Examining the Psychological and Spiritual Well-Being of Older Adult Individuals with Rheumatoid Arthritis in Turkey.
This study examined the psychological well-being (PWB) and spiritual well-being (SWB) of older adult individuals with rheumatoid arthritis (RA) who experienced the difficulties of both aging and RA. This descriptive and cross-sectional study was conducted in two centers located in the capital city of Turkey. A total of 136 individuals with a diagnosis of RA who met the inclusion criteria constituted the sample group of the study. Participant Information Form, SWB, and PWB Scales were used for data collection. The results showed that participants' PWB score was positively and significantly difference with marital status, presence of children, and regular participation in social activities. It was concluded that pain severity was not significantly difference with PWB and SWB. However, there was a significant negative correlation between PWB score and total SWB score and its two sub-dimensions, transcendence and anomie. Results emphasize the necessity of supportive interventions to increase psychological and spiritual well-being of older adult individuals with RA.


A Synthetic Route to β-Hydroxytyrosine-Derived Tetramic Acids: Total Synthesis of the Fungal Metabolite F-14329.
3-Acyltetramic acids derived from β-hydroxytyrosine are synthetically challenging. The first route to this structural motif, based upon a condensation between a Meldrum's acid conjugate bearing the acyl side chain, and a β-hydroxytyrosinate, N-protected by an ortho-nitrobenzyl group is presented. This group enables the Dieckmann cyclization of the resulting N-(β-ketoacyl)amino ester, after which it can be removed photolytically without compromising the delicate 3'-hydroxy group. This strategy was applied to the first total synthesis of the fungal metabolite F-14329 (1).


Challenges Working with Presidential Bioethics Commissions.
Presidential commissions come and go by design, and it is reasonable to wonder about the impact of their recommendations. I have been involved in the work of two presidential commissions: as a member of the Advisory Committee on Human Radiation Experiments (from 1994 to 1995) and as senior consultant to the National Bioethics Advisory Commission (from 1999 to 2000) for its report on multinational research. I continue to reflect on and look for the impact of both these commissions. ACHRE's charter included the review of experiments with ionizing radiation sponsored or conducted by the United States government since the 1940s. The committee was also charged with investigating specific intentional releases of radiation into the environment. ACHRE had a somewhat unique difficulty built into its work: the need to make retrospective ethical judgments. With the National Bioethics Advisory Commission, my main role as senior consultant consisted of writing chapters of the report on multinational research for the commissioners' approval. A more important concern for me as a hired consultant was how to maintain intellectual and moral integrity. Unlike when writing scholarly papers, where I can express my own views, when I was drafting text for a presidential commission, the commissioners' views took precedence over my own when we disagreed. I wondered, how much could I comply with the commissioners' positions without compromising my own integrity?


A flow-injection biamperometric method for determination of pantoprazole in pharmaceutical tablets.
A flow-injection biamperometric method for determination of pantoprazole (PTZ) in pharmaceutical tablets is reported for the first time. The reversible redox couples Fe3+/Fe2+, Fe(CN)6(3-)/Fe(CN)6(4-), Ce4+/Ce3+, VO3(-)NO2+, and I2/I- were tested as indicating redox systems for biamperometric determination of PTZ in a flow-injection assembly with optimized flow parameters. The best results were obtained using V03(-)NO2+, which showed to be a selective and sensitive biamperometric indicating system for PTZ even in the presence of excipients and antioxidants that typically are found in drugs. The analytical graph was linear (r = 0.99945) in the range from 10 to 100 mg/L using 25 mmol/L VO3(-) as the reagent and water as the carrier stream and applying 100 mV between the 2 platinum wire electrodes. The limits of detection and quantitation were 200 and 667 microg/L, respectively, with a sensibility of calibration of 22.6 mV/mg/L. The proposed method was successfully applied to determine PTZ in commercial pharmaceutical tablets with a mean relative error of 1.60% (n = 5) and mean relative standard deviation of 3.10%. Recoveries close to 100% showed good agreement between the expected amount of PTZ in tablets (40 mg) and the results found by the application of the proposed method and demonstrated that the formulations used in the tablet compositions do not interfere in the PTZ analysis. The system had good stability, with a relative standard deviation of 3.80% for 9 sequential injections of a 60 mg/L PTZ solution. A sampling rate of about 100 samples/h was obtained.


Medicinal Plants as Protective Strategies Against Parkinson's Disease.
Parkinson's disease is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra pars compacta region. An important mechanism contributing to its development is oxidative stress, induced by the imbalance between the endogenous antioxidant defenses and free radicals production. Naturally occurring bioactive compounds exhibit high antioxidant capacity that may help reducing oxidative stress and even reverse the damage induced by ROS. Fruits are particularly rich in phytochemicals with antioxidant effect, and their properties against the development of neurodegenerative diseases are of great interest. This review discusses how the fruits bioactive compounds and synthetic analogs have been assessed for their ability to regulate molecular pathways involved in neuronal survival such as MAPK, Nrf2, and NF-κB, thus elucidating the possible therapeutic and neuroprotective actions of these compounds.


Toxic effects of chlorate on three plant species inoculated with arbuscular mycorrhizal fungi.
Pot experiments were conducted to examine the toxic effects of chlorate on bermudagrass, bahiagrass, and longan seedling with a focus on arbuscular mycorrhizal fungi-plant associations. The results show that application of chlorate could cause slight soil acidification, but the resulting pH was still around 5.5, which is unlikely to adversely affect plant growth. Increase in the application rate of chlorate resulted in a decrease in colonization rate of arbuscular mycorrhizal fungi in plant roots, P uptake by the plants and plant biomass. This appears to suggest that the reduction in plant growth may be related to impeded uptake of P by the plants due to the failure of the plants to form sufficient mycorrhizal associations when chlorate is in sufficient amounts to cause toxicity to arbuscular mycorrhizal fungi. Under the experimental conditions set for this study, bermudagrass suffered from stronger chlorate stress than bahiagrass and longan seedling did in terms of plant-arbuscular mycorrhizal fungi (AMF) symbiosis development.


The obligate respiratory supercomplex from Actinobacteria.
Actinobacteria are closely linked to human life as industrial producers of bioactive molecules and as human pathogens. Respiratory cytochrome bcc complex and cytochrome aa3 oxidase are key components of their aerobic energy metabolism. They form a supercomplex in the actinobacterial species Corynebacterium glutamicum. With comprehensive bioinformatics and phylogenetic analysis we show that genes for cyt bcc-aa3 supercomplex are characteristic for Actinobacteria (Actinobacteria and Acidimicrobiia, except the anaerobic orders Actinomycetales and Bifidobacteriales). An obligatory supercomplex is likely, due to the lack of genes encoding alternative electron transfer partners such as mono-heme cyt c. Instead, subunit QcrC of bcc complex, here classified as short di-heme cyt c, will provide the exclusive electron transfer link between the complexes as in C. glutamicum. Purified to high homogeneity, the C. glutamicum bcc-aa3 supercomplex contained all subunits and cofactors as analyzed by SDS-PAGE, BN-PAGE, absorption and EPR spectroscopy. Highly uniform supercomplex particles in electron microscopy analysis support a distinct structural composition. The supercomplex possesses a dimeric stoichiometry with a ratio of a-type, b-type and c-type hemes close to 1:1:1. Redox titrations revealed a low potential bcc complex (Em(ISP)=+160mV, Em(bL)=-291mV, Em(bH)=-163mV, Em(cc)=+100mV) fined-tuned for oxidation of menaquinol and a mixed potential aa3 oxidase (Em(CuA)=+150mV, Em(a/a3)=+143/+317mV) mediating between low and high redox potential to accomplish dioxygen reduction. The generated molecular model supports a stable assembled supercomplex with defined architecture which permits energetically efficient coupling of menaquinol oxidation and dioxygen reduction in one supramolecular entity.


Circulating levels of active transforming growth factor beta1 are reduced in diffuse cutaneous systemic sclerosis and correlate inversely with the modified Rodnan skin score.
To determine the relationship between clinical features and circulating levels of active transforming growth factor (TGF) beta1 in the major subsets of systemic sclerosis (SSc). In a cross-sectional study cases of diffuse cutaneous SSc (dose) (n = 27) or limited cutaneous SSc (dose) (n = 20) were compared with healthy controls (n = 22). Active and total TGFbeta1 was measured in serum and plasma by a high-sensitivity enzyme-linked immunosorbent assay. There were no significant differences between levels of total serum TGFbeta1. However, cases of dcSSc had lower levels of active TGFbeta1 than cases of lcSSc or controls. In addition, more cases of dcSSc (18/27; 66%, P < 0.025) had no detectable active TGFbeta1 than controls (7/22, 32%) or lcSSc (7/20, 35%). In dcSSc, serum active TGFbeta1 levels correlated negatively with skin score and positively with disease duration. Contrary to expectation, levels of active TGFbeta1 are reduced in dcSSc and this correlates with two variables known to associate with disease activity, shorter duration and more extensive skin sclerosis. This suggests that active TGFbeta1 may be sequestered in active involved SSc skin and that serum levels are reduced despite strong evidence implicating TGFbeta isoforms in the pathogenesis of fibrosis. Our findings may have implications for systemic TGFbeta-trapping therapies in this disease.


Studies on the antinociceptive effects of sodium nitroprusside and molsidomine in mice.
The participation of nitric oxide (NO) in antinociceptive activity of molsidomine and sodium nitroprusside (SNP) was studied in mice using the writhing test. Molsidomine (300 and 150 mg/kg) and SNP (1.52-0.38 mg/kg) induced antinociception that was antagonized by naloxone. L-arginine (500-62.5 mg/kg) did not produce antinociceptive effects, whereas N omega-nitro-L-arginine methyl ester (L-NAME) (37.5-150 mg/kg) induced antinociception which was suppressed by naloxone. Methylene blue did not change the molsidomine- and SNP-induced antinociception, but significantly intensified that produced by L-NAME. L-arginine increased antinociceptive effect of molsidomine but not that of SNP. Antinociceptive activity of L-NAME was partially reversed by L-arginine. D-arginine failed to influence these effects. The present findings suggest that the NO-cGMP pathway is not involved in the mechanism of molsidomine- and SNP-induced antinociception in the writhing test in mice.


