Ultrasonic-accelerated rapid protocol for the improved synthesis of pyrazoles.
A simple, catalyst-free, green synthetic protocol is described for the one-pot synthesis of pyrazoles via multicomponent reaction of aromatic aldehydes, hydrazine monohydrate and ethyl acetoacetate and malononitrile/ammonium acetate in water under ultrasound irradiation. This protocol avoids traditional chromatography and purification steps and it affords highly selective conversion with no byproducts.


Dexmedetomidine Maintains Its Direct Cardioprotective Effect Against Ischemia/Reperfusion Injury in Hypertensive Hypertrophied Myocardium.
Dexmedetomidine (DEX) has a direct cardioprotective effect against ischemia/reperfusion injury through endothelial nitric oxide synthase (eNOS) phosphorylation via α2-adrenoreceptor (α2-AR). By using spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat models, the cardioprotective effect of DEX in hypertrophied myocardium and the differential characteristics of cardiac α2-AR and the I1 imidazoline receptor (I1R) were examined. Langendorff-perfused rat hearts underwent 40 minutes of global ischemia followed by 120 minutes of reperfusion in the presence or absence of DEX before ischemia. Infarct size was measured, and eNOS phosphorylation was assessed by Western blotting. The presence and expression of the receptors were assessed by immunohistochemistry, real-time reverse transcriptase polymerase chain reaction, and Western blotting. In WKY, DEX significantly decreased infarct size and increased phosphorylated-eNOS/eNOS. These effects were counteracted by yohimbine (α2-AR antagonist) and efaroxan (α2-AR and I1R antagonist). In SHR, DEX significantly decreased infarct size, and the effect was counteracted by efaroxan but not yohimbine. DEX did not alter phosphorylated-eNOS/eNOS in SHR. α2-AR and I1R were observed in WKY and SHR hearts. Although alpha2A-AR and alpha2B-AR messenger RNA and protein levels were upregulated in SHR, I1R expression was comparable between the 2 species. In the hypertrophied heart, DEX maintains its direct cardioprotective effect against ischemia/reperfusion injury via I1R in an eNOS-nondependent manner despite upregulation of α2-AR.


[The structure of the centromeric region and chromosome behavior in the anaphase after incubating murine cells with the fluorochrome Hoechst 33258].
Mouse chromosome behaviour has been studied in the anaphase, after the cells (culture L) were incubated with fluorochrome Hoechst 33258, provoking the stretching of the chromosome centromeric regions. It was shown that in spite of marked structural changes in the centromere, the cells entered the anaphase and chromosomes preserved their ability to separate towards the spindle poles. At the same time, in the presence of Hoechst 33258, a reliable increase in the anaphase duration could be observed from 4.0 +/- 0.2 min in control to 6.0 +/- 0.5 min after a prolonged incubation of cells with the fluorochrome. Also, the increase in the frequency of chromosomal bridges in anaphase and the appearance of bridges in interphase cells were observed.


Model for light scattering in biological tissue and cells based on random rough nonspherical particles.
A random nonspherical model for biological tissue and cells permits a better description of their optical properties. Rough surface nonspherical particles have been employed to model biological tissue and cells. The phase function, the anisotropy factor of scattering, and the reduced scattering coefficient are derived. The effect of different size distributions is also discussed. The theoretical results show good agreement with experimental data.


Immunomodulatory activity of Aegle marmelos in freshwater fish (Catla catla) by non-specific protection.
The production of fish is limited by infectious diseases; when a fish grows in an immunosuppressed condition, it becomes highly susceptible to disease. The present research work investigates immunomodulatory action of Aegle marmelos (Linn.) Corr. Serr. (Rutaceae) in Catla catla Hamilton (Cyprinidae) for enhancing immune protection of the fish against bacterial infections. Doses of 0, 5, 10, 15, 20, 25 and 30 g aqueous plant leaf extract/kg feed were administered orally to the freshwater fish, Catla catla for a period of 30 days to investigate its efficiency to enhance the non-specific immune responses against the fish pathogen Pseudomonas aeruginosa (Schröter) Migula (Pseudomonadaceae). The fish were challenged with pathogens through water medium for 30 days and the immunomodulatory effect of the Aegle marmelos was evaluated on the blood samples every 5 days until 15 days after infection. The results obtained from the study shows that the 25 g leaf extract/kg of feed was found to be competent to enhance optimum immune response. The effectiveness of the immunostimulant action was found to be best for the first 5 days after challenging with pathogen and subsequently, the immune response was found to decline in all the concentrations of plant extract. The results of the study will be helpful for further investigation in the field to improve the immunocompetence of fish against bacterial pathogens.


Absorption of subcutaneously administered regular human and porcine insulin in different concentrations.
The influence of the insulin concentration on its absorption from the subcutaneous tissues was studied by direct measurement of the appearance of insulin in the circulation after its subcutaneous administration. 10 units of regular insulin of semisynthetic human and porcine origin in strength of 15 units/ml, 40 units/ml, and 100/units/ml were administered as bolus to 9 healthy male volunteers, using switched-off, manually handled insulin pumps. Insulinaemia rose significantly higher (p less than 0.05) and insulin levels peaked earlier after the delivery of the 15 units/ml insulin solutions compared to the 100 units/ml insulin solutions. These findings might be of interest for type-I diabetic patients using insulin pumps that are to be loaded with regular insulin in varying concentrations.


Evidence of two distinct oxygen complexes of reduced endothelial nitric oxide synthase.
Oxygen binding to the oxygenase domain of reduced endothelial nitric oxide synthase (eNOS) results in two distinct species differing in their Soret and visible absorbance maxima and in their capacity to exchange oxygen by CO. At 7 degrees C, heme-oxy I (with maxima at 420 and 560 nm) is formed very rapidly (k(on) approximately 2.5.10(6) m(-1).s(-1)) in the absence of substrate but in the presence of pterin cofactor. It is capable of exchanging oxygen with CO at -30 degrees C. Heme-oxy II is formed more slowly (k(on) approximately equal to 3.10(5) m(-1).s(-1)) in the presence of substrate, regardless of the presence of pterin. It is also formed in the absence of both substrate and pterin. In contrast to heme-oxy I, it cannot exchange oxygen with CO at cryogenic temperature. In the presence of arginine, heme-oxy II is characterized by absorbance maxima near 432, 564, and 597 nm. When arginine is replaced by N-hydroxyarginine, and also in the absence of both substrate and pterin, its absorbance maxima are blue-shifted to 428, 560, and 593 nm. Heme-oxy I seems to resemble the ferrous dioxygen complex observed in many hemoproteins, including cytochrome P450. Heme-oxy II, which is the oxygen complex competent for product formation, appears to represent a distinct conformation in which the electronic configuration is essentially locked in the ferric superoxide complex.


Developing a synchronous otolaryngology telemedicine Clinic: Prospective study to assess fidelity and diagnostic concordance.
To evaluate diagnostic concordance of a synchronous telemedicine otolaryngology clinic with use of currently available technology. Prospective. Patients in a rural otolaryngology clinic were enrolled in a pilot telemedicine clinic. To assess system fidelity, an on-site and remote (consulting) otolaryngologist conducted simultaneous patient evaluations using streaming telecommunication technology for all aspects of the clinical encounter, including high-definition examination and endoscopic images. Both physicians and patients were blinded and diagnoses recorded. Post-encounter physician surveys and an original patient-centered TeleENT Satisfaction Questionnaire (TESQ) were used to assess overall satisfaction. Twenty-one patients were enrolled consecutively. Visual technology was found acceptable in all cases, and audio technology was acceptable in 20 of 21 encounters. Patient satisfaction was 96%, and patients felt comfortable using a telemedicine system in the future. Encounters were not significantly longer than traditional encounters. Physician diagnostic agreement was found in 95% of cases, and the consulting physician indicated that all encounters provided sufficient history, examination, and high-quality images to generate an accurate diagnosis, order additional workup, and/or make an appropriate referral. A synchronous otolaryngology telemedicine clinic is comparable to a standard clinic in terms of diagnostic concordance and patient satisfaction when using streaming technology and high-definition images. Using telemedical technology may be a viable way to increase otolaryngology access in remote or underserved areas. With system validity now established, future studies will assess the feasibility of using trained on-site physician extenders (nurse practitioners or physician assistants) to conduct in-person patient encounters with remote otolaryngologist support. 2c. Laryngoscope, 128:1068-1074, 2018.


Flow Rate Through Pigtail Catheter Used for Left Heart Decompression in an Artificial Model of Extracorporeal Membrane Oxygenation Circuit.
In refractory cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (ECMO) can be initiated. Although left heart decompression can be accomplished by insertion of a left atrial (LA) or left ventricular (LV) cannula using a percutaneous pigtail catheter, the venting flow rate according to catheter size and ECMO flow rate is unknown. We developed an artificial ECMO circuit. One liter saline bag with its pressure set to 20 mm Hg was connected to ECMO to mimic LV failure. A pigtail catheter was inserted into the 1 L saline bag to simulate LV unloading. For each pigtail catheter size (5-8 Fr) and ECMO flow rate (2.0-4.0 L/min), the moving distance of an air bubble that was injected through a three-way stopcock was measured in the arterial pressure line between the pigtail catheter and ECMO inflow limb. The flow rate was then calculated. We obtained the following equation to estimate the pigtail catheter flow rate.Pigtail vent catheter flow rate (ml/min) = 8×ECMOflow rate(L /min)+9×pigtail catheter size(Fr)- 57This equation would aid in designing of a further study to determine optimal venting flow rate. To achieve optimal venting flow, our equation would enable selection of an adequate catheter size.


Customization of biomedical terminologies.
Within the biomedical area over one hundred terminologies exist and are merged in the Unified Medical Language System Metathesaurus, which gives over 1 million concepts. When such huge terminological resources are available, the users must deal with them and specifically they must deal with irrelevant parts of these terminologies. We propose to exploit seed terms and semantic distance algorithms in order to customize the terminologies and to limit within them a semantically homogeneous space. An evaluation performed by a medical expert indicates that the proposed approach is relevant for the customization of terminologies and that the extracted terms are mostly relevant to the seeds. It also indicates that different algorithms provide with similar or identical results within a given terminology. The difference is due to the terminologies exploited. A special attention must be paid to the definition of optimal association between the semantic similarity algorithms and the thresholds specific to a given terminology.


