Dietary vitamin C intake and concentrations in the body fluids and cells of male smokers and nonsmokers.
Inhaled cigarette smoke releases a variety of oxidizing agents. Ascorbic acid is recognized as an important biological antioxidant. To better characterize the antioxidant protective role of ascorbic acid, a comparison of ascorbic acid concentrations in plasma, leukocytes, bronchoalveolar lavage fluid and alveolar macrophages from a homogeneous group of healthy male smokers (n = 10) and nonsmokers (n = 14) was investigated. The resulting ascorbic acid contents were (means +/- SD) 91 +/- 25 (n = 10) and 87 +/- 25 (n = 14) mumol/L in plasma, 2.09 +/- 0.62 (n = 7) and 2.12 +/- 0.77 (n = 11) mumol/10(9) cells in mononuclear leukocytes, 3.2 +/- 2.2 (n = 10) and 1.7 +/- 1.5 (n = 13) mumol/L in bronchoalveolar lavage fluid and 3.4 +/- 2.3 (n = 8) and 1.6 +/- 1.3 (n = 6) mumol/10(9) cells in alveolar macrophages from smokers and nonsmokers, respectively. Mean daily dietary vitamin C intake was 116 +/- 68 and 107 +/- 59 mg/d for smokers and nonsmokers, respectively. The ascorbic acid contents of bronchoalveolar lavage [3.9 +/- 1.9 mumol/L (n = 8)] and alveolar macrophages [4.1 +/- 2.1 mumol/10(9) cells (n = 6)] of smokers consuming 15 to 20 cigarettes/d were significantly higher (P less than 0.05) than those of nonsmokers. The increased content of ascorbic acid in bronchoalveolar lavage and in alveolar macrophages of smokers compared with nonsmokers may reflect a defensive mechanism against free radical species derived from cigarette smoke.


The 5-item mental health index predicts the initial diagnosis of nonfatal stroke in older women.
Relatively little is known about psychosocial risk factors for the onset of stroke. The aim of this paper is to identify independent psychosocial risk factors for subsequent reported new diagnoses of stroke in older women. A prospective cohort study of women initially aged between 70 and 75 years was first surveyed in 1996 and again in 1999. During this interval, from a final sample of 7839 participants, 174 women reported that a doctor had diagnosed them with stroke for the first time. A range of psychosocial risk factors measured in 1996 (life events, Mental Health Index [MHI-5], having a partner, Perceived Stress Scale, Duke Social Support Index, educational attainment, location of residence, feelings of time pressure) were entered into binary logistic regression models to examine which would predict the self-reported new diagnosis of stroke over the 3-year period after adjusting for a range of biomedical risk factors and the frequency of general practitioner visits in 1996. Only the MHI-5 proved to be a significant predictor of self-reported new stroke diagnosis. The MHI-5 remained a significant risk factor (OR 1.61, 95% CI 1.01-2.55, p < 0.05) even after adjusting for a range of other possible risk factors (body mass index, physical activity, alcohol status, diabetes, heart disease, hypertension, nutritional risk) and frequency of general practitioner visits. Poor mental health appears to be a risk factor for the self-reported new diagnosis of stroke in older women. The 5-item MHI may be a useful instrument for researchers investigating the relationship between psychosocial variables and stroke in older women and for clinicians who wish to identify those at risk for stroke.


The role of intestinal mast cell infiltration in irritable bowel syndrome.
As an essential part of the immune system, mast cells (MCs) play an important role in the pathogenesis of irritable bowel syndrome (IBS). Accumulating evidence has identified altered MC count and density in intestinal mucosa of patients with IBS; however, conflicting findings yield inconsistent conclusions. Currently, most studies have suggested intestinal MC infiltration in IBS patients. Considering the pivotal role of MCs in IBS, it is necessary to achieve a better understanding about the pathological changes in the intestine. The risk factors for IBS, including dietary habits, psychological factors, infection, and dysbiosis, are implicated to induce intestinal MC infiltration. Mechanistically, food may trigger immune-related allergic reactions and affect the intestinal microbiota activity. Some exogenous pathogens and altered profile of commensal bacteria promote intestinal MC recruitment through promoted release of chemokines from epithelial cells or direct activation of the immune system. In addition, psychological factors may affect the microenvironment where MCs live. MCs have been proven to interact with the enteric neurons and other immunocytes, evidenced by the close proximity of MCs to neurons and regional altered immune system components. A variety of mediators released by the enteric neurons, immunocytes, and MCs per se, such as neurotrophins, neuropeptides, cytokines, and chemokines, may have stimulant effects on MCs by modulating the survival, proliferation, and recruitment process of MCs in the intestine. In this review, the associations between IBS and intestinal MC density and the underlying mechanisms are discussed.


Spatiotemporal evolution of groundwater nitrate nitrogen levels and potential human health risks in the Songnen Plain, Northeast China.
As one of the most widespread pollutants worldwide, nitrogen has long been a concern in the environment, including groundwater. However, due to the limitations of investigations and study progress, there is still a poor understanding of groundwater nitrogen pollution and its potential effects on human health in many areas, particularly in developing countries. The spatiotemporal evolution of groundwater nitrate nitrogen levels and potential human health risks in the Songnen Plain, Northeast China were comprehensively studied based on both our own test data and available published data that were collected by us over a study period from 1995 to 2015. Groundwater nitrate nitrogen concentrations exhibited significant temporal and spatial differences: there was an increasing trend with time; and the distribution of high concentration areas expanded from the central and western areas to the east with time. The similar pattern existed in the potential health risks posed to the residents considering the two exposure pathways including drinking water and dermal contact. The effects of groundwater nitrate nitrogen on human health depend on the nitrate concentration but there were also age differences, namely, in the order of infants > children > adult females ≈ adult males, according to the hazard quotient (HQ) used in the human health risk assessment (HHRA) model. The spatiotemporal evolution of groundwater nitrate nitrogen levels and potential human health risks indicate that the issue of nitrogen pollution in groundwater in the study area is worsening and needs further attention. The drivers that increased nitrate nitrogen concentrations in the groundwater of the study area were the increased fertilizer use due to the increased cultivated land area and implementation of a land fertility policy by the local government. It should be acknowledged that the results have uncertainties that not only come from the layout of sampling points and selection of spatial interpolation methods but also come from the parameter settings in the assessment model and assumptions of drinking water scenarios. However, the conclusions still have important reference value for groundwater pollution control and management and human health risk supervision and early warning.


Update on fenofibrate.
Fenofibrate is a fibric acid derivative that has been marketed since the mid-1970's (1998 in the United States). Its active metabolite, fenofibric acid, is responsible for the primary pharmacodynamic effects of the drug: reductions in total plasma cholesterol, low density lipoprotein cholesterol, triglycerides, and very low-density lipoprotein concentrations and increases in high-density lipoprotein cholesterol and apolipoproteins AI and AII concentrations. These effects are mediated by activation of peroxisome proliferator-activated receptor-alpha (PPAR(alpha)). The drug has broad spectrum utility, with documented efficacy in Fredrickson types IIa, IIb, III, IV, and V hyperlipidemias. Fenofibrate is well tolerated, with digestive and musculoskeletal side effects similar to those of other fibrates. Results of the initial cardiovascular morbidity/mortality outcomes study with fenofibrate (known as DAIS [Diabetes Atherosclerosis Intervention Study]) were encouraging vis-à-vis slowing of atherosclerotic progression in the coronary vasculature of type II diabetics. The results of other ongoing outcome trials are eagerly awaited. These results will help to establish the overall place of fenofibrate in the hypolipidemic armamentarium.


Allergenic and antigenic cross-reactivities of group IX grass pollen allergens.
The allergenic and antigenic cross-reactivities between a major recombinant Poa pratensis (Poa p) IX allergen, rKBG8.3, and its corresponding proteins of different grass pollens were examined. Immunoblotting of the proteins of thirteen different grass pollens using anti-rKBG8.3 antibodies indicated that Poa p IX-like proteins are present in ten other grass pollens, albeit in variable amounts and polymorphic forms. These proteins ranged in size from 20 to 88 kDa in different grass pollens. The percent relative binding determined for each grass pollen extract using allergic human sera showed a significant correlation (r = 0.891) with that of anti-rKBG8.3 antiserum. Moreover, there was a strong association (r = 0.901) between the Kentucky bluegrass extract and rKBG8.3 with respect to their inhibition of the binding of human IgE antibodies to allergens in grass pollen extracts. Taken together, these results suggest that the allergenic and antigenic epitopes of the Poa p IX-related proteins in some but not all grass pollens are similar in structure and specificities. It is concluded that the group IX allergens constitute a major family of homologous proteins in several grass pollens.


Analyzing Gastric Lavage of Gastric Cancer Patients: A Prospective Observational Study on Cytopathology and Determination of Intragastric CEA, CA 19.9, CA 72.4, and CA 50.
To investigate gastric lavage (GL) cytopathology and immunometric analysis as novel clinicopathologic and prognostic parameters for gastric cancer (GC). In 38 patients with gastric adenocarcinoma, we performed a cytopathologic analysis and an immunometric assay of GL using four tumor markers (CEA, CA 19.9, CA 72.4, and CA 50). The intragastric tumor marker levels were compared with a control group consisting of 41 non-GC patients to determine a statistically significant cutoff value. GL cytopathology demonstrated the presence of cancer cells in 13 (34.2%) of the 38 GC patients: such a finding correlated to the parameters pT and pN with a statistically significant validity (p < 0.0267 and p < 0.0306, respectively). Measurement of intragastric CA 19.9 and CA 50 attained a statistically significant cutoff value (p < 0.002 and p < 0.0096, respectively), which was invalidated by the low sensitivity of the ROC curve analysis. In contrast to determination of its tumor markers, GL cytopathology correlated well with pT and pN staging parameters. Should this and other features be corroborated by future studies, the GL cytology test could be routinely used to detect aggressive types of GC even at early stages and result in important progress in the knowledge, staging, prediction, as well as management and follow-up of this inauspicious type of cancer.


