Left ventricular strain patterns and their relationships with cardiac biomarkers in hypertrophic cardiomyopathy patients with preserved left ventricular ejection fraction.
This study aims to assess left ventricular (LV) function in hypertrophic cardiomyopathy (HCM) patients with preserved left ventricular ejection fraction (LVEF) by LV strain patterns based on cardiac magnetic resonance feature tracking (CMR-FT) and to explore the relationships between LV strain patterns and cardiac biomarkers in these patients, such as cardiac troponin (cTnT) and N-terminal prohormone of the brain natriuretic peptide (NT-proBNP). A total of 64 HCM patients with preserved LVEF and 33 healthy people were included in this study. All subjects underwent contrast-enhanced CMR, and all patients took blood tests for cTnT and NT-proBNP during hospitalization. Despite the absence of a significant difference in LVEF between HCM patients and healthy controls, almost all global and segmental strains in radial, circumferential, and longitudinal directions in the HCM group deteriorated significantly as compared to controls (p < 0.05). Moreover, some global and segmental strains correlated significantly with NT-proBNP and cTnT in HCM patients, and the best correlations were global radial strain (GRS) (r = -0.553, p < 0.001) and mid-ventricular radial strain (MRS) (r = -0.582, p < 0.001), respectively, with a moderate correlation. The receiver operating characteristic (ROC) results showed that among the LV deformation parameters, GRS [area under the curve (AUC), 0.76; sensitivity, 0.49; specificity, 1.00], MRS (AUC, 0.81; sensitivity, 0.77; specificity, 0.79) demonstrated greater diagnostic accuracy to predict elevated NT-proBNP, and abnormal cTnT, respectively. Their cut-off values were 21.17 and 20.94%, respectively. Finally, all global strains demonstrated moderate, good, and excellent intra- and inter-observer reproducibility. LV strain patterns can be used to assess the subclinical cardiac function of HCM patients on the merit of being more sensitive than LVEF. In addition, LV strain patterns can detect serious HCM patients and may be helpful to non-invasively predict elevated NT-proBNP and cTnT.


High voltage nanosecond pulse generator based on diode opening switch and magnetic switch.
Low-temperature plasma technology is widely used in various industrial fields, which require the plasma to be of large volume, diffuse, and stable. Furthermore, previous studies have shown that better plasma performance has been obtained by using generators with a high voltage, a high repetition rate, a fast rise time, and a short pulse duration. In this paper, a novel topology is proposed for such generators, which is based on magnetic switches and diode opening switches. A prototype is developed, and its output characteristics are investigated by varying essential parameters, such as the load resistance and the power supply voltage. The experimental results show that it can generate pulses with a voltage of 30.6 kV, a rise time of 7.1 ns, a pulse duration of 8.2 ns, and a maximum repetition rate of 12 kHz on a 300 Ω resistive load. The prototype has been successfully used to drive uniform plasma in ambient air. In the proposed topology, a diode is added to make the magnetic cores independent of each other, significantly simplifying the design calculation. It may help develop nanosecond solid-state generators.


[Clinical anatomic and urodynamic investigations in stress-incontinence women (author's transl)].
In 398 patients suffering from urinary incontinence seven urodynamic parameters were investigated. 75% resp. 78% had a normal max. urethral closure pressure. Only a part of the women was characterized by a descensus of the genital tract. Some more patients showed anatomic abnormalities in the urethrovesical configuration by x-ray urethrocystogram. 1/5 res. 1/3 of descendent anterior vaginal walls proved to have a cystocele. If one requires for successful incontinence operation a normal max. urethral closure pressure and an objectively proven abnormality of the urethrovesical configuration, only 65% resp. 67% of our incontinence women have a chance of being cured by incontinence operation.


Is formative assessment an effective way to improve learning? A Symposium at Experimental Biology 2008.
Formative assessment is designed to provide information about students' learning to help them and their teachers to identify deficiencies and misconceptions. It differs from summative assessment, which aims to rank students according to their achievements to determine which students pass or fail or to assign grades to students. This article reports on a symposium concerned with evidence for the effectiveness of formative assessment in improving learning. It was presented by the Teaching of Physiology Section of the American Physiological Society at the Experimental Biology Meeting of 2008.


Degradation pattern and risk assessment of carbendazim and mancozeb in mango fruits.
A supervised field trial was conducted at four different agroclimatic locations in India to evaluate the dissipation pattern and risk assessment of carbendazim and mancozeb in mango fruits following foliar application of mixed formulation of carbendazim 12% and mancozeb 63% fungicide (SAAF-75WP) at recommended dose (90 + 472.5) and double the recommended dose (180 + 945 g a.i. ha(-1)). Average initial deposition of carbendazim was in the range of 1.12 to 2.7 and 1.95 to 4.09 mg kg(-1) and for mancozeb in the range of 2.25 to 2.71 and 4.17 to 5.96 mg kg(-1), given at respective doses. Residues of carbendazim and mancozeb were dissipated to the below detectable limit 7 days after spray at recommended dosage in all the locations. The fungicide degradation followed a first order kinetics with half-lives of 1-5 and 1-3 days, for carbendazim and mancozeb, respectively. The TMRC values, calculated from residue data generated from all four locations, were found to be below the MPI in mango fruit, and hence, the fungicide will not cause any adverse effect after consumption of mango fruits. This data could provide guidance for the proper and safe use of this fungicide mixture for managing disease incidence in mango in India.


Prolonging photoperiod promotes testosterone synthesis of Leydig cells by directly targeting local melatonin system in rooster testes†.
The study investigated the effects of prolonging photoperiod on the synthesis of testosterone and melatonin in roosters, and the effect of melatonin on testosterone synthesis in rooster Leydig cells as well as its molecular mechanisms. We randomly divided one hundred and twenty 20-week-old roosters into three groups and provided 6, 12.5 and 16 h light, respectively. The results showed that prolonging photoperiod promoted testosterone synthesis, decreased melatonin production, and inhibited the expression of melatonin membrane receptors MEL1A, MEL1B, MEL1C, and aralkylamine N-acetyltransferase (AANAT) in rooster testes. Subsequently, rooster Leydig cells were isolated and treated with 0, 0.1, 1, 10, and 100 ng/mL melatonin for 36 h. The results suggested that melatonin inhibited testosterone synthesis in rooster Leydig cells, and silencing MEL1A and MEL1B relieved the inhibition of melatonin on testosterone synthesis. Additionally, melatonin reduced the intracellular cyclic adenosine monophosphate (cAMP) level and the phosphorylation level of cAMP-response element binding protein (CREB), and CREB overexpression alleviated the inhibition of melatonin on testosterone synthesis. Furthermore, pretreatment with cAMP activator forskolin or protein kinase A (PKA) activator 8-bromo-cAMP blocked the inhibition of melatonin on CREB phosphorylation and testosterone synthesis. These results indicated that prolonging photoperiod promoted testosterone synthesis associated with the decrease in melatonin production and membrane receptors and biosynthetic enzyme of melatonin in rooster testes, and melatonin inhibited testosterone synthesis of rooster Leydig cells by inhibiting the cAMP/PKA/CREB pathway via MEL1A and MEL1B. This may be evidence that prolonging photoperiod could promote testosterone synthesis through the inhibition of the local melatonin pathway in rooster testes.


Biomarkers for Helicobacter pylori infection and gastroduodenal diseases.
Helicobacter pylori infection is a major cause of gastric cancer. Although identifying H. pylori infected subjects is the first approach for delineating the high-risk population for gastric cancer, the presence of H. pylori antibodies is not sufficient for gastric cancer screening. Among H. pylori infected subjects, only a minority of infected individuals develop gastric cancer. Serologic markers of H. pylori infection can serve as potential predictors for the development of gastric cancer. Serum or urinary H. pylori antibodies, cytotoxin-associated gene A antibodies, pepsinogen and microRNAs were reported to be associated with precancerous lesions or gastric cancer. In this review, we summarized the utilities and limitations of each strategy.


The lung alveolar lipofibroblast: an evolutionary strategy against neonatal hyperoxic lung injury.
Oxygen, the main mode of support for premature infants with immature lungs, can cause toxicity by producing reactive oxygen species (ROS) that disrupt homeostasis; yet, these same molecules were entrained to promote vertebrate lung phylogeny. By providing a deeper understanding of this paradox, we propose physiologically rational strategies to prevent chronic lung disease (CLD) of prematurity. To prevent neonatal hyperoxic lung damage biologically, we have exploited the alveolar defense mechanism(s) that evolutionarily evolved to combat increased atmospheric oxygen during the vertebrate water to land transition. Over the course of vertebrate lung evolution, ROS promoted the formation of lipofibroblasts, specialized adepithelial cells, which protect the alveoli against oxidant injury; peroxisome proliferator-activated receptor gamma (PPARγ), the master switch for lipofibroblast differentiation, prevents such oxidant lung injury, both by directly promoting mesodermal differentiation and its antioxidant defenses, and indirectly by stimulating the developmental epithelial-mesenchymal paracrine interactions that have physiologically determined lung surfactant production in accord with the lung's phylogenetic adaptation to atmospheric oxygen, preventing Respiratory Distress Syndrome at birth. The molecular strategy (PPARγ agonists) to prevent CLD of prematurity, proposed by us, although seems to be robust, effective, and safe under experimental conditions, it awaits detailed pharmacokinetic and pharmacodynamic studies for its safe and effective clinical translation to human infants. Antioxid. Redox Signal. 21, 1893-1904. "I have procured air [oxygen]…between five and six times as good as the best common air that I have ever met with." -Joseph Priestley, 1775.