Applying high-throughput methods to develop a purification process for a highly glycosylated protein.
Micro-scale chromatography formats are becoming more routinely used in purification process development because of their ability to rapidly screen large number of process conditions at a time with minimal material. Given the usual constraints that exist on development timelines and resources, these systems can provide a means to maximize process knowledge and process robustness compared to traditional packed column formats. In this work, a high-throughput, 96-well filter plate format was used in the development of the cation exchange and hydrophobic interaction chromatography steps of a purification process designed to alter the glycoform distribution of a small protein. The significant input parameters affecting process performance were rapidly identified for both steps and preliminary operating conditions were identified. These ranges were verified in a packed chromatography column in order to assess the ability of the 96-well plate to predict packed column performance. In both steps, the 96-well plate format consistently led to underestimated glycoform-enrichment levels and to overestimated product recovery rates compared to the column-based approach. These studies demonstrate that the plate format can be used as a screening tool to narrow the operating ranges prior to further optimization on packed chromatography columns.


The hypoplastic left heart syndrome is not a risk factor for Fontan operation.
To show the mortality rate of children undergoing to Fontan operation and determine whether the hypoplastic left heart syndrome (HLHS) is a risk factor for hospital mortality. From August 2001 to June 2008, 76 patients underwent Fontan operation and were divided into two groups: group A with 54 patients, 31 (40.7%) patients with tricuspid atresia and variants, six (7.8%) of double-inlet left ventricle, four (5.3%) and atrioventricular septal defect and total 13 (17.1%) of other complex congenital heart disease and group B all patients with HLHS a total of 22 (28.9%) patients. Group A patients had a mean age of 6.47 years ± 4.83 and group B of 2.08 years ± 0.24 P <0.001, the average weight was 22.42 ± 11.04 against 12.99 ± 1.2 P = 0.016, the mean CPB time was 119.5 min versus 113.3 min P = 0.0, with a mean clamping time of 74.8 min and 73.5 min p = 0.75. The mean ICU stay was 4.1 days for group A versus 7.52 days for group B p = 0.0003. In total (group A + B) three patients died, with hospital mortality of 3.9%, and one patient with HLHS (4.54%) (P <0.001, 95% CI 0.001 to 0.228). Our study shows that despite higher morbidity in HLHS is not a risk factor for hospital mortality.


Global changes of chlorophyll excitonic interactions in photosystem II during thermal denaturation.
Photosystem II (PSII) is a multisubunit chlorophyll-binding enzyme that absorbs light to catalyze water oxidation and plastoquinone reduction. Chlorophyll excitonic interaction changes in PSII were studied by absorption and circular dichroism spectra from 25 degrees C to 80 degrees C, and protein subunit denaturation was monitored by differential scanning calorimetry. A four-stage process of chlorophyll excitonic interaction change was observed being correlated with the denaturation of protein subunits.


A novel role of CXCR4 and SDF-1 during migration of cloacal muscle precursors.
The cloaca acts as a common chamber into which gastrointestinal and urogenital tracts converge in lower vertebrates. The distal end of the cloaca is guarded by a ring of cloacal muscles or sphincters, the equivalent of perineal muscles in mammals. It has recently been shown that the development of the cloacal musculature depends on hindlimb muscle formation. The signaling molecules responsible for the outward migration of hindlimb myogenic precursors are not known. Based on the expression studies for CXCR4 and SDF-1, we hypothesized a role of this signaling pair during cloacal muscle precursor migration. The aim of our study was to investigate the role of SDF-1/CXCR4 during cloacal muscle precursor migration in the chicken embryos. We show that SDF-1 is expressed in the cloacal region, and by experimentally manipulating the SDF-1/CXCR4 signaling, we can show that SDF-1 guides the migration of CXCR4-expressing cloacal muscle precursors.


Single-dose versus multiple-dose piperacillin prophylaxis in primary cesarean operation.
A prospective, randomized double-blind study was undertaken to determine the safety and efficacy of single-dose versus multiple-dose piperacillin for primary cesarean operation prophylaxis. After informed consent was obtained, patients received either 4 gm of piperacillin intravenously as a single dose or three 2 gm doses of piperacillin intravenously 4 hours apart. One hundred sixteen patients were evaluated for response; postoperative infection at the operative site was prevented in 52/60 (86.6%) who received the single dose and 53/56 (94.6%) who received multiple doses. The types of postoperative infections that occurred were similar in those patients in each group who developed infection and all responded well to therapeutic drugs. No adverse reactions to piperacillin were noted. Demographic characteristics and risk factors for infection were comparable for the two groups. These data support the efficacy of single-dose prophylaxis with an appropriate antibiotic agent.


Target imaging diagnosis of human brain glioma. Clinical analysis of 40 cases.
To establish a method for localization and qualitative diagnosis of glioma. The monoclonal antibody SZ-39 against human glioma was labelled with 131I and injected intravenously into 40 patients with intracranial occupying lesions proved by X-CT. 72 hours after 131I-McAb-SZ39 administration, cranial bone nuclide-imaging agent 99mTc-MDP was injected intravenously, and the patients were examined by SPECT scan with dual nuclide double channel tomography and special software. On radio-immuno-image, the immunocomplex formed by specific conjugation of 131I-McAb-SZ39 with target tissue was red, while the cranial bone incorporated with 99mTc-MDP was green. The location of the immunocomplex area could be identified by the superimposition of the images. 21 patients with positive targeting diagnosis of glioma showed the accuracy rate checked by SPECT was 81%(17/21) and by X-CT 48% (10/21). Seven patients with negative targeting diagnosis showed the accuracy rate checked by SPECT was 86%(6/7) and by X-CT 14% (1/7). Pathologically, the sensitivity of targeting SPECT to glioma was 94.5%(17/18) and that of X-CT 55%(10/18). Targeting SPECT examination could be used for localization and qualitative diagnosis of glioma and make up the inadequacy of X-CT in the qualitative diagnosis of atypical incipient and recurrent glioma, meningioma, metastatic carcinoma, and inflammatory lesions of brain.


Invasive cervical carcinoma in two sisters.
The occurrence of pre-invasive cervical carcinoma among siblings and in mother-daughter pairs has been reported previously in Europe. Invasive cervical cancer diagnosed in two Nigerian sisters within a period of three months is reported. It is suggested that sisters and daughters of patients with cervical cancer may be at a higher risk of developing the lesion because of similar socio-economic and cultural backgrounds and should therefore have regular cervical screening.


The Effects of Temperature and Hydrostatic Pressure on Metal Toxicity: Insights into Toxicity in the Deep Sea.
Mineral prospecting in the deep sea is increasing, promoting concern regarding potential ecotoxicological impacts on deep-sea fauna. Technological difficulties in assessing toxicity in deep-sea species has promoted interest in developing shallow-water ecotoxicological proxy species. However, it is unclear how the low temperature and high hydrostatic pressure prevalent in the deep sea affect toxicity, and whether adaptation to deep-sea environmental conditions moderates any effects of these factors. To address these uncertainties we assessed the effects of temperature and hydrostatic pressure on lethal and sublethal (respiration rate, antioxidant enzyme activity) toxicity in acute (96 h) copper and cadmium exposures, using the shallow-water ecophysiological model organism Palaemon varians. Low temperature reduced toxicity in both metals, but reduced cadmium toxicity significantly more. In contrast, elevated hydrostatic pressure increased copper toxicity, but did not affect cadmium toxicity. The synergistic interaction between copper and cadmium was not affected by low temperature, but high hydrostatic pressure significantly enhanced the synergism. Differential environmental effects on toxicity suggest different mechanisms of action for copper and cadmium, and highlight that mechanistic understanding of toxicity is fundamental to predicting environmental effects on toxicity. Although results infer that sensitivity to toxicants differs across biogeographic ranges, shallow-water species may be suitable ecotoxicological proxies for deep-sea species, dependent on adaptation to habitats with similar environmental variability.


Perception of Jordanian male nursing students about caring for children in the pediatric units after graduation.
Jordan is one of the countries that witnessed a severe shortage in nursing and a rapid increase in the number of male nurses in the nursing workforce. Therefore, working in certain clinical settings resulted in failure to compensate for the severe shortage of nurses in other areas such as maternity and pediatrics. The scarcity of research in the area of male nurses, in general, and their perception in working in pediatric units, specifically, are the impetus of this qualitative study. The purpose of this study is to explore the opinions of male nursing students, regarding male nurses caring for children after graduation. The findings of this study were classified in to the following themes: communication issues, qualification and specialized care, social constraints, and characteristics of children's health care providers. The findings showed that gender and sociocultural issues might be the most important factors underlying all issues related to barriers to caring for children, as perceived by male nursing students. Strategies to promote and enhance the caring of children among male nursing students were emphasized and addressed at the administrative and educational levels.


[Reliability and survival of arterial catheters: optimal dynamic response].
Blood pressure is one of the most critical haemodynamic parameter in the intensive care unit (ICU). The measurement relies mainly on invasive methods (arterial lines) but also on noninvasive methods (Oscillometric and Manual). It is crucial to be instantaneous and accurate to adapt any decision making plan. The aim of this study is to evaluate the reliability of this measure given by an arterial catheter over time. This can determine the maintenance of catheter patency before clinical total occlusion. Observational prospective study. Damping coefficient (xi) and natural frequency (Fn) of the arterial catheter system are studied in vivo each 12 hours by a fast flush test (FFT) in 61 patients. The measurements of the arterial blood pressure invasively (arterial catheter method) and non invasively (oscillometric method) are compared each 12 hours until the catheter is removed. All over the study period for each catheter (till 240 hours), the mean arterial blood pressure measurements given by either the catheter method or the oscillometric method were very concordant (coefficient > 0.7). Only 3.39% of the catheters had their physical characteristics (xi and Fn) in the optimal zone at T0; reaching 66.67% at T19. The maximal inserted time was highly correlated with a good operating catheter (R = 0.739; P < 10(-4)). The measure of the arterial blood pressure invasively can still be reliable for a long period of time (10 days), as long as the catheter is inserted, especially when the mean arterial pressure is considered. Each time the distance of the catheter insertion site moves away 1 cm from the radiocarpal joint or the groin, the risk of troubleshooting is doubled; on each blood sample from the catheter, this risk is reduced by 20%.


