Computational modelling of atherosclerosis.
Atherosclerosis is one of the principle pathologies of cardiovascular disease with blood cholesterol a significant risk factor. The World Health Organization estimates that approximately 2.5 million deaths occur annually because of the risk from elevated cholesterol, with 39% of adults worldwide at future risk. Atherosclerosis emerges from the combination of many dynamical factors, including haemodynamics, endothelial damage, innate immunity and sterol biochemistry. Despite its significance to public health, the dynamics that drive atherosclerosis remain poorly understood. As a disease that depends on multiple factors operating on different length scales, the natural framework to apply to atherosclerosis is mathematical and computational modelling. A computational model provides an integrated description of the disease and serves as an in silico experimental system from which we can learn about the disease and develop therapeutic hypotheses. Although the work completed in this area to date has been limited, there are clear signs that interest is growing and that a nascent field is establishing itself. This article discusses the current state of modelling in this area, bringing together many recent results for the first time. We review the work that has been done, discuss its scope and highlight the gaps in our understanding that could yield future opportunities.


Leadership strategies for department chairs and program directors: a case study approach.
As a part of the 2000-01 American Dental Education Association (ADEA) Leadership Institute, the Leadership Institute Fellows conducted a faculty development workshop for department chairpersons and program directors during the 2001 ADEA Annual Session. A central premise of the workshop was that successful chairpersons and program directors are both effective leaders and effective managers and that leadership and management involve complementary activities. The workshop was case-based. The ADEA Leadership Institute Fellows developed the cases and led roundtable discussions of each case. A group facilitator led large group debriefings to apply management and leadership theory to each case. The purpose of this paper is to review leadership challenges and management concepts as they were applied in a case-based faculty development workshop. The program was structured to address leadership challenges relating to managing people, mission management, conflict recognition, and conflict management. The cases were developed to relate management theories to situations in academic administration. The situations were designed to encourage debate from numerous perspectives. Each case presented general dilemmas that could be addressed from the vantage point of the dean, chair, or individual faculty member. Reinforcing discussion followed and included identification of central issues, key management concepts, and action alternatives. Because of the breadth of possible discussion, group case analyses at the workshop and in the appended case reviews explore only one perspective. This overview article introduces concepts of leadership and management that provide the foundation for analysis of three case studies that follow. These cases address common leadership and management issues in academic dentistry through three typical cases: the frustrated faculty member (case 1), the misdirected faculty member (case 2), and the faculty member stuck in the middle (case 3).


The use of Preston enrichment broth for the isolation of 'thermophilic' campylobacters from water.
The application of Preston enrichment broth to isolation of 'thermophilic' campylobacters from water has been investigated. Enrichment substantially increased the yield of such organisms. The optimum timing for subculturing the broth was after 48 h incubation. Despite the addition of aerotolerant supplement to the broth the number and variety of isolates was greater when the broth was incubated microaerically than when it was incubated in air.


Mood states determine the degree of task shielding in dual-task performance.
Current models of multitasking assume that dual-task performance and the degree of multitasking are affected by cognitive control strategies. In particular, cognitive control is assumed to regulate the amount of shielding of the prioritised task from crosstalk from the secondary task. We investigated whether and how task shielding is influenced by mood states. Participants were exposed to two short film clips, one inducing high and one inducing low arousal, of either negative or positive content. Negative mood led to stronger shielding of the prioritised task (i.e., less crosstalk) than positive mood, irrespective of arousal. These findings support the assumption that emotional states determine the parameters of cognitive control and play an important role in regulating dual-task performance.


Effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin on cold water swimming stress-induced antinociception in the mouse.
1. The cold (4 degrees C) water swimming stress (CWSS) for 3 min significantly increased the inhibition of the tail-flick response in ICR mice. 2. Pertussis toxin (PTX, 0.05-0.5 microgram) in mice pretreated intrathecally (IT) for 6 days attenuated the inhibition of the tail-flick response induced by CWSS. However, intracerebroventricular (ICV) pretreatment with PTX at the same doses did not affect CWSS-induced inhibition of the tail-flick inhibition. 3. 3-Isobutyl-1-methylxanthine (IBMX, 0.01-1 ng) in mice pretreated IT for 10 min dose-dependently attenuated the inhibition of the tail-flick response induced by CWSS. However, IBMX in mice ICV pretreated ICV at the same doses was not effective in attenuating the CWSS-induced inhibition of the tail-flick response. 4. Neither IT nor ICV pretreatment with cholera toxin (CTX, 0.05-0.5 microgram) for 24 hr affected the inhibition of the tail-flick response induced by CWSS. 5. The ICV or IT injection of PTX, CTX, or IBMX did not affect the basal tail-flick response latency. 6. It is concluded that spinal, but not supraspinal, PTX-sensitive G-proteins and cAMP phosphodiesterase may be involved in the antinociception produced by CWSS. However, neither spinal nor supraspinal CTX-sensitive G-proteins appear to be involved in mediating the antinociception induced by CWSS.


[Quantitative analysis of contrast enhanced MRI of the inferior alveolar nerve in inflammatory changes of the mandible].
To evaluate the role of contrast enhanced MRI in quantifying signal changes of the inferior alveolar nerve following inflammatory changes of the mandible. 30 patients with inflammatory changes of the mandible underwent MRI of the face. Both sides of the mandible, the affected as well as the unaffected healthy side were evaluated retrospectively. Regions of interest were placed at 5 defined places on both sides to assess signal intensity before and after intravenous application of paramagnetic contrast agent. The results of the measurements were compared between the healthy and the affected side (t-test, p < 0.05) and correlated with clinical findings (t-test, p < 0.05). All patients with hypesthesia of the inferior alveolar nerve in areas of the lips or chin (n = 4) showed a marked increase in signal intensity from 35 % to 83 % distal to the inflammatory process. Patients without sensitivity disorders showed less increase in signal intensity with a maximum of 51 % distal to the inflammatory process. In nearly all patients no contrast enhancement was observed distal to the first molar on the unaffected side. Quantitative analysis of contrast enhanced MRI of the neurovascular bundle is able to show pathologic mandibular lesions. In case of inflammatory changes of the mandible the neurovascular bundle is able to show pathologic mandibular lesions. In case of inflammatory changes of the mandible, the neurovascular bundle shows a significant increase in signal intensity distal to the lesion compared to the unaffected healthy side of the mandible.


Recent Progress in Wireless Sensors for Wearable Electronics.
The development of wearable electronics has emphasized user-comfort, convenience, security, and improved medical functionality. Several previous research studies transformed various types of sensors into a wearable form to more closely monitor body signals and enable real-time, continuous sensing. In order to realize these wearable sensing platforms, it is essential to integrate wireless power supplies and data communication systems with the wearable sensors. This review article discusses recent progress in wireless technologies and various types of wearable sensors. Also, state-of-the-art research related to the application of wearable sensor systems with wireless functionality is discussed, including electronic skin, smart contact lenses, neural interfaces, and retinal prostheses. Current challenges and prospects of wireless sensor systems are discussed.


A simple electrode for metallic replication.
A simple resistive heating electrode has been designed for use in metallic replication procedures. The electrodes are relatively small, reliable, adaptable to most vacuum systems, and are compatible with ultra-high vacuums. They are easily aligned, have good electrical conductivity and ajustable tensions. Using these electrodes with full wave rectified a.c., we found reduced specimen heating, lower background granularity, and improved resolution compared to commercially available designs.


Quantitative vascular outgrowth and anatomic and refractive outcomes of eyes treated with bevacizumab in posterior zone Ⅰ.
To report the anatomic and refractive outcomes and retinal vascular outgrowth in eyes with posterior zone Ⅰ retinopathy of prematurity (ROP) treated with intravitreal bevacizumab (IVB). Thirty-eight eyes of 21 infants treated with IVB for type 1 and aggressive-ROP, and whose posterior border of retinal vascularization was shorter than the optic disc-to-fovea distance were defined as posterior zone Ⅰ and included in the study. Nine eyes of five infants whose follow-up time was lower than four months were accepted as insufficient for clinical outcomes. Additional treatment(s) had been performed up to 60 weeks postmenstrual age (PMA) in 10 of 29 eyes whose follow-up were higher than four months. Macula was attached at the final examination in all eyes with > 4 months follow-up. Anatomical outcome of two eyes of one infant was accepted as unfavorable whose routine follow-up was interrupted after successful initial treatment and who was presented with straightening of the temporal vascular arcade and residual fibrovascular tractional bands on the temporal periphery. The mean progression of temporal retinal vascularization was 3.6 ± 2.0 horizontal disc diameters (DD) within 7.3 weeks and 5.1 ± 2.5 horizontal DD within 69.1 weeks in the short-term (n=15) and long-term evaluated eyes (n=21), respectively. The mean spherical equivalent was -4.1 diopters at a mean age of 21 months (n=28). A favorable outcome had been achieved in almost all bevacizumab-treated eyes, but additional treatments were required. Significant progression of retinal vascularization was detected even in the eyes with short follow-up.


A promising candidate with D-A-A-A architecture as an efficient sensitizer for dye-sensitized solar cells.
A series of metal-free organic dyes with electron-rich (D) and electron-deficient units (A) as π linkers have been studied theoretically by means of density functional theory (DFT) and time-dependent DFT calculations to explore the effects of π spacers on the optical and electronic properties of triphenylamine dyes. The results show that Dye 1 with a structure of D-A-A-A is superior to the typical C218 dye in various key aspects, including the maximum absorption (λmax =511 nm), the charge-transfer characteristics (D/Δq/t is 5.49 Å/0.818 e(-) /4.41 Å), the driving force for charge-carrier injection (ΔGinject =1.35 eV)/dye regeneration (ΔGregen =0.27 eV), and the lifetime of the first excited state (τ=3.1 ns). It is thus proposed to be a promising candidate in dye-sensitized solar cell applications.