Comparison between MRI and Arthroscopy of the Wrist for the Assessment of Posttraumatic Lesions of Intrinsic Ligaments and the Triangular Fibrocartilage Complex.
Background Magnetic resonance imaging (MRI) has been considered the most appropriate examination for wrist ligament injuries diagnosis, but it frequently fails to assess the intrinsic ligament lesion. Therefore, wrist arthroscopy is required to enhance and define the diagnosis. Purpose We compare the MRI imaging with wrist arthroscopy for intrinsic wrist ligaments (scapholunate [SL] and lunotriquetral [LT]) and triangular fibrocartilage complex (TFCC) injuries detection. Patients and Methods From 2007 to 2014, 532 patients affected by suspected SL, LT, and TFCC posttraumatic ligament injury have been investigated by 1.5-Tesla MRI and wrist arthroscopy. Inclusion and exclusion criteria were adopted. Only for SL ligament injury, the arthroscopic findings of complete (stage IV) and partial (stages I-III) SL ligament injury were compared with MRI findings. Statistical analysis, including sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and the diagnostic odds ratio, was used to compare MRI with arthroscopic findings. Results A total of 146 patients were accepted in the study. In 68 cases of arthroscopic SL ligament lesion, MRI confirmed the diagnosis only in 50% of the cases. In partial SL lesions, MRI was positive in 24.3% and in complete SL lesions, MRI was positive in 80.6% of the cases. In 10 cases of arthroscopic LT ligament lesion, MRI was positive in 30.0% of the cases. In 33 patients with arthroscopic TFCC lesion, MRI was positive in 66.7% of the cases. Conclusion 1.5-T MRI demonstrated to fail in confirming the lesion of SL, LP, and TFCC ligaments respectively in 50, 70, and 33.3% of the cases positive at arthroscopy. In complete SL ligament lesion, MRI reaches a higher sensitivity than in partial lesion. Arthroscopy remains the best method to demonstrate the ligament lesion and obtain more information regarding the extent and quality of the ligament damage. Level of Evidence This is a Level II, retrospective comparative study.


Expression of desmoglein I in squamous cell carcinoma of the esophagus.
Desmoglein I (DGI) is major component of the desmosomal membrane core that plays an important role in epithelial cell adhesion. The aim of this study was to explore the correlation between the expression of DGI and the clinicopathological findings of esophageal cancer. DGI expression was immunohistochemically examined using an anti-DGI monoclonal antibody in 139 patients with squamous cell carcinoma of the esophagus. Normal squamous epithelial cells strongly expressed DGI at their cell-cell boundaries. According to the intensity and pattern of DGI expression, the cancerous tissues were divided into three groups: DGI (++), DGI (+), and DGI (-). Of the 139 tumors, 35 (25%) were DGI (++), 65 (47%) were DGI (+), and 39 (28%) were DGI (-). A good inverse correlation between DGI expression and tumor invasion, lymph node metastasis, lymphatic invasion, and vessel invasion was observed. These results indicate that DGI expression may be a significant factor for invasion, metastasis, and prognosis of human esophageal cancer.


Work-related respiratory disease in the United Kingdom, 1989-1992: report on the SWORD project.
The objective of this project is the creation of a reliable and cost-effective national system of surveillance for work-related respiratory disease as a basis for control and simple epidemiological research. With the voluntary participation of almost 800 chest and occupational physicians from throughout the UK, newly diagnosed cases of respiratory illness thought to be due to occupational factors have been reported regularly since January 1989. Since January 1992, reports from chest physicians have been submitted monthly by a core group with special interest in occupational lung disease (n = 32) and rotating random samples of the remainder. Between 1989 and 1991, 5576 new cases were reported, of which half were diseases of long latency mainly due to asbestos, 28% were occupational asthma, and the rest were divided between inhalation accidents (10%) and a variety of other acute diseases (14%). Disease incidence rates, with denominators from the Labour Force Survey, showed a very high risk of asthma among paint sprayers, chemical and food processors, laboratory staff, plastics and metal treatment workers, and in welding and electronic assembly. Some of the same groups also experienced high rates of inhalation accidents and bronchitis. The risk of diseases of long latency, using denominators from the 1961 census, was highest in shipyard and dock workers, miners and construction workers. The SWORD scheme has provided estimates of disease incidence not previously available, has encouraged awareness of occupational factors among chest physicians, has assisted those responsible for prevention and control, and has demonstrated the feasibility of this approach to surveillance.


[Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].
Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.


Sexual Modes in the Colonial Kamptozoan Genus Barentsia.
Sexual mode in colonial animals is expressed at the zooid, colony, and genet level; all three must be characterized to understand sexuality in these animals. I carried out such an examination of the sexual mode of a colonial kamptozoan (entoproct), Barentsia hildegardae, at Friday Harbor, Washington. Calyces never contained both ovaries and testes, and colonies never contained both male and female calyces. Calyces and colonies (including replicate colonies from the same genet) monitored over two years did not change sex. These results suggest that B. hildegardae is comprehensively gonochoric. For comparison, I examined the sexual mode of five other species in the genus Barentsia. Barentsia benedeni, B. conferta, and B. ramosa also appear to be comprehensively gonochoric. Barentsia discreta is hermaphroditic at the colony level, with gonochoric calyces whose sex is environmentally determined, as noted by previous workers. Barentsia aggregata has simultaneously hermaphroditic calyces; this was reported by the authors who described it, but has escaped notice in subsequent reviews of kamptozoan biology. There are thus three contrasting modes of sex within the genus Barentsia. All three modes also occur in colonial cnidarians, and two of them are known in bryozoans, colonial hemichordates, and colonial urochordates. These disparate sexual modes may have evolved as adaptations to differing environmental conditions or population densities.


Comfort and health: cause for concern.
Chancellor Lamont's announcement in his 1993 Budget of the proposed imposition of VAT on domestic fuel bills, quoted in Hansard (1993), poses the question as to what effect this projected increase in fuel costs will have upon the health of those at greatest risk in the community. This paper is based upon the premise that householders on low, or fixed incomes faced with a significant increase in fuel costs must either reduce their expenditure or reduce their heating costs. The paper considers these issues and considers the possible effects upon standards of heating and ventilation in the home confounded by increased levels of insulation, and the potential for significant increases in condensation associated with increased levels of indoor air pollution within dwellings. Suggestions for the mitigation of these perceived risks to health are also set out, including the need for increased financial assistance for those most at risk.


Postnatal growth defects in mice with constitutive depletion of central serotonin.
Although the trophic actions of serotonin (5-HT) are well established, only few developmental defects have been reported in mouse strains with constitutive hyposerotonergia. We analyzed postnatal growth and cortical development in three different mutant mouse strains with constitutive reductions in central 5-HT levels. We compared two previously published mouse strains with severe (-95%) depletions of 5-HT, the tryptophan hydroxylase (Tph) 2(-/-) mouse line and VMAT2(sert-cre) mice, with a new strain, in which VMAT2 deletion is driven by Pet1 (VMAT2(pet1-cre)) in 5-HT raphe neurons leading to partial (-75%) reduction in brain 5-HT levels. We find that normal embryonic growth and postnatal growth retardation are common features of all these mouse strains. Postnatal growth retardation varied from mild to severe according to the extent of the brain 5-HT reduction and gender. Normal growth was reinstated in VMAT2(sert-cre) mice by reconstituting central 5-HT stores. Growth abnormalities could not be linked to altered food intake or temperature control. Morphological study of the cerebral cortex over postnatal development showed a delayed maturation of the upper cortical layers in the VMAT2(sert-cre) and Tph2(-/-) mice, but not in the VMAT2(pet1-cre) mice. No changes in layer-specific gene expression or morphological alterations of barrel cortex development were found. Overall, these observations sustain the notion that central 5-HT signaling is required for the preweaning growth spurt of mouse pups. Brain development appeared to be immune to severe central 5-HT depletion for its overall growth during prenatal life, whereas reduced brain growth and delayed cortical maturation development occurred during postnatal life. Reduced developmental 5-HT signaling during postnatal development might modulate the function and fine structure of neural circuits in ways that affect adult behavior.


Creatine kinase and lactate dehydrogenase isoenzymes in serum of patients suffering burns, blunt trauma, or myocardial infarction.
Medical records of 53 burn and trauma patients were reviewed to assess the possibility of myocardial damage. Except for electrophoretically detectable creatine kinase MB isoenzyme, none showed evidence of myocardial injury. Lactate dehydrogenase isoenzyme tests, electrocardiograms, myocardial pyrophosphate scans, clinical course, and results of (two) autopsies were all negative for myocardial necrosis or ischemia. Types of patient, number, mean peak value (U/L) for serum creatine kinase, and ranges of percentage MB isoenzyme were as follows. Burns from direct electrical contact: 28, 16 600, 0-29; electrical flash or other thermal burns: 10, 4340, 0-22; blunt trauma (mostly from automobile accidents): 15, 3430, 0-18; myocardial infarction: 57, 1520, 4-46. Evidently creatine kinase MB isoenzyme is nonspecific in burn and trauma patients and should not be the only test result used to assess myocardial involvement.


Laser-assisted optoporation of cells and tissues - a mini-review.
Laser microbeam techniques are presented, which permit the introduction of molecules or small particles into living cells. Possible mechanisms - including photochemical, photothermal and opto-mechanical interactions (ablations) - are induced by continuous wave (cw) or pulsed lasers of different wavelength, power, and mode of operation. Laser-assisted optoporation permits the uptake of fluorescent dyes as well as DNA plasmids for cell transfection, and, in addition to its broad application to cultivated cells, may have some clinical potential.


Evaluating Droplet Digital Polymerase Chain Reaction for the Quantification of Human Genomic DNA: Lifting the Traceability Fog.
Digital polymerase chain reaction (dPCR) end point platforms directly estimate the number of DNA target copies per reaction partition, λ, where the partitions are fixed-location chambers (cdPCR) or aqueous droplets floating in oil (ddPCR). For use in the certification of target concentration in primary calibrant certified reference materials (CRMs), both λ and the partition volume, V, must be metrologically traceable to some accessible reference system, ideally, the International System of Units (SI). The fixed spatial distribution of cdPCR chambers enables real-time monitoring of PCR amplification. Analysis of the resulting reaction curves enables validation of the critical dPCR assumptions that are essential for establishing the SI traceability of λ. We know of no direct method for validating these assumptions for ddPCR platforms. The manufacturers of the cdPCR and ddPCR systems available to us do not provide traceable partition volume specifications. Our colleagues at the National Institute of Standards and Technology (NIST) have developed a reliable method for determining ddPCR droplet volume and have demonstrated that different ddPCR reagents yield droplets of somewhat different size. Thus, neither dPCR platform by itself provides metrologically traceable estimates of target concentration. We show here that evaluating split samples with both cdPCR and ddPCR platforms can transfer the λ traceability characteristics of a cdPCR assay to its ddPCR analogue, establishing fully traceable ddPCR estimates of CRM target concentration.


