Health and social precursors of later life retirement-community migration.
This study uses the developmental migration paradigm developed by Litwak and Longino (1987) as a framework to investigate the health and social determinants of late-life elderly mobility to retirement communities. Data from four waves of the Longitudinal Study of Aging are used to predict the likelihood of moving from the general community to two types of retirement communities--those with group meals and those without group meals. Multinomial logistic regression reveals that the likelihood of migrating to both types of retirement communities increases as disability advances to moderate levels, but declines as disability becomes severe. Migration to retirement communities is also more likely among elderly persons who live alone and among those whose children do not live nearby. The results suggest that retirement community migration in middle and late old age is motivated not only by social and amenity considerations, but also by the need for assisted living arising from physical frailty. Implications for developmental migration theory and long-term care policy are discussed.


An in vitro investigation of the effects of the ACTH/MSH(4-9) analogue, Org 2766, on guinea pig medial vestibular nucleus neurons.
Vestibular compensation is a process of CNS plasticity that is correlated to a return of resting activity in medial vestibular nucleus (MVN) neurons ipsilateral to a peripheral vestibular deafferentation. Systemic administration of melanocortin peptides accelerates the compensation process; the ACTH/MSH(4-9) analogue, Org 2766, accelerates this process at smaller doses than ACTH/MSH(4-10). The present study investigated the effect of Org 2766 on MVN neurons in vitro using extracellular single-cell recording. Org 2766 was less potent at the neuronal level than ACTH/MSH(4-10). When Org 2766 and ACTH/MSH (4-10) were tested consecutively on the same neuron, the response was often different. Org 2766 and ACTH/MSH (4-10) may have a different mode and/or site of action.


Integrated lipid production, CO2 fixation, and removal of SO2 and NO from simulated flue gas by oleaginous Chlorella pyrenoidosa.
CO2, SO2, and NO are the main components of flue gas and can cause serious environmental issues. Utilization of these compounds in oleaginous microalgae cultivation not only could reduce air pollution but could also produce feedstock for biodiesel production. However, the continuous input of SO2 and NO inhibits microalgal growth. In this study, the toxicity of simulated flue gas (15% CO2, 0.03% SO2, and 0.03% NO, balanced with N2) was reduced through automatic pH feedback control. Integrated lipid production and CO2 fixation with the removal of SO2 and NO was achieved. Using this technique, a lipid content of 38.0% DW was achieved in Chlorella pyrenoidosa XQ-20044. The lipid composition and fatty acid profile indicated that lipid production by C. pyrenoidosa XQ-20044 cultured with flue gas is suitable as a biodiesel feedstock; 81.2% of the total lipids were neutral lipids and 99.5% of the total fatty acids were C16 and C18. The ratio of saturated fatty acids to monounsaturated fatty acids in the microalgal lipid content was 74.5%. In addition, CO2, SO2, and NO from the simulated flue gas were fixed and converted to biomass and lipids with a removal efficiency of 95.9%, 100%, and 84.2%, respectively. Furthermore, the utilization efficiencies of CO2, SO2, and NO were equal to or very close to their removal efficiencies. These results provide a novel strategy for combining biodiesel production with biofixation of flue gas.


Loop electrosurgical excisional procedure.
Loop electrosurgical excisional procedure, or LEEP, also known as loop diathermy treatment, loop excision of the transformation zone (LETZ), and large loop excision of the transformation zone (LLETZ), is a new technique for outpatient diagnosis and treatment of dysplastic cervical lesions. This procedure produces good specimens for cytologic evaluation, carries a low risk of affecting childbearing ability, and is likely to replace cryotherapy or laser treatment for cervical neoplasias. LEEP uses low-current, high-frequency electrical generators and thin stainless steel or tungsten loops to excise either lesions or the entire transformation zone. Complication rates are comparable to cryotherapy or laser treatment methods and include bleeding, incomplete removal of the lesion, and cervical stenosis. Compared with other methods, the advantages of LEEP include: removal of abnormal tissue in a manner permitting cytologic study, low cost, ease of acquiring necessary skills, and the ability to treat lesions with fewer visits. Patient acceptance of the procedure is high. Widespread use of LEEP by family physicians can be expected.


Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26.
The simultaneous development of resistance to the cytotoxic effects of several classes of natural product anticancer drugs, after exposure to only one of these agents, is referred to as multiple drug resistance (MDR). At least two distinct mechanisms for MDR have been postulated: that associated with P-glycoprotein and that thought to be due to an alteration in DNA topoisomerase II activity (at-MDR). We describe studies with two sublines of human leukemic CCRF-CEM cells approximately 50-fold resistant (CEM/VM-1) and approximately 140-fold resistant (CEM/VM-1-5) to VM-26, a drug known to interfere with DNA topoisomerase II activity. Each of these lines is cross-resistant to other drugs known to affect topoisomerase II but not cross-resistant to vinblastine, an inhibitor of mitotic spindle formation. We found little difference in the amount of immunoreactive DNA topoisomerase II in 1.0 M NaCl nuclear extracts of the two resistant and parental cell lines. However, topoisomerase II in nuclear extracts of the resistant sublines is altered in both catalytic activity (unknotting) of and DNA cleavage by this enzyme. Also, the rate at which catenation occurs is 20-30-fold slower with the CEM/VM-1-5 preparations. The effect of VM-26 on both strand passing and DNA cleavage is inversely related to the degree of primary resistance of each cell line. Our data support the hypothesis that at-MDR is due to an alteration in topoisomerase II or in a factor modulating its activity.


[Clinical application of a digital method in mammographic image processing].
The authors describe digital processing of mammographic images based on simulation of the procedure performed by radiologists to analyse radiographs. Image processing allows automatically enhancing contrasts and expressing them as a range of different light intensities and colors. Minimum contrast differences that are difficult to perceive with the bare eye are thus highly enhanced. This processing of mammographic images has proved useful not only to detect discrete lesions, but also to differentiate benign and malignant lesions.


Standardisation of allergens in Europe.
A general monograph for allergen products has now been adopted by the European Pharmacopoeia Commission. It is based on the use of an In-House Reference Preparation (IHRP), which shall be used in the control of every production batch after appropriate characterization. This characterization will depend on the intended use of the product. When possible, the biological potency should be established by skin testing and expressed in biological units. The monograph is the first mandatory regulation in Europe for allergen products and will guarantee the consistent composition and potency of the products on the market.


Dynamics of hepatic and intestinal cholesterol and bile acid pathways: The impact of the animal model of estrogen deficiency and exercise training.
Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.


Prevalence of gastrointestinal parasites in working horses.
Fecal samples for detection of gastrointestinal parasites were collected from 221 working horses from September 2002 to May 2003 from 14 villages in Urmia, North West of Iran. Fecal samples of 46 horses (20.8%) were negative for parasite eggs or oocysts. One hundred and seventy five positive horses (48.9%) were infected with a single parasite type and 49 (22.2%) and 18 (8.1%) of horses had multiple infections with two and three parasites, respectively. The highest prevalence and intensity rate belonged to small strongyles. The overall prevalence of intestinal parasites eggs and oocyst in the positive horses were: strongyles 72.9%, Oxyuris equi 22.6%, Parascaris equorum 12.2%, Anoplocephalidae 6.3%, Fasciola spp. 3.2% and Eimeria leuckarti 0.5%. Larval identification showed that small strongyle larvae were most frequent (97.6%) followed by Strongylus edentatus (22.6%), S. equinus (18.5%) and S. vulgaris (6.5%). This study suggests that the high rate of infection with gastrointestinal parasites could contribute to low performance and life expectancy of working horses in the region.


Yeast techniques for modeling drugs targeting Bcl-2 and caspase family members.
Development of drugs targeting Bcl-2 relatives and caspases, for treating diseases including cancer and inflammatory disorders, often involves measuring interactions with recombinant target molecules, and/or monitoring cancer cell killing in vitro. Here, we present yeast-based methods for evaluating drug-mediated inhibition of Bcl-2 relatives or caspases. Active Bax and caspases kill Saccharomyces cerevisiae, and pro-survival Bcl-2 proteins can inhibit Bax-induced yeast death. By measuring the growth or adenosine triphosphate content of transformants co-expressing Bax with pro-survival Bcl-2 relatives, we found that the Bcl-2 antagonist drugs ABT-737 or ABT-263 abolished Bcl-2 or Bcl-xL function and reduced Bcl-w activity, but failed to inhibit Mcl-1, A1 or the poxvirus orthologs DPV022 and SPPV14. Using this technique, we also demonstrated that adenoviral E1B19K was resistant to these agents. The caspase inhibitor Q-VD-OPh suppressed yeast death induced by caspases 1 and 3. Yeast engineered to express human apoptotic regulators enable simple, automatable assessment of the activity and specificity of candidate drugs targeting Bcl-2 relatives or caspases.


Motion of the distal tibiofibular syndesmosis under different loading patterns: A biomechanical study.
The distal tibiofibular syndesmosis is an important structure for ankle stability. The objective of this study was to evaluate the motion of the syndesmosis under different loading patterns and determine the characteristics of the syndesmotic motion. Six fresh cadaveric lower extremity specimens with the knee reserved were tested in this study. The skin and muscles were removed with all ligaments around the syndesmosis and knee and ankle joint intact. An axial load of 600 N was applied to the specimens with the ankle joint in 10° dorsiflexion, neutral position, and 15° plantar flexion using a universal material testing machine. Then, with the ankle joint positioned neutrally, a combination of 600-N axial and 5-Nm torsional external rotation loading was applied to the specimens. The medial-lateral and anterior-posterior displacement and rotation of the distal fibula relative to the distal tibia were measured. Under the axial loading, the distal fibula tended to move medially and anteriorly and rotate internally with the ankle positioned from the neutral position to 15° plantar flexion. Meanwhile, when the ankle was positioned from the neutral position to 10° dorsiflexion, the distal fibula tended to move laterally and posteriorly and rotate externally. Under the combined loading, with respect to the isolated axial loading, the distal fibula tended to move medially and posteriorly, and rotate externally relative to the distal tibia. Micro motion existed in the syndesmosis. The relative motion of the syndesmosis was correlated to the ankle position and loading patterns.


