High-resolution imaging of Ca2+ , redox status, ROS and pH using GFP biosensors.
Many plant response systems are linked to complex dynamics in signaling molecules such as Ca(2+) and reactive oxygen species (ROS) and to pH. Regulatory changes in these molecules can occur in the timeframe of seconds and are often limited to specific subcellular locales. Thus, to understand how Ca(2+) , ROS and pH form part of plants' regulatory networks, it is essential to capture their rapid dynamics with resolutions that span the whole plant to subcellular dimensions. Defining the spatio-temporal signaling 'signatures' of these regulators at high resolution has now been greatly facilitated by the generation of plants expressing a range of GFP-based bioprobes. For Ca(2+) and pH, probes such as the yellow cameleon Ca(2+) sensors (principally YC2.1 and 3.6) or the pHluorin and H148D pH sensors provide a robust suite of tools to image changes in these ions. For ROS, the tools are much more limited, with the GFP-based H(2) O(2) sensor Hyper representing a significant advance for the field. However, with this probe, its marked pH sensitivity provides a key challenge to interpretation without using appropriate controls to test for potentially coupled pH-dependent changes. Most of these Ca(2+) -, ROS- and pH-imaging biosensors are compatible with the standard configurations of confocal microscopes available to many researchers. These probes therefore represent a readily accessible toolkit to monitor cellular signaling. Their use does require appreciation of a minimal set of controls but these are largely related to ensuring that neither the probe itself nor the imaging conditions used perturb the biology of the plant under study.


Anthocyanin composition of black carrot (Daucus carota ssp. sativus var. atrorubens Alef.) cultivars Antonina, Beta Sweet, Deep Purple, and Purple Haze.
This study aimed to identify the pigment composition of black carrot (Daucus carota ssp. sativus var. atrorubens Alef.) cultivars Antonina, Beta Sweet, Deep Purple, and Purple Haze. Cyanidin 3-xylosyl(glucosyl)galactosides acylated with sinapic acid, ferulic acid, and coumaric acid were detected as major anthocyanins by high-performance liquid chromatography with diode array detection (HPLC-DAD) and with electrospray ionization multiple mass spectrometry (HPLC-ESI-MS(n)) analyses. The preparative isolation of these pigments was carried out by means of high-speed countercurrent chromatography (HSCCC). The color activity concept was applied to the isolated anthocyanins at three pH values. Cyanidin 3-xylosyl(sinapoylglucosyl)galactoside was found to exhibit a lower visual detection threshold and a higher pH stability than cyanidin 3-xylosyl(feruloylglucosyl)galactoside and cyanidin 3-xylosyl(coumaroylglucosyl)galactoside. The color parameters of the fresh roots of the four cultivars were described by the CIELab coordinates L* (lightness), C* (chroma), and h(ab) (hue angles). Total phenolics varied among the cultivars and ranged from 17.9 to 97.9 mg gallic acid equivalents (GAE)/100 g fresh weight (fw). For the content of monomeric anthocyanins, values between 1.5 and 17.7 mg/100 g fw were determined.


A qualitative study of chronic pain in Operation Enduring Freedom/Operation Iraqi Freedom veterans: "A burden on my soul".
Over half of the veterans returning from the conflicts in Iraq and Afghanistan are burdened with chronic pain. Although these young veterans may have to live with pain for the rest of their lives, little is known about the struggles this new group of veterans faces, or their perceptions of support from family, friends, and others. The purpose of this study is to understand Operation Enduring Freedom/Operation Iraqi Freedom veterans' experiences with chronic pain and social support. In-depth qualitative interviews were conducted with veterans who participated in an intervention for chronic pain. Grounded theory guided data analysis. Veterans described a range of emotions associated with chronic pain, including hopelessness, anger, and fear that their pain would worsen. For some, talking about their pain was helpful, but others avoided talking about their pain, often because people did not understand or overreacted. Although support from friends and family is often effective, veterans and others with chronic pain are uniquely positioned to offer support to others with pain. Clinically, an approach to pain management in which veteran peers are integrated into chronic pain treatment approaches, similar to the Veterans Affairs' mental health model of care, might offer additional benefits for veterans with chronic pain.


Long-acting inhaled beta 2-agonists for stable COPD.
To describe the pathogenesis of chronic obstructive pulmonary disease (COPD) and mechanisms of benefit, formulations available, drug costs, pharmacokinetic profiles, and pertinent clinical studies for long-acting beta(2)-agonists. A MEDLINE search was conducted from July 1966 through October 2002. Pertinent articles related to COPD and long-acting beta(2)-agonists. The incidence and subsequent morbidity and mortality of COPD have increased during the last 4 decades, prompting worldwide initiatives to formulate guidelines to decrease the burden of this disease. COPD is a progressive, irreversible disease state characterized by chronic cough, dyspnea, sputum production, and wheezing, in which no medication has been shown to decrease mortality, excluding oxygen supplementation. Bronchodilators have been a mainstay of COPD treatment through their ability to work by both smooth- and non-smooth-muscle mechanisms. Long-acting beta(2)-agonists (i.e., formoterol, salmeterol) dosed twice daily provide more convenient dosing than 4-times-daily regimens of traditional short-acting bronchodilators. Both formoterol and salmeterol have acceptable adverse event profiles when used at recommended doses. There have been no direct clinical outcome studies comparing formoterol and salmeterol, but both have shown some benefits over ipratropium and theophylline in improving the symptoms, spirometric indices, exacerbations, and quality of life of patients with COPD. Based on current evidence, long-acting beta(2)-agonists are acceptable first-line agents for patients with COPD.


Bacterial community variations in an alfalfa-rice rotation system revealed by 16S rRNA gene 454-pyrosequencing.
Crop rotation is a practice harmonized with the sustainable rice production. Nevertheless, the implications of this empirical practice are not well characterized, mainly in relation to the bacterial community composition and structure. In this study, the bacterial communities of two adjacent paddy fields in the 3rd and 4th year of the crop rotation cycle and of a nonseeded subplot were characterized before rice seeding and after harvesting, using 454-pyrosequencing of the 16S rRNA gene. Although the phyla Acidobacteria, Proteobacteria, Chloroflexi, Actinobacteria and Bacteroidetes predominated in all the samples, there were variations in relative abundance of these groups. Samples from the 3rd and 4th years of the crop rotation differed on the higher abundance of groups of presumable aerobic bacteria and of presumable anaerobic and acidobacterial groups, respectively. Members of the phylum Nitrospira were more abundant after rice harvest than in the previously sampled period. Rice cropping was positively correlated with the abundance of members of the orders Acidobacteriales and 'Solibacterales' and negatively with lineages such as Chloroflexi 'Ellin6529'. Studies like this contribute to understand variations occurring in the microbial communities in soils under sustainable rice production, based on real-world data.


Risk prediction model of clinical mastitis in lactating dairy cows based on machine learning algorithms.
Mastitis is the most common disease among dairy cows and is known to have negative effects on both animal welfare and the profitability of dairy farms. Early detection of clinical mastitis cases is considered the best option for preventing cows from developing mastitis. In this study, we developed clinical mastitis prediction models that only required inputting common indicators from the automatic milking system. We utilized multidimensional data from the cow mastitis database of Afimilk (China) Agricultural Technology Co., Ltd. to predict mastitis in dairy cows. All data were screened for the period of 0-150 days of lactation. The data included parity, lactation day, period, mean and standard deviation of milk yield, of electrical conductivity, and of lying time, which were taken as input features. The classification of whether cows suffer from clinical mastitis was determined as output. We analyzed 426 cows with clinical mastitis and 2087 healthy cows by using four machine learning algorithms: Decision Tree, Random Forest, Back Propagation neural networks, and Support Vector Machines. In these four algorithms, the accuracy ranged from 94% to 98%, while the running times varied widely from seconds to minutes. The decision tree prediction model achieved an accuracy of 98% and the precision rate for healthy cows was 99%, while for mastitis cows it was 97%. Machine learning algorithms have played an important role in predicting cow mastitis, with the Decision Tree algorithm showing great performance and higher accuracy in our research.


Social network characteristics and cognition in middle-aged and older adults.
We examined the relationship between social network characteristics and global cognitive status in a community-based sample of 354 adults aged 50+ and with Mini-Mental State Examination (MMSE) scores of 28+ at baseline. Multivariate analyses indicated that interaction in larger social networks related to better maintenance of MMSE scores and reduced odds of decline to population-based lower quartile MMSE scores at follow-up 12 years later. At follow-up, higher levels of interpersonal activity (more frequent contacts in larger social networks) and exposure to emotional support independently related positively to MMSE. The findings suggest that interaction in larger social networks is a marker that portends less cognitive decline, and that distinct associational paths link interpersonal activity and emotional support to cognitive function.


The CO 2 laser in mastectomy: a ten-year follow-up.
We compared the healing process, postoperative course, and follow-up of patients who underwent modified radical mastectomy in the conventional way with those who underwent a laser procedure. Sixty women, aged 33 to 77 years, who suffered from carcinoma of the breast were randomly divided into two groups: Group 1: surgery was performed using scalpel and electrosurgery; Group 2: surgery was performed with a CO 2 Sharplan laser, skin-to-skin including the axilla dissection; maximal power, 40-60 W. The postoperative course was uneventful in both groups. Wound healing was normal. Sutures were removed on the tenth day. Patients were followed at the Outpatient Clinic for 10 years. The circumference of the arm and forearm was measured at fixed points before surgery and at follow-up. Mammography and liver and bone scans were performed every year. Four Group 1 patients developed swelling and edema of 2 to 3 cm at 6 to 8 months after surgery. Also two patients from subgroup A developed local recurrence. No edema or swelling or local recurrence could be detected in patients operated by laser. Surgery with laser is preferable to the conventional approach.