595-nm long pulsed dye laser and 1450-nm diode laser in combination with intralesional triamcinolone/5-fluorouracil for hypertrophic scarring following a phenol peel.
Hypertrophic scars and keloids are a therapeutic challenge because of the low response to treatment and recurrences after treatment. A variety of treatment regimens have been used with different degrees of success, with no universally accepted treatment protocol resulting in their complete and permanent resolution. We offer this case to demonstrate a combination approach for the treatment of hypertrophic scarring. A 75-year-old woman (with Fitzpatrick skin type II) presented with a 4-month history of scarring, which had developed following a phenol peel for perioral rhytides. The patient underwent 10 treatment sessions with the 595-nm long-pulsed dye laser followed immediately by the 1450-nm diode laser in combination with intralesional triamcinolone and 5-fluorouracil. After the fifth treatment session, about 90% improvement was noted; at the last treatment session, greater than 95% overall improvement was noted. Two and a half years after the last treatment session, the patient and treating physician noted no regression. A limitation of this therapy is that the combination approach makes it difficult to determine what individual contributions each treatment modality had on the final result. We have illustrated a successful multifaceted treatment regimen for hypertrophic scars and keloids using a combination approach.


Sirolimus eluting coronary stent implantation in patients on maintenance hemodialysis: the OUCH study (outcome of cypher stent inhemodialysis patients).
Pivotal studies on drug-eluting stents have excluded hemodialysis (HD) patients. No quantitative coronary angiography (QCA) analysis has been reported. The OUtcome of Cypher stent in Hemodialysis patients (OUCH) Study is a prospective non-randomized single-arm registry designed to assess the results of sirolimus-eluting stents in HD patients, with follow-up QCA in an independent core laboratory. The primary endpoint was the occurrence of target-vessel failure (TVF) defined as cardiac death, myocardial infarction (MI), and target-vessel revascularization (TVR) at 1 year. A total of 117 patients were enrolled. The TVF rate was 24.9% (2.6% cardiac death, 1.4% MI, 23.9% TVR), and stent thrombosis was documented in 1 patient (0.9%). Coronary calcification was a predictor of TVF. Late lumen loss (LLL) averaged 0.69±0.93mm. The histogram of LLL showed that a total of 76% of lesions were distributed the same normally as that in normal renal function (average LLL 0.20±0.29mm), but 24% of lesions were outliers (average LLL 2.07±0.62mm). This report describes different clinical and QCA results in HD patients as higher TVF rate, different predictive factors, and different histogram of LLL compared with normal renal function. The different histogram of LLL was the existence of many outliers with the same average and the same deviation, suggesting the loss of sirolimus had an effect on a significant number of HD patients.


Phasic brain activity related to the onset of rapid eye movements during rapid eye movement sleep: study of event-related potentials and standardized low-resolution brain electromagnetic tomography.
The function of rapid eye movements (REMs) during REM sleep is still a matter that is open to debate. In a previous study, we found positive brain potential (P200r) time-locked to the onset of REMs. This potential was not observed during saccades of wakefulness. In this study, we estimated the electrical generation of this potential to investigate the phasic brain activity related to REMs. Data were collected in a sleep laboratory from nine healthy university students. REMs during REM sleep were recorded during natural nocturnal sleep. Event-related potential time-locked to the onset of REMs were averaged. Standardized low-resolution brain electromagnetic tomography (sLORETA) was used to identify the current sources of P200r. The results showed that P200r have neuronal generators in the left premotor area, left primary motor and sensory cortices, left inferior parietal lobule and bilateral occipital areas (precuneus, cuneus and lingual gyrus). All these areas are known to contribute to visuomotor processing. These phasic brain activities might play a key role in explaining the function of REMs during REM sleep.


Anti-ischemia/reperfusion of C1 inhibitor in myocardial cell injury via regulation of local myocardial C3 activity.
C3 is common to all pathways of complement activation augmenting ischemia/reperfusion (I/R)-induced myocardial injury and cardiac dysfunction. Complement inhibition with the complement regulatory protein, C1 inhibitor (C1INH), obviously exerts cardioprotective effects. Here, we examine whether C1INH regulates C3 activity in the ischemic myocardial tissue. C1INH markedly suppressed C3 mRNA expression and protein synthesis in both a model of I/R-induced rat acute myocardial infarction (AMI) and the cultured rat H9c2 heart myocytes. At least, this regulation was at the transcriptional level in response to oxygen tension. In vitro, C3 deposition on, and binding to, the surface of rat myocardial cells were significantly blocked by C1INH treatment. C1INH could inhibit classical complement-mediated cell lysis via suppressing the biological activity of C3. Therefore, C1INH, in addition to inhibition of the systemic complement activation, prevents myocardial cell injury via a direct inhibitory role in the local myocardial C3 activity.


Indications for the surgical treatment of hydrocephalic dementia.
Eighteen patients with chronic hydrocephalic dementia who had a ventriculo-atrial or ventriculo-peritoneal shunt are reported. The indications for operating on this type of dementia are discussed on the basis of the clinical and instrumental protocol and the postoperative results.


Plasma ghrelin levels in children with chronic renal failure on peritoneal dialysis.
Malnutrition and loss of appetite represent a serious problem in children with chronic renal failure. Ghrelin is a newly described hormone involved in control of growth hormone secretion, stimulation of food intake, and regulation of energy balance. Plasma ghrelin levels were compared between 12 children on automated peritoneal dialysis (APD) and 9 children on conservative treatment of chronic renal failure. Eight healthy children matched for age and body mass index (BMI) served as a control group. Plasma ghrelin levels were similar in children on APD (698.3 +/- 59.7 pg/mL) and children on conservative treatment (675.4 +/- 41.9 pg/mL) compared to healthy controls (700.1 +/- 24.7 pg/mL). There was no difference in plasma ghrelin levels in children with chronic renal failure regardless of the method of treatment (peritoneal dialysis vs conservative treatment). The plasma ghrelin index was similar in all three investigated groups: APD 40.2 +/- 8.7 vs conservative treatment 39.1 +/- 5.6 vs controls 41.0 +/- 7.8 (pg/mL)/BMI (kg/m2). Plasma ghrelin levels did not correlate with age, duration of dialysis treatment, height, weight, BMI, creatinine and urea levels, adequacy parameters, or nightly glucose load. Plasma ghrelin levels in children on APD were not different from levels in children on conservative treatment or healthy controls with comparable BMI. The persistent state of toxic influence of uremic end-products could be responsible for such a lack of correlation with anthropometrical parameters. Further studies on a larger group of children on APD are needed to clarify the effect of ghrelin on nutritional status in children with chronic renal failure.


Boroxine benzaldehyde complex for pharmaceutical applications probed by electron interactions.
2,4,6-Tris(4-formylphenyl)boroxine (TFPB) is a substituted boroxine containing a benzaldehyde molecule bonded to each boron atom. Boroxine cages are an emerging class of functional nanostructures used in host-guest chemistry, and benzaldehyde is a potential radiosensitizer. Reactions initiated by low-energy electrons with such complexes may dictate and bring new fundamental knowledge for biomedical and pharmaceutical applications. The electron ionization properties of TFPB are investigated using a gas-phase electron-molecule crossed beam apparatus coupled with a reflectron time-of-flight mass spectrometer in an orthogonal geometry. Ionization and threshold energies are experimentally determined by mass spectra acquisition as a function of the electron energy. The abundance of the molecular precursor cation in the mass spectrum at 70 eV is significantly lower than that of the most abundant fragment C7 H5 O+ . Twenty-nine cationic fragments with relative intensities >2% are detected and identified. The appearance energies of six fragment cations are reported, and the experimental first ionization potential is found at 9.46 ± 0.11 eV. Moreover, eight double cations are identified. The present results are supported by quantum chemical calculations based on bound state techniques, electron ionization models and thermodynamic thresholds. According to these results, the TPFB properties may combine the potential radiosensitizer effect of benzaldehyde with the stability of the boroxine ring.


Emergence of vancomycin- and teicoplanin-resistant Enterococcus faecium via vanD5-harbouring large genomic island.
Treatment of VRE is of clinical concern. While certain numbers of vanD-type VRE have been isolated, only two vanD5-harbouring Enterococcus faecium isolates have been reported in Canada and Japan. We report the isolation of vanD5-type E. faecium and the first ever determination of the whole-genome sequence to investigate the possible mechanisms of the acquisition of the vanD5 gene cluster in E. faecium. Two vanD5-harbouring vancomycin-resistant E. faecium were isolated from the skin (SMVRE19) and faeces (SMVRE20) of a patient with a skin ulcer in Japan. The isolates exhibited vancomycin and teicoplanin MIC values of 128 mg/L, whilst the previous isolates of vanD5-harbouring E. faecium were only resistant to vancomycin. SMVRE19 and SMVRE20 were clones related to ST18, which is also seen in vanA- and vanB-type VRE. These isolates harboured an insertion element, ISEfm1, in the ddl gene, similar to a previously described teicoplanin-resistant vanD3-type E. faecium. The vanD5 gene cluster was integrated into the SMVRE20 chromosome as a part of a large genomic island (approximately 127 kb), similar to other recently spreading vanD variants in the Netherlands. The genomic island shared the greatest similarity with a part of the Blautia coccoides genome sequence, except for the region surrounding the vanD gene cluster. This study reports that emergence of vancomycin- and teicoplanin-resistant vanD5-type E. faecium occurred via acquisition of the vanD5 cluster and ISEfm1 insertion into ddl. Considering the genetic similarity between the various VRE strains, the current study should serve as a warning against the spread of vanD5-type VRE.


The role of obesity in sarcopenia and the optimal body composition to prevent against sarcopenia and obesity.
Elderly people with low lean and high fat mass, are diagnosed with sarcopenic obesity (SO), and often have poor clinical outcomes. This study aimed to explore the relationship between obesity and sarcopenia, and the optimal proportion of fat and muscle for old individuals. Participants aged 60 years or above were instructed to perform bioelectrical impedance analysis to obtain the muscle and fat indicators, and handgrip strength was also performed. Sarcopenia was diagnosed according to predicted appendicular skeletal muscle mass and function. Body mass index (BMI) and body fat percentage (BF%) were used to define obesity. The association of muscle and fat indicators were analyzed by Pearson's correlation coefficient. Pearson Chi-Square test was utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) on the risk of sarcopenia according to obesity status. 1637 old subjects (74.8 ± 7.8 years) participated in this study. Not only fat mass, but also muscle indicators were positively correlated to BMI and body weight (p < 0.05). Absolute muscle and fat mass in different positions had positive associations (p < 0.05). Muscle mass and strength were negatively related to appendicular fat mass percentage (p < 0.05). When defined by BMI (OR = 0.69, 95% CI [0.56, 0.86]; p = 0.001), obesity was a protective factor for sarcopenia, whilst it was a risk factor when using BF% (OR = 1.38, 95% CI [1.13, 1.69]; p = 0.002) as the definition. The risk of sarcopenia reduced with the increase of BMI in both genders. It was increased with raised BF% in males but displayed a U-shaped curve for females. BF% 26.0-34.6% in old females and lower than 23.9% in old males are recommended for sarcopenia and obesity prevention. Skeletal muscle mass had strong positive relationship with absolute fat mass but negative associations with the percentage of appendicular fat mass. Obesity was a risk factor of sarcopenia when defined by BF% instead of BMI. The management of BF% can accurately help elderly people prevent against both sarcopenia and obesity.