Impact of High-Sensitivity Troponin I Testing with Sex-Specific Cutoffs on the Diagnosis of Acute Myocardial Infarction.
High-sensitivity cardiac troponin I (hs-cTnI) assays show sex-dependent differences in the 99th percentile of healthy populations, with concentrations in women approximately 50% lower. The adoption of sex-specific cutoffs seems appropriate, although it is not yet clear what effect these will have on acute myocardial infarction (AMI) diagnosis and management. We conducted a retrospective pre- and postchangeover analysis of troponin I testing in the 6 months before and after moving from the contemporary Abbott Architect TnI assay (cTnI) to hs-cTnI at 2 tertiary centers in Australia and New Zealand. The cTnI cutoff was 30 ng/L for both sexes, whereas a female-specific cutoff of 16 ng/L was adopted upon changeover to hsTnI. Changeover from the cTnI assay to the hs-cTnI assay increased the number of female patients with increased troponin I concentrations at both sites (from 29.7% to 34.9% and from 22.4% to 30.8%; P < 0.001). There was no statistically significant change in the number of men with increased concentrations in the same time period (P = 0.09). The increased percentage of women with increased troponin I was not associated with an increase in the number of women with AMI diagnoses at either center. Angiographic data available from 1 center showed no change in the percentage of angiograms performed in women. Although increasing the proportion of women with increased troponin I, adopting sex-specific cutoffs with the hs-cTnI assay did not lead to an increase in AMI diagnoses in females, or in the number of women undergoing angiography.


Links between fluid mechanics and quantum mechanics: a model for information in economics?
This paper tallies the links between fluid mechanics and quantum mechanics, and attempts to show whether those links can aid in beginning to build a formal template which is usable in economics models where time is (a)symmetric and memory is absent or present. An objective of this paper is to contemplate whether those formalisms can allow us to model information in economics in a novel way.


Multisensory integration and attention in autism spectrum disorder: evidence from event-related potentials.
Successful integration of various simultaneously perceived perceptual signals is crucial for social behavior. Recent findings indicate that this multisensory integration (MSI) can be modulated by attention. Theories of Autism Spectrum Disorders (ASDs) suggest that MSI is affected in this population while it remains unclear to what extent this is related to impairments in attentional capacity. In the present study Event-related potentials (ERPs) following emotionally congruent and incongruent face-voice pairs were measured in 23 high-functioning, adult ASD individuals and 24 age- and IQ-matched controls. MSI was studied while the attention of the participants was manipulated. ERPs were measured at typical auditory and visual processing peaks, namely, P2 and N170. While controls showed MSI during divided attention and easy selective attention tasks, individuals with ASD showed MSI during easy selective attention tasks only. It was concluded that individuals with ASD are able to process multisensory emotional stimuli, but this is differently modulated by attention mechanisms in these participants, especially those associated with divided attention. This atypical interaction between attention and MSI is also relevant to treatment strategies, with training of multisensory attentional control possibly being more beneficial than conventional sensory integration therapy.


Reproducibility of spontaneous initiations of atrial fibrillation.
It has been suggested that some atrial regions may play a role in the maintenance of atrial fibrillation (AF), whereas little is known about the presence of critical areas for the initiation of AF. It is conceivable that the identification of such critical areas may lead to more localized and selective strategies of ablative therapy. A patient suffering from paroxysmal AF was extensively mapped in both the atria with a multielectrode basket catheter in right atrium and two decapolar catheters placed in the coronary sinus and along the left septum. During the mapping, seven identical patterns of initiation of AF were recorded. AF was initiated by an atrial premature beat (APB) arising from the superior right septum, followed by a reentrant beat originating from the same area that slowly propagated through the atria and resulted in late activation of the right lateral wall. During sinus rhythm, the majority of the electrograms were single potentials, whereas during the APB, and particularly during the first atrial reentrant beat, a high percentage of fragmented complexes was present, mainly located in the right superior septum. These fragmented complexes were present in the same sites in each initiating episode and remarkably, they showed an almost identical morphology. This case suggests that in some patients the initiation of AF could be caused by reentrant circuits localized in specific atrial regions and the reentrant circuits could be identical in the different episodes of AF. This highlights the importance of increasing our understanding of the mechanisms of the initiation of AF so that we can identify any critical area involved in the genesis of AF where selective RF lesions may be effective in curing this arrhythmia.


Planned gait termination in cerebellar ataxias.
This study set out to characterise the pattern of planned gait termination in a sample of patients with cerebellar diseases. The gait termination phase was recorded, using a motion analysis system, in ten patients with primary degenerative cerebellar disease and in ten controls. The subjects were instructed to walk at different gait speeds and to stop in response to an acoustic signal. Time-distance parameters (step length, step width, double support duration, time-to-slow, stopping time, centre of mass velocity and number of steps) and stability index-related parameters (distance between the "extrapolated centre of mass" (XCoM) and centre of pressure (CoP)) were measured at both matched and self-selected gait speeds. At matched speed the patients, compared with the controls, showed a reduced step length, a greater first and second step width and used more steps to stop. At self-selected speed, almost all the parameters differed from those of the controls. Furthermore, the patients showed an increased stability index, suggesting that they need to maintain a "safety margin" between the XCoM and CoP during the gait termination. Patients develop a series of compensatory strategies in order to preserve balance during planned gait termination, e.g. increasing their step width and number of steps. Ataxic patients need to maintain a safety margin in order to avoid instability when stopping. Given the potential risk of falls when stopping, walking ataxic patients may benefit from a rehabilitation treatment focused on preserving and improving their ability to terminate gait safely.


Immunohistochemical demonstration of mycobacterial antigens in intracranial tuberculoma.
Mycobacterial antigens have been demonstrated immunohistochemically in the paraffin sections of 10 intracranial tuberculous granulomas and the results were compared with the detection of acid fast bacilli by conventional Ziehl-Neelsen method. In none of the 10 specimens, acid fast bacilli were demonstrated while mycobacterial antigens were characterised as diffusely staining granular brownish-pink material within the cytoplasm of giant cells and macrophages. In 14 specimens of granulomatous lesions due to non-tuberculous aetiology, immunohistochemical stains were negative for mycobacterial antigen. Thus demonstration of mycobacterial antigen will be not only useful in establishing mycobacterial aetiology of a caseating intracranial granuloma but also can be used as an alternative method to the conventional Ziehl-Neelsen method.


Isolation and Structure Elucidation of Fujikurins A-D: Products of the PKS19 Gene Cluster in Fusarium fujikuroi.
Fusarium fujikuroi is a member of the Gibberella fujikuroi species complex and well known for the production of gibberellins and mycotoxins including fusarins and fusaric acid. A recent genome sequencing study revealed that the fungus has the genetic potential to produce many more secondary metabolites than have been reported. This paper describes the structure elucidation of the products of the cryptic and silent PKS19 gene cluster that were recently identified (fujikurins A-D). We present the complete NMR data for the structure elucidation of the main compound fujikurin D, which shows tautomeric 1,3-diketo elements. The different tautomeric structures could be confirmed using quantum chemical calculations. Additionally, the structures of the minor compounds fujikurins A-C were elucidated by high-resolution mass spectrometric fragmentation experiments. It emerged that fujikurin A was identical to the bioactive compound CR377 of the taxonomically unclassified Fusarium strain CR377, while fujikurins B-D have not been reported from other fungi.


Similar support for three different life course socioeconomic models on predicting premature cardiovascular mortality and all-cause mortality.
There are at least three broad conceptual models for the impact of the social environment on adult disease: the critical period, social mobility, and cumulative life course models. Several studies have shown an association between each of these models and mortality. However, few studies have investigated the importance of the different models within the same setting and none has been performed in samples of the whole population. The purpose of the present study was to study the relation between socioeconomic position (SEP) and mortality using different conceptual models in the whole population of Scania. In the present investigation we use socioeconomic information on all men (N = 48,909) and women (N = 47,688) born between 1945 and 1950, alive on January, 1st,1990, and living in the Region of Scania, in Sweden. Focusing on three specific life periods (i.e., ages 10-15, 30-35 and 40-45), we examined the association between SEP and the 12-year risk of premature cardiovascular mortality and all-cause mortality. There was a strong relation between SEP and mortality among those inside the workforce, irrespective of the conceptual model used. There was a clear upward trend in the mortality hazard rate ratios (HRR) with accumulated exposure to manual SEP in both men (p for trend < 0.001 for both cardiovascular and all-cause mortality) and women (p for trend = 0.01 for cardiovascular mortality) and (p for trend = 0.003 for all-cause mortality). Inter- and intragenerational downward social mobility was associated with an increased mortality risk. When applying similar conceptual models based on workforce participation, it was shown that mortality was affected by the accumulated exposure to being outside the workforce. There was a strong relation between SEP and cardiovascular and all-cause mortality, irrespective of the conceptual model used. The critical period, social mobility, and cumulative life course models, showed the same fit to the data. That is, one model could not be pointed out as "the best" model and even in this large unselected sample it was not possible to adjudicate which theories best describe the links between life course SEP and mortality risk.


In Silico Study to Develop a Lectin-Like Protein from Mushroom Agaricus bisporus for Pharmaceutical Application.
A lectin-like protein of unknown function designated as LSMT was recently discovered in the edible mushroom Agaricus bisporus. The protein shares high structural similarity to HA-33 from Clostridium botulinum (HA33) and Ricin-B-like lectin from the mushroom Clitocybe nebularis (CNL), which have been developed as drug carrier and anti-cancer, respectively. These homologous proteins display the ability to penetrate the intestinal epithelial cell monolayer, and are beneficial for oral administration. As the characteristics of LSMT are unknown, a structural study in silico was performed to assess its potential pharmaceutical application. The study suggested potential binding to target ligands such as HA-33 and CNL although the nature, specificity, capacity, mode, and strength may differ. Further molecular docking experiments suggest that interactions between the LSMT and tested ligands may take place. This finding indicates the possible use of the LSMT protein, initiating new research on its use for pharmaceutical purposes.


