Stability of nonfouling electroless nickel-polytetrafluoroethylene coatings after exposure to commercial dairy equipment sanitizers.
Application of nonfouling coatings on thermal processing equipment can improve operational efficiency. However, to enable effective commercial translation, a need exists for more comprehensive studies on the stability of nonfouling coatings after exposure to different sanitizers. In the current study, the influence of different commercial dairy equipment sanitizers on the nonfouling properties of stainless steel modified with electroless Ni-polytetrafluoroethylene (PTFE) coatings was determined. Surface properties, such as dynamic contact angle, surface energy, surface morphology, and elemental composition, were measured before and after the coupons were exposed to the sanitizers for 168 cleaning cycles. The fouling behavior of Ni-PTFE-modified stainless steel coupons after exposure was also evaluated by processing raw milk on a self-fabricated benchtop-scale plate heat exchanger. The results indicated that peroxide sanitizer had only minor effect on the Ni-PTFE-modified stainless steel surface, whereas chlorine- and iodine-based sanitizers influenced the surface properties drastically. The coupons after 168 cycles of exposure to peroxide sanitizer accumulated the least amount of fouling material (4.44±0.24mg/cm(2)) compared with the coupons exposed to the other 3 sanitizers. These observations indicated that the Ni-PTFE nonfouling coating retained antifouling properties after 168 cycles of exposure to peroxide-based sanitizer, supporting their potential application as nonfouling coatings for stainless steel dairy processing equipment.


Radiologic Considerations and Standardization of Malignant Pleural Mesothelioma Imaging Within Clinical Trials: Consensus Statement from the NCI Thoracic Malignancy Steering Committee - International Association for the Study of Lung Cancer - Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting.
Detailed guidelines pertaining to radiological assessment of malignant pleural mesothelioma are currently lacking due to the rarity of the disease, complex morphology, propensity to invade multiple planes simultaneously, and lack of specific recommendations within the radiology community about assessment, reporting, and follow-up. In March 2017, a multidisciplinary meeting of mesothelioma experts was co-sponsored by the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and the Mesothelioma Applied Research Foundation. One of the outcomes of this conference was the foundation of detailed, multidisciplinary consensus imaging and management guidelines. Here, we present the recommendations for radiologic assessment of malignant pleural mesothelioma in the setting of clinical trial enrollment. We discuss optimization of imaging parameters across modalities, standardized reporting, and response assessment within clinical trials.


Pediatric temporal lobe epilepsy surgery: resection based on etiology and anatomical location.
Advances in electrophysiological assessment with improved structural and functional neuroimaging have been very helpful in the use of surgery as a tool for drug-resistant epilepsy. Increasing interest in epilepsy surgery has had a major impact on adult patients; a refined evaluation process and new criteria for drug resistance combined with refined surgical techniques resulted in large surgical series in many centers. Pediatric surgery has lagged behind this evolution, possibly because of the diverse semiology and electrophysiology of pediatric epilepsy obscuring the focal nature of the seizures and frustrating the treatment of catastrophic epileptic syndromes specific to children. Unfortunately, refractory -epilepsy is more -devastating in children than in adults as it interferes with all aspects of neural development. Nevertheless, during the last few decades, the efforts of a small number of centers with encouraging results in pediatric epilepsy surgery have motivated pediatric neurologists to gain interest. Although well behind in the number of patients compared with that of adults, pediatric series are increasing exponentially. While temporal lobe epilepsy is the focus of interest in adults, with almost 70 % of resections in the temporal lobe, the pediatric epilepsy spectrum is different. Resective or functional surgery techniques devoted to resistant extratemporal epilepsy are the major improvements in pediatric epilepsy surgery. Temporal lobe epilepsy in adults has been studied extensively but only recently has begun to receive attention in children. Several aspects of temporal lobe epilepsy in childhood remain unclear or controversial in terms of seizure semiology and its pathology. This is reflected in the surgical treatment. Information on the major contributors to a favorable outcome, such as type or extent of resection, in terms of seizure control and morbidity is not available as in adult temporal lobe epilepsy. This chapter discusses the major discrepancies between adult and pediatric temporal lobe epilepsy and outlines the current concepts in surgical treatment. The resection strategy based on the different substrates at different locations in the temporal lobe causing seizures is emphasized with respect to available literature.


Contemporary psychoanalysis and homosexuality.
In this paper, I contrast older, traditional, psychoanalytic ideas about homosexuality, with those put forth at a panel on homosexuality at the American Psychoanalytic Association in 1983 (and subsequently). I focus particularly on relationships between cross-gender behavior during childhood and adulthood homosexuality; sexual orientation and personality functioning; determinants and intrapsychic consequences of homophobia, countertransference issues in working psychoanalytically with gay and bisexual patients; the sexual orientation of the analyst (i.e. should gay patients be treated only by gay analysts?). Changing psychoanalytic ideas about sexual orientation reflect the increasingly widespread recognition by psychoanalysts of the necessity to integrate psychoanalytic theory with advances in neurobiology, particularly neuroendocrinology.


Proton MR spectroscopic findings correspond to neuropsychological function in traumatic brain injury.
Traumatic brain injury (TBI) causes substantial irreversible damage to neurons. Our aim was to investigate whether proton MR spectroscopic measures of diffuse cellular integrity were related to neuropsychological dysfunction after TBI. Twelve patients with TBI (mean, 53 +/- 23 days postinjury) and 14 control subjects were included in the study using paired MR spectroscopy and neuropsychological assessment. N-acetylaspartate (NAA), creatine, and choline were measured in normal-appearing occipitoparietal white and occipital gray matter using short-echo quantitative spectroscopy. A composite measure of neuropsychological function was calculated from z-scored individual tests probing the major functional domains commonly impaired after head trauma. Patients with TBI displayed reduced NAA in white matter and elevated choline in gray matter, suggestive of neuronal injury and inflammation, respectively. NAA and creatine in white and gray matter were significantly associated with composite neuropsychological function and many individual neuropsychological tests. Gray matter choline, although abnormal, was not related to neuropsychological function. The concordance between neurometabolic levels and behavioral function supports the hypothesis that diffuse axonal injury is an important contributor to brain dysfunction after TBI.


Decision support systems for chemical structure representation, reaction modeling, and spectra simulation.
The choice of an appropriate structure coding scheme is the secret to success in QSAR studies. Depending on the problem at hand, 2D or 3D descriptors have to be chosen; the consideration of electronic effects might be crucial, conformational flexibility has to be of special concern. Artificial neural networks, both with unsupervised and with supervised learning schemes, are powerful tools for establishing relationships between structure and physical, chemical, or biological properties. The EROS system for the simulation of chemical reactions is briefly presented and its application to the degradation of s-triazine herbicides is shown. It is further shown how the simulation of chemical reactions can be combined with the simulation of infrared spectra for the efficient identification of the structure of degradation products.


Zinc and diabetes mellitus: is there a need of zinc supplementation in diabetes mellitus patients?
Diabetes mellitus is a group of metabolic disorders, the incidence of which varies widely throughout the world. The treatment of diabetes mellitus includes insulin, oral antidiabetic agents, and dietary regimens. Although the emphasis is on macronutrients intakes, there is strong evidence that there is an abnormal metabolism of several micronutrients in diabetic individuals. Zinc is one of the essential micronutrients of which status and metabolism is altered in this condition. This work is a short review about the close relation among zinc, glucose metabolism, and insulin physiology, as well as about the few experimental data about zinc absorption and zinc supplementation in diabetes mellitus patients.


Random number generators for microcomputers.
The feasibility of random number generation using microcomputers is discussed and the appropriateness of alternative algorithms is evaluated on the basis of several criteria of statistical randomness. The relative deficiencies of each algorithm are cited and a modified Fibonacci generator is recommended for use in the microcomputer environment.


Decreasing the Incidence of Postoperative Urinary Retention and Incontinence With Total Joint Replacement Patients After Spinal Anesthesia in the Postanesthesia Care Unit: A Quality Improvement Project.
Patients with postoperative urinary retention (POUR) can develop bladder atrophy, urinary incontinence, and hypertension. The purpose of this quality improvement project was to implement standardized guidelines for bladder scanning for patients who have total knee or hip replacement to decrease POUR and incontinent episodes. A retrospective descriptive study was implemented in a 425-bed Magnet community hospital. Patients were bladder scanned within the first hour of postanesthesia care unit admission. Straight catheterization was performed for those who had more than 400 mL of retained urine. The protocol included both total knee and total hip replacement surgeries with spinal anesthesia. Compliance with scanning, percentages with POUR, and incontinent episodes were reviewed. POUR was detected in 46% of total knee replacement patients and 36% of total hip replacement patients. Incontinence rates for knee replacement patients decreased by 14% and by 2% for patients with total hip replacements. A bladder scanning protocol decreases postoperative incontinence. Bladder scanning also helps to decrease POUR by decreasing the potential risk of complications.


Pediatric acute and chronic rhinosinusitis: comparison of clinical characteristics and outcome of treatment.
Rhinosinusitis (RS) is a common problem in children. There are very few published studies comparing acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) in children. To determine the clinical manifestations in children with ARS and CRS. One hundred and fifty-four patients with a clinical diagnosis of RS were enrolled. ARS was defined as persistent symptoms for more than 10 days but less than 4 weeks and CRS was defined as persistent symptoms for longer than 8 weeks. Patients were interviewed to obtain demographic and clinical data. Physical findings and medications were recorded. All patients underwent radiographic studies. Allergy and immunological testing were done in selected case. All data were compared between the ARS and CRS groups. One hundred and three patients were classified as having ARS and fifty-one had CRS. Their mean (+/- SD) age was 5.9 +/- 3.3 years. Allergic rhinitis was common in the chronic rhinosinusitis group. The most common main complaints in acute and chronic rhinosinusitis were cough and rhinorrhea. There was no significant difference in symptoms between both groups, except for periorbital pain and sleep apnea which were found more frequently in the chronic group. Sixty five percents of ARS and 58.8% of CRS had abnormal x-ray findings. Adenoid hypertrophy was found in the CRS group. There was overall improvement after 14.6 +/- 3.82 days and 22.35 +/- 5.04 days (mean) of antibiotic treatment in the ARS and CRS groups, respectively. None of the patient underwent sinus surgery. The most common RS symptoms were rhinorrhea and cough. Patients with allergic rhinitis had a higher risk of developing chronic rhinosinusitis. Patients with ARS and CRS were successfully treated with medical treatment.