[Adrenoleukodystrophy and adrenomyeloneuropathy. Clinical biochemical and molecular genetic findings].
Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disease affecting 1 in 20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy (AMN) in adulthood. Recently, the ALD gene has been identified by positional cloning. We report three males patients with AMN and a fourth patient with juvenile ALD. Biochemical studies showed elevated plasma concentration of saturated very-long-chain fatty acids. Genomic DNA of the patients was analysed for possible sequence variations in the ALD gene by PCR amplification and single strand conformation polymorphism analysis. Three missense mutations (Ser515Phe, Glu267Lys and Arg401Trp) and a 9-bp deletion were detected predicting, respectively, the replacement and absence of amino acids in the deduced amino acid sequence of the ALD protein. In the patients' families, detection of the respective mutations allows the identification of carriers of ALD/AMN. Mutational screening in ALD families is of practical importance in improving genetic counseling.


Diets varying in ratio of sweet sorghum silage to corn silage for lactating dairy cows: Feed intake, milk production, blood biochemistry, ruminal fermentation, and ruminal microbial community.
The objective of this study was to investigate the effects of partial substitution of corn silage (CS) with sweet sorghum silage (SS) in the diets of lactating dairy cows on dry matter (DM) intake, milk yield and composition, blood biochemistry, and ruminal fermentation and microbial community. Thirty mid-lactation Holstein dairy cows [mean ± standard deviation; 639 ± 42.0 kg of body weight; 112 ± 24.0 d in milk (DIM)] were assigned to 3 groups (n = 10/treatment) by considering parity, milk yield, and DIM. The cows were fed ad libitum total mixed rations containing 55% forage and 45% concentrate, with only the proportion of CS and SS varying in 3 treatments (DM basis): SS0 (0% substitution of CS), 40% CS and 0% SS; SS25 (25% substitution of CS), 30% CS and 10% SS; and SS50 (50% substitution of CS), 20% CS and 20% SS. Dry matter intake and milk protein concentration tended to linearly decrease with increasing proportion of SS in the diet. Yields of milk (mean ± standard deviation, 30.9 ± 1.12 kg/d), 4% fat-corrected milk (30.0 ± 0.81 kg/d), energy-corrected milk, milk protein, lactose, and total solids, concentrations of milk fat, lactose, somatic cell counts, and milk efficiency did not differ among diets. The concentrations in blood of urea nitrogen, phosphorus, aspartate aminotransferase, and malondialdehyde linearly increased with increasing SS proportion. Blood IgA decreased with increasing SS substitution rate, but blood IgG and IgM were not different among diets. Ruminal pH did not differ among diets, whereas ruminal NH3-N concentration quadratically changed such that it was greater for SS50 than for SS0 and SS25. Molar proportions of propionate and acetate to propionate ratio were less for SS25 than for SS0. Although the diversity and general ruminal microbial community structure were not altered by partially replacing CS with SS, the relative abundances of predominant bacteria were affected by diets at the phylum and genus levels. Firmicutes and Bacteroidetes were dominant phyla in the ruminal bacterial community for all diets, and their relative abundance linearly decreased and increased, respectively, with increasing SS substitution rate. Prevotella_1 and Ruminococcaceae_NK4A214_group were detected as the most and the second most abundant genera, with their relative abundance linearly increased and decreased, respectively, with increasing SS substitution rate. The relative abundance of Fibrobacter linearly increased with increasing dietary SS proportion, with greater abundance observed for SS25 and SS50 than for SS0. These results suggest that substitution of CS with SS altered the relative abundances of some predominant bacteria; however, these changes had little effect on ruminal fermentation and milk yield. Under the current experimental conditions, substituting up to 50% of CS with SS had no negative effects on milk yield, indicating that SS can partially replace CS in the diets of high-producing lactating dairy cows without adding extra grain, when diets are fed for a short time. As the effects of substituting CS with SS depend upon the chemical composition and digestibility of these silages and the nutrient requirements of the cows, additional grain may be required in some cases to compensate for the lower starch content of SS.


Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression.
GH, prolactin (PRL), and IGF-I stimulate lactation-related metabolic processes in mammary epithelial cells. However, the ability of these factors to stimulate milk production in animals varies depending on species and experimental variables. Previous work in our laboratory demonstrated that transgenic overexpression of des(1-3)IGF-I within the mammary glands of lactating mouse dams increased lactation capacity during prolonged lactation. This work also suggested that some of the effects of the overexpressed IGF-I may have been mediated through elevated concentrations of IGF-I or PRL in the systemic circulation. In the present study, murine GH and PRL, and a human IGF-I analog, long-R3-IGF-I (LR3), were administered as s.c. injections to compare their ability to enhance milk production, and alter mammary gland signaling and gene expression. Lactation capacity, as measured by litter gain, was increased (P<0.05) by GH, but not by PRL. LR3 increased (P<0.05) mammary phospho-Akt and suppressors of cytokines signaling 3 (SOCS3) gene expression, and had a modest ability to increase (P<0.05) lactation capacity. GH both increased (P<0.05) mammary SOCS1 expression and decreased (P<0.05) mammary expression of tryptophan hydroxylase 1, the rate-limiting enzyme in the synthesis of serotonin and a potential feedback inhibitor of lactation. These results suggest that while both GH and IGF-I stimulate milk production in the lactating mouse, the effect of GH may be additionally mediated through IGF-I-independent effects associated with repression of mammary serotonin synthesis.


DNA restriction polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster: a genetic determinant of atherosclerosis in type 2 (non-insulin-dependent) diabetes mellitus.
The presence of polymorphic restriction sites (S2, M2, P2) of the apolipoprotein AI-CIII-AIV gene cluster for the respective Sst1, Msp1, and Pst1 enzymes was assessed after hybridization with a radiolabelled apolipoprotein AI gene probe in 64 Type 2 diabetic patients and 67 healthy control subjects, all Europids. Twenty-two diabetic patients showed evidence of ischaemic heart disease or macrovascular arteriopathy and forty-two were free of cardiovascular complications. Control subjects were selected for the absence of personal or familial metabolic or cardiovascular diseases. The frequencies of polymorphic alleles were in agreement with previous studies in the control group: S2 6.3 (95% confidence interval (CI) 2.3-10.3) %, M2 5.5 (1.6-9.4) %, P2 6.3 (2.3-10.3) % and did not differ in the whole diabetic group: S2 4.2 (0.7-7.7) %, M2 6.5 (2.0-11.0) %, P2 6.6 (2.3-10.9) %. The relative prevalences of S2, M2, and P2 alleles were, respectively: 3.32, 1.54, and 2.00 (Woolf's ratio) in the macroangiopathic group but allele distribution frequencies were not statistically different from non-macroangiopathic patients. The allelic associations S2M2P1 and S1M1P2 showed a relative prevalence of 2.86 and 2.00 in the presence of cardiovascular complications but the difference was not significant in terms of polyallelic distribution frequencies in the absence of atherosclerosis. No serum lipid abnormalities could be related to the presence of any polymorphic allele or allelic association. These results suggest a genetic influence on the development of atherosclerosis in Type 2 diabetes, but the mechanism remains unclear.


The imbalance of sex-hormones related to depressive symptoms in obese men.
Obese men may present hypogonadothrofic hypogonadism, mainly related to higher insulinemia and aromatase activity. Our objectives were to evaluate the relationship of sex-hormones profiles and frequency of depressive symptoms in 43 obese men, in a cross-sectional study. They had 19-60 years, and body mass index 30-50 kg/m(2). LH, total and free testosterone (TT and FT), estradiol (E2), sex hormone binding globulin, estradiol/total testosterone ratio (E2/T) were analyzed. Depressive symptoms were evaluated by "beck depression inventory" (BDI), and significant depression was considered if BDI ≥ 16.Thirty-four (80%) presented low TT levels, but only 4 (14%) had low free testosterone and hypogonadism symptoms; 12 of 43 (28%) presented increased E2. Forty five (56%) presented depressive symptoms, but 16 (28% of the 45) had significant depression. BDI correlated positively with E2 (r = 0.407; p = 0.001) and E2/T (r = 0.473; p = 0.001), but not TT or FT. Patients with significant depressive showed higher levels of estradiol (136 ± 48 versus 103 ± 48 pg/ml, p = 0.02) and E2/T (16.0 ± 9.9 versus 9.8 ± 4.6; p = 0.002) (mean ± SD).In conclusion, obese men may present relatively excess of estradiol and deficiency in testosterone, leading to an imbalance between these two hormones. The greater this imbalance, the more depressive symptoms had our patients.


Lignin-Based Carbon Nanofibers as Electrodes for Vanadium Redox Couple Electrochemistry.
Three different types of lignin (kraft, organosolv and phosphoric acid lignin) were characterized and tested as precursors of electrospun nanofibers. Polyethylene oxide (PEO) was added as a plasticizer and dimethyl formamide (DMF) employed as a solvent. It was found that the molecular weight of lignin was the key parameter to understand the differences of the mechanical stability of the resultant fiber mats. In the case of kraft lignin (KL), the influence of some changes in the synthetic process was also tested: applied voltage, pretreatment in air or not, and the addition of a small amount of Ketjen black. After pyrolysis in nitrogen flow, the obtained carbon nanofibers (CNFs) were characterized by different techniques to analyze their differences in morphology and surface chemistry. Vanadium electrochemistry in 3M sulfuric acid was used to evaluate the different CNFs. All fibers allowed electrochemical reactions, but we observed that the oxidation of V(II) to V(III) was very sensitive to the nature of the raw material. Materials prepared from kraft and phosphorus lignin showed the best performances. Nevertheless, when 1 wt.% of Ketjen black was added to KL during the electrospinning, the electrochemical performance of the sample was significantly improved and all targeted reactions for an all-vanadium redox flow battery were observed. Therefore, in this work, we demonstrated that CNFs obtained by the electrospinning of lignin can be employed as electrodes for vanadium electrochemistry, and their properties can be tuned to improve their electrochemical properties.