Using Mendelian randomisation to assess causality in observational studies.
Mendelian randomisation (MR) is a technique that aims to assess causal effects of exposures on disease outcomes. The paper aims to present the main assumptions that underlie MR, the statistical methods used to estimate causal effects and how to account for potential violations of the key assumptions. We discuss the key assumptions that should be satisfied in an MR setting. We list the statistical methodologies used in two-sample MR when summary data are available to estimate causal effects (ie, Wald ratio estimator, inverse-variance weighted and maximum likelihood method) and identify/adjust for potential violations of MR assumptions (ie, MR-Egger regression and weighted Median approach). We also present statistical methods and graphical tools used to evaluate the presence of heterogeneity. We use as an illustrative example of a published two-sample MR study, investigating the causal association of body mass index with three psychiatric disorders (ie, bipolar disorder, schizophrenia and major depressive disorder). We highlight the importance of assessing the results of all available methods rather than each method alone. We also demonstrate the impact of heterogeneity in the estimation of the causal effects. MR is a useful tool to assess causality of risk factors in medical research. Assessment of the key assumptions underlying MR is crucial for a valid interpretation of the results.


Feed and feeding regime affect growth rate and gonadosomatic index of adult zebrafish (Danio rerio).
A 5-week study was conducted to evaluate commercially available Artemia, Ziegler zebrafish diet, and Calamac diet fed in five different feeding regimes on the growth and reproductive development of 7-month-old zebrafish. Zebrafish were fed to satiation three times daily during the normal work week and twice daily during the weekend and holidays. Zebrafish in dietary groups CCC (Calamac three times daily) and CCA (Calamac twice daily, Artemia once daily) had a significantly (p<0.05) greater weight gain and specific growth rate as compared to all other dietary groups. Male zebrafish in dietary group 5 had significantly larger gonadosomatic index (GSI) values than all other groups, while female zebrafish in dietary group CCC had significantly larger GSI values than all other groups. No differences in the fatty acid content of female gonads were detected. Zebrafish fed solely Artemia had the greatest weight loss and lowest GSI values. Preliminary evidence of protein sparing in zebrafish is reported. Collectively, this study sheds more light into the effects of the use of commercially available feeds and feeding regime on the rearing of zebrafish.


Novel therapeutics for metastatic renal cell carcinoma.
The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically during the past few years. Sunitinib malate, sorafenib tosylate, bevacizumab with interferon alpha, temsirolimus, and everolimus have improved clinical outcomes in randomized phase 3 trials by inhibiting the vascular endothelial growth factor and related pathways. Combinations and sequences of these agents are being evaluated. Other novel agents are in clinical development, some of which target novel pathways not yet exploited as therapy for RCC. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.


Planning for suicide prevention in Thai refugee camps: Using community-based system dynamics modeling.
Suicide and associated behaviors represent a significant health disparity among refugees and displaced persons. Despite this burden, evidence for prevention programing in these populations is limited. This study aimed to inform the selection and implementation of suicide prevention strategies in refugee camps in Northwestern, Thailand - camps that had experienced recent spikes in suicides and suicide attempts at the time of the study. We leveraged Community Based System Dynamics modeling through a series of four workshops with key local stakeholders and suicide prevention experts, to build a qualitative systems model that accounts for complexities and is aimed at assisting local partners with selecting the most promising strategies for implementation and evaluation. The process expanded local understanding of the causes and consequences of suicide and resulted in selection of priority interventions aimed at reducing suicide in this context. Our research illustrates the application of a novel methodology that aims to account for the complexities of suicide prevention in the context of displacement and helps to optimize local suicide prevention efforts.


Effect of oestradiol benzoate and tamoxifen on the growth of and induction of progesterone receptors in the uterus and mammary gland of immature pigs.
Intramuscular injection of oestradiol benzoate (0.1, 1 or 10 micrograms/kg per day) and tamoxifen (0.1 or 1 mg/kg per day) to 6-week-old immature pigs for 7 days induced a dose-dependent increase in the wet weight of the uterus and in the total content of uterine DNA, RNA and protein. Both compounds also stimulated a dose-dependent increase in the concentration of progesterone receptors in uterine cytosolic extracts (in terms of either fmol/mg DNA or fmol/g uterus). The concurrent administration of tamoxifen with oestradiol benzoate provoked significant (P less than 0.05) increases in total uterine protein and in the concentration of progesterone receptors (P less than 0.01) compared with treatment with oestradiol benzoate alone. Hence tamoxifen is an oestrogen agonist in the uterus of immature pigs. The effects of oestradiol benzoate and tamoxifen on mammary growth in immature pigs were assessed by image analysis of mammary sections across the gland (in a ventro-dorsal direction through the teat). Oestradiol benzoate at 10 micrograms/kg per day stimulated a fourfold increase in mammary duct area (P less than 0.01), and tamoxifen, at doses of 0.1 or 1 mg/kg per day, stimulated a threefold increase (P less than 0.05). Tamoxifen partially inhibited (P less than 0.05) the effect of oestradiol benzoate. The concentration of progesterone receptors was found to be very heterogeneous in cytosol extracts of mammary tissue of immature pigs and independent of treatment with oestradiol benzoate and/or tamoxifen.


The Roles of MicroRNAs in Tendon Healing and Regeneration.
Tendons connect the muscle abdomen of skeletal muscles to the bone, which transmits the force generated by the muscle abdomen contraction and pulls the bone into motion. Tendon injury is a common clinical condition occurring in certain populations, such as repeated tendon strains in athletes. And it can lead to substantial pain and loss of motor function, in severe cases, significant disability. Tendon healing and regeneration have attracted growing interests. Some treatments including growth factors, stem cell therapies and rehabilitation programs have been tried to improve tendon healing. However, the basic cellular biology and pathology of tendons are still not fully understood, and the management of tendon injury remains a considerable challenge. Regulating gene expression at post-transcriptional level, microRNA (miRNA) has been increasingly recognized as essential regulators in the biological processes of tendon healing and regeneration. A wide range of miRNAs in tendon injury have been shown to play vital roles in maintaining and regulating its physiological function, as well as regulating the tenogenic differentiation potential of stem cells. In this review, we show the summary of the latest information on the role of miRNAs in tendon healing and regeneration, and also discuss potentials for miRNA-directed diagnosis and therapy in tendon injuries and tendinopathy, which may provide new theoretical foundation for tenogenesis and tendon healing.


[An attempt at quantifying the role of demographic factors determining dependency ratios (II)].
"The contribution presents, evaluates and compares four recently elaborated quantitative procedures for estimating the immediate determinants of changing age structures. Two of them are used for evaluating the immediate determinants of changing proportions of populations of different age-groups and two of them are used for showing the immediate determinants of changing (or different) mean ages of populations studied....[The author uses] data for the Hungarian male population at the beginning, at the end and in the middle of 1990." (SUMMARY IN ENG)


Transcriptome Analysis of Lolium temulentum Exposed to a Combination of Drought and Heat Stress.
Drought and heat are two major stresses predicted to increase in the future due to climate change. Plants exposed to multiple stressors elicit unique responses from those observed under individual stresses. A comparative transcriptome analysis of Lolium temulentum exposed to drought plus heat and non-stressed control plants revealed 20,221 unique up-regulated and 17,034 unique down-regulated differentially regulated transcripts. Gene ontology analysis revealed a strong emphasis on transcriptional regulation, protein folding, cell cycle/parts, organelles, binding, transport, signaling, oxidoreductase, and antioxidant activity. Differentially expressed genes (DEGs) encoding for transcriptional control proteins such as basic leucine zipper, APETALA2/Ethylene Responsive Factor, NAC, and WRKY transcription factors, and Zinc Finger (CCCH type and others) proteins were more often up-regulated, while DEGs encoding Basic Helix-Loop-Helix, MYB and GATA transcription factors, and C2H2 type Zinc Finger proteins were more often down-regulated. The DEGs encoding heat shock transcription factors were only up-regulated. Of the hormones, auxin-related DEGs were the most prevalent, encoding for auxin response factors, binding proteins, and efflux/influx carriers. Gibberellin-, cytokinin- and ABA-related DEGs were also prevalent, with fewer DEGs related to jasmonates and brassinosteroids. Knowledge of genes/pathways that grasses use to respond to the combination of heat/drought will be useful in developing multi-stress resistant grasses.


A Factor Analysis Approach for Clustering Patient Reported Outcomes.
In the field of radiation oncology, the use of extensive patient reported outcomes is increasingly common to measure adverse side effects after radiotherapy in cancer patients. Factor analysis has the potential to identify an optimal number of latent factors (i.e., symptom groups). However, the ultimate goal of treatment response modeling is to understand the relationship between treatment variables such as radiation dose and symptom groups resulting from FA. Hence, it is crucial to identify clinically more relevant symptom groups and improved response variables from those symptom groups for a quantitative analysis. The goal of this study is to design a computational method for finding clinically relevant symptom groups from PROs and to test associations between symptom groups and radiation dose. We propose a novel approach where exploratory factor analysis is followed by confirmatory factor analysis to determine the relevant number of symptom groups. We also propose to use a combination of symptoms in a symptom group identified as a new response variable in linear regression analysis to investigate the relationship between the symptom group and dose-volume variables. We analyzed patient-reported gastrointestinal symptom profiles from 3 datasets in prostate cancer patients treated with radiotherapy. The final structural model of each dataset was validated using the other two datasets and compared to four other existing FA methods. Our systematic EFA-CFA approach provided clinically more relevant solutions than other methods, resulting in new clinically relevant outcome variables that enabled a quantitative analysis. As a result, statistically significant correlations were found between some dose-volume variables to relevant anatomic structures and symptom groups identified by FA. Our proposed method can aid in the process of understanding PROs and provide a basis for improving our understanding of radiation-induced side effects.


The Italian version of cognitive function instrument (CFI): reliability and validity in a cohort of healthy elderly.
The Alzheimer's disease Cooperative Study (ADCS)-Cognitive Function Instrument (CFI) is a 14-item questionnaire administered to the subject and the referent, aimed at detecting early changes in cognitive and functional abilities in individuals without clinical impairment. It is used for monitoring annual variations in cognitive functioning in prevention trials. The aim of the present study was to validate the Italian version of the CFI. A consecutive series of 257 functionally independent subjects was recruited among relatives of patients or as volunteers. They were administered CFI and global cognition measurements: Mini-Mental Status Examination (MMSE) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The reliability and criterion validity were comparable to the original in both self- and partner-report. Similarly to what reported in the original version, we found a corrected item-total correlation ranging between 0.38 and 0.54 in self-report and between 0.33 and 0.64 in partner-report. Cronbach's α was 0.77 (95% CI 0.72-0.83) in self-report and 0.78 (95% CI 0.73-0.84) in partner-report. Total partner- and self-report scores were significantly correlated (rS = 0.31, p < 0.001). CFI self-report and CFI total-score (partner + self-report) were negatively correlated with MMSE (rS = - 0.15, p = 0.022; rS = - 0.17, p = 0.008) and RBANS (rS = - 0.22, p < 0.001; rS = - 0.25, p < 0.001). Analogous trends were found in the partner score, with a correlation with RBANS (rS = - 0.17, p = 0.014) and MMSE (rS = - 0.11, p = 0.071). Our results support the reliability and validity of the Italian version of CFI. In order to definitely propose the use of CFI for tracking longitudinal changes of cognitive and functional abilities in subjects without clinical impairment, data from the follow-up of this cohort are needed.