Magnetic resonance imaging-guided coronary interventions.
Magnetic resonance imaging (MRI) guidance for coronary interventions offers potential advantages over conventional x-ray angiography. Advantages include the use of nonionizing radiation, combined assessment of anatomy and function, and three-dimensional assessment of the coronary arteries leading to the myocardium. These advantages have prompted a series of recent studies in this field. Real-time coronary MR angiography, with low-dose catheter-directed intraarterial (IA) infusion of contrast media, has achieved in-plane spatial resolution as low as 0.8 x 0.8 mm2 and temporal resolution as short as 130 msec per image. Catheter-based IA injection of contrast agent has proven useful in the collection of multislice and three-dimensional images, not only for coronary intervention guidance, but also in the assessment of regional myocardial perfusion fed by the affected vessel. Actively visible guidewires and guiding catheters, based on the loopless antenna concept, have been effectively used to negotiate tortuous coronary vessels during catheterization, permitting placement of coronary angioplasty balloon catheters. Passive tracking approaches have been used to image contrast agent-filled coronary catheters and to place susceptibility-based endovascular stents. Although the field is in its infancy, these early results demonstrate the feasibility for performing MRI-guided coronary interventions. Although further methodological and technical developments are required before these methods become clinically applicable, we anticipate that MRI someday will be included in the armamentarium of techniques used to diagnose and treat coronary artery disease.


PERCEPTIONS OF STIGMA AND DISCRIMINATION IN HEALTH CARE SETTINGS TOWARDS SUB-SAHARAN AFRICAN MIGRANT WOMEN LIVING WITH HIV/AIDS IN BELGIUM: A QUALITATIVE STUDY.
Stigma and discrimination within health care settings remain a public health challenge across diverse cultural environments and may have deleterious effects on mental and physical health. This study explores the causes, forms and consequences of HIV-related stigma and discrimination among migrant sub-Saharan African women living with HIV in Belgium. A qualitative study was conducted with 44 HIV-positive sub-Saharan African migrant women between April 2013 and December 2014 in health care settings in Belgium. Data were analysed using thematic content analysis. Twenty-five of the women reported overt stigma and discrimination and fifteen reported witnessing behaviours that they perceived to be stigmatizing and discriminatory in health care settings. The themes that emerged as to the causes of stigma and discrimination were: public perceptions of migrants and HIV, fear of contamination and institutional policies on HIV management. Reported forms of stigma and discrimination included: delayed or denied care, excessive precautions, blame and humiliation. The consequences of stigma and discrimination were: emotional stress, inconsistent health-care-seeking behaviour and non-disclosure to non-HIV treating personnel. Stigma and discrimination in health care settings towards people with HIV, and more specifically towards HIV-positive sub-Saharan African migrant women, impedes sustainable preventive measures. Specialized education and training programmes for non-HIV health care providers require in-depth investigation.


Long-term administration of probucol and QTc interval prolongation.
Electrocardiographic QTc intervals were measured in twenty-one hypercholesterolemic patients before and after long-term probucol (500-1,000 mg/day for 30 months) treatment. Probucol reduced serum total cholesterol (TC), triglyceride (TG), and high density lipoprotein-cholesterol (HDL-C). Mean QTc interval prolongation after probucol was 17 msec. A positive correlation was found between the change in QTc interval after probucol (delta QTc) and the total amount of probucol administered. delta QTc was negatively correlated to the pre-treatment QTc interval. No correlation was observed between serum probucol concentrations and delta QTc. Neither clinical evidence of cardiotoxicity nor critical arrhythmias were noted during the treatment period.


Topical epinephrine causes a decrease in density of beta-adrenergic receptors and cathecholamine-stimulated chloride transport in the rabbit cornea.
A single administration, or twice daily administration for 4.5 days, of topical 2% epinephrine to the rabbit eye in vivo causes a 30-40% decrease in the density of beta-adrenergic receptors on membranes prepared from the cornea. Such treatment also causes complete loss of the ability of excised corneas to respond to epinephrine in vitro with enhanced active chloride transport. These findings indicate that stimulation with a high concentration of catecholamine depresses the entire pathway from receptor to physiological response.


A partially purified outer membrane protein VirB9-1 for low-cost nanovaccines against Anaplasma marginale.
Anaplasma marginale is a devastating tick-borne pathogen causing anaplasmosis in cattle and results in significant economic loss to the cattle industry worldwide. Currently, there is no widely accepted vaccine against A. marginale. New generation subunit vaccines against A. marginale, which are much safer, more efficient and cost-effective, are in great need. The A. marginale outer membrane protein VirB9-1 is a promising antigen for vaccination. We previously have shown that soluble recombinant VirB9-1 protein can be expressed and purified from Escherichia coli and induce a high level of humoral and cellular immunity in mice. In this study, we re-formulated the nanovaccines using the partially-purified VirB9-1 protein as the antigen and hollow nano-size silica vesicles (SV-100) as the adjuvant. We simplified the purification method to obtain the partially-purified antigen VirB9-1 with a six-fold higher yield. The new formulations using the partially-purified VirB9-1 protein achieved higher antibody and cell-mediated immune responses compared to the purified ones. This finding suggests that the partially-purified VirB9-1 protein performs better than the purified ones in the vaccination against A. marginale, and a certain level of contaminants in the protein antigen can be self-adjuvant and boost immunogenicity together with the nanoparticle adjuvant. This may lead to finding a "Goldilocks" level of contaminants. The new nanovaccine formulation using partially-purified antigens along with nanoparticle adjuvants offers an alternative strategy for making cheaper veterinary vaccines.


With a different voice: integrating the psychosocial perspective into routine oncology care.
We have established a psychosocial support system that is highly integrated with physician activities and that is tailored to the special needs of our patient population. The core of this system is the close interaction between the physician and the patient counselor, who is a clinical social worker and psychotherapist. Viewed as a permanent member of the breast cancer team, the patient counselor provides psychosocial care in the oncology clinic using normal clinic events as vehicles for interaction. Thus, time spent waiting in the clinic and follow-up phone calls can be converted to sessions for psychological counselling. This approach has been effective in our patient population, where social biases and financial constraints limit the use of out-of-clinic psychiatric services.


Determination of garlic phenolic compounds using supercritical fluid extraction coupled to supercritical fluid chromatography/tandem mass spectrometry.
A rapid, simple and environmentally friendly supercritical fluid extraction and supercritical fluid chromatography coupled to mass spectrometry (SFE-SFC-MS/MS) method has been developed for the analysis of nine phenolic compounds in garlic. Through the optimization of the SFE parameters using response surface methodology (RSM), 15 phenolic compounds were successfully extracted at 50 °C in 9 min with the addition of 30% methanol using a method that was automatic, efficient, green and prevented oxidation. Moreover, the operating conditions of the SFC-MS/MS were also optimized for the analysis of the SFE extracts. 15 phenolic compounds in the garlic showed good separation performance on a Shim-pack UC-X Diol column, and 0.1 mM oxalic acid and 1 mM ammonium formate in methanol were chosen as the most suitable mobile phase components. Furthermore, a calibration curve was developed using a matrix-matched standard, and 9 phenolic compounds showed good linearity (R2 > 0.99). The limits of detection of the 9 phenolic compounds varied from 0.6 to 12 ng/g, and the quantifications ranged from 2 to 40 ng/g. The validation data also showed acceptable recoveries for 9 phenolic compounds, and the relative standard deviations (RSDs) for the overall precision were lower than 10%. The developed method has been utilized to analyze the phenolic compounds in garlic from different geographical areas of China (Cangshan, Jinxiang, Pizhou, Dali), which suggests that this off-line SFE-SFC-MS/MS method could be adapted to the quantitative analysis of phenolic compounds in garlic.


Nipple-areola complex sparing mastectomy with periareolar pexy for breast cancer patients with moderately ptotic breasts.
Nipple-areola complex sparing mastectomy (NSM) with immediate implant reconstruction has been recently introduced for breast cancer patients who are not candidates for breast preserving surgery. As the cosmetic results in moderately ptotic breasts may not be optimal, a modified NSM with a periareolar pexy (PP-NSM) was introduced at our Institution. Patients selection criteria and complication rates of PP-NSM were prospectively recorded and compared with those of the classical NSM. Over a period of 11 months, 22 PP-NSMs and 35 NSMs were performed. The mean jugular-nipple distance was significantly longer in the PP-NSM as compared with the NSM (22.6 vs. 19.6 cm; p=0.000), whereas the mean inframammary fold-areola distance was superimposable (5.4 cm). The periareolar mastopexy led to a mean cranial transposition of the nipple-areola complex (NAC) of 2.2 cm (range 1.5-4 cm). Mean breast weight was significantly higher in the PP-NSM as compared with the NSM cohort (336 vs. 236 g; p=0.003). The only case of total NAC necrosis occurred in the PP-NSM group. Partial NAC necrosis was slightly more frequent in the PP-NSM than in the NSM group (13.6% vs. 2.9%%; p=n.s.), possibly due to the higher percentage of smokers (41.0% vs. 14.0%; p=0.05). Early cosmetic results were good to excellent from the surgeon's and the patient's point of view in over 80% of the cases. PP-NSM allows good cosmetic results and low complication rates in patients with moderately ptotic breasts requiring a mastectomy. In particular, PP-NSM seems to be a good option for women at high risk for developing breast cancer and for selected patients affected by non-locally advanced breast cancer.


Nicotine concentrations with concurrent use of cigarettes and nicotine replacement: a review.
This paper reviews the data on blood nicotine or saliva cotinine concentrations with concomitant smoking and use of nicotine replacement (NR) products. Eleven studies that provided data on blood nicotine concentrations, carbon monoxide in exhaled air, and number of cigarettes smoked were reviewed. At least one day had to be spent on concurrent use of cigarette and NR products. With simultaneous use of smoking and acute NR products (gum and inhaler) the nicotine concentrations were unchanged, whereas they increased (+54%) with nicotine patches. With both types of NR products, the number of cigarettes smoked per day was reduced by approximately 50% and carbon monoxide (CO) by 30%. Where smokers had the intention or received instructions to reduce smoking, a greater reduction in cigarettes smoked and exhaled CO was observed. Despite substantially increased nicotine concentrations (e.g., up to 3 times the approved dose) there were no significant adverse reactions. Concurrent use of NR products and cigarette smoking appears to be safe.