Innovative Microemulsion Loaded with Unusual Dimeric Flavonoids from Fridericia platyphylla (Cham.) L.G. Lohmann Roots.
Fridericia platyphylla (Cham.) L.G. Lohmann is a species native to the Brazilian cerrado, with promising bioactivity. The organic fraction of the roots is rich in unusual dimeric flavonoids, reported as potential candidates for cancer treatment. The exploration of these flavonoids is very important, considering their diverse biological activities and the need for innovative therapeutic options. This work aimed to develop and characterize a microemulsion loaded with a non-polar fraction (DCM). The constituents were chosen, and the pseudo-ternary diagram was constructed to determine the region of microemulsion formation. The microemulsions blank (ME), with 3% (ME3) and 5% (ME5) of fraction DCM, were characterized in terms of droplet size, zeta potential, and polydispersity index. Both MEs showed particle sizes <100 nm; only ME3 exhibited better values for polydispersity index and zeta potential and was therefore selected for further study. The organoleptic and physicochemical characteristics were evaluated, revealing limpidity and transparency typical of these microstructures, physiologically acceptable pH, refractive index of 1.42±0.01, and density of 1.017 g/cm3±0.01. The stability tests showed good stability profiles even after exposure to extreme thermal conditions, with minimal changes in pH and the content of the incorporated fraction. The in vitro release study demonstrated that ME3 enabled the controlled release of the fraction, with a cumulative amount released over 60% within 6 h. Furthermore, fraction DCM and ME3 exhibited no toxicity in Tenebrio molitor larvae. The developed microemulsion exhibited excellent properties, so this study represents the first successful attempt to develop a formulation that incorporates the dimeric flavonoid fraction.


Capacitation and induction of the acrosome reaction in bull spermatozoa with norepinephrine.
Identification of norepinephrine (NE) within the microenvironment of the bovine oviduct suggests a potential role for catecholamines in the events surrounding fertilization. Previous studies have shown that the catecholamines capacitate and induce the acrosome reaction in spermatozoa from several species. The current project was undertaken to investigate the role of catecholamines in bovine sperm capacitation and the acrosome reaction. Freshly ejaculated bovine spermatozoa were incubated in NE (0-1000 ng/mL) and induced to acrosome-react with lysophosphatidylcholine (LPC). Additionally, spermatozoa capacitated with heparin were incubated with NE (0-1000 ng/mL) to assess its ability to induce the acrosome-reaction in capacitated spermatozoa. Concentrations of NE were chosen on the basis of physiological concentrations previously determined for bovine oviductal fluid. NE at concentrations of 10 and 20 ng/mL capacitated bovine spermatozoa after 2 hours of incubation. Additionally, spermatozoa incubated for 2 hours with heparin were induced to acrosome-react with 10 and 20 ng/mL NE. Interestingly, higher concentrations of NE inhibited both capacitation and the acrosome reaction. Incubating spermatozoa with dopamine or epinephrine did not result in capacitation or the acrosome reaction, suggesting that the action of NE was specific to that catecholamine. The ability of NE to capacitate or induce the acrosome reaction appears to be dependent on the presence of another membrane-destabilizing factor. Although adrenergic receptors have not been identified on spermatozoa from any species, the action of NE on spermatozoa may be a receptor-mediated event. This study suggests a possible function for oviductal catecholamines in sperm preparation prior to fertilization.


Heat stress increases apical glucose transport in the chicken jejunum.
In chickens, elevated environmental temperature reduces food intake. We have previously reported that, during heat stress, the intestinal mucosa has an increased capacity to take up sugars. To investigate whether the effects of warm environment on sugar uptake are an intestinal adaptation to lower energy intake or a response attributable to heat stress, we examined the glucose transport kinetics of apical and basolateral membranes of the jejunum and the mucosal morphology of broiler chickens maintained in climatic chambers for 2 wk. Experimental groups were 1) control ad libitum (CAL), fed ad libitum and in thermoneutral conditions (20 degrees C); 2) heat stress ad libitum (HSAL), fed ad libitum and kept in a heated environment (30 degrees C); and 3) control pair-fed (CPF), maintained in thermoneutral conditions and fed the same amount of food as that consumed by the HSAL group. Both the CPF and the HSAL groups showed reduced body weight gain, but only the HSAL chickens had lower plasma thyroid hormones and higher corticosterone than CAL and CPF groups. The fresh weight and length of the jejunum were only reduced in the HSAL group. The activity and expression of apical sodium-dependent glucose transporter 1 (SGLT-1) were increased by approximately 50% in the HSAL chickens, without effects in the CPF group. No changes in K(d) or in SGLT-1 and glucose transporter-2 K(m) were observed in the pair-fed and heated birds. These results support the view that increased intestinal hexose transport capacity is entirely dependent on adaptations of apical SGLT-1 expression to heat stress and is not due to reduced food intake.


Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans.
A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30mg/70kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. These coordinated studies successfully established drug versus non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use.


Gas chromatography/mass spectrometry versus liquid chromatography/fluorescence detection in the analysis of phenols in mainstream cigarette smoke.
A new gas chromatographic/mass spectrometric (GC/MS) technique for the analysis of hydroxybenzenes (phenols) in mainstream cigarette smoke has been developed. The technique allows the measurement of 24 individual compounds, and the sum of a few other alkyl-dihydroxybenzenes. A critical evaluation is done for the new technique and for an established high-performance liquid chromatographic (HPLC) technique reported in the literature for the analysis of hydroxybenzenes in cigarette smoke, which uses fluorescence detection. Compared with the HPLC procedure, the new technique has similar accuracy, precision, and robustness. However, the GC/MS procedure allows for a larger number of phenols to be analyzed simultaneously, and eliminates any potential interference that may appear in the HPLC method. Using the GC/MS analysis, it was found that besides the main phenols typically measured in mainstream cigarette smoke such as phenol, catechol, hydroquinone, and cresols, many other phenols that are present at lower levels can be quantitated in mainstream cigarette smoke.


Association of CYBA gene (-930 A/G and 242 C/T) polymorphisms with oxidative stress in breast cancer: a case-control study.
Oxidative stress (OS) is a key characteristic feature in cancer initiation and progression. Among multiple cancers, NADPH oxidase (NOX) dependent free radical production is implicated in oxidative stress. P22phox, a subunit of NADPH oxidase encoded by the CYBA gene has functional polymorphisms associated with various complex diseases. The present study was aimed to examine the importance and association of the functional polymorphisms of CYBA gene (-930 A/G and 242 C/T) with the oxidative stress in breast cancer (BC) development and progression. We have performed a case-control study on 300 breast cancer patients and 300 healthy individuals as controls to examine the role of CYBA gene -930 A/G and 242 C/T single nucleotide polymorphisms (SNPs) using As-PCR and PCR-RFLP assays and its association with OS as measured by plasma MDA levels. Linkage disequilibrium (LD) plots were generated using Haploviewtool and Multifactor dimensionality reduction (MDR) analysis was applied to assess high-order interactions between the SNPs. The Insilco analysis has been performed to predict the effect of SNPs on the gene regulation using online tools. We have found that genotype frequencies of CYBA gene -930 A/G and 242C/T polymorphism were significantly different between controls and BC patients (p < 0.05). The haplotype combination -930G/242C and -930G/242T were associated with 1.44 & 1.56 folds increased risk for breast cancer respectively. Further, the MDA levels were higher in the patients carrying -930G/242C and -930G/242T haplotype (p < 0.001). Our results have been substantiated by Insilco analysis. Results of the present study suggest that GG genotype of -930 A/G polymorphism, -930G/242C and -930G/242T haplotypes of CYBA gene polymorphisms have shown association with higher MDA levels in breast cancer patients, signify that elevated oxidative stress might aid in increased risk for breast cancer initiation and progression.


Intralobar bronchopulmonary sequestration with large aberrant vessel presenting as recurrent pneumonias.
Bronchopulmonary sequestration is a rare congenital malformation of the lower respiratory tract comprising of a nonfunctioning lung tissue mass that lacks normal communication with the tracheobronchial tree. The diagnosis may be easily missed as many of the symptoms of bronchopulmonary sequestration overlap with that of other pulmonary diseases. Bronchopulmonary sequestration can be complicated by recurrent infections, hemorrhage and malignant transformation and, therefore, needs to be timely diagnosed and resected to decrease both morbidity and mortality. A high degree of suspicion in the differential diagnosis helps diagnose the positive cases. The parenchymal abnormalities associated with bronchopulmonary sequestration are best visualized using computed tomography, although their appearance is variable. We report the case of a 14 years old boy with intralobar bronchopulmonary sequestration with the sole manifestation of recurrent pneumonias.


Risk Factors Related to Eating Disorders in a Romanian Children Population.
(1) Background: The complex known as avoidant/restrictive food intake disorder (ARFID) is one of the eating disorders that cannot be explained by chronic disease. The aim of this study was to determine the characteristics of patients who were identified as being at risk of developing ARFID and referred to paediatricians, according to their age and duration of symptoms. (2) Methods: Children aged 2-10 years (Group 1) presenting with eating disorders were initially recruited in the "Dr. Victor Gomoiu" Clinical Children Hospital in Bucharest. Group 2 included patients presenting for routine paediatric visits as controls. The study population was given the PARDI questionnaire as well as questions related to demographics, screening growth and development, physical and mental background, and current feeding and eating patterns. Items were scored on a 7-point scale ranging from 0 to 6. (3) Results: A total of 98 individuals were divided equally into the two study groups. There was no difference in terms of sex, living area, mothers' education level or living standards between the two groups. ARFID children were more likely to be underweight, were unsuccessful at weaning or have irregular feeding habits and a history of allergies. The mean age of onset for chronic symptoms was significantly lower than the onset of acute food refusal-4.24 ± 2.29 vs. 6.25 ± 3.65, p = 0.005. (4) Conclusions: feeding disorders are an important issue among paediatricians, and a proper awareness of them when treating these patients should be included in daily practice.