Perspectives on diabetes mortality as the result of residual confounding and reverse causality by common disease.
Type 2 diabetes (T2D) is associated with major global health burdens, including 2 to 4 times increased rates of morbidity and mortality from cardiovascular disease. However, T2D remains an exclusion diagnosis in individuals with arbitrarily elevated blood-glucose levels. While it is well-established that diabetes is associated with an elevated risk of cardiovascular disease and cancer, it has recently been shown that heart failure and cancer may precede, and even contribute to, the development of T2D. In the present review, we have summarized these findings and discuss their potential implications for our understanding of the T2D disease entity, including its treatment and associated increased mortality. We suggest that the existence of a hitherto unrecognized distinct T2D subtype, secondary to heart failure and/or cancer, may substantially contribute to the excess mortality reported in T2D patients with mild disease. Treatment and clinical care of this subtype needs to be defined separately from the general T2D phenotype.


Growth delay in 9L rat brain tumor spheroids after irradiation with single and split doses of X rays.
The response of 9L spheroids to irradiation with single and split doses of X rays has been investigated. Irradiation with single doses caused a dose-dependent decrease in spheroid growth rate, which eventually returned to the growth rate for unirradiated spheroids. This delay appeared to be related to cell survival. When spheroids were irradiated with two 4-Gy doses of X rays separated by various times the amount of growth delay was intermediate between that observed with single doses of 4 and 8 Gy. For relatively short times (15-90 min), recovery probably resulted from repair processes, but for longer times (up to 24 hr), recovery also appeared to depend on cellular redistribution and repopulation effects.


Endometrial cancer: Molecular markers and management of advanced stage disease.
Endometrial cancer is the most prevalent gynecologic cancer in the United States. Over the last 10 years, death rates from endometrial cancer have been rising about 1.4% per year. Traditionally endometrial cancer treatment has been driven by stage and histology. Recent studies have, however, shown that cancers of the same stage and histology have very distinct molecular and genomic profiles. Translational research is progressing rapidly and endometrial cancer-specific precision medicine is evolving. The first tissue agnostic therapy based on the molecular profile of the tumor was approved by the FDA this year. The approval of immune checkpoint inhibitor, pembrolizumab (anti-PD-1), for all solid tumors with defective DNA mismatch repair, could benefit 20-30% of patients with advanced endometrial cancer. Other genomic changes and molecular markers in endometrial cancer, such as hormone receptor status, could lead to more tailored therapy in the future. Pre-clinical and clinical investigations of targeted therapies suggest efficacy for some agents. Single agent targeted therapies, however, have modest activity. Identifying biomarkers that effectively determine response to targeted therapy remains a challenge. The next generation of clinical trials will focus on novel combinations and how to best utilize the advances that have been made in sequencing technology and bioinformatics. Although there is currently an immense body of data and many options for obtaining genomic characteristics of endometrial cancer, how to interpret and utilize this data is still being explored. This review will summarize the important trials that have led to the treatment options we have for advanced and/or recurrent endometrial cancer and discuss the important studies that have led to a better understanding of the distinctive molecular and genomic profiles within endometrial cancer. We will review the current status of biomarker-driven targeted therapy in endometrial cancer and the rationale behind ongoing clinical trials that are utilizing novel targeted agents.


Influence of the hydrophilic moiety of anionic and nonionic surfactants on their aerobic biodegradation in seawater.
The extent and kinetics of the primary biodegradation have been characterized for the most commonly-used surfactants, employing four homologues with the same alkyl chain: dodecyl ethoxy sulfate (C(12)AES), sodium dodecyl sulfate (SDS), dodecyl alcohol ethoxylate (C(12)AEO) and dodecyl benzenesulfonate (C(12)LAS). A brief acclimatization period has been required to enable an effective degradation of C(12)LAS and C(12)AES to take place, but this lag phase has not been detected for SDS and C(12)AEO. Primary biodegradation percentages at the end of these experiments were higher than 99%, showing a fast degradation rate in all cases (average half-life lower than 2 days). The secondary biodegradation of C(12)LAS was also monitored. C(12)LAS external isomers, which are predominant, are preferentially degraded by successive beta-oxidations, generating significant amounts of external even isomers of sulfophenylcarboxylic acid (SPC) (mainly 2,3PhiC(4,6)SPCs). In ontrast, internal isomers are converted into internal odd isomers of SPC (mostly 4,5PhiC(5,7)SPCs) by omega-oxidation followed by alpha-oxidation and/or beta-oxidations.


Identification of the UDP-glucuronosyltransferase isozyme involved in senecionine glucuronidation in human liver microsomes.
Senecionine (SEN) is a representative of the hepatotoxic pyrrolizidine alkaloids. Although phase I metabolism for cytochrome P450-mediated metabolic activation of SEN was investigated extensively, phase II metabolism for glucuronidation of this compound has not been investigated until now. In our present study, one unique glucuronidation product of SEN in human liver microsomes (HLMs) was identified as SEN N-glucuronide using an authentically synthesized product for which the structure was identified via (1)H and (13)C NMR analysis. Subsequently, kinetics indicated that SEN N-glucuronidation followed the typical Michaelis-Menten model and only one major isozyme participated in it. Finally, this isozyme was demonstrated to be UDP-glucuronosyltransferase (UGT) 1A4, with the direct evidence that recombinant UGT1A4 exhibited predominant and exclusive activity on SEN N-glucuronidation. This result was confirmed by other experiments including chemical inhibition by selective inhibitors and a correlation study between activities of SEN N-glucuronidation and various UGT isozymes. The exclusive role of UGT1A4 on SEN N-glucuronidation was strengthened additionally by its inhibitory kinetic study in which the selective inhibitor of UGT1A4 showed a similar inhibition pattern and K(i) values in both HLM and recombinant UGT1A4 systems. Because UGT2B10 activity failed to correlate with SEN N-glucuronidation in HLMs from 10 individuals, it was impossible for UGT2B10 to play an important role in this metabolism.


[Drug sensitivity of causative agents in ocular infection of external adnexa and anterior segments--multicenter study of causative agents and drug sensitivity of ocular infection by the Japanese Association for Ocular Infection part II].
To report the drug sensitivity of causative agents produced by ocular infection of external adnexa and anterior segments investigated by the nationwide survey conducted by Japanese Association for Ocular Infection between September, 2007 and August, 2008. Among all strains isolated, causative and presumed causative agents were selected according to the criteria described, and drug sensitivity tests were conducted by minimum inhibitory concentrations (MIC) with 10 kinds of antimicrobial agents including 5 fluoroquinolones. Among 281 causative isolates, cefmenoxime (CMX) showed the highest sensitivity, followed by fluoroquinolones. Staphylococci and Streptococci were more sensitive to fluoroquinolones when compared to the others. Haemophilus influenzae was very sensitive to all fluoroquinolones. Corynebacterium spp. and Propionibacterium acnes were most sensitive to CMX and erythromycin respectively. CMX and fluoroquinolones showed generally good sensitivity among causative pathogens of ocular infection.


Self-stigma, stages of change and psychosocial treatment adherence among Chinese people with schizophrenia: a path analysis.
Mental illness stigma is one of the key causes for poor psychosocial treatment adherence. The objective of this study was to explore the link between self-stigmatization and adherence via path analysis with insight and readiness for change conceptualized as the possible mediators. The direct effects of psychopathology causing non-adherence were also tested. One hundred and five participants with schizophrenia were recruited from five psychiatric settings in Hong Kong. Data concerning their level of stigma, insight, stages of change, psychopathology, and psychosocial treatment adherence were collected. Path analysis was used to test two hypothetical models. The findings supported the direct effects of self-stigma on reducing psychosocial treatment adherence, and its indirect influences mediated by insight and stages of change on treatment adherence. Psychopathology was also found to have a direct effect on undermining adherence. This model showed better model fit than the one which did not consider the direct effects of self-stigmatization and psychopathology. To conclude, this study deepened our understanding on the mechanism explaining how self-stigmatization undermines psychosocial treatment adherence. The findings provide direct implications on ways of formulating a self-stigma reduction program to combat self-stigma and its negative consequences.


Increased cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients.
To investigate the expression of cyclooxygenase (COX-2) and its association with clinicopathologic parameters and clinical outcome in patients with cervical cancer. The study included 84 patients with stage IB to IVA cervical cancer. Patients with early-stage cases (n = 21) underwent radical surgery, whereas patients with locally advanced cervical cancer (LACC) (n = 63) were first administered neoadjuvant cisplatin-based treatment and subjected to surgery in case of response. Immunohistochemical analysis was performed on paraffin-embedded sections with rabbit antiserum against COX-2. COX-2--integrated density values in the overall population ranged from 1.2 to 82.3, with mean plus minus SE values of 27.4 plus minus 2.4. According to the chosen cutoff value, 36 (42.9%) of 84 patients were scored as COX-2 positive. COX-2 levels were shown to be highly associated with tumor susceptibility to neoadjuvant treatment. COX-2 showed a progressive increase from mean plus minus SE values of 19.9 plus minus 8.0 in complete responders through 31.5 plus minus 3.5 in partial responses to 44.8 plus minus 3.9 in patients who were not responsive (P =.0054). When logistic regression was applied, only advanced stage and COX-2 positivity retained independent roles in predicting a poor chance of response to treatment. COX-2--positive patients had a shorter overall survival (OS) rate than COX-2--negative patients. In patients with LACC, the 2-year OS rate was 38% in COX-2--positive versus 85% in COX-2--negative patients (P =.0001). In the multivariate analysis, only advanced stage and COX-2 positivity retained independent negative prognostic roles for OS. The assessment of COX-2 status could provide additional information to identify patients with cervical cancer with a poor chance of response to neoadjuvant treatment and unfavorable prognosis.


