Lipoprotein (a) is associated with basal insulin levels in patients with type 2 Diabetes Mellitus.
It has not been clearly established whether insulin resistance/deficiency leads directly to atherogenesis or through its association with other risk factors such as lipoprotein(a) [Lp(a)]. This project aimed at studying the association between basal insulin, lipids and lipoprotein(a) levels in patients with type 2 diabetes mellitus. Fasting blood samples were analyzed for Insulin, Lipoprotein(a), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glucose and glycosylated hemoglobin (HbA1c) levels in 60 patients with type 2 Diabetes Mellitus (DM) and 28 healthy subjects. We divided patients into two groups based on basal insulin levels: > or = 10 microIU/ml and < 10 microIU/ml. Insulin levels were higher in diabetic versus control individuals [p < 0.05]. TC (p< 0.01), LDL-C (p< 0.05), TC/HDL ratio (p< 0.01) and TG levels (p< 0.05) were higher and HDL- C levels were significantly lower (p < 0.001) in both diabetic groups as compared to control. Lp(a) levels were significantly higher in both diabetic groups, when compared to the control group. Lp(a) levels were significantly lower in diabetics with basal insulin > or =10 microIU/ml when compared to those with basal insulin < 10 microIU/ml (p < 0.05). Regression analysis revealed a significant relationship of Lp(a) with insulin levels (r = 0.262, p < 0.05) and Insulin Glucose ratio (r = 0.257, p < 0.05). Lp(a) levels correlate inversely with insulin levels in Type 2 diabetic patients. Lp(a) may be one of the cardiovascular risk factor in type 2 diabetic patients with longer duration of DM.


Detection of antiranibizumab antibodies among patients with exudative age-related macular degeneration.
The aim of this study was to detect immune responses induced by intravitreal injection (IVT) of ranibizumab in patients with exudative age-related macular degeneration (AMD) in real life conditions. An ELISA protocol from blood samples, following 2 different steps, was used to detect antibodies directed against the variable regions of ranibizumab. Among 91 patients included, 46 received more than 10 IVTs, 36 had received 10 IVTs or fewer, and 9 were treatment naïve. Specific antiranibizumab immunoglobulins G were detected in 14/82 treated patients (17.1%). No immunization was detected among naïve patients. For patients with 10 or fewer previous IVTs, immunization against ranibizumab was detected in 4/36 patients (11.1%) whereas immunization was observed in 10/46 patients (21.7%) with more IVTs (p = 0.20). Immunization against ranibizumab can be detected in 17% of treated patients. Further clinical studies are needed to investigate the relationship between specific immunization to anti-vascular endothelial growth factor antibodies and response or resistance to ranibizumab treatments.


Photo-oxidation of ergosterol: indirect detection of antioxidants photosensitizers or quenchers of singlet oxygen.
Consumption of antioxidant supplements is associated to prevention of several diseases. However, recent studies suggest that antioxidants, besides scavenge free radicals could lead development of tumors. Due to conflicting reports on the antioxidant benefits, the capacity to photosensitize the generation of singlet oxygen of seven natural antioxidants was evaluated through photo-oxidation of ergosterol which proved to be an efficient method of indirect detection of singlet oxygen. Our results showed that curcumin, resveratrol and quercetin have pro-oxidant activity due they act as photosensitizers in generation of singlet oxygen. In addition, we observed that genistein, naringenin, β-carotene and gallic acid besides their antioxidant activity against ROS radicals, are capable of quenching ROS non-radicals as singlet oxygen. Finally, our results allow us to propose a new approach in classification of natural antioxidants scavengers of free radicals, based on their activity as quenchers of singlet oxygen or as photosensitizers in singlet oxygen generation.


Decorated Ag19 on Pt(111) or the "rare gas necklace".
Ag19 cluster ions are mass selected and deposited on a Pt(111) surface covered by five monolayers of Kr. Almost monodispersed hexagonal shaped Ag islands are observed after Kr evaporation at 125 K. The identification of the island shape and the exact number of atoms has been successful by decorating the clusters with Kr atoms which can be counted by high resolution scanning tunneling microscopy.


Developments in the CCP4 molecular-graphics project.
Progress towards structure determination that is both high-throughput and high-value is dependent on the development of integrated and automatic tools for electron-density map interpretation and for the analysis of the resulting atomic models. Advances in map-interpretation algorithms are extending the resolution regime in which fully automatic tools can work reliably, but at present human intervention is required to interpret poor regions of macromolecular electron density, particularly where crystallographic data is only available to modest resolution [for example, I/sigma(I) < 2.0 for minimum resolution 2.5 A]. In such cases, a set of manual and semi-manual model-building molecular-graphics tools is needed. At the same time, converting the knowledge encapsulated in a molecular structure into understanding is dependent upon visualization tools, which must be able to communicate that understanding to others by means of both static and dynamic representations. CCP4 mg is a program designed to meet these needs in a way that is closely integrated with the ongoing development of CCP4 as a program suite suitable for both low- and high-intervention computational structural biology. As well as providing a carefully designed user interface to advanced algorithms of model building and analysis, CCP4 mg is intended to present a graphical toolkit to developers of novel algorithms in these fields.


Efficacy of psychoeducation and relaxation interventions on stress-related variables in people with mental disorders: a literature review.
This paper aimed to critically review and summarize empirical evidence concerning the efficacy of psychoeducation or relaxation-based stress management interventions on stress-related variables in people with mental disorders. Electronic databases were used during the literature search. Thirteen articles that fulfilled the preset eligible criteria were included in the review. Findings indicated that psychoeducation and relaxation-based interventions mitigated stress and depression; and enhanced relaxation intensity and knowledge on stress management. However, mixed results were obtained on anxiety. In addition, interventions using virtual reality technology revealed positive effects on depression, relaxation intensity and anxiety. Limitations and recommendations for future research are discussed.


Stem cells in the pituitary gland: A burgeoning field.
The pituitary gland represents the endocrine core of the organism, and is well-known for its cellular plasticity in order to meet the body's fluctuating hormonal demands. In the past, it has repeatedly been postulated that the pituitary harbors tissue-specific stem cells that participate in the generation of new endocrine cells during this dynamic cell remodeling, as well as during the slow but robust homeostatic turnover of the gland. However, their presence and identity remained elusive until this conundrum recently attracted renewed interest. Our discovery of a 'side population' using flow cytometry was the first step towards a more convincing candidate stem/progenitor cell population in the endocrine anterior pituitary. Since then, several other groups have endeavored to search for pituitary stem/progenitor cells, which finally culminated in the identification of very strong candidates. Multiple markers were put forward, among which the pluripotency transcription factor Sox2 occupies center stage. Now that very plausible pituitary stem/progenitor cells can be isolated and assayed, detailed characterization of their involvement in pituitary cell remodeling during basal renewal, dynamic adaptation and potential response to injury is around the corner, and is expected to significantly advance our knowledge on pituitary biology. In addition, a comprehensive study of the stem/progenitor cells may guide us to a better understanding of pituitary hormonal deficiencies, as well as of pituitary tumorigenesis in which 'cancer stem cells' may play a central role. Nevertheless, many questions remain to be resolved, and future challenges are huge. In this review, we provide a detailed overview of the exciting recent developments in the pituitary stem cell quest. In addition we pinpoint some discordant findings and include a number of cautionary and critical reflections. The recent acceleration in pituitary stem cell research may initiate a very exciting era in the pituitary field. May we say that "La nouvelle hypofyse est arrivée"?


Cdk5: a new player at synapses.
Cdk5 is a member of the cyclin-dependent kinase family. Unlike other conventional Cdks that are major regulators of eukaryotic cell cycle progression, Cdk5 displays diverse functions in neuronal as well as non-neuronal tissues. In particular, accumulating evidence points to the roles of this kinase in CNS development and other cellular processes. In this article, we summarize the functional roles of Cdk5 pertaining to the formation and functions of synapse, a specialized structure for the fundamental functions of neurons.


Further studies on intratesticular testosterone concentration in patients with disturbed fertility.
32 patients with azoospermia or severe oligozoospermia were studied. In all cases testosterone was in the normal range. Luteinizing hormone (LH) in plasma was elevated in 10 patients and follicle stimulating hormone (FSH) was elevated in 18 cases. The testes were evaluated by morphometry. The higher the degree of tubular atrophy the smaller the testes and the more Leydig cells found in a given piece of tissue. The percentage of the testes occupied by Leydig cells correlated wtih the intratesticular testosterone concentration(r = 0.435, P < 0.001). In the subgroup of patients with normal plasma testosterone and elevated LH values the intratesticular testosterone was significantly (P < 0.001) elevated as compared to the patients with normal LH.


[Drowning: tematic review and casuistic analysis in the Intensive Care Medicine Service of University Hospital of Coimbra (1989-2002)].
Drowning is a major cause of accidental deaths, especially in childrens. In this review (part one) the definition, epidemiology, pathophysiology and treatments (with an enphasis on the ressuscitation) are discussed. From 1989 to 2002 part two) we recorded the clinical course of the 19 patients vitims of submersion admited to our ICU. We conclued that the majority of patients are young (mean = 37,3 years), mortality is high (26%), but the complete recovery is possible (63%). The cardio-respiratory arrest or Glasgow Coma Scale < or = 5 were related with poor prognosis, only with 3 survivors (1 without sequels). Trauma associated lesions were observed only in one patient.


Underlying host risk factors for nontuberculous mycobacterial lung disease.
Nontuberculous mycobacteria (NTM) are environmental microbes that cause a variety of human diseases, particularly chronic lung infections. Despite the fact that NTM are widespread in the environment, relatively few people develop NTM lung disease, suggesting intrinsic vulnerability in some individuals. This paper reviews the evidence that underlying disorders predispose to NTM lung disease, in particular primary conditions that result in bronchiectasis, chronic obstructive pulmonary disease, α-1-antitrypsin anomalies, pneumoconiosis, pulmonary alveolar proteinosis, and frank immunosuppressive states such as that associated with the use of anti-tumor necrosis factor-α biologics, posttransplantation immunosuppression, and HIV infection. Over the past several decades, NTM lung disease has been increasingly identified in postmenopausal women with slender body habitus. Thus we will also review the clinical and experimental evidence which supports the observation that such individuals are predisposed to NTM lung disease.