Music, evolution and language.
Darwin (1871) noted that the human musical faculty 'must be ranked amongst the most mysterious with which he is endowed'. Indeed, previous research with human infants and young children has revealed that we are born with variable musical capabilities. Here, the adaptive purpose served by these differing capabilities is discussed with reference to comparative findings regarding the acoustic behavior of nonhuman primates. The findings provide evidence supporting Darwin's hypothesis of an intermediate stage of human evolutionary history characterized by a communication system that resembles music more closely than language and possibly acting as a precursor for both current language and music.


The influence of anterior nasal packings on middle ear pressure.
In 27 patients, representing 53 ears, middle ear pressure was measured before and after septoplasty/rhinoplasty. On the fourth postoperative day there was no demonstrable statistical difference (Mann-Whitney test). The various possible reasons for postoperative tube occlusion are discussed, mucosa oedema being considered the most important reason.


Variable selection for case-cohort studies with failure time outcome.
Case-cohort designs are widely used in large cohort studies to reduce the cost associated with covariate measurement. In many such studies the number of covariates is very large, so an efficient variable selection method is necessary. In this paper, we study the properties of a variable selection procedure using the smoothly clipped absolute deviation penalty in a case-cohort design with a diverging number of parameters. We establish the consistency and asymptotic normality of the maximum penalized pseudo-partial-likelihood estimator, and show that the proposed variable selection method is consistent and has an asymptotic oracle property. Simulation studies compare the finite-sample performance of the procedure with tuning parameter selection methods based on the Akaike information criterion and the Bayesian information criterion. We make recommendations for use of the proposed procedures in case-cohort studies, and apply them to the Busselton Health Study.


The frequent occurrence of neurological disease in patients with late-onset systemic lupus erythematosus.
Ten patients with systemic lupus erythematosus, whose first disease manifestation appeared after age 50 years, have been studied prospectively for up to five years. Neurological manifestations attributable to lupus occurred in nine patients and were multiple and varied. In all nine patients the neurological features appeared within one year of disease onset, and in four were present as an initial manifestation. Clinical recovery was generally satisfactory, and was complete in four. The apparent high incidence of neurological disease observed in late-onset lupus may help to elucidate causative mechanisms.


Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities.
Membrane type 1-matrix metalloproteinase (MT1-MMP/MMP-14) is a major collagenolytic enzyme that plays a vital role in development and morphogenesis. To elucidate further the structure-function relationship between the human MT1-MMP active site and the influence of the haemopexin domain on catalysis, substrate specificity and inhibition kinetics of the cdMT1-MMP (catalytic domain of MT1-MMP) and the ecto domain DeltaTM-MT1-MMP (transmembrane-domain-deleted MT1-MMP) were compared. For substrate 1 [Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH(2), where Mca stands for (7-methoxycoumarin-4-yl)acetyl- and Dpa for N -3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl], the activation energy E (a) was determined to be 11.2 and 12.2 kcal/mol (1 cal=4.184 J) for cdMT1-MMP and DeltaTM-MT1-MMP respectively, which is consistent with k (cat)/ K (M) values of 7.37 and 1.46x10(4) M(-1).s(-1). The k (cat)/ K (M) values for a series of similar single-stranded peptide substrates were determined and found to correlate with a slope of 0.17 for the two enzyme forms. A triple-helical peptide substrate was predicted to have a k (cat)/ K (M) of 0.87x10(4) M(-1).s(-1) for DeltaTM-MT1-MMP based on the value for cdMT1-MMP of 5.12x10(4) M(-1).s(-1); however, the actual value was determined to be 2.5-fold higher, i.e. 2.18x10(4) M(-1).s(-1). These results suggest that cdMT1-MMP is catalytically more efficient towards small peptide substrates than DeltaTM-MT1-MMP and the haemopexin domain of MT1-MMP facilitates the hydrolysis of triple-helical substrates. Diastereomeric inhibitor pairs were utilized to probe further binding similarities at the active site. Ratios of K (i) values for the inhibitor pairs were found to correlate between the enzyme forms with a slope of 1.03, suggesting that the haemopexin domain does not significantly modify the enzyme active-site structure.


Molecular basis, clinical consequences and diagnosis of alpha-1 antitrypsin deficiency.
(1) Deficiency of alpha AT is one of the most common hereditary diseases affecting Caucasians in Europe. The alpha 1AT protein is extremely pleomorphic, and around 90 variants due to mutations have been recognized. The prime functions of alpha 1AT is to inhibit neutrophil elastase, and a proportion of individuals who are deficient in alpha 1AT develop emphysema. The most common deficiency variant (Z) is also associated with liver disease. The main site of alpha 1AT synthesis is in the liver. Not all deficient individuals are affected by lung or liver disease, however, so that other factors (genetic and environmental) are clearly important. (2) Investigation of alpha 1AT status is essential in any child or adult presenting with chronic liver disease. The genetic cause cannot be identified clinically or by any other laboratory investigation. The diagnosis carries important prognostic consequences and is important for other family members. Patients with emphysema should have their Pi type determined, especially if they are under the age of 50, have never smoked or there is a suggestive family history. Asymptomatic individuals who are homozygous type Z should be referred to a chest physician for a clinical and radiological assessment together with lung function tests. (3) Several laboratory tests are available to detect alpha 1AT deficiency, and the choice of test(s) will depend on circumstances. Quantitation of the serum protein is simple and cheap. Because alpha 1AT is an acute phase protein, however, quantitation used in isolation may give false negative results which are clearly unacceptable, particularly in association with paediatric liver disease. Phenotyping by isoelectric focusing requires some experience in distinguishing SZ and ZZ phenotypes, and phenotyping should ideally be used in conjunction with quantitation because heterozygous null phenotypes may appear identical to homozygous normal phenotypes. (4) Prenatal diagnosis is usually performed by DNA analysis of CVS samples obtained at 11-13 weeks. Because of the risk that CVS samples might be contaminated by maternal tissue, assays which are less likely to detect minor contaminants are preferable. At present, use of DNA tests is confined to prenatal diagnosis, but the availability of simple tests and the possibility of unequivocal identification of S and Z alleles means that these tests are likely to find greater use in the near future.


Presentation of a benign fibroepithelial polyp with frank haematuria: an unusual diagnosis.
Fibroepithelial polyps are rare benign lesions which can mimic malignant disease symptomatically and radiologically. They should form part of the differential diagnosis in patients presenting with frank haematuria but they can present a diagnostic dilemma for clinicians. This is a case of a 30-year-old female who initially presented with a small palpable urethral lump, thought to be a urethral caruncle by her general practitioner, obstructive voiding and intermittent frank painless haematuria. A rigid cystoscopy identified a polypoid lesion protruding out of the left ureteric orifice. This was resected and pathology showed it to be a fibroepithelial polyp. A post-operative computerized tomography scan showed no hydronephrosis on either side and no lymphadenopathy was identified but the distal left ureter could not be visualised. Further resection with a flexible ureteroscopy confirmed the presence of a benign fibroepithelial polyp and the stalk remnant was ablated with a laser. Fibroepithelial polyps mimic malignant disease symptomatically and radiologically and need to be considered in the differential diagnosis of frank haematuria.


Cellular Midpalatal Suture Changes after Rapid Maxillary Expansion in Growing Subjects: A Case Report.
The present case report aimed to investigate immediate histologic changes in midpalatal suture in humans following rapid maxillary expansion compared to control. Three patients (mean age 8.3 +/- 0.9 years) were enrolled in the case report and underwent midpalatal suture biopsy. Two patients underwent treatment before biopsy. The third patient did not show transversal maxillary deficiency and was enrolled as a control. Biopsy samples of midpalatal suture at 7 (subject 1) and 30 days (subject 2) after maxillary expansion as well as of one control (subject 3) were collected and processed for histology. In the control (subject 3) inter-digitations at the palatal suture gap were observed. At 7 days (subject 1) mature bone with small marrow spaces and trabecular bone with the peculiar storiform appearance inside the soft tissue and collagen fibers running parallel only in the central part were present. At 30 days (subject 2), a greater number of newly-formed bone trabeculae with a perpendicular orientation to the long axis of the suture could be seen. At 30 days the fibrous component of bone tissue was less represented compared to the sample at 7 days. Data from the preliminary histological results showed that bone formation was observed in the gap after rapid maxillary expansion, although the healing process was still ongoing.


Association among cognitive function, physical fitness, and health status in older women.
This study examined the association among cognitive function, physical fitness, and health status in healthy older women. Ninety-four females aged from 62 to 86 years (72.66±5.38 years) from community healthcare centers and an exercise club in Seoul, South Korea. Cognitive function was assessed using the Seoul Neuropsychological Screening Battery. Physical performance comprised cardiorespiratory endurance, lower extremity strength, active balance ability, and walking speed. Health status included blood pressure and waist circumference. Multiple linear regression analyses were performed to determine the relationship among cognitive function, fitness components, and health status, with age and educational attainment as covariates. In the unadjusted model, attention was significantly associated with cardiovascular endurance (B=0.19, P<0.05). Memory was significantly associated with lower limb strength (B=0.77, P<0.05) and active balance ability (B=2.35, P<0.05). In the adjusted model, attention was significantly associated with cardiovascular endurance (B=0.15, P<0.05). Memory was significantly associated with lower limb strength (B=0.87, P<0.05). In both models, cognitive function was not significantly associated with any health status variable. Though limited by a relatively small sample of female participants, who were healthy registrants of a community exercise program with normal cognitive function, the current study demonstrates that cognitive function is significantly associated with physical fitness, but not with health status, in healthy older women.


