition. A secondary analysis looked at patients who dropped out during the first year. A total of 1,144 RA participants were enrolled (509 completed 5 years of followup, 227 were still actively enrolled, and 408 dropped out). The attrition rate was 4.31% per 6-month cycle. Shorter disease duration, higher disease activity (3-variable Disease Activity Score in 28 joints using the C-reactive protein level), less education, RA drug therapy, and lower arthritis self-efficacy were statistically significant in multivariate survival analyses. In a secondary analysis, sex and age were the only additional factors found that contributed to attrition. The attrition rate for this registry was similar to rates reported by other registries. Shorter disease duration, higher disease activity, and several other socioeconomic factors were associated. Men and younger patients tended to drop out during the first year. Population differences in each registry may result in different attrition patterns and ultimately, each longitudinal registry should consider conducting its own analyses.


Development of a version of the Schizotypy Traits Questionnaire (STA) for screening children.
Schizotypy may be seen as both a dimension of normal individual differences and an indicator of the predisposition to schizophrenia and schizophrenia-spectrum disorders. Schizotypal traits have been widely investigated in adults but little research has explored schizotypy in younger samples. The aim of the present study was to examine the factor structure of schizotypal traits in a sample of normal children aged 11 to 15 years-a younger sample than investigated in the few previous studies. Schizotypal traits were assessed with the children's version of the adult Schizotypy Traits Questionnaire (STA). A principal components analysis was carried out on data from 317 subjects and yielded a three-factor solution, similar to several previous studies of adult samples. Factor one was characterised by unusual perceptual experiences, factor two by paranoid ideation/social anxiety, and factor three by magical thinking. The factor structure of the STA of this young sample was comparable with the previous studies of adults. The findings suggest that the children's version of STA is a scale suitable for the measurement of schizotypy in young populations, and that this scale could be useful in clinical assessment of children at risk for psychosis, as well as in research.