The Werner syndrome protein is distinguished from the Bloom syndrome protein by its capacity to tightly bind diverse DNA structures.
Loss of Werner syndrome helicase-exonuclease (WRN) or of its homolog Bloom syndrome helicase (BLM) results in different inherited disorders. Whereas Werner syndrome is characterized by premature onset of aging and age-associated diseases, Bloom syndrome involves developmental abnormalities and increased predisposition to diverse malignancies. To identify biochemical differences between WRN and BLM that might contribute to the dissimilar outcomes of their loss, we compared their abilities to unwind and bind in vitro diverse DNA structures. Full-length recombinant WRN and BLM proteins expressed in and purified from Sf9 insect cells unwound to comparable extents and with similar K(m) values partial DNA duplex, splayed arm DNA and G'2 bimolecular quadruplex DNA. However, WRN resolved bubble DNA ∼25-fold more efficiently than BLM. The two enzymes were mainly distinguished by their contrasting abilities to bind DNA. WRN bound partial duplexes, bubble and splayed arm DNA and G'2 bimolecular and G4 four-molecular quadruplexes with dissociation constants of 0.25 to 25 nM. By contrast, BLM formed substantial complexes with only G4 quadruplex DNA while binding only marginally other DNA structures. We raise the possibility that in addition to its enzymatic activities WRN may act as a scaffold for the assembly on DNA of additional DNA processing proteins.


In-vitro study on the identification of gastrointestinal stromal tumor tissues using laser-induced breakdown spectroscopy with chemometric methods.
Early-stage detection of tumors helps to improve patient survival rate. In this work, we demonstrate a novel discrimination method to diagnose the gastrointestinal stromal tumor (GIST) and its healthy formalin fixed paraffin embedded (FFPE) tissues by combining chemometric algorithms with laser-induced breakdown spectroscopy (LIBS). Chemometric methods which include partial least square discrimination analysis (PLS-DA), k-nearest neighbor (k-NN) and support vector machine (SVM) were used to build the discrimination models. The comparison of PLS-DA, k-NN and SVM classifiers shows an increase in accuracy from 94.44% to 100%. The comparison of LIBS signal between the healthy and infected tissues shows an enhancement of calcium lines which is a signature of the presence of GIST in the FFPE tissues. Our results may provide a complementary method for the rapid detection of tumors for the successful treatment of patients.


Intravenous Foreign Body at the Hand: Case Report.
Intravenous foreign bodies following trauma to the hand are relatively uncommon with sparse reports of this condition being published in the literature. They have been reported to migrate as far as the thoracic cavity and the heart. In the following case report, we describe a case of an intravenous foreign body following hand trauma, and the treatment and potential complications are also discussed.


Flux Growth of Uranyl Titanates: Rare Examples of TiO4 Tetrahedra and TiO5 Square Bipyramids.
Single crystals of four new uranyl titanates have been grown via the flux growth method using mixed alkali halide fluxes. Na2(UO2)(TiO)O3 and KNa(UO2)(TiO)O3 have analogous layered structures containing titanyl (TiO2+) units coordinated into TiO5 square pyramids. Cs2(UO2)TiO4 crystallizes in the Cs2USiO6 structure type and is a rare example of a structure containing TiO4 tetrahedra. Cs2(UO2)Ti2O6 crystallizes in a new tunnel structure and contains the also rare TiO5 trigonal bipyramids. DFT studies were performed to understand the bonding in the observed titanate polyhedra. Furthermore, the luminescence properties of the compounds are reported, and leaching studies are reported for Cs2(UO2)Ti2O6.


Hepatobiliary nutrition: history and future.
The liver is a master metabolic gland; consequently, liver disease commonly results in significant malnutrition. Complex metabolic derangements always accompany liver failure, often reflect the magnitude of hepatic insufficiency, and are characterized by accentuated catabolism. Nutritional assessment is problematic in these patients, because many of the usual indicators of nutritional status are altered directly by the hepatic pathophysiology rather than, or in addition to, preexisting or subsequent secondary malnutrition. The objective of nutritional support in patients with liver failure is to provide adequate nutrients to ensure the availability of specific substrates for energy and protein synthesis and for normal hepatocyte survival and function, without inducing or accentuating encephalopathy or otherwise compounding hepatic insufficiency. In the near future, guidelines must be developed for the specific nutritional support of patients with fulminant hepatic failure, cholestatic liver disease, steatosis, and cirrhosis. Currently, work is underway to develop an artificial liver for patients awaiting transplantation; to use genetic engineering technology to provide an alternative source of hepatic tissue; and to test the utility of various intermediary metabolites for hepatobiliary nutrition support. No ideal regimen for nutritional support of all forms of liver failure exists, and this also represents a significant challenge for future basic and clinical investigations. However, it is mandatory to attempt to maintain optimal nutrition in patients with severe liver failure if morbidity and mortality are to be reduced and survival is to be maximized.


Obesity and breast cancer: role of inflammation and aromatase.
Obesity is now recognised to be an inflammatory condition in which dysregulated metabolism plays an integral role. Inflammatory mediators regulate aromatase expression in the human breast as one mechanism whereby they increase the risk of breast cancer, especially in women who are obese.


Patterns and predictors of adaptive skills in 2- to 7-year-old children with Down syndrome.
There is substantial variability in adaptive skills among individuals with Down syndrome. Few studies, however, have focused on the early developmental period or on the potential sources of variability in adaptive skills. This study characterizes adaptive skills in young children with Down syndrome and investigates child characteristics associated with adaptive skills. Participants were 44 children with Down syndrome ranging in age from 2.50 to 7.99 years (M = 4.66 years, SD = 1.46). The Vineland Adaptive Behavior Scales-3 (VABS-3) Comprehensive Interview Form was used to assess adaptive behavior in the three core domains: socialization, daily living, and communication skills. Caregivers also reported on motor skills and autism spectrum disorder symptoms. Child cognitive abilities were assessed. Analyses comparing mean standard score performance across the three VABS-3 core domains demonstrated significant differences between all pairs of domains, resulting in a group-level pattern of socialization > daily living > communication skills. At the individual level, 10 different patterns of relative strength and weakness were identified, with only 18% of participants evidencing significant differences between adaptive skill domain standard scores corresponding to the group-level pattern of significant differences. Child characteristics (cognitive abilities, motor skills, and autism spectrum disorder symptoms) were significantly associated with VABS-3 adaptive domain standard scores. These findings underscore the importance of individualizing intervention programs focused on improving the adaptive skills of young children with Down syndrome based on consideration of the child's relative adaptive strengths and weaknesses.


Hemodynamic effects of combined beta-adrenoceptor blockade and precapillary vasodilatation in hypertension.
Carvedilol (BM14190) is a new compound with combined properties of nonselective beta-adrenoceptor blockade, devoid of ISA, and precapillary vasodilatation. Its acute hemodynamic effects were studied with invasive technique (dye-dilution using Cardio-Green) in 10 patients taking 25 mg orally and noninvasive (fore-arm plethysmography) in 10 patients taking 25 mg and in 10 patients taking 50 mg orally, all with essential hypertension. Significant reductions of systolic and diastolic blood pressures (p less than 0.05 - 0.001) were observed in all groups. TPR did not change acutely whereas resistance in the fore-arm was reduced by 16% (p less than 0.05). When a comparison with propranolol (80 mgx2) was made in a randomized, double-blind placebo controlled trial comprising 30 patients with essential hypertension, carvedilol acutely reduced blood pressure significantly 13/6 mm Hg (25 mg) and 17/10 mm Hg (50 mg) in contrast to propranolol. Resistance in the fore-arm (plethysmography) fell significantly with carvedilol 50 mg whereas propranolol caused a significant rise. After 4 weeks both compounds had reduced blood pressure significantly and to the same extent. Blood flow was still reduced with propranolol in contrast to the findings with carvedilol. We conclude that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment. It has an attractive hemodynamic profile.


Ac23, an envelope fusion protein homolog in the baculovirus Autographa californica multicapsid nucleopolyhedrovirus, is a viral pathogenicity factor.
Viral envelope fusion proteins are important structural proteins that mediate viral entry and may affect or determine the host range of a virus. The acquisition, exchange, and evolution of such envelope proteins may dramatically affect the success and evolutionary divergence of viruses. In the family Baculoviridae, two very different envelope fusion proteins have been identified. Budded virions of group I nucleopolyhedroviruses (NPVs) such as the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), contain the essential GP64 envelope fusion protein. In contrast group II NPVs and granuloviruses have no gp64 gene but instead encode a different envelope protein called F. F proteins from group II NPVs can functionally substitute for GP64 in gp64null AcMNPV viruses, indicating that GP64 and these F proteins serve a similar functional role. Interestingly, AcMNPV (and other gp64-containing group I NPVs) also contain an F gene homolog (Ac23) but the AcMNPV F homolog cannot compensate for the loss of gp64. In the present study, we show that Ac23 is expressed and is found in budded virions. To examine the function of F protein homologs from the gp64-containing baculoviruses, we generated an Ac23null AcMNPV genome by homologous recombination in E. coli. We found that Ac23 was not required for viral replication or pathogenesis in cell culture or infected animals. However, Ac23 accelerated the mortality of infected insect hosts by approximately 28% or 26 h. Thus, Ac23 represents an important viral pathogenicity factor in larvae infected with AcMNPV.


Analysis of recurrent patterns in toroidal magnetic fields.
In the development of magnetic confinement fusion which will potentially be a future source for low cost power, physicists must be able to analyze the magnetic field that confines the burning plasma. While the magnetic field can be described as a vector field, traditional techniques for analyzing the field's topology cannot be used because of its Hamiltonian nature. In this paper we describe a technique developed as a collaboration between physicists and computer scientists that determines the topology of a toroidal magnetic field using fieldlines with near minimal lengths. More specifically, we analyze the Poincaré map of the sampled fieldlines in a Poincaré section including identifying critical points and other topological features of interest to physicists. The technique has been deployed into an interactive parallel visualization tool which physicists are using to gain new insight into simulations of magnetically confined burning plasmas.