Additive effects of dexamethasone and calcium on the calcitonin mRNA level in adrenalectomized rats.
Northern hybridizations were used to evaluate the effects of dexamathasone and calcium on calcitonin mRNA levels in adrenalectomized female rats. Two weeks after adrenalectomy, a 3.6-fold decrease in the calcitonin mRNA level was observed (28% vs 100% in sham-operated controls). After 5 days of dexamethasone treatment (1.5 mg/kg b. wt), a 2.6-fold rise in calcitonin mRNA occurred in adrenalectomized rats (73% vs 28%). This increment was higher when dexamethasone treated animals were injected with calcium (100% vs 73%). The effect of calcium on the calcitonin mRNA level of adrenalectomized rats treated or not with dexamethasone was similar, and additive in the former case. Our data suggest that calcium and dexamethasone elevate calcitonin mRNA by two different mechanisms.


Nonsteroidal Anti-inflammatory Drugs Sensitize CD44-Overexpressing Cancer Cells to Hsp90 Inhibitor Through Autophagy Activation.
Recently, novel therapeutic strategies have been designed with the aim of killing cancer stem-like cells (CSCs), and considerable interest has been generated in the development of specific therapies that target stemness-related marker of CSCs. In this study, nonsteroidal anti-inflammatory drugs (NSAIDs) significantly potentiated Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-mediated cytotoxicity through apoptotic and autophagic cell death induction, but COX-2-inhibitory function was not required for NSAID-induced autophagy in CD44-overexpressing human chronic myeloid leukemia K562 (CD44highK562) cells. Importantly, we found that treatment with NSAIDs resulted in a dose-dependent increase in LC3-II level and decrease in p62 level and simultaneous reduction in multiple stemness-related markers including CD44, Oct4, c-Myc, and mutant p53 (mutp53) in CD44highK562 cells, suggesting that NSAIDs could induce autophagy, which might mediate degradation of stemness-related marker proteins. Activation of AMPK and inhibition of Akt/mTOR/p70S6K/4EBP1 participated in NSAID-induced autophagy in CD44highK562 cells. In addition, treatment of CD44highK562 cells with NSAIDs inhibited expression of HSF1/Hsps, which resulted in suppression of 17-AAG-induced activation of Hsp70, leading to reversal of 17-AAG resistance and sensitization of CD44highK562 cells to 17-AAG by NSAIDs. In conclusion, combining NSAIDs with Hsp90 inhibitor may offer one of the most promising strategies for eradication of CD44-overexpressing CSCs.


Variable prospective financing in the Danish hospital sector and the development of a Danish case-mix system.
This article aims to describe and assess the Danish case-mix system, the cost accounting applied in setting national tariffs and the introduction of variable, prospective payment in the Danish hospital sector. The tariffs are calculated as a national average from hospital data gathered in a national cost database. However, uncertainty, mainly resulting from the definition of cost centres at the individual hospital, implies that the cost weights may not fully reflect the hospital treatment cost. As variable prospective payment of hospitals currently only applies to 20% of a hospital's budget, the incentives and the effects on productivity, quality and equality are still limited.


[Provision of workers and employees of Kuzbass industrial enterprises with vitamins C, E, A and beta-carotene].
The content of vitamins C, E, A and beta-carotene was studied in the blood serum of 404 workers and employees of the Kuzbass industrial enterprises. Insufficient providing of the body with ascorbic acid, tocopherol and beta-carotene has been revealed. The number of workers and employees with vitamin C deficiency comprises at an average 95%, with vitamin E deficiency--9%, and with beta-carotene deficiency--34%. Industrial enterprises characterized by hard physical labor and occupational health hazard have been found to be most unfavourable with respect to providing with vitamins. The results of the investigations conducted have evidenced the necessity of correcting the vitamin nutrition of the subjects studied.


Behavioral treatment for chronic low back pain: a systematic review within the framework of the Cochrane Back Review Group.
A systematic review of randomized controlled trials. The treatment of chronic low back pain is not primarily focused on removing an underlying organic disease but at the reduction of disability through the modification of environmental contingencies and cognitive processes. Behavioral interventions are commonly used in the treatment of chronic (disabling) low back pain. To determine whether behavioral therapy is more effective than reference treatments for chronic nonspecific low back pain and which type of behavioral treatment is most effective. The authors searched the Medline and PsychLit databases and the Cochrane Controlled Trials Register up to April 1999, and Embase up to September 1999. Also screened were references of identified randomized trials and relevant systematic reviews. Methodologic quality assessment and data extraction were performed independently by two reviewers. The magnitude of effect was assessed by computing a pooled effect size for each domain (i.e., behavioral outcomes, overall improvement, back pain-specific and generic functional status, return to work, and pain intensity) using the random effects model. Only six (25%) studies were high quality. There is strong evidence (level 1) that behavioral treatment has a moderate positive effect on pain intensity (pooled effect size 0.62; 95% confidence interval [CI] 0.25, 0.98), and small positive effects on generic functional status (pooled effect size 0.35; 95% CI: -0.04, 0.74) and behavioral outcomes (pooled effect size 0.40; 95% CI: 0.10, 0.70) of patients with chronic low back pain when compared with waiting-list controls or no treatment. There is moderate evidence (level 2) that a addition of behavioral component to a usual treatment program for chronic low backpain has no positive short-term effect on generic functional status (pooled effect size 0.31; 95% CI: -0.01, 0.64), pain intensity (pooled effect size 0.03; 95% CI:-0.30, 0.36), and behavioral outcomes (pooled effect size 0.19; 95% CI: -0.08, 0.45). Behavioral treatment seems to be an effective treatment for patients with chronic low back pain,but it is still unknown what type of patients benefit most from what type of behavioral treatment.


Cellular and humoral immune response in pigs given vaccinal and chronic hog cholera viruses.
Humoral immune response (seroneutralization) and cellular immune response (lymphocyte-stimulation test) were analyzed in pigs inoculated with low virulent strains of hog cholera virus or vaccinated with a live-virus vaccine. Vaccinated animals exhibited an intense neutralizing antibody production, but cellular immune response was not detected. Neutralizing antibodies were not found in infected pigs, but a brief cellular immune response (18 days after inoculation) was observed.


Bcl-rambo induces apoptosis via interaction with the adenine nucleotide translocator.
The Bcl-2 family proteins plays a central role in apoptosis. The pro- or anti-apoptotic activities of Bcl-2 family are dependent on the Bcl-2 homology (BH) regions. Bcl-rambo, a new pro-apoptotic member, is unusual in that its pro-apoptotic activity is independent of its BH domains. However, the mechanism underlying Bcl-rambo-induced apoptosis is largely unknown. Mitochondrial localization is indispensable for the pro-apoptotic function of Bcl-rambo. Bcl-rambo interacts physically with the adenine nucleotide translocator (ANT), suppresses the ADT/ATP-dependent translocation activity of ANT. Collectively, our data indicate Bcl-rambo is a pro-apoptotic member of the Bcl-2 family, induces the permeability transition via interaction with ANT.


Intracavity Faraday modulation spectroscopy (INFAMOS): A tool for radical detection.
We present the intra-cavity Faraday modulation spectroscopy technique, whereby optical feedback cavity-enhanced spectroscopy is coupled with Faraday modulation spectroscopy to greatly enhance the interaction path length of a laser beam with a paramagnetic sample in a magnetic field. We describe a first prototype based upon a cw quantum cascade laser targeting a selection of fundamental rovibrational R-branch transitions of nitric oxide (1890 cm-1), consisting of a linear cavity (finesse F=6300) and a water-cooled solenoid. We demonstrate a minimum detectable Verdet constant of Vmin=4.7×10-14 rad cm-1 G-1 Hz-1/2 (at SNR = 1), corresponding to a single-pass rotation angle of 1.6×10-10 rad Hz-1/2 and a limit of detection of 0.21 ppbv Hz-1/2 NO.


The role of 111indium-octreotide brain scintigraphy in the diagnosis of cranial, dural-based meningiomas.
Meningiomas are common brain tumors with somatostatin receptors that bind octreotide. We report the use of (111)indium-octreotide brain scintigraphy (OBS) for the non-invasive differentiation of meningiomas from other cranial dural-based pathology. A retrospective analysis of our experience with OBS for non-invasive identification of meningiomas was performed. Two neuroradiologists, blinded to clinical data, utilized a standardized grading scheme to define the uptake of octreotide at 6 and 24 h post-administration. The correlation between (18) F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), magnetic resonance imaging (MRI) scans, and octreotide uptake was assessed. The cohort consisted of 50 patients having a mean age of 62.4 years and a median follow-up time of 24 months. Management consisted of biopsy (n = 4); resection (n = 10); observation (n = 16); radiosurgery (n = 21); and external beam radiotherapy (n = 3). OBS was correlated with MRI (n = 50); FDG-PET brain studies (n = 38); histology (n = 14), and angiography (n = 1). In cases where definitive diagnosis could be made, the sensitivity, specificity, positive and negative predictor values for OBS alone were 100; 50; 75; and 100, respectively. OBS provided false positive data in 3 patients (metastasis, chronic inflammation, lymphoma). Use of OBS with MRI to differentiate meningiomas from other lesions was highly significant (P < 0.001). FDG-PET correctly identified malignant pathology with 100% sensitivity and specificity. OBS may increase the diagnostic specificity of conventional MRI when differentiating meningioma from other dural-based pathologies, while the addition of FDG-PET differentiates benign from malignant lesions.


Finding balance: Virus populations reach equilibrium during the infection process.
Virus populations, mixtures of viral strains or species, are a common feature of viral infection, and influence many viral processes including infection, transmission, and the induction of disease. Yet, little is known of the rules that define the composition and structure of these populations. In this study, we used three distinct strains of Citrus tristeza virus (CTV) to examine the effect of inoculum composition, titer, and order, on the virus population. We found that CTV populations stabilized at the same equilibrium irrespective of how that population was introduced into a host. In addition, both field and experimental observations showed that these equilibria were relatively uniform between individual hosts of the same species and under the same conditions. We observed that the structure of the equilibria reached is determined primarily by the host, with the same inoculum reaching different equilibria in different species, and by the fitness of individual virus variants.