Synthesis and structure-activity relationships of 4,10-dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazine derivatives: highly potent and selective AMPA receptor antagonists with in vivo activity.
The excitatory neurotransmitter glutamate interacts with ionotropic and metabotropic receptors that mediate a variety of normal signalling processes in the brain. However, excessive stimulation of these receptors appears to be involved in neurodegenerative processes, at least in animal models. Ionotropic glutamate receptors can be divided into NMDA and non-NMDA (AMPA and KA) subtypes on the basis of t heir preferential affinities for the synthetic excitatory amino acids N-methyl-D-aspartic acid (NMDA) or 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA), respectively. Although most of the early evidence favoured a role for NMDA receptors in the excitotoxic processes, it has been recognised that AMPA receptors may also be significantly involved in neuronal death. As a consequence, the synthesis of specific AMPA antagonists has raised much interest as source of potential drugs for epilepsy and acute and chronic neurodegenerative diseases. The discovery of RPR117824, a potent and selective AMPA receptors antagonist endowed with anticonvulsant and neuroprotective properties, induced growing interest on dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazine series. This review covers the main chemical course leading to the most promising compounds as well as the pharmacological properties of this original class of AMPA receptor antagonists.


A motor speech assessment for children with severe speech disorders: reliability and validity evidence.
In this article, the authors report reliability and validity evidence for the Dynamic Evaluation of Motor Speech Skill (DEMSS), a new test that uses dynamic assessment to aid in the differential diagnosis of childhood apraxia of speech (CAS). Participants were 81 children between 36 and 79 months of age who were referred to the Mayo Clinic for diagnosis of speech sound disorders. Children were given the DEMSS and a standard speech and language test battery as part of routine evaluations. Subsequently, intrajudge, interjudge, and test-retest reliability were evaluated for a subset of participants. Construct validity was explored for all 81 participants through the use of agglomerative cluster analysis, sensitivity measures, and likelihood ratios. The mean percentage of agreement for 171 judgments was 89% for test-retest reliability, 89% for intrajudge reliability, and 91% for interjudge reliability. Agglomerative hierarchical cluster analysis showed that total DEMSS scores largely differentiated clusters of children with CAS vs. mild CAS vs. other speech disorders. Positive and negative likelihood ratios and measures of sensitivity and specificity suggested that the DEMSS does not overdiagnose CAS but sometimes fails to identify children with CAS. The value of the DEMSS in differential diagnosis of severe speech impairments was supported on the basis of evidence of reliability and validity.


Asymptomatic carotid bruit in patients who undergo coronary artery surgery.
The clinical significance of the presence of carotid bruit was evaluated in 643 patients who underwent coronary artery surgery alone or in combination with other cardiac procedures. Carotid bruit was heard in 31 patients (5%) who were neurologically asymptomatic. All of them underwent coronary artery surgery without additional carotid procedures, and none of them developed neurological deficits during the postoperative period. Of the remaining 612 patients, 18 were identified as having a history of focal neurological disorders, and 9 of them had carotid bruit. All were analyzed by means of noninvasive tests and angiography. Five underwent carotid endarterectomy prior to (2 patients) and simultaneously with (3 patients) a coronary bypass procedure. Seven patients developed neurological deficits postoperatively. Most of the deficits were not lateralized or focal but diffuse, which suggests global cerebral ischemia not related to carotid disease. Only 1 patient had proven carotid obstructive disease and underwent successful carotid thrombendarterectomy 10 days postoperatively. This study, although based on limited material, supports the hypothesis that patients with asymptomatic carotid bruit can safely undergo coronary artery surgery. In the group of patients without neurological symptomatology, postoperative neurological deficits were rarely caused by occlusive carotid disease. However, patients with asymptomatic carotid bruit should be closely followed with the goal of identifying those who are at risk of developing neurological deficits.


Is fatigue associated with short-term health-related quality of life in stroke?
Tang WK, Lu JY, Chen YK, Mok VC, Ungvari GS, Wong KS. Is fatigue associated with short-term health-related quality of life in stroke? To evaluate the relation between poststroke fatigue and short-term health-related quality of life (HRQOL) in Chinese patients with first or recurrent stroke. Cross-sectional survey. Acute stroke unit of a general hospital. A total of 458 patients with acute ischemic stroke admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong. Not applicable. HRQOL was assessed with the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) at 3 months after the subjects' index stroke. Fatigue was evaluated by using the Fatigue Severity Scale (FSS). The correlation between the FSS and SF-36 scores was examined and adjusted for potential confounders, including age, sex, marital status, previous stroke, social support, global cognitive functions, neurologic deficits, and depressive symptoms. Univariate analysis revealed that fatigue was a significant correlate of all SF-36 domain scores. The magnitude of correlation was highest for the vitality domain (r=-.605, Bonferroni corrected P<.05) and lowest for the physical functioning domain (r=-.202, Bonferroni corrected P<.05). Canonic correlation analysis indicated that FSS was strongly related to the HRQOL with a loading of -.678. Increasing fatigue was associated with a lower HRQOL. The association between FSS and HRQOL remained significant in the subsequent multivariate regression analysis, having adjusted for possible confounders. These findings suggest that fatigue has an impact on short-term HRQOL in Chinese stroke patients. The early identification and treatment of fatigue may improve HRQOL of stroke patients.


ICSD diagnostic criteria for narcolepsy: interobserver reliability. Intemational Classification of Sleep Disorders.
To estimate the reliability of the diagnosis of narcolepsy after clinical interview and polysomnographic evaluation among sleep medicine doctors, before and after training in application of the International Classification of Sleep Disorders (ICSD). Videotaped semi-structured interviews of 10 patients complaining of daytime sleepiness of different etiologies. Questions referred to ICSD criteria for narcolepsy. A further series of 10 cases of narcolepsy without cataplexy were simulated, with at least a random one to three of the ICSD polysomnographic criteria at pathological levels. Seventeen doctors were required to classify each videotaped case as "ascertained," "possible," or "excluded" narcolepsy, in two sessions: one before and one after discussion of ICSD criteria. The observers were invited to confirm or exclude the diagnosis of narcolepsy in the 10 simulated cases, according to the given polysomnographic findings, before and after an agreed proposal of the interpretation of ICSD polysomnographic criteria. Interobserver reliability was calculated using Kappa statistics. N/A. Interobserver reliability of clinical judgement improved from "substantial" at baseline (Kappa 0.61) to "almost perfect" after training (Kappa 0.95). Interobserver reliability of polysomnographic findings was "fair" at baseline (Kappa 0.24), unanimous after the proposed interpretation of ICSD polysomnographic criteria. Baseline reliability of diagnostic judgement in suspected narcolepsy was found satisfactory among Italian sleep medicine doctors. Educational training, based on discussion of ICSD criteria, further improved agreement. Diagnosis based on polysomnographic findings, not reliable at baseline, needed a strict interpretation of ICSD criteria to attain standardization.


Research and development progress of radio frequency ion source for neutral beam injector at ASIPP.
Neutral beam injection (NBI) is one of the most effective tools of four auxiliary plasma heating methods for fusion plasma heating and current drive. Now, a next generation fusion device, China Fusion Engineering Test Reactor, is under design, and a large negative NBI is foreseen. In order to demonstrate the key technology and performance of a negative ion source, a negative radio frequency (RF) ion source test facility has been developed since 2017 in the Institute of Plasma Physics, Chinese Academy of Science. A prototype RF ion source with double drivers (having the same structure with an inner diameter of 200 mm) was developed and tested on the test facility to preresearch the key technology of the RF plasma generator. The driver is equipped with a water-cooled Faraday shield to protect the alumina cylinder from the plasma, and the plasma expands into the rectangular expansion chamber. The RF power of 100 kW with a frequency of 1 MHz is transferred to the RF driver by a matching unit. The characteristics of plasma discharge were studied with classical diagnostic tools, such as the Langmuir probe and water flow calorimeter. Based on the plasma performance tests, a high power of 82 kW plasma discharge for a long pulse of 1000 s was achieved. In this paper, the details of the ion source design, characteristics of plasma, and future research plan will be presented.


Effect of heat stress on the inhibition and recovery of the ribulose-1,5-bisphosphate carboxylase/oxygenase activation state.
Experiments were conducted to determine the relative contributions of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) activation state vis-a-vis Rubisco activase and metabolite levels to the inhibition of cotton (Gossypium hirsutum L.) photosynthesis by heat stress. Exposure of leaf tissue in the light to temperatures of 40 or 45 degrees C decreased the activation state of Rubisco to levels that were 65 or 10%, respectively, of the 28 degrees C control. Ribulose-1,5-bisphosphate (RuBP) levels increased in heat-stressed leaves, whereas the 3-phosphoglyceric acid pool was depleted. Heat stress did not affect Rubisco per se, as full activity could be restored by incubation with CO2 and Mg2+. Inhibition and recovery of Rubisco activation state and carbon dioxide exchange rate (CER) were closely related under moderate heat stress (up to 42.5 degrees C). Moderate heat stress had negligible effect on Fv/Fm, the maximal quantum yield of photosystem II. In contrast, severe heat stress (45 degrees C) caused significant and irreversible damage to Rubisco activation, CER, and Fv/Fm. The rate of Rubisco activation after alleviating moderate heat stress was comparable to that of controls, indicating rapid reversibility of the process. However, moderate heat stress decreased both the rate and final extent of CER activation during dark-to-light transition. Treatment of cotton leaves with methyl viologen or an oxygen-enriched atmosphere reduced the effect of heat stress on Rubisco inactivation. Both treatments also reduced tissue RuBP levels, indicating that the amount of RuBP present during heat stress may influence the degree of Rubisco inactivation. Under both photorespiratory and non-photorespiratory conditions, the inhibition of the CER during heat stress could be completely reversed by increasing the internal partial pressure of CO2 (Ci). However, the inhibition of the CER by nigericin, a K+ ionophore, was not reversible when the Ci was increased at ambient or high temperature. Our results indicate that inhibition of photosynthesis by moderate heat stress is not caused by inhibition of the capacity for RuBP regeneration. We conclude that heat stress inhibits Rubisco activation via a rapid and direct effect on Rubisco activase, possibly by perturbing Rubisco activase subunit interactions with each other or with Rubisco.