FDG PET/CT appearance of benign pilomatricoma.
A 56-year-old patient was referred for FDG PET/CT with a right preauricular lymph node fine-needle biopsy, suggesting poorly differentiated carcinoma and no obvious primary lesion. There was intense FDG uptake in the right preauricular nodule. The node was excised, and formal histology demonstrated a benign pilomatricoma rather than malignancy. Pilomatricoma is uncommon in adults and an unusual cause for marked FDG uptake, likely due to foreign body inflammation. Pilomatricoma can be either benign or malignant. The marked FDG uptake demonstrated in our patient with benign pilomatricoma also suggests that FDG PET cannot reliably grade this rare condition.


Effect of Controlled Deposition of ZnS Shell on the Photostability of CdTe Quantum Dots as Studied by Conventional Fluorescence and FCS Techniques.
The effect of one and two monolayers of ZnS shells on the photostability of CdTe quantum dots (QDs) in aqueous and nonaqueous media has been studied by monitoring the fluorescence behavior of the QDs under ensemble and single-molecule conditions. ZnS capping of the CdTe QDs leads to significant enhancement of the fluorescence brightness of these QDs. Considerable enhancement of the photostability of the shell-protected QDs, including the suppression of photoactivation, is also observed. Fluorescence correlation spectroscopy measurements reveal an increase in the number of particles undergoing reversible fluorescent on-off transitions in the volume under observation with increasing excitation power; this effect is found to be more pronounced in the case of core-only QDs than for core-shell QDs.


Kolaviron, a natural antioxidant and anti-inflammatory phytochemical prevents dextran sulphate sodium-induced colitis in rats.
The beneficial effects of kolaviron, a natural biflavonoid from the seeds of Garcinia kola, have been attributed mainly to its antioxidant and anti-inflammatory effects. This study investigated these effects on dextran sulphate sodium (DSS)-induced ulcerative colitis in rats. Sulfasalazine served as standard reference in this study. Kolaviron and sulfasalazine were separately co-administered orally at 200 mg/kg and 500 mg/kg, respectively, to dextran sulphate sodium-exposed rats for 5 days. The result indicated that kolaviron or sulfasalazine significantly prevented DSS-induced body weight loss as well as the incidence of diarrhoea and bleeding in DSS-exposed rats. Kolaviron suppressed the DSS-mediated increase in colonic nitric oxide concentration and myeloperoxidase activity and significantly prevented the increase in inflammatory mediators, interleukin-1β and tumour necrosis factor alpha, in the colon of DSS-treated rats. The significant depletion in colonic antioxidant status in rats exposed to DSS alone was evident by marked reduction in colonic catalase and glutathione S-transferase activities as well as glutathione content, leading to elevated hydrogen peroxide and lipid peroxidation levels. Histopathologically, DSS alone resulted in severe epithelial erosion, total absence of goblet cells, destruction of the crypts, necrotic and distorted glands, accompanied by marked cellular mononuclear cells infiltration. However, administration of kolaviron and sulfasalazine ameliorated DSS-induced colitis by increasing the antioxidant status decreased hydrogen peroxide and lipid peroxidation levels and attenuated the adverse effect of DSS on colon architecture. In conclusion, the anti-colitis effect of kolaviron is related to its intrinsic anti-inflammatory and anti-oxidative properties.


Anxiety Associated With High-resolution Anorectal Manometry in Pediatric Patients and Parents.
High-resolution anorectal manometry is an increasingly common procedure performed in pediatric patients to rule out Hirschsprung and assess anorectal function and sensation. The purpose of the present study was to evaluate anxiety of patients and their parents associated with high-resolution anorectal manometry. Preprocedural anxiety was assessed by standardized questionnaire in all parents and children older than 8 years and observed behavioral distress was recorded by the attending pediatric gastroenterologist. Thirty-five children (mean age = 7.2 years, ±2.8) and their parents completed the study. Patient anxiety was found to be markedly elevated. Observed behavioral distress was elevated compared to more invasive procedures. Self-reported parental anxiety was comparable to adults undergoing endoscopic procedures themselves. Despite the low risk of this procedure, healthcare providers should be aware of the high levels of anxiety and distress that occur in patients and their parents associated with anorectal manometry.


Coarctation of the aorta.
The surgical treatment of an aortic coarctation requires a resection of the stenotic area and direct suture of the aorta. An extended mobilization allows an enlargement of a hypoplastic distal aortic arch. In ductal dependent circulation, the distal aortic arch can be enlarged with a patch before tackling the coarctation itself. Postsurgical aortic arch stenoses often require a surgical intervention. Our preferred method is an anatomic correction with an enlargement plasty either on the concavity or on the convexity of the arch, depending on the local anatomy. An extra-anatomic bypass is also an option.


The burden of atrial fibrillation and other cardiac arrhythmias in an employed population: associated costs, absences, and objective productivity loss.
To establish the burden of atrial fibrillation (AF) and other cardiac arrhythmias (CA) in an employed population. Regression model analysis comparing objective work output, employee turnover, comorbidity prevalence, total health benefit (health care, drug, sick leave, disability, workers' compensation) costs, and absence days for AF versus Non-AF and CA versus Non-CA cohorts, while controlling for differences in patient characteristics. Cohort sizes were 1403 (AF), 323,333 (Non-AF), 4497 (CA), and 318,917 (Non-CA) employees. Annual AF benefit costs exceeded Non-AF costs by $3958. CA costs exceeded Non-CA costs by $2897. AF and CA cohorts had significantly more sick leave and short-term disability absence days than Non-AF and Non-CA cohorts, respectively. Annual CA work output was significantly lower than Non-CA output. AF and CA place significant cost, absence, and productivity burdens on employers.


Changing patterns in dental education.
Since the first dental school was founded nearly 130 years ago, dental education has followed an expanding but relatively unchanging pattern. During the last decade the many social changes taking place in our society have been influencing the profession in such a way that dental education and dental practice must necessarily adjust to satisfy the increasing demands for dental care. The profession is studying ways in which these adjustments can be made most efficiently. It is quite possible that the procedures of dental training and dental practice will change significantly in the future.


Evaporation-reducing Culture Condition Increases the Reproducibility of Multicellular Spheroid Formation in Microtiter Plates.
Tumor models that closely imitate in vivo conditions are becoming increasingly popular in drug discovery and development for the screening of potential anti-cancer drugs. Multicellular tumor spheroids (MCTSes) effectively mimic the physiological conditions of solid tumors, making them excellent in vitro models for lead optimization and target validation. Out of the various techniques available for MCTS culture, the liquid-overlay method on agarose is one of the most inexpensive methods for MCTS generation. However, the reliable transfer of MCTS cultures using liquid-overlay for high-throughput screening may be compromised by a number of limitations, including the coating of microtiter plates (MPs) with agarose and the irreproducibility of uniform MCTS formation across wells. MPs are significantly prone to edge effects that result from excessive evaporation of medium from the exterior of the plate, preventing the use of the entire plate for drug tests. This manuscript provides detailed technical improvements to the liquid-overlay technique to increase the scalability and reproducibility of uniform MCTS formation. Additionally, details on a simple, semi-automatic, and universally applicable software tool for the evaluation of MCTS features after drug treatment is presented.


[Cardiovascular risk factors in diabetic nephropathy].
Diabetic nephropathy is associated with increased cardiovascular mortality. This may be contributed to by changes in plasma lipids, fibrinogen and hemorheology. Cardiovascular autonomic dysfunction, which is related to an increased incidence of arrhythmic death, may also play a role. Therefore, we investigated in 58 IDDM-patients with none (n = 28), incipient (albuminuria 30 to 300 mg/day, n = 11) and overt clinical nephropathy (albuminuria > 300 mg/day, n = 19) plasma concentrations of lipoproteins and fibrinogen, plasma viscosity, erythrocyte aggregation and erythrocyte rigidity. Assessments of neuropathy included tibial nerve motor conduction velocity, perception of vibration, beat-to-beat variation during rest and during forced respiration, heart-rate response to Valsalva maneuver and heart-rate response to standing (30:15). Patients with clinical overt nephropathy had, compared to those without nephropathy, significantly higher concentrations of LDL-cholesterol, triglycerides and fibrinogen, significantly lower concentrations of HDL-cholesterol and significantly higher plasma viscosity, erythrocyte aggregability and erythrocyte rigidity. Regarding the assessments of neuropathy we found in patients with nephropathy, compared to those without nephropathy, significantly reduced tibial nerve motor conduction velocity, reduced perception of vibration thresholds and reduced heart rate variability during rest, during forced respiration, in response to Valsalva maneuver and in response to standing. In diabetic patients with microalbuminuria erythrocyte aggregability and erythrocyte rigidity were significantly higher and heart rate variability during rest was significantly lower than in patients without nephropathy. In clinical overt nephropathy there is an aggregation of different cardiovascular risk factors, namely, disturbances in lipoprotein concentrations, increased fibrinogen concentration and disturbances in hemorheology. Furthermore marked deterioration in peripheral and autonomic cardial nerve function in these patients is evident accounting for a part of the greatly increased cardiovascular mortality of these patients.