Genetic diversity in wild (Sus scrofa scrofa) and domestic (Sus scrofa domestica) pigs and their hybrids based on polymorphism of a fragment of the D-loop region in the mitochondrial DNA.
We examined the variation in mitochondrial DNA by sequencing the D-loop region in wild and domestic (large-white breed) pigs, in hybrids between domestic and wild pigs, and in Monteiro pigs. A D-loop fragment of approximately 330 bp was amplified by PCR. Sequencing of DNA amplicons identified haplotypes previously described as European and Asian types. Monteiro pigs and wild pigs had European haplotypes and domestic pigs had both European and Asian haplotypes.


4D Printing of a Digital Shape Memory Polymer with Tunable High Performance.
Shape memory polymers (SMP) with 3D geometries and tunable shape-shifting behavior can open up new opportunities in intelligent devices. Achieving both simultaneously is difficult for conventional approaches. 4D printing allows fabrication of complex 3D SMP geometries that can change shapes (i.e., the fourth dimension is time), but tuning the shape memory response is challenging because of the printing constraints. Here, we report a material and process concept that allows digital light fabrication of SMP with fine control of not only the geometries but also the shape memory characteristics, within a printing time of 30 s. Digital light modulation allows spatio-temporal tuning of the material properties including shape memory transition temperature, rubbery modulus, and maximum elongation (up to 250%). Consequently, the process allows producing multiple-SMP within a single material construct using the same printing precursor. We demonstrate that this unique attribute is beneficial in constructing unusual shape-shifting 3D nano-photonic and electronic devices. The simplicity and versatility of our approach facilitates its future expansion into a wide range of geometrically complex devices with advanced functions.


Below the knee PTA in critical limb ischemia results after 12 months: single center experience.
Evaluation of angioplasty with bare metal stents in infrapopliteal occlusions or severe stenoses in patients with critical limb ischemia. Percutaneous stent angioplasty was performed in 58 limbs in 47 patients with critical limb ischemia (CLI) in Rutherford stage 4-6. Lesions with up to 5 cm in length with at least one patent vessel below the obstruction were treated. 121 bare metal stents (diameter of 2.5-4 mm; length of 18-38 mm) were implanted. Follow-up examinations were performed up to 12 months postinterventionally using clinical examination, ABI calculation, and color-coded duplex sonography. Patency rates were calculated on the basis of the Kaplan-Meier analysis. Technical success was achieved in 100%. Minor complications (hematoma, distal emboli, vessel dissection) were documented in 5.17% (n=3) limbs, respectively. The 3-month, 6-month, and 1-year primary patency rate was 93.0%, 78.9% and 66.7%, respectively. 86.9% of the lesions healed postinterventionally. The cumulative limb salvage rate was 96.6%. Stent angioplasty in infrapopliteal arteries is a safe and effective technique for the treatment of patients with CLI. By consequent clinical monitoring high secondary patency rates can be achieved. The use of a bare metal stent seems to result in high limb salvage, primary and secondary patency rates in the mid-term follow-up.


Information mastery and the 21st century doctor: change management for general practitioners.
The Internet and computers have brought immense change in how society deals with information. Uptake of these technologies has been disjointed and has occurred in a non-uniform way among general practitioners, compared with other professionals. Information mastery is a key 21st century skill that GPs should acquire. Applying "change management" concepts may help improve uptake of information mastery skills in general practice.


TM4SF5-CTD-2354A18.1-miR-4697-3P may play a key role in the pathogenesis of gastric cancer.
Our aim is to identify important lncRNAs and mRNAs which may play a key role in contributing to pathogenesis of gastric cancer. Different LncRNAs and mRNAs are identified by microarray in gastric cancer tissue and corresponding normal tissues. The function and relationship of different LncRNAs and mRNAs is performed by GO analysis and Pathway analysis and made code-non-code network (CNC) by Pearson correlation coefficients (PCC). Then mRNA-miRNA relationship is predicted through mRNA-miRNA relationship software (http://www.targetscan.org). Lastly, mRNA-miRNA-LncRNA network is established for further research. The expression proﬁles of 3732 lncRNAs showed different expression (fold change (FC)≥2.0, p<0.05) in gastric cancer tissue and normal tissue and expression proﬁles of 3994 mRNAs also showed different expression (FC≥2.0, p<0.05) in gastric cancer and corresponding normal tissue. The expression of TM4SF5, CTD-2354A18.1 and miR-4697-3P is in balance at physiological conditions, however, the balance is disrupted by some situations, which may contribute to gastric cancer. GO analysis and Pathway analysis also showed TM4SF5 played an important role in proliferation, differentiation and apoptosis. Therefore, TM4SF5-miR-4697-3P- CTD-2354A18.1 may play a key role in the pathogenesis of gastric cancer (Tab. 2, Fig. 4, Ref. 30).


A Dicyanomethylene-4H-Pyran Based NIR Ratiometric Fluorescent Probe for Diazane and its Bioimaging.
A near-infrared ICT-based fluorescent probe LX was successfully obtained. LX which detection limit is low as 22.2 nm shows excellent selectivity and high sensitivity to diazane. LX can selectively detected diazane from other species over a wide pH (3-10) range. A obvious color change of solution from yellow to orange can be found, allowing the naked eye to detect. The sensing mechanism was reasonably detected by ESI-MS and DFT calculations. In addition, LX succeed in the visualization of diazane in living cells and the detection of diazane in water samples.


Medical oncology: the new subspecialty.
The creation of medical oncology as a new subspecialty of internal medicine required a definition of the scope of involvement of the physician in this new area. Objectives for training programs were established and provisions provided for certification of specialists as medical oncologists. The area of medical oncology encompasses a broad aspect of medicine and requires a frim foundation in the principles of internal medicine. As an advocate of the cancer patient, and in many instances the primary physician, the medical oncologist has the opportunity to effectively interact with many scientific skills in order to effectively control or even cure neoplastic diseases.


Bio-inspired antifouling approaches: the quest towards non-toxic and non-biocidal materials.
Biofouling is an undesirable process in which organisms and their by-products encrust a surface. Antifouling solutions are of great importance since biofouling has negative effects on numerous species, ecosystems, and areas including water treatment facilities, health-care systems, and marine devices. Many useful solutions have been developed in the last few decades. However, with the emergence of environmental issues, the search for new promising non-toxic materials has expanded. One approach tries to mimic natural antifouling surfaces and relies on mechanisms of action derived from nature. Since these materials are based on natural systems, they are mostly biocompatible and more efficient against complex fouling. In this review, we cover the latest advances in the field of antifouling materials. We specifically focus on biomaterials that are based on the chemical and physical behavior of biological systems.


IgG rheumatoid factor in human and rabbit transplantation sera.
Sera of human recipients of kidney allografts and rabbit recipients of skin allografts were tested by means of enzyme immunoassays (EIA) for IgG rheumatoid factor (RF) combining with human IgG (RF-H) or rabbit IgG (RF-R). In humans, the mean OD value in EIA for RF-H was significantly higher in 185 sera of allograft recipients than in 46 pretransplantation sera and 100 sera of normal subjects. Furthermore, the mean OD in patients who rejected their grafts was higher than in patients with satisfactory graft function. Interestingly, there was no difference in OD values for RF-R between sera of graft recipients and sera of normal subjects. Of 52 rabbit recipients of skin allografts, 24 were positive for both RF-R and RF-H, 4 were positive only for RF-R, another 4 only for RF-H, and 20 were negative for both. Renal allografts originating from the previous donors of skin grafts resulted, in most instances, in a significant decrease in the strength of the reaction for both RF-R and RF-H. The possible role of graft rejection in stimulation of RF formation as well as the possible role of RF in graft rejection should be considered.


Biochemistry of cardiomyopathy in the mitochondrial disease Friedreich's ataxia.
FRDA (Friedreich's ataxia) is a debilitating mitochondrial disorder leading to neural and cardiac degeneration, which is caused by a mutation in the frataxin gene that leads to decreased frataxin expression. The most common cause of death in FRDA patients is heart failure, although it is not known how the deficiency in frataxin potentiates the observed cardiomyopathy. The major proposed biochemical mechanisms for disease pathogenesis and the origins of heart failure in FRDA involve metabolic perturbations caused by decreased frataxin expression. Additionally, recent data suggest that low frataxin expression in heart muscle of conditional frataxin knockout mice activates an integrated stress response that contributes to and/or exacerbates cardiac hypertrophy and the loss of cardiomyocytes. The elucidation of these potential mechanisms will lead to a more comprehensive understanding of the pathogenesis of FRDA, and will contribute to the development of better treatments and therapeutics.


Effect of exposure to evening light on sleep initiation in the elderly: a longitudinal analysis for repeated measurements in home settings.
Epidemiologic data have demonstrated associations of sleep-onset insomnia with a variety of diseases, including depression, dementia, diabetes and cardiovascular diseases. Sleep initiation is controlled by the suprachiasmatic nucleus of the hypothalamus and endogenous melatonin, both of which are influenced by environmental light. Exposure to evening light is hypothesized to cause circadian phase delay and melatonin suppression before bedtime, resulting in circadian misalignment and sleep-onset insomnia; however, whether exposure to evening light disturbs sleep initiation in home settings remains unclear. In this longitudinal analysis of 192 elderly individuals (mean age: 69.9 years), we measured evening light exposure and sleep-onset latency for 4 days using a wrist actigraph incorporating a light meter and an accelerometer. Mixed-effect linear regression analysis for repeated measurements was used to evaluate the effect of evening light exposure on subsequent sleep-onset latency. The median intensity of evening light exposure and the median sleep-onset latency were 27.3 lux (interquartile range, 17.9-43.4) and 17 min (interquartile range, 7-33), respectively. Univariate models showed significant associations between sleep-onset latency and age, gender, daytime physical activity, in-bed time, day length and average intensity of evening and nighttime light exposures. In a multivariate model, log-transformed average intensity of evening light exposure was significantly associated with log-transformed sleep-onset latency independent of the former potential confounding factors (regression coefficient, 0.133; 95% CI, 0.020-0.247; p = 0.021). Day length and nighttime light exposure were also significantly associated with log-transformed sleep-onset latency (p = 0.001 and p < 0.001, respectively). In conclusion, exposure to evening light in home setting prolongs subsequent sleep-onset latency in the elderly.