[Use of collagen with gentamycin in abdominal and thoracic surgery].
Based on an analysis of a group of 16 patients operated at the Surgical Clinic of the Third Medical Faculty, Charles University Prague the indication of collagen with gentamycin was established. Collagen with gentamycin is used locally for prophylaxis and treatment of intraabdominal and intrathoracic infections. In a group of patients it was used for prophylaxis of postoperative infections in elective abdominal operations such as plastic operations of the abdominal wall, anastomoses in the aboral part of the GIT, in operations of fistulae as part of treatment of intraabdominal abscesses and advanced cholecystitis and appendicitis. In thoracic surgery for prophylaxis of postoperative infections in plastic operations of the thoracic wall and also after surgery on account of inflammatory complications (lung abscess, bronchopleural fistula).


Feto-placental vascular dysfunction as a prenatal determinant of adult cardiovascular disease.
Low birthweight is associated with increased rates of coronary heart disease, stroke, hypertension and non-insulin-dependent diabetes during adult life. This is thought to be the consequence of a 'programming', whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may, hence, result from adaptations to a condition where placental nutrient supply fails to match fetal demand. Recently, compensatory feto-placental up-regulation of the nitric oxide system during fetal growth restriction (FGR) was shown. Particularly, restricted hypoxic fetuses present an elevation of nitrites and a reduction of asymmetric dimethylarginine. S-nitrosohemoglobin is consumed under hypoxic conditions. These events are followed by nitric oxide pathway down-regulation postnatally, increasing susceptibility to cardiovascular disorders later in life. The relative hyperoxia would favor any such occurrence through depletion of tetrahydrobiopterin secondary to oxygen radical formation. This concept may lead to new therapeutic strategies, based on tetrahydrobiopterin supplementation, free-radical scavenging, L-arginine administration and/or inhaled NO therapy in FGR hypoxic newborns, to improve their postnatal adaptation and to reduce the risk of metabolic pathologies in adult age.


Plyometric vs. isometric training influences on tendon properties and muscle output.
The purpose of this study was to concurrently determine the effect that plyometric and isometric training has on tendon stiffness (K) and muscle output characteristics to compare any subsequent changes. Thirteen men trained the lower limbs either plyometrically or isometrically 2-3 times a week for a 6-week period. Medial gastrocnemius tendon stiffness was measured in vivo using ultrasonography during ramped isometric contractions before and after training. Mechanical output variables were measured using a force plate during concentric and isometric efforts. Significant (p < 0.05) training-induced increases in tendon K were seen for the plyometric (29.4%; 49.0 +/- 10.8 to 63.4 +/- 9.2 N x mm(-1)) and isometric groups (61.6%; 43.9 +/- 2.5 to 71.0 +/- 7.4 N x mm(-1)). Statistically similar increases in rate of force development and jump height were also seen for both training groups, with increases of 18.9 and 58.6% for the plyometric group and 16.7 and 64.3% for the isometric group, respectively. Jump height was found to be significantly correlated with tendon stiffness, such that stiffness could explain 21% of the variance in jump height. Plyometric training has been shown to place large stresses on the body, which can lead to a potential for injury, whereas explosive isometric training has been shown here to provide similar benefits to that of plyometric training with respect to the measured variables, but with reduced impact forces, and would therefore provide a useful adjunct for athletic training programs within a 6-week time frame.


Spatiotemporal expression of cochlin in the inner ear of rats during postnatal development.
Cochlin (encoded by COCH) constitutes 70% of non-collagenous protein in the inner ear, and the expression of cochlin is highly specific to the inner ear. Eleven missense mutation and one in-frame deletion have been reported in the COCH gene, causing hereditary progressive sensorineural hearing loss and vestibular dysfunction, DFNA9. These data imply that cochlin should bear an essential and crucial role in the inner ear function. However, the role of cochlin has not been fully clarified. We have investigated the spatiotemporal expression of cochlin in the inner ear of rats during postnatal development to better understand the functional role of cochlin. By immunohistochemistry, cochlin expression was faint in the cochlea and vestibule on the 6th day after birth (DAB6). At DAB70, strong expression of cochlin was detected in the spiral limbus and spiral ligament within the cochlea, and in the stromata of the maculae of otolithic organs and crista ampullaris within the vestibule. Immunoreactivity for cochlin increased during the postnatal development. Western blot analysis also showed an increase in the expression of cochlin isoforms. Furthermore, the dominant isoform of cochlin expressed changed from p63s to p40s between DAB24 and DAB70. These results suggest that the expression of cochlin may be related to the maturation of inner ear function, and the change in isoforms of cochlin expressed will provide important insight into the understanding of both cochlin function and formation of cochlin isoforms. This is the first to report about the spatiotemporal expression of cochlin in the developing rat inner ear.


[Prognostic study of 229 follicular lymphoma patients treated with rituximab combined with chemotherapy].
Objective: To explore the clinical characteristics of follicular lymphoma (FL) in the era of rituximab combined with chemotherapy and the prognostic significance of the follicular lymphoma international prognostic index (FLIPI), follicular lymphoma international prognostic index 2 (FLIPI2), international prognostic index (IPI), revised international prognostic index (R-IPI), National Comprehensive Cancer Network international prognostic index (NCCN-IPI) among Chinese patients. Methods: 229 FL patients who were treated initially with rituximab combined with CHOP-like (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy from November 2008 to April 2018 were analyzed retrospectively and all were scored by the above clinical index. Univariate and multivariate survival analysis were performed on 201 patients who completed the treatment and were followed regularly. Results: In the univariate survival analysis, age>60 years, hemoglobin<120 g/L, elevated serumβ(2)- macroglobulin, involvement of bone marrow and elevated CRP were the risk prognostic factors for overall survival (OS) and progression free survival (PFS). Moreover, the analysis of the OS and PFS between rituximab (R) maintenance (RM) group and non-maintenance (non-RM) group showed that the OS and PFS of RM group were better than those of non-RM. In the multivariate analysis of OS, hemoglobin<120 g/L, involvement of bone marrow, elevated CRP and non-RM were independent prognostic factors. In the multivariate analysis of PFS, hemoglobin<120 g/L, CRP and non-RM were independent prognostic factors. When FLIPI2 was included in the multivariate analysis, CRP and FLIPI2 were independent prognostic factors in both OS and PFS, and non-RM was independent prognostic factors in PFS. Conclusion: FLIPI2 is the better risk stratification in FL patients in the era of rituximab.


Entrance skin dose measured with MOSFETs in children undergoing interventional radiology procedures.
Interventional procedures frequently employ fluoroscopy or digital subtraction angiography (DSA). Few studies have documented radiation doses received by children during these procedures. To measure skin entrance dose received during common pediatric interventional procedures. MOSFET dosimeters were placed to record skin doses in 143 children undergoing any of five procedures: 30 PICC insertions, 34 CVL/port insertions, 30 G/GJ tube insertions, 25 sclerotherapy/vascular anomaly procedures, 24 cerebral angiography procedures. The highest recorded dose (HRD) from the five MOSFET probes was assumed to be the peak skin dose per child. HRD values were averaged for children within each group and correlated with patient weight, fluoroscopy time and number of DSA frames. Average HRD was 1.8 mGy for PICC insertions, 1.4 mGy for CVL/port insertions, 3.9 mGy for G/GJ tube insertions, 39.1 mGy for sclerotherapy/vascular anomaly procedures, and 149.9 and 101.6 mGy for frontal and lateral portions of cerebral angiography procedures. These entrance doses corresponded to effective dose estimates in the range 0.4-3 mSv. There were only modest correlations between peak skin dose and fluoroscopy time, patient weight and DSA frames (r (2)<0.4, P < 0.01). Pediatric interventional procedures are associated with a wide range of doses; those at the higher end require careful monitoring.


Do aphids actively search for ant partners?
The aphid-ant mutualistic relationships are not necessarily obligate for neither partners but evidence is that such interactions provide them strong advantages in terms of global fitness. While it is largely assumed that ants actively search for their mutualistic partners namely using volatile cues; whether winged aphids (i.e., aphids' most mobile form) are able to select ant-frequented areas had not been investigated so far. Ant-frequented sites would indeed offer several advantages for these aphids including a lower predation pressure through ant presence and enhanced chances of establishing mutuaslistic interactions with neighbor ant colonies. In the field, aphid colonies are often observed in higher densities around ant nests, which is probably linked to a better survival ensured by ants' services. Nevertheless, this could also result from a preferential establishment of winged aphids in ant-frequented areas. We tested this last hypothesis through different ethological assays and show that the facultative myrmecophilous black bean aphid, Aphis fabae L., does not orientate its search for a host plant preferentially toward ant-frequented plants. However, our results suggest that ants reduce the number of winged aphids leaving the newly colonized plant. Thus, ants involved in facultative myrmecophilous interactions with aphids appear to contribute to structure aphid populations in the field by ensuring a better establishment and survival of newly established colonies rather than by inducing a deliberate plant selection by aphid partners based on the proximity of ant colonies.


Evaluation of toluene exposure via drinking water on levels of regional brain biogenic monoamines and their metabolites in CD-1 mice.
Toluene, a potentially neurotoxic substance, is found in trace amounts in groundwater. Adult male CD-1 mice were continuously fed drinking water ad libitum containing 0, 17, 80, and 405 mg/liter toluene. After a 28-day treatment, animals were tested for endogenous levels of the biogenic monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their respective metabolites. 3-methoxy-4-hydroxymandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in six discrete brain regions. The maximum toluene-induced increases of biogenic amines and their metabolites generally occurred at a toluene concentration of 80 mg/liter. In the hypothalamus, a major NE-containing compartment, the concentrations of NE significantly increased by 51, 63, and 34% in groups dosed with 17, 80, and 405 mg/liter, respectively. Significant increases of NE were also observed in the medulla oblongata and midbrain. Concomitantly, concentrations of VMA increased in various brain regions. Concentrations of DA were significantly higher in the corpus striatum and hypothalamus. Alterations in levels of DA metabolites, DOPAC and HVA, were marginal. Toluene significantly increased concentrations of 5-HT in all dissected brain regions, except cerebellum, and increased the 5-HIAA levels in the hypothalamus, corpus striatum, and cerebral cortex.