[High risk groups in health behavior defined by clustering of smoking, alcohol, and exercise habits: National Heath and Nutrition Examination Survey].
We investigated the clustering of selected lifestyle factors (cigarette smoking, heavy alcohol consumption, lack of physical exercise) and identified the population characteristics associated with increasing lifestyle risks. Data on lifestyle risk factors, sociodemographic characteristics, and history of chronic diseases were obtained from 7,694 individuals >/=20 years of age who participated in the 2005 Korea National Health and Nutrition Examination Survey (KNHANES). Clustering of lifestyle risks involved the observed prevalence of multiple risks and those expected from marginal exposure prevalence of the three selected risk factors. Prevalence odds ratio was adopted as a measurement of clustering. Multiple correspondence analysis, Kendall tau correlation, Man-Whitney analysis, and ordinal logistic regression analysis were conducted to identify variables increasing lifestyle risks. In both men and women, increased lifestyle risks were associated with clustering of: (1) cigarette smoking and excessive alcohol consumption, and (2) smoking, excessive alcohol consumption, and lack of physical exercise. Patterns of clustering for physical exercise were different from those for cigarette smoking and alcohol consumption. The increased unhealthy clustering was found among men 20-64 years of age with mild or moderate stress, and among women 35-49 years of age who were never-married, with mild stress, and increased body mass index (>30 kg/m(2)). Addressing a lack of physical exercise considering individual characteristics including gender, age, employment activity, and stress levels should be a focus of health promotion efforts.


Effects of sex and reproductive experience on the number of orexin A-immunoreactive cells in the prairie vole brain.
Large populations of cells synthesizing the neuropeptide orexin (OX) exist in the caudal hypothalamus of all species examined and are implicated in physiological and behavioral processes including arousal, stress, anxiety and depression, reproduction, and goal-directed behaviors. Hypothalamic OX expression is sexually dimorphic in different directions in laboratory rats (F>M) and mice (M>F), suggesting different roles in male and female physiology and behavior that are species-specific. We here examined if the number of hypothalamic cells immunoreactive for orexin A (OXA) differs between male and female prairie voles (Microtus ochrogaster), a socially monogamous species that pairbonds after mating and in which both sexes care for offspring, and if reproductive experience influences their number of OXA-immunoreactive (OXA-ir) cells. It was found that the total number of OXA-ir cells did not differ between the sexes, but females had more OXA-ir cells than males in anterior levels of the caudal hypothalamus, while males had more OXA-ir cells posteriorly. Sexually experienced females sacrificed 12 days after the birth of their first litter, or one day after birth of a second litter, had more OXA-ir cells in anterior levels but not posterior levels of the caudal hypothalamus compared to females housed with a brother (incest avoidance prevents sibling mating). Male prairie voles showed no effect of reproductive experience but showed an unexpected effect of cohabitation duration regardless of mating. The sex difference in the distribution of OXA-ir cells, and their increased number in anterior levels of the caudal hypothalamus of reproductively experienced female prairie voles, may reflect a sex-specific mechanism involved in pairbonding, parenting, or lactation in this species.


The mitochondrial message-specific mRNA protectors Cbp1 and Pet309 are associated in a high-molecular weight complex.
In Saccharomyces cerevisiae, the nuclear-encoded protein Cbp1 promotes stability and translation of mitochondrial cytochrome b transcripts through interaction with the 5' untranslated region. Fusion of a biotin binding peptide tag to the C terminus of Cbp1 has now allowed detection in mitochondrial extracts by using peroxidase-coupled avidin. Cbp1 is associated with the mitochondrial membranes when high ionic strength extraction conditions are used. However, the protein is easily solubilized by omitting salt from the extraction buffer, which suggests Cbp1 is loosely associated with the membrane through weak hydrophobic interactions. Gel filtration analysis and blue native PAGE showed that Cbp1 is part of a single 900,000-Da complex. The complex was purified using the biotin tag and a sequence-specific protease cleavage site. In addition to Cbp1, the complex contains several polypeptides of molecular weights between 113 and 40 kDa. Among these, we identified another message-specific factor, Pet309, which promotes the stability and translation of mitochondrial cytochrome oxidase subunit I mRNA. A hypothesis is presented in which the Cbp1-Pet309 complex contains several message-specific RNA binding proteins and links transcription to translation of the mRNAs at the membrane.


The presence of Aspergillus fumigatus in asthmatic airways is not clearly related to clinical disease severity.
It is suggested that airway fungi, in particular Aspergillus may impinge on clinical phenotype in asthma. Indeed, the term severe asthma with fungal sensitization (SAFS) has been coined. We aimed to ascertain whether the presence of fungi, in particular Aspergillus fumigatus, in the airway correlated with asthma severity and control. Furthermore, we aimed to determine whether traditional markers of Aspergillus sensitization related to the presence of Aspergillus within the airway. Sixty-nine patients characterized by asthma severity (GINA) and level of control (ACQ-7) underwent bronchoscopy and bronchoalveolar lavage (BAL). Serum was assessed for A fumigatus-specific IgE and total IgE. Galactomannan and relevant cytokine levels were assessed in serum, plasma and BAL. BAL was analyzed for the presence of A fumigatus. In BAL, fungi were visible by microscopy in 70% and present by qPCR in 86% of patients, while A fumigatus was detectable by qPCR in 46%. Plasma and BAL IL-4, IL-6, IL-10, IL-13 and TNF-α correlated with BAL fungal presence, while plasma IL-17 correlated with BAL fungal presence. Aspergillus positive BAL correlated with increased plasma and BAL IL-6 and BAL IL-13. There was no relationship between fungal airway presence and steroid dose, asthma severity or control. The presence of Aspergillus within the airway did not relate to serum IgE positivity for Aspergillus. Fungi were present in a large proportion of our asthmatic patients' airways, but their presence was not predicted by traditional markers of sensitization, nor did it appear to be related to measures of disease severity or control.


A cyclodextrin formulation to improve use of the anesthetic tribromoethanol (Avertin(®)).
Efficacy and safety concerns have been raised in the literature with the use of tribromoethanol (TBE) (Avertin(®)) for anesthesia in rats and mice when administered by intraperitoneal (IP) injection. Despite the controversy, it remains in common usage as an anesthetic agent in laboratory rodents for short-term surgical procedures. Cyclodextrins have been shown to improve drug solubility and were investigated here as an improved anesthetic formulation for mice. The phase solubility of TBE with hydroxypropyl-β-cyclodextrin (HP-β-CD) was estimated. The efficacy of two anesthetic regimens was compared in this study; the conventional TBE formulation solubilized in tert-amyl alcohol and a HP-β-CD formulation containing TBE. Mice (n = 6) were administered the formulations by IP injection and the pharmacodynamic parameters of time to induction of anesthesia, duration of anesthesia and recovery time were measured using a combined reflex score (CRS). Phase solubility studies showed a linear increase in the solubility of TBE with increasing HP-β-CD concentration and suggested >1:1 binding of the drug in the cyclodextrin complex. At a dose of 260 mg/kg the standard TBE formulation appeared to produce deeper anesthesia than the cyclodextrin formulation, with a minimum average CRS of 1.8 compared with 5.2. No post-mortem pathology was observed in mice that received either the conventional or cyclodextrin formulation. The cyclodextrin TBE formulation did not conclusively provide an improved anesthetic response at a dose of 260 mg/kg compared with the conventional formulation. The improved solubility of TBE with HP-β-CD and the reduced variability in anesthetic response warrants the further investigation of this formulation. This study has also identified the value of using the anticholinergic atropine in association with TBE for anesthesia.


Low-cost, programmable infusion pump with bolus mode for in-vivo imaging.
Syringe pumps are routinely used in biomedical imaging laboratories for delivering contrast agents and either infusing or injecting a precise amount of liquids. Commercial syringe pumps that are developed by specialized companies are expensive and only have standard functions, which often do not meet the requirements of individual experiments. In this paper, we demonstrate an open-source single syringe pump with the possibility of adapting to the needs of a researcher. The device that was designed, is controlled by an Arduino Leonardo, along with the stepper motor driver. For sending commands and receiving the current plunger position, a C# software was developed with serial communication via USB. Additionally, the 3D models were made in a universal way, which allows for the use of any syringe size. An example of the application of the syringe pump for biomedical applications was demonstrated using electron resonance imaging (ERI). The single syringe pump tests were demonstrated by simulating the filling of a particular volume inside the resonator. This example reflects the clearance process after an intravascular (I.V) drug administration in the murine model. The experiments were performed on an ERI TM 600 tomograph. The results confirmed that the designed syringe pump allowed for controlling the infusion speed and injected volume. Moreover, we present a user-friendly and open-source graphical interface that is a low-cost alternative for commercial devices.


Influence of correlated antigen presentation on T-cell negative selection in the thymus.
The thymus is the primary organ for the generation of naive T cells, a key component of the immune system. Tolerance of T cells to self is achieved primarily in the thymic medulla, where immature T cells (thymocytes) sample self-peptides presented by medullary thymic epithelial cells (mTECs). A sufficiently strong interaction activates the thymocytes leading to negative selection. A key question of current interest is whether there is any structure in the manner in which mTECs present peptides: can any mTEC present any peptide at any time, or are there particular patterns of correlated peptide presentation? We investigate this question using a mathematical model of negative selection. We find that correlated patterns of peptide presentation may be advantageous in negatively selecting low-degeneracy thymocytes (that is, those thymocytes which respond to relatively few peptides). We also quantify the probability that an auto-reactive thymocyte exits the thymus before it encounters a cognate antigen. The results suggest that heterogeneity of gene co-expression in mTECs has an effect on the probability of escape of autoreactive thymocytes.


Relationship of unkeratinized skin to bovine fetal mummification: an hypothesis.
Evidence is reviewed in support of the hypothesis that immature unkeratinized fetal skin must be present if bovine fetal mummification is to occur. The reduction in fetal and amniotic fluid is considered to be the result of intrafetal (fetal death) or prefetal (caruncular damage) effects on the normal net fluid flow from the maternal circulation through the fetal circulation and then across the fetal skin into the amniotic cavity. As the skin is keratinized permeability is reduced drastically thus limiting fluid loss from the fetus.