Reproductive efficiency of the bethylid wasp Cephalonomia tarsalis: the influences of spatial structure and host density.
The parasitoid wasp Cephalonomia tarsalis (Ashmead) (Hymenoptera: Bethylidae) is commonly present in stored product facilities. While beneficial, it does not provide a high degree of biological pest control against its host, the saw-toothed beetle Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae). A candidate explanation for poor host population suppression is that adult females interfere with each other's foraging and reproductive behavior. We used simple laboratory microcosms to evaluate such mutual interference in terms of its overall effects on offspring production. We varied the density of the hosts and also the spatial structure of the environment, via the extent of population sub-division and the provision of different substrates. Production of C. tarsalis offspring was positively influenced by host density and by the isolation of females. With incomplete sub-division within microcosms offspring production was, in contrast, low and even zero. The provision of corrugated paper as a substrate enhanced offspring production and partially mitigated the effects of mutual interference. We recommend simple improvements to mass rearing practice and identify promising areas for further behavioral and chemical studies towards a better understanding of the mechanisms of mutual interference.


The pancreas: Bandmaster of glucose homeostasis.
The pancreas is a centralized organ vital for whole body metabolic control. Recent advances in the field of metabolism have reinforced its importance for orchestrating endocrine hormone secretion in response to several nutrients including glucose, lipids and amino acids, in addition to hormones and inflammatory signals. Cell types within the pancreas, in particular the insulin-producing β cells, control nutrient breakdown and energy production and are essential to maintain not only efficient hormone secretion, but also cell integrity, survival, and the ability to sense and adapt to changing metabolic environments. The present review highlights recent research advances on how glucolipotoxicity, mitochondrial dysfunction, and systemic inflammation affects pancreatic metabolism, and how new technologies and more advanced research models are improving our ability to study this organ system. Taken together, careful characterization and understanding of the importance of nutrient metabolism within this important, yet complex organ, will help us to better understand pathologies intimately associated with the pancreas and possibly discover new and more effective therapeutic strategies.


International variations in the ischemic burden post-acute myocardial infarction: prognostic implications.
To determine if there is a variation in the ischemic burden post-acute myocardial infarction (AMI), as assessed by myocardial perfusion imaging (MPI), between different populations in different geographic locations and to see if this variation is associated with different clinical outcomes. We characterized the MPI findings in 104 stable patients who were hospitalized with AMI at the American University of Beirut Medical Center (AUBMC), a tertiary referral hospital in an East Mediterranean country and we compared them to 126 patients who were enrolled according to a similar protocol in a previous study done at Baylor College of Medicine (BCM), Houston, Texas. There were no differences between the two populations with respect to prevalence of diabetes, hypertension, smoking, the use of thrombolysis, percentage of anterior MIs, Q-wave MIs, and multivessel disease on coronary angiography. However, the quantified ischemic defect size in the BCM population was double that in the AUBMC population (12 +/- 12% vs 6 +/- 8%, P < .01). This was associated with almost doubling of the 1 year event rate of death/myocardial infarction (18.3% vs 10.6%, P = .02) in the BCM population. Our study suggests that the ischemic burden post-AMI, as assessed by MPI, might vary between different populations in different geographic locations. This variation carries important prognostic implications and is associated with different patient outcomes.


PVL-positive MRSA in Austria.
The objective of this study was to present, for the first time, an overview of the existing Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA) strains in Austria and to compare the situation with that found in other countries. Between 2001 and 2006 we analysed 1150 MRSA isolates - from infections as well as from colonisation - for the presence of PVL genes. The most common multilocus sequence types of the 94 PVL-positive MRSA strains were ST8, ST152, ST30, ST80, and ST5; the ST22, and ST777 sequences were also detected. During 2005 and 2006, 3.7-7.7% of the isolates were PVL-positive. The age distribution of the patients revealed that nosocomial MRSA mainly occurs in elderly people, whereas PVL-positive MRSA mainly appears in younger people. We observed a relatively high prevalence of PVL-positive isolates. Several MRSA clones containing the PVL genes are spreading throughout Austria, including two strains not yet widespread in Western Europe.


Determination of polychlorinated biphenyls in transformer oil using various adsorbents for solid phase extraction.
Various adsorbents for a solid phase extraction (SPE) method were used to study their ability to separate PCBs from transformer oil to rapidly determine their sub-ppm concentration in the transformer oil. Approximately 90% of the transformer oil could be removed from the PCBs by using a hydrophilic-lipophilic balanced copolymer (HLB) adsorbent, but the recovery of deca-chlorobiphenyl (deca-CB) used as a surrogate was only 24.5% due to lose during this cleanup process. The use of a silica adsorbent gave good results with 89.9% recovery of the deca-CB. The recovery of Aroclor 1242 and 1260 were 95.4 and 90.3% on silica, and 98.9 and 83.5% on HLB, respectively. Acid treatment was an essential step in removing the ambiguous interference peaks to help identify the PCBs. A decreased sensitivity of the electron capture detection (ECD) for PCBs was observed due to the presence of the remaining trace oil after the workup procedure. This loss in sensitivity was allowed for by using tetrachloroxylene as an internal standard, and this was found to be reliable for the criteria of quality control by employing an experiment in which LCS was spiked with 2mg/l of Aroclor 1260 and analyzed each day over a 25 day period. The MDL for the analytical method established in this study is 0.05 mg/l.


Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children.
To describe the safety and efficacy of voriconazole in children treated within the compassionate release program. Children received voriconazole on a compassionate basis for treatment of an invasive fungal infection if they were refractory to or intolerant of conventional antifungal therapy. Voriconazole was administered as a loading dose of 6 mg/kg every 12 h i.v. on Day 1 followed by 4 mg/kg every 12 h i.v. thereafter. When feasible the route of administration of voriconazole was changed from i.v. to oral (100 or 200 mg twice a day for patients weighing < 40 or > or = 40 kg, respectively). Outcome was assessed by investigators at the end of therapy or at the last visit as success (complete or partial response), stable infection, or failure, based on protocol-defined criteria. Sixty-nine children (ages 9 months to 15 years; median, 7 years) received voriconazole; 58 had a proven or probable fungal infection. Among these 58 patients 27 had hematologic malignancies and 13 had chronic granulomatous disease as the most frequent underlying conditions. Forty-two patients had aspergillosis, 8 had scedosporiosis, 4 had invasive candidiasis and 4 had other invasive fungal infections. The median duration of voriconazole therapy was 93 days. At the end of therapy 26 patients (45%) had a complete or partial response. Four patients (7%) had a stable response, 25 (43%) failed therapy and 4 (7%) were discontinued from voriconazole because of intolerance. Success rates were highest in patients with chronic granulomatous disease (62%) and lowest in patients with hematologic malignancies (33%). Two patients experienced treatment-related serious adverse events (ulcerated lips with rash, elevated hepatic transaminases or bilirubin). A total of 23 patients had voriconazole-related adverse events, 3 (13%) of which caused discontinuation of voriconazole therapy. The most commonly reported adverse events included elevation in hepatic transaminases or bilirubin (n = 8), skin rash (n = 8), abnormal vision (n = 3) and a photosensitivity reaction (n = 3). These data support the use of voriconazole for treatment of invasive fungal infections in pediatric patients who are intolerant of or refractory to conventional antifungal therapy.


Resection of giant adrenal cortical carcinoma: a case report.
We report a case of nonfunctioning giant adrenal cortical carcinoma undergoing complete resection. We report the case and evolution of a woman who underwent resection of a giant adrenal carcinoma at Santa Marcelina Hospital. A 49-year-old female presented with palpable mass in the right hypochondrium extending 5 cm down from the right costal margin. Abdominal CT Scan found a large mass occupying the right adrenal region with areas suggestive of necrosis, in close contact with the liver, pushing the right kidney inferiorly and extending to the midline. Biochemical tests to evaluate hormonal secretion resulted in levels within the normal range characteristic of a non-functioning adrenal neoplasm. The treatment of choice was resection of the abdominal mass; the surgical specimen greatest diameter was 21 cm and weighed 2106 grams. It was an adrenal cortical carcinoma. Options for the treatment of adrenal cortical carcinoma showed no significant advances in recent decades and complete surgical resection remains the most effective treatment for adrenal cortical carcinoma, even in patients with bulky tumor masses.


Changes in external ear position modify the spatial tuning of auditory units in the cat's superior colliculus.
This study examines the influence of external ear position on the auditory spatial tuning of single units in the superior colliculus of the anesthetized cat. Unit responses to broad-band stimuli presented in a free sound field were measured with the external ears in a forward symmetrical position or with one or the other ear turned 40 degrees to the side; the ears are referred to as contra- or ipsilateral with respect to the side of the recording site. Changes in the position of either ear modified the spatial tuning of units. The region of space from which a stimulus was most effective in activating a unit is referred to as the unit's "best area". Whenever the contralateral ear was turned to the side, best areas shifted peripherally and somewhat upward, roughly in proportion to the magnitude of the change in ear position. A turn of the ipsilateral ear to the side had more variable effects, but best areas generally shifted frontally. Best areas located between approximately 10 and 40 degrees contralateral when the ears were forward were least affected by changes in ipsilateral ear position. Changes in ear position also modified the maximum response rates of many units. Units with best areas located within approximately 20 degrees of the frontal midline when the ears were forward exhibited a pronounced decrease in responsiveness when either ear was turned. Units with more peripheral best areas tended to show no change or a slight increase in responsiveness. The influence of ear position on the directionality of the external ears was determined by mapping the cochlear microphonic response to tones or one-third-octave bands of noise before and after turning the ear. When the ears were forward, maximum interaural intensity differences (IIDs) were produced by high-frequency sound sources (greater than or equal to 20 kHz) located 20-40 degrees from the frontal midline and by lower frequency sources located further peripherally. The influence of ear position on the locations from which maximum IIDs were produced was similar to the influence of ear position on unit best areas. Changes in ipsilateral ear position had different effects on high- and low-frequency IIDs that were comparable with the effects of changes in ear position on frontally and peripherally located best areas, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)


Anti-tumor effects of pNEgr-mIL-12 recombinant plasmid induced by X-irradiation and its mechanisms.
To study the effect of gene radiotherapy combining injection of recombinant plasmid pNEgr-mIL-12 with local X-irradiation on cancer growth and to elucidate the mechanisms of tumor inhibition. Alkaline lysis was used to extract the plasmid and polyethylene glycol 8000 (PEG 8000) was applied for further purification of plasmids. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of IL-12 protein. C57BL/6J mice were subcutaneously inoculated with B16 melanoma cells and the plasmid was injected directly into the tumor. Gene-radiotherapy combining pNEgr-mIL-12 recombinant plasmid with X-irradiation was given three times to C57BL/6J mice bearing B16 melanoma. Changes in immunologic parameters of tumor-bearing mice were detected with relevant immunologic assays. Results showed a significant decrease in tumor growth rate (P<0.05-0.001) after 3 times of gene-radiotherapy with IL-12 and X-irradiation. Immunologic studies showed a significant increase in CTL and NK cytolytic activity (P<0.05-0.001) and an up-regulated secretion of IFN-gamma and TNF-alpha (P<0.01-0.001). Moreover, the expression of mIL-12 in B16 melanoma cells of the treated tumor-bearing mice was found to be higher than that of control. pNEgr-mIL-12 plasmid combined with X-irradiation can increase tumor control and the mechanism of increased tumor inhibition is related to the enhancement of anticancer immunity in tumor-bearing mice.