Metabolism of monoepoxides of methyl linoleate: bioactivation and detoxification.
Leukotoxin (ltx) and isoleukotoxin (iltx) methyl esters, are metabolites of methyl linoleic acid, an essential fatty acid. They have been associated with acute respiratory distress syndrome. The observed toxicity of ltx and iltx is, in fact, due to the metabolism of the epoxides to their corresponding diols by soluble epoxide hydrolase (sEH). Herein, we demonstrate that ltx/iltx are toxic in a time-dependent manner to human sEH expressing cells with a LT(50) of 10.6 +/- 0.8 h and that ltx and iltx have K(M) of 6.15 +/- 1.0 and 5. 17 +/- 0.56 microM, respectively, and V(max) of 2.67 +/- 0.04 and 1. 86 +/- 0.06 micromol/min/mg, respectively, which can be inhibited by sEH inhibitors. We show that four major metabolites of ltx/iltx are formed in our system, including ltx/iltx free acid, ltxd/iltxd, free acid, and phosphotidylcholine and phosphotidylethanolamine containing the carboxylic acid forms of both ltx/iltx and ltxd/iltxd, but that the only metabolite associated with toxicity is the carboxylic acid form of ltxd/iltxd, suggesting the involvement of cellular esterases. We demonstrate that a serine esterase inhibitor provides some protection from the toxicity of epoxy fatty esters to sEH expressing cells as do intercellular free sulfhydryls, but that this protection is not due to glutathione conjugation. With these data, we have proposed an extension of the metabolic pathway for ltx/iltx in eukaryotic cells.


Complexity complicates lean: lessons from seven emergency services.
The purpose of this paper is to explain how different emergency services adopt and adapt the same hospital-wide lean-inspired intervention and how this is reflected in hospital process performance data. A multiple case study based on a realistic evaluation approach to identify mechanisms for how lean impacts process performance and services' capability to learn and continually improve. Four years of process performance data were collected from seven emergency services at a Swedish University Hospital: ear, nose and throat (ENT) (two), pediatrics (two), gynecology, internal medicine, and surgery. Performance patterns were linked with qualitative data collected through realist interviews. The complexity of the care process influenced how improvement in access to care was achieved. For less complex care processes (ENT and gynecology), large and sustained improvement was mainly the result of a better match between capacity and demand. For medicine, surgery, and pediatrics, which exhibit greater care process complexity, sustainable, or continual improvement were constrained because the changes implemented were insufficient in addressing the higher degree of complexity. The variation in process performance and sustainability of results indicate that lean efforts should be carefully adapted to the complexity of the care process and to the educational commitment of healthcare organizations. Ultimately, the ability to adapt lean to a particular context of application depends on the development of routines that effectively support learning from daily practices.


MS-2 fibrosarcoma characterization by laser induced autofluorescence.
MS-2 fibrosarcoma implanted in BALB-CDF1 mice was investigated by frequency and time domain measurements of the autofluorescence (AF) radiation emitted upon excitation by a N(2) laser beam (337.1 nm). AF spectra were obtained by using a spectrograph, a multichannel plate and an optical multichannel analyzer for the steady state detection. Time-resolved spectra were performed by means of a monochromator, a photomultiplier, and a digital signal analyzer. Spectral measurements show that the autofluorescence intensity of pathologic tissue is lower than that of healthy one in the 400- to 500- spectral region. In the same spectral range, we found the fluorescence decay to be the sum of a fast and a slow component. The lifetime of the fast component of tumoral tissue is significantly lower than that of healthy samples. Frequency and time domain measurements used in combination show that MS2-fibrosarcoma is characterized by the probable presence of the free form of NADH.


Copper Deficiency: Causes, Manifestations, and Treatment.
The metabolism of the essential trace element copper remains incompletely understood and, until recently, nearly ignored in acute medicine. Menkes disease was for long the only known copper deficiency condition, but several case reports and investigations conducted over the last 2 decades have shown that deficiency is more frequent than previously suspected, with devastating individual consequences and potential public health consequences. The copper needs in healthy individuals are 0.9 mg/d, which translates to 0.3 mg/d intravenously in parenteral nutrition; the present review aims at gathering actual knowledge. A review of literature was conducted in PubMed and Cochrane systematic reviews to identify the most recent information about copper deficiency and generate a narrative review. Copper deficiency has hereditary and acquired origins, the latter being the most frequent. Clinical manifestations are nonspecific but affect all organs and systems, particularly the hematologic (anemia) and the neurologic (myeloneuropathy) systems. Deficiency also affects the cardiovascular, cutaneous, and immune systems. Severe copper deficiency due to reduced absorption after bariatric bypass surgery has become frequent. Deficiency is more frequent than previously recognized, probably because of changing nutrition patterns but also because of some treatments that have become very common such as bypass bariatric surgery and, in acute medicine, prolonged continuous renal replacement therapy. The patients may present with severe hematologic and neurologic complications that go untreated because copper deficiency was not considered in the differential diagnosis: These complications often need active intravenous repletion with doses 4-8 times the usual nutrition recommendations.


The evolution of synapse models--from numbers to networks to spaces.
We review the evolution of synapse models over the last sixty-five years in terms of the changing paradigms: initially, the synapse was modelled only as part of a neuronal system, both as a number (weight of an edge in a connectionist network) and as a channel in a conductance-based model. With the availability of more structural and kinetic data, it came to be seen as a full-fledged biochemical network, accompanied by a shift from the previous "top-down" approach to a more "bottom-up" network reconstruction. Most recently, the synapse is seen as a geometric 3-dimensional space with various processes driving the dynamics. A particular focus is placed on models of the dopamine synapse and their connections to schizophrenia. The advances of detailed modelling on the synaptic level have highlighted the challenges of integrating the various functional levels, which are tightly coupled with processes on different scales in time and space. On the other hand, this effort will contribute to bridging the currently perceived gap between computational neuroscience and (computational) systems biology.


A dual-purpose guide for optimum placement of dental implants.
Correct placement of implants is a requirement for implant treatment. The use of computed tomography and precise surgical guides is required when inadequate bone support is anticipated. This article describes the fabrication and use of an acrylic resin dual-purpose guide for radiographic evaluation of recipient sites and implant placement, which uses internally stacked stainless steel surgical guide channels. The drill guides are machined to allow consecutive surgical drills to be used without changing the implant angulation during surgery.


In vivo assessment of stent recoil in normal porcine arteries: evaluation of contemporary stent designs.
Acute stent recoil has been observed following balloon deflation in normal and diseased coronary arteries, and the magnitude varies by stent design. We sought to evaluate acute stent recoil in five new stents. Twenty-five stents (four Crown, five Nir Conformer Royale, five Crossflex, five SupraG, and six GFX) were implanted in six Yorkshire pigs. All stents were expanded using a noncompliant balloon (balloon:artery ratio 1.2:1.0). Continuous ultrasound imaging was performed during stepwise balloon inflation and deflation using a 0.018" imaging core. Maximum cross-section areas (CSA) and minimal luminal diameter (MLD) were measured at 12 atm and immediately following balloon deflation. Maximum stent CSA matched expected balloon CSA. Area and diameter recoil were calculated as 1 - (CSAdeflation/CSAmax) and 1 - (MLDdeflation/MLDmax), respectively. Upon deflation, all stents showed recoil from maximal CSA. Area recoil was significantly lower for slotted-tube stents than modular stents (12.6% +/- 1.6% vs. 23.2 +/- 3.5%; P < 0.05). In compliant, nonatherosclerotic porcine coronary arteries, acute stent recoil for the four slotted-tube designs ranged from 8.4% to 18.0% by area. The modular stent tested was associated with significantly greater acute recoil than the slotted-tube stents.


Statistical mechanics of supercoils and the torsional stiffness of the DNA double helix.
The distribution of closed unknotted polymer chains over the writhing number is calculated by the Monte-Carlo method. For circular duplex DNA the variance of the distribution equals approximately half the observed variance of equilibrium distribution over the linking number. The balance which arises from fluctuations in DNA twisting makes it possible to estimate the torsional stiffness of the double helix.


Endoscopic transnasal resection of ameloblastoma with intracranial extension.
Ameloblastoma is a rare odontogenic tumor with characteristics of epithelial tissue that produces enamel for the developing tooth. This lesion is generally considered benign, but has malignant forms that invade locally and metastasize. We present a 60-year-old man with maxillary ameloblastoma that after multiple recurrences developed intracranial extension with dural involvement of the middle cranial fossa and was treated by endoscopic transnasal resection followed by radiation therapy. Our technique and intraoperative findings are described with a review of the literature on intracranial ameloblastoma. This patient represents a unique account of endoscopic transnasal resection being utilized in the treatment of intracranial extension of ameloblastoma and demonstrates potential for application in similar cases.