Sleep-dependent memory processing.
While the functions of sleep remain largely unknown, one exciting hypothesis is that sleep contributes importantly to processes of memory and brain plasticity. Over the last decade, a large body of work has provided substantive evidence supporting this role of sleep in what is becoming known as sleep-dependent memory processing. This review offers a summary of these data, focusing specifically on the role of sleep in (1) memory encoding, (2) memory consolidation (along with the brain basis of this process), and (3) neural plasticity. The clinical ramifications of such findings are also explored.


A tutorial on creating logfiles for event-driven applications.
This paper describes the practical steps necessary to write logfiles for recording user actions in event-driven applications. Data logging has long been used as a reliable method to record all user actions, whether assessing new software or running a behavioral experiment. With the widespread introduction of event-driven software, the logfile must enable accurate recording of all the user's actions, whether with the keyboard or another input device. Logging is only an effective tool when it can accurately and consistently record all actions in a format that aids the extraction of useful information from the mass of data collected. Logfiles are often presented as one of many methods that could be used, and here a technique is proposed for the construction of logfiles for the quantitative assessment of software from the user's point of view.


Quantitative distribution of protein kinase C alpha, beta, gamma, and epsilon mRNAs in the hippocampus of control and nictitating membrane conditioned rabbits.
We used oligonucleotide in situ hybridization and film autoradiography to quantitate the distributions of protein kinase C (PKC) alpha, beta, gamma, and epsilon mRNAs in subregions of rabbit hippocampus. Levels of each of the hippocampal PKC isozyme mRNAs and patterns of their regional distributions were remarkably invariant between individuals. Within stratum pyramidale, the highest levels of PKC alpha mRNA were in the CA2 region, while PKC beta mRNA was maximally expressed in CA1, and PKC epsilon mRNA in CA3; PKC gamma mRNA was abundantly expressed throughout Ammon's horn. Previous experiments employing quantitative autoradiography for [3H]PDBU (Olds et al., Science, 245 (1989) 866-869) revealed an increase in membrane-bound PKC in the CA1 region of rabbit hippocampus up to 3 days following classical conditioning of the nictitating membrane response. We report here that there were no differences in levels of PKC alpha, beta, gamma, or epsilon mRNA between conditioned and control rabbits in any hippocampal region one day after training. These data are consistent with the hypothesis that PKC is post-translationally activated and translocated to the membrane during memory storage.


Minimally invasive options in Dupuytren's contracture: aponeurotomy, enzymes, stretching, and fat grafting.
After studying this article, the participant should be able to: (1) Perform needle aponeurotomy, fat grafting, Digit Widget insertion, and collagenase injection for Dupuytren's cords. (2) Describe how cords can be stretched without surgery. (3) Explain to patients the risks and benefits of these new alternatives of treatments. Surgery for Dupuytren's contracture used to be the only alternative of treatment. The past 5 years have seen the widespread adoption of minimally invasive treatments in the form of needle aponeurotomy and collagenase injection to disrupt the cords and restore range of motion. Even newer and perhaps as effective treatments such as fat grafting and mechanical stretching with the Digit Widget may also end up being important tools of treatment. The reader will be introduced to all of these modalities with text, illustration, and videos.


Rural population estimates: an analysis of a large secondary data set.
Health services research often utilizes secondary data sources such as the Behavioral Risk Factor Surveillance System (BRFSS). Since 2006, the released BRFSS data do not include respondents who live in counties with 10,000 or fewer residents, and the CDC no longer offers the opportunity to access the unrestricted data set. As a result, rural residents can be underrepresented in BRFSS data after 2005. The purpose of this analysis is to examine the potential for bias introduced by rural underestimation. We utilized 6 BRFSS data sets; the 2005 full data and the 2005-2009 restricted data. We estimated population sizes for each survey year, and we compared these estimates to comparable data from the US Census intercensal estimates. We also compared estimates of preventive service utilization (mammography, Pap tests, colorectal cancer screening, and influenza vaccinations) between the two 2005 data versions. Rural populations were underrepresented, particularly with the smaller counties excluded. Remote rural residents were the most consistently underrepresented. Preventive service delivery estimates differed between the full and restricted 2005 data versions. Mammography and Pap test estimates tended to be higher in the restricted data, while colorectal cancer screening and influenza vaccinations were similar or inconsistent. These results indicate that restricting by county size introduced bias in these estimates. Having quality, nationally representative data is important to study disparities in service delivery. The potential bias introduced by the BRFSS county restriction may result in rural research being less effective for policy recommendations and interventions.


Catecholamine-induced desensitization of brain beta adrenoceptors in vivo and reversal by corticosterone.
The function of beta adrenoceptors in the brain was studied with a new technique involving the microdialysis collection of extracellular cyclic AMP (cAMP). Prolonged infusion of isoproterenol (2 hr) was found to induce a marked desensitization of the beta receptor-cAMP response. Administration of corticosterone (10 mg/kg) 3 hrs prior to the infusion markedly attenuated the desensitization. The results indicate that the catecholamine-induced densensitization of brain beta adrenoceptors can be studied in vivo and that corticosterone is capable of reversing this effect in the brain as has been reported previously for peripheral tissues.


Pharmacokinetics and brain uptake of AM-36, a novel neuroprotective agent, following intravenous administration to rats.
The plasma pharmacokinetics and brain uptake of the novel neuroprotective agent AM-36 (1-(2-(4-chlorophenyl)-2-hydroxy)ethyl-4-(3,5-bis-(1,1dimethylethyl)-4-hydroxyphenyl) methylpiperazine) were assessed over 72 h following i.v. administration to male Sprague-Dawley rats. At nominal i.v. doses of 0.2, 1 and 3mg kg(-1), AM-36 exhibited an extremely large volume of distribution (18.2-24.6 L kg(-1)) and a long terminal elimination half-life, ranging from 25.2 to 37.7 h. Over this dose range, AM-36 exhibited linear pharmacokinetics, with no apparent change in clearance, volume of distribution or dose-normalised area under the plasma concentration - time curve. AM-36 was very highly bound to plasma proteins (> 99.6%); however, this did not appear to affect the ability of AM-36 to permeate the blood-brain barrier. Following a single i.v. dose of AM-36 at 3mg kg(-1) to rats, brain concentrations were detected for up to 72 h, and the brain-to-plasma ratios were high at all time points (ranging from 8.2 at 5 min post-dose to 0.9 at 72 h post-dose). The very high brain uptake of AM-36 supports previous in-vivo efficacy studies demonstrating the neuroprotective effects of this compound when administered to rats with middle cerebral artery occlusion.


Influence of theophylline on both bronchoconstriction and plasma extravasation induced by acetaldehyde in guinea-pigs.
Acetaldehyde administered intravenously at various doses (20, 40 and 80 mg/kg) elicits a dose-dependent increase in intratracheal pressure (ITP) and a proportional rise in histamine blood concentration in anaesthetized guinea-pigs. Similar effects were observed in ovalbumin-sensitized guinea-pigs upon aerosol of acetaldehyde (20 mg/ml) which has been administered at the flow rate of 0.1 ml/min for 2 min. Theophylline (CAS 58-55-9) antagonized both the increase of ITP values and the rise of histamine in the blood caused by acetaldehyde given intravenously (ED50 = 5.8 mg/kg i.v.) or by aerosol (ED50 = 4.9 mg/kg i.v.). Furthermore, in animals where combined treatment with pyrilamine (2 mg/kg i.v.) and captopril (2 mg/kg i.v.) resulted in a remarkable potentiation of the bronchoconstrictor response to acetaldehyde (20 mg/kg i.v.), the administration of theophylline (5 mg/kg i.v.) or of the substance P (SP) receptor antagonist, [D-Pro4, D-Trp7.9] SP 4-11 (10 mg/kg i.v.) reduced the augmented action of acetaldehyde on respiratory airways induced by captopril by more than 50%. Moreover, the bronchoconstriction induced by acetaldehyde (40 mg/kg i.v.) was also associated with a significant increase of extravasation of Evans blue in tracheal tissue. Both these effects of acetaldehyde were inhibited by theophylline (10 mg/kg i.v.), whereas a NK1-TK (neurokinin 1-tachykinin) receptor antagonist (412 micrograms/kg i.v.) reduced (81%; p < 0.001) only the vascular permeability changes caused by acetaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)


Studies with flavin analogs provide evidence that a protonated reduced FMN is the substrate-induced transient intermediate in the reaction of Escherichia coli chorismate synthase.
Chorismate synthase catalyzes the 1,4-elimination of phosphate and the C-(6-pro-R) hydrogen from 5-enolpyruvylshikimate 3-phosphate (EPSP) to generate chorismate. Although this reaction does not involve an overall change in redox state, the enzyme requires reduced FMN. To investigate the role of the flavin in catalysis we have employed chemically modified flavins: 1- and 5-deaza-, 2- and 4-thio-, 6-hydroxy-, 8-nor-6-methyl-, 8-methyl-sulfonyl-, 8-chloro-, 8-fluoro-, 8-nor-methyl-, 8-S-methyl-, 8-methoxy, 8-mercapto- and 8-amino-FMN. Photoreduction of 4-thio-FMN in the presence of chorismate synthase at pH 7.5 produced a reduced flavin species with an absorbance maximum at lambda = 410 nm indicative of monoanionic, reduced 4-thio-FMN. Binding of 8-mercapto- and 6-hydroxy-FMN to chorismate synthase in the presence of EPSP or (6R)-6-fluoro-EPSP resulted in an increase of the flavin analogs' pKa values by 4 and 1 pH units, respectively. On the basis of these findings it is concluded that chorismate synthase preferentially binds neutral flavin species, including the protonated reduced form, rather than anionic flavin species in the presence of EPSP or the 6-fluoro-substrate analog. Further support for this conclusion was obtained using 5-deaza- and 4-thio-FMN. Addition of EPSP to enzyme-bound, reduced 5-deaza-FMN produced spectral changes consistent with protonation of the flavin. Photoreduction of 4-thio-FMN in the presence of enzyme and the (6R)-6-fluoro-EPSP generated a reduced flavin species with absorbance properties of a neutral, reduced 4-thio-flavin. These results and their implications for the nature and kinetic properties of an observed flavin intermediate are discussed in the context of a possible role of reduced flavin as an electron donor to bound EPSP.