Aurones: interesting natural and synthetic compounds with emerging biological potential.
Aurones [2-benzylidenebenzofuran-3(2H)-ones] are either natural or synthetic compounds, belonging to the flavonoid family. They are isomeric to flavones and provide a bright yellow color to the plants in which they occur. Today, a literature survey indicates that the related flavonoids have been studied not only for their physiological properties and effects on Nature, but also for their therapeutic potential. Aurones are recently attracting the interest of an increasing number of research groups, and, since the last review, some interesting advances have been made in understanding the aurones. In this review, we report the recent advances made on the synthetic routes towards aurones. We also highlight their activity in different biological areas, as well as applied genetic plant modifications to produce these colored compounds. Their synthesis, structure-activity relationships and the importance of the substitution pattern will also be mentioned. Finally, some aspects regarding the possible development of aurones will be discussed briefly.


Structural and functional characterisation of the DNA binding domain of the Aspergillus nidulans gene regulatory protein AreA.
The 876-aa protein AreA regulates the expression of numerous genes involved in nitrogen metabolism in Aspergillus nidulans, and interacts with GATA sequences upstream of the relevant genes. We have carried out limited proteolysis of the C-terminal domain of the AreA protein in order to identify possible structural domains within the protein. A stable 156-amino-acid fragment was identified that contained the zinc finger region, and this sequence was cloned and expressed in E. coli. Fluorescence spectroscopy of the purified protein showed that the proteolytic domain was folded and could be denatured by high concentrations of urea (approximately 4 M), exhibiting a sharp transition. Fluorescence spectroscopy was also used to monitor binding to a DNA duplex containing the AreA recognition site, demonstrating tight binding of the domain to its DNA recognition sequence. The DNA binding affinity of the domain is comparable with that of the native AreA protein and much higher than that of the minimal zinc finger region of AreA.


[Crimes against life in the material of Cracow's Institute of Forensic Medicine--comparative analysis in the years 1986-2000 and 1996-2000].
The authors presented a comparative analysis of crimes against life in five year periods of the past and present political systems based on autopsy material of Cracow's Institute of Forensic Medicine. Investigation of these types of crime confirmed sociological observations of arising the criminal trends in the last years. The incident of these types of crimes arose in the last period by about 40% in a relation of male to female victims 3.7:1. Probable motives of these crimes were: drinking 8%, decline in family relationships 12%, fight and revenge 9% robbery 8%, sexual offenses only in 1%. In 61% of analyzed cases the motives were unknown. Among the weapons of crime the most often used were blunt objects and death due to stabbings and cuts. A very high incidence of fire arm crimes in comparison to previous period was observed--from 2 cases in 1986-1990 to 25 in the five year period of 1996-2000. 78% of victims were in a state of insobriety at the moment of crime.


On the correct use of stepped-sine excitations for the measurement of time-varying bioimpedance.
Many electrochemical/bioelectrochemical systems are intrinsically nonstationary and are affected by time-dependent phenomena. The requirement of stationarity in the classical version of impedance spectroscopy appears to be in conflict with the essential properties of the object, therefore a post-experimental mathematical/analytical procedure is necessary for the reconstruction of the 'true' impedance spectra. In this communication, a method for the correction of the impedance data is discussed.


[Diagnosing and treating of onychomycosis].
Onychomycosis is a frequent disorder, which accounts for approximately 50% of nail changes. Many patients are treated for onychomycosis without a mycological verification being done. The patients may be in risk of being treated for a non-existent fungal infection with lack of effect and potential adverse events. This review highlights the importance of choosing the correct sampling and diagnostic methods, as genus and/or species identification is essential when choosing the optimal treatment strategies.


Evaluation of the severity of mitral regurgitation by transesophageal Doppler flow echocardiography.
The severity of mitral regurgitation (MR) was assessed by transesophageal Doppler flow echocardiography (TEE) using new criteria in 87 patients. The severity of MR assessed by TEE (TEE-MR) was compared with that obtained by left ventriculography (LVG-MR). Although the severity of TEE-MR has been evaluated by MR jet area, it is often difficult because the MR jet extends beyond a single frame image in severe MR. We found that (1) when the MR area was larger than 3 cm2, the severity of MR was more than second-degree by LVG; (2) there was systolic turning flow (STF) of the MR jet within the left atrial cavity in 27 of 30 patients with third- and fourth-degree LVG-MR; and (3) there was late systolic backward flow (SBF) in the pulmonary veins in 9 of 10 patients with fourth-degree LVG-MR. A new grading of the severity of MR by TEE was proposed, which combined the findings of STF, SBF, and the MR area. These new criteria of the severity of TEE-MR excellently correlated with that by LVG (y = 0.94x + 0.08; r = 0.95, p less than 0.01). The criteria for MR by TEE were also useful for assessment of MR in patients with prosthetic mitral valve dysfunction (y = 0.96x + 0.04; r = 0.97, p less than 0.01). We conclude from this study that the severity of MR can be accurately assessed with TEE by measuring the MR area and the specific flow patterns in the left atrium and pulmonary veins.


Slow quench dynamics of a one-dimensional Bose gas confined to an optical lattice.
We analyze the effect of a linear time variation of the interaction strength on a trapped one-dimensional Bose gas confined to an optical lattice. The evolution of different observables such as the experimentally accessible on site particle distribution are studied as a function of the ramp time by using time-dependent numerical techniques. We find that the dynamics of a trapped system typically displays two regimes: For long ramp times, the dynamics is governed by density redistribution, while at short ramp times, local dynamics dominates as the evolution is identical to that of an homogeneous system. In the homogeneous limit, we also discuss the nontrivial scaling of the energy absorbed with the ramp time.


[Report of five cases of major surgery during anticoagulant therapy after prosthetic valve replacement].
The major surgery for gastroduodenal ulcer, gastric cancer, esophageal cancer, and mediastinal tumor, were performed on 5 patients during anticoagulant therapy after prosthetic valve replacement. In the postoperative management, Dipyridamole (30 mg/day) was given in case 1, Heparin sodium (24,000 mu/day) in case 2, 3, and Gabexate Mesilate in case 4, 5. Postoperative course was uneventful in case 1, 3, 4, 5, intratracheal bleeding was recognized on the 3rd postoperative day and treated by reducing of heparin dose in case 2. Gabexate Mesilate was thought to be effective and free from complication in case 4, 5.


Thermoresponsive polymers as gene delivery vectors: cell viability, DNA transport and transfection studies.
A range of gene delivery vectors containing the thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAm) was evaluated for effects on cell viability, intracellular trafficking and transgene expression in C2C12 mouse muscle cells. Polymers were complexed with plasmid DNA at pH 7.4 and the ability of the resulting particles to transfect cells was assessed via confocal microscopy and protein expression studies in tissue culture. Cell viability assays indicated that these polymers were toxic at high concentrations when not complexed to DNA or at certain polymer:DNA ratios. Poly(ethyleneimine) co-polymers with side-chain grafted PNIPAm were shown to be less toxic than poly(ethyleneimine) alone or PNIPAm-co-(N,N'-dimethylaminoethylmethacrylate) linear co-polymers and the effects were concentration dependent. Confocal micrographs of labeled polymers and DNA indicated rapid cellular entry for all the complexes but expression of Green Fluorescent Protein was achieved only when the branched PEI-PNIPAm co-polymers were used as vectors. The results indicate that design of appropriate co-polymer components and overall polymer architecture can be used to mediate, and perhaps ultimately control, DNA transport and transgene expression.


The electrophysiological actions of neurotensin in the central nervous system.
The endogenous neuropeptide, neurotensin (NT) alters the firing frequencies of certain neurons in the central nervous system (CNS). This is one of the findings that support the hypothesis that NT is a neurotransmitter substance. The direct application of NT on CNS neurons causes predominantly excitatory effects. These effects occur in a dose-related fashion via a calcium-dependent postsynaptic mechanism. The C-terminal hexapeptide fragment, NT 8-13 exerts similar electrophysiological effects to NT, while the N-terminal octapeptide fragment, NT 1-8 is devoid of such activity. NT produces a significant increase in the firing rates of individual neurons in the substantia nigra (SN), ventral tegmental area (VTA), medial prefrontal cortex (MPF), hypothalamus, and periaqueductal grey (PAG). This excitation occurs with a rapid onset and is readily reversible after cessation of NT application. In contrast, NT has no effect or weak inhibitory effects on the firing rates of neurons in the locus coeruleus (LC) and cerebellum. These electrophysiological actions of NT appear to be unique and not shared by other neurotransmitter and neuropeptide receptor antagonists and agonists that have been studied via direct co-application. NT attenuates dopamine (DA)-induced inhibition associated with direct application onto neurons in the SN and VTA both in vivo and in vitro. Intracellular recordings suggest that direct application of higher concentrations of NT appears to produce 'depolarization block' on individual neurons in the SN, VTA, MPF, and hypothalamus. The electrophysiological consequences of NT application not only show similarities to clinically efficacious antipsychotic medications, but also demonstrate the ability of NT to modulate the activity of dopamine (DA) neurons at the cellular level via specific NT binding sites. These findings further underscore the possibility that NT may play a pre-eminent role in the pathogenesis of, and psychopharmacological management of neurological and psychiatric disorders purportedly related to perturbation of CNS DA systems including schizophrenia.