Clinical value of the Ottawa ankle rules for diagnosis of fractures in acute ankle injuries.
The Ottawa ankle rules (OAR) are clinical decision guidelines used to identify whether patients with ankle injuries need to undergo radiography. The OAR have been proven that their application reduces unnecessary radiography. They have nearly perfect sensitivity for identifying clinically significant ankle fractures. The purpose of this study was to assess the applicability of the OAR in China, to examine their accuracy for the diagnosis of fractures in patients with acute ankle sprains, and to assess their clinical utility for the detection of occult fractures. In this prospective study, patients with acute ankle injuries were enrolled during a 6-month period. The eligible patients were examined by emergency orthopedic specialists using the OAR, and then underwent ankle radiography. The results of examination using the OAR were compared with the radiographic results to assess the accuracy of the OAR for ankle fractures. Patients with OAR results highly suggestive of fracture, but no evidence of a fracture on radiographs, were advised to undergo 3-dimensional computed tomography (3D-CT). 183 patients with ankle injuries were enrolled in the study and 63 of these injuries involved fractures. The pooled sensitivity, specificity, positive predictive value and negative predictive value of the OAR for detection of fractures of the ankle were 96.8%, 45.8%, 48.4% and 96.5%, respectively. Our results suggest that clinical application of the OAR could decrease unnecessary radiographs by 31.1%. Of the 21 patients with positive OAR results and negative radiographic findings who underwent 3D-CT examination, five had occult fractures of the lateral malleolus. The OAR are applicable in the Chinese population, and have high sensitivity and modest specificity for the diagnosis of fractures associated with acute ankle injury. They may detect some occult fractures of the malleoli that are not visible on radiographs.


Microstructure and Thermal Deformation Behavior of Hot-Pressing Sintered Zr-6Al-0.1B Alloy.
Zr-6Al-0.1B alloy rich in Zr3Al phase is prepared by hot-pressing sintering. The thermal deformation behavior of sintered Zr-6Al-0.1B is analyzed by isothermal compression tests at deformation temperatures of 950, 1050, and 1150 °C with strain rates of 0.01, 0.1, and 1 s-1. The results indicate that at the early stage of thermal deformation, the stress increases rapidly with the increase of strain and then reaches the peak value. Subsequently, the stress decreases with the increase of strain under the softening effect. On the whole, the true stress-strain curve shifts to the high stress area with the increase of strain rate or the decrease of deformation temperature, so the sintered Zr-6Al-0.1B alloy belongs to the temperature and strain rate sensitive material. For the microstructure evolution of sintered Zr-6Al-0.1B during the isothermal compression, the high strain rate can improve the grain refinement. However, because sintered Zr-6Al-0.1B is a low plastic material, too high strain rate will exceed the deformation capacity of the material, resulting in an increase in defects. The increase of deformation temperature also contributes to grain refinement, but when the temperature is too high, due to the decomposition of Zr3Al phase, the deformation coordination of the material decreases, leading to the increase of the probability of the occurrence of defects. This study verified the feasibility of hot-pressing sintering to prepare Zr-6Al-0.1B alloy rich in Zr3Al phase and laid the foundation of "hot-pressing sintering + canning hot-extrusion" process of Zr-6Al-0.1B alloy components.


Heart rate and heart rate variability during a novel object test and a handling test in young horses.
Forty-one Dutch Warmblood immature horses were used in a study to quantify temperamental traits on the basis of heart rate (HR) and heart rate variability (HRV) measures. Half of the horses received additional training from the age of 5 months onwards; the other half did not. Horses were tested at 9, 10, 21 and 22 months of age in a novel object and a handling test. During the tests, mean HR and two heart variability indices, e.g. standard deviation of beat-to-beat intervals (SDRR) and root mean square of successive beat-to-beat differences (rMSSD), were calculated and expressed as response values to baseline measures. In both tests, horses showed at all ages a significant increase in mean HR and decrease in HRV measures, which suggests a marked shift of the balance of the autonomic nervous system towards a sympathetic dominance. In the novel object test, this shift was more pronounced in horses that had not been trained. Furthermore, statistical analysis showed that the increase in mean HR could not be entirely explained by the physical activity. The additional increase in HR, the nonmotor HR, was more pronounced in the untrained horses compared to the trained. Hence, it is suggested that this nonmotor HR might be due to the level of emotionality. HR variables showed consistency between years, as well as within the second year. These tests bring about a HR response in horses, part of which may indicate a higher level of emotionality; and horses show individual consistency of these HR variables over ages. Therefore, it is concluded that mean HR and HRV measures used with these tests quantify certain aspects of a horse's temperament.


Heteromeric mixing of connexins: compatibility of partners and functional consequences.
Cx43 is widely expressed in many different cell types, and many of these cells also express other connexins. If these connexins are capable of mixing, the functional properties of channels containing heteromeric connexons may substantially influence intercellular communication between such cells. We used biochemical strategies (sedimentation through sucrose gradients, co-immunoprecipitation, or co-purification by Ni-NTA chromatography) to examine heteromeric mixing of Cx43 with other connexins (including Cx26, Cx37, Cx40, Cx45, and Cx56) in transfected cells. These analyses showed that all of the tested connexins except Cx26 formed heteromeric connexons with Cx43. We used the double whole-cell patch-camp technique to analyze the electrophysiological properties of gap junction channels in pairs of co-expressing cells. Cx37 and Cx45 made a large variety of functional heteromeric combinations with Cx43 based on detection of many different single channel conductances. Most of the channel event sizes observed in cells co-expressing Cx40 and Cx43 were similar to those of homomeric Cx43 or Cx40 hemichannels in homo- or hetero-typic configurations. Our data suggest several different possible consequences of connexin co-expression: (1) some combinations of connexins may form heteromeric connexons with novel proeprties; (2) some connexins may form heteromeric channels that do not have unique properties, and (3) some connexins may be incompatible for heteromeric mixing.


The capacity for dynamic process scale (CDPS) and patient engagement in opiate addiction treatment.
This study examined the relationship between continuation in an opiate treatment program and patient characteristics such as affect regulation, insight, and capacity for interpersonal relations. Participants consisted of 63 patients randomly selected from those completing an initial interview at a short-term heroin detoxification program. Patient characteristics were assessed using the Capacity for Dynamic Process Scale (CDPS). Results of this study indicated that the CDPS total score for each patient was related to the subsequent number of treatment sessions attended by that patient and significantly differentiated dropouts from completers. These findings support previous use of the CDPS in psychotherapy research. In addition, this study extends use of the CDPS to research on brief pharmacotherapy treatment of opiate addiction.


[The medicinal leech Hirudo medicinalis: clinical use of the animal and therapeutic prospects of hirudin].
Blood sucking leech, Hirudo medicinalis, used in Medicine for very long, knew an intensive employment during early 18e century but its excess was responsible of the temporary disparition of the animal from the therapeutics. Leech has currently recovered a clinical use, especially in microsurgery. On the other hand, hirudin, main active compound isolated from leech extract and also known and used for long, offers interesting outlooks by its anticoagulant and antithrombic properties. This explains the great interest of hirudin preparation by molecular genetics.


Aspiration biopsy findings in amyloid tumor of the cervical vertebra. A case report.
The differential diagnosis of destructive lytic lesions of the spine includes amyloid tumors. The diagnosis of amyloid tumor with fine needle aspiration biopsy (FNA) is challenging. Previous reports of FNA of osseous amyloid tumors have detailed the cytologic appearance of amyloid along with lymphocytes, plasma cells and histiocytes, occasionally multinucleate or forming granulomatous lesions. An 84-year-old man presented with neck pain. Radiologic studies showed a destructive, lytic lesion of C-6, with a large, soft tissue mass. FNA yielded many acellular smears containing abundant amyloid that was confirmed with special stains of corresponding tissue cores and subsequent surgical biopsies. Osseous amyloid tumors are destructive, lytic lesions that mimic other processes. Amyloid can be distinguished from other substances in FNA samples and amyloid tumor identified, even when amyloid is present without typical cellular components.


A New Miniaturized Gas Sensor Based on Zener Diode Network Covered by Metal Oxide.
The development of "portable, low cost and low consumption" gas microsensors is one of the strong needs for embedded portable devices in many fields such as public domain. In this paper, a new approach is presented on making, on the same chip, a network of head-to-tail facing PN junctions in order to miniaturize the sensor network and considerably reduce the required power for heating each cell independently. This paper is about recognizing a device that integrates both sensing and self-heating. This first study aims to evaluate the possibilities of this type of diode network for use as a gas sensor. The first part concerns the description of the technological process that is based on a doped polysilicon wafer in which a thin layer of metal oxide (a gallium-doped zinc oxide in our case) is deposited by RF sputtering. An electrical model will be proposed to explain the operation and advantage of this approach. We will show the two types of tests that have been carried out (static and dynamic) as well as the first encouraging results of these electrical characterizations under variable atmospheres.