Analysis of volatile and semivolatile hydrocarbons recovered from steam-classified municipal solid waste.
Hazardous household wastes comprise a significant proportion of municipal solid waste (MSW), and therefore serve as the source of many toxic or carcinogenic organic chemicals that are released in the environment through landfill gases or leachates. In the present study, we demonstrate the utility of the steam classification process in removing hazardous semivolatile organic compounds (SVOCs) and volatile organic compounds (VOCs) from MSW. Steam classification is a patented technology that involves the treatment of MSW with steam under pressure to yield a cellulosic biomass product that can be used as a fuel or in building materials. The SVOCs and VOCs from the waste off-gases are collected in the steam condensate and in an effluent charcoal filter. The results of this study show that at least two SVOCs and at least 17 VOCs can be removed from the waste. The most commonly identified compounds were diethylphthalate, styrene, 1,4-dichlorobenzene, and toluene in the condensates, and styrene, 1,1,1-trichloroethane, and toluene in the charcoal filters. On a weight basis, aromatic hydrocarbons were primarily recovered in the condensates, while the chloroaliphatic hydrocarbons were recovered almost exclusively from the charcoal filters. 1,3-Dichlorobenzene, 1,4-dichlorobenzene, and chloroform together comprised nearly 50% of the 4470 micrograms kg(-1) average mass of SVOCs and VOCs recovered from about 454 kg of MSW in these experiments. Toxicity characteristic leaching procedure (TCLP) analyses showed that steam classification recovered at least 75 to 91% of tested analytes. Overall, these results suggest that steam classification represents an effective technology for a significant reduction or the removal of hazardous organics from the waste stream, and, consequently, in reducing the extent of environmental contamination associated with landfill leachates and gases.


Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice.
Ospemifene is a new selective estrogen receptor modulator (SERM) that is being developed for the treatment of urogenital atrophy and osteoporosis. Similarly to other SERMs, ospemifene exhibits antiestrogenic effects in breast tissue, which led to the hypothesis that it may be a potential breast cancer chemopreventive agent. We first assessed the ability of ospemifene, compared to tamoxifen and raloxifene, to prevent dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sencar mice. Ospemifene (N = 18), tamoxifen (N = 20) and raloxifene (N = 17), each dosed at 50 mg/kg, were administered daily by oral gavage, in combination with 20 microg DMBA for the first 6 weeks. Control mice (N = 21) received vehicle plus DMBA only for the first 6 weeks. Daily treatment then continued for 37 weeks. As hypothesized, ospemifene greatly reduced the incidence of mammary carcinomas compared to control mice (p = 0.003), similar to tamoxifen (p = 0.0004); however, in the raloxifene group, no significant effect was seen in mammary tumor prevention (p = 0.20). A follow-up study comparing ospemifene (N = 20) to tamoxifen (N = 20) in the same model was then performed to confirm the results of the first study. The results of the follow-up study, which extended the treatment to 52 weeks, confirmed the results of our previous study, with ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly decreasing mammary carcinomas compared to controls. The results of these two studies suggest that women taking ospemifene for osteoporosis and/or urogenital atrophy may further benefit from ospemifene's breast cancer chemopreventive effects.


GolP: an atomistic force-field to describe the interaction of proteins with Au(111) surfaces in water.
A classical atomistic force field to describe the interaction of proteins with gold (111) surfaces in explicit water has been devised. The force field is specifically designed to be easily usable in most common bio-oriented molecular dynamics codes, such as GROMACS and NAMD. Its parametrization is based on quantum mechanical (density functional theory [DFT] and second order Möller-Plesset perturbation theory [MP2]) calculations and experimental data on the adsorption of small molecules on gold. In particular, a systematic DFT survey of the interaction between Au(111) and the natural amino acid side chains has been performed to single out chemisorption effects. Van der Waals parameters have been instead fitted to experimental desorption energy data of linear alkanes and were also studied via MP2 calculations. Finally, gold polarization (image charge effects) is taken into account by a recently proposed procedure (Iori, F.; Corni, S. J Comp Chem 2008, 29, 1656). Preliminary validation results of GolP on an independent test set of small molecules show the good performances of the force field.


Importance of the day 7 bone marrow biopsy as a prognostic measure of the outcome in children with acute lymphoblastic leukemia.
The presence of > or = 25% blasts in a marrow aspirate obtained on day 7 of induction followed by a remission at day 28 has been associated with a poor prognosis in children with acute lymphoblastic leukemia (ALL). We evaluated whether a day 7 marrow biopsy may be used to more accurately assess therapeutic reduction of leukemia tumor burden. Studied were 76 children with ALL enrolled on CCG protocols at B.C's Children's Hospital who received both a day 7 aspirate and biopsy and were in remission by day 28. Evaluation for the correlation of the percentage aspirate blasts on day 7 with the biopsy demonstrated a moderate correlation with the percentage biopsy blasts (R = 61), but not correlation with the biopsy cellularity. We saw a similar prediction of outcome by the percentage blasts on day 7 marrow aspirate in the study as reported previously although it was not significant. Outcome analysis was done using leukemia burden as measured by the day 7 absolute blast index-aspirate (ABI-aspirate) calculated as the product of the biopsy cellularity with the percentage blasts on the aspirate. The ABI-aspirate significantly predicted patient outcome with 83% survival in those with an ABI-aspirate of < .06 compared to 51% in those > or = .06 (P = .01) and was highly significant when analyzed as a continuous predictor (P = .004). This is the first study to demonstrate that information gained from the day 7 marrow biopsy can improve prediction of outcome in children with ALL. Based on this preliminary study, we recommend that large population ALL therapy trials evaluate the role of the day 7 marrow biopsy for outcome prediction in children with ALL.


Nanocomposite liposomes containing quantum dots and anticancer drugs for bioimaging and therapeutic delivery: a comparison of cationic, PEGylated and deformable liposomes.
Multifunctional liposomes loaded with quantum dots (QDs) and anticancer drugs were prepared for simultaneous bioimaging and drug delivery. Different formulations, including cationic, PEGylated and deformable liposomes, were compared for their theranostic efficiency. We had evaluated the physicochemical characteristics of these liposomes. The developed liposomes were examined using experimental platforms of cytotoxicity, cell migration, cellular uptake, in vivo melanoma imaging and drug accumulation in tumors. The average size of various nanocomposite liposomes was found to be 92–134 nm. Transmission electron microscopy confirmed the presence of QDs within liposomal bilayers. The incorporation of polyethylene glycol (PEG) and Span 20 into the liposomes greatly increased the fluidity of the bilayers. The liposomes provided sustained release of camptothecin and irinotecan. The cytotoxicity and cell migration assay demonstrated superior activity of cationic liposomes compared with other carriers. Cationic liposomes also showed a significant fluorescence signal in melanoma cells after internalization. The liposomes were intratumorally administered to a melanoma-bearing mouse. Cationic liposomes showed the brightest fluorescence in tumors, followed by classical liposomes. This signal could last for up to 24 h for cationic nanosystems. Intratumoral accumulation of camptothecin from free control was 35 nmol g(−1); it could be increased to 50 nmol g(−1) after loading with cationic liposomes. However, encapsulation of irinotecan into liposomes did not further increase intratumoral drug accumulation. Cationic liposomes were preferable to other liposomes as nanocarriers in both bioimaging and therapeutic approaches.


[Study of scan parameters using three-dimensional cine phase contrast imaging for pulmonary artery velocity measurement].
Pulmonary artery flow velocity, flow volume and their derived biomarkers, such as acceleration time (AT), acceleration volume (AV) and peak velocity (PV), vary depending on the severity and type of pulmonary disease. Therefore, accurate measurements of pulmonary artery velocity are very important for assessing the severity of pulmonary disease. The purpose of this study was to optimize the imaging parameters for pulmonary artery flow velocity using 3D cine PC MR, and to evaluate AT, AV, and PV for pulmonary hypertension. We changed the flip angle (FA) and view per segment (VPS). FA influenced the signal intensity, which was calculated from the magnitude images. Smaller VPS improved the accuracy of PV. Consequently, optimal setting of FA and VPS was important for hemodynamic analysis. We established the optimal FA and VPS for use in the hemodynamic analysis. AV and PV at the right pulmonary artery differed significantly between healthy volunteers and patients with pulmonary hypertension. Hemodynamic analysis of 3D cine PC MR imaging was considered promising for the evaluation of pulmonary disease.


[A case of splenic pseudocyst difficult to differentiate from splenic lymphangioma].
Splenic pseudocyst is a rare complication of abdominal trauma. Although it is rare, splenic pseudocyst is well-documented in the literature. According to the current classification, approximately 30% of all splenic cysts or pseudocysts result from direct abdominal trauma. In addition, chronic pancreatitis leads to change of nearby organs with possible acute and chronic complications including splenic lesions. This unusual complication can occur in both emergent and non-emergent conditions. The useful diagnostic procedures to assess intrasplenic pseudocyst are sonogram, CT scan, splenic scan, and occasionally angiography. However, definite diagnosis of pseudocyst is possible only after splenectomy when the absence of epithelial lining is confirmed histologically. Splenic pseudocyst requires surgical resection. We experienced a 31-year-old man who confirmed of warmness in the left side of back with left upper quadrant abdominal pain for several months. First impression was splenic lymphangioma based on CT scan and sonogram finding. Splenectomy was performed. Microscopic examination revealed splenic pseudocyst with fibrous capsule without epithelial lining.


A novel endothelin receptor type-B-like gene enriched in the brain.
We report here our effort of cloning and characterization of a novel human gene, which encodes a putative human endothelin receptor type B like protein (hET(B)R-LP), from a human hippocampus tissue cDNA library. hET(B)R-LP consists of 614 amino acids with seven putative transmembrane domains. The deduced amino acid sequence of hET(B)R-LP is 52% similar and 26.7% identical to human endothelin type B receptor. A 4.0 kb mRNA of hET(B)R-LP is abundantly expressed in the human brain. The results of in situ hybridization and reverse transcriptase in situ gene amplification reveal tissue distribution and cellular localization of signals of hET(B)R-LP mRNA in the neuronal cells, particularly concentrated in Purkinje cells of the cerebellum, and neuronal cells of the hippocampus of human brain, including pyramidal cells of Ammon's horn and granule cells of the dentate gyrus. A 4.0 kb mRNA of hET(B)R-LP is also less abundantly expressed in the liver and the placenta. Expression of recombinant protein, hET(B)R-LP/HA, in cells of COS7 and HEK293 transfected with plasmid DNA, hET(B)R-LP/HA/pcDNA1/Amp, was confirmed by Northern blot analysis and by immunofluorescence staining of cells with anti-HA antibody. Specific binding of radiolabeled ET-1 and ET-3 to membrane preparations and to intact cells expressing recombinant protein of hET(B)R-LP/HA did not show any significant difference of binding properties between cells transfected with plasmid DNA, hET(B)R-LP/HA/pcDNA1/Amp, and cells untransfected, including both COS7 cells and HEK293 cells. The results of assays of measuring Ca++ mobilization and cAMP production in HEK293 cells indicate that ET-1, ET-3, bombesin and neuropeptide Y are unable to produce any kind of significant difference of Ca++ mobilization and cAMP production between HEK293 cells expressing recombinant protein and HEK293 cells untransfected or HEK293 cells transfected with vector DNA only (pcDNA1/Amp) in functional assays performed. Therefore, its ligand and physiological significance of hET(B)R-LP remains to be discovered.