Agoraphobic cognitions in old and young patients with panic disorder.
To compare the agoraphobic cognitions of younger and older patients suffering from panic disorder with agoraphobia by means of existing questionnaires. Agoraphobic cognitions were assessed using the Agoraphobic Cognitions Questionnaire (ACQ) in 205 patients confirmed with confirmed panic disorder with agoraphobia (Diagnostic and Statistical Manual, Fourth Edition, Text Revision) and analyzed at the item level applying a Bonferroni correction. The 48 patients who were older than 60 years had a significantly lower mean (SD) ACQ total score than their younger counterparts (1.6 [0.5] versus 2.1 [0.6]; t = 5.7, df = 203, p < 0.001), with their scores on the items fear of going crazy, acting foolishly, losing control, passing out, and brain tumors (p < 0.004) being significantly lower. The differential effect at the ACQ item level suggests that some cognitions seem less relevant for agoraphobic panic disorder in later life. Future research should explore whether and which agerelated cognitions are missed in the current questionnaires.


Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review.
The concept of hypertension as primarily a consequence of altered hemodynamics has changed. Many factors are now implicated in the development of hypertensive vascular disease, and the renin-angiotensin-aldosterone system (RAAS) appears to be one of the most significant. Angiotensin II, the principal effector peptide of the RAAS, has far-reaching effects on vascular structure, growth and fibrosis, and is a key regulator of vascular remodeling and inflammation. Reactive oxygen species and a network of signaling pathways mediate angiotensin II and cellular mechanisms that promote remodeling and inflammation. The involvement of aldosterone in vessel-wall and myocardial remodeling has also come under intensive research scrutiny. Treatments that block the pathologic effects of the RAAS at several points have been shown to limit target-organ damage in hypertension and to decrease cardiovascular morbidity and mortality. Understanding the molecular and cellular mechanisms that participate in the early development of hypertensive vascular disease may lead to more targeted treatment and improved outcomes.


Comparative chromosome studies in species of subtribe Orchidinae (Orchidaceae).
In our study, FISH mapping using 18S-5.8S-25S rDNA and 5S rDNA sequences was performed for the first time on Ophrystenthredinifera Willdenow, 1805, Serapiasvomeracea (Burman f., 1770) Briquet, 1910 and Himantoglossumhircinum (Linnaeus, 1753) Sprengel, 1826. A detailed study was also performed on O.tenthredinifera using Giemsa-staining, silver-staining, CMA fluorescence banding and fluorescence in situ hybridisation (FISH) with rDNA probes. We analysed two subspecies, i.e. O.tenthrediniferasubsp.neglecta (Parlatore, 1860) E.G. Camus, 1908 and O.tenthrediniferasubsp.grandiflora (Tenore, 1819) Kreutz, 2004 by the traditional Feulgen method and constructed the karyotype. The cytotaxonomic implications for both taxa are also discussed. In Himantoglossumhircinum, FISH and silver staining highlighted differences in the number of two rDNA families (35S and 5S) with respect to Barliarobertiana (Loiseleur-Deslongchamps, 1807) Greuter, 1967. In addition, fluorescence in situ hybridisation was also applied to diploid (2n = 2x = 36) and triploid (2n = 3x = 54) Anacamptismorio (Linnaeus, 1753) R.M. Bateman, Pridgeon et M.W. Chase, 1997. As far as we are aware, this is the first case of autotriploidy observed in A.morio.


Biochemical characterization of soluble proteins in pecan [Carya illinoinensis (Wangenh.) K. Koch].
Pecans (cv. Desirable) contained approximately 10% protein on a dry weight basis. The minimum nitrogen solubility (5.9-7.5%) at 0.25-0.75 M trichloroacetic acid represented the nonprotein nitrogen. Among the solvents assessed for protein solubilization, 0.1 M NaOH was the most effective, while borate saline buffer (pH 8.45) was judged to be optimal for protein solubilization. The protein solubility was minimal in the pH range of 3-7 and significantly increased on either side of this pH range. Increasing the NaCl concentration from 0 to 4 M significantly improved ( approximately 8-fold increase) protein solubilization. Following Osborne protein fractionation, the alkali-soluble glutelin fraction (60.1%) accounted for a major portion of pecan proteins followed by globulin (31.5%), prolamin (3.4%), and albumin (1.5%), respectively. The majority of pecan polypeptides were in the molecular mass range of 12-66 kDa and in the pI range of 4.0-8.3. The pecan globulin fraction was characterized by the presence of several glycoprotein polypeptides. Lysine was the first limiting essential amino acid in the defatted flour, globulin, prolamin, and alkaline glutelin fractions. Leucine and tryptophan were the first limiting essential amino acids in albumin and acid glutelin fractions, respectively. Rabbit polyclonal antibodies detected a range of pecan polypeptides in the 12-60 kDa range, of which the globulin fraction contained the most reactive polypeptides.


Risk Factors for Short-Term Lung Cancer Survival.
Lung cancer is typically diagnosed in an advanced phase of its natural history. Explanatory models based on epidemiological and clinical variables provide an approximation of patient survival less than one year using information extracted from the case history only, whereas models involving therapeutic variables must confirm that any treatment applied is worse than surgery in survival terms. Models for classifying less than one year survival for patients diagnosed with lung cancer which are able to identify risk factors and quantify their effect for prognosis are analyzed. Two stepwise binary logistic regression models, based on a retrospective study of 521 cases of patients diagnosed with lung cancer in the Interventional Pneumology Unit at the Hospital "Virgen de las Nieves", Granada, Spain. The first model included variables age, history of pulmonary neoplasm, tumor location, dyspnea, dysphonia, and chest pain. The independent risk factors age greater than 70 years, a peripheral location, dyspnea and dysphonia were significant. For the second model, treatments were also significant. Age, history of pulmonary neoplasm, tumor location, dyspnea, dysphonia, and chest pain are predictors for survival in patients diagnosed with lung cancer at the time of diagnosis. The treatment applied is significant for classifying less than one year survival time which confirms that any treatment is markedly inferior to surgery in terms of survival. This allows to consider applications of more or less aggressive treatments, anticipation of palliative cares or comfort measures, inclusion in clinical trials, etc.


Health and mortality in Eastern Europe, 1965-85.
The author explores reasons and indicators for the high morbidity and mortality rates of Eastern Europe and the USSR during the period 1965 to 1985. "Epidemiological reasoning would prompt profound questions about the impact of governance on health conditions in these areas. The populations...have different languages, cultures and histories....[and] vary in material and technical attainment. The most obvious common characteristic of these countries is that they have all been ruled by Marxist-Leninist states.... After more than two decades of health decline...it is perhaps not premature to inquire into whether the health problems evidenced in these countries might be in part systemic."


Creating satisfaction: a psychological perspective on stress and coping in families of handicapped children.
This paper briefly reviews the literature on stress and coping in families of developmentally handicapped children and proposes an alternative way for conceptualizing some of the psychological processes involved. The approach specifies how threats to certain human needs lead to predictable patterns of appraisal and coping. The usefulness of this alternative is demonstrated for families of autistic children and the theoretical and clinical implications are discussed.


Topical Reformulation of Valsartan for Treatment of Chronic Diabetic Wounds.
Chronic wounds are among the most devastating and difficult to treat consequences of diabetes. Dysregulation of the skin renin-angiotensin system is implicated in abnormal wound healing in diabetic and older adults. Given this, we sought to determine the effects of topical reformulations of the angiotensin type 1 receptor blockers losartan and valsartan and the angiotensin-converting enzyme inhibitor captopril on wound healing in diabetic and aged mice with further validation in older diabetic pigs. The application of 1% valsartan gel compared with other tested formulations and placebo facilitated and significantly accelerated closure time and increased tensile strength in mice, and was validated in the porcine model. One percent of valsartan gel-treated wounds also exhibited higher mitochondrial content, collagen deposition, phosphorylated mothers against decapentaplegic homologs 2 and 3 and common mothers against decapentaplegic homolog 4, alpha-smooth muscle actin, CD31, phospho-vascular endothelial growth factor receptor 2, and p42/44 mitogen-activated protein kinase. Knockout of the angiotensin subtype 2 receptors abolished the beneficial effects of angiotensin type 1 receptor blockers, suggesting a role for angiotensin subtype 2 receptors in chronic wound healing.


Psychomotor effects of alprazolam and diazepam during acute and subacute treatment, and during the follow-up phase.
Psychomotor effects of alprazolam (AZ) and diazepam (DZ) were compared in a controlled double-blind and cross-over trial in 24 student volunteers, who received, three times daily, placebo for the first 4 days, then an active drug (AZ) 0.25 mg or DZ 5 mg) for 7 days, and again placebo for 3 days. After a 3 week wash-out period the procedure was repeated with the comparative drug. Objective and subjective measurements were made on day 3 (placebo), on days 4 and 10 (active drug) and on days 11, 12 and 13 (follow-up placebo). Baseline levels were measured in the morning, a capsule was taken, and the tests were repeated 2 hours and 8 hours later. Blood samples were taken in the afternoon of day 10 for the bioassay of serum benzodiazepine concentrations. Single doses of both AZ 0.25 mg and DZ 5 mg showed similar degree of impairment in several objective tests. At the end of the 7-day maintenance DZ (15 mg daily) proved significantly more sedative and impaired more psychomotor performance than AZ (0.75 mg daily) did. Improvement of the complex test performances (a learning effect) was counteracted by DZ more than by AZ. No actual development of tolerance was demonstrated after either drug. During the follow-up placebo phase, DZ showed more objective residual effects than AZ. The Maddox wing test (exophoria) showed a significant DZ effect to be still present on the third post-treatment day. However, during the follow-up period subjects reported subjectively more sedation and clumsiness after AZ than after DZ, but this was not associated with impairment of objective skills.