PLXNC1: A Novel Potential Immune-Related Target for Stomach Adenocarcinoma.
Gastric cancer is associated with tumor microenvironment and chronic inflammation, but the underlying tumor-promoting mechanisms still remain unknown. The ATAC-seq was used to identify genes with chromatin accessibilities in promoter regions. The RNA-seq datasets were performed to identify differentially expressed genes (DEGs). Pearson correlation analysis with the mRNA expression of three families of tumor-related inflammation TFs was used to filter downstream DEGs. Cox univariate survival analysis was performed to identify the prognostic value. The ImmPort database and CIBERSORTx algorithm were used to investigate the regulatory relationship between hub DEGs and immune cells. Immunohistochemistry (IHC) and multidimensional database were performed to verification. In this case, we require 2,454 genes with chromatin accessibility in promoter regions by ATAC-seq. Based on the gene expression profiles (RNA-seq), we identified 365 genes with chromatin accessibility and differential expression. Combined with the Cox univariate survival analysis, we identified 32 survival-related DEGs with chromatin accessibility. According to ImmPort database, CXCL3, PLXNC1, and EDN2 were identified as immune- related genes in STAD. By applying the CIBERSORTx algorithm and Pearson correlation, PLXNC1 was the only gene correlated with various immune cells, significantly associated with M2 macrophages. Furthermore, gene set variation analysis (GSVA) suggests the "hallmark_interferon_gamma_response" pathway was most significantly correlated with PLXNC1. Immunohistochemistry results revealed that PLXNC1 protein level was significantly higher in STAD tissues than in normal tissues (p < 0.001). PLXNC1, regulated by IRF5, is an immune-related gene that was significantly associated with M2 macrophages and poor outcome in stomach adenocarcinoma.


The management of superficial disorders of the forefoot.
Superficial disorders of the forefoot are frequently seen in any office practice. Soft corns, ingrown toenails, plantar calluses, and plantar warts are the most common of these disorders. Their etiology, recognition, and operative and nonoperative management are discussed.


Pediatric Maisonneuve: case report of a rare pattern of injury.
A 12-year-old boy presented to our emergency department complaining of pain and functional limitation on his right ankle after an indirect trauma. Plain radiographs were taken identifying a type II epiphysiolysis of the distal tibia and a proximal fibula fracture. An open reduction and internal fixation was performed without transyndesmal fixation. Maisonneuve fractures are an uncommon injury in the pediatric population. This fracture pattern has not been described by the Dias-Tachdjian classification. It is important to bear in mind that, based on the need for osteosynthesis for the epiphysiolysis, the treatment of these fractures in children usually differs from that in the adults as no transyndesmal screw fixation is required.


Changing prescription patterns: impact on costs.
The cost of treating hypertension is high. In the Federal Republic of Germany the total sales of antihypertensive compounds increased, from 1981 to 1984, from 1075 million to 1525 million DM per year, corresponding to 7.4 and 9.1%, respectively, of total drug expenditure. Economists have calculated that about two-thirds of this increase is caused by structural changes within the market, i.e. changing prescription patterns. The proportion of prescribed daily doses of reserpine combinations dropped from 52 to 34% whereas that of most other compounds increased. The approximate daily costs of treatment vary from 0.5 DM (reserpine combinations) to 2.5 DM [angiotensin converting enzyme, (ACE) inhibitors], but the decline of the cheaper compounds and their substitution by newer and more expensive drugs has resulted in additional costs of 309-328 million DM. The higher prices of the new drugs should be justified by greater benefits compared with conventional compounds. Assessment of new antihypertensive drugs should include potency, efficacy, number and quality of adverse effects, and impact on quality of life. The evaluation should be performed separately for mild and for more severe forms of hypertension. Some advantages or drawbacks of the newer drugs may be important for small subgroups only.


High-frequency oscillatory ventilation in pediatric respiratory failure.
To evaluate the safety and effectiveness of high-frequency oscillatory ventilation using a protocol designed to achieve and maintain optimal lung volume in pediatric patients with respiratory failure. Tertiary care pediatric ICU in a university hospital. A prospective, clinical study. Seven patients aged 1 month to 15 yrs with diffuse alveolar disease and airleak with a variety of primary diagnoses, including pneumonia, adult respiratory distress syndrome, and pulmonary hemorrhage. After varying periods of conventional mechanical ventilation (16 to 216 hrs), patients were managed with high-frequency oscillatory ventilation using a "high-volume" strategy that consisted of incremental increases in mean airway pressure and lung volume to achieve an arterial oxygen saturation of > or = 90%, with an FIO2 of < or = 0.6. Ventilatory settings, including FIO2 and mean airway pressure, hemodynamic parameters (cardiac index, systemic and pulmonary vascular resistance indices, oxygen delivery [DO2] and oxygen extraction ratio) and the oxygenation index (oxygenation index = [FIO2 x mean airway pressure x 100]/PaO2) were monitored during the transition to high-frequency oscillation and throughout the course of the high-frequency oscillatory ventilation with rapid and sustained reductions in mean airway pressure (p = .0001, repeated-measures analysis of variance [ANOVA]) and a trend toward decreasing oxygenation index (p = .08, repeated-measures ANOVA). In the four patients from whom hemodynamic data were obtained, there were no compromises of cardiac index or DO2 despite a significant increase in mean airway pressure (26 +/- 2 to 35 +/- 2 cm H2O) during conversion from conventional ventilation to high-frequency oscillation. High-frequency oscillatory ventilation, using a high-volume strategy, may be used safely and effectively in pediatric patients with respiratory failure and with high predicted mortality rates. High mean airway pressure during oscillatory ventilation does not appear to compromise DO2. Whether this technique can alter morbidity or mortality rates in this population awaits prospective randomized study.


Rapid and Quantitative Determination of S-Adenosyl-L-Methionine in the Fermentation Process by Surface-Enhanced Raman Scattering.
Concentrations of S-Adenosyl-L-Methionine (SAM) in aqueous solution and fermentation liquids were quantitatively determined by surface-enhanced Raman scattering (SERS) and verified by high-pressure liquid chromatography (HPLC). The Ag nanoparticle/silicon nanowire array substrate was fabricated and employed as an active SERS substrate to indirectly measure the SAM concentration. The linear relationship between the integrated intensity of peak centered at ~2920 cm-1 in SERS spectra and the SAM concentration was established, and the limit of detections of SAM concentrations was analyzed to be ~0.1 g/L. The concentration of SAM in real solution could be predicted by the linear relationship and verified by the HPLC detection method. The relative deviations (δ) of the predicted SAM concentration are less than 13% and the correlation coefficient is 0.9998. Rolling-Circle Filter was utilized to subtract fluorescence background and the optimal results were obtained when the radius of the analyzing circle is 650 cm-1.


Nicotine-Induced Neuroprotection against Cognitive Dysfunction after Partial Hepatectomy Involves Activation of BDNF/TrkB Signaling Pathway and Inhibition of NF-κB Signaling Pathway in Aged Rats.
The main purpose of this study was to investigate the effects and possible mechanisms of nicotine pre-treatment on postoperative cognitive dysfunction (POCD) in aged rats. Nicotine (0.5 mg/kg) was given i.p. immediately after anesthesia induction. After the Morris water maze test was used to evaluate the rats' spatial learning and memory, serum and hippocampal tissues were harvested 1 and 3 days after intervention. Inflammatory cytokines in the serum were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). Brain-derived neurotrophic factor (BDNF), p-TrkB, neuroinflammation cytokines, NF-κB p65, and cleaved caspase-3 were measured by western blotting; neuronal apoptosis in the hippocampal CA1 region was also evaluated by TUNEL staining. We found that nicotine markedly attenuated the POCD and reduced the elevated levels of inflammatory cytokines in the serum, including IL-1β and high mobility group box-1 (HMGB1), on postoperative day 1. Additionally, nicotine suppressed the surgery-induced release of IL-1β, TNF-ɑ, HMGB1, and NF-κB p65 in the hippocampus on postoperative day 1 and day 3. In addition, operated rats displayed lower BDNF and p-TrkB in the hippocampus on postoperative day 1, returning to baseline by postoperative day 3. However, nicotine pre-treatment clearly reversed the surgical stress-induced decrease in both BDNF and p-TrkB expression in the hippocampus. Furthermore, nicotine pre-treatment significantly alleviated the surgery-induced increase in the neuronal apoptosis in the hippocampus on postoperative day 1 and day 3. Our results showed that nicotine-induced neuroprotection against POCD may involve activation of the BDNF/TrkB signaling pathway and inhibition of the NF-κB signaling pathway. Nicotine has long been considered a potent therapeutic agent for neuroprotection. This study reported the positive effect of nicotine treatment on cognitive dysfunction after partial hepatectomy in aged rats. Furthermore, the underlying mechanism may involve activation of the BDNF/TrkB signaling pathway and inhibition of the NF-κB signaling pathway in the hippocampus.


Spinal Decompression Sickness in an Experienced Scuba Diver: A Case Report and Review of Literature.
Decompression sickness from diving is a rare but potentially reversible cause of spinal injury. Early treatment with hyperbaric oxygen is associated with a better neurologic outcome, making prompt recognition and management clinically important. We describe a case of a 65-year-old diver who presented with thoracic back pain and bilateral leg weakness after a 70 feet of sea water (fsw) (21 meters of sea water [msw]) dive, with no acute abnormality on spinal magnetic resonance imaging (MRI). He made a partial recovery after extended hyperbaric oxygen therapy. We discuss the epidemiology and pathophysiology of central nervous system injury in decompression sickness, as well as acute management and prognostic factors for recovery, including the role of adjunctive therapies and the implications of negative MRI. Ultimately, clinicians should make the diagnosis of spinal cord decompression sickness based primarily on clinical evaluation, not on MRI findings.


[Skeletal muscle tissue engineering--current concepts and future perspectives].
Tissue engineering of skeletal muscle could have great advantages in every clinical setting in need of neurovascular muscle transfer, e. g., facial palsy or Volkmann's contracture. There are 2 great obstacles for the clinical application of engineered muscle tissue at the moment: firstly, finding a three-dimensional matrix that matches the demands concerning biocompatibility, stability and elasticity; secondly, the insufficient differentiation of implanted myoblasts, since myoblast differentiation in vivo is barely controllable and subject to a variety of influences. Furthermore axial vascularisation and neurotisation of such tissue-engineered skeletal muscle constructs play a pivotal role for any later application. An overview of the current status of skeletal muscle tissue engineering technologies and concepts for future perspective in this emerging field is presented in this article.