Effects of acetylsalicylic acid on human platelet function in vivo at salicylate steady state.
The results of clinical trials concerning the use of acetylsalicylic acid (ASA) as antithrombotic drug are contradictory. Inhibition by ASA of platelet prostaglandin synthesis and aggregation is prevented by its metabolite salicylic acid (SA) in animals and in human platelets in vitro. It was suggested that ASA might produce its own inhibitor, thereby diminishing its efficiency in thromboembolic disease. In four healthy male subjects there was no difference in inhibition of collagen-induced platelet aggregation after the administration of 500 mg ASA alone or at salicylate steady state (3 g SA daily). But the inhibition of tissue-extract-induced platelet shape change was diminished and shortened by pretreatment with SA. We conclude that SA does not inhibit the effects of ASA on human platelet aggregation in vivo in therapeutic dose ranges. The clinical importance of the SA/ASA-interaction on tissue-extract-induced platelet shape change remains to be clarified.


Bilateral central scotomata due to intracranial tumour.
Bilateral centrocaecal scotomata have been recognised as a sign of intrinsic optic nerve disease, usually associated with hereditary optic neuropathy, and nutritional or toxic amblyopias. This report describes four patients with central scotomata due to intracranial masses, three of whom recovered after surgical intervention. The clinician should be alerted to the association in patients with headaches, other neurological signs, and central visual loss.


Effect of Morris 7777 hepatoma on microsomal glucose-6-phosphatase latent activity.
The change in the activity of several hepatic enzymes during hepatocarcinogenesis suggests a pattern of dedifferentiation. This category of enzymes includes glucose-6-phosphatase and gamma-glutamyltranspeptidase (GGT). A detailed kinetic analysis of microsomal glucose-6-phosphatase activity revealed that both the translocase and phosphohydrolase activities were markedly reduced in Morris 7777 hepatoma transplanted in male Buffalo rats. In addition, the activity of the translocase component increased 2.4-fold, while the phosphohydrolase activity decreased 1.6-fold in the liver of tumor-bearing animals. GGT activity in the host liver was not effected by the presence of the tumor. These results suggest differences in the effect of Morris 7777 hepatoma on: the phosphohydrolase and translocase activities of microsomal glucose-6-phosphatase and the sensitivity of glucose-6-phosphatase and GGT activities in the host liver.


Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study.
The aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study. Data were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index. Compared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069-1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032-1.736; p = 0.0277). High carbohydrate antigen 19-9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261-2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199-1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001). Our large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes.


Measuring social class in US public health research: concepts, methodologies, and guidelines.
Increasing social inequalities in health in the United States and elsewhere, coupled with growing inequalities in income and wealth, have refocused attention on social class as a key determinant of population health. Routine analysis using conceptually coherent and consistent measures of socioeconomic position in US public health research and surveillance, however, remains rare. This review discusses concepts and methodologies concerning, and guidelines for measuring, social class and other aspects of socioeconomic position (e.g. income, poverty, deprivation, wealth, education). These data should be collected at the individual, household, and neighborhood level, to characterize both childhood and adult socioeconomic position; fluctuations in economic resources during these time periods also merit consideration. Guidelines for linking census-based socioeconomic measures and health data are presented, as are recommendations for analyses involving social class, race/ethnicity, and gender. Suggestions for research on socioeconomic measures are provided, to aid monitoring steps toward social equity in health.


Inhibition of protein synthesis in intact HeLa cells by Shigella dysenteriae 1 toxin.
Shiga toxin purified to near homogeneity from cell lysates of Shigella dysenteriae 1 inhibited protein and deoxyribonucle acid syntheses in intact HeLa cells. Inhibition was dependent on toxin concentration and time of incubation. A minimal latent period of 30 min was observed with saturating doses of toxin. Ribonucleic acid synthesis, uptake of alpha-aminoisobutyric acid, and maintenance of intracellular K+ concentrations were not affected until well after maximal inhibition of protein and deoxyribonucleic acid syntheses. The inhibitory effect of toxin was sensitive to heat inactivation and was prevented by antibody neutralization. Several cytotoxic components were separated by polyacrylamide gel electrophoresis of the purified toxin preparations; all inhibited protein and deoxyribonucleic acid syntheses equally.


[A clinical analysis of 10 cases with cardiac lymphoma].
Objective: To analyze the morbidity, clinical characteristics, therapeutic outcomes and prognosis of cardiac lymphoma. Methods: Individual patient data were obtained from pathology defined 10 cases of cardiac lymphoma from Jan 2000 to Jun 2016. The patient's general information, clinical manifestation, pathological diagnosis, laboratory examination, cardiac involvement feature, cardiac complications, treatment, therapeutic effect and prognosis were analyzed. Results: Of 3 918 cases of lymphoma patients, 10 cases of cardiac involvement were identified, including primary cardiac lymphoma (PCL) in 1 case, secondary cardiac lymphoma (SCL) in 9 cases. Of the 10 patients in our analysis, the male-to-female ratio was 3∶2, with a median age of 55 (19-88) years old. The most presenting complaints were dyspnea in 7 cases, followed by chest pain in 5 cases, fatigue in 2 patients and edema in 2 cases. Pathological types included diffuse large B cell lymphoma (DLBCL) in 7 cases, T cell lymphoma (T-LBL) in 1 case, Hodgkin's lymphoma (HL) in 1 case, and Burkitt lymphoma (BL) in 1 case. The sites of the heart affected by lymphoma in the PCL patient were right and left atriums with multiple nodules; and for SCL, the sites were mainly pericardium associated with a pericardial effusion in 5 cases, a pericardial mass in 2 cases. Congestive heart failure affects 7 patients and cardiac arrhythmias were identified in 4 cases mainly sinus tachycardia, atrial fibrillation and atrioventricular block. Except one untreated because of old age and poor performance, the rest of 9 patients were treated by either chemotherapy in 4 cases or chemotherapy combined radiotherapy (including the extracardiac sites) in 5 patients. With the median follow-up of 9 months, the one PCL patient achieved partial response (PR) , progress free survival (PFS) for 6 months and the overall survival (OS) for 21 months; in the cohort of 6 SCL patients cardiac involved at diagnosis, complete response (CR) was achieved in 1 case (16.7%) , PR in 3 cases, progressing disease (PD) in 2 cases, with the median PFS for 5 months and the median OS for 19 months; and for the other 3 SCL patients cardiac involved at progression, PR was achieved in 2 case and death in 1 case, with the median PFS for 4 months and the median OS unavailable because of censored data. Conclusion: Cardiac lymphoma represents a rare subset of lymphoma, the most common type is DLBCL, and the main clinical manifestations are dyspnea and chest pain, always combined by arrhythmia and congestive heart failure. The main therapeutic regimen for cardiac lymphoma includes combined chemotherapy and the prognosis for patients with either PCL or SCL is usually poor.


A 55-kDa endonuclease of mammalian mitochondria: comparison of its subcellular localization and endonucleolytic properties with those of endonuclease G.
A novel endonuclease of 55-kDa was found in rat liver mitochondria by a zymographic assay, in addition to the 29 kDa enzyme that is well-known as endonuclease G (Endo G). Subcellular localization of these enzymes in rat liver cells was examined by biochemical fractionation. Endo G was located in both nuclei and mitochondria as has been previously reported, while the 55-kDa enzyme was only detected in the mitochondrial fraction. The levels of the endonucleases in the mitochondria varied greatly among the rat organs, and the activity in the heart was about 30 times higher than that in the liver. The 55-kDa enzyme and Endo G were extracted from bovine heart mitochondria with 0.4 M NaCl. During purification the 55-kDa enzyme and Endo G were copurified because of their similar chromatographic behavior, so they were separated by gel filtration or electrophoresis in the presence of SDS and the proteins were then renatured. The nucleolytic properties of the 55-kDa enzyme resembled those of Endo G and other known mitochondrial nucleases. The enzyme degraded single-stranded DNA more rapidly than duplex DNA at a weak alkaline pH1 requiring Mg2+ or Mn2+ but not Ca2+ or Zn2+. Nicks generated by the enzyme had 5'-P and 3'-OH ends. The 55-kDa enzyme, like Endo G, displayed an unusually strong preference to nick within a (dG)n.(dC)n tract.


Mitochondrial heteroplasmy and paternal leakage in natural populations of Silene vulgaris, a gynodioecious plant.
It is currently thought that most angiosperms transmit their mitochondrial genomes maternally. Maternal transmission limits opportunities for genetic heterogeneity (heteroplasmy) of the mitochondrial genome within individuals. Recent studies of the gynodioecious species Silene vulgaris and Silene acaulis, however, document both direct and indirect evidence of mitochondrial heteroplasmy, suggesting that the mitochondrial genome is at times transmitted via paternal leakage. This heteroplasmy allows the generation of multi-locus recombinants, as documented in recent studies of both species. A prior study that employed quantitative PCR (q-PCR) on a limited sample provided direct evidence of heteroplasmy in the mitochondrial gene atp1 in S. vulgaris. Here, we apply the q-PCR methods to a much larger sample and extend them to incorporate the study of an additional atp1 haplotype along with two other haplotypes of the mitochondrial gene cox1 to evaluate the origin, extent, and transmission of mitochondrial genome heteroplasmy in S. vulgaris. We first calibrate our q-PCR methods experimentally and then use them to quantify heteroplasmy in 408 S. vulgaris individuals sampled from 22 natural populations located in Virginia, New York, and Tennessee. Sixty-one individuals exhibit heteroplasmy, including five that exhibited the joint heteroplasmy at both loci that is a prerequisite for effective recombination. The heteroplasmic individuals were distributed among 18 of the populations studied, demonstrating that heteroplasmy is a widespread phenomenon in this species. Further, we compare mother and offspring from 71 families to determine the rate of heteroplasmy gained and lost via paternal leakage and vegetative sorting across generations. Of 17 sibships exhibiting cox1 heteroplasmy and 14 sibships exhibiting atp1 heteroplasmy, more than half of the observations of heteroplasmy are generated via paternal leakage at the time of fertilization, with the rest being inherited from a heteroplasmic mother. Moreover, we show that the average paternal contribution during paternal leakage is about 12%. These findings are surprising, given that the current understanding of gynodioecy assumes that mitochondrial cytoplasmic male sterility elements are strictly maternally inherited. Knowledge of the dynamics of mitochondrial populations within individuals plays an important role in understanding the evolution of gynodioecy, and we discuss our findings within this context.