[Chronic hypereosinophilia: a model of Th2 disorders].
Interleukin-5 produced by Th2-type lymphocytes is involved in the pathogenesis of a number of hypereosinophilic disorders. We and others have identified clonal Th2 cells with abnormal surface phenotypes in peripheral blood of certain patients presenting the idiopathic hypereosinophilic syndrome. We took advantage of the CD3- CD4+ phenotype of our patients' T cells to determine the activation signals involved in their production of Th2 cytokines and expansion, independently of T cell receptor engagement. In vitro cocultures performed with dendritic cells demonstrated the critical role of co-stimulatory signalling through B.7/CD28 and LFA-3/CD2 pathways and the involvement of an autocrine IL2/IL2R loop in the activation of these Th2-type cells. The high-level spontaneous apoptosis displayed by these cells in vitro was drastically inhibited by IL2 and IFN-alpha. New therapeutic strategies could result from our observations. Indeed, the hypereosinophilic syndrome may represent an unexpected application of new immunomodulatory molecules such as CTLA4-Ig and anti-IL2R-alpha.


Cantonese-style salted fish as a cause of nasopharyngeal carcinoma: report of a case-control study in Hong Kong.
Two hundred fifty incident cases of nasopharyngeal carcinoma under age 35 years in Hong Kong Chinese and an equal number of age- and sex-matched friend controls were interviewed. Mothers of cases and controls were interviewed also, if available, to obtain information on childhood events concerning the study subjects. Consumption of Cantonese-style salted fish during all time periods was significantly associated with nasopharyngeal carcinoma; the association was especially strong during childhood. The relative risk for having Cantonese-style salted fish as one of the first solid foods during weaning was 7.5 (95% confidence limits, 3.9, 14.8), and the relative risk for consuming the food at least once a week compared to less than once a month at age 10 years was 37.7 (95% confidence limits, 14.1, 100.4). It is estimated that over 90% of young nasopharyngeal carcinoma cases in Hong Kong Chinese can be attributed to consumption of this food during childhood.


Changes in expression of cartilaginous genes during chondrogenesis of Wharton's jelly mesenchymal stem cells on three-dimensional biodegradable poly(L-lactide-co-glycolide) scaffolds.
In cartilage tissue regeneration, it is important to develop biodegradable scaffolds that provide a structural and logistic template for three-dimensional cultures of chondrocytes. In this study, we evaluated changes in expression of cartilaginous genes during in vitro chondrogenic differentiation of WJ-MSCs on PLGA scaffolds. The biocompatibility of the PLGA material was investigated using WJ-MSCs by direct and indirect contact methods according to the ISO 10993-5 standard. PLGA scaffolds were fabricated by the solvent casting/salt-leaching technique. We analyzed expression of chondrogenic genes of WJ-MSCs after a 21-day culture. The results showed the biocompatibility of PLGA and confirmed the usefulness of PLGA as material for fabrication of 3D scaffolds that can be applied for WJ-MSC culture. The in vitro penetration and colonization of the scaffolds by WJ-MSCs were assessed by confocal microscopy. The increase in cell number demonstrated that scaffolds made of PLGA copolymers enabled WJ-MSC proliferation. The obtained data showed that as a result of chondrogenesis of WJ-MSCs on the PLGA scaffold the expression of the key markers collagen type II and aggrecan was increased. The observed changes in transcriptional activity of cartilaginous genes suggest that the PLGA scaffolds may be applied for WJ-MSC differentiation. This primary study suggests that chondrogenic capacity of WJ-MSCs cultured on the PLGA scaffolds can be useful for cell therapy of cartilage.


[A comparative evaluation of different methods of esophagoplasty].
Intraoperative comparative oxyhemo- and thermometry of fragments of the gastrointestinal tract used for creation of the artificial esophagus were performed in 41 patients. The relationship of the degree of ischemic alterations in the transplant tissues and the development of postoperative complications was determined.


Pulmonary Arteriovenous Malformations Are Associated with Silent Brain Infarcts in Hereditary Hemorrhagic Telangiectasia Patients.
There is a high prevalence of right-to-left shunting pulmonary arteriovenous malformations (PAVMs), which are stroke risk factors, in hereditary hemorrhagic telangiectasia (HHT) patients. While the prevalence of ischemic complications in HHT patients is known, the prevalence of silent brain infarcts (SBI) remains unknown. The purpose of this study was to determine the prevalence and risk factors for SBI in HHT patients. Our institutional HHT database was queried to identify HHT patients who received a baseline screening brain MRI from January 2000 to February 2017. This study group was further refined by excluding patients who had a history of clinical ischemic disease as defined by having a stroke or transient ischemic attack (TIA). Brain MRIs were reviewed for SBI. Baseline data on demographics, Curacao criteria, presence of PAVMs, and cardiovascular risk factors were collected. The primary outcome was SBI prevalence. We also examined which baseline patient characteristics were associated with SBI through univariate chi-square and Student t tests and multivariate logistic regression analyses. Three hundred fifty three consecutive HHT patients from January 2000 to February 2017 with a screening brain MRI and no prior history of stroke/TIA were included. SBI prevalence was 9.9% (35/353). SBI patients were more likely to have PAVMs than non-SBI patients (80.6 vs. 53.1%, p = 0.005). The median age was 66 in the SBI group and 52 in the non-SBI group (p = 0.006). SBI patients had higher prevalence of hyperlipidemia (34.3 vs. 9.8%, p < 0.0001), hypertension (48.6 vs. 22.0%, p = 0.005), and tobacco use (25.7 vs. 9.8%, p = 0.005). No patients under 30 had SBI. In the 60-69 age group, the prevalence of SBI was 18.8% with rates of 28.6% in the PAVM group and 10.5% in the non-PAVM group. For patients ≥70 years old, the prevalence of SBI was 21.4% overall and 27.6% in the PAVM group and 10.5% in the non-PAVM group. On multivariate analysis, PAVMs (OR 3.62, 95% CI 1.46-10.40) and increasing age (OR 1.04, 95% CI 1.01-1.07) were independently associated with SBI. Overall, a similar 10% SBI prevalence in the HHT cohort was noted as compared to the general population. However, the prevalence of SBI was higher in HHT patients with PAVMs when compared to that of the general population, particularly among patients than 60 years old. These findings highlight the need to accurately identify, and when appropriate, treat PAVMs in the HHT population especially given the multiple significant, clinical consequences of SBI.


Application of statistical and computational methodology to predict brainstem dosimetry for trigeminal neuralgia stereotactic radiosurgery.
To apply advanced statistical and computational methodology in evaluating the impact of anatomical and technical variables on normal tissue dosimetry of trigeminal neuralgia (TN) stereotactic radiosurgery (SRS). Forty patients treated with LINAC-based TN SRS with 90 Gy maximum dose were randomly selected for the study. Parameters extracted from the treatment plans for the study included three dosimetric output variables: the maximum dose to the brainstem (BSmax), the volume of brainstem that received at least 10 Gy (V10BS), and the volume of normal brain that received at least 12 Gy (V12). We analyzed five anatomical variables: the incidence angle of the nerve with the brainstem surface (A), the nerve length (L), the nerve width as measured both axially (WA) and sagittally (WS), the distance measured along the nerve between the isocenter and the brainstem surface (D), and one technical variable: the utilized cone size (CS). Univariate correlation was calculated for each pair among all parameters. Multivariate regression models were fitted for the output parameters using the optimal input parameters selected by the Gaussian graphic model LASSO. Repeated twofold cross-validations were used to evaluate the models. Median BSmax, V10BS, and V12 for the 40 patients were 35.7 Gy, 0.14 cc, and 1.28 cc, respectively. Median A, L, WA, WS, D, and CS were 43.7°, 8.8 mm, 2.8 mm, 2.7 mm, 4.8 mm, and 6 mm, respectively. Of the three output variables, BSmax most strongly correlated with the input variables. Specifically, it had strong, negative correlations with the input anatomical variables and a positive correlation with CS. The correlation between D and BSmax at -0.51 was the strongest correlation between single input and output parameters, followed by that between CS and V10BS at 0.45, and that between A and BSmax at -0.44. V12 was most correlated with cone size alone, rather than anatomy. LASSO identified an optimal 3-feature combination of A, D, and CS for BSmax and V10BS prediction. Using cross-validation, the multivariate regression models with the three selected features yielded stronger correlations than the correlation between the BSmax and V10BS themselves. For the first time, an advanced statistical and computational methodology was applied to study the impact of anatomical and technical variables on TN SRS. The variables were found to impact brainstem doses, and reasonably strong correlation models were established using an optimized 3-feature combination including the nerve incidence angle, cone size, and isocenter-brainstem distance.


Applying the resource-based relative value scale to the Emory angioplasty versus surgery trial.
The resource-based relative value scale developed for use in the Medicare fee schedule can also be very useful in profiling and comparing physicians' cardiovascular utilization across different medical activities. This article applies relative value units (RVUs) to data from the Emory Angioplasty versus Surgery Trial. The Emory Angioplasty versus Surgery Trial was a randomized clinical trial to determine the efficacy of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass surgery (CABG). All physician services in the clinical trial provided to 2 groups of patients--those undergoing CABG and those receiving PTCA-over the course of 4 years were assigned physician work RVUs (representing the intensity of physician work required) and total RVUs (representing both the intensity and practice costs). Physician charges were also compiled. These data were used to profile and compare physician services to the 2 groups of patients by type of service, distribution over time, and clinical department. Comparisons based on RVUs contrast sharply with differences based on charges. Mean physician charges, in 1996 dollars, were $27,158 for CABG patients and $21,491 for PTCA patients, a 26% difference (p <0.001). Physician work RVUs generated an 18.3% difference (p = <0.001). Using total RVUs, the difference between the 2 groups was 3.3% (p = 0.249). Resource-based relative value weights are a valuable tool for analyzing and comparing physicians' use of cardiovascular resource. The results suggest that conclusions about physician resource utilization based on physician charges should be carefully evaluated. When possible, physician work RVUs should be compiled and evaluated along with physician charges.