Inhibition of fast- and slow-phase depolarization-dependent synaptosomal calcium uptake by ethanol.
Uptake of 45Ca++ by synaptosomes isolated from cerebral cortex, cerebellum, midbrain and brain stem of male, Sprague-Dawley rats was measured at 1-, 3-, 5-, 15-, 30- and 60-sec time periods. At 1 sec, the Ca++ uptake rate by cerebrocortical synaptosomes was 1.45 mumol/sec/g of protein, whereas the 60-sec rate was 0.03 mumol/sec/g of protein. In vitro addition of ethanol, 80 mM, inhibited depolarization-dependent (65 mM KCl) 45Ca++ uptake by synaptosomes but the time-response relationships varied depending upon the brain region studied. In cerebrocortical synaptosomes, ethanol significantly inhibited only the fast-phase component of 45Ca++ uptake (1 and 3 sec). Ethanol inhibited 45Ca++ uptake by midbrain synaptosomes at all measurement times studied (1, 3, 5 and 15 sec), whereas in cerebellum and brain stem ethanol inhibited 45Ca++ uptake at 3- and 5-sec time periods. Ethanol at concentrations of 25, 50, 100 and 150 mM inhibited 45Ca++ uptake by 9.0, 15.9, 24.8 and 30.7%, respectively, in cerebrocortical synaptosomes. In vitro ethanol, 80 mM, added to cerebrocortical synaptosomes isolated from rats fed a nutritionally adequate liquid ethanol diet did not significantly inhibit depolarization-dependent 45Ca++ uptake. The results of this study show that pharmacologically relevant ethanol concentrations inhibit voltage-dependent 45Ca++ uptake into synaptosomes. This inhibitory action may, at least in part, underlie some of the intoxicating effects of ethanol. In addition, chronic administration of ethanol resulted in an apparent adaptive response such that addition of ethanol no longer blocked 45Ca++ uptake. This adaptive response involving the calcium channel may represent a cellular mechanism for functional tolerance development.


Genetics of blood-injury fears and phobias: a population-based twin study.
Data on unreasonable fears of blood, needles, hospitals, and illness (BNHI) were collected by telephone interview from 541 MZ and 388 DZ pairs of female twins from the population-based Virginia Twin Registry. BNHI phobia was defined as the presence of fear accompanied by interference. Age at onset of phobia was found to be very similar to that of situational phobias previously assessed in the sample. Using a multiple threshold model, we found no evidence for qualitative differences between BNHI fears and BNHI phobia. The familial aggregation of fears appears to be entirely due to additive genetic variance. The possible exception to this is fear of illness, which, like BNHI phobias, seems to aggregate within families because of shared environmental factors. Although power to discriminate between the causes of familial resemblance is low, results suggest that random traumatic events and some social learning may be responsible for the onset of BNHI phobias. About two-thirds of variance is individual-specific environmental, and could include genotype x environment interaction and measurement error.


Cyclin and cyclin-dependent kinase expression in the remnant glomerulus.
Recent studies suggest that subtotal renal ablation is associated with an early phase of mesangial cell proliferation. Because the mechanism(s) responsible for this response have not been elucidated, the study presented here sought to determine if changes in expression of positive cell cycle regulators, including pRb, cyclin E, and cdk2, occurred in the glomerulus during the early period of compensatory renal hypertrophy that follows 5/6 renal ablation. A first group of rats underwent sham operation and served as the control group. A second group of rats underwent 5/6 renal ablation. Ninety-six hours after subtotal ablation, protein was extracted from sieved glomeruli for Western blot analysis of proliferating cell nuclear antigen (PCNA) and retinoblastoma protein expression (pRb). RNA was extracted from sieved glomeruli for Northern blot analysis of cyclin E and cdk2 mRNA levels, and renal cortical tissue was subjected to immunohistochemical analysis of PCNA. On average, one PCNA-positive nucleus was present every 22 glomerular profiles in normal rats. The number of PCNA-positive nuclei increased fivefold in glomeruli, 96 h after renal ablation (P < 0.05). pRb was present only in the unphosphorylated state in normal glomeruli, but the increase in PCNA was accompanied by the appearance of phosphorylated pRb in remnant glomeruli. mRNA levels for cyclin E increased twofold in remnant glomeruli, whereas mRNA levels for cdk2 were unchanged. It was concluded that renal ablation leads to cell cycle progression in the glomerulus and an increase in the G1 cyclin, cyclin E, is associated with the appearance of phosphorylated retinoblastoma protein.


Estimating neonatal mortality risk: an analysis of clinicians' judgments.
Clinicians' estimates of mortality risk in the neonatal intensive care unit (NICU) have implications for patient triage, transfer, initiation and termination of life support, and allocation of medical resources. The accuracy of these judgments has not been studied, nor the differences between nurses and attending physicians. 1) evaluate the accuracy of subjective judgments of NICU unit mortality risk, 2) identify the key components of clinician judgments, 3) compare accuracy between attending physicians and nurses, and 4) examine the utility of combining an objectively computed risk and clinician judgments to improve predictions. We obtained estimates of mortality risk on 544 admissions to two NICUs on the day of admission from the attending physician and primary nurse. These were compared with an objective computed mortality risk based on birth weight and the Score for Neonatal Acute Physiology (SNAP) using a linear judgment analysis model, as well as with actual outcomes. Physicians and nurses had good discriminating power with actual mortality rates ranging from 0% among low risk patients to 67% among those with the highest mortality estimates. Physicians had a tendency to overestimate mortality risk. Clinicians base their estimates on the same factors and similar judgment weights as the empiric mortality risk model (22% birth weight, 62% illness severity (SNAP), 13% low Apgar, and 3% for intrauterine growth restriction). Clinicians place additional emphasis on therapeutic as well as physiologic factors. When the computed risk and physician judgment were combined, both made significant contributions in a logistic mortality risk model. Clinician judgments of mortality risk are fairly accurate and similar to an objective illness severity index. This simple method provides insight into clinical decision making and has important applications in improving direct patient care, appropriate allocation of medical resources, and medical training.


"Knowing that I'm not alone": client perspectives on counselling for self-injury.
Self-injury is an increasingly common phenomenon among clinical and non-clinical populations. Health care providers generally recommend behavioural interventions that address coping skills for people who self-injure despite a lack of a consistent evidence base about their effectiveness. There is limited understanding about experiences of counselling for self-injury from the perspectives of clients. To understand clients' experiences of counselling for self-injury. Ten interviews were conducted, audio-recorded and transcribed. Data were analysed using Grounded Theory (GT). One central category, "Developing a healing reconnection with self and others" and four categories: (i) Building trust; (ii) seeing beyond the cutting; (iii) human contact and (iv) integrating experiences. Overcoming self-injury is possible within the context of a trusting and accepting therapeutic relationship. Participants perceived counselling to be helpful when counsellors were willing to work with underlying issues rather than focus primarily on the cessation of self-injury. Counsellors and mental health practitioners must look beyond the behaviour to meet with the person and facilitate the development of a therapeutic relationship, which promotes a healing reconnection with self and others.


Third-generation cephalosporins resistance in clinical isolates of Enterobacteriaceae.
Seven clinical isolates of Enterobacteriaceae resistant to third-generation cephalosporins were investigated in order to assess the role played in resistance by permeability barrier and by beta-lactamase production. The addition of subinhibitory concentrations of EDTA increased susceptibility to ceftriaxone in five strains showing that the permeability barrier is involved. All strains produced different amounts of beta-lactamases that were always increased by cefoxitin induction. Hydrolytic activity of investigated enzymes varied in different cephalosporins; ceftriaxone and ceftazidime are the most stable compounds.


The role of maternal diabetes in repetitive spontaneous abortion.
The role of maternal diabetes as a cause of repetitive early pregnancy loss was evaluated by examining the reproductive performance of 154 diabetic patients in 489 pregnancies. The overall incidence of spontaneous abortion among gestational diabetics (12.7%) and frank diabetics (12.2%) was not significantly different from that of matched controls (10.9% and 14.5%, respectively). The frequencies of repetitive (two or more) miscarriage were also similar among both gestational diabetics versus matched controls (10.6% versus 9.1%) and frank diabetics versus matched controls (14.6% versus 16.7). It is concluded that diabetes per se is not a frequent cause of repetitive pregnancy loss and that routine glucose tolerance testing is not indicated in the evaluation of patients with a history of habitual abortion.


Genetic variation of inbreeding depression among floral and fitness traits in Silene nutans.
The magnitude and variation of inbreeding depression (ID) within populations is important for the evolution and maintenance of mixed mating systems. We studied ID and its genetic variation in a range of floral and fitness traits in a small and large population of the perennial herb Silene nutans, using controlled pollinations in a fully factorial North Carolina II design. Floral traits and early fitness traits, that is seed mass and germination rate, were not much affected by inbreeding (delta<0.2). In contrast, 'late' fitness traits and multiplicative fitness suffered severely from inbreeding (delta>0.4). Lack of genetic correlations indicated that ID in floral, early and late traits is genetically decoupled. There was a trend that the smaller population was less affected by ID than the large one, although the differences were not significant for most traits. Hence, evidence for purging of deleterious alleles remains inconclusive in this study. Genetic variation in ID among paternal families was statistically significant in most floral and all seed traits, but not in late fitness traits. However, some paternal families had delta<0.5, even in the multiplicative fitness measure that suffered most from ID (delta=0.74), suggesting that the mixed mating system of S. nutans might be evolutionary stable.


Tailoring structure-property relationships in dithienosilole-benzothiadiazole donor-acceptor copolymers.
Four new DTS-BTD copolymers (P1-P4) differing by the concentration of electron-donating and -withdrawing substituents along the backbone have been synthesized and characterized by 2D-WAXS and in bottom-contact FETs. While all copolymers can self-assemble into lamellar superstructures, only P2 and P4 show a propensity to pi-stack. P4 exhibits a hole mobility as high as 0.02 cm(2) V(-1) s(-1) in excellent agreement with the close pi-stacking and lamellar distances found by structural analysis (0.36 and 1.84 nm, respectively) and absorbs homogenously across the entire visible spectrum as solar cell applications require.


4-Piperazinyl-10H-thieno[2,3-b][1,5]benzodiazepines as potential neuroleptics.
A series of 4-substituted 10H-theino[2,3-b][1,5]benzodiazepines has been synthesized. These compounds have been assessed for their ability to block a conditioned avoidance response (CAR) and to produce catalepsy in rats and have been compared with several typical and atypical neuroleptics. The compounds which inhibit CAR at doses which produce no catalepsy are believed to cause less extrapyramidal side effects in the clinic. A number of compounds (9, 12, 17, 29, and 34) show potent neuroleptic activity, yet maintain a favorable separation of activity on these two parametrs. Three 5-piperazinyl-10H-thieno[2,3-b][1,4]benzodiazepine derivatives (46-48) analogous to compounds in the [1,5] series have been prepared for comparison and were found to be inactive.