[Large loop transformation zone excision in premalignant cervical lesions].
Colposcopic expertise is necessary in cases of cervical intraepithelial neoplasia (CIN) to avoid conservative treatment of microinvasive and invasive lesions. Large loop excision of the transformation zone (LLETZ) enables the pathologist to examine the entire tumor, and especially its margins. We describe this method and its indications, and review the results of our first 100 cases (mean age 28 years, range 19-46). Indications for LLETZ were biopsy findings of CIN III or of a large CIN II, a lesion entering the endocervical canal, and recurrent CIN after CO2-laser treatment. The procedure was performed under local anesthesia in 93 patients; complications were minimal (8 cases of bleeding requiring local tamponade). In 14% marginal involvement was found, but in only 4 was re-treatment necessary during follow-up of 12-33 months. Only 3 developed recurrent CIN, which was again treated by LLETZ. The cure rate of the initial treatment was 97%. This ablative, nondestructive method is easy to perform, requires only local anesthesia, has few, mild complications and gives an accurate histopathological result, including information on margins. The procedure is becoming the method of choice for treating high-grade and recurrent CIN.


Partial arc beam filtration: a novel approach to reducing CT breast radiation dose.
We sought to assess the effectiveness of a novel CT radiation dose reduction strategy in which filtration was added at the x-ray tube output port between the x-ray beam and the breast area of three sizes of anthropomorphic phantoms. To evaluate the dose-reduction potential of partial arc x-ray beam filtration, copper foil filtration or lead foil filtration was placed over CT scanners' covers when scanning anthropomorphic phantoms representative of a 5-year-old child, a 10-year-old child, and an adult female. Dose reduction was calculated as the percentage difference between the mean entrance radiation dose (on the phantoms' surfaces at locations representing the sternum and left breast) in unshielded scans compared with the mean dose in scans shielded by copper or lead foil. We also compared the CT numbers and noise sampled in regions representing the lung and the soft tissues near the sternum, left breast, and spine in CT images of the phantoms during unshielded scans relative to acquisitions shielded by copper or lead foil. Entrance dose at the sternum and left breast in the three anthropomorphic phantoms was reduced by 28-66% and 54-79% when using copper or lead foil filtration, respectively. However, copper foil filtration affected the CT numbers and noise in the CT images less than the lead foil filtration did (8.2% vs 32% mean increase in noise). By incorporating partial arc beam filtration into CT scanners, substantial dose reductions may be achieved with a minimal increase in image noise.


Diffusion of aroma compounds in stirred yogurts with different complex viscosities.
To better understand aroma release in relation to yogurt structure and perception, the apparent diffusivity of aroma compounds within complex dairy gels was determined using an experimental diffusion cell. Apparent diffusion coefficients of four aroma compounds (diacetyl, ethyl acetate, ethyl hexanoate, and linalool) at 7 degrees C in yogurts (varying in composition and structure) ranged from 0.07 x 10 (-10) to 8.91 x 10 (-10) m (2) s (-1), depending on aroma compounds and on product structure. The strong effect of yogurt fat content on the apparent diffusivity of hydrophobic compounds was revealed (15-fold and 50-fold decreases in the apparent diffusion coefficient of linalool and ethyl hexanoate, respectively). Protein composition seemed to have a greater effect than that of mechanical treatment. However, variations in the apparent diffusion coefficient for the considered products remained limited and cannot completely explain differences in flavor release and in perception that were previously observed.


Extensive endoscopic sinus surgery from the viewpoint of out-patients in a metropolitan area.
Extensive functional endoscopic sinus surgery (FESS) was assessed retrospectively from the viewpoint of out-patients on the basis of their responses to a postal questionnaire, particularly in the Tokyo metropolitan area. Seventeen patients were included in this study (six females and 11 males) with an age range of 22-70 years. All the patients had at least ethmoid sinusitis. Additionally, some patients had maxillary or sphenoid sinusitis or polyps obstructing the nasal cavities. The average operation time and blood loss were 36 minutes and 31 ml, respectively. Four patients had to travel more than one hour to reach home. All of them used the train for travelling to and from the hospital. 'Doctors' advice' was the most common reason for the decision to undergo this ambulatory surgery. Nine (53 per cent) had some unexpected problems post-operatively. The establishment of a care pathway may improve the outcome of extensive FESS on an out-patient basis.


A Hirschsprung disease locus at 22q11?
We report a boy with truncus arteriosus, dysmorphic features, developmental delay, passing hypotonia, short segment Hirschsprung disease (HSCR), and paroxysmal hypoventilation. FISH analysis showed an interstitial deletion in chromosome band 22q11.2 coinciding with the deletions found in DiGeorge syndrome and velocardiofacial syndrome. Mutation scanning of RET, GDNF, EDNRB, and EDN3, genes associated with Hirschsprung disease, showed no aberrations. Since we know of two more patients with velocardiofacial syndrome and HSCR, we hypothesise that a gene responsible for proper development of the enteric nervous system may be included in the 22q11.2 region.


Genetic parameters for five traits in Africanized honeybees using Bayesian inference.
Heritability and genetic correlations for honey (HP) and propolis production (PP), hygienic behavior (HB), syrup-collection rate (SCR) and percentage of mites on adult bees (PMAB) of a population of Africanized honeybees were estimated. Data from 110 queen bees over three generations were evaluated. Single and multi-trait models were analyzed by Bayesian Inference using MTGSAM. The localization of the hive was significant for SCR and HB and highly significant for PP. Season-year was highly significant only for SCR. The number of frames with bees was significant for HP and PP, including SCR. The heritability estimates were 0.16 for HP, 0.23 for SCR, 0.52 for HB, 0.66 for PP, and 0.13 for PMAB. The genetic correlations were positive among productive traits (PP, HP and SCR) and negative between productive traits and HB, except between PP and HB. Genetic correlations between PMAB and other traits, in general, were negative, except with PP. The study permitted to identify honeybees for improved propolis and honey production. Hygienic behavior may be improved as a consequence of selecting for improved propolis production. The rate of syrup consumption and propolis production may be included in a selection index to enhance honeybee traits.


Changes in plasma, red blood cell and cerebrospinal fluid mineral concentrations in calves during magnesium depletion followed by repletion with rectally infused magnesium chloride.
Hypomagnesemic and normomagnesemic calves were infused rectally with MgCl2 X 6H2O to determine effects on magnesium (Mg), calcium (Ca) and potassium (K) concentrations in plasma, red blood cells (RBC) and cerebrospinal fluid (CSF). Sixteen Holstein bull calves were fed one of four semipurified diets containing low or adequate Mg and normal or excess K in a 2 X 2 factorial arrangement. When CSF Mg concentration began to decrease in calves fed low Mg diets, each calf was given a rectal infusion of 50 ml of 30% MgCl2 X 6H2O solution while under general anesthesia. Blood and CSF were then sampled periodically for 3 hours and plasma, RBC and CSF were analyzed for Mg, Ca and K concentration. Plasma Mg increased (P less than 0.001) within 5 minutes after rectal infusion in all calves regardless of diet. An increase (P less than 0.01) in CSF Mg was also observed within 30 minutes in hypomagnesemic calves with CSF Mg levels less than 1.8 mg/dl. Rectal infusions had no effect on K in plasma, Ca or K in CSF, Mg, Ca or K in RBC, or packed cell volume but plasma Ca had increased (P less than 0.05) within 120 minutes in calves fed low Mg and high K and within 60 minutes in those fed adequate Mg, normal K diets.


Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells.
We investigated the mechanisms by which cytokines lead to a diminished responsiveness of vascular smooth muscle to vasoconstrictors. The attenuation of noradrenaline-induced contraction by 6 to 24 h incubations with the cytokines, tumor necrosis factor and interleukin-1, in endothelium-denuded rabbit aorta was associated with an increase in intracellular cyclic GMP level. This increase was abolished by the stereoselective inhibitor of nitric oxide-synthase, NG-nitro-L-arginine and by cycloheximide. Formation of nitric oxide was detected in the cytosol of cytokine-treated native and cultured smooth muscle cells by activation of purified soluble guanylate cyclase, and depended on tetrahydrobiopterin, but not on Ca2(+)-calmodulin. The results indicate that cytokines induce a nitric oxide-synthase of the macrophage-type in vascular smooth muscle.


Cancer arising from the remnant mucosa of the ileoanal anastomosis leading to pouchectomy.
Ileal pouch-related adenocarcinoma remains a rarity; thus, guidelines on treatment are currently lacking. We present this case of a 54-year-old man who underwent restorative proctocolectomy with stapled ileal pouch-anal anastomosis formation for familial adenomatous polyposis during the 1980s. Despite undergoing annual surveillance endoscopy, the patient was noted to be anaemic and passing fresh blood per anus Endoscopy and radiological investigation revealed the presence of a pouch-related adenocarcinoma. This was subsequently treated with short-course radiotherapy and pouch excision. The patient remains well until now and will follow six-monthly surveillance protocols with a transition to annual surveillance after 2 years.


Improved sample dispersion in cryo-EM using "perpetually-hydrated" graphene oxide flakes.
For many macromolecular complexes, the inability to uniformly disperse solubilized specimen particles within vitreous ice films precludes their analysis by cryo-electron microscopy (cryo-EM). Here, we introduce a sample preparation process using "perpetually-hydrated" graphene oxide flakes as particle support films, and report vastly improved specimen dispersion. Furthermore, we provide evidence that the presence of graphene oxide flakes in vitreous ice results in a significant reduction in electron beam-induced specimen decomposition. The new method introduced in this study incorporates hydrated graphene oxide flakes into a standard sample preparation regime, without the need for additional tools or devices, making it a cost-effective and easily adoptable alternative to currently available sample preparation approaches.