Effect of combined anti-PD-1 and temozolomide therapy in glioblastoma.
Background: Although programmed death-1 (PD-1) blockade is effective in treating several types of cancer, the efficacy of this agent in glioblastoma (GBM) is largely unknown. Methods: We evaluated therapeutic effects of anti-PD-1, temozolomide (TMZ), and their combination in an orthotopic murine GBM model. The phenotype, number, and composition of lymphocytes were evaluated using flow cytometry. Transcriptional profiles of tumor tissues were analyzed using microarrays. Generation of antitumor immunological memory was investigated upon rechallenge. Results: Combined treatment with anti-PD-1 and TMZ yielded synergistic antitumor efficacy in the presence of donor-originated PD-1+CD8+ T cells in vitro, necessitating in vivo validation. Whereas TMZ did not rescue GBM-implanted mice, anti-PD-1 completely eradicated GBM in 44.4% of mice, and combination of anti-PD-1 and TMZ in all mice. Anti-PD-1 significantly increased the number of tumor-infiltrating lymhpocytes (TILs), and reduced frequencies of exhausted T cells and regulatory T cells. However, combining TMZ with anti-PD-1 significantly decreased the number of TILs, which was also observed with TMZ treatment alone. A transcriptome analysis of tumor tissues revealed that anti-PD-1 monotherapy perturbed immune-related genes, distinctly with combined therapy. Upon rechallenge, tumor growth was not observed in mice cured by anti-PD-1 monotherapy, whereas tumors regrew in the combination group. Furthermore, an analysis of peripheral blood revealed that antitumor memory T cells were generated in mice cured by anti-PD-1 monotherapy, not in the combination group. Conclusion: PD-1 blockade induces long-term therapeutic response, and combination with TMZ further enhances antitumor efficacy. However, immunological memory is provoked by anti-PD-1 monotherapy, not by combined therapy.


Coping styles in European sea bass: The link between boldness, stress response and neurogenesis.
Coping styles consist of a coherent set of individual physiological and behavioral differences in stress responses that are consistent across time and context. Such consistent inter-individual differences in behavior have already been shown in European sea bass (Dicentrarchus labrax), but the associated mechanisms are still poorly understood. Here, we combine physiological measurements with individual behavioral responses in order to characterize coping styles in fish. Fish were tagged and placed in a tank for group risk-taking tests (GRT) at 8 months of age to evaluate boldness using the proxy latency of leaving a sheltered area towards an open area. A subsample of these fish were individually challenged 16 months later using an open field test (OFT), in which the boldness was assessed after being placed in a shelter within an open arena. Latency to exit the shelter, time spent in the shelter, and distance travelled were recorded for this purpose. The blood and brain were then collected to evaluate plasma cortisol concentration and neurotransmitter levels (dopamine, norepinephrine, serotonin, and related metabolites), as well as brain transcription of key genes involved in stress axis regulation (gr1, gr2, mr, crf), neurogenesis (neurod1, neurod2, pcna), and neuronal development (egr1). Fish acting bolder in the GRT were not necessarily those acting bolder in the OFT, highlighting the relatively low consistency across different types of tests performed with a 16-months interval. There was, however, a significant correlation between stress markers and boldness. Indeed, mRNA levels of mr, crf, gr2, egr1, and neurod2, as well as norepinephrine levels were higher in shy than bold fish, whereas brain serotonergic activity was lower in shy fish. Overall, our study highlights the fact that boldness was not consistent over time when testing context differed (group vs. alone). This is in agreement with previous literature suggesting that social context play a key role in boldness measurement and that the particular life history of each individual may account in shaping the personality fate of a fish.


Recalling safety: cooperative functions of the ventromedial prefrontal cortex and the hippocampus in extinction.
Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.


Developmental bias in evolution: evolutionary accessibility of phenotypes in a model evo-devo system.
The success of the modern synthesis has resulted in forces of evolutionary change other than natural selection being marginalized. However, recent work has attempted to show the importance of non-selective influences in shaping organic form. One such force is developmental bias, in which phenotypes are differentially produced. We use a simulation model of neural development to explore questions of general interest about developmental systems. From this analysis, we find that the pattern of developmental bias varies strongly with the genotype even among phenotypically-neutral genotypes. In addition to this genotype-dependent developmental bias (local bias), an intrinsic bias exists in the developmental system (global bias). We also show that developmental bias varies among related genotypes that produce the same phenotype. Finally, we illustrate how a pattern of bias emerges from the manner in which mutations affect the regulatory structure of the wild-type genotype. These results suggest that developmental bias could have a strong influence on the direction of evolutionary modification.


Lack of restriction of T cell receptor beta variable gene usage in cerebrospinal fluid lymphocytes in acute optic neuritis.
There have been many studies reporting restricted patterns of T cell receptor usage in established multiple sclerosis and these have led to clinical trials of immunomodulation directed at deleting clonal T cell populations. The present study aims to test the hypothesis that highly restricted T cell populations are also present in the CSF in the earliest clinical stages of acute demyelinating disease of the CNS. T cell receptor Vbeta (TCRBV) gene expression was studied in CSF and blood in nine patients with acute optic neuritis within 7 days of onset of symptoms, six patients with an acute relapse of multiple sclerosis, and 13 control subjects. RNA was extracted and cDNA synthesised from unstimulated CSF and blood lymphocytes, and TCRBV gene segments were amplified from the cDNA by polymerase chain reaction (PCR) using 21 family specific primers. PCR products were separated by polyacrylamide gel electrophoresis and detected via a labelled oligonucleotide probe. A semiquantitative analysis of band intensity was performed by laser densitometry. TCRBV mRNA was detected in the CSF of eight of nine patients with optic neuritis, six of six patients with multiple sclerosis, and five of 13 controls, and was closely correlated with the presence of oligoclonal IgG. Usage of a single TCRBV family was demonstrated in two of nine patients with optic neuritis and two of six patients with multiple sclerosis. The number of TCRBV families expressed in the other patients ranged between 5 and 15 (optic neuritis) and 4 and 17 (multiple sclerosis). There is a relative lack of restriction of TCRBV usage by CSF lymphocytes in the very earliest stages (<7 days) of acute optic neuritis. This may imply either that multiple sclerosis is not a monoclonal disease even at onset, or that the autoimmune response has widened before the disease becomes clinically evident. This may have important consequences for the design of immune therapies in multiple sclerosis. Further studies are required to determine whether the CSF T cell repertoire at presentation has prognostic importance. Longitudinal studies are required to follow the CSF T cell repertoire from the time of presentation and to determine whether it may have prognostic significance.


Ex Vivo MRI Analytical Methods and Brain Pathology in Preterm Lambs Treated with Postnatal Dexamethasone †.
Postnatal glucocorticoids such as dexamethasone are effective in promoting lung development in preterm infants, but are prescribed cautiously due to concerns of neurological harm. We developed an analysis pipeline for post-mortem magnetic resonance imaging (MRI) to assess brain development and hence the neurological safety profile of postnatal dexamethasone in preterm lambs. Lambs were delivered via caesarean section at 129 days' (d) gestation (full term ≈ 150 d) with saline-vehicle control (Saline, n = 9), low-dose tapered dexamethasone (cumulative dose = 0.75 mg/kg, n = 8), or high-dose tapered dexamethasone (cumulative dose = 2.67 mg/kg, n = 8), for seven days. Naïve fetal lambs (136 d gestation) were used as end-point maturation controls. The left-brain hemispheres were immersion-fixed in 10 % formalin (24 h), followed by paraformaldehyde (>6 months). Image sequences were empirically optimized for T1- and T2-weighted MRI and analysed using accessible methods. Spontaneous lesions detected in the white matter of the frontal cortex, temporo-parietal cortex, occipital lobe, and deep to the parahippocampal gyrus were confirmed with histology. Neither postnatal dexamethasone treatment nor gestation showed any associations with lesion incidence, frontal cortex (total, white, or grey matter) or hippocampal volume (all p > 0.05). Postnatal dexamethasone did not appear to adversely affect neurodevelopment. Our post-mortem MRI analysis pipeline is suitable for other animal models of brain development.


Epithelioid sarcoma metastatic to the tongue: a rare entity.
Epithelioid sarcoma (ES) typically arises as a firm nodule on the extremities of young men. The tumor is remarkable for diagnostic difficulties both clinically and histopathologically resulting in a high frequency of initial misdiagnosis. ES is also known to have a high rate of recurrence and high rate of metastasis predominantly to the lymph nodes, lungs, and scalp. Herein, the second case of ES with metastasis to the tongue is reported.


Estimating the Size of Key Populations in Kampala, Uganda: 3-Source Capture-Recapture Study.
Key populations, including people who inject drugs (PWID), men who have sex with men (MSM), and female sex workers (FSW), are disproportionately affected by the HIV epidemic. Understanding the magnitude of, and informing the public health response to, the HIV epidemic among these populations requires accurate size estimates. However, low social visibility poses challenges to these efforts. The objective of this study was to derive population size estimates of PWID, MSM, and FSW in Kampala using capture-recapture. Between June and October 2017, unique objects were distributed to the PWID, MSM, and FSW populations in Kampala. PWID, MSM, and FSW were each sampled during 3 independent captures; unique objects were offered in captures 1 and 2. PWID, MSM, and FSW sampled during captures 2 and 3 were asked if they had received either or both of the distributed objects. All captures were completed 1 week apart. The numbers of PWID, MSM, and FSW receiving one or both objects were determined. Population size estimates were derived using the Lincoln-Petersen method for 2-source capture-recapture (PWID) and Bayesian nonparametric latent-class model for 3-source capture-recapture (MSM and FSW). We sampled 467 PWID in capture 1 and 450 in capture 2; a total of 54 PWID were captured in both. We sampled 542, 574, and 598 MSM in captures 1, 2, and 3, respectively. There were 70 recaptures between captures 1 and 2, 103 recaptures between captures 2 and 3, and 155 recaptures between captures 1 and 3. There were 57 MSM captured in all 3 captures. We sampled 962, 965, and 1417 FSW in captures 1, 2, and 3, respectively. There were 316 recaptures between captures 1 and 2, 214 recaptures between captures 2 and 3, and 235 recaptures between captures 1 and 3. There were 109 FSW captured in all 3 rounds. The estimated number of PWID was 3892 (3090-5126), the estimated number of MSM was 14,019 (95% credible interval (CI) 4995-40,949), and the estimated number of FSW was 8848 (95% CI 6337-17,470). Our population size estimates for PWID, MSM, and FSW in Kampala provide critical population denominator data to inform HIV prevention and treatment programs. The 3-source capture-recapture is a feasible method to advance key population size estimation.