3D-segmentation and characterization of visceral and abdominal subcutaneous adipose tissue on CT: influence of contrast medium and contrast phase.
Adipose tissue as part of body composition analysis may serve as a powerful biomarker. Validation of segmented adipose tissue and correlation to clinical data has been performed on non-enhanced scans (NES). As many patients require a contrast enhanced scan (CES) for other aspects of clinical decision making, the utility of CES for body composition analysis would be most useful. Therefore, we analyzed the influence of iodinated contrast medium (ICM) and contrast phase on the characterization and segmentation of adipose tissue. Exams of 31 patients undergoing multi-phasic CT at identical scan settings containing an NES were retrospectively included. In addition to NES, patients received an arterial (ART) (n=23), portal-venous (PVN) (n=10), and/or venous scan (VEN) (n=31) after intravenous injection of 90 mL ICM. Density and volume of adipose tissue were quantified semi-automatically with thresholds between -190 HU and -30 HU and recorded separately for visceral (VAT) and subcutaneous adipose tissue (SAT). Density and volume of total adipose tissue (TAT) were computed. For conversion of values from CES into those of NES regression analyses were performed and tested. Density of adipose tissue increased after application of ICM more on later scans (VEN ≈ PVN > ART) and more markedly in VAT than SAT (VAT > TAT > SAT). Except in SAT on ART, all changes were significant (P<0.001). Measured volume of adipose tissue decreased on all CES (VEN ≈ PVN > ART) (P<0.001), but only reached statistical significance for VAT and TAT (VAT > TAT) on all CES (P<0.05). Density and volume in CES correlate extremely well with NES and may be calculated from one another [root-mean-square error (RMSE): <6 HU; <0.85 dm3]. Density and volume of segmented adipose tissue are altered by the injection of ICM in differing degrees between compartments and contrast phases. However, as the effect of ICM is fairly constant for a given compartment and contrast phase, values may be converted into those of NES with relative precession. This conversion allows body composition analysis to be carried out also in contrast enhanced CT examinations, e.g., for risk stratification and the comparison of the obtained results to previous studies.


Peri-operative blood pressure changes in normotensive and hypertensive patients.
Controversy surrounds the acceptance of hypertension as an independent risk factor for anaesthesia. In an attempt to identify variables that are associated with increased haemodynamic instability during surgery, the blood pressure profiles of 128 patients were analysed. The two variables that contributed most to the instability were pre-operative control of blood pressure and anaesthetic technique. To reduce the fluctuation in blood pressure, it is advisable for patients to be given a regional anaesthetic. Current therapy for hypertension appears to exaggerate the depressant effects of anaesthetic drugs. Care must be taken not only to prevent hypertensive episodes during surgery, but also hypotension.


On the relation of PAG neurons to laryngeal and respiratory muscles during vocalization in the monkey.
Despite evidence from previous unit recording, microstimulation, lesioning and anatomical studies, the functions of the midbrain periaqueductal gray (PAG) remain unclear. We attempted to clarify the function of the PAG by recording activity of PAG units along with laryngeal and respiratory electromyograms (EMG) during vocalization in awake monkeys. PAG units were classified with respect to vocalization on the basis of their discharge patterns as 'early burst', 'late burst', 'tonic-increase' and 'tonic-off', with the vast majority being of the early- and late-burst type. Early-burst cells were correlated most frequently with inspiratory muscles of the respiratory system and laryngeal abductor muscles. Late-burst cells were most clearly correlated with laryngeal adductor and expiratory respiratory muscles. Data from spike-triggered averaging and parametric correlations indicate that most cells are related to single muscles, but a significant number were related to functionally related groups of two or more muscles. The results suggest that the PAG determines qualitative aspects of vocalization by the multisynaptic action its cells have on laryngeal and respiratory motoneurons.


Frequency and risk factors for antegrade ureteral stone migration after percutaneous nephrolithotomy.
Percutaneous nephrolithotomy (PCNL) is the minimally invasive procedure of choice for the treatment of large and/or complex nephrolithiasis. Migration of residual fragments (RFs) into the ureter after PCNL is presumed to be uncommon. However, should associated stone-related events (SREs) occur, ancillary procedures may be required. The objective of this study was to describe the frequency and to analyze predictors of antegrade migration of RFs after PCNL. A case-control study of patients who underwent PCNL for nephrolithiasis and had a postoperative computed tomography available within 48 hours was performed. Descriptive statistics and logistic regression analysis were carried out. The final sample included 169 interventions. Mean age was 49 ±13 years, median maximum stone size was 26 (7 to 87) mm and mean stone density was 835 (70 to 2022) Hounsfield Units (HUs). 7.1% of the patients experienced migration of RFs into the ureter after PCNL, of whom 41.6% suffered SREs. Lithotripsy was performed using ultrasonic (67.5%), laser (23.7%), and pneumatic (14.8%) technologies. Univariate analysis found female gender (OR 4.1, p = 0.02) height ≥1.68 m (OR 5.52, p = 0.009), middle (OR 6.71, p = 0.01) and upper (OR 3.59, p = 0.04) caliceal location, staghorn calculi (OR 4.72, p = 0.02), stone area (OR 1.001, p = 0.03), lasertripsy (OR 3.61, p = 0.03) and operative time (OR 1.007, p = 0.02) statistically significant for migration of SFs into the ureter after PCNL. Of these, only height ≥1.68 m (OR 7.17, p = 0.01) and staghorn nephrolithiasis (OR 13.27, p = 0.02) remained independent predictors in the multivariate analysis with an area under the curve of 0.69. 71.% of patients undergoing PCNL had a SF migrating to the ureter. Of these 41% suffered a SRE that required ancilliary interventions. Staghorn nephrolithiasis and ≥1.68 mts of height were found to predict this event.


An aberrant anatomic variation along the course of the ulnar nerve above the elbow with coexistent cubital tunnel syndrome.
We report on a patient with an unusual anatomic variation along the course of ulnar nerve above the elbow who had cubital tunnel syndrome. The variation consisted of a cutaneous neural branch that was originating at a distance of approximately 40 mm proximal to the medial epicondyle, and from the radial aspect of the main trunk of ulnar nerve. The branch had a superficial course and it was passing distally, anterior to the medial epicondyle without penetrating the fascia of the flexor muscles origin. Anterior intramuscular transposition of the ulnar nerve was performed leaving the newly found branch over the fascia between the muscles and the adipose subcutaneous tissue.


Ventricular assist devices as a bridge to cardiac transplantation. A prelude to destination therapy.
Ventricular assist devices (VADs) have been used for temporary circulatory support pending transplantation or recovery of the native heart. Outcome in 38 patients treated at the authors' institution with VADs pending transplantation was analyzed to provide information relevant to the future use of VADs as permanent implants. Thoratec (Thoratec Laboratories, Pleasanton, CA) or HeartMate (Thermo Cardiosystems, Woburn, MA) VADs were used in all cases. Patients were considered for VAD placement if they were candidates for cardiac transplantation and fulfilled the criteria for the Food and Drug Administration investigational Device Exemption trials. The following adverse events were included in the analysis; death during VAD support, device malfunction, bleeding, neurologic events, support-related events that preclude transplantation, and device-related infections. Patient survival and complication rates were quantified using the Kaplan-Meier method, competing risk analysis, and hazard functions. Nineteen patients had transplantation. Three patients had VAD removal after cardiac recovery and 16 died without transplantation. The duration of VAD support ranged from 0 to 279 days. The hazard function for death during VAD support had an early phase that lasted for 2 weeks after VAD placement, and early death was related to the preimplant condition of the patient. Device-related infections were noted in 11 patients. Seven of these patients had transplantation after clearing the infection, whereas four died without transplantation. Neurologic events occurred in seven patients. There were no device malfunctions that led to patient death. The absence of fatal device malfunctions suggests that longer term support with current VAD designs is feasible. Appropriate patient selection, infection control, and avoidance of thromboembolic neurologic complications will be crucial to the success of permanent VAD use.


International labour migration statistics in Asia: an appraisal.
"The present paper attempts a critical review of the data systems of seven major labour-exporting countries--Bangladesh, India, Indonesia, Pakistan, Philippines, Sri Lanka and Thailand--which account for over 90 per cent of labour outflows from Asia....Data...are discussed under separate sections focusing on limitations as well as potential for further exploitation.... For all countries reviewed here, these data significantly understate total labour outflows, and the magnitude of the error seems to vary between countries and reflect both differences relating to the coverage and efficiency of the approval and monitoring procedure. This throws serious doubts on the appropriateness of official outmigration series for cross country comparison. Frequent changes in reporting procedures also make for discrete changes and spurious shifts in data which render trend analysis quite hazardous." (SUMMARY IN FRE AND SPA)


Fullerene-sp2-iminosugar balls as multimodal ligands for lectins and glycosidases: a mechanistic hypothesis for the inhibitory multivalent effect.
Concerted functioning of lectins and carbohydrate-processing enzymes, mainly glycosidases, is essential in maintaining life. It was commonly assumed that the mechanisms by which each class of protein recognizes their cognate sugar partners are intrinsically different: multivalency is a characteristic feature of carbohydrate-lectin interactions, whereas glycosidases bind to their substrates or substrate-analogue inhibitors in monovalent form. Recent observations on the glycosidase inhibitory potential of multivalent glycomimetics have questioned this paradigm and led to postulate an inhibitory multivalent effect. Here the mechanisms at the origin of this phenomenon have been investigated. A D-gluco-configured sp(2)-iminosugar glycomimetic motif, namely 1-amino-5N,6O-oxomethylydenenojirimycin (1N-ONJ), behaving, simultaneously, as a ligand of peanut agglutinin (PNA) lectin and as an inhibitor of several glycosidases, has been identified. Both the 1N-ONJ-lectin- and 1N-ONJ-glycosidase-recognition processes have been found to be sensitive to multivalency, which has been exploited in the design of a lectin-glycosidase competitive assay to explore the implication of catalytic and non-glycone sites in enzyme binding. A set of isotropic dodecavalent C60-fullerene-sp(2)-iminosugar balls incorporating matching or mismatching motifs towards several glycosidases (inhitopes) was synthesized for that purpose, thereby preventing differences in binding modes arising from orientational preferences. The data supports that: 1) multivalency allows modulating the affinity and selectivity of a given inhitope towards glycosidases; 2) multivalent presentation can switch on the inhibitory capacity for some inhitope-glycosidase pairs, and 3) interactions of the multivalent inhibitors with non-glycone sites is critical for glycosidase recognition. The ensemble of results point to a shift in the binding mode on going from monovalent to multivalent systems: in the first case a typical ''key-lock'' model involving, essentially, the high-affinity active site can be assumed, whereas in the second, a lectin-like behavior implying low-affinity non-glycone sites probably operates. The differences in responsiveness to multivalency for different glycosidases can then be rationalized in terms of the structure and accessibility of the corresponding carbohydrate-binding regions.