Respiratory effects of morphine in awake unrestrained rats.
This report describes a systematic analysis of opiate drug effects on ventilation and its components tidal volume and frequency in intact, awake and unrestrained rats. A whole-body plethysmographic method was used to measure these parameters of respiration while animals breathed air or various concentrations of CO2 in air. Subcutaneous doses of morphine lower than 40 mg/kg exerted little or no apparent effect in rats breathing air; in rats breathing 4 to 8% of CO2 these doses of morphine also failed to depress any of the ventilatory parameters below the level of saline controls breathing air. Doses (0.16 to 160 mg/kg) of morphine blunted the frequency response to CO2 in a biphasic manner. The effects of morphine on tidal volume consisted of a slight increase at 0.16 and 0.63 mg/kg, a dose-dependent decrease at 2.5 to 40 mg/kg and a paradoxical rise at 160 mg/kg. These complex effects of morphine on tidal volume and frequency resulted in a simple sigmoid depression of minute volume. The slope of this sigmoid dose-response curve varied with the inspirate; it increased as the concentration of CO2 was higher. Naloxone antagonized the frequency depression produced by 40 mg/kg of morphine in a dose-dependent manner at doses ranging from 0.01 to 0.16 mg/kg, but frequency decreased again at 0.63 mg/kg. The effects of naloxone on the tidal volume depression consisted of a paradoxical further decrease at 0.01 mg/kg, a dose-dependent antagonism of depression at 0.04 to 0.16 mg/kg and a stimulation above the normal control level at 0.63 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)


Vestibular investigations in acoustic neuroma.
Forty-eight patients with surgically proven acoustic neuroma were examined preoperatively with a comprehensive battery of vestibular tests. In 87% of the patients, reduced caloric responses were measured on the side of the lesion. In 60% of the patients a non-responsive labyrinth was found. Spontaneous nystagmus was observed in 29% of the patients. A significant correlation with the size of the tumour was found in the occurrence of abnormal saccades in the calibration test, pathological smooth pursuit movements and the occurrence of gaze nystagmus, respectively. There was no correlation between the magnitude of the caloric response reduction and the mean hearing loss, which suggests that the hearing loss and the vestibular function loss do not occur synchronously. This study shows that in most cases of acoustic neuroma, the peripheral part of the vestibular system is severely disturbed. Abnormalities in the central and peripheral part of the vestibular system are more easily recognized with increasing tumour size. We conclude that a complete battery of vestibular tests is essential in combination with audiometric, neurologic and radiologic analysis for the early clinical diagnosis of acoustic neuroma.


Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study.
In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT). We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors. In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 μmol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality. In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.


Behavioural hearing tactics: a controlled trial of a short treatment programme.
Nineteen elderly hearing impaired subjects participated in an experimental treatment study and received either behavioural hearing tactics or served as untreated controls. Treatment was supplied in the form of a self-help treatment manual supplied with telephone contacts during 4 consecutive weeks. The treatment manual included applied relaxation, communication strategies training, advice to relatives, information, and coping skills. Assessments (pre-post) were conducted in a structured interview measuring coping behaviour. In order to evoke behavioural compensation small acoustic provocations were included in the interview. Pre-post assessments also included questionnaires, daily registered hearing problems, and hours of daily hearing aid use. Results showed significant beneficial effects in favour of the treatment in terms of self-assessed problems and behaviour change.


Ingi, a 5.2-kb dispersed sequence element from Trypanosoma brucei that carries half of a smaller mobile element at either end and has homology with mammalian LINEs.
A dispersed repetitive element named ingi, which is present in the genome of the protozoan parasite Trypanosoma brucei, is described. One complete 5.2-kilobase element and the ends of two others were sequenced. There were no direct or inverted terminal repeats. Rather, the ends consisted of two halves of a previously described 512-base-pair transposable element (G. Hasan, M.J. Turner, and J.S. Cordingley, Cell 37:333-341, 1984). Oligo(dA) tails and possible insertion site duplications suggested that ingi is a retroposon. The sequenced element appears to be a pseudogene copy of an original retroposon with one or more open reading frames occupying most of its length. Significant homologies of the encoded amino acid sequences with reverse transcriptases and mammalian long interpersed nuclear element sequences suggest a remote evolutionary origin for this kind of retroposon.


Development of an HT29 liver metastases model in nude rats.
The liver is the most frequent and fatal site of distant spreading of colorectal cancer. Most liver metastases animal models involve nude mice and an injection of tumour cells through the spleen or portal vein, or orthotopic implantation of tumour cells in the colon wall. The aim of this study was to develop a reliable rat model of liver metastases with human colorectal HT29 cells. Seventy male athymic Rowett nude rats weighing 300+/-30 g were separated into three groups. The first group (n=20) consisted of untreated rats, rats in the second group (n=20) were immunosuppressed by cyclosporin A, and those in the third group (n=30) were irradiated the day before cell grafting. Tumour cells (2 x 10(7)) were subcapsulary injected into the liver, and rats were sacrificed after 60 days. The livers were excised, and tumours were serially sectioned to determine size and volume, then fixed for histological studies. The take-rate was 55% in the first group, 35% in the second and 74% in the third group. The mean volume of tumours in the first group was 537+/-162 mm(3), 613+/-232 mm(3) in the second group and 2949+/-629 mm(3) in the third group. In conclusion, subcapsular injection of the human colonic HT29 cancer cells into the liver of preoperatively irradiated nude rats is a reliable, reproducible and easily obtained model, which should be useful for preclinical studies.


Effects of Lorazepam on the automatic online evaluation of sleep EEG data in healthy volunteers.
In earlier publications we described an automatic algorithm to detect rapid eye movement (REM) sleep from a single-channel EEG recording without using EMG or EOG information. This system consisted of an artificial neural network operating on the basis of preprocessed EEG data and was composed to provide a maximum of robustness for online applications. In the present study the influence of acute administration of lorazepam on the performance of the REM detection procedure was evaluated. Following an adaptation to laboratory conditions, sleep EEG data were obtained from healthy subjects in three nights each. On the evening of the second night the volunteers received a single dosage of 2.5 mg Lorazepam; the other two nights were drug-free. The sleep profile and the quantitative EEG data reflected the known changes following acute administration of benzodiazepines: during the treatment night the amount of non-REM sleep and the relative power of the EEG signal in the beta and gamma frequency bands was increased relative to the first night, while the amount of REM sleep was reduced. The night of drug discontinuation still showed some characteristics of the treatment night. The discordance rate of the REM detection algorithm relative to the manual evaluation ranged from 9% to 14.2% for the different nights. Surprisingly, the percentage of correctly classified time periods was even higher for the lorazepam night as compared to the other nights.


B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells.
The immunoregulatory protein B7-H3, a member of the B7 family, has been confirmed to be highly expressed in colon cancer. However, the exact influence of B7-H3 on the features and antitumor ability of γδT cells in colon cancer remains unknown. In the present study, we investigated that the proportions of B7-H3+ γδT cells were distinctly increased in the peripheral blood and tumor tissues of colon cancer patients. B7-H3 blockade or knockdown promoted proliferation, inhibited cell apoptosis and induced the expression of activation markers (CD25 and CD69) on Vδ2 T cells. In contrast, treatment with the B7-H3 agonist 4H7 had the opposite effect. Furthermore, B7-H3 suppressed IFN-γ expression by inhibiting T-bet in Vδ2 T cells. Moreover, B7-H3 mediated the inhibition of Vδ2 T cell cytotoxicity via the downregulation of IFN-γ and perforin/granzyme B expression. More importantly, blocking the B7-H3 function significantly enhanced the cytotoxicity of Vδ2 T cells against colon cancer cells in vivo. Therefore, the inhibition or blockade of B7-H3 is a potential immunotherapeutic approach for colon cancer.


[Paediatric mechanical cardiac assistance].
The mechanical cardiac assistance, once limited only to the adult patients, is now progressively extended to the paediatric population, including neonates. Currently for children with cardiorespiratory insufficiency requiring for a mechanical assistance there are available several options: Intra-Aortic Balloon Pump, Extra-Corporeal Membrane Oxygenation (ECMO) et le Ventricular Assist Device. From April 1999 in our Department of Cardiovascular Surgery at CHUV 8 children, including 4 neonates, have been treated with ECMO. Indications, contra-indications, advantages, disadvantages, results and complications of the available options of paediatric mechanical cardiac assistance are described.


Absent circle of Willis with vascular pollarding in an adult with colpocephaly: A developmental perspective.
Absent circle of Willis (COW) has been described in cases of severe forms of cerebral developmental anomalies such as alobar prosencephaly. However, there are no reports of absent COW in patients with a milder form of cerebral abnormality such as colpocephaly. We report a unique case of an adult with colpocephaly and absent COW and discuss their association from a developmental perspective.


Human RAD6 promotes G1-S transition and cell proliferation through upregulation of cyclin D1 expression.
Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1) in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics.


The B-type cyclin CYB-1 maintains the proper position and number of centrosomes during spermatogenesis in Caenorhabditis elegans.
Depletion of cyb-1, a major B-type cyclin expressed during Caenorhabditis elegans spermatogenesis, causes a meiotic division arrest in diakinesis-stage spermatocytes with multiple and mispositioned centrosomes. Association of the two nuclear membrane proteins SUN-1 and ZYG-12 is essential for centrosome-nuclear envelope attachment. We found that depletion of sun-1 causes centrosome defects similar to those caused by cyb-1 depletion in diakinesis-stage spermatocytes. In addition, Ser8 and Ser43 residues in SUN-1 are dephosphorylated in cyb-1-depleted diakinesis-stage spermatocytes. Nevertheless, dephosphorylation of these residues was not sufficient to reproduce the cyb-1-related centrosome defects. We then found that the ZYG-12::GFP signal in the nuclear envelope was significantly reduced in the cyb-1-depleted diakinesis-stage spermatocytes. However, only mispositioned but not multiplied centrosomes were observed in zyg-12 mutant diakinesis-stage spermatocytes, suggesting that zyg-12 is not involved in the centrosome duplication at this stage. Our results suggest that CYB-1 functions to maintain proper positioning of centrosomes during spermatogenesis by regulating phosphorylation of SUN-1, which is possibly crucial for the association between SUN-1 and ZYG-12. This phosphorylation of SUN-1 may also regulate centrosome duplication independently of ZYG-12.