Guanine nucleotide regulatory proteins in the spontaneously hypertensive rat.
We compared guanine nucleotide regulatory protein (G protein) levels and function in plasma membranes from resistance vessels (mesenteric arteries) isolated from spontaneously hypertensive (SHR) and normotensive Wistar rats. G protein function was deduced from studies of adenylate cyclase activity. Although the basal level of adenylate cyclase activity (+/- Mn2+ ions) was significantly greater in SHR membranes, addition of agents that function via the stimulatory G protein--i.e., NaF (10(-2) M), (-)-isoproterenol (10(-4) M), and prostaglandin E1 (10(-5) M)--resulted in a significantly lower stimulatory response in SHR membranes. Ligands that function via the inhibitory G protein--i.e., adrenaline (10(-5) M)/propranolol (10(-5) M) (this combination being equivalent to an alpha 2-receptor agonist), carbachol (10(-3) M), and serotonin (10(-5) M)--were responsible for only slight inhibitory responses in both SHR and Wistar rat membranes, which were not significantly different. Western blotting identified the presence of Gs, Gi2, and Gi3 alpha-subunits in rat vascular smooth muscle, but there were no differences in the levels of these G protein alpha-subunits found in SHR and Wistar rat plasma membranes. The levels of the beta-subunit in the two sets of membranes were also similar. In conclusion, there is a reduced response in adenylate cyclase activity to agents that function via the stimulatory G protein in SHR membranes. However, this is not a consequence of altered levels of the different G protein subunits.


Infectious canine hepatitis in red foxes (Vulpes vulpes) in the United Kingdom.
The pathological findings are described in three cases of infectious canine hepatitis in free-ranging red foxes (Vulpes vulpes) in England. The foxes died after short periods of clinical illness. Mild jaundice and hepatic congestion were evident grossly. On histopathological examination, intranuclear inclusion bodies were visible in hepatocytes, in association with hepatocyte dissociation and necrosis, as well as in renal glomeruli, renal tubular epithelial cells and vascular endothelial cells. Canine adenovirus type 1 (CAV-1) was isolated from all three foxes. In a serological study, antibodies to CAV-1 were detected in tissue fluid extracts taken from 11 of 58 (19 per cent) frozen red fox carcases from England and Scotland.


Granuloma Annulare - A Manifestation of Primary Cutaneous Mucinous Carcinoma?
The objective of this report is to present a rare case of primary cutaneous mucinous carcinoma (PCMC) manifesting with granuloma annulare (GA), and to discuss the association as a paraneoplastic phenomenon. A 65-year-old female presented with a painless, slow-growing, cystic nodule less than 1 cm over the left lateral canthus. The clinical presentation was highly suspicious of sebaceous cyst. The histopathologic examination revealed variable sizes of neoplastic cell clusters in a pool of abundant mucin. A focus of palisading lympho-histiocytic infiltrate surrounding a necrobiosis suggestive of granuloma annulare adjacent to the tumor is identified. Series of extensive investigations performed did not reveal any primary origin. GA can rarely be associated with various malignant conditions. Its association and prognostic importance to these conditions are unclear. The presence with certain malignancies and the resolution of GA with the treatment of underlying malignancy are an indicator that this condition can very well be a paraneoplastic phenomenon.


[Molecular pathophysiology of schizophrenia and preventive strategy in pubertal period].
A novel frameshift mutation in glyoxalase 1 (GLO1) gene was detected in a patient with schizophrenia of a pedigree with multiple affected individuals. The patient carrying the mutation showed decreased enzymatic activity by 50%, 3.7 times high level of advanced glycation end products (AGEs) that is substrate of GLO1 and 20% of serum vitamin B6 compared to controls. Case-control study of GLO1 gene suggested that Ala allele of Glu111Ala was associated with schizophrenia. In vitro study using COS-7 cells transfected with cDNA of GLO1 yielded that enzymatic activity is lower in GLO1 with Ala111 than that of Glu111. The homozygotes of Ala111 showed 16% decreased GLO1 activities in RBC as compared with that of Glu111/Ala111 and Glu111/Glu111. Plasma AGEs levels were significantly high and serum vitamin B6 was significantly low in 45 schizophrenics than that of 61 control subjects. Supplementation of vitamin B6 to cases with the genetic defect of GLO1 before onset of psychosis is suggested to be possible strategy for prevention of schizophrenia until pubertal stage since such mutation carriers could have been exposed by high level of AGEs for a long time before disease onset.


Time-Dependent Distribution of Hydroxychloroquine in Cynomolgus Macaques Using Population Pharmacokinetic Modeling Method.
To evaluate the biodistribution of hydroxychloroquine (HCQ) in cynomolgus macaques and receive dynamic quantitative relationship between plasma, blood, and lung tissue concentration using the population pharmacokinetic modeling method, seventeen cynomolgus macaques were divided into six groups according to different HCQ dosing regimens over 5 days. The monkeys were euthanized, and blood, plasma, urine, feces and ten tissues were collected. All the samples were prepared by protein precipitation and analyzed by HPLC-MS/MS detection. The population pharmacokinetics of HCQ in the plasma, red blood cells, and lung tissue was conducted and simulated via ADAPT program. Results demonstrated that the maximum concentration (C max) of HCQ was 292.33 ng/mL in blood and 36.90 ng/mL in plasma after single dose of 3 mg/kg. The value of area under curve (AUC0-∞) was determined as 5,978.94 and 363.31 h* ng/mL for the blood and plasma, respectively. The descending order of the tissue-to-plasma concentration ratio was liver > spleen > kidney > lung > heart > subcutaneous fat > brain. The tissue-to-plasma concentration ratio and the tissue-to-blood concentration ratio for lung were found to be time-dependent with 267.38 and 5.55 at 120 h postdose, respectively. A five-compartment model with first-order oral absorption and elimination best described the plasma, blood, and lung tissue pharmacokinetics. The estimated elimination rate constant (ke) for a typical monkey was 0.236 h-1. The volume of distribution in central (Vc/F) and other two peripheral compartments (Vb/F and Vl/F) were 114, 2.68, and 5.55 L, respectively. Model-based simulation with PK parameters from cynomolgus macaques showed that the ratio of the blood or plasma to lung tissue was a dynamic change course, which suggested that the rate of HCQ concentration decrease in the blood or plasma was faster than that in the lung tissue. HCQ was found to be accumulated in tissues, especially in the liver, kidney, lung, and spleen. Also, the tissue-to-plasma concentration ratio increased over time. The population pharmacokinetic model developed could allow for the assessment of pharmacokinetics-pharmacodynamics relationships, especially relevant tissue concentration-response for HCQ. Determining appropriate treatment regimens in animals allows translation of these to clinical studies.


Establishment and characterization of a nerve cell line (NC-HIMT) from HIMT cells derived from a human ovarian immature teratoma with special reference to the induction of neuron differentiation by retinoic acid.
A nerve cell line designated NC-HIMT was established from a HIMT cell line derived from a benign ovarian, three germ layer immature teratoma removed from a 21-year-old Japanese female. The HIMT cells were elongated, ellipsoid or spherical in shape, whose karyotype was on the high side of normal diploidy. Small amounts of retinoic acid enhanced differentiation and maturation of the HIMT cells into nervous tissue, and the NC-HIMT cell line was established by the colony isolating technique when the HIMT cell line was cultured in the presence of retinoic acid-supplemented medium. After establishment, the NC-HIMT cell line was cultured and maintained in retinoic acid-free growth medium. Even though these cells were cultured without retinoic acid, the phenotype of nerve cells remained and the cells were also maintained in a state of high normal diploidy. The nerve cells contacted each other with their long cell projections and formed networks. Immunocytochemical observations using anti-bovine NSE, alpha-internexin, neurofilament 200kD, peripherin and GFAP confirmed that the cells were either nerve cells or glia cells. These results assume that HIMT cells, which were derived from an immature teratoma, have progenitor and/or stem cells which can differentiate into nerve and/or glial cells.


Effects of Pelargonium sidoides extract EPs 7630 on acute cough and quality of life - a meta-analysis of randomized, placebo-controlled trials.
Cough is a leading symptom of viral acute respiratory infections such as acute bronchitis (AB) and the common cold (CC), which can be debilitating and may persist for several weeks. We investigated whether treatment with Pelargonium extract EPs 7630 may reduce cough and improve disease-related quality of life (QoL). We performed a meta-analysis of randomized, placebo-controlled trials investigating the efficacy of EPs 7630 in AB or CC. Efficacy analyses included change from baseline in a cough intensity score, remission of cough, and disease-associated impairments of QoL. Data of 2,195 participants from 11 trials (3 in children/adolescents with AB, 3 in adults with AB, 5 in adults with CC) were eligible. In children/adolescents with AB, 79.6% of participants treated with EPs 7630 and 41% treated with placebo showed a reduction in the intensity of cough by at least 50% of baseline values at day 7 [meta-analysis rate/risk ratio (RR), EPs 7630 / placebo: 1.86 (95% CI: 1.34; 2.95)], and 18.0% vs 5.5% presented with complete remission of cough [RR: 2.91 (95% CI: 1.26; 6.72)]. In adults with AB, 88.7% of participants in the EPs 7630 group and 47.6% in the placebo group showed a ≥50% response for cough intensity [RR: 2.13 (95% CI: 1.37; 3.31)], while 26.0% vs 6.3% did not cough any more at day 7 [RR: 5.00 [95% CI: 3.10; 8.07)]. Cough scale results were supported by significant improvements over placebo in the pursuit of normal daily activities and other QoL measures. In CC, 56.8% of participants treated with EPs 7630 and 38.8% treated with placebo showed a ≥50% cough intensity reduction [RR: 1.40 (95% CI: 1.19; 1.65)] at day 5, while 26.1% versus 18.4% showed complete remission of cough for EPs 7630 and placebo, respectively [RR: 1.40 (95% CI: 1.06; 1.84)]. CCassociated pain/discomfort and impairment of usual activities were no longer present in 41.5% and 48.8% of participants treated with EPs 7630 compared to less than 40% of patients in the placebo group. The results show that EPs 7630 reduces the burden and leads to earlier remission of cough. Advantages for EPs 7630 were also reflected in self-rated measures of disease-associated QoL. Of note, patients treated with the herbal product felt able to resume their usual daily activities sooner.


[A rare case of sarcoidosis localization: the cavum].
We present a single case of isolated sarcoidosis pseudo-tumour of the cavum. The patient presented with progressive nasal obstruction. A well confirmed mass at the roof of the cavum was seen with the endoscope. Histological diagnosis was made following endoscopic biopsy of the mass. The general examination was negative. There were no further signs of disease progression after 8 months of treatment.