Factors related to muscle strength in postmenopausal women aged younger than 65 years with normal vitamin D status.
Objective: The study aimed to determine the impact of age, age at menopause, body mass index (BMI), and lumbar and hip bone mineral density (BMD) on muscle strength in young postmenopausal women with normal vitamin D levels. Methods: This was a cross-sectional study performed in 392 postmenopausal women aged <65 years with normal serum 25-hydroxyvitamin D levels (≥30 ng/ml) and no physical disabilities. The following variables were recorded: age, age at menopause, BMI, BMD (measured by dual-energy X-ray absorptiometry [DXA] scanning and expressed as lumbar and hip T-scores), and dominant hand grip strength (measured with a digital dynamometer). Results are reported as mean ± standard deviation or odds ratio (OR) and 95% confidence interval (CI) as appropriate. Results: The mean age of the whole sample was 57.30 ± 3.69 years with a mean age at menopause of 50.46 ± 2.16 years and a mean BMI of 24.93 ± 3.78. Mean DXA results were lumbar T-score of -1.16 ± 1.18 and hip T-score of -0.98 ± 0.93. The mean dominant hand grip force was 24.10 kg. A total of 12.2% (48/392) of women were diagnosed with dynapenia using a cut-off value of <20 kg. A weak but significant inverse correlation was found between grip strength in the dominant hand and age (r = -0.131, p = 0.009). Multivariable logistic regression analysis determined that earlier age at menopause (50 years or younger) was significantly associated with a higher risk of dynapenia (OR 2.741, 95% CI 1.23-6.11, p = 0.014). No other significant association was found with the other variables. Conclusions: A total of 12.2% of the studied young postmenopausal women with normal vitamin D status had dynapenia. There was a weak inverse correlation between grip strength and age, and earlier age at menopause was associated with an increased dynapenia risk.


Perspective: Teaching Kitchens: Conceptual Origins, Applications and Potential for Impact within Food Is Medicine Research.
There is a need to identify innovative strategies whereby individuals, families, and communities can learn to access and prepare affordable and nutritious foods, in combination with evidence-based guidance about diet and lifestyle. These approaches also need to address issues of equity and sustainability. Teaching Kitchens (TKs) are being created as educational classrooms and translational research laboratories to advance such strategies. Moreover, TKs can be used as revenue-generating research sites in universities and hospitals performing sponsored research, and, potentially, as instruments of cost containment when placed in accountable care settings and self-insured companies. Thus, TKs can be considered for inclusion in future health professional training programs, and the recently published Biden-Harris Administration Strategy on Hunger, Nutrition and Health echoes this directive. Recent innovations in the ability to provide TK classes virtually suggest that their impact may be greater than originally envisioned. Although the impact of TK curricula on behaviors, outcomes and costs of health care is preliminary, it warrants the continued attention of medical and public health thought leaders involved with Food Is Medicine initiatives.


Rapid patterning of Dictyostelium discoideum cells under confined geometry and its relation to differentiation.
The following was recently reported by Bonner et al. (1995): (1) Rapid differentiation occurred into two zones in Dictyostelium discoideum cells confined in a fine glass capillary. The cells in the anterior zone exposed to the air appear similar to prestalk cells, while the posterior zone isolated from the air mimics prespore cells. (2) The volumes of the two zones are proportional to each other for different sized cell masses, and the proportion is the same as that in normal migrating slugs. We investigated the nature of this newly discovered rapid differentiation in a slightly modified geometry. Exponentially growing cells were harvested, washed to remove external nutrients, and pelleted by centrifugation. Subsequently, a small drop of the pelleted (starved) cells was placed on a slide glass and then confined in a two-dimensional space between the slide glass and a coverslip, with help of spacers whose thickness varied from 25 to 100 microm. As a result, a dark zone, which looked optically different, emerged within several minutes in the periphery of the disc of the confined cells, corresponding to the zonation in a capillary as previously reported. When the width of the peripheral zone was measured for more than 30 samples of different diameters for each thickness of the spacers, the width was found to be always about 100 microm, irrespective of the size difference of the cell mass placed. This seems to be contradictory to the previous observation made by Bonner et al. (1995). We also examined oxygen concentration dependence on the zone width. The zone width was found to be independent of the oxygen concentration at low concentrations, but increased rapidly at high concentrations. A reaction-diffusion mechanism for formation of the zone and possible involvement of atmospheric oxygen (O2) in the initial steps of cell differentiation and pattern formation is discussed.


Interactions between 5-Lipoxygenase Polymorphisms and Adipose Tissue Contents of Arachidonic and Eicosapentaenoic Acids Do Not Affect Risk of Myocardial Infarction in Middle-Aged Men and Women in a Danish Case-Cohort Study.
Background: The 5-lipoxygenase pathway has been linked to atherothrombotic disease, and a functional tandem repeat polymorphism in the arachidonate lipoxygenase-5 (ALOX-5) gene has been associated with the risk of myocardial infarction (MI). Interestingly, 2 studies have reported an interaction between dietary intakes of the ALOX-5 substrates, arachidonic acid (AA) and eicosapentaenoic acid (EPA), and genotype.Objective: We investigated whether the interactions between the ALOX-5 tandem repeat polymorphism (rs59439148) and adipose tissue AA and EPA were associated with incident MI.Methods: In the Danish Diet, Cancer and Health study, we conducted a case-cohort study including 3089 participants with incident MI identified from national registries and a randomly selected subcohort of 3000 participants. Participants were men and women with a median age of 56 y at baseline and no previous history of cancer. Adipose tissue and blood samples were collected at baseline along with comprehensive questionnaires on lifestyle and demographic data. The ALOX-5 tandem repeat polymorphism was genotyped by multititer plate sequencing. Associations were analyzed by using Cox proportional hazards models.Results: We observed a higher risk of MI for homozygous carriers of the variant alleles in the fifth quintile of AA content than for the reference group with the lowest quintile of AA and carrying the wild-type allele (HR: 3.02; 95% CI: 1.41, 6.44). In contrast, homozygotes for the variant alleles tended to have a higher risk of MI when comparing the lowest quintile of EPA content with the reference group with the highest quintile of EPA and carrying the wild-type allele (HR: 2.15; 95% CI: 0.91, 5.09; P = 0.08). Although our results suggested interactions between the polymorphism and adipose tissue AA and EPA, a quantitative evaluation of interaction by calculating the relative excess risk due to interactions was not significant.Conclusions: Adipose tissue EPA and AA and the ALOX-5 tandem repeat polymorphism did not significantly interact to affect the risk of MI. However, the results should be replicated in larger, heterogeneous populations.


Affect and outcome in short-term group therapy for loss.
Affect and work variables were monitored for 12 of 16 groups involved in a controlled outcome study of psychoanalytically oriented short-term group therapy. Groups were conducted by experienced therapists for outpatients who experienced difficulties adapting to personal losses through death, separation, or both. Postsessional ratings of positive and negative affect were provided by individual patients, therapists, and other patients. Psychodynamic work was rated independently using a content analysis system. Patients who had experienced separation were more inhibited in their affective expression. Rating sources agreed that positive affect increased over time. Direct relationships were found between positive affect and favorable outcome. Concerning negative affect, the strongest predictors of favorable outcome involved the interaction of affect and work. Implications of these findings are discussed in terms of the cathartic hypothesis.


Selectivity enhancement of an Escherichia coli bacterial electrode using enzyme and transport inhibitors.
The feasibility of using specific enzyme and transport inhibitors to minimize the glutamine response of a potentiometric microbial sensor is demonstrated. The glutamine response of a bacterial electrode prepared with Escherichia coli as the biocatalyst in conjunction with an ammonia gas-sensing electrode was greatly reduced by treating the electrode with the enzyme inhibitor 6-diazo-5-oxo-L-norleucine (DONL) and the transport inhibitor gamma-L-glutamylhydrazide. Each inhibitor effectively decreased glutamine response to a level sufficiently low to be considered negligible in clinical studies. Although the sensor ultimately recovered from the effects of a single exposure to an inhibitor, continuous exposure at an optimum concentration maintained a low response to glutamine. Furthermore, the treatment of the sensor with both inhibitors simultaneously resulted in a negligible response to glutamine of <1 mV, indicating that both inhibitors are necessary for optimum inhibition of glutamine response. This approach is promising as a means of enhancing the selectivity of microbial sensors.


[Separating independent components in heart period signal].
To extract sub-signal of heart period signal (HPS), a new statistical signal processing approach, namely independent component analysis (ICA) was addressed. Electrocardiosignal (ECS) was acquired from ten volunteers. ECS was sampled 8 minutes when the volunteer was in supine position, and then when the same volunteer was in erect position. HPS was extracted from ECS. According to time-delay, HPS was divided into five groups as mixed signals. Five signals were reconstructed into two groups by ICA. The rebuilt signals were transformed by Fourier transformation. One centralized in low frequency (called IC1); the other did in high frequency (called IC2). The power of IC1 was significantly increased (P<0.01) while that of IC2 showed no significant change (P>0.05), and the ratio of IC1 to total power also significantly increased with the change from supine position to erect position. Comparsion between the two postural results reveals that IC1 may express sympathetic activity, and IC2 represents parasympathetic activity. Sympathetic and parasympathetic nervous functions can be evaluated respectively and quantitatively by use of data and graphs from the two decomposed components.