Global Analysis and Optimal Control Model of COVID-19.
COVID-19 remains the concern of the globe as governments struggle to defeat the pandemic. Understanding the dynamics of the epidemic is as important as detecting and treatment of infected individuals. Mathematical models play a crucial role in exploring the dynamics of the outbreak by deducing strategies paramount for curtailing the disease. The research extensively studies the SEQIAHR compartmental model of COVID-19 to provide insight into the dynamics of the disease by underlying tailored strategies designed to minimize the pandemic. We first studied the noncontrol model's dynamic behaviour by calculating the reproduction number and examining the two nonnegative equilibria' existence. The model utilizes the Castillo-Chavez method and Lyapunov function to investigate the global stability of the disease at the disease-free and endemic equilibrium. Sensitivity analysis was carried on to determine the impact of some parameters on R 0. We further examined the COVID model to determine the type of bifurcation that it exhibits. To help contain the spread of the disease, we formulated a new SEQIAHR compartmental optimal control model with time-dependent controls: personal protection and vaccination of the susceptible individuals. We solved it by utilizing Pontryagin's maximum principle after studying the dynamical behaviour of the noncontrol model. We solved the model numerically by considering different simulation controls' pairing and examined their effectiveness.


Rapid, nonradioactive detection of mutations in the human genome by allele-specific amplification.
A simple, rapid, nonradioactive method has been developed to facilitate the direct detection of point mutations that cause genetic disease. The method operates on the basis of the specific amplification of a target allele by the polymerase chain reaction with extension primers designed such that their 3' end is placed at the mutation site. When this base is complementary to that of the specific allele, the DNA segment is amplified; when it is not complementary, the polymerase chain reaction cannot proceed. When alpha 1-antitrypsin (alpha 1AT) deficiency was used as a model, the technique of allele-specific amplification was capable of selective detection of five different mutations that cause the alpha 1AT deficiency state, including three different naturally occurring single-base substitution mutations (alleles Z, S, and Nullbellingham), an insertion mutation (Nullmattawa), and a deletion mutation (Nullgranite falls). Double-blind evaluation of 47 samples of genomic DNA demonstrated 100% accuracy of the method. The technique of allele-specific amplification is rapid, simple, and does not require the existence of a convenient restriction endonuclease site or the use of radioactive materials, and thus should have broad applicability for the detection of known genetic diseases in a highly sensitive and specific fashion.


Heterogeneity of glandular cells in the human salivary glands: an immunohistochemical study using elderly adult and fetal specimens.
Using immunohistochemical staining for alpha-smooth muscle actin (α-SMA), glial fibrillary acidic protein (GFAP), S100 protein (S100), p63, cytokeratin 14 (CK14), and cytokeratin 19 (CK19), we studied acinar and myoepithelial cells of major and minor salivary glands obtained from 14 donated cadavers (78-92 years old) and 5 donated fetuses (aborted at 15-16 weeks of gestation). CK and p63 expression was investigated only in the adult specimens. SMA was detected in all adult glands as well as in fetal sublingual and pharyngeal glands. GFAP expression was seen in a limited number of cells in adult glands, but was highly expressed in fetal pharyngeal glands. S100-positive myoepithelial-like cells were present in adult minor glands as well as in fetal sublingual and pharyngeal glands. Expression of p63 was evident in the ducts of adult glands. CK14 immunoreactivity was observed in a limited number of glandular cells in adults, in contrast to consistent expression of CK19. In both adults and fetuses, a mosaic expression pattern was usually evident for each of the examined proteins. A difference in immunoreactivity for the nerve markers GFAP and S100 was observed between the major and minor glands. Thus, in the present histologic study, we distinguished between the specific gland types on the basis of their immunohistochemical staining. A mosaic expression pattern suggested that the immunoreactivity against nerve protein markers in myoepithelial cells could not be due to the persistence of neural crest remnants or the physiological status of the gland, such as age-related degeneration.


Management of a high-output stoma in the community: case study.
Nursing care of patients with high-output stomas in the community can be challenging. Large quantities of liquid effluent make containment and skin care high priorities. These issues can in some cases be further complicated by the need for parenteral nutrition (PN). Issues related to high output stomas will be briefly discussed and then a case study will show how one team of community nurses assisted a patient with a jejunostomy.


Biotransformation of ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, hesperidin, poncirin, glycyrrhizin, and baicalin by human fecal microflora and its relation to cytotoxicity against tumor cells.
To understand the role of intestinal microflora in the biological effect of functional herbs, which have been used in Korea, Japan, and China as traditional medicines, and suggest new bioactive compounds transformed from herbal constituents, the metabolic activities of the functional herb components (ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, poncirin, hesperidin, glycyrrhizin, and baicalin) toward their bioactive compounds (compound K, crocetin, benzaldehyde, genipin, daidzein, ginsenoside Rh1, ponciretin, hesperetin, 18b-glycyrrhetic acid, and baicalein) were measured in fecal specimens. The metabolic activities of these components were 882.7 +/- 814.5, 3,938.1+/- 2,700.8, 2,375.5 +/- 913.7, 1,179.4 +/- 795.7, 24.6 +/- 10.5, 11.4 +/- 10.8, 578.8+/- 206.1, 1,150.0+/- 266.1, 47.3 +/- 58.6, and 12,253.0 +/- 6,527.6 mmol/h/g, respectively. No differences were found in the metabolic activities of the tested components between males and females, although these metabolic activities between individuals are extensively different. The metabolites of functional herb components showed more potent cytotoxicity against tumor cells than nonmetabolites. These findings suggest that intestinal microflora may activate the pharmacological effect of herbal food and medicines and must be the biocatalytic converter for the transformation of herbal components to bioactive compounds.


Combinatorial screening of photoelectrocatalytic system with high signal/noise ratio.
Solar energy is the most abundant nature resource and plays important roles in the sustainable developments of energy and environment. Scanning photoelectrochemical microscopy provides a high-throughput screening method by introducing the combinatorial technique to prepare the substrate with photoelectrochemical catalyst array. However, the signal/noise (S/N) ratio suffers from the background current of indium-tin oxide or fluorine-doped tin oxide itself, including a transient charge-discharge current of electric double layer and a steady-state photocatalytic current. Here we adopt a facile microfabrication method to isolate the substrate area other than the catalyst array from not only the electrolyte solution but also the light illumination. Consequently, the imaging quality has been promoted dramatically due to suppressed background current. This method provides a high S/N ratio screening method, which will be valuable for the high-throughput optimization of the photoelectrocatalytic system.


The effects of pre-sleep consumption of casein protein on next-morning measures of RMR and appetite compared between sedentary pre- and postmenopausal women.
The purpose of the present study was to compare next-morning responses of RMR and appetite to pre-sleep consumption of casein protein (CP) in pre- and postmenopausal women. The study was a randomised, crossover, double-blind, placebo-controlled trial. Seven sedentary premenopausal (age: 19·9 (sd 1·2) years; BMI: 23·1 (sd 2·6) kg/m2) and seven sedentary postmenopausal (age: 56·4 (sd 4·9) years; BMI: 26·3 (sd 3·5) kg/m2) women participated. During visit one, anthropometrics and body composition were measured. Following visit one, subjects consumed either CP (25 g) or placebo (PL) ≥2 h after their last meal and ≤30 min prior to sleep on the night before visits two and three. Visits two and three occurred ≥1 week after visit one and were 48 h apart. During visits two and three, RMR (VO2), RER and appetite were measured via indirect calorimetry and visual analogue scale, respectively. Anthropometrics and body composition were analysed by one-way ANOVA. RMR and measures of appetite were analysed using a 2 × 2 (menopause status × CP/PL) repeated-measures ANOVA. Significance was accepted at P ≤ 0·05. RMR was significantly lower in postmenopausal compared with premenopausal women under both conditions (P = 0·003). When consumed pre-sleep CP did not alter RMR, RER or appetite compared with PL when assessed next morning in pre- and postmenopausal women. These data contribute to growing evidence that pre-sleep consumption of protein is not harmful to next-morning metabolism or appetite. In addition, these data demonstrate that menopause may not alter next-morning RMR, RER or appetite after pre-sleep consumption of CP.


Biotechnology of intensive aerobic conversion of sewage sludge and food waste into fertilizer.
Biotechnology for intensive aerobic bioconversion of sewage sludge and food waste into fertilizer was developed. The wastes were treated in a closed reactor under controlled aeration, stirring, pH, and temperature at 60 degrees C, after addition of starter bacterial culture Bacillus thermoamylovorans. The biodegradation of sewage sludge was studied by decrease of volatile solids (VS), content of organic carbon and autofluorescence of coenzyme F420. The degradation of anaerobic biomass was faster than biodegradation of total organic matter. The best fertilizer was obtained when sewage sludge was thermally pre-treated, mixed with food waste, chalk, and artificial bulking agent. The content of volatile solid and the content of organic carbon decreased at 24.8% and 13.5% of total solids, respectively, during ten days of bioconversion. The fertilizer was a powder with moisture content of 5%. It was stable, and not toxic for the germination of plant seeds. Addition of 1.0 to 1.5% of this fertilizer to the subsoil increased the growth of different plants tested by 113 to 164%. The biotechnology can be applied in larger scale for the recycling of sewage sludge and food wastes in Singapore.