Tardive dyskinesia: developmental factors.
Tardive dyskinesia (TD) is an involuntary movement disorder predominantly the result of long-term neuroleptic administration. Several factors have been studied with conflicting results. In this paper, the authors compare a group of 17 TD patients with 17 non-TD controls to delineate possible etiological factors in the development of this syndrome. Factors like total neuroleptic and antiparkinsonian medication intake and organicity were not different in the groups. Only drug-free periods in the past history of TD patients were found to be statistically more significant (P less than 0.025) in these patients than in non-TD controls.


Frequency stabilization of a high power argon laser.
A technique for frequency stabilizing a high power, single frequency argon laser is described which offers certain advantages over those that have already been reported. This system is capable of maintaining a relative short term frequency stability of the order of +/-2 parts in 10(9) and a long term stability (2 h) of about +/-5 parts in 10(9) for the 5145-A line at a power level of 750 mW. This short and long term stability is achieved by means of a multiple feedback loop composed of an optical cavity discriminator which is stabilized against an iodine vapor absorption line.


Human red blood cells--an ideal model system for the action of calcium agonists and antagonists.
To characterize the pharmacological properties of the slow calcium channel of human red blood cells, we studied the action of various calcium antagonists and two agonists on the 45Ca2+-influx. The Ca2+-ejecting ATPase was inhibited by vanadate. All dihydropyridine derivatives tested showed their inhibiting or stimulating effect on the channel at concentrations attainable in vivo (nitrendipine:Ki = 2.5; Bayer K 6244:Ki 5 microM; nicardipine:Ki = 15 microM, Ks = 0.5 microM; Ciba 28 392:Ki = 20, Ks = 0.3 microM; Ki = inhibition constant, Ks = stimulation constant). Of special interest was the biphasic behaviour (stimulation and inhibition) of the calcium antagonist nicardipine and the agonist Ciba 28 392. The maximum inhibition by the phenylalkylamine derivative verapamil was obtained at much higher concentrations (250 microM; Ki = 100). These data suggest that the calcium channel of human red blood cells has pharmacological properties very similar to the channel in heart and smooth muscle cells with respect to dihydropyridine action. Therefore, human red blood cells are an ideal model to study the action of calcium agonists and antagonists.


Glutamate receptor-like channel3.3 is involved in mediating glutathione-triggered cytosolic calcium transients, transcriptional changes, and innate immunity responses in Arabidopsis.
The tripeptide reduced glutathione (GSH; γ-glutamate [Glu]-cysteine [Cys]-glycine) is a major endogenous antioxidant in both animal and plant cells. It also functions as a neurotransmitter mediating communication among neurons in the central nervous system of animals through modulating specific ionotropic Glu receptors (GLRs) in the membrane. Little is known about such signaling roles in plant cells. Here, we report that transient rises in cytosolic calcium triggered by exogenous GSH in Arabidopsis (Arabidopsis thaliana) leaves were sensitive to GLR antagonists and abolished in loss-of-function atglr3.3 mutants. Like the GSH biosynthesis-defective mutant PHYTOALEXIN DEFICIENT2, atglr3.3 showed enhanced susceptibility to the bacterial pathogen Pseudomonas syringae pv tomato DC3000. Pathogen-induced defense marker gene expression was also decreased in atglr3.3 mutants. Twenty-seven percent of genes that were rapidly responsive to GSH treatment of seedlings were defense genes, most of which were dependent on functional AtGLR3.3, while GSH suppressed pathogen propagation through the AtGLR3.3-dependent pathway. Eight previously identified putative AtGLR3.3 ligands, GSH, oxidized glutathione, alanine, asparagine, Cys, Glu, glycine, and serine, all elicited the AtGLR3.3-dependent cytosolic calcium transients, but only GSH and Cys induced the defense response, with the Glu-induced AtGLR3.3-dependent transcription response being much less apparent than that triggered by GSH. Together, these observations suggest that AtGLR3.3 is required for several signaling effects mediated by extracellular GSH, even though these effects may not be causally related.


Prediction of clinically relevant Pancreatico-enteric Anastomotic Fistulas after Pancreatoduodenectomy using deep learning of Preoperative Computed Tomography.
Rationale: Clinically relevant postoperative pancreatic fistula (CR-POPF) is among the most formidable complications after pancreatoduodenectomy (PD), heightening morbidity/mortality rates. Fistula Risk Score (FRS) is a well-developed predictor, but it is an intraoperative predictor and quantifies >50% patients as intermediate risk. Therefore, an accurate and easy-to-use preoperative index is desired. Herein, we test the hypothesis that quantitative analysis of contrast-enhanced computed tomography (CE-CT) with deep learning could predict CR-POPFs. Methods: A group of 513 patients underwent pancreatico-enteric anastomosis after PD at three institutions between 2006 and 2019 was retrospectively collected, and formed a training (70%) and a validation dataset (30%) randomly. A convolutional neural network was trained and generated a deep-learning score (DLS) to identify the patients with higher risk of CR-POPF preoperatively using CE-CT images, which was further externally tested in a prospective cohort collected from August 2018 to June 2019 at the fourth institution. The biological underpinnings of DLS were assessed using histomorphological data by multivariate linear regression analysis. Results: CR-POPFs developed in 95 patients (16.3%) in total. Compared to FRS, the DLS offered significantly greater predictability in training (AUC:0.85 [95% CI, 0.80-0.90] vs. 0.78 [95% CI, 0.72-0.84]; P = 0.03), validation (0.81 [95% CI, 0.72-0.89] vs. 0.76 [95% CI, 0.66-0.84], P = 0.05) and test (0.89 [95% CI, 0.79-0.96] vs. 0.73 [95% CI, 0.61-0.83], P < 0.001) cohorts. Especially in the challenging patients of intermediate risk (FRS: 3-6), the DLS showed significantly higher accuracy (training: 79.9% vs. 61.5% [P = 0.005]; validation: 70.3% vs. 56.3% [P = 0.04]; test: 92.1% vs. 65.8% [P = 0.013]). Additionally, DLS was independently associated with pancreatic fibrosis (coefficients: -0.167), main pancreatic duct (coefficients: -0.445) and remnant volume (coefficients: 0.138) in multivariate linear regression analysis (r2 = 0.512, P < 0.001). The user satisfaction score in the test cohort was 4 out of 5. Conclusions: Preoperative CT based deep-learning model provides a promising novel method for predicting CR-POPF occurrences after PD, especially at intermediate FRS risk level. This has a potential to be integrated into radiologic reporting system or incorporated into surgical planning software to accommodate the preferences of surgeons to optimize preoperative strategies, intraoperative decision-making, and even postoperative care.


A modified measurement-based care approach to improve mental health treatment engagement among racial and ethnic minoritized youth.
Despite high levels of need, racial and ethnic minoritized (REM) youth are much less likely than their White peers to engage in mental health treatment. Concerns about treatment relevance and acceptability and poor therapeutic alliance have been shown to impact treatment engagement, particularly retention, among REM youth and families. Measurement-based care (MBC) is a client-centered practice of collecting and using client-reported progress data throughout treatment to inform shared decision-making. MBC has been associated with increased client involvement in treatment, improved client-provider communication, and increased satisfaction with treatment services. Despite its promise as a treatment engagement strategy, MBC has not been studied in this capacity with REM youth or systematically modified to address the needs of culturally-diverse populations. In this article, we propose a culturally-modified version of MBC, Strategic Treatment Assessment with Youth (STAY), to improve treatment engagement among REM youth and families. Specifically, STAY is designed to target perceptual barriers to treatment to improve treatment retention and ultimately, client outcomes. The four STAY components (i.e., Introduce, Collect, Share, and Act) are based on an existing MBC practice framework and modified to address perceptual barriers to treatment among REM youth. The clinical application of this model is presented via a case example. Finally, future research directions to explore the use of MBC as a treatment retention strategy with REM client populations are provided. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria: studies on clonality.
We used X-chromosome methylation patterns to study clonality in aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). AA is usually not considered to be a clonal stem cell disorder, although this has not been directly investigated. PNH is generally assumed to be a clonal disorder, although there is contradictory evidence. Methylation analysis was performed on DNA from separated granulocytes and mononuclear cells, using the M27 beta and hypoxanthine phosphoribosyl transferase (HPRT) probes. Six of seven AA patients showed a polyclonal pattern of X inactivation. In contrast, five of five PNH patients showed a monoclonal pattern. These results imply that at least 80% of the cell population derives from a single stem cell. Because this high proportion of PNH cells might be considered surprising, three patients were studied for membrane expression of decay accelerating factor (DAF). In support of the DNA data, more than 95% of the granulocytes were DAF--ve in all three cases. We conclude that AA is predominantly a polyclonal disorder, whereas PNH is a clonal stem cell disorder. Our data support a model in which a single PNH stem cell has a growth advantage over other remaining stem cells and eventually dominates hematopoiesis.


Regulation of lymphokine-activated killer activity in T-replete and T-cell-depleted human bone marrow by interleukin 4.
Donor-derived lymphokine-activated killer (LAK) cells appear to play a role in mediating an antileukemia effect in recipients of both T-replete and T-cell-depleted (TCD) bone marrow transplants. LAK activity, however, is subject to regulation by cytokines other than interleukin 2 (IL-2). The purpose of this study was to examine the effect of interleukin 4 (IL-4) on the induction of LAK activity in both T-replete and TCD bone marrow. IL-4 inhibited the induction of LAK activity in a time- and dose-dependent manner in both T-replete and TCD bone marrow cultures, although there appeared to be a differential effect, suggesting that T and non-T LAK precursors have different thresholds of sensitivity to IL-4. Single-cell cytotoxicity assays indicated that IL-4 did not inhibit binding of LAK effectors to targets but did reduce the frequency of lytic conjugates. Kinetic analysis techniques demonstrated that IL-4 decreased the maximal rate of target cell lysis by IL-2-activated LAK precursors and inhibited the rate of lytic programming. These data indicate that IL-4 is able to regulate the induction of LAK activity in both T-replete and TCD bone marrow and may play a role in modulating the generation of effector cells with potential antileukemia reactivity in vivo.