Human alpha-L-iduronidase. II. Comparative biochemical and immunologic properties of the purified low and high uptake forms.
The physicokinetic and immunologic properties of the purified low and high uptake forms of the human lysosomal hydrolase, alpha-L-iduronidase, have been determined and compared. The apparent Km and Vmax values for the low and high uptake forms were similar toward two artificial substrates, 4-methylumbelliferyl-alpha-L-iduronide (0.07 and 0.06 mmol/l; 16.15 and 14.85 mumol/min/mg, respectively), and phenyl-alpha-L-iduronide (1.42 and 1.66 mmol/l; 0.83 and 1.05 mumol/min/mg, respectively), and one natural substrate, anhydro-[3H]-mannitol-iduronide (0.86 and 1.04 mmol/l; 2.50 and 2.79 mumol/min/mg, respectively). The pH optima for both purified forms also were similar for each of the three substrates ( approximately 3.50, approximately 3.50, and approximately 4.50, respectively). Heparin markedly inhibited the 4-methylumbelliferyl-alpha-L-iduronide activities of both the low and high uptake forms, while dermatan sulfate and heparan sulfate were more inhibitory toward the low uptake activity. EDTA was a potent inhibitor of both enzyme forms; the divalent cations, Mg2+ and Ca2+, could recover up to 30% of the enzymatic activities after EDTA treatment. p-Chloromercuribenzoate and maleate also were inhibitory, whereas dithiothreitol and 2-mercaptoethanol were stimulatory. Both enzyme forms had similar thermostabilities ; the half-lives at 45, 52, and 60 degrees C were about 38, 24 and 12 min, respectively. The low and high uptake forms were immunologically cross-reactive as demonstrated by Ouchterlony double immunodiffusion and immunotitration studies using anti-human low uptake antibodies.


Femtosecond nanocrystallography using X-ray lasers for membrane protein structure determination.
The invention of free electron X-ray lasers has opened a new era for membrane protein structure determination with the recent first proof-of-principle of the new concept of femtosecond nanocrystallography. Structure determination is based on thousands of diffraction snapshots that are collected on a fully hydrated stream of nanocrystals. This review provides a summary of the method and describes how femtosecond X-ray crystallography overcomes the radiation-damage problem in X-ray crystallography, avoids the need for growth and freezing of large single crystals while offering a new method for direct digital phase determination by making use of the fully coherent nature of the X-ray beam. We briefly review the possibilities for time-resolved crystallography, and the potential for making 'molecular movies' of membrane proteins at work.


Preoperative cardiovascular risk factor control in elective coronary artery bypass graft patients: a failure of present management.
After coronary artery bypass graft (CABG) patients are at high risk for disease progression and future cardiac events. Risk factor control can reduce subsequent clinical events and mortality. The appropriateness of cardiovascular risk factor management in CABG patients is largely unknown. To evaluate the presence of cardiovascular risk factors, their treatment and the adequacy of that treatment in patients just before elective CABG PATIENTS AND METHODS: Over a six-month period in 1999, 120 patients who underwent elective CABG at a single centre were assessed. All patients were assessed for the presence of important, known, modifiable cardiovascular risk factors (smoking, hypertension, hypercholesterolemia, obesity and diabetes), and the adequacy of the control of these risk factors, as determined by published consensus conference guidelines. Ninety-five per cent of patients were receiving treatment for their risk factors. Twenty of 86 patients had their hyperlipidemia controlled, only 10 of 36 patients with diabetes had their glucose well controlled, 56 of 82 patients had adequate control of their hypertension, 21 of 120 patients were current smokers, 78 of 120 patients were obese and only 13 of 120 patients had all risk factors under control. As expected, the prevalence of all the risk factors was very high. Despite a high level of medical treatment, risk factor management was very poor. More effort needs to go into active, long term management, and patient education and motivation, if any substantial progress is to be made in reducing future cardiac events in patients after CABG.


Robustness, flexibility, and the role of lateral inhibition in the neurogenic network.
Many gene networks used by developing organisms have been conserved over long periods of evolutionary time. Why is that? We showed previously that a model of the segment polarity network in Drosophila is robust to parameter variation and is likely to act as a semiautonomous patterning module. Is this true of other networks as well? We present a model of the core neurogenic network in Drosophila. Our model exhibits at least three related pattern-resolving behaviors that the real neurogenic network accomplishes during embryogenesis in Drosophila. Furthermore, we find that it exhibits these behaviors across a wide range of parameter values, with most of its parameters able to vary more than an order of magnitude while it still successfully forms our test patterns. With a single set of parameters, different initial conditions (prepatterns) can select between different behaviors in the network's repertoire. We introduce two new measures for quantifying network robustness that mimic recombination and allelic divergence and use these to reveal the shape of the domain in the parameter space in which the model functions. We show that lateral inhibition yields robustness to changes in prepatterns and suggest a reconciliation of two divergent sets of experimental results. Finally, we show that, for this model, robustness confers functional flexibility. The neurogenic network is robust to changes in parameter values, which gives it the flexibility to make new patterns. Our model also offers a possible resolution of a debate on the role of lateral inhibition in cell fate specification.


Sinus tachycardia is associated with impaired exercise tolerance following heart transplantation.
Sinus tachycardia often presents in heart transplantation (HTx) recipients, but data on its effect on exercise performance are limited. Based on mean heart rate (HR) value 3 months after HTx, 181 patients transplanted from 2006 to 2015 at University of Nebraska Medical Center were divided into two groups: (i) HR<95 beats/min (bpm, n=93); and (ii) HR≥95 bpm (n=88). Cardiopulmonary exercise testing (CPET) was performed 1 year after HTx. Mean HR at 3 months post-HTx was 94±11 bpm and did not change significantly at 1 year post-HTx (96±11 bpm, P=.13). HR≥95 bpm at 3 months was associated with younger donor age (OR 1.1; CI 1.0-1.1, P=.02), female donors (OR -2.4; CI 1.16-5.24 P=.02), and lack of donors' heavy alcohol use (OR -0.43; CI 0.17-0.61; P=.04). HR≥95 bpm at 3 months post-HTx was independently associated with decreased exercise capacity in metabolic equivalent (P=.008), reduced peak VO2 (P=.006), and percent of predicted peak VO2 (P=.002) during CPET. HR≥95 at 3 months following HTx is associated with reduced exercise tolerance in stable HTx recipients. Medical HR reduction after HTx could improve exercise performance after HTx and merits further investigation.


The end of the Strecknitz asylum at Lübeck - a contribution to the social history of psychiatry during National Socialism.
At a first place the NS-policy of psychiatry is outlined -its global planning as well as its excecution. The picture is supplemented by and contrasted with its local implementation exemplified by the Strecknitz asylum at Lübeck. It becomes clear how much the global concept of the extermination of patients was interwoven with pragmatic plans of local authorities. At Lübeck only the partial identity of these interests led to the deportation of more than 600 patients. They were distributed to several transit camps in Hesse where more than 80% had died by the end of the Second World War. The main causes of death were hunger and infectious diseases - consequences of a deliberate and well-organized neglect. The behaviour and the reactions on the part of the relatives were shaped by supply shortages during the war, by internalized propaganda and by fear. The long-term effects beyond the end of the NS-regime vary a lot. Some of the relatives' coping strategies are portrayed. In some cases the murder of close family members continues to have its effects in the form of family secrets.


Flammability of disposable surgical drapes.
We discuss the high degree of flammability of disposable surgical drapes. The results of two separate tests and corresponding photographs are presented to verify the flammability. We stress the importance of the flame spread rate.


Increased base rate of atrial pacing for prevention of atrial fibrillation after implantation of a dual-chamber pacemaker: insights from the Atrial Overdrive Pacing Study.
Different pacing sites and various algorithms have been utilized to prevent atrial fibrillation (AF) in pacemaker recipients. However, the optimal pacing rate settings have not yet been established. In this randomized, prospective, multicentre, single-blinded, cross over study, rate-adaptive pacing at a high base rate (BR) in patients, age 60 years or above, or a history of paroxysmal AF, who underwent dual-chamber (DDD) pacemaker implantation for standard pacing indications, was evaluated for prevention of AF. In the study cohort of 145 patients implanted with DDD pacemakers with a programmable rest rate (RR) feature, the BR/RR settings were sequentially but randomly adjusted as follows: 60 bpm/Off for the baseline quarter (initial 3 months) and then to either 'A-B-C' or 'C-B-A' settings (A = 70/65 bpm, B = 70/Off, C = 80/65 bpm) for the subsequent quarters each of 3 months duration. Data on automatic mode switch episodes, device diagnostics, and a questionnaire evaluating pacemaker awareness and palpitations were collected. Ninety-nine patients, mean age 77 +/- 10 years, who completed the study protocol and followed for 12 months did not show significant differences in the number of mode switch episodes between any settings used. The percentage of atrial pacing was lower during baseline pacing compared to settings A, B, and C (P < 0.0001). Setting C produced a higher percentage of atrial pacing than A and B (P < 0.01). Although a higher percentage of atrial pacing correlated with a lower incidence of mode switch episodes, there was no statistically significant difference in the number of mode switch episodes between settings A, B, and C. There were no significant differences in the questionnaire scores relating to pacemaker awareness or palpitation. Overdrive single-site pacing in the right atrium achieved by programming analysed settings in the present study did not reduce AF as assessed by mode switch episodes. Additionally, no change in the symptoms of arrhythmia or awareness of pacing was seen.


Protective role of cortistatin in pulmonary inflammation and fibrosis.
Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary fibrosis remain major causes of morbidity, mortality and a healthcare burden in critically ill patient. There is an urgent need to identify factors causing susceptibility and for the design of new therapeutic agents. Here, we evaluate the effectiveness of the immunomodulatory neuropeptide cortistatin to regulate pulmonary inflammation and fibrosis in vivo. ALI/ARDS and pulmonary fibrosis were induced experimentally in wild-type and cortistatin-deficient mice by pulmonary infusion of the bacterial endotoxin LPS or the chemotherapeutic drug bleomycin, and the histopathological signs, pulmonary leukocyte infiltration and cytokines, and fibrotic markers were evaluated. Partially deficient mice in cortistatin showed exacerbated pulmonary damage, pulmonary inflammation, alveolar oedema and fibrosis, and subsequent increased respiratory failure and mortality when challenged to LPS or bleomycin, even at low doses. Treatment with cortistatin reversed these aggravated phenotypes and protected from progression to severe ARDS and fibrosis, after high exposure to both injury agents. Moreover, cortistatin-deficient pulmonary macrophages and fibroblasts showed exaggerated ex vivo inflammatory and fibrotic responses, and treatment with cortistatin impaired their activation. Finally, the protective effects of cortistatin in ALI and pulmonary fibrosis were partially inhibited by specific antagonists for somatostatin and ghrelin receptors. We identified cortistatin as an endogenous inhibitor of pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of poor prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin-based therapies could emerge as attractive candidates to treat severe ALI/ARDS, including SARS-CoV-2-associated ARDS.