Hospital pharmacy and emergency department availability of parenteral pyridoxine.
Pyridoxine is a recommended antidote that should be available in emergency departments (EDs). A pediatric use of this preparation is the treatment of acute seizures secondary to pyridoxine dependency or responsiveness. Two cases of children with pyridoxine-dependent and pyridoxine-responsive seizures whose treatment was affected by the unavailability of pyridoxine in local EDs are presented. These cases prompted the development of a survey to ascertain the availability of parenteral pyridoxine in the pharmacies and EDs of both children's and general hospitals in the United States. A survey of 203 pharmacy directors in 100 pediatric hospitals (42 self-governing and 58 within a hospital) and 103 general hospitals was conducted. The questionnaire asked for the number of licensed beds and whether injectable pyridoxine was on the formulary and stocked by the ED. The overall response rate was 73% (83% pediatric and 64% general hospitals). Injectable pyridoxine was on the formulary of 99% of pediatric hospitals and 91% of general hospitals (P = 0.044). Of those hospitals that had pyridoxine on the formulary, the availability of injectable pyridoxine in EDs was low in both pediatric (20.7%) and general hospitals (16.7%). Given the number of possible uses of parenteral pyridoxine in the ED, it is suggested that there is a case for all pediatric and general hospital pharmacies to have it on the formulary and further for all EDs in these hospitals to have injectable pyridoxine available for immediate use.


Oral ondansetron in the prophylaxis of nausea and vomiting induced by cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in women with breast cancer. Results of a prospective, randomized, double-blind, placebo-controlled study.
The combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) is a widely used chemotherapy regimen in breast cancer patients. However, the control of nausea and vomiting induced by oral CMF is a rarely examined problem. Therefore we felt a randomized, placebo controlled study justified in order to improve currently available antiemetic therapy. In a randomised double-blind trial ondansetron given orally, 8 mg three times a day for 15 days, was compared with placebo in 82 breast cancer patients receiving chemotherapy with CMF (cyclophosphamide 100 mg/m2 orally days 1-14, methotrexate 40 mg/m2 i.v. days 1 and 8 and 5-fluorouracil 600 mg/m2 i.v. days 1 and 8). The patients recorded nausea and the number of vomits and retches daily on diary cards. Forty-two patients received ondansetron and 40 received placebo. Significantly more patients who received ondansetron experienced neither vomiting nor retching (emesis) compared to those receiving placebo over a 15 day treatment period (60% vs. 35%, p = 0.027). The difference, with 95% confidence limits, was estimated at 25 (4.45%). Furthermore, there was a trend in favour of ondansetron in the control of nausea. Ondansetron was well tolerated, with 25 patients (59%) reporting at least 1 adverse event compared to 18 patients (45%) receiving placebo (p = 0.191). The results indicate that ondansetron given orally for 15 days is safe and effective in the control of emesis induced by CMF. It is however too early to recommend ondansetron as standard antiemetic therapy for oral CMF, as the treatment of nausea and vomiting in this setting has not been studied thoroughly enough.


Case II: Conflict recognition--the case of the misdirected faculty.
Early recognition is fundamental to managing conflict. Successful leaders rely upon their ability to recognize conflict before it escalates into crisis. This article reviews the signs and sources of conflict along with related management theories. Conflict management includes understanding the sources and types of conflict as well as the impact potential; in the case presented, the leaders were unaware of conflict. Dr. Forester, the faculty member "in the middle," was in a precarious position. Her performance evaluation reflected unacceptable accomplishments. However, her self-assessment, based on the hiring agreement, was successful. Her requests for guidance and clarification were unproductive. What does she do now? The management theories that apply to the case of "the misdirected faculty" include analysis and discussion of communication, feedback, and expectancy theory. Action alternatives are presented to explore some of the options available to stimulate discussion and to provide readers with an eclectic approach to applying a case analysis.


Prototype app for voice therapy: a peer review.
Voice speech therapy promotes changes in patients' voice-related habits and rehabilitation. Speech-language therapists use a host of materials ranging from pictures to electronic resources and computer tools as aids in this process. Mobile technology is attractive, interactive and a nearly constant feature in the daily routine of a large part of the population and has a growing application in healthcare. To develop a prototype application for voice therapy, submit it to peer assessment, and to improve the initial prototype based on these assessments. a prototype of the Q-Voz application was developed based on Apple's Human Interface Guidelines. The prototype was analyzed by seven speech therapists who work in the voice area. Improvements to the product were made based on these assessments. all features of the application were considered satisfactory by most evaluators. All evaluators found the application very useful; evaluators reported that patients would find it easier to make changes in voice behavior with the application than without it; the evaluators stated they would use this application with their patients with dysphonia and in the process of rehabilitation and that the application offers useful tools for voice self-management. Based on the suggestions provided, six improvements were made to the prototype. the prototype Q-Voz Application was developed and evaluated by seven judges and subsequently improved. All evaluators stated they would use the application with their patients undergoing rehabilitation, indicating that the Q-Voz Application for mobile devices can be considered an auxiliary tool for voice speech therapy.


The role of vasopressin in hypothalamo-pituitary-adrenal axis activation during stress: an assessment of the evidence.
The hypothalamo-pituitary-adrenal (HPA) axis is a key component of the stress reaction. Most contemporary reviews mention the corticotropin-releasing hormone and arginine vasopressin (AVP)-containing parvocellular neurons of the hypothalamic paraventricular nucleus as the endocrinomotor component of the system. Although there are many studies about the role of AVP in the stress activation, there is evidence consistent and inconsistent with the general view on the importance of AVP. We propose a list of experiments that may provide critical evidence for or against the widely held opinion. The naturally AVP-deficient Brattleboro rat seems to be a good tool for studying the role of AVP. Our experiments on Brattleboro rats with restraint and ip hypertonic saline injection did not support the prominent role of AVP in acute stress, although in forced swim the lack of AVP influenced the HPA axis activation. Among different chronic stress situations (14 days' restraint, chronic morphine or ip hypertonic saline treatment, streptozotocin-induced diabetes mellitus), the role of AVP was not confirmed by changes in somatic parameter (i.e., body, thymus, and adrenal weight changes).


[The advantages and disadvantages of Artemisia princeps and A. montana].
In Japan, Moxa is made from Artemisia princeps and A. montana P. which are plants of the composiae family. Evaluations of the superiority or inferiority of these raw materials for Moxa have been confusing. The judgement of superiority or inferiority is roughly based on the strenght of the fragrance and somewhat of down. When I investigated 14 kinds of documents from the Edo period to the Showa period, 10 of the documents gave good evaluations for Artemisia princeps. On the other hand the remaining four gave good evaluations for A. montana P. But there is quite an opposite opinion, because the four deemed good for Artemisia princeps were misunderstood regarding the discrimination of Artemisia princeps and A. montana P. Since correcting them, each material has seven good evaluations, tying the score. Therefore, I researched the contents of the principal ingredient, Cineole, using an important evaluation index and the fragrances were compared measuring both materials, which were collected from different places. The results to examining six kinds of Artemisia princeps, and eight kinds of A. montana P. (14 kinds in total) are as follows: The A. montana P. contents Cineole was more abundant than the other on average. However, it is from three to five times the change by the growing both ground, and superiority or inferiority cannot be decided indiscriminately. When quality is evaluated, it is necessary to clarify the materials orgin. Generally speaking, the fragrance of A. montana P. is stronger than the other.


Behavioral and physiological changes around estrus events identified using multiple automated monitoring technologies.
This study included 2 objectives. The first objective was to describe estrus-related changes in parameters automatically recorded by the CowManager SensOor (Agis Automatisering, Harmelen, the Netherlands), DVM bolus (DVM Systems LLC, Greeley, CO), HR Tag (SCR Engineers Ltd., Netanya, Israel), IceQube (IceRobotics Ltd., Edinburgh, UK), and Track a Cow (Animart Inc., Beaver Dam, WI). This objective was accomplished using 35 cows in 3 groups between January and June 2013 at the University of Kentucky Coldstream Dairy. We used a modified Ovsynch with G7G protocol to partially synchronize ovulation, ending after the last PGF2α injection (d 0) to allow estrus expression. Visual observation for standing estrus was conducted for four 30-min periods at 0330, 1000, 1430, and 2200h on d 2, 3, 4, and 5. Eighteen of the 35 cows stood to be mounted at least once during the observation period. These cows were used to compare differences between the 6h before and after the first standing event (estrus) and the 2wk preceding that period (nonestrus) for all technology parameters. Differences between estrus and nonestrus were observed for CowManager SensOor minutes feeding per hour, minutes of high ear activity per hour, and minutes ruminating per hour; twice daily DVM bolus reticulorumen temperature; HR Tag neck activity per 2h and minutes ruminating per 2h; IceQube lying bouts per hour, minutes lying per hour, and number of steps per hour; and Track a Cow leg activity per hour and minutes lying per hour. No difference between estrus and nonestrus was observed for CowManager SensOor ear surface temperature per hour. The second objective of this study was to explore the estrus detection potential of machine-learning techniques using automatically collected data. Three machine-learning techniques (random forest, linear discriminant analysis, and neural network) were applied to automatically collected parameter data from the 18 cows observed in standing estrus. Machine learning accuracy for all technologies ranged from 91.0 to 100.0%. When we compared visual observation with progesterone profiles of all 32 cows, we found 65.6% accuracy. Based on these results, machine-learning techniques have potential to be applied to automatically collected technology data for estrus detection.


Effects of the genotype, cage type and time period on the behaviour of laying hybrids at the same egg production level.
Hybrids with different morphological and yield characteristics are used in the table egg production. There is no change in the cage systems according to the different hybrids in the regulation. This study aimed to investigate the effects of genotype (brown laying hybrids (BLH) and white laying hybrids (WLH)) and cage type (conventional and enriched cages) on behaviours of hens at the 90% egg production level. Behavioural data were recorded with video cameras during the 4 days. Data were analysed in 6 time periods as 05.00-08.00 am, 09.00-12.00 am, 01.00-04.00 pm, 05.00-08.00 pm, 09.00-12.00 pm and 01.00-04.00 am. Behaviour inspection each hour was divided into 4 quarters and the first 3 min of each quarter were evaluated. Behaviours were represented as the proportion of the total behaviour performed in the time period by a given hen. There was no interaction between hens' behaviour and the genotype at the same egg production level. The frequency of feeding behaviour was found to be significantly lower (P < 0.01), but comfort behaviour was higher (P < 0.05) in hens that were reared in the enriched cages. Only preening was seen as a comfort behaviour due to the cage size. The feeding, drinking, pecking hen, comforting, walking, sitting, resting and perching behaviours changed during the day (P < 0.01). Especially, the transition from light to dark influenced the perching behaviour negatively. No interactions were detected amongst genotype, cage type and time period. Feeding behaviour decreased and the comfort behaviour increased in the hens that were reared in the enriched cages because there were materials that would exhibit different behaviours. Hens in the enriched cage could not suddenly adapt to the dark and light period. For this reason, transitions to light and dark periods in poultry houses should be provided gradually, as in natural life.