Synergistic antifibrinolytic action of the potato protease inhibitor and epsilon-aminocaproic acid.
Fibrinolysis inhibition by a mixture of potato inhibitor and E-aminocaproic acid was greater than might be expected from the sum of the antifibrinolytic effects of these inhibitors investigated separately. This inhibition was observed in studies on the plasma euglobulin fraction and in a system containing isolated elements of the fibrinolytic system. The synergistic antifibrinolytic action of the potato protease in hibitor and E-aminocaproic acid is probably due to the fact that these inhibitors have different mechanisms of action and thus there is no competition between them for the effectors in the enzyme molecule.


Circadian changes in CSF dopaminergic measures in restless legs syndrome.
Restless legs syndrome (RLS) has a circadian component with symptoms being prominent at night. The dopaminergic (DAergic) system, which plays a role in RLS, entails circadian changes that parallel RLS symptom changes. The aim of this study was to look for relative and diurnal differences in DAergic activity. All RLS subjects were treated prior to their enrollment in the study but were all drug-free for at least 2 weeks prior to evaluation. Cerebrospinal fluid (CSF) collected at 10 p.m. was used to determine DA-related co-factors and metabolites. These were compared to CSF values collected in a previous study at 10 a.m. The only significant finding from the 10 p.m. samples (30 RLS; 22 control) was increased 3-ortho-methyldopa (3OMD) for RLS compared to controls. A comparison of the 10 p.m. to 10 a.m. values (16 RLS; 9 controls) showed small, non-significant diurnal changes for controls but large diurnal changes in tetrahydrobiopterin (BH4), HVA:5HIAA ratio and 3OMD for RLS, with the 10 a.m. sample showing increases in all three CSF factors compared to the 10 p.m. sample. The greater diurnal changes in RLS suggest greater fluctuations than normal in DAergic circadian dynamics. The increased 3OMD concentration in the absence of concurrent exogenous levodopa (l-dopa) suggests changes in synthesis or metabolism of l-dopa in RLS.


[Comparative characteristics of adenosine triphosphatase activity in the erythrocytes of patients with acute and chronic liver diseases, chronic cholecystitis and in HBs antigen carriers].
A decrease in sodium, potassium and anion (HCO3)-activated erythrocyte ATPases is noted in patients with acute viral hepatitides A and B, chronic persisting hepatitis, liver cirrhosis, chronic cholecystitis and in HBs-antigen carriers, the reduction of HCO8-ATPase being more noticeable. A degree of expression of the above changes depends on the severity of a pathological process in the liver. The most serious changes are noted in liver cirrhosis. In this disease calcium ATPase activity is also on a decrease. Erythrocyte ATPase activity is lowered in chronic cholecystitis to a lesser degree. In patients with chronic persisting hepatitis and liver cirrhosis erythrocyte ATPase activity slightly increases, however it remains significantly lowered as compared to the control level. The determination of erythrocyte ATPase activity can be used for assessment of the status of patients with acute and chronic liver diseases.


Organochlorine and mercury contamination in fish tissues from the River Nestos, Greece.
Polychlorinated biphenyls (PCBs), hexachlorocyclohexane (HCH) isomers, dichlorodiphenyltrichloroethane (DDT) and its metabolites, other organochlorine pesticides such as hexachlorobenzene (HCB), chlordane compounds (CHLs, including trans-chlordane and cis- and trans-nonachlor) and the heavy metal mercury were quantified in muscle and liver of the European chub (Leuciscus cephalus, Linnaeus, 1758) and in the muscle of the barbel (Barbus cyclolepis, Heckel, 1837) at two sampling sites of the River Nestos, Greece. PCBs in muscle and DDTs in the liver tissues were the predominant organochlorinated contaminants. Among the PCBs, congeners 47 (up to 9.60 ng g(-1) wet wt.), 180 (up to 1.15 ng g(-1) wet wt.) and 190 (up to 1.50 ng g(-1) wet wt.) were the most frequent and abundant. The contamination degree by the sum of PCBs on the fish tissue samples from the River Nestos is lower or similar to PCB levels found in other ecosystems. Among the organochlorine pesticides, essentially only p,p'-DDD, p,p'-DDE and alpha-, beta- and gamma-HCH were found, with the former appearing at mean levels up to 30.71 ng g(-1) wet wt. From a public health standpoint, residue organochlorine pesticide levels from our work are considerably lower than the recommended tolerance limits. Finally, mean values of Hg in chub were significant lower (up to 31.04 ng g(-1) wet wt.) compared to those detected on barbel (up to 169.27 ng g(-1) wet wt.). The concentrations of Hg in fresh water fish from the River Nestos did not exceed WHO and US EPA health guidelines, and were suitable for human consumption.


Acute retinal necrosis caused by reactivation of herpes simplex virus type 2.
Acute retinal necrosis is a severe form of necrotizing retinitis. Acute retinal necrosis has been demonstrated to be caused by varicella-zoster virus and herpes simplex virus type 1. We treated three patients with acute retinal necrosis apparently caused by recrudescence of latent herpes simplex virus type 2. Primary viral infection was probably congenital, with documented perinatal herpes simplex virus type 2 infection in two patients. Bilateral chorioretinal scars were present in two patients, neither of whom had a history of ocular herpetic infection, suggesting that earlier subclinical chorioretinitis had occurred. In each case, periocular trauma preceded the development of retinitis by two to three weeks. These cases are evidently caused by trauma-induced reactivation of latent virus rather than the onset of a primary infection.


Thermodynamic parameters for the reduction reaction of membrane-bound cytochrome c in comparison with those of the membrane-free form: spectropotentiostatic determination with use of an optically transparent thin-layer electrode.
An optically transparent thin-layer electrode cell with a very small volume has been developed to investigate the formal reduction potential (E0) of horse heart cytochrome c with and without cardiolipin-containing lecithin liposomes. Temperature-dependent experiments of membrane-free cytochrome c (10-40 degrees C) yielded standard thermodynamic parameters in agreement with literature values. On the other hand, membrane-bound cytochrome c had a break point(s) at the range between 10 and 30 degrees C when the formal reduction potential was displayed with respect to temperature. Both enthalpy and entropy changes had large negative values in the high-temperature region (greater than 30 degrees C) relative to those of the membrane-free form, suggesting membrane participation during the reduction course of cytochrome c. In addition, we observed an extrathermodynamic relationship between enthalpy and entropy values among different cytochrome c's and horse heart cytochrome c with and without membrane.


Unusual forms of T cell gamma mRNA in a human T cell leukemia cell line: implications for gamma gene expression.
The expression and rearrangement of T cell rearranging (TRG) gamma genes in human leukemic cell lines has been examined. The cell line MOLT-17 produces abundant gamma mRNA which is translated into a protein found on the cell surface which is associated with the CD3 molecule. The analysis of the gamma mRNA sequences in MOLT-17, by cDNA cloning, shows transcripts of aberrantly rearranged genes as well as the productively rearranged allele. The productive allele consists of a rearranged V gamma 8 gene joined to J gamma 2. Two forms of aberrant transcript originate from the other rearranged gamma allele. One of these initiates just upstream of the unrearranged J gamma 2 segment, and the other initiates from a V gamma 8 gene segment joined to another J gamma segment, upstream of J gamma 2. An unusual feature of the latter transcript is that polyadenlyation has occurred at the end of the first exon of C gamma 2, where two conserved poly(A) addition signals occur. The MOLT-4 cell line, on the other hand, has productively and nonproductively rearranged gamma alleles, from which relatively little transcription occurs. These results define new J gamma segments in the human TRG gamma locus and suggest that positive activation of the gamma locus is necessary for high level transcription after rearrangement.


Saponins of plants of Panax species collected in Central Nepal, and their chemotaxonomical significance. III.
Panax pseudo-ginseng subsp. pseudo-ginseng has a carrot like root with a small rhizome. It was shown that the saponin composition of roots and rhizomes of this subspecies collected in Tibet and China was extremely poor. From the roots and rhizomes collected in Central Nepal, (specimen-PNct), only a small amount of an oleanolic acid saponin, beta-D-glucopyranosyl-oleanolate (2) was isolated together with a polyacetylene-alcohol, panaxynol (3). In another specimen (specimen-PNs), also collected in Central Nepal, two oleanolic acid saponins, stipleanoside R2 (4) and chikusetsusaponin IV (5) were detected. No dammarane saponin was identified in either specimen. P. pseudo-ginseng subsp. himalaicus (Subsp-H) has a big rhizome with a small round root. From rhizomes and roots of this subsp. collected in Central Nepal (specimen-HNct), a fairly large amount of dammarane saponins, ginsenosides-Rb1 (6), -Rd (7), -Re (9) and -Rg1 (10), gypenoside XVII (8), notoginsenoside-R1 (11), majonoside-R2 (12) and pseudo-ginsenoside-F11 (13) were isolated, while no oleanane saponin (oleanolic acid saponin) was identified in this subsp. Based on the present and previous studies, medicinal evaluation and chemogeographical correlation of Himalayan Panax spp. are discussed.


One column operation for (90)Sr/(90)Y separation by using a functionalized-silica.
Organo-ceramic hybrid materials have been developed as the separation media for a (90)Sr/(90)Y generator system. Currently available (90)Y is generally extracted from a mother solution by a solvent extraction or a successive column operation. Both processes are successfully applied to produce (90)Y with a high quality standard. However, such processes are highly dependent on what kind of extracting materials are employed. Hence, some of the previously developed technologies are not adequate for a (90)Y production because of a waste generation or leaching of radiolytic end-products from the extracting materials. In this study, high performance organo-ceramic hybrid materials have been applied for the extraction of (90)Y. The hybrid materials have properties of both a ceramic and a solvent extractant by molecularly implanting the extracting molecules on to the ceramic surfaces. In this study, organo-phosphorus functionalized hybrid materials are synthesized and tested as the separation media for the (90)Y/(90)Sr generator system. An adsorptive extraction with a small Sep-Pak type column can recover more than 92% of (90)Y with a contamination ratio of (90)Sr/(90)Y=1.2x10(-5) from the mother solution and 70% with 5x10(-7).