The effect of head-related filtering and ear-specific decoding bias on auditory attention detection.
We consider the problem of Auditory Attention Detection (AAD), where the goal is to detect which speaker a person is attending to, in a multi-speaker environment, based on neural activity. This work aims to analyze the influence of head-related filtering and ear-specific decoding on the performance of an AAD algorithm. We recorded high-density EEG of 16 normal-hearing subjects as they listened to two speech streams while tasked to attend to the speaker in either their left or right ear. The attended ear was switched between trials. The speech stimuli were administered either dichotically, or after filtering using Head-Related Transfer Functions (HRTFs). A spatio-temporal decoder was trained and used to reconstruct the attended stimulus envelope, and the correlations between the reconstructed and the original stimulus envelopes were used to perform AAD, and arrive at a percentage correct score over all trials. We found that the HRTF condition resulted in significantly higher AAD performance than the dichotic condition. However, speech intelligibility, measured under the same set of conditions, was lower for the HRTF filtered stimuli. We also found that decoders trained and tested for a specific attended ear performed better, compared to decoders trained and tested for both left and right attended ear simultaneously. In the context of the decoders supporting hearing prostheses, the former approach is less realistic, and studies in which each subject always had to attend to the same ear may find over-optimistic results. This work shows the importance of using realistic binaural listening conditions and training on a balanced set of experimental conditions to obtain results that are more representative for the true AAD performance in practical applications.


The Effect of Brilliant Blue-Based Plaque-Staining Agents on Aesthetic Orthodontic Appliances.
Orthodontic appliances discolour over treatment time, and a yellowish plaque builds up on the contact area of the brackets, adhesive and teeth. Brilliant Blue-based plaque-staining agents (BBPSAs), which increase tooth brushing efficiency, have the potential to support the maintenance of proper oral hygiene during orthodontic treatment. However, they exhibit strong colouring properties, and their impact on the aesthetics of braces remains unclear. Therefore, the aim of this study was to investigate the influence of commercially available BBPSAs on the colour of aesthetic orthodontic materials. A light-cured, colour-changing orthodontic adhesive and new-generation, monocrystalline, sapphire brackets were chosen for the experiments. The effect of the staining agent on the tested materials was investigated in terms of the reaction temperature and time, as well as the presence of black tea-induced impurities on the materials. The CIELAB (Commission Internationale de L'éclairage L* a* b*) colour system parameters were measured, and the colour differences (ΔE*ab and ΔE00-the Commission Internationale de L'éclairage 2000 colour-difference) were determined for the materials under several experimental conditions. The braces' green-red colour expression was positively affected by the BBPSA. Under in vitro conditions, the regular use of the BBPSA for 90 days visibly improved the unfavourable colour change caused by the black tea.


Exploiting Photoelectric Activities and Piezoelectric Properties of NaNbO3 Semiconductors for Point-of-Care Immunoassay.
Point-of-care testing (POCT) technology has made major breakthroughs in community medicine and physician office situations, in tandem with the more ubiquitous and intensive usage of highly integrated quick detection equipment for illness diagnosis, personal care, and mobile healthcare. Although the photoelectrochemical (PEC)-based POCT platform offers the benefits of cheap cost and good user engagement, its commercialization is still limited by the photodetection components' downsizing and mobility, among other factors. In this work, a novel highly integrated PEC biosensor aided by piezophototronics to enhance the efficiency of PEC testing was reported for flexible detection of cancer-associated antigens in biological fluids (prostate-specific antigen, PSA, used as an example). Multiple signal enhancement strategies, including a magnetic bead-linked enzyme-linked immune system catalyzing the production of ascorbic acid from the substrate and a piezoelectric-assisted enhancement strategy, were used for sensitive detection of the analyte to be tested in human body fluids. Unlike the electron transfer mechanism in heterojunctions, piezoelectric semiconductors promote the transfer of electrons and holes by generating piezoelectric potentials in the ultrasonic field, thus contributing to the performance of the PEC testbed. Under optimized conditions, the test platform achieves good correspondence for PSA at 0.02-40 ng mL-1. Impressively, the test devices are comparable to or even superior to gold standard ELISA kits in terms of cost approval and batch testing. This research demonstrates the potential of piezoelectric semiconductors for POC applications in revolutionary PECs and offers innovative thoughts for the development of new PEC bioanalytical components.


Effect of gutkha chewing on periodontal health and oral hygiene of peoples in Delhi NCR region of North India: A cross-sectional multicentered study.
In India, gutkha is popular among all socioeconomic groups, since it is available easily and is of less cost. Various investigations have demonstrated the relationship of gutkha biting with periodontal status and oral hygiene. The aim of this study is to assess the effect of gutkha chewing on periodontal health and oral hygiene of patients attending the dental department in India. A cross-sectional investigation was directed among 200 patients going to dental camps. Among them, 100 were gutkha chewers and 100 were smokers. The oral hygiene status of selected patients was determined by using the Simplified Oral Hygiene Index. Various periodontal parameters like a gingival recession, clinical attachment loss, mobility, and furcation were used to evaluate the periodontal status. Data were collected and analyzed with the help of SPSS software version 20. Among the 200 subjects, 102 were males and 78 were females. In 100 gutkha chewers, 67% were male and 33% were females. About 68% gutkha chewers showed poor oral hygiene as compared to nonchewers (41%). The values of all the periodontal parameters were significantly higher in gutkha smokers compared to nonchewers. Gutkha chewing has a strong effect on oral hygiene. The findings can contribute to the evidence of smokeless tobacco (gutkha) as a risk factor for periodontal disease.


Pediatric bipolar disorder.
Pediatric bipolar disorder differs from the adult form of the disorder, marked by longer episodes, rapid cycling, prominent irritability, and high rates of comorbid attention-deficit/hyperactivity disorder and anxiety disorders. A careful assessment by families of children's symptoms, including their duration and intensity, helps with accurate diagnosis. After the diagnosis is made and careful psychopharmacological intervention is initiated, psychiatric nursing treatment of children and adolescents with pediatric bipolar disorder should involve child-and family-focused cognitive-behavioral therapies, family support, and psychoeducation.


Gouy Phase Radial Mode Sorter for Light: Concepts and Experiments.
We present an in principle lossless sorter for radial modes of light, using accumulated Gouy phases. The experimental setups have been found by a computer algorithm, and can be intuitively understood in a geometric way. Together with the ability to sort angular-momentum modes, we now have access to the complete two-dimensional transverse plane of light. The device can readily be used in multiplexing classical information. On a quantum level, it is an analog of the Stern-Gerlach experiment-significant for the discussion of fundamental concepts in quantum physics. As such, it can be applied in high-dimensional and multiphotonic quantum experiments.


High prevalence of inherited prothrombotic risk factors in 134 consecutive patients with von Willebrand disease.
We screened 134 consecutive patients with von Willebrand disease (VWD) (106 type 1, 26 type 2, and 2 type 3 VWD) for the most important inherited prothrombotic risk factors. One hundred eight patients (80.6%) were positive for at least one of the prothrombotic risk factors screened for. A high prevalence of prothrombin G20210A (10.5%) and factor V Leiden (11.9%) mutations was found with allele frequencies of 5.2 and 6%, respectively. Three carriers of multiple prothrombotic gene mutations experienced a thrombotic event. Our study suggests that the recent evidence of an association between inherited thrombotic and hemorrhagic disorders also holds true in VWD patients.


[Absorbed dose in CT: comparison by CT dose index].
Few reports have discussed the absorbed dose on CT units with increased scanning capacity even with the current widespread adoption of multi-slice CT units. To compare and investigate the dose indexes among CT units, we measured the absorbed dose on CT units operating in Nagano Prefecture Japan. The measurements showed proportionality between phantom absorbed dose and the exposured mAs values in conventional scanning operation. Further, the measurements showed that the absorbed dose in the center of the phantom differed by about 2.1-fold between the highest and lowest levels on individual CT units. Within a single company, multi-slice CT units of the same company gave absorbed doses of about 1.3 to 1.5 times those of conventional single-slice CT units under the same exposured conditions of conventional scanning. When the scanning pitch was reduced in helical scanning, the absorbed dose at the center of the phantom increased.


Fiberoptic-Guided Blue Rhino Dilator-Assisted Dilation of Postintubation Tracheal Stenosis: A Case Report About a Novel Technique.
Posttracheostomy tracheal stenosis is a rare complication of prolonged tracheal intubation. Treatment modalities that may be used include surgical resection and anastomosis, endoscopic tracheal dilation, laser resection, and tracheal stenting. We describe a novel salvage modality for dilation of a symptomatic tracheal stenosis using a percutaneous tracheostomy dilator wherein rigid bronchoscopic dilation was not feasible and balloon tracheal dilation had failed.


Application of information theory to clinical diagnostic testing. The electrocardiographic stress test.
The inherent imperfection of clinical diagnostic tests introduces uncertainty into their interpretation. The magnitude of diagnostic uncertainty after any test may be quantified by information theory. THe information content of the electrocardiographic ST-segment response to exercise, relative to the diagnosis of angiographic coronary artery disease, was determined using literature-based pooled estimates of the true- and false-positive rates for various magnitudes of ST depression from less than 0.5 mm to greater than or equal to 2.5 mm. This analysis allows three conclusions of clinical relevance. First, the diagnostic information content of exercise-induced ST-segment depression, interpreted by the standard 1.0-mm criterion, averages only 15% of that of coronary angiography. Second, there is a 41% increase in information content when the specific magnitude of ST-segment depression is analyzed, as opposed to the single, categorical 1-mm criterion. Third, the information obtained from ECG stress testing is markedly influenced by the prevalence of disease in the population tested, being low in the asymptomatic and typical angina groups and substantially greater in groups with nonanginal chest pain and atypical angina. The quantitation of information has broad relevance to selection and use of diagnostic tests, because one can analyze objectively the value of different interpretation criteria, compare one test with another and evaluate the cost-effectiveness of both a single test and potential testing combination.