Low-dose intravenous acetaminophen versus oral ibuprofen for the closure of patent ductus arteriosus in premature neonates.
Patent ductus arteriosus (PDA) is a common disease in premature neonates, which could occur in up to 50% of the neonates weighting <1000 g. PDA might induce hemodynamic and respiratory disorders and increase mortality and morbidity. This study aimed to compare the effectiveness of oral ibuprofen and a low dose of intravenous acetaminophen in the management of PDA. This randomized double-blind clinical trial was conducted on the preterm neonates with an equal gestational age of <34 weeks and weight of >1000 g with symptomatic PDA, who were admitted in Shahid Beheshti and Al-Zahra Hospitals Affiliated to Isfahan University of Medical Sciences, Iran. In total, 40 preterm neonates were examined, 20 of whom received 15 mg/kg/6 h of intravenous acetaminophen for 2 days and 20 infants received 10 mg/kg of intravenous ibuprofen on the 1st day and 5 mg/kg for the next 2 days, and the results include vital signs and echocardiography findings were compared. In the acetaminophen and ibuprofen groups, 16 (80%) and 17 neonates (85%) responded (PDA closure rate) to the treatment, respectively (P = 0.68). Furthermore, acetaminophen and ibuprofen have a similar effect on vital signs. Both drugs did not change in blood pressure, but they reduced the respiratory rate and heart rate after treatment. Low-dose acetaminophen compared to ibuprofen has an equal effectiveness in the closure of PDA.


Phylotranscriptomics: saturated third codon positions radically influence the estimation of trees based on next-gen data.
Recent advancements in molecular sequencing techniques have led to a surge in the number of phylogenetic studies that incorporate large amounts of genetic data. We test the assumption that analyzing large number of genes will lead to improvements in tree resolution and branch support using moths in the superfamily Bombycoidea, a group with some interfamilial relationships that have been difficult to resolve. Specifically, we use a next-gen data set that included 19 taxa and 938 genes (∼1.2M bp) to examine how codon position and saturation might influence resolution and node support among three key families. Maximum likelihood, parsimony, and species tree analysis using gene tree parsimony, on different nucleotide and amino acid data sets, resulted in largely congruent topologies with high bootstrap support compared with prior studies that included fewer loci. However, for a few shallow nodes, nucleotide and amino acid data provided high support for conflicting relationships. The third codon position was saturated and phylogenetic analysis of this position alone supported a completely different, potentially misleading sister group relationship. We used the program RADICAL to assess the number of genes needed to fix some of these difficult nodes. One such node originally needed a total of 850 genes but only required 250 when synonymous signal was removed. Our study shows that, in order to effectively use next-gen data to correctly resolve difficult phylogenetic relationships, it is necessary to assess the effects of synonymous substitutions and third codon positions.


Hydrophobic interactions in urea-trimethylamine-N-oxide solutions.
The influence of osmolytes urea and trimethylamine- N-oxide (TMAO) on hydrophobic interactions is investigated employing molecular dynamics simulations. These osmolytes are of interest because of their opposing influence on proteins in solution; the denaturing effect of urea can be countered with TMAO. A neopentane pair is used to model typical nonpolar entities. Binary water-urea and water-TMAO as well as ternary water-urea-TMAO systems are considered. Neopentane-neopentane potentials of mean force, neopentane-water, and neopentane-osmolyte distribution functions are reported. Urea is found to have only modest influence on the neopentane-neopentane potential of mean force, but the hydrophobic attraction is completely destroyed by the presence of TMAO. It is shown that TMAO tends to act as a simple "surfactant" displacing water and urea (if it is present) from the first solvation shell of neopentane. It is likely the surfactant-like influence of TMAO that accounts for the elimination of the hydrophobic attraction. The implications of our results for explanations of the action of TMAO in protein solutions are discussed.


Radial frequency patterns describe a small and perceptually distinct subset of all possible planar shapes.
The visual system is exposed to a vast number of shapes and objects. Yet, human object recognition is effortless, fast and largely independent of naturally occurring transformations such as position and scale. The precise mechanisms of shape encoding are still largely unknown. Radial frequency (RF) patterns are a special class of closed contours defined by modulation of a circle's radius. These patterns have been frequently and successfully used as stimuli in vision science to investigate aspects of shape processing. Given their mathematical properties, RF patterns can not represent any arbitrary shape, but the ability to generate more complex, biologically relevant, shapes depicting the outlines of objects such as fruits or human heads raises the possibility that RF patterns span a representative subset of possible shapes. However, this assumption has not been tested before. Here we show that only a small fraction of all possible shapes can be represented by RF patterns and that this small fraction is perceptually distinct from the general class of all possible shapes. Specifically, we derive a general measure for the distance of a given shape's outline from the set of RF patterns, allowing us to scan large numbers of object outlines automatically. We find that only between 1% and 6% of naturally smooth outlines can be exactly represented by RF patterns. We present results from a visual search experiment, which revealed that searching an RF pattern among non-radial frequency patterns is efficient, whereas searching an RF pattern among other RF patterns is inefficient (and vice versa). These results suggest that RF patterns represent only a restricted subset of possible planar shapes and that results obtained with this special class of stimuli can not simply be expected to generalise to any arbitrary planar shape.


Parasites causing cutaneous wounds: Theory and practice from a dermatological point of view.
A wide range of parasites can infest open wounds, or cause wounds due to the effects of the infestation. Parasitic infestations can involve the skin and subcutaneous tissues, with various clinical manifestations. In case of cutaneous wounds related to infestations, protozoa, helminths and arthropods are the main groups of parasites involved and emerging new aspects have been recently reported. Treating the wound correctly is fundamental in these patients in order to reduce the development of pathological scars and prevent complications. In particular, a gentle debridement for devitalized/infested tissue removal, the appropriate use of topical antiseptics and dressings such as hydrogel, hydrocolloids and antimicrobial dressings can be useful to control superinfections, moisture balance, inflammation and to promote edge proliferation.


[Analyse on the epidemiological characteristics of brucellosis and in Inner Mongolia through the observation of the change among Brucella species].
This article analysed the epidemiological characteristics of Brucellosis in Inner Mongolia. Data had been collected for the last fourty years since 1,937 on the changes of Brucella species in their distribution, variation, toxicity, types, etc. The authors pointed out that changes of Brucella species played a decisive role in changing the epidemiological patterns, while intentionally active or passive intervention importantly contributed to the change of Brucella species. It was emphasized that the survey on Brucella species and the dynamic change of epidemiological features were closely related which should not be ignored for the forecasting of Brucellosis epidemics.


[Metacarpal bone chondrosarcoma. Apropos of a case].
On the basis of a personal case of non-symptomatic chondrosarcoma of the metacarpal bone and a review of the literature, the authors advise the biopsy of any lesion which resembles a chondroma of the hand. Only histological examination can provide evidence for diagnosis and guide effective treatment.


Student's Experiences on Learning Therapeutic Relationship: A Narrative Inquiry.
Despite the importance of the therapeutic relationship on nursing practice, the literature regarding teaching and learning therapeutic relationship is limited. This paper discussed how an undergraduate nursing student learned therapeutic relationship in an acute care setting. Narrative inquiry was applied as a research methodology. The student's reflection served as the narrative in this paper. Collaboratively, researchers conducted data analysis, common themes were drawn, and a summative narrative was presented. Based on the student's narrative, a three-dimensional model, including practical knowledge, theory, and reflection, has been created as our summative narrative. This model suggests that, to facilitate a learning process on creating therapeutic nurse-patient relationship, practical knowledge is the foundation, theory is a leading guide, and constant reflection is a learning tool which transforms learning into a reflective and meaningful experience. To promote learning on therapeutic relationship, nurse educators should emphasize the importance of both practical knowledge and theory. Constant reflection as a learning tool should be encouraged and embedded in nursing curriculum. Diverse approaches of reflection should be promoted.


Draft Genome Sequence of Novel Metschnikowia sp. Strain JCM 33374, a Nectar Yeast Isolated from a Bumblebee.
Here, we report the draft genome sequence of Metschnikowia sp. strain JCM 33374, a nectar yeast isolated from a bumblebee (Bombus diversus). The genome of 20.1 Mb is a naturally heterozygous diploid. Phylogenetic analysis with related taxa demonstrated that the strain is very likely a novel species.


Flap and stromal bed thickness in laser in situ keratomileusis enhancement.
To evaluate whether flap thickness changes after the primary laser in situ keratomileusis (LASIK) procedure and to assess the accuracy of intraoperative pachymetry and ablation depth measurements in predicting stromal bed thickness before enhancement in eyes that have had primary myopic LASIK. Bascom Palmer Eye Institute, Miami, Florida, USA. This retrospective noncomparative interventional case series comprised 57 eyes of 42 patients who had LASIK enhancement between June 2001 and September 2002. Exclusion criteria included previous ocular surgery or complications during the first LASIK procedure. Only patients who had had LASIK and enhancement by the same surgeon at our institution and had intraoperative pachymetry readings for both procedures were included. The original flap was relifted in all enhancement procedures. Corneal thickness was routinely measured intraoperatively by ultrasound pachymetry. The age, eye, refraction, date of primary LASIK, central corneal thickness (CCT) and central stromal bed thickness at primary LASIK, depth of ablation, flap thickness (subtraction pachymetry), date of enhancement, CCT and central stromal bed thickness at enhancement, and flap thickness at enhancement were recorded. Thirty-one eyes of 26 patients were myopic and 26 eyes of 16 patients were hyperopic before primary LASIK. The mean time between LASIK and enhancement was 218 days +/- 115 (SD) (193 +/- 88 days in myopic eyes and 248 +/- 136 days in hyperopic eyes [P = .068]). The flap tended to be thicker at enhancement than in the primary LASIK procedure by 9.3 +/- 25.7 microm in myopic eyes (P = .054) and 10.5 +/- 16.6 microm in hyperopic eyes (P = .004). A strong correlation was found between flap thickness in the first and second procedures in myopic and hyperopic eyes (r = 0.6). In myopic eyes, the mean difference between the estimated stromal bed thickness after the first procedure (central bed thickness- ablation depth) and the stromal bed thickness measured directly at enhancement was not statistically significant (3 +/- 29 microm; P = .54, paired t test). A strong correlation was found between the 2 measurements (r = 0.8, P<.001). Another strong correlation was found in myopic eyes between the estimated corneal thickness after the primary LASIK and the corneal thickness measured at enhancement (r = 0.81, P<.001). No correlation was found between the difference in flap thickness and the time to enhancement (r = 0.09 in myopic eyes and r = 0.01 in hyperopic eyes). Flap thickness tended to be thicker at enhancement than at primary LASIK. Intraoperative pachymetry and ablation depth measurements proved to be precise tools to predict stromal bed thickness before enhancement in eyes that had had primary myopic LASIK. This information may help in planning LASIK enhancements.