Determination of solubility parameters of ionic liquids and ionic liquid/solvent mixtures from intrinsic viscosity.
The total and partial solubility parameters (dispersion, polar and hydrogen-bonding solubility parameters) of ten ionic liquids were determined. Intrinsic viscosity approaches were used that encompassed a one-dimensional method (1D-Method), and two different three-dimensional methods (3D-Method1 and 3D-Method2). The effect of solvent type, the dimethylacetamide (DMA) fraction in the ionic liquid, and dissolution temperature on solubility parameters were also investigated. For all types of effect, both the 1D-Method and 3D-Method2 present the same trend in the total solubility parameter. The partial solubility parameters are influenced by the cation and anion of the ionic liquid. Considering the effect on partial solubility parameters of the solvent type in the ionic liquid, it was observed that in both 3D methods, the dispersion and polar parameters of a 1-ethyl-3-methylimidazolium acetate/solvent (60:40 vol %) mixture tend to increase as the total solubility parameter of the solvent increases.


[Breast cancer: age and tumor diameter. Partial results of a long-term study since 1966].
From 1963 to 1985 approximately 2,800 patients underwent primary treatment for breast cancer at Erlangen University Gynecological Clinic. In the same period just under 60,000 women underwent thorough clinical, mammographic, and in some cases sonographic examination. In the last 20 years the age of patients with breast cancer has shifted toward the younger age groups. Peak incidence is found among 40 to 49-year-old and 60 to 64-year-old women. The data indicate that women should undergo screening for breast cancer from the age of 35 on, and in high-risk cases from age 25. The majority of the carcinomas are 1-2 cm in diameter. This has not changed in the last 10 years. Only in every tenth patient is the tumor less than 1 cm in diameter.


Predicting disease progression in cirrhotic patients after transjugular intrahepatic portosystemic shunt implantation: A sex-stratified analysis.
Transjugular intrahepatic portosystemic shunt (TIPS) has been extensively used to treat portal hypertension-associated complications, including cirrhosis. The prediction of post-TIPS prognosis is important for cirrhotic patients, as more aggressive liver transplantation is needed when the post-TIPS prognosis is poor. To construct a nutrition-based model that could predict the disease progression of cirrhotic patients after TIPS implantation in a sex-dependent manner. This study retrospectively recruited cirrhotic patients undergoing TIPS implantation for analysis. Muscle quality was assessed by measuring the skeletal muscle index (SMI) by computed tomography. Multivariate Cox proportional hazard models were utilized to determine the association between SMI and disease progression in cirrhotic patients after TIPS implantation. This study eventually included 186 cirrhotic patients receiving TIPS who were followed up for 30.5 ± 18.8 mo. For male patients, the 30-mo survival rate was significantly lower and the probability of progressive events was higher (3.257-fold) in the low-level SMI group than in the high-level SMI group. According to the multivariate Cox analysis of male patients, SMI < 32.8 was an independent risk factor for long-term adverse outcomes after TIPS implantation. A model was constructed, which involved creatinine, plasma ammonia, SMI, and acute-on-chronic liver failure and hepatic encephalopathy occurring within half a year after surgery. This model had an area under the receiver operating characteristic curve of 0.852, sensitivity of 0.926, and specificity of 0.652. According to the results of the DeLong test, this model outperformed other models (Child-Turcotte-Pugh, Model for End-Stage Liver Disease, and Freiburg index of post-TIPS survival) (P < 0.05). SMI is strongly associated with poor long-term outcomes in male patients with cirrhosis who underwent TIPS implantation.


[Patterns in the restoration of skin derivatives in warm-blooded animals].
It is known that the skin derivatives in homeothermic animals appear in the early prenatal period of development and do not form during postnatal development. However, during skin regeneration, a process of secondary development, it was shown experimentally on eight homeothermic animals, in which full-layered fragments of skin were removed from different morphofunctional regions of skin, that in the skin regenerates its derivatives are formed: hair, sebaceous and sweat glands, and skin folds. The data obtained suggest that formation of the hair and sebaceous glands requires the presence of special dermal fibroblasts in the young connective tissue of regenerants, which are capable of induction of the potencies of regenerating epidermis for organogenesis.


An exploratory randomized controlled trial of body psychotherapy for patients with chronic depression.
Chronic major depressive disorder and dysthymia are associated with a high burden and substantial care costs. New and more effective treatments are required. This is the first randomized controlled trial designed to evaluate the effectiveness of Body Psychotherapy (BPT) in patients with chronic depression. Patients with chronic depressive syndromes (more than 2 years symptomatic) and a total score of ≥ 20 on the Hamilton Rating Scale for Depression (HAMD) were randomly allocated to either immediate BPT or a waiting group which received BPT 12 weeks later. BPT was manualized, delivered in small groups in 20 sessions over a 10 weeks period, and provided in addition to treatment as usual. In an intention to treat analysis, primary outcome were depressive symptoms at the end of treatment adjusted for baseline symptom levels. Secondary outcomes were self-esteem and subjective quality of life. Thirty-one patients were included and twenty-one received the intervention. At the end of treatment patients in the immediate BPT group had significantly lower depressive symptom scores than the waiting group (mean difference 8.7, 95% confidence interval 1.0-16.7). Secondary outcomes did not show statistically significant differences. When the scores of the waiting group before and after BPT (as offered after the waiting period) were also considered in the analysis, the differences with the initial waiting group remained significant. The results suggest that BPT may be an effective treatment option for patients with chronic depression. Difficulty recruiting and subsequent attrition was one of the limitations, but the findings merit further trials with larger samples and process studies to identify the precise therapeutic mechanisms.


Inactivation of macromolecules by ionizing radiation. Deterministic single-hit or stochastic multievent process?
A stochastic theory concerning the radiation inactivation of macromolecules such as enzymes or receptors is elaborated. In contrast with the single-hit theory, which assumes a complete inactivation of the target as the result of one hit, the stochastic theory postulates that the degree of inactivation by one hit is a random variable. This distinguishing feature has been considered in order to give a possible interpretation to the observed effect of temperature on the radiation-sensitivity of enzymes. As a consequence of the progressive inactivation during irradiation, the binding affinity of a ligand for the macromolecule is impaired by irradiation. Although this property might discriminate the stochastic theory from the classical single-hit theory on the basis of a statistical analysis of experimentally obtained data, it is shown that the commonly obtained degree of inaccuracy may render the statistical test non-conclusive.


FASTING IN ELECTIVE SURGICAL PATIENTS: COMPARISON AMONG THE TIME PRESCRIBED, PERFORMED AND RECOMMENDED ON PERIOPERATIVE CARE PROTOCOLS.
Prolonged preoperative fasting may impair nutritional status of the patient and their recovery. In contrast, some studies show that fasting abbreviation can improve the response to trauma and decrease the length of hospital stay. Investigate whether the prescribed perioperative fasting time and practiced by patients is in compliance with current multimodal protocols and identify the main factors associated. Cross-sectional study with 65 patients undergoing elective surgery of the digestive tract or abdominal wall. We investigated the fasting time in the perioperative period, hunger and thirst reports, physical status, diabetes diagnosis, type of surgery and anesthesia. The patients were between 19 and 87 years, mostly female (73.8%). The most performed procedure was cholecystectomy (47.69%) and general anesthesia the most used (89.23%). The most common approach was to start fasting from midnight for liquids and solids, and most of the patients received grade II (64.6%) to the physical state. The real fasting average time was 16 h (9.5-41.58) was higher than prescribed (11 h, 6.58 -26.75). The patients submitted to surgery in the afternoon were in more fasting time than those who did in the morning (p<0.001). The intensity of hunger and thirst increased in postoperative fasting period (p=0.010 and 0.027). The average period of postoperative fasting was 18.25 h (3.33-91.83) and only 23.07% restarted feeding on the same day. Patients were fasted for prolonged time, higher even than the prescribed time and intensity of the signs of discomfort such as hunger and thirst increased over time. To better recovery and the patient's well-being, it is necessary to establish a preoperative fasting abbreviation protocol.


Yoga interventions in pregnancy: a qualitative review.
Every second 4.3 births occur in the world, signifying the magnitude and importance of pregnancy. This study looked at yoga interventions done from 2008 to December 2013 and examined whether yoga can be an efficacious approach for influencing maternal and birth outcomes in pregnancy. A systematic search of MEDLINE (PubMed), CINAHL, Alt HealthWatch, Cochrane Database of Systematic Reviews, and ACP Journal Club databases was conducted for quantitative articles of pregnancy involving all schools of yoga. A total of 15 articles met the inclusion criteria: 6 from the United States, 6 from India, 2 from Taiwan, and 1 each from Korea and Thailand. Of the 15 studies, 10 showed positive changes in maternal psychological or birth outcomes. The included studies have some limitations. Nonetheless, yoga appears to be a promising intervention for pregnancy.


Metal contamination at a wood preservation site: characterisation and experimental studies on remediation.
The aim of this investigation was to determine the occurrence of As, Cu, Cr and Zn in the soil at an abandoned wood preservation unit and to examine some possible extractants for the contaminants in the soil. The mean As content of the contaminated surface soils (0-10 cm) was 186 mg kg(-1), where as the mean concentrations of Cu, Cr and Zn in soils from the contaminated area were 26, 29 and 91 mg kg(-1), respectively. The elevated As content in the mineral soils is related to adsorption of inorganic As phases in the fine grained fractions, which are characterised by large surface area and high positive surface charge under the current acidic conditions. Cu and Cr were found to be rather mobile, which is reflected in their lower abundance in soils and significant accumulation in sediments in the drainage leaving the area. The fine fraction of the soil (<0.125 mm) has an average metal content increased by nearly 34% as compared to the <2-mm fraction conventionally used for the analysis and assessment of soil contamination. The <2-mm fraction constitutes approximately 65% of the total weight while the fine fraction (<0.125 mm) constitutes approximately 10%. These facts, taken together, are essential for the choice of remediation measures. Oxalate solutions have been tested as extractants for soil remediation. Dark acid oxalate extraction dissolves the amorphous Al- and Fe-oxides and hydroxides and mobilises the adsorbed inorganic As species. Oxalate also acts as a ligand for the cationic heavy metals, releasing them from exchangeable sites. With a three-step sequential leaching, up to 98-99% of the metals could be removed. At lower concentrations and higher pH, the leaching decreased to approximately 70%.