Physiological role of the endothelin system in human cardiovascular and renal haemodynamics.
Based on studies with a number of endothelin antagonists, endothelin-1 is now known to play a key physiological role in the maintenance both of basal systemic vascular resistance and of blood pressure in healthy people. Factors that regulate activity of the vascular endothelin system, and its physiological effects on the heart and kidney, now need to be determined.


Trace element intakes should be revisited in burn nutrition protocols: A cohort study.
Due to inflammatory and hypermetabolic responses and to extensive exudative trace element (TEs) losses, major burn patients have substantially increased nutritional requirements. To date, information is only available for Cu, Se, and Zn. We aimed at analyzing losses of 12 TEs and Mg through burn wound exudation and corresponding plasma concentrations during the first week after burn injury, and to evaluate the impact of current TE repletion protocols. Burn wound exudate was collected under negative pressure in 15 adult patients burned 29 ± 20% of body surface (TBSA) for 8 days after injury. Two samples were collected daily. The TE concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Losses and serum concentrations were compared to intakes. For the majority of 12 TEs, the highest losses were observed on day 1, and declined thereafter. Despite Cu supplementation (4.23 mg/day) serum levels remained below reference values. Se supplements (745 μg/day) normalized and even increased serum levels to upper normal value. Despite large supplements (Zn 67.5 mg/day), serum Zn values remained below reference range. Large exudative losses of B, Br and Mg were found, as well as of Fe and I, with the latter being probably due to contamination. Current nutritional Cu, Se, Zn repletion protocols in major burn patients which were based on measured exudative losses should be revised to include higher Cu and lower Se doses, as well as planned Mg administration. In burns <20% TBSA and for the other TEs the recommended parenteral nutrition TE doses appear sufficient.


Estimation of mean and median particle size of ruminant digesta.
An alternative exponential equation with a parameter as an exponent was compared to a recently published exponential procedure for estimating mean and median particle size. Both equations were fit to literature values for particle size distributions of esophageal extrusa, rumen digesta, and feces. In addition, 112 observations of particle-size distributions of esophageal extrusa were fit to both equations for comparison. Both equations gave adequate fits of rumen digesta and feces, but the earlier model was biased by regular deviations from observed data for esophageal extrusa. Use of the previously published model overestimated mean particle size in esophageal extrusa from 4.5 to 10.3%. Median particle size was underestimated from 4.9 to 5.6%. Analytic solutions exist for mean and median particle sizes for the earlier model, but it is necessary to estimate numerically the mean and median particle sizes when using the proposed equation. Even though the solution for the proposed equation must be determined numerically, it will prevent bias between experimental treatments, give more accurate estimates of mean and median particle size, and result in a lower residual sums of squares. In addition, a single equation can be used to model particle size reduction throughout the digestive tract.


Does modifying dietary lipids influence the progression of renal failure?
Recent studies have identified important effects of dietary fatty acid composition in animals with chronic renal disease, particularly in dogs. The theoretic basis for these effects provides a rationale for the use of diets enriched with omega-3 (but not omega-6) polyunsaturated fatty acids. A therapeutic trial with a diet enriched with omega-3 polyunsaturated fatty acids should be considered as a maneuver designed to slow the rate of progression of chronic renal disease in dogs.


Computer assisted structure-activity studies of chemical carcinogens. An N-nitroso compound data set.
N-nitroso compounds, consisting of nitrosamines and nitrosamides, are potentially important in the etiology of human cancer. An attempt to study the molecular structure-carcinogenicity relations of these compounds is reported. A pattern-recognition approach was used to develop predictive ability for carcinogenic potential. A set of 15 calculated molecular structure descriptors that supported a linear discriminant function able to successfully separate 116 carcinogens from 28 noncarcinogens was identified. Predictive ability of an overall of 91%--93% for carcinogens and 85% for noncarcinogens--was obtained in the randomized testing. This relatively high predictability demonstrates that pattern-recognition methods can be useful in analyzing these compounds for carcinogenic activity. The inclusion of two electronic descriptors implicitly supports the alpha-hydroxylation hypothesis. The relations of descriptors used and possible mechanism of action are discussed.


General Medical Council. A clear case of....
A review of how the GMC handles complaints against doctors found shortcomings in consistency and transparency of decision-making. The lack of a common definition of what constitutes serious professional misconduct is a major problem. The review found no evidence of discrimination or racial bias in complaints handling. Protocols should be developed for dealing with complaints alleging poor treatment, which account for some 70 per cent of complaints received by the GMC. The whole process of complaints handling should be subject to continual audit, and written records should be kept of all decisions taken.


[Treatment of external intestinal fistulas].
The paper based on own extensive clinical material of 29 cases stresses the value of conservative treatment of external intestinal fistulae as illustrated by a case of small intestine fistula associated with large bowel fistula treated previously many times surgically without success. Besides that the importance is emphasized of radiological treatment in the diagnosis and treatment of external intestinal fistulae.


A new entry to doubly N-confused [26]hexaphyrins(1.1.1.1.1.1) from normal [26]hexaphyrins(1.1.1.1.1.1) through an unprecedented double pyrrolic rearrangement.
Treatment of hexakis(pentafluorophenyl)-substituted [26]hexaphyrin(1.1.1.1.1.1) (1) with CuCl in the presence of pyridine and molecular oxygen led to formation of doubly N-confused [26]hexaphyrin(1.1.1.1.1.1) 2 in a moderate yield through an unprecedented double pyrrolic rearrangement. Macrocycle 2 has been shown to serve as an effective bis-metal-coordinating ligand and exhibits attractive optical properties such as a sharp Soret-like band at 566 nm and low-energy fluorescence at 1058 nm.


Educational paper. The development of new therapies for pediatric oncology.
Although cure rates for children with cancer are approximately 70%, improvements in cure rates have slowed in the past decade, likely due to our inability to further improve outcome using currently available drugs. Novel drug approaches are needed for children with difficult-to-treat malignancies, such as stage IV neuroblastoma, sarcomas, brain tumors, and relapsed leukemia. Several novel agents show promise for improving outcome in patients with either high risk or recurrent disease. For leukemia, inhibitors of cell cycle progression, such as clofarabine and nelarabine, have shown great promise in their ability to increase treatment efficacy in high-risk disease. Targeted agents such as tyrosine kinase inhibitors, DNA binding compounds (trabectedin), and monoclonal antibodies (GD2 inhibitors for neuroblastoma and anti-CD22 antibodies for pre-B acute lymphocytic leukemia (ALL)) also show promise for future treatment. Extensive reviews of each of these agents are presented elsewhere; this article provides an overview of molecular agents at different stages of FDA/EMA approval; those that are currently approved for use in children, currently approved for use in adults, as well as those that show promise in early clinical trial testing, or are supported by strong preclinical data.


Contribution of the ocean sector to the United States economy.
The national income accounts have been reorganized to estimate the contribution to the gross national product of the ocean sector and its various subsectors for the year 1972. The new account is the first within the national income accounts to be organized along geographic, rather than productive, sectors. If properly updated and disseminated, this new account will give government and business interests a solid and consistent data base to measure, and choose among, the alternative uses of the oceans.


[Application of the racial algorithm in energy dispersive X-ray fluorescence overlapped spectrum analysis].
In the energy dispersive X-ray fluorescence spectrum analysis, scintillation detector such as NaI (Tl) detector usually has a low energy resolution at around 8%. The low energy resolution causes problems in spectral data analysis especially in the high background and low counts condition, it is very limited to strip the overlapped spectrum, and the more overlapping the peaks are, the more difficult to peel the peaks, and the qualitative and quantitative analysis can't be carried out because we can't recognize the peak address and peak area. Based on genetic algorithm and immune algorithm, we build a new racial algorithm which uses the Euclidean distance as the judgment of evolution, the maximum relative error as the iterative criterion to be put into overlapped spectrum analysis, then we use the Gaussian function to simulate different overlapping degrees of the spectrum, and the racial algorithm is used in overlapped peak separation and full spectrum simulation, the peak address deviation is in +/- 3 channels, the peak area deviation is no more than 5%, and it is proven that this method has a good effect in energy dispersive X-ray fluorescence overlapped spectrum analysis.


Studies on the development of infant foods from plant protein sources. Part III. Preparation, processing and properties of various products developed.
Studies have been carried out on the development of a low-cost, high-quality infant food of low paste viscosity from rice, chickpea (Cicer arietinum) and cow's milk. In order to improve the overall quality of the product, chickpea was processed by different methods prior to its incorporation. A number of formulations was prepared by mixing 52% rice, 30% each, the processed chickpea sample, and 18% whole milk powder. These mixtures were processed by extrusion cooking or drum drying. In the case of the extrusion cooking method, from the nutritional and technological points of view, it was found advantageous to incorporate milk powder after cooking a mixture of rice and chickpea. The values of net protein ratio (NPR) of the products developed, whether processed by extrusion cooking or drum-drying methods, were statistically equal, and not significantly different from those of casein. Supplementing the product with methionine and threonine showed no effect in improving the NPR value, suggesting that these amino acids were not limiting. There were slight differences in the digestibilities of proteins in the products developed and all were lower than that of casein. Depending on the processing method, differences were observed in paste viscosities of the products. After partial hydrolysis of the products with pounds amylase, both the cold and hot paste viscosities were greatly reduced and were comparable with those of whole milk powder. From the results herein reported, it can be concluded that the drum-dried product prepared using rice:chickpea (carbonate presoaked):milk (52:30:18) is the best of all the products developed. Its amino acid composition compares favorably with that of the milk proteins.


Studies on the mechanism of lymphocyte-mediated cytolysis. VI. A reappraisal of the requirement for protein synthesis during T cell-mediated lysis.
The role of protein synthesis in the mechanism of T cell-mediated cytolysis has been re-investigated. Cytolytically active (C57BL/L anti-DBA/2) spleen cells treated with pactamycin (10-7 M to 10-6 M) exhibited suppressed protein synthesis (100 +/- 5%), but unimpeded lytic activity. Drug-treated effector cells, incubated for prolonged (up to 24 hr) periods of time in the presence and absence of antigen, showed no siginificant diminution of lytic activity although the incorporation of 3H-leucine into protein was totally ablated. Studies with emetine, another irreversible inhibitor of protein synthesis, gave identical results. These findings are difficult to reconcile with the hypothesis that effector T cells lysis via a soluble protein mediator.