Expression of green fluorescent protein in pollen of oilseed rape (Brassica napus L.) and its utility for assessing pollen movement in the field.
Transgene movement via pollen is an important component of gene flow from transgenic plants. Here, we present proof-of-concept studies that demonstrate the monitoring of short distant movement of pollen expressing a genetically encoded fluorescent tag in oilseed rape (Brassica napus L. cv. Westar). Transgenic oilseed rape plants were produced using Agrobacterium-mediated transformation method with the pBINDC1 construct containing a green fluorescent protein (GFP) variant, mGFP5-ER, under the control of the pollen-specific LAT59 promoter from tomato. Transgenic pollen was differentiated from non-transgenic pollen in vivo by a unique spectral signature, and was shown to be an effective tool to monitor pollen movement in the greenhouse and field. GFP-tagged pollen also served as a practical marker to determine the zygosity of plants. In a greenhouse pollen flow study, more pollen was captured at closer distances from the source plant plot with consistent wind generated by a fan. Under field conditions, GFP transgenic pollen grains were detected up to a distance of 15 m, the farthest distance from source plants assayed. GFP-tagged pollen was easily distinguishable from non-transgenic pollen using an epifluorescence microscope.


Production of intestinal and other tumors by 1, 2-dimethylhydrazine dihydrochloride in mice. I. A light and transmission electron microscopic study of colonic neoplasms.
Single or ten weekly subcutaneous injection(s) of 1, 2-dimethylhydrazine dihydrochloride were administered separately to Swiss mice. The repeated application gave rise mainly to high incidences of tumors in the large intestine. These neoplasms occurred most frequently in the colorectal area and in cecum adjacent to ileum. Light microscopically, these lesions were classified as polypoid adenomas and adenocarcinomas. Most of the adenocarcinomas were highly invasive, although they metastasized rarely. The fine structure of the malignant cells exhibited features typical of columnar absorptive cells. A distinctive alteration was the disorderly arrangement and abnormal size and shape of the microvilli. In addition, the cells exhibited numerous free ribosomes, little RER, priminent Golgi bodies, and uniformly dispersed nuclear chromatin. Morphologically, the intestinal tumors were similar to those found in man. In addition, the repeated administration of 1, 2-DMH also induced significant incidences of neoplasms in blood vessels, lungs, anus, and kidneys while the single application produced tumors in blood vessels and liver. The main hypotheses attempting to explain the selective induction of large intestinal neoplasms are discussed.


Cognitive screening instruments in neuropsychiatry: a report of the Committee on Research of the American Neuropsychiatric Association.
A 1994 survey by the Research Committee of the American Neuropsychiatric Association revealed that 58% of respondents employed formal assessment of cognitive status; the Mini-Mental State Examination (MMSE) and neuropsychological testing were the commonest techniques. Literature review on common cognitive screening instruments found that the MMSE has widespread popularity, ease of use, and a large body of research demonstrating its sensitivity to common neuropsychiatric disorders. The Committee recommends that clinicians who employ the MMSE 1) use it as a minimum screening for cognitive dysfunction; 2) employ age- and education-normative corrections; and 3) supplement it with specific measures of spatial functions, delayed memory, and executive abilities. The Modified MMSE and the Neurobehavioral Cognitive Status Examination also show promise as screening tools.


At the Bench: Neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases.
The putative role of neutrophils in host defense against pathogens is a well-recognized aspect of neutrophil function. The discovery of neutrophil extracellular traps has expanded the known range of neutrophil defense mechanisms and catalyzed a discipline of research focused upon ways in which neutrophils can shape the immunologic landscape of certain autoimmune diseases, including systemic lupus erythematosus. Enhanced neutrophil extracellular trap formation and impaired neutrophil extracellular trap clearance may contribute to immunogenicity in systemic lupus erythematosus and other autoimmune diseases by promoting the externalization of modified autoantigens, inducing synthesis of type I IFNs, stimulating the inflammasome, and activating both the classic and alternative pathways of the complement system. Vasculopathy is a central feature of many autoimmune diseases, and neutrophil extracellular traps may contribute directly to endothelial cell dysfunction, atherosclerotic plaque burden, and thrombosis. The elucidation of the subcellular events of neutrophil extracellular trap formation may generate novel, therapeutic strategies that target the innate immune system in autoimmune and vascular diseases.


Blood pressure measurement by eye care practitioners.
We surveyed a random sample of 250 optometrists (OD) and 250 ophthalmologists (MD) in November 1991 to determine if they were involved in blood pressure measurement. A 50.4 percent and 34.8 percent response rate was obtained from ODs and MDs, respectively. Of those responding, 85 percent of the optometrists and 87 percent of the ophthalmologists reported that they did routinely question their patients about blood pressure, while 65.9 percent of the optometrists and 94.2 percent of the ophthalmologists reported owning blood pressure measurement equipment. Of those owning blood-pressure measuring equipment, approximately 20 percent of both professions reported measuring blood pressure on patients with a defined set of historical or observed risk factors. More optometrists should own blood pressure measurement equipment and measure blood pressure on a routine basis. The detection, referral, and co-management of hypertension by optometrists is important in providing primary health care.


Hypopituitarism in association with postaxial polydactyly.
We report four patients, three boys and one girl, with polydactyly and hypopituitarism. All patients had postaxial polydactyly and subnormal growth hormone responses to standard provocative stimuli. Three of these patients had a family history of polydactyly and few other abnormalities. The remaining patient had a major malformation syndrome including a CNS hamartomatous tumor and early death; this patient had no family history of polydactyly. We believe that the association of postaxial polydactyly with hypopituitarism and possible CNS hamartomatous tumors is an important clinical consideration in the evaluation of children with suspected growth hormone deficiency.


Application of soluble dietary fibres in treatment of hyperlipoproteinemias.
Soluble dietary fibres as ingredients of our meal play an important role in both the prevention and treatment of hyperlipoproteinemias. We studied the effect of highly esterified sorbitol-granulated apple pectin on lipid metabolism in patients with hyperlipoproteinemia. They were all female (aged 40 to 60 years)-24 with type IIa and 23 with type IIb hyperlipoproteinemia. The levels of the total plasma cholesterol, the cholesterol in low- and high-density lipoproteins, plasma triglycerides, as well as the lipidogram in these patients were dynamically monitored for three months. Favourable changes of the basic parameters of lipid metabolism were the most essential being the changes in the plasma cholesterol in the first six weeks (P < 0.001). This parameter can adequately be used as a working criterion in controlling the therapeutic effect of pectin in hyperlipoproteinemias types IIa and IIb.


NMR methodology for complex mixture 'separation'.
Mixture 'separation' by NMR is demonstrated through the development of a pseudo 4D NMR experiment, 3D IPAP INEPT-INADEQUATE-HSQC, designed for the structural elucidation of (13)C tagged compounds.


Multi-slice MRI with the dynamic multi-coil technique.
To date, spatial encoding for MRI is based on linear X, Y and Z field gradients generated by dedicated X, Y and Z wire patterns. We recently introduced the dynamic multi-coil technique (DYNAMITE) for the generation of magnetic field shapes for biomedical MR applications from a set of individually driven localized coils. The benefits for B0 magnetic field homogenization have been shown, as well as proof of principle of radial and algebraic MRI. In this study the potential of DYNAMITE MRI is explored further and the first multi-slice MRI implementation in which all gradient fields are purely DYNAMITE based is presented. The obtained image fidelity is shown to be virtually identical to that of a conventional MRI system with dedicated X, Y and Z gradient coils. Comparable image quality is a milestone towards the establishment of fully functional DYNAMITE MRI (and shim) systems.


Non-porous thrombi are less pervious and easier to be retrieved: implication from scanning electron microscopy study.
Scanning electron microscopy (SEM) studies found that the porosity of thrombi might vary among individuals. However, its relationship with the clinical presentation and efficacy of mechanical thrombectomy (MT) remains unknown. We aimed to characterize the ultrastructure of thrombi and explore its association with the complexity of MT and clot perviousness. SEM was used to observe the morphological features of different components of thrombi obtained from patients with anterior circulation large vessel occlusion undergoing MT and to determine the porosity of thrombi by semi-quantitative analysis. Non-porous thrombi were defined as thrombi with porosity <2%. Clot perviousness was also evaluated using thrombus attenuation increase on CT perfusion (TAIctp). We assessed the complexity of MT by attempts of retrieval >3 and procedural duration >60 min, defined as the time interval between groin puncture and recanalization. A total of 49 thrombi were analyzed and 31 (63.3%) were classified as non-porous thrombi. The presence of non-porous thrombi was negatively associated with procedure >60 min (OR 0.152, 95% CI 0.031 to 0.734, p=0.019) and attempts >3 (OR 0.194, 95% CI 0.046 to 0.822, p=0.026) after adjustment. Additionally, receiver operating characteristic curve analysis indicated that TAIctp <17.9 Hounsfield units could predict the presence of non-porous thrombi with an area under the curve of 0.915. Non-porous thrombi on SEM are easier to be retrieved during MT and could be identified as less pervious clots on CT images.


[Development of antibiotherapy at the General Hospital Center R Ballanger of Aulnay-sous-Bois between 1978 and 1986: comparison of 2 prevalence surveys].
Two investigations of the prevalence of antibiotherapy and pathology due to infections have been conducted in 1978 and 1986 in a General Hospital (650 beds). In the first investigation, 29%, and, in the second one, 20% of hospitalized patients received a curative antibiotherapy. Among these patients, microbiology tests scored positive in 44% of cases in the first investigation and in 36% of cases in the second one. In the last inquiry, it was found that: the prescription was adapted to the infection in 95% of cases; the choice of antibiotic was adequate in 78% of curative treatments. Preventive antibiotherapy accounts for 30% of treatments in both investigations. In the second investigation, the prescription was adequate in 97% of cases and the length of treatment was less than 72 hours in 53% of cases. The frequency of Gram-positive cocci infections was increased while Gram-negative bacilli infections were reduced. Between the two investigations, antibiotic treatments have changed. Most noticeably, there is an increase in the number of prescriptions of macrolides, cephalosporins, nitro-imidazole derivatives and a reduction of tetracyclines, urinary antiseptics, quinolones of the 1st generation, sulfamides and penicillins. However, penicillins remain the most commonly used antibiotics family.