Advertisement call of Dendropsophus studerae (Carvalho-e-Silva, Carvalho-e-Silva and Izecksohn, 2003) (Anura: Hylidae), with new record and geographic distribution extension.
The treefrog genus Dendropsophus Fitzinger comprises 95 species, with geographic distribution from northern Argentina and Uruguay north through tropical South and Central America to tropical southern Mexico (Frost 2014). Dendropsophus studerae was included in the D. microcephalus clade by Faivovich et al. (2005), which currently consists of 39 species (Frost 2014). The species that most resembles D. studerae is D. bipunctatus (Spix), as already stated in the original description of the former (Carvalho-e-Silva et al. 2003). Thus far, Dendropsophus studerae was only known from its type locality, in the municipality of Quebrangulo (09º19'08"S, 36º28'16"W), State of Alagoas, northeastern Brazil. The original description of the species also included data on its eggs, tadpole (oral disc and external morphology) and some natural history information of adults and larvae, but its advertisement call remains undescribed.


Endocrine Manifestations in a Monocentric Cohort of 64 Patients With Erdheim-Chester Disease.
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by infiltration of foamy histiocytes in multiple organs. Endocrine involvement has mostly been described in case reports. We performed systematic endocrine evaluation in a large cohort of patients with ECD. This was a single-center observational study conducted between October 2007 and May 2013. The evaluation was conducted in Pitié-Salpêtrière Hospital (Paris, France), a tertiary care hospital. Sixty-four consecutive patients with ECD (sex ratio, 3.6; mean age, 57.6 years [range, 20-80 years]). Thirty-six patients had follow-up assessments. There were no interventions. Clinical, biological, and morphological evaluations of pituitary, gonadal, adrenal, and thyroid functions, as well as metabolic evaluation, were performed. Diabetes insipidus was found in 33.3% of patients, frequently as the first manifestation of ECD. Anterior pituitary dysfunction was found in 91.3% of patients with full anterior pituitary evaluation, including somatotropic deficiency (78.6%), hyperprolactinemia (44.1%), gonadotropic deficiency (22.2%), thyrotropic deficiency (9.5%), and corticotropic deficiency (3.1%). Thirty-five patients (54.7%) had ≥2 anterior pituitary dysfunctional axes, rising to 69.6% (16 of 23) when only patients with complete evaluations were considered. Two patients had panhypopituitarism. Infiltration of the pituitary and stalk was found with magnetic resonance imaging in 24.4% of patients. Testicular insufficiency was found in 53.1% of patients, with sonographic testicular infiltration in 29% of men, mostly bilateral. Computed tomography adrenal infiltration was found in 39.1% of patients, and 1 case of adrenal insufficiency was observed. No patient was free of endocrine hormonal or morphological involvement. Endocrine dysfunctions were most often permanent, and new deficits appeared during follow-up. Endocrine involvement is very frequent in ECD and should be evaluated carefully at diagnosis and during follow-up.


A comparative test of the adaptive plasticity hypothesis: relationships between habitat and phenotype in anuran larvae.
The hypothesis that phenotypic plasticity is maintained by divergent natural selection acting across different environments predicts that populations and species exposed to highly variable environments will express high levels of plasticity. I tested this prediction by measuring the behavioral and morphological responses to aeshnid dragonfly larvae of 16 tadpole species and asking whether predator-induced plasticity is greater in species that experience more variable densities of predators in nature. Tadpole phenotypes were measured in a series of similar experiments in outdoor artificial ponds carried out over a 9-yr period. I quantified tadpole habitats by soliciting evaluations by seven to 36 experienced field observers for each species. There were large differences among species in phenotype, mostly in agreement with earlier descriptions. Nearly all species responded to dragonflies by decreasing activity and body length relative to overall body size and by increasing relative tail fin depth, although the magnitude of the responses differed among species. There was a significant positive phylogenetic correlation between morphological plasticity and variability in exposure to predators, thus upholding the adaptive hypothesis. The correlation between behavioral responses and habitat variability was not significant, and there was little relationship between behavioral and morphological plasticity, raising the possibility that behavioral responses evolve under different scales of environmental variation than morphological responses.


Tumor necrosis factor receptor 1 signaling resistance in the female myocardium during ischemia.
Tumor necrosis factor-alpha (TNF) is increased in myocardial tissue after ischemia and reperfusion (I/R). TNF contributes to postischemic myocardial dysfunction and induces proinflammatory signaling, which may be mediated by the 55-kDa TNF receptor (TNFR1). In humans, there is a direct correlation between functional capacity, survival, and circulating TNF levels. Although decreasing the TNF level in animals was beneficial after myocardial ischemia, simply decreasing the bioavailability of TNF in humans with heart failure was not beneficial. This led to the important appreciation that TNF may have beneficial or deleterious effects in the heart, depending on which of its receptors is activated. Females have a lower incidence of heart failure and a higher heart failure survival than males. We hypothesized that TNFR1 signaling resistance occurs in the female myocardium during ischemia. Hearts from male and female TNFR1-knockout and wild-type (WT) mice were subjected to I/R. Female WT mice had better postischemic recovery than did male WT mice, an effect that appeared to be due to TNFR1 signaling resistance in females. Female WT mice had less myocardial depression after TNF infusion despite equivalent TNFR1 expression. Interestingly, TNFR1 ablation improved postischemic myocardial function, decreased activation of p38 mitogen-activated protein kinase, and reduced expression of interleukins-1beta and -6 in males but not in females. Furthermore, WT females expressed more of the suppressor of cytokine signaling protein 3 after I/R, which may in part explain TNFR1 signaling resistance in the female myocardium. This study demonstrates that sex differences exist in myocardial TNF signaling by TNFR1 after I/R.


[Disorders of psychological performance in mentally normal school children].
The authors deal with such psychic factors as weaknesses in concentration, reading and spelling which are to a major degree responsible for failure at school. These factors often occur in combination and may indicate early brain damage, in complex interaction with milieu conditions. Ample evidence of this is given in a literature survey. Principles of concentration training and a diagnostic verification procedure are then outlined, which have been derived from an analysis of attention requirements made at school. A therapy for reading and spelling weaknesses is dealt with, followed by a presentation of the results of training and catamneses. Using the method of Kossow mistakes were reduced by 78 percent and spelling marks improved considerably, after the children had returned to their original schools. In conclusion information is given on future projects for better assistance and prevention in the case of reading and spelling weaknesses at the elementary stage.


Incomplete Currarino triad as an embryological variant. Case report and review of the literature.
Currarino triad is a rare embryological complex of congenital caudal anomalies, including anorectal malformation, sacral osseous defect, and presacral mass, that results from abnormal separation of the neuroectoderm from the endoderm. The authors present an unusual case of a patient who had, in addition to the classic features of this syndrome, holocord syringomyelia, low conus medullaris, and tethered cord demonstrated by magnetic resonance imaging. They also discuss the embryological significance of this clinical entity and briefly review the relevant literature.


Comparison of human mesenchymal stem cells proliferation and differentiation on poly(methyl methacrylate) bone cements with and without mineralized collagen incorporation.
Poly(methyl methacrylate) bone cement is widely used in vertebroplasty, joint replacement surgery, and other orthopaedic surgeries, while it also exposed many problems on mechanical property and biocompatibility. Better performance in mechanical match and bone integration is highly desirable. Recently, there reported that incorporation of mineralized collagen into poly(methyl methacrylate) showed positive results in mechanical property and osteointegration ability in vivo. In the present study, we focused on the comparison of osteogenic behavior between mineralized collagen incorporated in poly(methyl methacrylate) and poly(methyl methacrylate). Human marrow mesenchymal stem cells are used in this experiment. Adhesion and proliferation were used to characterize biocompatibility. Activity of alkaline phosphatase was used to assess the differentiation of human marrow mesenchymal stem cells into osteoblasts. Real-time PCR was performed to detect the expression of osteoblast-related markers at messenger RNA level. The results show that osteogenic differentiation on mineralized collagen incorporated in poly(methyl methacrylate) bone cement is more than two times higher than that of poly(methyl methacrylate) after culturing for 21 days. Thus, important mechanism on mineralized collagen incorporation increasing the osteogenetic ability of poly(methyl methacrylate) bone cement may be understood in this concern.


Role of neoadjuvant treatment in clinical T2N0M0 oesophageal cancer: results from a retrospective multi-center European study.
The aims of this study were to compare short- and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy. Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short- and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics. No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short- or long-term outcomes. The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.


Use of segmental multifrequency bioimpedance spectroscopy in hemodialysis.
Whole body bioimpedance (BI) appears to be accurate and reproducible in the assessment of body composition, but does not appear useful for estimation of dry weight. Segmental BI has been used for the assessment of muscle mass in body segments, such as arms or legs and may be useful for rehabilitation studies. A promising new development is the application of segmental BI for dry weight determination. Changes in extracellular volume of the calf are recorded continuously during HD, thereby allowing the detection of a time-point at which no further volume is removed from the calf despite ongoing ultrafiltration (UF). Continuation of UF beyond this point is associated with an increased risk of intradialytic hypotension. This new technology may help optimizing the prescription of dry weight and UF rates in hemodialysis patients.


Stability of the Professional Development Assessment.
The Professional Development Assessment was constructed and pilot-tested with 76 students in three occupational therapy programs. A comparison of pretest and posttest scores yielded a significant correlation of .48, supporting the stability of responding over 1 to 2 years and suggesting usefulness of further development for evaluation of professional behaviors in students.


[Health risk factors for deer-breeders of Kolsky North].
The article deals with results of complex hygienic and psychologic study of medical and ecologic situation in two deer-breeding settlements of Kolsky North. The authors presented data on nutritional features, some aspects of deer-breeders' household character, psychologic state of population. The materials contain hygienic evaluation of the deer-breeders' radiation load caused by incorporated cesium.


The -491A/T polymorphism of the Apolipoprotein E gene is associated with the ApoEepsilon4 allele and Alzheimer's disease.
Several studies have attempted to confirm the association between the recently reported polymorphism located at position -491 in the transcriptional regulatory region of the Apolipoprotein E (ApoE) gene and Alzheimer's disease (AD). Results have been inconclusive, possibly due to the use of clinically diagnosed subjects and controls only. In this retrospective case-control study of 149 (96 AD and 53 controls) brain samples we show that homozygosity for the -491A variant is associated with an increased risk of development of AD. The genotype is also strongly associated with the presence of at least one epsilon4 allele (an established risk factor for AD) in women but not in men.