Polyphenol metabolism provides a screening tool for beneficial effects of Onobrychis viciifolia (sainfoin).
Onobrychis viciifolia (sainfoin) is a traditional fodder legume showing multiple benefits for the environment, animal health and productivity but weaker agronomic performance in comparison to other legumes. Benefits can be mainly ascribed to the presence of polyphenols. The polyphenol metabolism in O. viciifolia was studied at the level of gene expression, enzyme activity, polyphenol accumulation and antioxidant activity. A screening of 37 accessions regarding each of these characters showed a huge variability between individual samples. Principal component analysis revealed that flavonols and flavan 3-ols are the most relevant variables for discrimination of the accessions. The determination of the activities of dihydroflavonol 4-reductase and flavonol synthase provides a suitable screening tool for the estimation of the ratio of flavonols to flavan 3-ols and can be used for the selection of samples from those varieties that have a specific optimal ratio of these compounds for further breeding.


Expression of soluble HLA-G identifies favorable outcomes in liver transplant recipients.
Human leukocyte antigen (HLA)-G displays immunotolerogenic properties toward the main effector cells involved in graft rejection through inhibition of natural killer cell- and cytotoxic T-lymphocyte-mediated cytolysis, and CD4 T-cell alloproliferation. An increase in serum and graft levels of HLA-G has been noted in transplant patients with improved allograft survival. However, the clinical relevance of soluble serum HLA-G molecules in tolerant pediatric and young adult liver transplant patients remains to be studied. We examined the serum HLA-G levels in 42 pediatric and young adult liver transplant patients with a mean age of 15 years; 13 patients had operational tolerance (TOL), with complete immunosuppression withdrawal for 2.3 to 13.2 years. Median HLA-G level in patients with acute rejection (AR) was similar to the level in pediatric healthy volunteers (9.9 vs. 4.2 U/mL, P=0.13). HLA-G was higher in patients with stable liver function on immunosuppression (54.6 U/mL) than in patients with AR (P=0.01) and healthy volunteers (P=0.003), but almost 6-fold lower than in TOL patients (325.4 U/mL). HLA-G did not correlate with clinical confounders or a history of posttransplant lymphoproliferative disease or Epstein-Barr virus; although levels in the TOL group were negatively correlated with time after immunosuppression withdrawal (r=-0.75, P=0.003). In rejectors, HLA-G levels trended to negatively correlate with a higher number (r=-0.58) and greater severity of AR episodes (r=-0.56) after 1 year posttransplantation. Increased serum HLA-G levels track with operational tolerance of liver grafts and support favorable outcomes in pediatric and young adult recipients.


Social cognition in patients at ultra-high risk for psychosis: What is the relation to social skills and functioning?
Patients at ultra-high risk (UHR) for psychosis show significant impairments in functioning. It is essential to determine which factors influence functioning, as it may have implications for intervention strategies. This study examined whether social cognitive abilities and clinical symptoms are associated with functioning and social skills. The study included 65 UHR patients and 30 healthy controls. Social cognitive function, social skills, and a broad range of functioning measures were assessed. The UHR patients demonstrated significant decrements on The Awareness of Social Inferences Task total score (p = .046, d = .51), and on the CANTAB emotion recognition task total percent correct (p = .023, d = .54) displaying particular difficulties in negative affect recognition. The patients exhibited significant impairments in social skills measured with the High Risk Social Challenge (p˂.001, d = 1.05). Aspects of emotion recognition were associated with role functioning and social skill performance. The level of attributional bias was associated with overall functioning, and theory of mind ability was associated with self-reported functioning. Negative symptoms were associated with all measures of functioning (p ≤ .05). Significant impairments in social cognition and social skills were found in UHR patients. The patients' social cognitive function was associated with overall functioning and social skills. Negative symptoms appear to play an important role for functioning. Research is needed to investigate how the relations between social cognition, social skills and functioning develop from the UHR state to the stage of manifest illness. Research into how deficits in social cognition and social skills can be ameliorated in UHR patients is warranted.


Current tips for ensuring successful transfemoral short limb cannulation in modular aortic endografts: a new method for incorporation in practice.
One of the most crucial steps in endovascular infrarenal abdominal aortic aneurysm repair is the short limb catheterization of the modular device and the confirmation of the intrastent position of the guidewire. Failed connection of the contralateral iliac limb to the main body because of malposition of the catheterizing guidewire may lead to serious complications. A new method confirming successful passage of the guidewire in the short leg of the main body of the modular stent graft, thus ensuring that the extension will be accurately docked within the short limb, is described in detail. Furthermore, current tips for ensuring successful short limb cannulation are also described in brief.


Should botulinum toxin A injections be repeated in children with cerebral palsy? A systematic review.
The aim of this study was to determine the effects of repeat botulinum toxin A (BoNT-A) injections in children with spastic cerebral palsy (CP) on the basis of a best evidence synthesis. This study included 13 original articles after searching the literature to retrieve information. We used the critical review form produced by McMaster University to determine the methodological quality of the studies, and then confirmed the levels of evidence from Sackett. The studies were also evaluated using the International Classification of Function, Disability and Health - Children and Youth Version (ICF-CY). A total of 893 children with spastic CP who had been administered repeat BoNT-A injections were evaluated. The evidence level was II in four of the thirteen studies, III in four studies, and IV in five studies. The McMaster review form score was 14 in two studies, 13 in four studies, and 12 in seven studies. The results showed that repeat BoNT-A may be a safe and an effective approach. The first two injections/one repeat especially relieve spasticity and improve fine and gross motor activities. Future studies to investigate the effectiveness of repeat BoNT-A in children with spastic CP may be planned within the framework of the ICF-CY to include well-designed randomized controlled trials and those conducted on larger homogenous groups.


Psychophysiological reactions during the trauma-film paradigm and their predictive value for intrusions.
Background: Adequate adaptation of the autonomic nervous system (ANS) is crucial in potentially life-threatening situations. The defence cascade provides a descriptive model of progressing dominant physiological reactions in such situations, including cardiovascular parameters and body mobility. The empirical evidence for this model is scarce, and the influence of physiological reactions in this model for predicting trauma-induced intrusions is unresolved.Objectives: Using a trauma-film paradigm, we aimed to test physiological reactions to a highly stressful film as an analogue to a traumatic event along the defence cascade model. We also aimed to examine the predictive power of physiological activity for subsequent intrusive symptoms.Method: Forty-seven healthy female participants watched a stressful and a neutral film in randomized order. Heart rate (HR), heart rate variability (HRV), and body sway were measured. Participants tracked frequency, distress, and quality of subsequent intrusions in a diary for 7 consecutive days.Results: For the stressful film, we observed an initial decrease in HR, followed by an increase, before the HR stabilized at a high level, which was not found during the neutral film. No differences in HRV were observed between the two films. Body sway and trembling frequency were heightened during the stressful film. Neither HR nor HRV predicted subsequent intrusions, whereas perceived distress during the stressful film did.Conclusions: Our results suggest that the physiological trauma-analogue response is characterized by an orientation response and subsequent hyperarousal, reaching a high physiological plateau. In contrast to the assumptions of the defence cascade model, the hyperarousal was not followed by downregulation. Potential explanations are discussed. For trauma-associated intrusions in the subsequent week, psychological distress during the film seems to be more important than physiological distress. Understanding the interaction between physiological and psychological responses during threat informs the study of ANS imbalances in mental disorders such as post-traumatic stress disorder.


Cinobufacini injection delays hepatocellular carcinoma progression by regulating lipid metabolism via SREBP1 signaling pathway and affecting macrophage polarization.
Cinobufacini injection, an aqueous extract of the toad, is a commonly used anti-tumor animal herbal medicine in clinical practice. It has the effects of detoxifying, reducing swelling, and relieving pain. To investigate the effects of Cinobufacini injection on hepatocellular carcinoma progression by regulating lipid metabolism and macrophage polarization in the tumor microenvironment and to identify the potential molecular mechanisms. To establish the axillary transplantation tumor model of hepatocellular carcinoma Hepa1-6 in C57BL/6 mice, and to evaluate the inhibitory effect of Cinobufacini injection on hepatocellular carcinoma in vivo as well as drug delivery security. Combined metabolomics and transcriptomics analysis of the effect of Cinobufagin Injection on tumor microenvironment. An in vitro mouse co-culture model of peritoneal macrophages and Hepa1-6 cells was established to research the effects of Cinobufacini injection on macrophage polarization, hepatocellular carcinoma cell growth, migration, and changes in lipid metabolism. Cinobufacini injection inhibition of the AMPK/SREBP1/FASN signaling pathway regulating cholesterol metabolism and affecting macrophage polarization was examined using qRT-PCR, lentiviral transfection, immunofluorescence, and Western blot. In vivo experiments demonstrated that Cinobufacini injection treatment significantly inhibited the growth of Hepa1-6 hepatomas, along with a reduction in cholesterol content and a decrease in the percentage of M2 macrophages in tumor tissue. In vitro, we found that Cinobufacini injection inhibits IL-4-induced M2 macrophage polarization, reduces the cholesterol content of Hepa1-6 cells in a co-culture system, and inhibits the promotion of hepatocellular carcinoma cells by M2 macrophages. In addition, successful overexpression of SREBP1 in Hepa1-6 cells showed more pronounced cellular activity whereas Cinobufacini injection inhibited this change and reduced intracellular lipid levels. Cinobufacini injection inhibits cholesterol synthesis within the tumor microenvironment via the AMPK/SERBP1/FASN signaling pathway, which in turn blocks the M2 polarization of macrophages, leading to the weakening of hepatocellular carcinoma growth and migration, and the promotion of its apoptosis. Our findings provide an important Introduction to understanding the molecular mechanism of Cinobufacini injection's anticancer activity and provide reliable theoretical and experimental support for its clinical application.


CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas.
CD44 and CD44 variant isoforms have been reported as contributing factors to cancer progression. In this study, we aimed to assess whether CD44 and its variant isoforms were correlated with the prognostic factors for distant metastasis in stage I lung adenocarcinomas using tissue microarray and immunohistochemistry. In this single-center retrospective study, we analyzed the data of 490 patients with stage I lung adenocarcinoma resected between 1999 and 2016. We constructed tissue microarrays and performed immunohistochemistry for CD44s, CD44v6, and CD44v9. The risk of disease recurrence and its associations with clinicopathological risk factors were assessed. CD44v6 expression was significantly associated with recurrence. Patients with CD44v6-negative tumors had a significantly increased risk of developing distant recurrence than patients with CD44v6-positive tumors (5-year cumulative incidence of recurrence (CIR), 10.7% vs. 4.6%; P = 0.009). However, CD44v6-negative tumors were not associated with an increased risk of locoregional recurrence compared to CD44v6-positive tumors (5-year CIR, 6.0% vs. 4.0%; P = 0.39). The overall survival (OS) of patients with CD44v6-negative tumors was significantly lower than that of patients with CD44v6-positive tumors (5-year OS: 87% vs. 94%, P = 0.016). CD44v6-negative tumors were also associated with invasive tumor size and lymphovascular invasion. Even in stage I disease, tumors with negative-CD44v6 expression had more distant recurrences than those with positive-CD44v6 expression and were associated with poor prognosis in resected stage I lung adenocarcinomas. Thus, CD44v6 downregulation may be a prognostic factor for distant metastasis in stage I lung adenocarcinomas.


A signal sequence mutant defective in export of ribose-binding protein and a corresponding pseudorevertant isolated without imposed selection.
Ribose-binding protein is exported to the periplasmic compartment of Escherichia coli by a process that involves proteolytic cleavage of an amino-terminal extension of amino acids from the precursor form of the protein. In a collection of mutants isolated as defective in the Rbs transport system, a strain was identified that contained only precursor ribose-binding protein, none of which was exported to its normal location in the periplasm. The mutated rbsB contained a base substitution that results in a change of leucine to a proline at position-17 in the signal sequence. A pseudorevertant of the mutant contained proteolytically processed, active ribose-binding protein in the periplasm. The pseudorevertant rbsB carried a second mutation: serine at position-15 in the signal sequence was changed to phenylalanine. Isolation of a signal sequence mutant and a corresponding pseudorevertant without specific selection or site-directed mutagenesis emphasizes the possibility of obtaining export mutants without the use of procedures that could bias or limit the range of mutations found. Explanation of the extreme phenotype of the mutant and the effective correction of that phenotype in the pseudorevertant requires extension of current notions of critical features of signal sequences.


Biological validation of plant-derived anti-human colorectal cancer monoclonal antibody CO17-1A.
We validated expression and biological activities of plant-derived monoclonal antibody (MAb(P)) CO17-1A for its efficacy in cancer immunotherapy. PCR and immunoblot analyses demonstrated insertion and expression of heavy and light chains of MAb CO17-1A in transgenic plants, respectively. Confocal analysis revealed that MAb(P) CO17-1A was accumulated throughout the cytoplasm near the outer membrane, suggesting its secretion to the outer membrane via a default pathway. Cell ELISA analysis confirmed that the MAb(P) CO17-1A heavy and light chains in crude plant leaf samples assembled to specifically bind SW948 human colorectal carcinoma cells. Flow cytometry analysis showed that the Fc domains of both the purified MAb(P) and the mammalian-derived MAb (MAb(M)) evidenced similar binding activity to the FcgammaRI receptor (CD64). The biological activities of both MAbs were similar, although the glycosylation pattern of MAb(P) CO17-1A is distinct from that of MAb(M). These results point to the potential use of MAb(P) CO17-1A for colorectal cancer immunotherapy.


Induction of expert system rules based on rough sets and resampling methods.
Automated knowledge acquisition is an important research issue in developing medical expert systems. While several methods of symbolic inductive learning have been proposed, most of the approaches focus on inducing some rules to classify cases correctly. On the contrary, medical experts also learn other information important for medical diagnostic procedures from clinical cases. In order to acquire both kinds of knowledge, we developed a program that extracts not only classification rules for differential diagnosis, but also other medical knowledge needed for diagnosis. This system is based on a diagnosing model of a medical expert system RHINOS, which diagnoses causes of headache and facial pain. We apply this program to the same domain and compared the induced results with expert rules. The results show that the combination of a rule induction method with resampling methods is effective to estimate the performance of induced results, especially when only small training samples are available without domain knowledge.


Compassion fatigue and compassion satisfaction among psychologists: Can supervision and a reflective stance be of help?
The pleasure derived from helping others is referred to as compassion satisfaction (CS). When a psychologist feels a too heavy demand to be compassionate and effective in helping, however, this may result in compassion fatigue (CF). CF may take the form of burnout or secondary traumatic stress (STS). The present paper focuses on two factors that may possibly protect against the development of CF, and facilitate the development of CS: (1) access to supervision and (2) a reflective stance. An online survey was distributed to two closed Swedish Facebook groups of psychologists, and complete data were obtained from 374 psychologists (320 women and 63 men). Both variable-oriented and person-oriented analyses were carried out. Correlational analysis showed that both supervision and reflection was associated with more CS, whereas only supervision but not reflection was significantly associated with less CF. Cluster analysis gave a more nuanced picture, suggesting a non-linear and multi-faceted association between reflection and CF. Some clusters of psychologists showed the expected association between level of reflection and level of CF. This was balanced, however, by other clusters that showed an association in the opposite direction, indicating high levels of reflection in clinicians with high levels of CF, and low levels in clinicians with low levels of CF. The results are discussed in terms of these differences in associative patterns possibly being due to different patient populations being involved. Among the limitations of the present study are its cross-sectional design, absence of data on patient characteristics, and a crude measure of supervision and reflection.


The requirement of thymus competence for both humoral and cell-mediated steps in expulsion of Nippostorngylus brasiliensis from mice.
The worm damaging process (step 1 of Nippostrongylus brasiliensis expulsion from rodents) does not occur in congenitally thymus-deficient (nude) mice as determined by worm morphology, female worm fecundity, and kinetics of worm expulsion upon transfer into normal rats. Expulsion of damaged N. brasiliensis (step 2) does not occur subsequent to transfer of such worms from rats into nude mice. Morphological changes and reduced fecundity appeared in adult worms from normal thymus-bearing mice as early as the first day of patency (day 6 of infection). Thus, the worm damaging process is initiated several days earlier in mice than in rats and may, therefore, account for the reduced longevity of N. brasiliensis in mice compared with rats.


Update: seabather's eruption and swimmer's itch.
Swimmer's itch and seabather's eruption, while similar in morphology, differ in important aspects. Seabather's eruption occurs chiefly in salt water and involves covered parts of the body. Swimmer's itch occurs chiefly in fresh water and involves uncovered parts. The cause of swimmer's itch is definitely known to be schistosome cercariae, while the cause of seabather's eruption is for the most part unknown. Algae, coelenterates and schistosomes as well as other organisms found in seawater have been suggested. Control of swimmer's itch is best accomplished by decreasing the snail population.


Sociocultural risk factors for compulsive exercise: a prospective study of adolescents.
The risk factors for compulsive exercise are unknown. This study aims to explore longitudinal sociocultural risk factors for compulsive exercise, using a 12-month prospective design. A sample of 332 male and female adolescents (aged 13-15 years at baseline) completed self-report measures of sociocultural risk factors and compulsive exercise at baseline and eating disorder psychopathology and compulsive exercise at 12-month follow-up assessment. Hierarchical regressions found that family and peer messages to become more muscular predicted compulsive exercise in boys, whereas feeling pressure from the media to be thin was a significant predictor of compulsive exercise in girls. These relationships remained significant when controlling for eating disorder psychopathology but became nonsignificant when initial levels of compulsive exercise were entered into the model. The findings suggest that sociocultural risk factors may contribute to the development of compulsive exercise but future research should utilise a younger sample and employ a longer follow-up period to identify true longitudinal effects.


Cutaneous Manifestations of Dermatomyositis: a Comprehensive Review.
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by the presence of skin lesions and inflammation of skeletal muscles; however, this feature may be absent in amyopathic DM. DM is a rare disease, occurring at any age, and has two peaks of incidence: one in childhood between 5 and 15 years of age and one in adulthood between 40 and 60 years, with a female preponderance. DM has been associated with malignancy; therefore, every newly diagnosed patient should undergo screening investigations, but evidence-based guidelines on their extension are lacking. The etiopathogenesis is still unclear, but a range of factors such as genetic predisposition, environment triggers, and immune- and non-immune-mediated mechanisms play a role in the development of the disorder. Some dermatological findings and new discoveries on immunological mechanisms in DM, including the association of certain autoantibodies with cancer, can be helpful in clinical practice. Therapy should consider both skin and muscle or internal organ involvement. Photoprotection, including the use of antimalarial drugs, plays an important role in the therapeutic approach of skin involvement. Treatment of muscle and internal organ involvement is based on systemic corticosteroids, alone or in association with disease-modifying antirheumatic drugs. Intravenous immunoglobulins have been demonstrated to be effective as second-line therapy. Rituximab is an emerging treatment for difficult-to-treat DM, both in adults and children. In this review article, we discuss DM subforms, focusing on their dermatological manifestations that can be classified as pathognomonic, characteristic, compatible, less common, rare, recently-described, and non-specific skin lesions.


Defining critical residues for substrate binding to 1-deoxy-D-xylulose 5-phosphate synthase--active site substitutions stabilize the predecarboxylation intermediate C2α-lactylthiamin diphosphate.
1-Deoxy-D-xylulose 5-phosphate (DXP) synthase catalyzes the formation of DXP from pyruvate and D-glyceraldehyde 3-phosphate (GraP) in a thiamin diphosphate-dependent manner, and is the first step in the essential pathway to isoprenoids in human pathogens. Understanding the mechanism of this unique enzyme is critical for developing new anti-infective agents that selectively target isoprenoid biosynthesis. The present study used mutagenesis and a combination of protein fluorescence, CD and kinetics experiments to investigate the roles of Arg420, Arg478 and Tyr392 in substrate binding and catalysis. The results support a random sequential, preferred order mechanism, and predict that Arg420 and Arg478 are involved in binding of the acceptor substrate, GraP. D-Glyceraldehyde, an alternative acceptor substrate lacking the phosphoryl group predicted to interact with Arg420 and Arg478, also accelerates decarboxylation of the predecarboxylation intermediate C2α-lactylthiamin diphosphate (LThDP) on DXP synthase, indicating that this binding interaction is not absolutely required, and that the hydroxyaldehyde sufficiently triggers decarboxylation. Unexpectedly, Tyr392 contributes to GraP affinity, and is not required for LThDP formation or its GraP-promoted decarboxylation. Time-resolved CD spectroscopy and NMR experiments indicate that LThDP is significantly stabilized on R420A and Y392F variants as compared with wild-type DXP synthase in the absence of acceptor substrate, but these substitutions do not appear to affect the rate of GraP-promoted LThDP decarboxylation in the presence of high levels of GraP, and LThDP formation remains the rate-limiting step. These results suggest a role of these residues in promoting GraP binding, which in turn facilitates decarboxylation, and also highlight interesting differences between DXP synthase and other thiamin diphosphate-dependent enzymes.