Development of a novel prognostic assessment model for hepatitis B virus-related acute-on-chronic liver failure based on reexamination results.
Acute-on-chronic liver failure (ACLF) is a common clinical emergency and critical illness with rapid progression and poor prognosis. This study aims to establish a more efficient system for the prognostic assessment of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), which will provide a guiding scheme for subsequent treatment and improve the survival rate of patients. Data on 623 patients with HBV-ACLF were recorded. Univariate and multivariate analyses were performed to determine the discriminative abilities of the novel prognostic assessment model in predicting 90-day mortality. The area under the receiver operating characteristic curve was used to evaluate the accuracy of the models. Patients were divided into high- and low-scoring groups based on the best critical values, and survival rates were analyzed using Kaplan-Meier survival analysis and compared by applying log-rank tests. The area under the curve of the new scoring system established using the results of the first reexamination, the results of the first examination, the mean daily change in these results (MDCR) and the results of other first examinations were 0.911 (95% confidence interval [CI]: 0.889, 0.933), 0.893 (95% CI: 0.868, 0.917), and 0.895 (95% CI: 0.871, 0.919), respectively. The final prognostic scoring system established using the results of the first reexamination was chosen as a novel prognostic assessment model, and patients with lower scores (first reexamination results [FRER] score ≤ 3.65) had longer survival times (P < .001). The prognostic scoring system established using the FRER combined with other examination results can better assess the prognosis of HBV-ACLF at 90 days.


Culpability, blame, and stigma after pregnancy loss in Qatar.
Following a miscarriage many women report feeling guilty and culpable for what has happened particularly when aspects of societal blame and stigma are involved. This research investigated the impact of cultural context on the experience of miscarriage. In particular, it focused on how elements of stigma and blame are linked to notions of miscarriage etiology and risk among Qatari women. The research used an ethnographic approach. The data was collected over 18 months of fieldwork in Qatar, using semi-structured face to face interviews, and participant observation. A purposive sample of 40 women (primary participants) who had recently miscarried, participated in the study. Potential subjects were initially identified in the Women's Hospital and were consented, and then interviewed in Arabic either in the hospital or at their preferred location. The interviews were audio recorded, transcribed and translated into English. Additional key interviews were performed with 20 secondary participants related to the miscarriage cohort including family members and husbands. Inductive thematic analysis of content was performed manually to extract themes. Two main themes emerged from the material looking specifically at miscarriage aftermaths: rhetorics of blame, self-blame and feelings of guilt; and miscarriage attitudes. Overall society is sympathetic and miscarriage is seen as normal and not particularly worrying, but understood to be upsetting to women. However, findings suggest there is some ambivalence around blame, culpability and stigma applied to miscarriage; some participants perceived miscarriage as a relatively normal and common event, whereas, others felt that miscarriage is resounding stigma and shame. Miscarriage aftermaths are embedded in social, cultural and religious frameworks in relation to notions of risk and causation. Attention should be paid to ensure women and those around them are given appropriate and robust information about miscarriage causation to deflect discourses of blame that may be employed and reduce harm to women who suffer miscarriage.


Effects of the cone angle on the SERS detection sensitivity of tapered fiber probes.
In this paper, we investigate the effects of taper angle on the SERS detection sensitivity using tapered fiber probes with single-layer uniform gold spherical nanoparticles (GSNs). We show that the photothermal damage caused by excessive excitation laser power is the main factor that restricts the improvement of detection sensitivity of tapered fiber probes. Only when the cone angle is appropriate can a balance be achieved between increasing the excitation laser power and suppression of the transmission and scattering losses of the nanoparticles on the tapered fiber surface, thereby obtaining the best SERS detection sensitivity. Furthermore, the optimal cone angle depends on the complex refractive index of the equivalent composite dielectric (ECD) layer containing GSNs. For three SERS fiber probes with different ECD layers, the optimal cone angles measured are between 11-13°.


Interdisciplinary approach to the management of medical supplies in the nursing home setting.
Given the impact of pressure ulcers in institutionalized elderly people, an interdisciplinary approach to the care of ulcers and the management of medical supplies is essential. The aim of this study is to describe and evaluate the management of medical supplies by an interdisciplinary team in order to promote their rational use in the nursinghome setting. An interdisciplinary team was set up, coordinated by a Pharmacy Unit including representatives of 18 elderly nursing homes (1,599 beds). Team interventions were assessed in terms of improvements in the management of wound care supplies. In addition, a retrospective descriptive study was carried out on those patients with pressure ulcers, in order to consider future interventions. The team interventions led to a selection of 15% of the 180 wound care supplies from the public tender process. The monthly savings in wound dressing material purchases was at least 17%. Furthermore, a reduction in consumption greater than 50% was found in 7 centres. The prevalence of ulcers was 5.59%. A fourth of these ulcers were originatedoutside nursing homes. The creation of an interdisciplinary team, in which the pharmacist gets closer to patient needs, and where nurses share responsibility for the selection and management of medical supplies, leads to positive results and represents an opportunity for improvement in elderly care.


Syndrome Differentiation Analysis on Mars500 Data of Traditional Chinese Medicine.
Mars500 study was a psychological and physiological isolation experiment conducted by Russia, the European Space Agency, and China, in preparation for an unspecified future manned spaceflight to the planet Mars. Its intention was to yield valuable psychological and medical data on the effects of the planned long-term deep space mission. In this paper, we present data mining methods to mine medical data collected from the crew consisting of six spaceman volunteers. The synthesis of the four diagnostic methods of TCM, inspection, listening, inquiry, and palpation, is used in our syndrome differentiation. We adopt statistics method to describe the syndrome factor regular pattern of spaceman volunteers. Hybrid optimization based multilabel (HOML) is used as feature selection method and multilabel k-nearest neighbors (ML-KNN) is applied. According to the syndrome factor statistical result, we find that qi deficiency is a base syndrome pattern throughout the entire experiment process and, at the same time, there are different associated syndromes such as liver depression, spleen deficiency, dampness stagnancy, and yin deficiency, due to differences of individual situation. With feature selection, we screen out ten key factors which are essential to syndrome differentiation in TCM. The average precision of multilabel classification model reaches 80%.


Plasmid marker rescue transformation proceeds by breakage-reunion in Bacillus subtilis.
Bacillus subtilis carrying a plasmid which replicates with a copy number of about 1 was transformed with linearized homologous plasmid DNA labeled with the heavy isotopes 2H and 15N, in the presence of 32Pi and 6-(p-hydroxyphenylazo)-uracil to inhibit DNA replication. Plasmid DNA was isolated from the transformed culture and fractionated in cesium chloride density gradients. The distribution of total and donor plasmid DNA was examined, using specific hybridization probes. The synthesis of new DNA, associated with the integration of donor moiety, was also monitored. Donor-specific sequences were present at a density intermediate between that of light and hybrid DNA. This recombinant DNA represented 1.4% of total plasmid DNA. The latter value corresponded well with the transforming activity (1.7%) obtained for the donor marker. Newly synthesized material associated with plasmid DNA at the recombinant density amounted to a minor portion of the recombinant plasmid DNA. These data suggest that, like chromosomal transformation, plasmid marker rescue transformation does not require replication for the integration of donor markers and, also like chromosomal transformation, proceeds by a breakage-reunion mechanism. The extent of donor DNA replacement of recipient DNA per plasmid molecule of 54 kilobases (27 kilobase pairs) was estimated as 16 kilobases.


High-glucose media enhance the responsiveness of tubular cells to growth promoters: effect on lysosomal cathepsins and protein degradation.
Nephromegaly is a prominent feature of diabetic nephropathy and predominantly reflects increased renal tubule mass, mostly due to hypertrophy. To elucidate pathogenetic factors involved, we studied the effects of high glucose (HG) alone, and in combination with hormones/growth promoters: angiotensin II (10(-7) M); parathyroid hormone (10(-7) M); insulin-like growth factor-1 (10(-7) M), or transforming growth factor-beta1 (TGF-beta1, 10 ng/ml) in a renal cell line (LLC-PK1) with many characteristics of the proximal tubule. Activities of lysosomal cathepsins (B, L+B and H) and the protein turnover were investigated. Exposure to HG (25 mM) for up to 48 h increased cellular protein content, due to enhanced protein synthesis, while protein degradation rate and cathepsin activities tended to lower values. Hyperosmotic mechanisms of glucose action were excluded, since these effects were not induced by mannitol. In normoglycemic conditions only TGF-beta1 decreased cathepsin activities and protein degradation rate significantly. However, in HG media all applied hormones/growth factors significantly lowered the protein degradation rate, as well as lysosomal cathepsin activities. The enhanced responsiveness could contribute to the impaired protein turnover, with consequent hypertrophy of the tubulointerstitium in diabetic nephropathy.


Multiscale behavior analysis and molar behaviorism: An overview.
In the context of evolutionary theory, behavior is the interaction between the organism and its environment. Two implications follow: (a) behavior takes time; and (b) behavior is defined by its function. That behavior takes time implies that behavioral units are temporally extended patterns or activities. An activity functions as an integrated whole composed of parts that are themselves smaller-scale activities. That behavior is defined by its function implies that behavior functions to change the environment in ways that promote reproductive success. Phylogenetically important events (PIEs) are enhanced or mitigated by activities they induce as a result of natural selection. Induction explains all the phenomena that have traditionally been explained by reinforcement. This multiscale view replaces discrete responses and contiguity with multiscale activities and covariance. A PIE induces operant activity as a result of covariance in the form of a feedback relation between the activity and the PIE. A signal (conditional inducer) induces PIE-induced activities as a result of covariance between the PIE and the signal. In an ontological perspective, behavior is a process, and an activity is a process individual. For example, ontological considerations clarify the status of delay and probability discounting. A true natural science of behavior is possible.


Searching for the major histocompatibility complex psoriasis susceptibility gene.
Psoriasis, a common skin disorder, is widely regarded to be multifactorial in origin including gene-gene and gene-environment interactions. Genetic and allelic heterogeneity, multifactorial inheritance, and low penetrance of susceptibility alleles substantially complicate both study design and interpretation of results. Notwithstanding these difficulties, genome-wide scans for psoriasis susceptibility have generated robust evidence for a major locus lying within the major histocompatibility complex (PSORS1, Psoriasis Susceptibility 1), on the short arm of chromosome 6. Subsequent studies have sought to refine the PSORS1 boundaries by means of linkage disequilibrium fine mapping. Studies of positional candidate genes have also been undertaken, focusing on HLA-C, corneodesmosin, and alpha-helix coiled-coil rod homolog genes. Methodologic approaches, results, and interpretations of these studies are discussed, as well as future research objectives. In particular, we emphasize the importance of characterizing PSORS1 linkage disequilibrium patterns and developing functional assays for disease-associated alleles.