Arachidonyl-2-Chloroethylamide Alleviates Cerebral Ischemia Injury Through Glycogen Synthase Kinase-3β-Mediated Mitochondrial Biogenesis and Functional Improvement.
Arachidonyl-2-chloroethylamide (ACEA), a highly selective agonist of cannabinoid receptor 1 (CB1R), has been reported to protect neurons in ischemic injury. We sought to investigate whether mitochondrial biogenesis was involved in the therapeutic effect of ACEA in cerebral ischemia. Focal cerebral ischemic injury was induced in adult male Sprague Dawley rats. Intraperitoneal injection of 1 mg/kg ACEA improved neurological behavior, reduced infarct volume, and inhibited apoptosis. The volume and numbers of mitochondria were significantly increased after ACEA administration. Expression of mitochondrial transcription factor A (Tfam), nuclear transcription factor-1 (Nrf-1), and cytochrome C oxidase subunit IV (COX IV) were also significantly up-regulated in animals administered ACEA. One thousand nanomoles of ACEA inhibited mitochondrial dysfunction in primary rat cortical neurons exposed to oxygen-glucose deprivation (OGD). Furthermore, ACEA administration increased phosphorylation of glycogen synthase kinase-3β (GSK-3β) after reperfusion. Phosphorylation of GSK-3β induced mitochondrial biogenesis and preserved mitochondrial function whereas inhibition of phosphatidylinositol 3-kinase (PI3K) dampened phosphorylation of GSK-3β and reversed induction of mitochondrial biogenesis and function following ACEA administration. In conclusion, ACEA could induce mitochondrial biogenesis and improve mitochondrial function at the beginning of cerebral ischemia, thus alleviating cerebral ischemia injury. Phosphorylation of GSK-3β might be involved in the regulation of mitochondrial biogenesis induced by ACEA.


Socio-economic inequality in oral healthcare coverage: results from the World Health Survey.
The objective of this study was to assess socio-economic inequality in oral healthcare coverage among adults with expressed need living in 52 countries. Data on 60,332 adults aged 18 years or older were analyzed from 52 countries participating in the 2002-2004 World Health Survey. Oral healthcare coverage was defined as the proportion of individuals who received any medical care from a dentist or other oral health specialist during a period of 12 months prior to the survey, among those who expressed any mouth and/or teeth problems during that period. In addition to assessment of the coverage across wealth quintiles in each country, a wealth-based relative index of inequality was used to measure socio-economic inequality. The index was adjusted for sex, age, marital status, education, employment, overall health status, and urban/rural residence. Pro-rich inequality in oral healthcare coverage was observed within most of the countries, although lower income countries showed greater levels of relative inequality than higher income countries. Overall, lowest coverage and highest relative inequality were found in the low-income countries. The findings of this study may inform policies for oral health at global and national levels. To achieve universal coverage in oral healthcare, relevant interventions should reach the poorest population groups.


Neuroimmunopathogenesis of ts1 MoMuLV viral infection.
Newborn mice infected with ts1, a mutant of the Moloney murine leukemia virus, develop neuroimmunodegeneration with death and damage of thymocytes, astrocytes, and motor neurons by 24-38 days. T cells, B cells, and astrocytes, but not neurons, are infected by the virus. Primary splenocytes and thymocytes isolated from age-matched infected or control mice, when incubated in serum-deficient media containing phytohemagglutinin-L, either homotypically aggregate and survive or swell, expose their inner membrane phospholipids, and then shrink as they fragment their nuclei and excrete DNA-containing hypoploid minicells. In our present studies, the rates of these apoptotic changes were greatly increased in the infected cells. This thymocyte death was ameliorated in vitro by addition of Th2 cytokines, but not by Th1 cytokines, or by redox agents. In contrast, death of splenocytes, which were already mitogenically activated in vivo by the virus, was prevented by Th1 and Th2 cytokines plus redox support. In vivo, this ts1-induced neuroimmunodegenerative syndrome could be completely prevented by the immunomodulator polyinosine-cytosine and partially prevented by cytokines or redox modifiers. Viral titer primarily in the brain was also diminished by polyinosine-cytosine therapy. These observations indicate that the cell death in T cells and neurons in these ts1-infected neonatal mice can be prevented in vitro and in vivo by appropriate upregulation of the immune system.


Mild traumatic brain injuries: a 10-year follow-up.
Long-term consequences of mild traumatic brain injuries were investigated based on a 10-year follow-up of patients from a previously-published randomized controlled study of mild traumatic brain injuries. One aim was to describe changes over time after mild traumatic brain injuries in terms of the extent of persisting post-concussion symptoms, life satisfaction, perceived health, activities of daily living, changes in life roles and sick leave. Another aim was to identify differences between the intervention and control groups. The intervention group comprised 142 persons and the control group 56 persons. Postal questionnaires with a response rate of 56%. No differences over time were found for the intervention and control groups in terms of post-concussion symptoms. In the intervention group some variables in life satisfaction, perceived health and daily life were decreased. Some roles had changed over the years for both groups. No other differences between the intervention and control groups were found. However, in both groups sick leave decreased. Early individual intervention by a qualified rehabilitation team does not appear to impact on the long-term outcome for persons with symptoms related to mild traumatic brain injuries. The status after approximately 3 weeks is indicative of the status after 10 years.


The Management Academy for Public Health: the South Carolina experience.
In the late 1990s, the South Carolina Department of Health and Environmental Control (SCDHEC) was faced with the challenges of a workforce that was not prepared in public health; the impending loss of significant agency expertise, leadership, and institutional knowledge through retirement; the lack of available and accessible training; and continuing state budget cuts. Preparedness for bioterrorism and other public health emergencies was also of concern, a need made more urgent after 2001. To respond to current and emerging public health challenges, the SCDHEC had to have a workforce with the knowledge and skills necessary for the delivery of essential public health services. To address these challenges, the department partnered with the University of North Carolina in the pilot of the Management Academy for Public Health. The Management Academy is now integrated into the South Carolina workforce development strategy, and 199 staff members and 22 community partners have graduated from the program. Along with increased knowledge, skills, and abilities of individual staff and increased organizational and community capacity, a significant result of South Carolina's experience with the Management Academy for Public Health is the development of a training program for emergency preparedness modeled on the Management Academy. This highly successful program illustrates the replicability of the Management Academy model.


Anticipatory contrast effect in rats: a new view with lick response analysis and the effect of dopamine blocking.
A negative anticipatory contrast effect (NACE) is manifested as a suppression of the effect of a reward stimulus to elicit consummatory or instrumental responses when a second more potent reward is presented right afterward. No well-supported theory explains the effect. We analyzed NACE with rats' licking responses to 3 solutions with varying reward value: 8% sucrose mixed with 0.008% quinine (A), 8% sucrose with 0.002% quinine (B), and 32% sucrose with 0.008% quinine (C). 3 groups (n = 4) of rats were given 2 solutions in succession, each 5 min with 15 s in between, for a total of 11 days: Group AA (control), A then A; Group AB, A then B; Group AC, A then C. On days 13 to 16, and 12 and 17, pimozide (0.4 mg/kg, i.p.), and the vehicle solution were injected, respectively. Results show that the licking of A was a function of what solution to follow: In AC, the total number of licks, the short interlick interval (SILI), and the number of licks per s during the initial contact were less than AA. In AB, only SILI was less. Licking of A was initially low but increased over days, except for AC. The failure of AC to increase the licking was attributed to a "retroactive overshadowing" effect of a more potent stimulus C blocking stimulus A to form a reward learning, thus preventing its rewarding property to be fully manifested. It may also be due to stimulus A becoming a "signal" for incoming reward, thus degrading its own rewarding function. The shorter SILI in AB and AC suggested a reward devaluation; however, devaluation alone did not predict the consummatory response. Pimozide reduced licking number overall without altering the relative reward property or SILI suggesting that NACE was not a dopamine-mediated motivated choosing behavior.


Diurnal variation in total and undercarboxylated osteocalcin: influence of increased dietary phylloquinone.
A diurnal variation exists in blood levels of the vitamin K-dependent bone protein osteocalcin. However, it is not known whether the carboxylated and undercarboxylated constituents of osteocalcin also vary. Therefore, osteocalcin and undercarboxylated osteocalcin were measured in specimens collected every 4 hours over a 24-hour period in nine healthy subjects (five males, four females) ages 20-33 years who were consuming a mixed diet containing 100 microg of phylloquinone. Osteocalcin and undercarboxylated osteocalcin were measured by radioimmunoassay (RIA) before and after treatment with barium sulfate. Although the percent undercarboxylated osteocalcin did not change, a diurnal variation was observed in total osteocalcin, carboxylated osteocalcin, and undercarboxylated osteocalcin, with peak concentrations at 4 a.m. and the lowest concentrations between 12 p.m. and 4 p.m. The difference between the total osteocalcin peak and trough concentrations averaged 28 +/- 7 (SEM)%. There were no gender differences in these rhythms. The effect of dietary phylloquinone as a modulator of these rhythms was evaluated in a randomized study by increasing phylloquinone intake to 420 microg/day with fortified corn oil, split between the lunch and dinner meals. Total and carboxylated osteocalcin fluctuations and concentrations were not affected by the dietary treatment. The diurnal variation in undercarboxylated osteocalcin was abolished with supplementation and concentrations at 8 a.m. (14 hours following supplementation) (2.3 +/- 0.2 ng/ml) were significantly lower than the unsupplemented levels (2.7 +/- 0.2 ng/mL, P = 0.006). The percentage of undercarboxylated osteocalcin was similarly decreased after supplementation (19.7 +/- 1.3%) in relation to the mixed diet cycle (24.2 +/- 1.6%, P = 0.006) at 8 a.m. on the second day. Dietary supplementation induced a fluctuation in percentage undercarboxylated osteocalcin with a decline in levels starting at approximately 12 a.m. Therefore, additional dietary phylloquinone does not appear to modulate the total osteocalcin diurnal rhythm, but can influence its undercarboxylated component.