Improved enzymatic method to measure processing effects and starch availability in sorghum grain.
A modified enzymatic method to measure processing effects and starch availability in steam-flaked sorghum grain (SFSG) was developed. To establish the method, experiments were conducted to determine the required enzyme concentration, color reagents, precipitants, sample particle size, shaking frequency and buffer pH. Glucose release at different incubation times (0 to 48 h) from uncooked (UNC) or fully cooked (CK, 100% gelatinized) ground sorghum grain, a 50:50 mixture of UNC and CK (C50) and SFSG was determined. Glucose release from UNC, CK and SFSG was expressed as one-component equations with rate constant k and r2 of .119 and .98, 1.781 and .98, and .368 and .99, respectively; C50 was characterized by having two starch components, one with a fast rate constant, 2.624/h, and one with a slow rate constant, .066/h (R2 = .99). Different degrees of gelatinization were obtained by mixing different proportions of CK and UNC. Glucose release from these samples was highly correlated with starch gelatinization (r2 = .99). By adjusting the tension between mill rollers, five SFSG samples with bulk densities ranging from 476 to 283 g/liter (37 to 22 lb/bu) were produced; respective roller mill electrical load ranged from 21 to 51.5 amps. Enzymatic determination of glucose release resulted in values of 422, 512, 588, 618 and 678 mg/g, which were more closely related to bulk density than birefringence measurements. The modified method for starch availability determination was found to be relatively simple, fast and sensitive, and is recommended.


Efficacy of high dose systemic versus combined (systemic and intratympanic) corticosteroid therapy in idiopathic sudden sensorineural hearing loss: A prospective randomized trial and risk factor analysis.
The pathophysiology and the proper treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) are an ongoing subject of debate. Locally or systemic administered corticosteroids are the most accepted drugs of treatment in reference to ISSNHL (idiopathic sudden sensorineural hearing loss), however, no strong evidence nor guidelines regarding their effectiveness yet exists. In our prospective, randomized, controlled trial 78 participants were enrolled. Patients were randomly assigned based on the day of admission to two groups according to treatment: group SS (n = 43) received intravenous systemic methylprednisolone alone, and group CT (n = 35) received intratympanic dexamethasone + systemic methylprednisolone. The primary outcome was to compare the hearing outcomes between the treatment groups based on different, widely accepted categories (Siegel, Kanzaki, modified Siegel and PTA4 gain). In consideration of the secondary outcome, we examined the effect of the various risk factors on the hearing improvement. No differences were detected regarding hearing improvement between the two groups, based on any criteria [Siegel's criteria (p = 0.604); Kanzaki's criteria (p = 0.720); modified Siegel's criteria (p = 0.524) and PTA 4 gain (p = 0.569)]. However, several clinical factors such as vertigo (p = 0.039), or cardiovascular comorbidity (p = 0.02) and the severity of initial hearing loss (p = 0.033) were found to bear a significant impact upon the hearing outcome. To the best of our knowledge, this is the first randomized controlled trial comparing high dose systemic and combination corticosteroid therapy in ISSNHL patients. Our findings suggest coexisting cardiovascular comorbidity, vertigo and severity of the initial hearing loss may bear a significantly higher impact upon hearing improvement, than the additional intratympanic steroid administration. The presented trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (name: Combinated systemic and intratympanic steroid therapy in idiopathic sudden sensorineural hearing loss, No.: 2017-000658-20) and with the ethical approval of The National Institute of Pharmacy and Nutrition (OGYÉI) (protocol No.: 7621, on 2017.02.16.).


Vascular events associated with the appearance of the secondary center of ossification in the murine distal femoral epiphysis.
Although the formation of a secondary center of ossification is often compared with that of the primary center, there are striking differences between these processes. In the formation of the primary center, vascular invasion is always associated with the maturation of chondrocytes, whereas vascularization of the epiphysis can proceed in two different ways. In some species, the epiphysis is vascularized by cartilage canals before the appearance of the secondary center. However, in the mouse, the distal femoral epiphysis is vascularized by peripheral vascular invasion without pre-existing cartilage canals. Histological study of serial sections and studies of vascularization by injection with India ink demonstrated the relationship between hypertrophic chondrocyte formation, vascular invasion, and the formation of the secondary center of ossification in the murine distal femoral epiphysis.


Demographic study of parkinson's disease in Iran: Data on 1656 cases.
There is no documented demographical study on Iranian Parkinson's disease (PD) patients, so this study was conducted to identify demographic information about patients with PD in Iran, and to explore demographical differences between PD patients in Iran and other countries. We reviewed medical records of 1656 patients diagnosed with PD, who referred from all parts of Iran to a referral Parkinson's disease clinic in Tehran. We collected data about their age, gender, age of onset, side of motor symptoms' onset, and drug history. This study was performed on 1656 patients with idiopathic Parkinson's disease, and the results showed that, out of 1656 cases, 1132 patients were males (68.4%) and 524 patients were females (31.6%). The mean age of these patients was 65.16 ±11.9 years (16-99 years). The mean age of onset in these patients was 53.16 ±12.5 years (12-90 years). Among 697 patients, 345 patients (49.5%) had right onset PD, and the remaining 352 cases had left onset PD (50.5%). Side of motor symptoms onset was not associated with the age of the patients at disease onset (P > 0.05). The incidence of right onset PD in males was 50.1% and 48.2% in females, although this difference was not statistically significant (P > 0.05). There was no significant difference between males and females in age of onset (P > 0.05). Our data suggests that the male to female ratio among Iranian Parkinson's disease patients is much higher than other countries. Additional investigation is required in this field.


The effect of prenatal exposure to 900-MHz electromagnetic field on the 21-old-day rat testicle.
The aim of this study was to investigate the effect of exposure to a 900-MHz electromagnetic field (EMF) in the prenatal term on the 21-old-day rat testicle. Pregnant rats were divided into control (CG) and EMF (EMFG) groups. EMFG was exposed to 900-MHz EMF during days 13-21 of pregnancy. Newborn CG rats were obtained from the CG and newborn EMFG (NEMFG) rats from the EMFG. Testicles were extracted at postnatal day 21. Lipid peroxidation and DNA oxidation levels, apoptotic index and histopathological damage scores were compared. NEMFG rats exhibited irregularities in seminiferous tubule basal membrane and epithelium, immature germ cells in the lumen, and a decreased diameter in seminiferous tubules and thickness of epithelium. Apoptotic index, lipid peroxidation and DNA oxidation were higher in NEMFG rats than in NCG. 21-day-old rat testicles exposed to 900-MHz EMF in the prenatal term may be adversely affected, and this effect persists after birth.


Review of 61 cases of odontoma. Presentation of an erupted complex odontoma.
Odontomas are benign tumors of odontogenic origin characterized by their slow growth. They consist of enamel, dentine, cementum and pulpal tissue and constitute 22% of all odontogenic tumors. Two types of odontoma are recognized: compound and complex. The first is approximately twice as common as complex odontomas. The purpose of this study is to value the prevalence of this kind of tumors in the ambulatory-surgical gambit and their clinical symptoms. We want to emphasize the exceptional spontaneous eruption of this tumors and we report a case of erupted complex odontoma. We made the revision of the cases of diagnosed odontomas between 1983 and 2001 in the Clínica Ntra. Sra. del Remei, in the Centro Médico Teknon and the Master de Cirugía e Implantología Bucal of the Odontologic Clínic (Barcelona University). We analyzed their prevalence, distribution in gender, age of the patients, anatomic location, adjacent structures affectation, symptoms, histologic classification and treatment. 52.4% of the cases were diagnosed in females. 37.7% of the tumors were complex odontomas and 62.3% were diagnosed as compound odontomas. 55.7% of all cases were in the maxilla and 44.3% in the mandible. The anterior portion of maxilla was the most common location (54% of cases). Only a case (1.6%) was erupted, in the molars area of the maxilla.


Shiga Toxins Induce Apoptosis and ER Stress in Human Retinal Pigment Epithelial Cells.
Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are the most potent known virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications such as acute renal failure, blindness and neurological abnormalities. Although numerous studies have defined apoptotic responses to Shiga toxin type 1 (Stx1) or Shiga toxin type 2 (Stx2) in a variety of cell types, the potential significance of Stx-induced apoptosis of photoreceptor and pigmented cells of the eye following intoxication is unknown. We explored the use of immortalized human retinal pigment epithelial (RPE) cells as an in vitro model of Stx-induced retinal damage. To the best of our knowledge, this study is the first report that intoxication of RPE cells with Stxs activates both apoptotic cell death signaling and the endoplasmic reticulum (ER) stress response. Using live-cell imaging analysis, fluorescently labeled Stx1 or Stx2 were internalized and routed to the RPE cell endoplasmic reticulum. RPE cells were significantly sensitive to wild type Stxs by 72 h, while the cells survived challenge with enzymatically deficient mutant toxins (Stx1A- or Stx2A-). Upon exposure to purified Stxs, RPE cells showed activation of a caspase-dependent apoptotic program involving a reduction of mitochondrial transmembrane potential (Δψm), increased activation of ER stress sensors IRE1, PERK and ATF6, and overexpression CHOP and DR5. Finally, we demonstrated that treatment of RPE cells with Stxs resulted in the activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK), suggesting that the ribotoxic stress response may be triggered. Collectively, these data support the involvement of Stx-induced apoptosis in ocular complications of intoxication. The evaluation of apoptotic responses to Stxs by cells isolated from multiple organs may reveal unique functional patterns of the cytotoxic actions of these toxins in the systemic complications that follow ingestion of toxin-producing bacteria.