Promoting nursing as a career choice.
Fewer young people are considering nursing as a career. This project was designed to present nursing as a viable career option to middle school students. A questionnaire was administered to six classes of middle school students before and after a presentation on nursing as a career. Results showed the presentation improved student attitudes and perceptions toward nursing as a career. Nurses can use this project as a stepping stone to develop additional programs to interest students in nursing as a career before the students discard the notion altogether.


Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI.
Recently, extracellular vesicles (EVs) have been attracting strong research interest for use as natural drug delivery systems. We report an approach to manufacturing interleukin-10 (IL-10)-loaded EVs (IL-10+ EVs) by engineering macrophages for treating ischemic acute kidney injury (AKI). Delivery of IL-10 via EVs enhanced not only the stability of IL-10, but also its targeting to the kidney due to the adhesive components on the EV surface. Treatment with IL-10+ EVs significantly ameliorated renal tubular injury and inflammation caused by ischemia/reperfusion injury, and potently prevented the transition to chronic kidney disease. Mechanistically, IL-10+ EVs targeted tubular epithelial cells, and suppressed mammalian target of rapamycin signaling, thereby promoting mitophagy to maintain mitochondrial fitness. Moreover, IL-10+ EVs efficiently drove M2 macrophage polarization by targeting macrophages in the tubulointerstitium. Our study demonstrates that EVs can serve as a promising delivery platform to manipulate IL-10 for the effective treatment of ischemic AKI.


[Role and Applicability of Spontaneous Reporting Databases in Medical Big Data].
In recent years, a variety of medical information has been digitized, and hence, various medical big data have become available. Spontaneous reporting databases are a part of the medical big data. In Japan, the Pharmaceuticals and Medical Devices Agency has developed the "Japanese Adverse Drug Event Report (JADER) database" which has been available since 2012. Thus, everyone can publish safety signal information based on the results of disproportionality analysis using the spontaneous reporting database. Since the release of JADER, many researchers and healthcare professionals are interested in it, and many reports have been prepared using JADER. Although we tend to focus on the fact that it is a publicly available database with many cases, it also has various limitations such as lack of the denominator information, under-reporting, and reporting biases. Detected signals do not necessarily imply a causal relationship between the drug and adverse event. In the "Guideline on good pharmacovigilance practices (GVP) Module IX by European Medicines Agency", signal detection is the first step in the signal management process. Signal detection alone does not complete pharmacovigilance activities. It is important to understand that spontaneous reporting databases are not only for researchers but also for those who are considering to apply them to clinical work by referring to research using these databases. In this symposium review, I will discuss the role and applicability of spontaneous reporting databases in medical big data.


Negative and positive symptoms in schizophrenia and depression: a followup.
Negative and positive symptoms were investigated in a sample of 72 young schizophrenic and depressed patients at followup approximately 1 1/2 years after hospital discharge. Flat affect, poverty of speech, and psychomotor retardation were included as negative symptoms, and delusions, hallucinations, and florid thought disorder as positive symptoms. Marked negative symptoms were found to occur in a subgroup of schizophrenic subjects at followup, but were infrequent in depressed subjects. Educational difficulties and poor social functioning before initial hospitalization were associated with later negative symptoms at followup for schizophrenic subjects. Negative symptoms were also related to concurrent outcome measures of instrumental and social functioning at followup. Contrary to some hypotheses, negative and positive symptoms, when assessed concurrently, were not at opposite ends of a bipolar continuum. Rather, they appeared to be independent phenomena in schizophrenia during the early posthospital phase. Overall, these results suggest that negative symptoms are important for a subgroup of schizophrenic patients during the early course of their disorder and that they have important correlates with specific aspects of role functioning.


How Thermal Aging Affects Ignition and Combustion Properties of Reactive Al/CuO Nanolaminates: A Joint Theoretical/Experimental Study.
The paper reports a joint experimental/theoretical study on the aging of reactive Al/CuO nanolaminates, investigating both structural modifications and combustion properties of aged systems. We first show theoretically that the long-term storage (over several decades) in ambient temperature marginally affects nanolaminates structural properties with an increase in an interfacial layer of only 0.3 nm after 30 years. Then, we observe that the first thermal aging step occurs after 14 days at 200 °C, which corresponds to the replacement of the natural Al/CuO interfaces by a proper ~11 nm thick amorphous alumina. We show that this aging step does impact the nanolaminates structure, leading, for thin bilayer thicknesses, to a substantial loss of the energetic reservoir: considering a stoichiometric Al/CuO stack, the heat of reaction can be reduced by 6-40% depending on the bilayer thickness ranging from 150 nm (40%) to 1 µm (6%). The impact of such thermal aging (14 days at 200 °C) and interfacial modification on the initiation and combustion properties have been evaluated experimentally and theoretically. Varying Al to CuO ratio of nanolaminates from 1 to 3, we show that ignition time of aged systems does not increase over 10% at initiation power densities superior to 15 W·mm-2. In contrast, burn rate can be greatly impacted depending on the bilayer thickness: annealing a stoichiometric nanolaminates with a bilayer thickness of 300 nm at 200 °C for 14 days lowers its burn rate by ~25%, whereas annealing a fuel rich nanolaminates with the same bilayer thickness under the same thermal conditions leads to a burn rate decrease of 20%. When bilayer thickness is greater than 500 nm, the burn rate is not really affected by the thermal aging. Finally, this paper also proposes a time-temperature diagram to perform accelerated thermal aging.


Transient response of a signal through a dispersive invisibility cloak.
The transient response of the invisibility cloak has long been an interesting research topic, since it is valuable to further understand the steady-state process and to design more effective cloaks. Here we investigate the transient response of a set of dispersive invisibility cloaks impinged on by a sinusoidal signal or a modulated Gaussian pulse using the finite difference time domain method. Cylindrical cloaks with linear, convex, and concave transformation functions are studied. We find that their time to reach a steady state is different and they grow significantly when the thickness of the cloak decreases. Moreover, a centrally depressed ladder-like spatial time delay distribution is observed with a modulated Gaussian pulse. We show that the central frequency of the Gaussian pulse suffers a blue-shift in the forward scattering direction in agreement with previous theoretical predictions.


Cell mechanics: dissecting the physical responses of cells to force.
It is now widely appreciated that normal tissue morphology and function rely upon cells' ability to sense and generate forces appropriate to their correct tissue context. Although the effects of forces on cells have been studied for decades, our understanding of how those forces propagate through and act on different cell substructures remains at an early stage. The past decade has seen a resurgence of interest, with a variety of different micromechanical methods in current use that probe cells' dynamic deformation in response to a time-varying force. The ability of researchers to carefully measure the mechanical properties of cells subjected to a variety of pharmacological and genetic interventions, however, currently outstrips our ability to quantitatively interpret the data in many cases. Despite these challenges, the stage is now set for the development of detailed models for cell deformability, motility, and mechanosensing that are rooted at the molecular level.


Factors affecting outcome of extensor tendon lacerations in the distal limb of horses. A retrospective study of 156 cases (1994-2003).
Distal limb lacerations are common injuries in horses, with a better prognosis reported for extensor tendons lacerations compared to flexor tendons lacerations. The objective of the present study was to determine the influence of type and location of injury, modalities of treatment and post surgical complications on the outcome of extensor tendon lacerations. The medical records of 156 horses surgically treated for extensor tendon lacerations over a 10-year period were analysed retrospectively. Information was obtained for 124 horses with a minimum of 18 months follow-up. Statistical analysis was performed on 129 horses (five horses were euthanatized during hospitalization) in order to determine factors affecting outcome. Seventy-four percent of the horses returned to soundness, 17% had moderate gait impairment and 9% remained lame. Approximately 60% of the sports horses returned to an equal or higher level of performance, and 17.5% returned to a lower level. In the multivariate statistical analysis, the only significant factor that favourably influenced outcome was complete suture of the wound. A significant association could not be detected between outcome and absence of a functional extensor tendon, The most important post-surgical complication was extensive scarring of the wound. The present results report outcome of extensor tendon lacerations in a large number of horses and outline the importance of primary wound healing in order to avoid major scarring with potential functional consequences.


Increased In-Hospital Lengths of Stay, Readmission Rates, Complications, and Costs in Patients Who Have Depressive Disorders Following Primary Total Hip Arthroplasty.
Recent studies have shown the prevalence of depressive disorders has increased within the United States. Studies investigating the impact of depressive disorders following primary THA are limited. Therefore, the purpose of this study was to determine whether patients with depressive disorders have higher rates of: 1) in-hospital lengths of stay (LOS); 2) readmission rates; 3) medical complications; and 4) implant-related complications. A retrospective query of the Humana claims database was performed. Patients undergoing primary THA with a history of depressive disorders were identified by International Classification of Disease, Ninth Revision (ICD-9), and Current Procedural Terminology (CPT) codes. Study group patients were matched to controls in a 1:5 ratio by age, sex, and comorbidities. The query yielded 67,245 patients with (n=11,255) and without (n=55,990) depressive disorders. Welch's t-tests were used to test for significance in LOS between the cohorts; whereas, logistics regression analyses were used for complications and readmissions. A p-value less than 0.003 was statistically significant. Patients with depressive disorders undergoing primary THA had significantly longer in-hospital LOS (6.59 days vs. 2.96 days, p <0.0001). Additionally, patients with depressive disorders had higher incidence and odds of readmission rates (46.02 vs. 35.43%; OR: 1.55, p <0.0001), medical complications (7.05 vs. 1.84%; OR: 4.04, p <0.0001), and implant-related complications (5.76 vs. 2.75%; OR: 2.16, p <0.0001) compared to patients without depressive disorders. After matching age, sex, and medical comorbidities, the results of the study demonstrate patients with depressive disorders have longer in-hospital LOS and increased rates of complications and readmission rates. The study is useful as it can allow orthopedic surgeons to properly counsel these patients of the potential complications which may arise following their procedure.