[Thymolipoma. A case report].
Thymolipoma is an uncommon benign tumor of the thymus. Asymptomatic, it is an incidental discovery. Pathogenesis remains controversial. We report a new case in a 36-year-old woman that was discovered on a chest x-ray ordered for pneumonia. The MRI findings suggested the diagnosis which was confirmed at the pathology examination of the surgical specimen.


Tissue iron distribution and urinary mineral excretion vary depending on the form of iron (FeSO4 or NaFeEDTA) and the route of administration (oral or subcutaneous) in rats given high doses of iron.
Sodium iron ethylenediaminetetraacetate (NaFeEDTA) has considerable promise as an iron fortificant in food. However, effects of administering high levels of NaFeEDTA on tissue iron distribution and mineral excretion are not well understood. The objectives of this study were to assess nonheme iron distribution in the body and urinary excretion of Ca, Mg, Cu, Fe, and Zn after daily administration of high levels of iron to rats over 21 days. Iron was either given orally with food or injected subcutaneously, as either FeSO 4 or NaFeEDTA. Selected tissues were collected for nonheme iron analysis. Estimated total body nonheme iron levels were similar in rats fed NaFeEDTA or FeSO 4, but the tissue distribution was different: it was 53% lower in the liver and 86% higher in the kidneys among rats fed NaFeEDTA than among those fed FeSO 4. In contrast, body nonheme iron was 3.2-fold higher in rats injected with FeSO 4 than in rats injected with NaFeEDTA. Administering NaFeEDTA orally elevated urinary Cu, Fe, and Zn excretion compared with FeSO 4 (1.41-, 11.9-, and 13.9-fold higher, respectively). We conclude that iron is dissociated from the EDTA complex prior to or during intestinal absorption. A portion of intact FeEDTA may be absorbed via a paracellular route at high levels of intake but is mostly excreted in the urine. Metal-free EDTA may be absorbed and cause elevated urinary excretion of Fe, Cu, and Zn.


CT virtual sialendoscopy versus conventional sialendoscopy in the visualization of salivary ductal lumen: an in vitro study.
To evaluate the feasibility of computed tomographic (CT) virtual sialendoscopy and its performance characteristics for the visualization of salivary ductal lumen as compared with conventional sialendoscopy. An in vitro study. Conventional sialendoscopy was performed in 16 submandibular glands in vitro and the surgical findings were recorded. Then a contrast agent was injected into the Wharton's duct via orifice. After CT scanning, the CT data were transferred to an independent workstation and were postprocessed with commercially available software to generate three-dimensional reconstructive and virtual sialendoscopic images. Finally, the plastination of submandibular glands was performed with 20% perchloroethylene ethyl acetate plastics filler to make cast specimens. CT three-dimensional reconstruction of the ductal system was compared with the cast specimen, and the performance of conventional sialendoscopy and CT virtual sialendoscopy for the visualization of salivary ductal lumen was also compared. The CT data acquisition and postprocessing protocol were feasible. CT three-dimensional reconstruction enabled clear visualization of the ductal system from any directions and angles, which showed close resemblance to the cast specimens. And CT virtual sialendoscopy created clear endoluminal views of salivary ducts simulating those obtained with conventional sialendoscopy. Our initial experience shows that CT virtual sialendoscopy has the potential to be an attractive imaging technique for the visualization of salivary ductal lumen.


Fabrication of a laser patterned flexible organic light-emitting diode on an optimized multilayered barrier.
The fast-growing market of organic electronics stimulates the development of versatile technologies for structuring thin-film materials. Ultraviolet lasers have proven their full potential for patterning organic thin films, but only a few studies report on interaction with thin-film barrier layers. In this paper, we present an approach in which the laser patterning process is optimized together with the barrier film, leading to a highly selective patterning technology without introducing barrier damage. This optimization is crucial, as the barrier damage would lead to moisture and oxygen ingress, with accelerated device degradation as a result. Following process optimization, a laser processed flexible organic LED has been fabricated and thin-film encapsulated and its operation is shown for the first time in atmospheric conditions.


Immunodepression in hamsters experimentally infected with Opisthorchis viverrini.
Hamsters experimentally infected with Opisthorchis viverrini had significant depression of the antibody response to sheep red blood cells. The depression was more severe with prolonged infections. Lymphoproliferative response to phytohaemagglutinin stimulation was also depressed when compared with uninfected controls. The immunodepression in these animals was abolished by anthelmintic treatment, suggesting that the immunodepressive effect is reversible and is associated with active infection.


The interactions of hyperactive and normal boys with their fathers and mothers.
This study examined the interactions of fathers and mothers with their hyperactive and normal children during both free-play and task periods. Eighteen hyperactive and 18 normal boys were observed interacting separately with their mothers and fathers in a playroom setting. Behavioral observations indicated, with minor exceptions, that fathers and mothers did not differ in their interactions with their sons. Substantial differences were found between hyperactive and normal boys in their parent-child interactions, particularly during the task setting. Hyperactive boys were generally less compliant and their parents more directive than normal parent-child dyads. Methodological problems are discussed that may have precluded the emergence of differences between mothers and fathers in their interactions with their sons.


Correlation between shiftide activity and HIV-1 integrase inhibition by a peptide selected from a combinatorial library.
The human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein is an emerging target for the development of anti-HIV drugs. We recently described a new approach for inhibiting IN by "shiftides"--peptides that inhibit the protein by shifting its oligomerization equilibrium from the active dimer to the inactive tetramer. In this study, we used the yeast two-hybrid system with the HIV-1 IN as a bait and a combinatorial peptide aptamer library as a prey to select peptides of 20 amino acids that specifically bind IN. Five non-homologous peptides, designated as IN-1 to IN-5, were selected. ELISA studies confirmed that IN binds the free peptides. All the five peptides interact with IN with comparable affinity (K(d approximately )10 microM), as was revealed by fluorescence anisotropy studies. Only one peptide, IN-1, inhibited the enzymatic activity of IN in vitro and the HIV-1 replication in cultured cells. In correlation, fluorescence anisotropy binding experiments revealed that of the five peptides, only the inhibitory IN-1 inhibited the DNA binding of IN. Analytical gel filtration experiments revealed that only the IN-1 and not the four other peptides shifted the oligomerization equilibrium of IN towards the tetramer. Thus, the results show a distinct correlation between the ability of the selected peptides to inhibit IN activity and that to shift its oligomerization equilibrium.


Contribution to the elucidation of the structure of the bacterial flagellum nano-motor through AFM imaging of the M-Ring.
The flagellar nano-motor of bacteria is one of the most interesting and amazing natural nano-machine. Despite its discovery 30 years ago, some details of its structure and mechanisms are not yet elucidated. Several studies have revealed some important aspects of its structure and numerous data are available today; however, the inner mechanisms of the nano-motor have not been yet resolved, partially due to the lack of information about the 3D assembly, shape and interactions of the different parts in experimental environment as close as possible as the native cellular conditions. We have developed an approach using atomic force microscopy imaging in liquid media, which allows us to study part of the motor in native liquid environment. In this work, we are interested in the FliG proteins, identified as the key functional proteins of this nano-machine. We report 3D images of their assembly on surfaces, which could be representative of the so-called M-ring part of the nano-motor. These images have been acquired on both mica surfaces and on supported bilayer membranes mimetics of E. coli native membrane. The systematic analysis of the shape and the size of different recorded assemblies made us believe that the FliG organization we observed could lead to a new model for the structure and mechanism of the flagellar nano-motor.


Development and validation of an HPLC-MS-MS method for quantitating bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate (Tinuvin 770) and a related substance in aqueous extracts of plastic materials.
Tinuvin 770 is a light stabilizer present in numerous polymers utilized in medical or pharmaceutical applications (e.g., manufacturing, packaging, delivery systems and devices). Under conditions of use, Tinuvin 770 and its related substances may leach from the polymers and accumulate in pharmaceutical products that are administered to subjects to produce a therapeutic benefit. In order to establish the amounts of Tinuvin 770 that may be extracted from such systems and devices, sensitive and selective analytical methodologies are required. A liquid chromatographic method with tandem mass spectrometric detection (LC-MS-MS; API-ES, positive ion mode) has been developed for the purpose of quantitating Tinuvin 770 and a related substance at low concentrations [200 ng/mL (ppb) or less] in aqueous extracting media. Issues related to injection-to-injection carryover and sample matrix effects were mitigated by the addition of potassium chloride to the test samples, where the potassium ion increases Tinuvin solubility via a "salting in" effect. The developed method was validated for this application by assessing performance characteristics including accuracy, response linearity, precision, specificity, and solution stability. The validated method is suitable for the quantitation of these analytes in the concentration range of 1-200 ng/mL.


Colonization and infection of mothers and neonates with group B streptococci in three Italian hospitals.
In the absence of previous published studies from Italy on the epidemiology of group B streptococci we investigated 1516 mothers at delivery and 1294 neonates in three hospitals. Of mothers in labour, 7.5% were colonized with group B streptococci and 4.9% of their babies. Of the neonates born to a positive mother 45.1% were colonized, whilst only 2.2% of babies born to a negative mother were colonized. For the mothers, the vagina was colonized more often (7.3% of all women) than the cervix (6.0%), the urethral meatus (3.9%) or the rectum (2.9%). For the neonates, the rates of colonization of the throat, external auditory canal, and the umbilicus were 3.2%, 3.0% and 2.6%, respectively. The distributions of the serotypes were similar to that reported from other parts of Europe and the USA and vertical transmission of group B streptococci was demonstrated in most of the mothers and their neonates. Of 30 mother-neonate pairs, 25% of mothers carried group B streptococci intermittently and 58% had persistent carriage until the 90th day postpartum, the rectum being the commonest positive site. Of 20 infants that were positive at birth, only six were still positive on the 15th day and none by the 90th day of life. Of 1294 infants, four (0.3%) developed early-onset sepsis with group B streptococci and one died. The overall incidence of clinical infection amongst colonized infants was 6.2%.