Unique gene organization of thioredoxin and thioredoxin reductase in Mycobacterium leprae.
The thioredoxin system comprising thioredoxin (Trx), thioredoxin reductase (TR) and NADPH operates via redox-active disulphides and provides electrons for a wide variety of different metabolic processes in prokaryotic and eukaryotic cells. Thioredoxin is also a general protein disulphide reductase involved in redox regulation. In bacteria, the Trx and TR proteins previously identified were encoded by separate genes (trxA and trxB). In this study, we report a novel genomic organization of TR and Trx in mycobacteria and show that at least three modes of organization of TR and Trx genes can exist within a single bacterial genus: (i) in the majority of mycobacterial strains the genes coding for TR and Trx are located on separate sites of the genome; (ii) interestingly, in all pathogenic Mycobacterium tuberculosis complex mycobacteria both genes are found on the same locus, overlapping in one nucleotide; (iii) in the pathogen Mycobacterium leprae, TR and Trx are encoded by a single gene. Sequence analysis of the M. leprae gene demonstrated that the N-terminal part of the protein corresponds to TR and the C-terminal part to Trx. A corresponding single protein product of approximately 49 kDa was detected in cell extracts of M. leprae. These findings demonstrate the very unusual phenomenon of a single gene coding for both the substrate (thioredoxin) and the enzyme (thioredoxin reductase), which seems to be unique to M. leprae.


A review of the application of reinforced hydrogels and silk as biomaterials for intervertebral disc repair.
The degeneration of the intervertebral disc (IVD) within the spinal column represents a major pain source for many patients. Biological restoration or repair of the IVD using "compressive-force-resistant" and at the same time "cytocompatible" materials would be desirable over current purely mechanical solutions, such as spinal fusion or IVD implants. This review provides an overview of recent research on the repair of the inner (nucleus pulposus = NP) and the outer (annulus fibrous = AF) parts of the IVD tissue. Many studies have addressed NP repair using hydrogel-like materials. However, only a few studies have so far focused on AF repair. As the AF possesses an extremely low self-healing capacity and special attention to shear-force resistance is essential, special repair designs are required. In our review, we stated the challenges in IVD repair and highlighted the use of composite materials such as silk biomaterials and fibrin cross-linked reinforced hydrogels. We elaborated on the origin of silk and its many in tissue engineering. Furthermore, techniques such as electrospinning and 3D printing technologies allow the fabrication of versatile and functionalised 3D scaffolds. We summarised the research that has been conducted in the field of regenerative medicine over the recent years, with a special focus on the potential application and the potential of combining silk and reinforced - and thus mechanically tailored - hydrogels for IVD repair.


Virtual and augmented reality in the treatment of phantom limb pain: A literature review.
Phantom limb pain (PLP), the perception of discomfort in a limb no longer present, commonly occurs following amputation. A variety of interventions have been employed for PLP, including mirror therapy. Virtual Reality (VR) and augmented reality (AR) mirror therapy treatments have also been utilized and have the potential to provide an even greater immersive experience for the amputee. However, there is not currently a consensus on the efficacy of VR and AR therapy. The aim of this review is to evaluate and summarize the current research on the effect of immersive VR and AR in the treatment of PLP. A comprehensive literature search was conducted utilizing PubMed and Google Scholar in order to collect all available studies concerning the use of VR and/or AR in the treatment of PLP using the search terms "virtual reality," "augmented reality," and "phantom limb pain." Eight studies in total were evaluated, with six of those reporting quantitative data and the other two reporting qualitative findings. All studies located were of low-level evidence. Each noted improved pain with VR and AR treatment for phantom limb pain, through quantitative or qualitative reporting. Additionally, adverse effects were limited only to simulator sickness occurring in one trial for one patient. Despite the positive findings, all of the studies were confined purely to case studies and case report series. No studies of higher evidence have been conducted, thus considerably limiting the strength of the findings. As such, the current use of VR and AR for PLP management, while attractive due to the increasing levels of immersion, customizable environments, and decreasing cost, is yet to be fully proven and continues to need further research with higher quality studies to fully explore its benefits.


Investigation of Mechanical Properties of Large Shape Memory Alloy Bars under Different Heat Treatments.
Shape memory alloys (SMAs) are a class of functional materials that possess unique thermomechanical properties, such as shape memory effect (SME), superelasticity (SE), damping, and good fatigue and corrosion resistance, which enable them to become ideal materials for applications in earthquake engineering. Numerous studies have shown that the mechanical properties of superelastic SMAs mainly depend on the wire form, or the relationship between the microstructure and thermally induced phase transitions. However, extremely few studies have elucidated the effects of the heat-treatment strategy, size effect of large diameters, and cyclic loading. Herein, the mechanical properties of SMA bars, such as residual strain, energy dissipation, and equivalent damping ratio, were studied with different heat-treatment strategies, cyclic loadings, and strain amplitudes; this was achieved by conducting cyclic tensile tests on SMA bars with four different diameters. The results indicate that the maximum phase transformation stress was obtained with a 14 mm SMA bar subjected to heat treatment at 400 ℃ for 15 min. The mechanical properties were relatively stable after five loading-unloading cycles, which should be considered in engineering applications. The test results provide a mechanical basis for using large SMA bars in self-centering structures in seismic regions.


Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques.
SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10-17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure.


Association of metabolic syndrome with development of new-onset diabetes after transplantation.
New-onset diabetes after transplantation (NODAT) is a major posttransplant complication associated with lower allograft and recipient survival. Our objective was to determine whether metabolic syndrome pretransplant is independently associated with NODAT development. We recruited 640 consecutive incident nondiabetic renal transplant recipients from three academic centers between 1999 and 2004. NODAT was defined as the use of hypoglycemic medication, a random plasma glucose level more than 200 mg/dL, or two fasting glucose levels more than or equal to 126 mg/dL beyond 30 days posttransplant. Metabolic syndrome was common pretransplant (57.2%). NODAT developed in 31.4% of recipients 1 year posttransplant. Participants with metabolic syndrome were more likely to develop NODAT compared with recipients without metabolic syndrome (34.4% vs. 27.4%, P=0.057). Recipients with increasing number of positive metabolic syndrome components were more likely to develop NODAT (metabolic syndrome score prevalence at 1 year: 0 components-0.0%, 1-24.2%, 2-29.3%, 3-31.0%, 4-34.8%, and 5-73.7%, P=0.001). After adjustment for demographics, age by decade (hazard ratio [HR] 1.34 [1.20-1.50], P<0.0001), African American race (HR 1.35 [1.01-1.82], P=0.043), cumulative prednisone dosage (HR 1.18 [1.07-1.30], P=0.001), and metabolic syndrome (HR 1.34 [1.00-1.79], P=0.047) were independent predictors of development of NODAT at 1 year posttransplant. In a multivariable analysis incorporating the individual metabolic syndrome components themselves as covariates, the only pretransplant metabolic syndrome component to remain an independent predictor of NODAT was low high-density lipoprotein (hazard ratio [HR] 1.37 [1.01-1.85], P=0.042). Metabolic syndrome is an independent predictor for NODAT and is a possible target for intervention to prevent NODAT. Future studies to evaluate whether modification of metabolic syndrome factors pretransplant reduces NODAT development are needed.


Sex-Related Procedural Aspects and Complications in CRT Survey II: A Multicenter European Experience in 11,088 Patients.
This study sought to compare sex difference for procedural aspects and complications in the European Society of Cardiology CRT Survey II, exploring whether adverse events were related to the type of CRT device implanted. Sex-related differences in procedural aspects and complications in patients undergoing cardiac resynchronization therapy (CRT) implantation has not been explored in a real-life population. A post-hoc analysis of procedural data and complications in different sexes and factors associated with events was performed from data collected in the European Society of Cardiology CRT Survey II. Of all patients (n = 11,088) included, 24.3% were women. The mean age (70 years of age) of male and female recipients was similar. Female patients more frequently had an idiopathic cardiomyopathy (67.4% vs. 44.1%) and fewer comorbidities, including atrial fibrillation (34.8% vs. 42.8%), diabetes (29.1% vs. 32.1%), chronic obstructive lung disease (10.3% vs. 12.6%), and renal failure (28.7% vs. 31.9%), compared with men. More women compared with men had a pacemaker (56.6% vs. 46.3%) and much less often an implantable cardioverter-defibrillator (CRT-D) (19.0% vs. 34.7%) implant. Periprocedural event rate was the highest in women with CRT with defibrillator (7.1% vs. 4.8% in men), followed by women with a CRT with pacing (5.5% vs. 4.4% in men). The higher periprocedural event rate in CRT-D women was attributable primarily to the occurrence of pneumothorax (1.4%), coronary sinus dissection (2.1%), and pericardial tamponade (0.3%). The rate of in-hospital major adverse events (6.0%) and complications necessitating reoperation (4.0%) was not different among sex and device type. Women are more likely to experience adverse procedure-related events during CRT implantation. Thus, preventive strategies should be employed to minimize complication rate.


Ethylene evolution from cucumber plants as related to sex expression.
Ethylene evolved from monoecious and gynoecious cucumber (Cucumis sativus) plants grown under short and long day conditions was determined. More ethylene was evolved from floral buds and apices bearing buds than from whole seedlings of comparable weight. More ethylene also was evolved from apices of the gynoecious than from those of the monoecious type. Furthermore, quantities evolved from female buds were greater than from male ones and plants grown under short day conditions which promote femaleness evolved more ethylene than those grown under long day conditions. The data suggest that ethylene participates in the endogenous regulation of sex expression by promoting femaleness.


Psychological distress and workload as predictors of satisfaction with life in Peruvian female university professors with a family burden.
This study aims to determine whether psychological distress and workload predict satisfaction with life in Peruvian female university professors caring for dependent relatives. A total of 157 Peruvian female university professors aged 26-58 years who were caring for dependent relatives (M = 40.50; SD = 7.72) participated in the study. Of the female university professors participating in the study, 87.3% worked in a private university. The Psychological Distress Scale (K6), the Workload Scale (ECT) and the Satisfaction with Life Scale (SWLS) were applied to them. Through a multiple regression analysis, it was found that psychological distress (β = .559, p < .01) and workload (β = .173, p < .01) are variables that significantly predict satisfaction with life in university professors who are also housewives (adjusted R2 = .43), being psychological distress the variable with the highest predictive power. These findings provide evidence for the usefulness of considering both psychological distress and workload as predictors of satisfaction with life in female Peruvian university professors.