Stable folding intermediates prevent fast interconversion between the closed and open states of Mad2 through its denatured state.
Different states of metamorphic proteins can interconvert under physiological conditions to realize corresponding functions. The mechanism behind the conversion is critical for understanding how these proteins work. We report a combined thermodynamic and kinetic study on the folding/unfolding process of the open and closed conformers of mitotic arrest deficient protein 2 (Mad2), a metamorphic protein. It has been observed that open Mad2 (O-Mad2) can convert to closed Mad2 (C-Mad2). Our results show that O-Mad2 and C-Mad2 have similar thermodynamic stability, which explains the presence of metamorphosis. The folding/unfolding kinetics suggest that the conversion between O-Mad2 and C-Mad2 would be much faster than that reported previously if this conversion goes through the denatured state (U) directly, i.e. through an O-Mad2-denatured state (U)-C-Mad2 (O-U-C) pathway. This inconsistency implies that there exist stable intermediates in between the native and denatured states of Mad2, which would either slow down the O-U-C interconversion or prevent it going through the denatured state.


Genetic dissection of QTLs for starch content in four maize DH populations.
Starch is the principal carbohydrate source in maize kernels. Understanding the genetic basis of starch content (SC) benefits greatly in improving maize yield and optimizing end-use quality. Here, four double haploid (DH) populations were generated and were used to identify quantitative trait loci (QTLs) associated with SC. The phenotype of SC exhibited continuous and approximate normal distribution in each population. A total of 13 QTLs for SC in maize kernels was detected in a range of 3.65-16.18% of phenotypic variation explained (PVE). Among those, only some partly overlapped with QTLs previously known to be related to SC. Meanwhile, 12 genes involved in starch synthesis and metabolism located within QTLs were identified in this study. These QTLs will lay the foundation to explore candidate genes regulating SC in maize kernel and facilitate the application of molecular marker-assisted selection for a breeding program to cultivate maize varieties with a deal of grain quality.


Different chemo- and endocrino-sensitivity of MCF-7 cells with or without estradiol supplement in vitro.
The sensitivity of MCF-7 cells to tamoxifen (TAM) and mitomycin C (MMC) was assessed in rapidly and slowly growing cells with or without estradiol supplementation, respectively. The growth of MCF-7 was inhibited by MMC in a concentration-dependent manner with or without estradiol (E2) supplementation. Preincubation with MMC suppressed subsequent E2 stimulated growth of MCF-7. TAM inhibited the growth of MCF-7 supplemented with E2 and preincubation with TAM prevented subsequent E2 stimulated growth of MCF-7. However, TAM did not inhibit the growth of MCF-7 cells in E2 free medium. These results suggested that MMC may be more effective than TAM on breast cancer cells in the dormant or slow-growth phase.


Genetic Diversity Analysis of Surface-Related Antigen (SRA) in Plasmodium falciparum Imported From Africa to China.
Plasmodium falciparum surface-related antigen (SRA) is located on the surfaces of gametocyte and merozoite and has the structural and functional characteristics of potential targets for multistage vaccine development. However, little information is available regarding the genetic polymorphism of pfsra. To determine the extent of genetic variation about P. falciparum by characterizing the sra sequence, 74 P. falciparum samples were collected from migrant workers who returned to China from 12 countries of Africa between 2015 and 2019. The full length of the sra gene was amplified and sequenced. The average pairwise nucleotide diversities (π) of P. falciparum sra gene was 0.00132, and the haplotype diversity (Hd) was 0.770. The average number of nucleotide differences (k) for pfsra was 3.049. The ratio of non-synonymous (dN) to synonymous (dS) substitutions across sites (dN/dS) was 1.365. Amino acid substitutions of P. falciparum SRA could be categorized into 35 unique amino acid variants. Neutrality tests showed that the polymorphism of PfSRA was maintained by positive diversifying selection, which indicated its role as a potential target of protective immune responses and a vaccine candidate. Overall, the ability of the N-terminal of PfSRA antibodies to evoke inhibition of merozoite invasion of erythrocytes and conserved amino acid at low genetic diversity suggest that the N-terminal of PfSRA could be evaluated as a vaccine candidate against P. falciparum infection.


Effect of the root canal final rinse protocols on the debris and smear layer removal and on the push-out strength of an epoxy-based sealer.
The aim of the present study was to evaluate the efficacy of QMiX, SmearClear, and 17% EDTA for the debris and smear layer removal from the root canal and its effects on the push-out bond strength of an epoxy-based sealer by scanning electron microscopy (SEM). Forty extracted human canines (n = 10) were assigned to the following final rinse protocols: G1-distilled water (control), G2-17% EDTA, G3-SmearClear, and G4-QMiX. The specimens were submitted to a SEM analysis to evaluate the presence of debris and smear layer, respectively, in the apical or cervical segments. In sequence, forty extracted human maxillary canines with the root canals instrumented were divided into four groups (n = 10) similar to the SEM analysis study. After the filling with AH Plus, the roots were transversally sectioned to obtain dentinal slices. The specimens were submitted to a push-out bond strength test using an electromechanical testing machine. The statistical analysis for the SEM and push-out bond strength studies were performed using the Kruskal-Wallis and Dunn tests (α = 5%). There was no difference among the G2, G3, and G4 efficacy in removing the debris and smear layer (P > 0.05). The efficacy of these groups was superior to the control group. The push-out bond strength values of G2, G3, and G4 were superior to the control group. The ability to remove the debris and smear layer by SmearClear and QMiX was as effective as the 17% EDTA. The final rinse with these solutions promoted similar push-out bond strength values.


Mechanisms of disease: PI3K/AKT signaling in gastrointestinal cancers.
The lipid kinase phosphoinositide 3-OH kinase (PI3K) and its downstream target Akt, also known as protein kinase B (PKB), are crucial effectors in oncogenic signaling induced by various receptor-tyrosine kinases. In recent years, data are accumulating that PI3K/Akt signaling components are frequently altered in a variety of human malignancies. This review summarizes the major effects of PI3K/Akt signaling on proliferation, survival and resistance to apoptosis, angiogenesis and cell motility in gastrointestinal cancers. In addition, activation of PI3K/Akt by various growth factors, the modulation of downstream targets by Akt-induced phosphorylation as well as novel treatment strategies targeting this pathway in gastrointestinal tumors are discussed.


[Chronic circulatory disorders of the digestive organs of the abdominal cavity. Causes, clinical aspects and treatment].
Chronic arterial insufficiency of blood supply to digestive organs in the abdominal region is a specific manifestation of circulatory diseases. It is rare but may cause substantial danger to the patient. Reference is made in this paper to international literature as well as to cases involved in vascular surgery at the Berlin School of Medicine (Charité) for an account of present knowledge on aetiology, pathogenesis, symptoms, diagnosis, and therapy of chronic disorders of abdominal blood supply. Techniques of vascular repair represent an appropriate therapeutic concept, accurate diagnosis and critical indication provided.


Neoadjuvant chemotherapy for radiation-associated soft-tissue sarcoma: A case report.
Radiation-associated sarcomas are rare and aggressive types of sarcomas that can occur after exposure to ionizing radiation. We examine a case of radiation-associated undifferentiated/unclassified soft-tissue sarcoma with primary disease in the chest wall. The optimal treatment of these patients is surgical resection if possible; however, the role of chemotherapy has not been well defined. The patient described herein had a central tumor in the chest wall. Since many of these patients have borderline resectable tumors, the use of neoadjuvant chemotherapy may be helpful to downstage the tumors for possible surgical resection. In this case, doxorubicin plus ifosfamide chemotherapy was employed with a favorable therapeutic effect prior to being resected. To our knowledge this is the first report of greater than 90% necrosis in a patient with radiation-associated undifferentiated/unclassified soft-tissue sarcoma treated with chemotherapy for a borderline resectable mass.


Pulsed-field ionization photoelectron and IR-UV resonant photoionization spectroscopy of Al-thymine.
Al-thymine (Al-C(4)H(3)N(2)O(2)CH(3)) is produced by laser vaporization of a rod made of Al and thymine powders in a molecular beam and studied by single-photon pulsed-field ionization-zero electron kinetic energy (ZEKE) photoelectron and IR-UV resonant two-photon ionization spectroscopy and density functional theory calculations. The ZEKE experiment determines the adiabatic ionization energy of the neutral complex and 22 vibrational modes for the corresponding ion with frequencies below 2000 cm(-1). The IR-UV photoionization experiment measures two N-H and three C-H stretches for the neutral species. The theoretical calculations predict a number of low-energy isomers with Al binding to single oxygen or adjacent oxygen and nitrogen atoms of thymine. Among these isomers, the structure with Al binding to the O4 atom of the diketo tautomer is predicted to be the most stable one by the theory and is probed by both ZEKE and IR-UV measurements. This work presents the first application of the IR-UV resonant ionization to metal-organic molecule systems. Like ZEKE spectroscopy, the IR-UV photoionization technique is sensitive for identifying isomeric structures of metal association complexes.


Role of proteasomes in T cell activation and proliferation.
The role of proteasomes in T cell activation, proliferation, and apoptosis was investigated using a proteasome-specific inhibitor lactacystin (LAC). Inhibition of the proteasome activity by LAC repressed the mitogen-induced T cell proliferation. The proteasome activity was definitively required for the T cells to progress from the G0 to S phase. It was necessary to optimize the progress from the G1/S boundary to the G2/M phase, but not for the progress from the G2/M phase to the next G1 phase. Probably as a result of a blockage of cell cycle progress, the cycling, but not the resting, T cells underwent apoptosis when treated with LAC. Mechanistically, we have found that cyclin-dependent kinase-2 (CDK2) and the cyclin E-associated kinase (largely CDK2), but not CDK4, in the G1 phase were strongly inhibited by LAC. This could be an important mechanism for the proteasome to regulate the cell cycle. The degradation of cyclin E in the late G1 and early S phases was dependent on the proteasome, although it was unlikely that this accounted for the observed inhibition of T cell proliferation. There was a reduced decay of p27Kip1 in the late G1 phase when the proteasome activity was suppressed, and this might be a contributing mechanism for the observed inhibition of CDK2 activity. Interestingly, p21Cip1 was up-regulated during the G1 phase, and the up-regulation was inhibited by LAC. Our study shows that the proteasome plays pivotal roles in regulating T cell activation and proliferation, and its effect is probably exerted through multiple mechanisms.