It's time to retire. Retirement.
Companies have been so focused on down-sizing to contain costs that they've largely neglected a looming threat to their competitiveness: a severe shortage of talented workers. The general population is aging and with it, the labor pool. People are living longer, healthier lives, and the birthrate is at a historical low. During the next 15 years, 80% of the native-born workforce growth in North America--and even more in much of Western Europe--is going to be in the over-50 age cohort. When these mature workers begin to retire, there won't be nearly enough young people entering the workforce to compensate. The Bureau of Labor Statistics projects a shortfall of 10 million workers in the United States in 2010, and in countries where the birthrate is well below the population replacement level (particularly in Western Europe), the shortage will hit sooner, be more severe, and remain chronic. The problem won't just be a lack of bodies. Skills, knowledge, experience, and relationships walk out the door every time somebody retires--and they take time and money to replace. And while the brain drain is beginning now, the problem is going to become much more acute in the next decade or so, when baby boomers--more than one-quarter of all Americans, amounting to 76 million people--start hitting their mid sixties. Based on the results of their yearlong research project, the authors of this article offer recommendations for gaining the loyalty of older workers and creating a more flexible approach to retirement that allows people to continue contributing well into their sixties and seventies. Companies can no longer afford to think of retirement as a onetime event, permanently dividing work life from leisure.


Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease.
Lafora disease (LD) is an autosomal recessive form of progressive myoclonus epilepsy with onset in childhood or adolescence and with fatal outcome caused by mutations in two genes: EPM2A and NHLRC1. The aim of this study was to characterize the mutation spectrum in a cohort of unrelated patients with presumed LD. Sequencing of the two genes and search for large rearrangements was performed in 46 unrelated patients with suspected LD, 33 originating from France and the others from different countries. Patients were classified into two groups according to the clinical presentation. Mutations of various types were found in EPM2A in 10 patients and in NHLRC1 in 4 patients. Mutations were found in 14 (93%) of 15 patients with classical clinical and electroencephalography (EEG) presentation of LD and in no patients with an atypical presentation. Ten mutations were novel, including the first substitution reported in a donor splice site of EPM2A, leading to the deletion of exon 2 at the RNA level. Four large deletions, including two deletions of exon 2 with different sizes and breakpoints, were found in EPM2A, corresponding to 20% of the alleles of this gene. We described several novel mutations of EPM2A and NHLRC1 and brought additional data to the genetic epidemiology of LD. This study emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy.


The effects of distraction during exposure to phobic stimuli.
Theoretical conceptualizations regarding the role of attentional focus during exposure-based treatments for fear and anxiety suggest that distraction interferes with the mechanisms required for fear reduction, typically by preventing emotional and/or cognitive processing of the phobic stimulus and response. The present discussion reviews the current literature and demonstrates the paucity of empirical evidence supporting such notions. Seemingly conflicting findings are integrated upon close examination of the various qualitative dimensions of the distracters employed. These characteristics, which differed substantially across studies, include the nature of the attentional demand posed by the distracter (e.g. cognitive vs sensory demand) as well as the distracter's affective quality (e.g. neutral vs relaxing). The effects of differing dimensions of distraction on fear reduction, in addition to interaction with aspects of the exposure situation, are discussed. The need for further investigation of the qualitative dimensions of distraction, including their operational specification, is recognized. Finally, recommendations for future research are made.


Evaluation of DNA extraction methods for dried blood spots in the diagnosis of congenital cytomegalovirus infection.
Dried blood spots (DBS) may be valuable in the diagnosis of congenital cytomegalovirus (CMV) infection. However, the 2007 European Quality Control for Molecular Diagnostics (QCMD) proficiency testing programme showed that CMV DNA detection in DBS was lacking sensitivity in a considerable number of participating laboratories. To compare DNA extraction methods for DBS for detecting CMV. Sensitivity and applicability of the methods for high-throughput usage were assessed. Guthrie cards were spotted with CMV DNA-positive whole blood (n=15). DNA was extracted from the DBS using different extraction methods, followed by CMV amplification by means of real-time PCR. Significant differences between the extraction methods with respect to the sensitivity were found. Optimal sensitivity was achieved when samples were tested in triplicate, demonstrating that the methods in general operated around their detection limits. Triplicate testing using the protocol by Barbi et al. [Barbi M, et al. Cytomegalovirus DNA detection in Guthrie cards: a powerful tool for diagnosing congenital infection. J Clin Virol 2000;17:159-65], representing the most sensitive methods, resulted in sensitivities of 100%, 86%, and 50% for DBS with CMV DNA loads of 5-4, 4-3, and 3-2log(10)copies/ml, respectively. This indicates that sensitivity limitations apply in the clinically relevant concentration range. Few methods appeared suitable for 96-well format high-throughput testing. When considering universal neonatal screening for congenital CMV infection, an assay which is both sensitive and applicable for high-throughput testing is required. The protocol by Barbi et al. and the BioRobot Universal System appear appropriate candidates currently available for 96-well format application in neonatal screening using DBS.


Dynamics of polyelectrolyte solutions under a constant gradient of base concentration.
Phase-separation dynamics of weakly charged polyacid solutions under a constant gradient of base concentration is studied both theoretically and numerically. The time-evolution equation of polymer volume fraction is derived by assuming that the chemical equilibrium of the dissociation reaction is locally established. Numerical simulations of the system in contact with two reservoirs in which the base concentrations differ are performed. The numerical results show that the polymer volume fraction can be transported by the concentration gradient of the base, which leads to the dynamic behavior of mesophase domain structures.


Three-dimensional electromagnetic imaging of dielectric targets by means of the multiscaling inexact-Newton method.
A novel approach for three-dimensional electromagnetic imaging is presented. This technique is a combination of an iterative multiscaling approach with an inexact-Newton method. The multiscaling procedure allows one to iteratively focus the region of interest on the detected target, whereas the inexact-Newton method provides an efficient regularized solution of the nonlinear electromagnetic inverse scattering problem for each scaling step. The proposed method is validated against numerical data with different configuration settings. A preliminary experimental validation is also reported.


Equally increased hypercoagulability irrespective of using minimized or conventional ECC systems.
Minimized extracorporeal circulation systems in coronary artery bypass may have less impairing effect on hematological parameters and bleeding compared to conventional systems. The aim of this study was to investigate whether the use of mini systems does result in an increased postoperative hypercoagulative status. Patients with increased risk of postoperative blood transfusion were randomly allocated to coronary bypass surgery using conventional or minimized extracorporeal circulation. Serial thrombelastographic analysis was performed preoperatively, at day 1 and 5. Forty-six patients were included. In 56% of the patients in the experimental and in 62% in the control group an activated coagulation system, measured as maximal amplitude above normal reference was found preoperatively. This was normalized the day after operation. At day 5 a significant number of patients in the experimental group (p = 0.03) overshooted the preoperative maximal clot strength compared to the control group (p = 0.15); however, a direct intergroup analysis showed no difference. In both groups, hemoglobin levels and platelet counts decreased at day one after surgery. At day 5, hemoglobin was partly and platelets completely normalized. No differences were found with respect to transfusion needs. Mini systems seem to induce at least an equal increased state of hypercoagulability after coronary surgery. No clinical relevant differences could be demonstrated. This could indicate that patients after using mini systems are not protected against a postoperative state of increased hypercoagulability.


Twenty years of pharmacology.
During the past 20 years in pharmacology, a number of innovations have appeared that have resulted in significant changes in the drugs available for people with traumatic brain injury. Among the anticonvulsants, antidepressants, and antipsychotics, new drugs have appeared with fewer cognitive side effects. In these classes of drugs, as well as among central nervous system stimulants, once-daily or other sustained-release preparations have been introduced that make it considerably more likely that the patient will take his or her medication, with smaller fluctuations in drug levels as well. New drugs have also resulted in a greater number of medications for the clinician to choose from. The overall effect has been a dramatic change in pharmacology that has benefited people with traumatic brain injury.


Focused, evanescent, hollow, and collimated beams formed by microaxicons with different conical angles.
Diffraction patterns formed by axicons with different tip (vertex) angles are analytically and numerically investigated. Results show that the axicon (or tapered dielectric probe) can form an extended axial light beam, a compact evanescent field, a hollow beam, and a collimated beam, depending on the vertex angle. Two-dimensional and three-dimensional models of a tapered dielectric probe show that, with small changes to the vertex angle, light transmitted by the probe is scattered rather than focused, and vice versa. Angle meanings corresponded to boundary transitions have a quantum character and densify as the angle approaches zero. These features should be taken into consideration when manufacturing microaxicons intended for various applications.


[Estimate of daily cases of influenza from the cases notified to the Reportable Disease System: usefulness in time series studies].
In time series analyses assessing the relationship between risk factors and respiratory diseases or mortality, influenza incidence is a potential cofounder and, therefore, must be controlled. Available influenza data come from weekly compulsory notifiable disease (EDO system). Furthermore, its graphical distribution, suggests that information may be underestimated in holiday periods. We have applied a procedure for estimate daily influenza series from the weekly cases, using less, a non-parametric local fit. Findings show that smoothing could avoid stepping and sudden peaks in the original series.


Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C.
The healthy liver of adult humans has little or no lymphocyte component and the histological finding of intrahepatic lymphocytes (IHL) is evidence of liver pathology. In a liver injured by chronic hepatitis C, the most common chronic liver disease, most IHL are activated/pro-inflammatory cells, which are particularly enriched for effectors of innate immunity (natural killer (NK), natural T, and other NK-like T cells). IHL do not undergo clonal expansion in the liver but migrate from extrahepatic sites to the chronically infected liver, where they display effector function and subsequently die, suggesting that maintenance of the IHL pool depends on continuous lymphocyte migration. The cytotoxic and inflammatory functions of these IHL have three potential outcomes: 1) they could be helpful in clearing the virus (a rare case in hepatitis C virus (HCV) infection); 2) they could be useless and have no effect on the infection; or 3) they could be harmful, whereby overaggressive lymphocyte responses destroy the liver in a continuous and unsuccessful attempt to clear the virus. Unfortunately, we do not know as of yet which of these possibilities is the case and, therefore, a more complete picture of the intrahepatic immune response will be relevant to the development of new therapeutic strategies against HCV. Additionally and from a more general perspective, due to the availability of biopsied material and the high prevalence (approximately 3%) of HCV infection worldwide, studying the chronically inflamed liver of hepatitis C patients is an ideal model to investigate the poorly understood processes of lymphocyte trafficking, activation and death to non-lymphoid sites of chronic inflammation in man.