Standardizing the clinical content of a third-year family medicine clerkship.
The increasing presence of family medicine as a required clinical experience during medical school has created a need to provide quality experiences for a large number of students. Use of community private practices is one way to address this need. An important issue with this approach is standardization of clinical content among diverse teaching sites. This paper investigates whether students on required one-month family medicine clerkships occurring at university and private practice sites obtain comparable experiences. The experiences of 185 third-year medical students were compared in the following areas: patient volume, patient mix, and performance on end-of-clerkship oral and written examinations. Of the 20 core problems seen most frequently by students, four were seen by significantly different numbers of university and private practice students overall; only two remained significantly different when analysis was restricted to the second half of the reporting period. Differences between the number of university and private practice students seeing the minimum targeted number of patients per session were nonsignificant (P = .895), as were differences between the two groups' oral and written examination scores (P = .507 and P = .595, respectively). We found that clinical content of a required third-year clerkship could be successfully standardized, as measured by patient volume, mix, and student performance on examinations.


Organic solvent-induced proximal tubular cell apoptosis via caspase-9 activation.
Long-term exposure to solvents is associated with apoptosis, which is implicated in the development and progression of tubulo-interstitial fibrosis and chronic renal failure. In our previous study, we demonstrated that toluene and p-xylene as the most commonly used organic solvents induced proximal tubular cells apoptosis. This study was conducted to assess the apoptotic pathway of toluene and p-xylene induced proximal tubular apoptosis. This was assessed by measuring the caspase-9 activity LLC-PK1 cells exposed to both compounds. A model of proximal tubular cell (LLC-PK1) cytotoxicity exposed to 1mM of either p-xylene or toluene was compared to untreated control for caspase-9 activity and Bax/Bcl-2 protein level. Furthermore, DNA fragmentation in the presence of caspase-9 inhibitor (Z-LEHD-FMK) in a dose-dependent manner was assessed. Both compounds induced caspase-9 activity, which was accompanied by up-regulation of Bax, whereas Bcl-2 level did not change. DNA fragmentation induced by both solvents was inhibited by caspase-9 inhibitor in dose-dependent manner. This data suggest that p-xylene or toluene induces nephrotoxicity via mitochondrial caspase-9 pathway. This mechanism involves up-regulation of the apoptotic protein, Bax.


Genetic variants of thyroxine-binding globulin (TBG).
New genetic variants of decreased TBG binding capacity observed in our studies are described and discussed in relation to previously reported variant types. Although single factor inheritance may explain the strikingly different phenotypes found in X-linked variants it cannot explain the wide variation discerned in the majority of individuals in our control population or the phenomenon of nonpentrance in one of our families. TBG binding capacity may be a polygenic trait with many loci contributing to the observed phenotypes.


Interdependent Diversities: Reflections on the Community-Diversity Dialectic.
This commentary reflects on the Community-Diversity Dialectic, summarizing its development and reviewing its impact on community psychology research and practice. Two contemporary examples are presented to illustrate both the possibilities of and challenges to bridging the gap between sense of community and diversity: the rise of the so-called "alt-right" on the one hand, and the popularity of Pokémon Go on the other. The article concludes with a brief discussion of Kurt Lewin's contributions to group dynamics theory, recommending that an emphasis on our interdependent fates and goals is paramount to reconciling the tensions between sense of community and diversity that persist in an increasingly complex multicultural world.


Retrospective analysis of patients clinical manifestations before and after pheochromocytoma surgery.
A retrospective analysis of presurgical clinical picture and blood pressures of 34 patients with histologically verified pheochromocytoma. Assessment of clinical state, blood pressure and prognosis in the course of patients control hospitalizations from 2001 to 2002. The study was designed as a synoptic one, based on a retrospective analysis of 34 patients records with histologically verified pheochromocytoma (26 women and 8 men). Our assessments of clinical symptomatology, maximum paroxysmal hypertension values, average blood pressure values in patients with persistent arterial hypertension, arterial hypertension grade and circadian index were based on patients records. Patients epinephrectomies were followed during their control hospitalizations to assess their clinical state. Their blood pressures were evaluated by means of their circadian monitoring. From the 34 patients, 21 were diagnosed with solitary pheochromocytomas. The circadian index persistence analysis prior to the surgery was associated with circadian blood pressure monitoring in 21 patients. It was lost in 57% of patients. During their control hospitalization as many as 82% of patients preserved their circadian blood pressure variability with a more than 10% decrease in the night time, 5 patients did not preserve their circadian blood pressure variability. Seven from the original 34 patients died: Three of them died from their primary disease, one 63-year old man died from shock following tumour extirpation. The death of other 3 patients was not associated with their primary disease. Long-lasting survival of patients with pheochromocytoma after surgical treatment--except for those with malignant disease--was demonstrated. Although our assessment of the resulting treatment effects was positive, a long-term follow-up is inevitable because of a difficult pathologic-anatomical verification of the malignant nature of the disease as well as of the risk of tumour relapse assessment. (Tab. 1, Fig. 5, Ref 36.)


The venous pump of the first metatarsophalangeal joint: clinical implications.
Although the anatomy and physiology of the venous circulation of the ankle and midfoot are well documented, the physiologic importance of forefoot mobility has not been reported in the literature. The question of this study was whether the first metatarsophalangeal (MTP) joint may operate, like the ankle, as a "pump" to encourage venous return. Forty-nine cadaver foot specimens were examined using dissection, plastination, vessel infiltration, and maceration, and radiographic (including venography, MRI, and magnetic resonance angiography) techniques. The anatomy and physiology were described and compared to the ankle joint. Forty patients had biphasic Doppler flow studies. The major finding was the medial drainage of the plantar venous sinus, which is fibrotically bound to the joint capsule. Functional venous valves were evident distally and within fibrous vascular lumens. Mobilization of the first MTP joint led to compression and emptying of the veins. Passive mobilization of the first MTP joint led to an average flow increase of 55% +/- 7 (p < 0.0001), while active movement led to an average increase of 78% +/- 7 (p < 0.0001). Our described connection between the joint capsule and veins indicates a "toe-ankle pump" with a significant increase of venous blood flow during motion of the MTP joint. Possible clinical applications for an external MTP pump include anti-edema or thromboprophylactic therapy, especially in patients with foot or ankle injuries. A new toe-pump has been designed based on these results.


Pressure mapping to assess seated pressure distributions and the potential risk for skin ulceration in a population of sledge hockey players and control subjects.
Ice sledge (or sled) hockey is a fast-paced sport that enables individuals with physical disabilities to play ice hockey. As the attraction to the sport continues to rise, the need for developing better equipment and installing preventative measures for injury will become increasingly important. One such injury includes skin pressure ulceration. A total of 26 subjects including active controls and those with spinal cord injury, multiple sclerosis, limb amputation and traumatic brain injury were studied using a pressure mapping device at the 2012 National Disabled Veterans Winter Sports Clinic to determine the risk for skin pressure ulceration and the impact of cushioning and knee angle positioning on seated pressure distributions. Sledge hockey athletes may be at increased risk for skin pressure ulceration based on seated pressure distribution data. This experiment failed to demonstrate a benefit for specialty cushioning in either group. Interestingly, knee angle positioning, particularly, knee extension significantly lowered the average seated pressures. When considering the risk for skin pressure ulceration, knee angle positioning is of particular clinical importance. More research is warranted, specifically targeting novel cushion and sledge designs and larger groups of individuals with sensory loss and severe spinal deformities. Implications for Rehabilitation Ice sledge (or sled) hockey is a fast-paced and growing adaptive sport played at the Paralympic level. Rehabilitation professionals should consider the potential for skin ulceration in this population of athletes. The effects of cushioning used in the sledge design warrants further investigation. Knee angle positioning; particularly, knee extension significantly lowers seated pressures and may reduce the potential for skin ulceration.


How registered nurses, licensed practical nurses and resident aides spend time in nursing homes: An observational study.
Calls for improved conditions in nursing homes have pointed to the importance of optimizing the levels and skills of care providers. Understanding the work of care providers will help to determine if staff are being used to their full potential and if opportunities exist for improved efficiencies. To explore the activities of care providers in different nursing homes and to identify if variations exist within and across homes and shifts. A multi-centre cross-sectional observational work flow study was conducted in seven different nursing homes sites in one Canadian province. Data were collected by a research assistant who conducted 368 h of observation. The research assistant collected data by following an identical route in each site and recording observations on staff activities. Findings indicate staff activities vary across roles, sites and shifts. Licensed practical nurses (nursing assistants) have the greatest variation in their role while registered nurses have the least amount of variability. In some sites both registered nurses and licensed practical nurses perform activities that may be safely delegated to others. Care providers spend as much as 53.7% of their time engaged in non-value added activities. There may be opportunities for registered nurses and licensed practical nurses to delegate some of their activities to non-regulated workers. The time care providers spend in non-value activities suggest there may be opportunities to improve efficiencies within the nursing home setting.


Thermal ablation of hepatocellular carcinoma in patients with abnormal coagulation function.
To evaluate the safety of thermal ablation for hepatocellular carcinoma (HCC) in patients with abnormal coagulation function. Fifty-seven HCC tumours in 50 patients were treated with thermal ablation. All patients had a meted platelet count <50 × 109/L or international normalised ratio (INR) ≥ 1.7. Gastroscopy before ablation, platelet concentrate or fresh frozen plasma transfusion during ablation and contrast enhanced ultrasoundgraphy (CEUS)-guided ablation to cease needle tract bleeding were performed to reduce haemorrhage. The incidences of haemorrhage and other major complications were recorded and patients were followed up to observe the local tumour progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS) and recurrence-free survival (RFS) rates. Two incidences of needle tract bleeding and one needle tract bleeding together with bleeding at the suture of the spleen fossa were found. Three needle tract bleeding events were detected by CEUS and ceased after CEUS-guided complementary ablation. CEUS failed to detect bleeding at the suture of the spleen fossa. Therefore, a laparotomy was conducted for haemostasis. No other major complications were found after ablation. The median follow-up periods were 18.7 ± 12.0 months (range 1 ∼ 42 months) and 1 LTP and 15 IDRs occurred. The 1-, 2- and 3-year OS rates were 84.8%, 82.7% and 82.7%, and RFS rates were 67.9%, 64.0% and 64.0%, respectively. With gastroscopy before ablation, platelet concentrate or fresh frozen plasma transfusion during ablation and CEUS-guided ablation to cease needle tract bleeding, thermal ablation is a safe treatment for HCC in patients with abnormal coagulation function.