[Resection and reconstruction of the carina].
A case of recurrent adenoid cystic carcinoma after right middle lobectomy is reported. A right lower lobectomy with resection of carina was performed as the lesion involved the right main bronchus, the carina and the orifice of right lower lobe. The carina was reconstructed by the anastomosis of right upper lobe bronchus to the left main bronchus. The postoperative course was uneventful. After two months, the stitch granuloma at the site of anastomosis developed and it was satisfactorily managed by local palliative measures. No recurrence has been found during a follow-up of 1.5 years.


Formation of brine channels in sea ice.
Liquid salty micro-channels (brine) between growing ice platelets in sea ice are an important habitat for CO2-binding microalgaea with great impact on polar ecosystems. The structure formation of ice platelets is microscopically described and a phase field model is developed. The pattern formation during solidification of the two-dimensional interstitial liquid is considered by two coupled order parameters, the tetrahedricity as structure of ice and the salinity. The coupling and time evolution of these order parameters are described by a consistent set of three model parameters. They determine the velocity of the freezing process and the structure formation, the phase diagram, the super-cooling and super-heating region, and the specific heat. The model is used to calculate the short-time frozen micro-structures. The obtained morphological structure is compared with the vertical brine pore space obtained from X-ray computed tomography.


Evolution of polyphenolic, anthocyanin, and organic acid components during coinoculation fermentation (simultaneous inoculation of LAB and yeast) and sequential fermentation of blueberry wine.
This research aims to investigate the effects of both sequential fermentation and coinoculation fermentation with yeast and lactic acid bacterial (LAB) on the dynamics of changes in basic quality parameters and organic acid, anthocyanin, and phenolic components as well as antioxidant activity during the fermentation of blueberry. The coculture-fermented blueberry wine showed significant decreases in total phenolics, flavonoids, and anthocyanins,by 23.9%, 15.9%, and 13.7%, respectively, as compared with those before fermentation Fermentation changed the contents of organic acids in each group, with a more than 7-fold increase in lactic acid contents as well as a more than 4-fold reduction in quinic acid and malic acid contents. The content of all investigated anthocyanins first increased and then decreased. Moreover, different fermentation strategies exerted a profound influence on the dynamic change in phenolic components during fermentation; specifically, most of the phenolic acids showed a trend of increasing first, then decreasing, and finally increasing. Gallic acid, p-coumaric acid, quercetin, and myricetin were increased by 116.9%, 130.1%, 127.2% and 177.6%, respectively, while syringic acid, ferulic acid, cinnamic acid, and vanillic acid were decreased by 49.5%, 68.5%, and 37.1% in sequentially fermented blueberry wine. Coinoculation fermentation with yeast and LAB produces faster dynamic variations and higher organic acid, anthocyanin, and phenolic profiles than sequential inoculation fermentation. PRACTICAL APPLICATION: In this work, brewing technology of sequential fermentation and coinoculation fermentation with yeast and LAB (Lactobacillus plantarum SGJ-24 and Oenococcus oeni SD-2a) was adopted to ferment blueberry wine. This is an innovative technology of fruit wine brewing technology to produce wine products. Compared with traditional sequential brewing, simultaneous inoculation brewing can significantly accelerate the brewing process of fruit wine and slightly improve the quality of fruit wine in terms of active ingredients.


Low-load prolonged stretch vs. high-load brief stretch in treating knee contractures.
This study was designed to compare the results of a traditional method of stretching knee flexion contractures by high-load brief stretch (HLBS) with the results of an experimental method of prolonged knee extension by skin traction, low-load prolonged stretch (LLPS). End range of passive knee extension was measured by standard goniometry. Subjects were 11 nonambulatory residents of a nursing home who had demonstrated gradually progressive bilateral knee contractures. Each subject served as his or her own control with one lower limb receiving LLPS and the other limb receiving HLBS and passive range of motion (PROM). Sequential medical trials were used as the clinical research design. Whether comparing the LLPS limb PROM measurements pretreatment and posttreatment (p less than or equal to .05) or the HLBS to the LLPS limb PROM recordings posttreatment (p less than or equal to .05), the results demonstrated a preference for LLPS in the treatment of knee contractures in the immobile nursing home resident.


Roles of High Mobility Group Box 1 in Cardiovascular Calcification.
Calcific disease of the cardiovascular system, including atherosclerotic calcification, medial calcification in diabetes and calcific aortic valve disease, is an important risk factor for many adverse cardiovascular events such as ischemic cardiac events and subsequent mortality. Although cardiovascular calcification has long been considered to be a passive degenerative occurrence, it is now recognized as an active and highly regulated process that involves osteochondrogenic differentiation, apoptosis and extracellular vesicle release. Nonetheless, despite numerous studies on the pathogenesis of cardiovascular calcification, the underlying mechanisms remain poorly understood. High mobility group box 1 (HMGB1), a nuclear protein bound to chromatin in almost all eukaryotic cells, acts as a damage-associated molecular pattern (DAMP) when released into the extracellular space upon cell activation, injury or death. Moreover, HMGB1 also functions as a bone-active cytokine participating in bone remodeling and ectopic calcification pathogenesis. However, studies on the roles of HMGB1 in promoting cardiovascular calcification are limited to date, and the mechanisms involved are still unclear. In this review, we summarize recent studies investigating the mechanism of cardiovascular calcification and discuss multiple roles of HMGB1 in its development.


An Umbrella Review of the Literature on Perinatal Domestic Violence: Prevalence, Risk Factors, Possible Outcomes and Interventions.
Perinatal domestic violence (P-DV) is a common form of violence experienced by women and is associated with adverse impacts on their own physical and mental health and that of their offspring. Illuminating the risk factors for, potential effects of, and promising interventions to reduce P-DV is essential for informing policies to tackle P-DV and mitigate its negative impacts. This umbrella review of recent high-quality systematic reviews and meta-analyses of worldwide research on P-DV provides a systematic synthesis of current knowledge relating to the prevalence, risk factors for, possible outcomes of and interventions to reduce and prevent P-DV. 13 reviews identified through systematic searches of computerised databases, manual search and expert consultation met our inclusion criteria (i.e. English systematic reviews and/or meta-analyses that were from recent 10 years, focused on women exposed to P-DV, assessed risk factors, possible outcomes and/or interventions, and were of fair to high methodological quality). Our results suggest that while there is a growing understanding of risk factors and possible outcomes of P-DV, this knowledge has thus far not been translated well into effective interventions. P-DV intervention programmes that have been subject to rigorous evaluation are mostly relatively narrow in scope and could benefit from targeting a wider range of maternal and child wellbeing outcomes, and perpetrator, relationship and community risk factors. The overall quality of the evidence syntheses in this field is reasonable; however, future studies should involve multiple reviewers at all key stages of systematic reviews and meta-analyses to help enhance reliability.


Comparative study of postoperative stability between conventional orthognathic surgery and a surgery-first orthognathic approach after bilateral sagittal split ramus osteotomy for skeletal class III correction.
The purpose of this study is to compare the postoperative stability of conventional orthognathic surgery to a surgery-first orthognathic approach after bilateral sagittal split ramus osteotomy (BSSRO). The study included 20 patients who underwent BSSRO for skeletal class III conventional orthognathic surgery and 20 patients who underwent a surgery-first orthognathic approach. Serial lateral cephalograms were analyzed to identify skeletal changes before surgery (T0), immediately after surgery (T1), and after surgery (T2, after 1 year or at debonding). The amount of relapse of the mandible in the conventional orthognathic surgery group from T1 to T2 was 2.23±0.92 mm (P<0.01) forward movement and -0.87±0.57 mm (non-significant, NS) upward movement on the basis of point B and 2.54±1.37 mm (P<0.01) forward movement and -1.18±0.79 mm (NS) upward movement on the basis of the pogonion (Pog) point. The relapse amount of the mandible in the surgery-first orthognathic approach group from T1 to T2 was 3.49±1.71 mm (P<0.01) forward movement and -1.78±0.81 mm (P<0.01) upward movement on the basis of the point B and 4.11±1.93 mm (P<0.01) forward movement and -2.40±0.98 mm (P<0.01) upward movement on the basis of the Pog. The greater horizontal and vertical relapse may appear because of counter-clockwise rotation of the mandible in surgery-first orthognathic approach. Therefore, careful planning and skeletal stability should be considered in orthognathic surgery.


Should sentinel lymph node mapping be performed for colorectal cancer?
Correct determination of lymphatic nodal statement is essential to stage correctly and to predict survival. As it is vital to make an assessment about the adjacent lymph node(s), this study was designed to compose a sensitive detection on the sentinel lymph nodes (SLN) indicating tumoral lymphatic basin using advanced pathologic examination. From June 2002 to June 2003, this prospective study was performed in 41 patients undergoing standard resection for colorectal cancer. In this study we employed the ex-vivo SLN mapping technique. At least one SLN in 37 of 41 patients was identified (90.2%). The lymph nodes (LN) from those patients were studied by hematoxylin and eosin dye (H&E) and multisectioning. Twenty of 37 patients with trace of the metastasis were found. The remaining 17 patients without any metastatic LN by H&E underwent clarification of micrometastases (MM) using immunohistochemical (IHC) staining technique. Two patients (11.7%) had MM in the SLN(s). Upstaging was evaluated in those two. The sensitivity of SLNs was obtained as 90%. Two patients with no metastatic SLN had metastasis in the non-sentinel LNs. In the LNs from the basin of tumor, MM exposed by IHC staining was still not obvious to indicate poor prognosis. The need for treatment adjustment in those patients is clear since the upstaging was evident.