Sir David Cuthbertson Medal Lecture. The impact of dietary protein restriction on insulin secretion and action.
The goal of this review is to develop the hypothesis, and review the evidence, that protein restriction, through synergistic effects on multiple organ systems predisposes to loss of normal regulation of fuel homeostasis that plays the central role in the development of type 2 (non-insulin-dependent) diabetes mellitus. The ability of insulin to regulate glucose production and disposal varies between individuals. These differences, together with the various compensatory mechanisms that are invoked to attempt to normalize fuel homeostasis, are of fundamental importance in the development and clinical course of type 2 diabetes mellitus. Protein deprivation impacts on both insulin secretion and insulin action. These effects may persist even when a diet containing adequate protein is presented subsequently. Data are presented that suggest that protein restriction results in an impaired ability of pancreatic beta-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. This persistent impairment of insulin secretion resulting from protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of a diabetogenic challenge. This inability to maintain the degree of compensatory hyperinsulinaemia necessary to prevent loss of glucose tolerance may have relevance to the increased incidence of diabetes on changing from a nutritionally-poor diet to a Western diet, and to the hypothesis that some cases of type 2 diabetes in adulthood may be related to poor early nutrition.


Storage, display and access--innovations at the Harry Daly Museum and the Richard Bailey Library of the Australian Society of Anaesthetists, Sydney.
Open storage with simple access to collection items and books is a well-established form of museum display. It is particularly suited to collections in which many examples of slightly differing artefacts are acquired during the process of research and field work. In the long run, open storage saves curatorial time, relieves storage space problems and increases visitor interest and participation. Simple access procedures are essential when busy professionals require information for their ongoing research or immediate application.


In vivo micromechanical measurements of the organ of Corti in the basal cochlear turn.
Cochlear mechanical measurements of organ of Corti motion are generally accomplished in the apical or basal turn as in vivo or in vitro studies. In the apex it is possible to observe and measure tectorial membrane vibration as well as vibrations of structures such as the reticular lamina or the basilar membrane (BM). However, compared to the basal turn, cochlear amplification and nonlinearity are not strong in the apex. Basal turn studies have typically been limited to point location measurements of the BM but improved technology for laser interferometry is now making possible the spatial mapping of BM motion. The 'complexity' of BM motion in the radial direction (particularly the phase variation) is important to new models of cochlear wave amplification. In future work it may be possible to learn about vibration of structures within the organ of Corti.


Human polynucleotide phosphorylase (hPNPase old-35): an RNA degradation enzyme with pleiotrophic biological effects.
Identification of small inhibitory RNAs and microRNA established that regulation of RNA metabolism plays an essential role in controlling intracellular biochemical processes. Interferons induce a number of RNA degradation enzymes involved in innate immunity by degrading viral RNAs. We cloned human polynucleotide phosphorylase (hPNPase(old-35)), a type I interferon-inducible 3'-5' exoribonuclease, as a transcript induced during terminal differentiation and senescence, two physiological processes marked by irreversible growth arrest. Our studies in the last four years show that hPNPase(old-35) plays an essential role in mediating IFN-mediated growth inhibition and its upregulation might mediate chronic inflammatory pathological processes during aging. The present review recaps these findings and provides a framework for the future understanding of the versatile functions of this interesting molecule.


[The clinical classification systems and surgical methods for nasal inverted papilloma].
Nasal inverted papilloma (NIP) is one primary benign lesion that occurs in the nasal cavity and paranasal sinuses. In this paper, several clinical classifications of NIP were summarized. The most important classification, which was developed by Krouse in 2000, and endoscopic technique was applied to treat NIP in different Surgical methods.


Single case study and evidence-based practice.
Single case study and evidence-based practice With the current emphasis upon evidence-based medicine in statutory health care provision in the UK, mental health nursing is challenged to justify its approaches. Psychological theories, once taken for granted in mental health nursing, are now being challenged by new definitions of evidence. In this paper the authors focus upon the use of individual case study. The discussion questions the validity of applying the hierarchies of evidence proposed by evidence-based medicine to mental health nursing theory and practice. The role of case study as the prime source of evidence is argued and is justified in mental health nursing research and practice.


Toxoplasmosis and Alzheimer: can Toxoplasma gondii really be introduced as a risk factor in etiology of Alzheimer?
Alzheimer is a progressive neurological disease that results in irreversible loss of neurons and includes about two thirds of all cases of dementia. Toxoplasma gondii may be an important infectious agent involved in neurodegenerative diseases. The aim of this study was to investigate the correlation between Toxoplasma as an etiologic agent in the progress of Alzheimer's disease. This case control study was conducted on 75 Alzheimer's patients and 75 healthy volunteers. Blood samples were obtained and anti-Toxoplasma IgG and IgM tests were done by using ELISA technique. DNA was extracted from buffy coat and then GRA6 gene and SAG2 loci were amplified by PCR and nested PCR, respectively. Chi-square, Fisher's test, and binary logistic regression were used for data analysis. A percentage of 61.3 % of Alzheimer's patients and 62.6 % of healthy volunteers were positive for anti-Toxoplasma IgG but all participants were negative for anti-Toxoplasma IgM. There were no significant differences between Alzheimer's patients with their controls in terms of anti-Toxoplasma IgG antibody (P = 0.5). Due to lack of positive IgM sample, results of the molecular methods were negative by GRA6 and SAG2 fragments amplification. This result shows that, infection with T. gondii cannot be considered as a risk factor for etiology and developing Alzheimer's disease.


Pathologic prion protein infects cells by lipid-raft dependent macropinocytosis.
Transmissible spongiform encephalopathies, including variant-Creutzfeldt-Jakob disease (vCJD) in humans and bovine spongiform encephalopathies in cattle, are fatal neurodegenerative disorders characterized by protein misfolding of the host cellular prion protein (PrP(C)) to the infectious scrapie form (PrP(Sc)). However, the mechanism that exogenous PrP(Sc) infects cells and where pathologic conversion of PrP(C) to the PrP(Sc) form occurs remains uncertain. Here we report that similar to the mechanism of HIV-1 TAT-mediated peptide transduction, processed mature, full length PrP contains a conserved N-terminal cationic domain that stimulates cellular uptake by lipid raft-dependent, macropinocytosis. Inhibition of macropinocytosis by three independent means prevented cellular uptake of recombinant PrP; however, it did not affect recombinant PrP cell surface association. In addition, fusion of the cationic N-terminal PrP domain to a Cre recombinase reporter protein was sufficient to promote both cellular uptake and escape from the macropinosomes into the cytoplasm. Inhibition of macropinocytosis was sufficient to prevent conversion of PrP(C) to the pathologic PrP(Sc) form in N2a cells exposed to strain RML PrP(Sc) infected brain homogenates, suggesting that a critical determinant of PrP(C) conversion occurs following macropinocytotic internalization and not through mere membrane association. Taken together, these observations provide a cellular mechanism that exogenous pathological PrP(Sc) infects cells by lipid raft dependent, macropinocytosis.


Prevalence of suicidal ideation and suicide attempt in patients with migraine: A systematic review and meta-analysis.
Suicidality is common in patients with migraine. Here, we performed a systematic review and estimated the prevalence of suicidal ideation (SI) and suicide attempt (SA) in patients with migraine. We searched Pubmed, Embase, Web of Science, Cochrane database library, CINAHL, and PsycINFO for relevant publications. A random-effects model was used to pool the estimates of the prevalence of SI and SA, which were also stratified by the geographical location of the research institutions from the studies included in this meta-analysis. Fifteen studies involving 2,247,648 participants with migraine were selected. Pooled prevalence estimates of SI and SA were 15.5% [95% confidence interval (CI) 10.4-21.3%] and 3.9% (95% CI 0.9-8.8%), respectively, and the prevalence of SI was higher in Asian countries (21.5%, 95%CI 16.8-26.6%) compared with non-Asian countries (11.0%, 95%CI 6.1-17.2%). Measures of heterogeneity between studies were high for all outcomes (I2 = 89-100%), indicating that the substantial between-study heterogeneity in estimated proportions was not attributed to sampling error. The leave-one-out analysis showed that no single study significantly affected the final pooled results. This meta-analysis indicated a high prevalence of SI and SA in migraine patients. Thus, it is necessary to design targeted preventive measures for the management of migraine-related suicide.


[Surveillance of wild birds for avian influenza A virus (AIV) in Bavaria in the years 2007 and 2008].
A monitoring programme has been initiated in Bavaria to continuously control wild birds for the presence of avian Influenza A virus (AIV) and to monitor the possible occurrence and accumulation of notifiable AIV subtypes as an early-warning system. In addition information about the regional, seasonal and species-specific distribution of AIV could be obtained. Between July 2007 and December 2008 samples from 5864 wild birds of twelve different zoological orders had been collected (cloacal- and tracheal swab samples, droppings, and organs) and analysed. AIV genomes were detected in 3.7% of the 5864 wild birds by RT real time PCR. The subtype component H5 was identified in 52 samples (0.9%) and the N1 subtype component in 13 samples (0.2%), but never in combination with each other. The hemagglutinine subtype component H7 could not be detected. Most of the positive AIV genome results originated from samples in the district Swabia, which is situated in the central area of the south-west bird migration route across southern Germany and harbours favourable resting areas for migrating birds. Mallards (Anas platyrhynchos) were the most frequently sampled bird species and had the highest AIV infection rate of 6.4%, followed by Tufted ducks (Aythya fuligula) (AIV prevalence of 5.4%), Mute Swans (Cygnus olor) (1.6%), Coots (Fulica atra) (0.3%) and Greylag Goose (Anser anser) (0.1%). The detection rate of AIV in Bavarian wild birds showed a seasonal peak in autumn/winter. Ten virus isolates could be obtained after sample inoculation in embryonated hen's eggs.