Catatonia associated with disulfiram therapy.
This is the first report of a catatonic syndrome occurring in a patient receiving disulfiram treatment. A causal relationship is strongly suggested by the mode of onset, the absence of a previous history of catatonia, and the rapid resolution of the syndrome within 72 hours of discontinuance of the disulfiram therapy. Neurophysiological mechanisms which aid in elucidating the role of disulfiram in the etiology of catatonia are discussed. It is important that physicians be alerted to this serious, potentially lethal, complication, as it is readily reversible if the disulfiram is discontinued and appropriate supportive measures are taken. Also, it appears that these patients may be more susceptible to complications with future disulfiram usage and should be strongly counseled to seek alternative therapies for their alcohol problems in the future.


Lead toxicity, defense strategies and associated indicative biomarkers in Talinum triangulare grown hydroponically.
Talinum species have been used to investigate a variety of environmental problems for e.g. determination of metal pollution index and total petroleum hydrocarbons in roadside soils, stabilization and reclamation of heavy metals (HMs) in dump sites, removal of HMs from storm water-runoff and green roof leachates. Species of Talinum are popular leaf vegetables having nutrient antinutrient properties. In this study, Talinum triangulare (Jacq.) Willd (Ceylon spinach) grown hydroponically were exposed to different concentrations of lead (Pb) (0, 0.25, 0.5, 0.75, 1.0 and 1.25 mM) to investigate the biomarkers of toxicity and tolerance mechanisms. Relative water content, cell death, photosynthetic pigments, sulphoquinovosyldiacylglycerol (SQDG), anthocyanins, α-tocopherol, malondialdehyde (MDA), reactive oxygen species (ROS) glutathione (GSH and GSSG) and elemental analysis have been investigated. The results showed that Pb in roots and shoots gradually increased as the function of Pb exposure; however Pb concentration in leaves was below detectable level. Chlorophylls and SQDG contents increased at 0.25 mM of Pb treatment in comparison to control at all treated durations, thereafter decreased. Levels of carotenoid, anthocyanins, α-tocopherol, and lipid peroxidation increased in Pb treated plants compared to control. Water content, cells death and elemental analysis suggested the damage of transport system interfering with nutrient transport causing cell death. The present study also explained that Pb imposed indirect oxidative stress in leaves is characterized by decreases in GSH/GSSG ratio with increased doses of Pb treatment. Lead-induced oxidative stress was alleviated by carotenoids, anthocyanins, α-tocopherol and glutathione suggesting that these defense responses as potential biomarkers for detecting Pb toxicity.


Assessments of trust in intimate relationships and the self-perception process.
Assessments of trust in intimate relationships are often based on perceptions of a partner's behaviors; however, people's own actions, increased self-awareness, and individual differences (e.g., exchange or communal orientation) may also affect their trust in their partners. Communally or exchange-oriented members of heterosexual dating couples, students in a U.S. university, displayed either trusting or irrelevant behaviors under conditions of increased self-awareness. They then completed measures of interpersonal trust. The participants' trusting behaviors significantly determined their level of trust; heightened self-awareness and a communal orientation further enhanced the participants' trust in their partners.


Frequency of upper gastrointestinal lesions in patients with liver cirrhosis.
The frequency of gastroduodenal lesions has been investigated in 142 patients with liver cirrhosis of various degrees of severity and in 63 patients with mild liver disease (controls) in whom liver biopsy excluded nodular regeneration. Cirrhotic patients were subdivided in three groups according to the Pugh modification of the Child-Turcotte criteria. Although the frequency of peptic ulcer was not different, gastroduodenal erosions were observed more frequently in cirrhotics than in controls (29.6% vs 11.1%, P less than 0.01). The occurrence of erosions was related to the severity of the disease: in Child A and B patients their frequency was 21 and 26% respectively, but rose to 48.4 (15 of 31 vs 7 of 63 in controls, P less than 0.001) in the Child C group. Both mild and severe gastroduodenitis occurred more frequently, although not significantly, in patients with liver cirrhosis. All together one or more endoscopic lesions were observed in almost 60% of cirrhotics but only in 25.4% of controls (P less than 0.001). In conclusion, our data do not show an increased prevalence of peptic ulcer in cirrhotic patients; in contrast, liver cirrhosis is significantly associated with the endoscopic finding of gastroduodenal erosions, especially in the more advanced stages of the disease. These findings would suggest a cautious use, in cirrhotic patients, of drugs which may damage the gastroduodenal mucosa; moreover, long-term administration of antacids or of other drugs with a protective effect on gastroduodenal mucosa might be taken into consideration for Child C patients.


Bile acids in bile after monensin treatment.
Bile derived from monensin treated bile-fistula rats has been analysed for bile acids content. Bile flow and bile acids decrease in bile following monensin treatment, in agreement with the disruption of the Na+ gradient determined by the ionophore and necessary for the vectorial Na+-cotransport of taurocholate at the sinusoidal pole of the hepatocyte.


Discovery of small molecules that enhance astrocyte differentiation in rat fetal neural stem cells.
1,3,4-Oxadiazole derivatives were found to enhance astrocyte differentiation in rat fetal neural stem cells (NSCs). Differentiation activity was assessed by immunocytochemistry and analysis of mRNA expression of astrocyte markers, GFAP and S100. Compounds 7 and 8 showed approximately a two-fold increase in astrocyte differentiation without engagement of neuronal differentiation and detectable cytotoxicity.


Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study.
To test the hypothesis that enzymes conventionally associated with liver dysfunction (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes. From a population-based diabetes survey, we selected 1,441 men and women in whom serum enzyme levels were < or =3 SDs of the mean population value, alcohol intake was <250 g/week, and hepatitis B and C virus testing was negative. At follow-up (7 years), 94 subjects developed diabetes and 93 impaired glucose tolerance (IGT). At baseline, all four enzymes were related to most of the features of the metabolic syndrome. After controlling for sex, age, adiposity/fat distribution, alcohol intake, serum lipids, and blood pressure, higher alanine aminotransferase and GGT values were significantly (P < 0.01) associated with both IGT and diabetes, whereas alkaline phosphatase was associated with diabetes only (P = 0.0004) and aspartate aminotransferase with IGT only (P = 0.0001). Raised GGT alone was associated with all the features of the metabolic syndrome. Raised GGT was a significant predictor of either IGT or diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose plasma glucose concentrations. Although mild elevations in liver enzymes are associated with features of the metabolic syndrome, only raised GGT is an independent predictor of deterioration of glucose tolerance to IGT or diabetes. As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress.


Prepared for sudden cardiac arrest? A cross-sectional study of automated external defibrillators in amateur sport.
Sudden cardiac arrest (SCA) is a rare but tragic part of professional and amateur sport. Following multiple high profile deaths in professional sport over the past two decades, there has been a significant trend towards the widespread availability of automated external defibrillators (AEDs) at amateur sports grounds. To examine the availability of AEDs in amateur sports clubs in Cork, Ireland, and to investigate club practices with respect to the purchase, accessibility, maintenance and use of AEDs. A cross-sectional survey of 218 amateur Gaelic Athletic Association (GAA), soccer and rugby clubs was conducted between July and September 2012. Club committee representatives answered a 22-point questionnaire. 126 GAA clubs and 28 soccer and 17 rugby (n=171) clubs were enrolled in this study. A total of 81.3% of amateur clubs own an AED. We estimate an AED-use rate of one AED use for every 54.5 years an AED is available. Almost 50% of club representatives thought the location of their club AED could be improved while 12.9% of clubs admitted to not maintaining their club AED on a regular basis. A large proportion of amateur clubs in Cork City and County own an AED. Many clubs engage in regular maintenance and storage of AEDs. However, this study identifies several areas for improvement in facilitating a secure chain of survival for players in the event of an SCA.


Percutaneous radiofrequency ablation of sonographically unidentifiable liver tumors. Feasibility and usefulness of a novel guiding technique with an integrated system of computed tomography and sonographic images.
The purpose of this study was to evaluate the safety and feasibility of a real-time integrated system with computed tomography (CT) and sonographic images for radiofrequency (RF) ablation of hepatic malignancies poorly defined on B-mode sonography, and to clarify the suitable phase of CT images for using this virtual sonography. Between September 2004 and December 2004, 12 patients with 16 hepatocellular carcinomas and two metastatic lesions arising from colorectal adenocarcinoma (n = 1) and rectal carcinoid (n = 1) were treated. The maximum diameter of nodules ranged from 1.0 to 2.5 cm (mean +/- SD; 1.5 +/- 0.6 cm) on CT images. Complete tumor necrosis was achieved in a single session in 19 lesions (90%), while a second session was required for the remaining two lesions (10%). Portal phase multi-planar reconstruction images were displayed under a suitable position corresponding to the ultrasound images in 9 patients (HCC = 7, metastasis = 2), and arterial phase multi-planar reconstruction images were displayed in the 3 remaining patients with hepatocellular carcinoma. Percutaneous RF ablation guidance using virtual sonography is an effective treatment for patients with hepatic malignancies. The portal phase of CT images may be the most suitable to indicate the 3-dimensional relationship between the liver vasculature and tumors on virtual sonography.


Multicentric eighth cranial nerve schwannoma.
To our knowledge, only 3 histopathologically proved cases of multicentric eighth cranial nerve schwannoma have been described in the literature since 1981. We describe a patient with 2 isolated eighth cranial nerve schwannomas arising separately from the left cochlea and internal auditory canal. These 2 tumors were diagnosed using magnetic resonance imaging prior to resection, and the diagnosis was further confirmed by intraoperative findings and histopathologic analysis. The genetic molecular basis and clinical features of this rare tumor have been overlooked. The value of the transotic approach for total tumor removal is emphasized.