MicroRNA-543 acts as an oncogene by targeting PAQR3 in hepatocellular carcinoma.
MicroRNAs (miRNAs) are small, non-coding RNAs that can act as oncogenes or tumor suppressor genes in human cancer. Increasing evidences indicate that deregulation of miRNAs contributes to the hepatocarcinogenesis. In this study, we demonstrated that the levels of miR-543 were dramatically increased in clinical hepatocellular carcinoma (HCC) tissues and cell lines. Moreover, forced expression of miR-543 promoted the proliferative and invasive potential of HepG2. We also identified PAQR3 as a direct target gene for miR-543 using a fluorescent reporter assay and western blot. The levels of PAQR3 were dramatically decreased in clinical hepatocellular carcinoma (HCC) tissues and cell lines. The mRNA levels of PAQR3 were inversely correlated with the miR-543 expression level.Thus, our finding provides a new insight into the mechanism of hepatocarcinogenesis, indicating a therapeutic potential of miR-543 in the treatment of HCC.


Neural Correlates of Verbal Working Memory: An fMRI Meta-Analysis.
Verbal Working memory (vWM) capacity measures the ability to maintain and manipulate verbal information for a short period of time. The specific neural correlates of this construct are still a matter of debate. The aim of this study was to conduct a coordinate-based meta-analysis of 42 fMRI studies on visual vWM in healthy subjects (n = 795, males = 459, females = 325, unknown = 11; age range: 18-75). The studies were obtained after an exhaustive literature search on PubMed, Scopus, Web of Science, and Brainmap database. We analyzed regional activation differences during fMRI tasks with the anisotropic effect-size version of seed-based d mapping software (ES-SDM). The results were further validated by performing jackknife sensitivity analyses and heterogeneity analyses. We investigated the effect of numerous relevant influencing factors by fitting corresponding linear regression models. We isolated consistent activation in a network containing fronto-parietal areas, right cerebellum, and basal ganglia structures. Regarding lateralization, the results pointed toward a bilateral frontal activation, a left-lateralization of parietal regions and a right-lateralization of the cerebellum, indicating that the left-hemisphere concept of vWM should be reconsidered. We also isolated activation in regions important for response inhibition, emphasizing the role of attentional control in vWM. Moreover, we found a significant influence of mean reaction time, load, and age on activation associated with vWM. Activation in left medial frontal gyrus, left precentral gyrus, and left precentral gyrus turned out to be positively associated with mean reaction time whereas load was associated with activation across the PFC, fusiform gyrus, parietal cortex, and parts of the cerebellum. In the latter case activation was mainly detectable in both hemispheres whereas the influence of age became manifest predominantly in the left hemisphere. This led us to conclude that future vWM studies should take these factors into consideration.


Age and sex related alterations in serum and platelet monoamine oxidase.
The process of aging presents itself with various alterations in physiological events. Although the turnover of catecholamines increases with aging, there is a lack of response to catecholamines in target tissues. One of the key enzymes in catecholamine metabolism is monoamine oxidase. It has been suggested that tissue and serum monoamine oxidase activities show pathological alterations in various diseases while physiological fluctuations can also be detected in normals. The aim of this study is to determine the sex and age related changes of platelet and serum monoamine oxidase in healthy volunteers. In this study, 75 healthy volunteers of different ages (21-80 a) and sexes (40 females, 35 males) were included. Serum and platelet monoamine oxidase determinations were performed spectrophotofluorometrically by Tufvesson's (Scand J Clin Lab Invest 1970; 26:151-4) and Kraml's (Biochem Pharmacol 1965; 14:1684-6) modified methods, respectively. While there was no significant difference in serum monoamine oxidase activities related to age and sex, platelet monoamine oxidase manifested a significant increase in females compared to males (p < 0.05) and the mean values in both sexes showed an increase with age (p < 0.001). The results of this study imply that platelet monoamine oxidase shows an age related increase which is more prominent in females.


Inflammation and myointimal hyperplasia. Correlation with hemodynamic forces.
The aim of our study was to correlate flow dynamics and the release of inflammatory cytokines Interleukin 1, 2, 6, TNF (Tumour Necrosis Factor) alfa, both in vitro and in vivo. Endothelial cells were exposed to laminar flow (6dyne/cm2) in an in vitro circulatory system and the release of Interleukin 1, 2, 6 and TNF alfa was quantified by ELISA. Interleukin 1, 2, 6 and TNF alfa release was also assessed in vein grafts implanted in the arterial circulation of Lewis rats. Arterial vein grafts were explanted at different time intervals from 3days to 12weeks after surgery. Vein grafts implanted in the arterial circulation for 4weeks, were re implanted in the venous circulation of syngenic Lewis rats, and the release of Interleukin 1, 2, 6 and TNF alfa, was assessed in an organ culture. Six vein grafts (4 occluded, 2 patent) implanted in humans as femorodistal bypass were examined for the presence of myointimal hyperplasia and perigraft inflammatory cells. In vitro, endothelial cells exposed to laminar flow released an increased amount of Interleukin 1, 2, 6 and TNF alfa in comparison to endothelial cells not exposed to flow. In experimental vein grafts implanted in the arterial circulation there was an increased release of inflammatory cytokines associated to inflammatory changes in the adventitia. Once the vein grafts were re implanted in the venous circulation, the release of these cytokines diminished, while the inflammatory changes in the adventitia regressed. Increased shear stress induces release of cytokines and inflammatory changes in the adventitia. These inflammatory changes can contribute to plaque progression and to un stable plaque. These findings support the use of anti-inflammatory therapy in patients prone to develop atherosclerosis and in those who had arterial reconstructive surgery.


Evaluation of the Effectiveness of Protective Patches on Acupoints to Preserve the Bioenergetic Status against Magnetic Fields.
The potentially harmful nature of electromagnetic fields (EMF) and static magnetic fields (SMF) has become a major problem in recent years. All these elements could be combined to produce cellular responses. For example, the orientation of molecules of water or other complex molecules, growth and cell viability, cell morphology, and intracellular metabolic pathways have demonstrated binding to magnetic fields. The effect of EMF and SMF on humans is a topic of great importance, especially because modern technology has introduced artificial magnetic fields such as those generated by power lines, mobile communications, and medical imaging equipment. A relevant problem is certainly that of professional exposure. The aim of this study was the evaluation of the effectiveness of a commercially available device, Skudo® patches (Edil Natura S.r.l., Novara, Italy), in protecting magnetic resonance operators from the influence of magnetic fields such as those present in the workplace. Skudo® patches are designed to protect microareas of the body from external electromagnetic disturbances. In this study, 10 male Italian volunteers aged between 50 and 60 were enrolled in the hospital. All participants were subjected to measurements at 4 specific time points to evaluate the effectiveness of Skudo® to counteract both EMF and SMF magnetic fields by evaluating the level of bioenergetic reactivity. To perform the measurements, a variant of the Ryodoraku method has been used, based upon the assessment of electropermeability. In particular, 12 acupoints were measured, one for each of the main meridians. This study shows that both SMF and EMF cause an alteration of the body's water system. The application of Skudo® patches determines a regularization of bioenergetic levels related to the water system. The application of Skudo® on the EMF source has suppressed the imbalance effect of the water system found in the subject without any protection.


Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms.
Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FcεRI crosslinking. Mast cell degranulation was assessed in bone marrow-derived mast cells isolated from 23 strains of mice following exposure to AgNPs or FcεRI crosslinking with dinitrophenyl (DNP). Utilizing strain-dependent mast cell degranulation, an association mapping study identified 3 chromosomal regions that were significantly associated with mast cell degranulation by AgNP and one non-overlapping region associated with DNP-mediated degranulation. Two of the AgNP-associated regions correspond to genes previously reported to be associated with allergic disorders (Trac2 on chromosome 1 and Traf6 on chromosome 2) and an uncharacterized gene identified on chromosome 1 (Fam126b). In conjunction, RNA-sequencing performed on mast cells from the high and low responder strains revealed 3754 and 34 differentially expressed genes that were unique to DNP and AgNP exposures, respectively. Select candidate genes include Ptger4, a gene encoding a G-protein coupled receptor in addition to a multifunctional adaptor protein, Txnip, that may be driving mast cell degranulation by AgNP. Taken together, we identified novel genes that have not been previously shown to play a role in nanoparticle-mediated mast cell activation. With further functional evaluation in the future, these genes may be potential therapeutic targets in the treatment of non-IgE mediated mast cell-linked disorders.


An overview of current techniques for tonsillectomy.
Tonsillectomy remains a commonly performed surgical procedure. Although common, it has complications and associated morbidity. In an era of cost containment, indications for surgery have been promulgated by the American Academy of Otolaryngology-Head and Neck Surgery (2000) to aid the healthcare practitioner in appropriate referral to the surgeon, as well as clinical indicators to help insure that surgical intervention is in the best interest of the patient. Surgical techniques are constantly evolving, with the goal of reducing complications and improving postoperative recovery and healing. Review of the literature suggests that new technologies may or may not be better than the tried-and-true surgical techniques combined with good post-operative nursing care.


A simple and fast technique for on-line fMRI data analysis.
In the present work a simple technique for fMRI data analysis is presented. Artifacts due to random and stimulus-correlated motions are corrected without image registration procedures. The first step of our procedure is the calculation of the raw activation map by correlation analysis. The task related motion artifacts arise at the tissue interfaces, including vessels: when image intensity gradient is calculated the high values correspond to interface regions. To eliminate stimulus-correlated motion artifacts the intensity gradient image, obtained from the fMRI data set, is compared to the raw activation map. Since small random motions decrease the value of the correlation coefficient (R) of the external pixels of the activation areas, in the last step of our analysis procedures the clusters are extended to connected pixels having R values smaller than the defined threshold. Each cluster is expanded until the R value of the cluster average intensity is kept constant. The procedure has been tested with both GRE and EPI studies. The presented approach is a fast and robust technique useful for preliminary or on-line analysis of fMRI data.