Selected mutations in Bacillus subtilis levansucrase semi-conserved regions affecting its biochemical properties.
Levansucrases (LS) are fructosyltransferases (FTFs) belonging to family 68 of glycoside hydrolases (GH68) using sucrose as substrate to synthesize levan, a fructose polymer. From a multiple sequence analysis of GH68 family proteins, nine residues were selected and their role in acceptor and product specificity, as well as in biochemical Bacillus subtilis LS properties, was investigated. A product specificity modification was obtained with mutants Y429N and R433A that no longer produce levan but exclusively oligosaccharides. An effect of the mutation S164A was observed on enzyme stability and kinetic behavior; this mutation also induces a levan activation effect that enhances the reaction rate. We report the crystallographic structure of this mutant and found that S164 is an important residue to maintain the nucleophile position in the active site. We also found evidence of the important role of Y429 in acceptor specificity: this is a key residue coordinating the sucrose position in the catalytic domain-binding pocket. Some of these mutations resulted in LS with a broad range of specificities and new biochemical properties.


Completely aqueous procedure for the growth of polymer brushes on polymeric substrates.
The growth of polymer brushes on polymer substrates is often challenging because of substrate incompatibility with the organic solvents used for initiator attachment. This letter reports the use of layer-by-layer adsorption of macroinitiators and subsequent aqueous ATRP from these immobilized initiators to prepare polymer brushes on polymeric substrates. Polyethersulfone (PES) films and porous membranes were modified with polyelectrolyte multilayer films, and a previously developed polycationic initiator, poly(2-(trimethylammonium iodide)ethyl methacrylate-co-2-(2-bromoisobutyryloxy)ethyl acrylate), was then electrostatically adsorbed onto these polyelectrolyte films. The immobilized macroinitiator is very efficient in initiating the growth of polymer brushes on PES, as demonstrated by aqueous syntheses of poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) films. PHEMA (250 nm thick) and PDMAEMA (40 nm thick) brushes were grown in 2 h from surfaces modified with polycationic initiators. Moreover, this procedure is effective for growing brushes in the pores of PES membranes.


A comparative study on the release of leukotrienes and histamine by guinea pig lung and trachea after challenge with antigen or stimulation with ionophore A23187 or melittin.
The release of leukotrienes and histamine from guinea pig lung and trachea after immunological and nonimmunological stimulation were compared. Antigen, ionophore A23187 and melittin caused the release of leukotriene (LT)B4, LTC4, LTD4 and LTE4 from lung and trachea as determined by reverse-phase high performance liquid chromatography (RP-HPLC) and bioassay. The release of LTB4 by lung and trachea was maximum after 5 min of ionophore stimulation (128 +/- 40 and 142 +/- 29 pmol/g tissue, respectively). Lung, but not trachea, also released the 20-OH-LTB4 and 20-COOH-LTB4. The release of LTC4 by lung tissues was maximum after 5 min, whereas maximal tracheal responses occurred at 10 min (27 +/- 11 and 9 +/- 3.5 pmol/g tissue, respectively). Maximal release of LTD4 by lung and trachea respectively occurred after 10 and 15 min (103 +/- 21 and 20 +/- 6 pmol/g tissue, respectively). The release of LTD4 in response to ionophore by both tissues decreased after 15 min, whereas the release of LTE4 continued to increase. Release of leukotrienes from melittin stimulated lung was 2-3-fold less than in ionophore stimulation. In contrast, tracheal responses to melittin and ionophore for the release of LTB4 were equivalent, whereas release of peptidoleukotrienes in response to melittin was approximately 50% that resulting from ionophore. Antigen challenge was the least potent stimulus for LTB4 release in both tissues, whereas it was at least as potent as melittin for the release of peptidoleukotrienes. The release of histamine by lung tissue was approximately 2-3-fold greater than by trachea (7 +/- 1 and 2 +/- 0.5 nmol/g tissue, respectively) after 5 min of stimulation with either ionophore, melittin or antigen. These data demonstrate that lung tissues and trachea respond to immunologic stimulations by releasing the mediators of inflammation and immediate hypersensitivity. The lung releases peptidoleukotrienes and histamine 2-5-fold greater than the trachea, whereas the release of LTB4 in both tissues are approximately equal.


Control of the inflammatory response mechanisms mediated by natural and induced regulatory T-cells in HCV-, HTLV-1-, and EBV-associated cancers.
Virus infections are involved in chronic inflammation and, in some cases, cancer development. Although a viral infection activates the immune system's response that eradicates the pathogen mainly through inflammatory mechanisms, it is now recognized that this inflammatory condition is also favorable to the development of tumors. Indeed, it is well described that viruses, such as hepatitis C virus (HCV), Epstein Barr virus (EBV), human papillomavirus (HPV) or human T-cell lymphotropic virus type-1 (HTLV-1), are important risk factors for tumor malignancies. The inflammatory response is a fundamental immune mechanism which involves several molecular and cellular components consisting of cytokines and chemokines that are released by various proinflammatory cells. In parallel to this process, some endogenous recruited components release anti-inflammatory mediators to restore homeostasis. The development of tools and strategies using viruses to hijack the immune response is mostly linked to the presence of regulatory T-cells (Treg) that can inhibit inflammation and antiviral responses of other effector cells. In this review, we will focus on current understanding of the role of natural and induced Treg in the control and the resolution of inflammatory response in HCV-, HTLV-1-, and EBV-associated cancers.


Cholesteatoma presenting as a late complication of cochlear implant surgery: Case report and literature review.
A male patient with post lingual hearing loss was implanted at 16 years of age with a Nucleus cochlear implant (Cochlear) in his left ear. Twenty two years later, he developed a cholesteatoma in relation to the mastoid portion of the facial nerve and in contact with the electrodes array. The cholesteatoma was removed and the ear canal reconstructed. There was no post-operative facial palsy and the cochlear implant was preserved. Although cholesteatoma is a rare complication of the cochlear implant surgery, it still can occur and can be a source of potential damage to the implant. The origin of this late-presenting complication could be excessive bone drilling associated with the pressure caused by the loop of the electrodes array on the posterior canal wall. Implanted patients must have a close and particular long-term follow-up, especially when a surgical breach of the canal wall or a tear of the tympanic membrane have occurred during surgery, as well as in those patients in whom excessive thinning-out of the posterior meatal wall was done.


Clinical differences between choledochal cysts in infancy and childhood: an analysis of 160 patients.
Choledochal cysts (CDC) can become symptomatic at any age. Clinical features of infants and older children are different and have been documented by many authors. The aim of this report was to study the differences in clinical spectrum of CDC between the infants and children treated at our hospital during a 17-year period. A retrospective study was conducted of 160 patients with CDC treated at Queen Sirikit National Institute of Child Health between 1996 and 2012. The patients were categorized into 2 groups based on age at clinical presentation: an infantile group (up to one year old) and a childhood group (over one year old). Clinical characteristics of patients in the infantile and childhood groups were compared with statistical analysis using the Chi-square and Fisher's exact test. Of the 160 patients with CDC, 48 cases (30%) were categorized in the infantile group and 112 cases (70%) in the childhood group. Over three-quarters ofthe patients in the infantile group presented with jaundice and acholic stool, and this incidence was significantly higher than in the childhood group (77% vs. 46.4%, p = 0.001 and 50% vs. 13.4%, p < 0.001). Abdominal pain was the most common symptom of patients in the childhood group, whereas it was noted in only a small number of those in the infantile group (82.1% vs. 8.3%, p < 0.001). Average amylase level in CDC content was markedly elevated in the childhood group but much lower in the infantile group (43,630.5±90,234.5 vs. 79±189.9, p < 0.001). Only type I and type IV CDC as defined by Todani's classification were found in our patients, and there were no statistical differences in incidences of type I and type IV in the two groups (79.2% vs. 67.8% and 20.8% vs. 32.2% p > 0.05). Neonates and infants with CDC had a significantly higher risk of liver cirrhosis than did the childhood group (25% vs. 8%, p < 0.001). However, surviving patients with cirrhosis in both groups were doing well at least 3 years after surgical CDC excision. Neonates and infants with CDC were more likely to present with jaundice and acholic stool, whereas older children were more likely to present with abdominal pain. Amylase level in CDC content was markedly elevated in the childhood group but at a much lower level in the infantile group. Neonates and infants with CDC tended to develop liver cirrhosis earlier and more often than older children.


Simultaneous measurement of free and esterified fatty acids by gas chromatography from normal and type IV hyperlipoproteinaemic sera.
A transmethylated reaction of esterified fatty acids with sodium- methoxide in a mixture of serum, petroleum ether and methanol is presented. In the conditions used the free fatty acids in the sample were not esterified. 1-2 microliters of the organic phase was injected into an OV-351 fused silica capillary column of gas liquid chromatography (GLC) fitted with flameionizing detector (FID) temperature program, and calculating integrator. By this method both free and esterified fatty acids were measured in a single run. The development of the present method for the better quantitation of free fatty acids is in progress as using gas chromatography/mass spectrometry for identification of the peaks. In thirteen healthy subjects, the serum free fatty acid content was 538 +/- 176 mumol/l and free glycerol 107 +/- 39 mumol/l, while in seven type IV hyperlipoproteinaemic sera the corresponding values were 1049 +/- 529 and 86 +/- 38 mumol/l. The most prominent differences between healthy and type IV hyperlipoproteinaemic subjects for esterified fatty acids were found in palmitic, oleic and arachidonic acids. The correlations between free and bound fatty acids has been discussed.