Ten years of tension: single-molecule DNA mechanics.
The basic features of DNA were elucidated during the half-century following the discovery of the double helix. But it is only during the past decade that researchers have been able to manipulate single molecules of DNA to make direct measurements of its mechanical properties. These studies have illuminated the nature of interactions between DNA and proteins, the constraints within which the cellular machinery operates, and the forces created by DNA-dependent motors.


Distinct Phenotypes Associated with Increasing Dosage of the PLP Gene: Implications for CMT1A Due to PMP22 Gene Duplication.
Increased dosage of the proteolipid protein (Plp) gene causes CNS disease (Pelizaeus-Merzbacher disease [PMD]), which has many similarities to disorders of the PNS associated with duplication of the peripheral myelin protein-22 (PMP22) gene locus. Transgenic mice carrying extra copies of the wild-type Plp gene provide a valid model of PMD. Variations in gene dosage can cause a wide range of phenotypes from severe, lethal dysmyelination through late-onset demyelination. A predilection for different fiber diameters may occur within the various phenotypes with dysmyelination being more obvious in large fibers and late-onset degeneration predominantly affecting small fibers. Although the frequency of apoptotic oligodendrocytes is increased with high gene dosage, the number of mature oligodendrocytes appears adequate. Oligodendrocytes in the dysmyelinated CNS express a range of genes typical of mature cells, yet are unable to assemble sufficient myelin. Oligodendrocytes contain abnormal vacuoles and stain intensely for PLP and other proteins such as MAG. The findings suggest that with high gene dosage much of the PLP, and possibly other proteins, is missorted and degraded in the lysosomal system.


Phonomechanocardiographic parameters in patients with atrial septal defect.
The purpose of the present study was to noninvasively evaluate left (LV) systolic and diastolic function in patients with atrial septal defect (ASD) using the phonomechanocardiogram. We studied 40 patients with atrial septal defect, 16 males and 24 females, ages ranging from 6 to 56 years (mean 21.1 years), consecutively observed before surgery in our institution, during a four year period. We measured the systolic time intervals (Q-A2c, Q-S1, ICT, PEP, LVETc, PEP/LVET), the Apex Cardiographic (ACG) diastolic parameters A2-Oc and A/H and the hemodynamic variables Qp/Qs, Pulmonary Vascular Resistance (PVR) and Left Ventricular End Diastolic Pressure (LVEDP). We compared the data with 74 normal individuals using the Student t-test and linear regression analysis. We found significant Q-S1 lengthening (81.2 +/- 16.4 ms, p < 0.001); PEP, ICT and A2-Oc were significantly reduced (101.2 +/- 21.7 ms, p < 0.001, 20.0 +/- 5.3 ms, p < 0.05 and 117.1 +/- 26.3 ms, p < 0.001, respectively) and A/H was significantly increased (17.4 +/- 12.1%, p < 0.005). Except for the case of Q-S1, where there was a weak positive linear correlation with Qp/Qs (r = 0.37), we found no correlation between the other parameters and Qp/Qs or PVR. Sixty-seven percent of the patients had Q-S1 prolongation and a Q-S1 > 76.2 ms identified left-right shunts > 2 with a positive predictive value of 82%; 62% of the patients had a reduced A2-Oc and a A2-Oc < 110 ms identified shunts > 2 with a positive predictive value of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)


[Satisfaction and recovery of normal activity with rizatriptan 10 mg. Results from the open, prospective, observational 4M study].
To evaluate the impact of the treatment with rizatriptan 10 mg (Maxalt) on the return to normal activity and satisfaction with treatment in the general population with migraine. We conducted an open, prospective study in patients with migraine (International Headache Society [IHS] criteria) who were followed for up to 3 migraine attacks. We measured the degree of functional disability at 0 and 2 hours after treatment, and satisfaction at 24 hours. Other domains of satisfaction were evaluated after three migraine attacks. The relationship between baseline pain severity, satisfaction after 24 hours and functional disability was analyzed. 2,469 patients were enrolled who experienced 6,323 migraine attacks. A return to normal activity was achieved two hours after treatment in 67% of all attacks treated with rizatriptan 10 mg. The percentage of attacks causing severe functional disability decreased from 39% before therapy to 3.6% two hours after treatment. In more than 90% of moderate or severe attacks, a normal or slightly impaired functional capacity was restored two hours after treatment. In 76.3% of the attacks the patients were fully or very satisfied 24 hours after treatment with rizatriptan 10 mg. After treating three migraine attacks, the proportion of patients fully or very satisfied with rizatriptan was over 79% for all the domains explored. The patients were highly satisfied after 24 hours and following three migraine attacks treated with rizatriptan 10 mg. In more than two-thirds of the attacks treated with rizatriptan 10 mg, the patients returned to normal activity two hours after treatment.


Prevalence of myocardial bridging and correlation with coronary atherosclerosis studied with 64-slice CT coronary angiography.
This study aimed to assess the prevalence and characteristics of myocardial bridging in patients who underwent multislice computed tomography coronary angiography (MSCT-CA) and to evaluate the correlation between bridged coronary segments and atherosclerosis. A total of 277 patients (mean age 60+/-11 years) we consecutively examined with 64-slice MSCT-CA for suspected or known coronary atherosclerosis were retrospectively reviewed for myocardial bridging. Segments proximal and distal to the bridging were evaluated for atherosclerotic plaque, as were the remaining coronary segments. Myocardial bridging was present in 82 patients (30%, mean age 59+/-12). Bridges were of variable length (<1 cm 58%; 1-2 cm 32%; >2 cm 10%) and depth (superficial 69%, intramyocardial 31%) and frequently localised in the mid-distal segment of the left anterior descending artery (95%). Myocardial bridging cannot be considered a significant risk factor for coronary atherosclerosis (odds ratio 0.49) compared with traditional cardiovascular risk factors. Coronary segments proximal to the bridge showed no atherosclerotic disease (33%), positive remodelling (27%), <50% stenosis (20%) or >50% stenosis (20%). We identified 12 noncalcified, 32 mixed and 17 calcified plaques. The distal segments were significantly less affected (p<0.0001). MSCT-CA is a reliable, noninvasive method that is able to depict myocardial bridging and associated atherosclerotic plaque in the proximal segments.


Effects of tibolone and combined 17beta-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial.
Serum C-reactive protein (CRP) is an independent risk factor for the development of cardiovascular diseases in healthy post-menopausal women. Oral unopposed and progestin-combined 17beta-estradiol (E(2)) increase serum CRP in post-menopausal women. The aim of this study was to compare the effects of tibolone, a steroid with estrogenic, androgenic or progestogenic properties, with a combination of E(2) and norethisterone acetate (E(2) + NETA) on serum CRP levels in healthy post-menopausal women. A total of 139 post-menopausal women (mean age: 55 years, range 44-48) was randomly assigned to receive tibolone 1.25 mg/day (n = 52), tibolone 2.5 mg/day (n = 39) or E(2) 2 mg/day plus NETA 1 mg/day (n = 48) for 2 years. Serum CRP was measured at baseline and at 6, 12 and 24 months. Both doses of tibolone and E(2) + NETA increased serum CRP by a similar extent as soon as 6 months with a sustained effect over the 24 month treatment period. For example, after 6 months of treatment, serum CRP increased by a median of +106% (P < 0.001), +89% (P < 0.05) and +139% (P < 0.001) for tibolone 1.25 mg/day, tibolone 2.5 mg/day and E(2) + NETA respectively. Tibolone and E(2) + NETA significantly increase serum CRP levels in healthy post-menopausal women to a comparable extent. Relationships between induced elevated CRP levels with tibolone and E(2) + NETA and cardiovascular events require further studies.


Increased atrial natriuretic peptide binding sites in the rat subfornical organ after water deprivation.
Binding sites for rat atrial natriuretic peptide (99-126) were localized and quantified in the subfornical organ and choroid plexus of control and water-deprived rats. Brain sections were analyzed after incubation with 125I-rat atrial natriuretic peptide (99-126), autoradiography, computerized microdensitometry and comparison to 125I-standards. Higher numbers of atrial natriuretic peptide binding sites were present in both the subfornical organ and the choroid plexus after 4 days of water deprivation. Our results indicate a central role for atrial natriuretic peptide in the regulation of water balance.


Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach.
From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H(4)R compounds. This approach led to the discovery of 6-chloro-N-(furan-3-ylmethyl)2-(4-methylpiperazin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)quinazolin-4-amine (VUF10497, 55) as potent human H(4)R inverse agonists (pK(i) = 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine H(1) receptor (H(1)R) and therefore represent a novel class of dual action H(1)R/H(4)R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quinazolines are antagonists at the rat H(4)R and were found to possess anti-inflammatory properties in vivo in the rat.


The French model of psychoanalytic training: Ethical conflicts.
Research on psychoanalytical education within the IPA may be clarified by reflecting on the ethic behind each of the three main models (Eitingonian, French and Uruguayan). In fact, the ethic underpinning psychoanalytical education, whatever the model, is confronted by irreducible conflicts between transmitting psychoanalysis by means of analytical experience or by means of academic teaching. Transmission by experience is essentially based on the ethic of psychoanalytic practice, which is difficult to regulate through institutional standards, whereas the academic aspect can be evaluated by objective and public criteria. The importance of both aspects and their relative weight in the training process depend on the conception of psychoanalysis underlying each model. This paper will look primarily at the French training model, the essentially analytical aspects of which favour the transmission of the very ethical foundations of psychoanalytic practice itself: the application of the method both as a working tool and as a tool of evaluation. It presupposes expanding the observation and analysis of transference beyond the framework of treatment to that of supervision. From this analysis, the paper will attempt to demonstrate how the French model proposes dealing with the inevitable conflicts between transmission by means of analysis and training by means of apprenticeship.


Phosphine-catalyzed annulation of thioamides and 2-alkynoates: a new synthesis of thiazolines.
The annulation of thioamides with 2-alkynoates and 2,3-dienoates under the catalysis of tri-n-butylphosphine was described. The annulation reaction provided a new entry to thiazolines, particularly those with 2-aryl substituents.