Is BCG vaccination against tuberculosis still indicated?
More than 70 years after the introduction of BCG vaccination into clinical practice many questions remain to be answered. Major trials produced conflicting results regarding the degree of protection of this vaccine against tuberculosis. Several factors which may contribute to the inconsistent results of these trials, are discussed. In developing countries continuation of routine BCG vaccination of infants is highly recommended considering the ease of administration, low cost, wide availability and safety on the one hand and the protection provided particularly against haematogenous spread of tuberculosis on the other hand. In developed countries the vaccine is reserved for high risk groups since the prevalence of tuberculosis in the general population declined dramatically during the past decades. However, as the incidence of tuberculosis in the Western world no longer decreases steeply and indeed increases again in some countries, and because (para-) medical personnel risks to be among the prime victims of this re-emergence of tuberculosis, rigorously sustained preventive measures to protect this professional category deserve renewed interest. Among those, BCG vaccination can be considered, especially in case of a high prevalence of multidrug-resistant tuberculosis, but also for the Belgian situation with a high degree of non-immune health care workers. Therefore, we believe that BCG vaccination still has a future.


Geographical pattern of malignant neoplasm by cluster analysis using standardized mortality ratios (SMRs) in Ibaraki Prefecture, Japan.
We investigated the geographical patterns of mortality from eight (males)/ten (females) sites of malignant neoplasm, using cluster analysis with Standardized Mortality Ratios (SMRs), and examined the relationship between the mortality structure and urbanization. To explore the geographical tendencies is important for the prevention of cancers; such as noticing risk factors associated with regional variance. The death rates, by site, gender and age from 1990 to 1994 in Japan, were obtained from Vital Statistics. The deaths and population in municipalities were obtained from "Population of Ibaraki Prefecture". These were represented as averaged values in five-year periods. As an indicator of urbanization and mortality structure, the population density of municipalities and the overall rank scores of SMRs were used, respectively. Cluster analysis formed some distinctive structures. For males, Cluster 1 included four municipalities and three of these were located in the mountainous area in northwest Ibaraki, characterized by high SMRs from bone marrow. Cluster 5 consisted of the mid-south areas, characterized by high SMRs from stomach cancer. For females, the clusters seemed to be characterized by SMRs from esophagus cancer. An association between mortality structure and urbanization was found for females, 0.364 (p<0.01), but not for males, 0.162 (p=0.14).


Single molecular dissection of the ligand binding property of epidermal growth factor receptor.
The understanding of ligand binding interactions is an important component of understanding the fundamental mechanism of receptor function. In this study, the binding abilities of EGF and TGF-α to EGFR on human bladder cancer (T24) cells were investigated by single molecular force spectroscopy (SMFS) based on atomic force microscopy (AFM). By approaching the specifically functionalized AFM tips to the T24 cell surface and subsequent retraction, specific unbinding events of the EGF/EGFR complexes and TGF-α/EGFR complexes were investigated. Further, the unbinding forces and the kinetic off rate constants that govern the bond stabilities were calculated through varying the external mechanic forces applied. Meanwhile, the distances from the energy minimum to the transition states along the separation paths of the EGF/EGFR complexes and TGF-α/EGFR complexes were deduced. This study at single-molecule level may enrich our understanding of the ligand binding properties of EGFR and provide some new information to the development of improved EGFR inhibitors. In addition, the results present new insight into the study of the energy landscape of the dissociation of ligand-EGFR system.


Effects of tendon elastic energy and electromyographic activity pattern on jumping height and pre-stretch augmentation during jumps with different pre-stretch intensity.
The present study aimed to investigate the effects of tendon elastic energy and electromyographic activity patterns (ratio of pre-landing to concentric: mEMG PLA/CON; ratio of eccentric to concentric; mEMG ECC/CON) on jump performance. Twenty-nine males performed five kinds of unilateral jumps using only ankle joint (no-countermovement jump: noCMJ; countermovement jump: CMJ; drop jumps at 10, 20 and 30 cm drop height: DJ10, DJ20 and DJ30). Jumping height, pre-stretch augmentation and electromyographic activity of the plantar flexor muscles were measured. The elastic energy of the Achilles tendon was measured during isometric contractions. Relative tendon elastic energy (to body mass) was highly correlated with jumping heights of CMJ, DJ10 and DJ20 but not with noCMJ and DJ30, whereas that was significantly correlated with pre-stretch augmentation in CMJ, but not with three DJs. The mEMG PLA/CON was significantly correlated with the pre-stretch augmentation of DJ20 and DJ30, but not with DJ10, whereas the mEMG ECC/CON was significantly correlated with the pre-stretch augmentation of DJ20 and DJ30, but not with CMJ and DJ10. These results suggested that jumping exercises with low pre-stretch intensity benefited from tendon elastic energy, but those with high pre-stretch intensity benefited from electromyographic activity patterns.


[Effectiveness of otolith strontium marking for juvenile Cyprinus carpio.]
In this study, we evaluated the effectiveness of SrCl2·6H2O to mark otoliths of juvenile common carp (Cyprinus carpio). The carp fish were immersed with four concentrations of the Sr compound (i.e., 0, 4, 8, 12 mg·L-1) for 2 d to determine the essential concentration for immersing. Then, the carp fish were immersed in 8 mg·L-1 of the Sr compound for five different immersing times (i.e., 1, 2, 3, 4, 5 d) to establish the essential immersing time. Results from electron microprobe analysis (EPMA) showed that otolith Sr marks were very obvious in all C. carpio fish of the aforementioned Sr immersed group with high ratio of Sr/Ca concentration and red color (high Sr level) ring map, compared to the control group with low ratio of Sr/Ca concentration and basic blue color (low Sr level) map. We obtained a 100% mark-success rate of otolith Sr marking in juvenile C. carpio. No significant difference were observed on the average body length, mass and mortality between the immersed group and the control group, suggesting that Sr marking had no negative impact on fish. As clear and complete otolith Sr marked rings occurred at concentration of 8 mg·L-1 or more, and immersing time of 2 d or more for the Sr compound, 8 mg·L-1 and 2 d were suggested as the essential immersing Sr concentration and immersing time, respectively. Our results demonstrated the strong feasibility of otolith Sr marking for juvenile C. carpio.


Bacteriophage lambda lysis gene product modified and inserted into Escherichia coli outer membrane: Rz1 lipoprotein.
Lysis proteins of bacteriophage lambda were localized in different parts of the host envelope: S in the inner membrane,36 Rz in the membrane adhesion sites,14 and Rz1 in the outer membrane. The R gene product, the transglycosylase destroying bacterial murein, is a soluble protein. Computer-assisted analysis of the Rz1 protein amino acids sequence revealed that its N-terminal part contained the site 15VVVG [symbol: see text] C20, which could be recognizable for the SPase II and cleaved leaving lipid modified C20 as the N-terminal amino acid of the mature protein. Microsequencing of the Rz1 protein isolated from the expression products of E. coli [pSB54] carrying the Rz1 gene showed that the N-terminal part of the protein was cleaved as predicted. Lipid labeling with [3H]palmitate confirmed the expectation that Rz1 was a lipoprotein. E. coli [pSB54] treated with globomycin accumulated prolipoprotein, the Rz1 precursor, which was detectable by the anti-Rz1 serum on electropherograms as the 6.5-kDa protein, larger than mature protein. Physiological function of the Rz1 protein remains to be discovered, but as a first hint we noticed that it evokes increase of the fraction of adhesion sites of outer and inner membranes when overproduced from pSB54. The same effect was observed in induced E. coli (lambda) just before the lysis onset, however, one should be cautious in interpreting the results obtained in conditions of the overproduction of the Rz1 lipoprotein.


Compost suppressiveness against Phytophthora spp. on Skimmia japonica and azalea.
Suppression of soil-borne plant diseases with composts has been widely studied. Composts have been found to be suppressive against several soil-borne pathogens in various cropping systems. Ornamental plants are generally cultivated in pots, allowing the use of suppressive substrates to control zoospore-producing pathogens, like Phytophthora sp. The objective of the present work was to assess compost suppressiveness against Phytophthora cinnamomi on Rhododendron spp., and against Phytophthora nicotianae, an emerging pathogen on Skimmia japonica. A municipal compost that showed a good suppressive activity in previous trials on vegetable crops was used. Compost was mixed at 10, 20 e 40% (v/v) with a commercial peat substrate, used as control. Substrates have been inoculated at 1g/l dosage of wheat and hemp kernels of Phytophthora spp. and after one week 15-20 plants were transplanted for each treatment in 2 liters volume pots and placed in greenhouse at 20 degrees C. A chemical control (Metalaxil-M) was also used. Diseased plants were assessed weekly after transplanting and above-ground biomass of plants was assessed at the end of the trials. Results showed a significant disease control when compost was used at 20-40% on S. japonica, without showing any phytotoxic effect. Disease suppression was shown at 40% on azalea, but compost was slightly phytotoxic on plants. The use of compost based substrates can be a suitable strategy for controlling soil-borne diseases on ornamentals, but results depend also on alkalinity tolerance of plants.


LFA-1 is a key determinant for preferential infection of memory CD4+ T cells by human immunodeficiency virus type 1.
Memory CD4+ T cells are considered a stable latent reservoir for human immunodeficiency virus type 1 (HIV-1) and a barrier to eradication of this retroviral infection in patients under therapy. It has been shown that memory CD4+ T cells are preferentially infected with HIV-1, but the exact mechanism(s) responsible for this higher susceptibility remains obscure. Previous findings indicate that incorporation of host-derived intercellular adhesion molecule 1 (ICAM-1) in HIV-1 increases virus infectivity. To measure the putative involvement of virus-anchored ICAM-1 in the preferential infection of memory cells by HIV-1, quiescent and activated naive and memory T-cell subsets were exposed to isogenic virions either lacking or bearing ICAM-1. Memory CD4+ T cells were found to be more susceptible than naive CD4+ T cells to infection with ICAM-1-bearing virions, as exemplified by a more important virus replication, an increase in integrated viral DNA copies, and a more efficient entry process. Interactions between virus-associated host ICAM-1 and cell surface LFA-1 under a cluster formation seem to be responsible for the preferential HIV-1 infection of the memory cell subset. Altogether, these data shed light on a potential mechanism by which HIV-1 preferentially targets long-lived memory CD4+ T cells.