Expression of a connexin31 mutation causing erythrokeratodermia variabilis is lethal for HeLa cells.
The autosomal dominant skin disorder erythrokeratodermia variabilis (EKV) has been linked to mutations in the human connexin31 (hCx31) gene, which is expressed in the epidermis. We characterized and compared a pathogenic mutation resulting in replacement of amino acid glycine 12 with arginine (G12R) with wild-type hCx31 protein. HeLa cells were transfected with wild-type and mutant hCx31 cDNA, respectively, using different-constitutive and inducible-vector systems. Independent of the expression vector, wild-type and mutant hCx31 were expressed at comparative levels and localized at the plasma membranes. Mutated channels (hCx31G12R) showed higher conductance in dye coupling studies than wild type channels. Furthermore, HeLa cells died within 5 days after constitutive expression of the mutant protein. Using an inducible expression system, we demonstrated a direct correlation between survival/life span of transfected HeLa cells and expression level of the mutant protein, indicating a gain-of-function mechanism due to a defective channel closure mechanism.


[Is it necessary to prescribe oral anticoagulant therapy for paroxysmal atrial fibrillation during acute coronary syndrome, and for how long?]
There is limited knowledge on the occurrence of new-onset, transient atrial fibrillation during acute coronary syndromes; compared with patients in sinus rhythm, patients with paroxysmal atrial fibrillation have an increased risk of in-hospital and long-term recurrence of the arrhythmia, all-cause mortality and ischemic stroke. There is a lack of prospective, randomized studies on anticoagulant therapy modalities in this specific subset of patients. In the absence of a widely accepted anticoagulation algorithm, the international guidelines for the management of atrial fibrillation recommend to initiate anticoagulant treatment during acute coronary syndromes estimating in each patient the thrombotic and bleeding risk using the CHA2DS2-VASc and HAS-BLED scores, respectively. In the last updates of the guidelines for the management of atrial fibrillation, non-vitamin K oral anticoagulants are recommended over warfarin and, in patients with atrial fibrillation who have undergone percutaneous coronary intervention with stenting for acute coronary syndromes, dual antiplatelet therapy with rivaroxaban or dabigatran and clopidogrel is reasonable to reduce the risk of bleeding compared with triple therapy. Neither scientific evidences nor recommendations from the guidelines are available about the duration of anticoagulant therapy in case of paroxysmal atrial fibrillation during acute coronary syndromes.


Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis.
Eosinophilic esophagitis (EE) is characterized by high numbers of eosinophils in the esophagus and epithelial hyperplasia, and is being increasingly recognized. IL-5 promotes eosinophil trafficking to the esophagus, and positively regulates eosinophil growth, activation, survival, and tissue recruitment. We hypothesized that the humanized monoclonal IgG(1) antibody against human IL-5 (mepolizumab) may be useful in the control of EE. An open-label phase I/II safety and efficacy study of anti-IL-5 in 4 adult patients with EE and longstanding dysphagia and esophageal strictures was conducted. Patients received 3 infusions of anti-IL-5 (750 mg intravenously monthly) without change in their current therapy. The levels of plasma IL-5, peripheral blood eosinophils, and CCR3+ cells in blood, quality of life measurements, and histological analysis of esophageal biopsies were determined before and 1 month after treatment. Peripheral blood eosinophilia and percent of CCR3+ cells decreased by 6.4-fold and 7.9-fold (P < .05), respectively, after anti-IL-5 treatment. Notably, mean and maximal esophageal eosinophilia decreased from 46 to 6 and from 153 to 28 eosinophils/high-power field (x400; average, 8.9-fold, P < .001, and 6-fold, P < .05), respectively. Patients reported a better clinical outcome and improved quality of life (P = .03). Therapy was generally well tolerated, and responsiveness to anti-IL-5 therapy did not correlate with plasma IL-5 levels. Anti-IL-5 therapy is associated with marked decreases in peripheral blood and esophageal eosinophilia (including the number of CCR3+ blood cells) in patients with EE and improved clinical outcomes. Anti-IL-5 is a promising therapeutic intervention for EE.


Breast Radiotherapy with Mixed Energy Photons; a Model for Optimal Beam Weighting.
Utilization of high energy photons (>10 MV) with an optimal weight using a mixed energy technique is a practical way to generate a homogenous dose distribution while maintaining adequate target coverage in intact breast radiotherapy. This study represents a model for estimation of this optimal weight for day to day clinical usage. For this purpose, treatment planning computed tomography scans of thirty-three consecutive early stage breast cancer patients following breast conservation surgery were analyzed. After delineation of the breast clinical target volume (CTV) and placing opposed wedge paired isocenteric tangential portals, dosimeteric calculations were conducted and dose volume histograms (DVHs) were generated, first with pure 6 MV photons and then these calculations were repeated ten times with incorporating 18 MV photons (ten percent increase in weight per step) in each individual patient. For each calculation two indexes including maximum dose in the breast CTV (Dmax) and the volume of CTV which covered with 95% Isodose line (VCTV, 95%IDL) were measured according to the DVH data and then normalized values were plotted in a graph. The optimal weight of 18 MV photons was defined as the intersection point of Dmax and VCTV, 95%IDL graphs. For creating a model to predict this optimal weight multiple linear regression analysis was used based on some of the breast and tangential field parameters. The best fitting model for prediction of 18 MV photons optimal weight in breast radiotherapy using mixed energy technique, incorporated chest wall separation plus central lung distance (Adjusted R2=0.776). In conclusion, this study represents a model for the estimation of optimal beam weighting in breast radiotherapy using mixed photon energy technique for routine day to day clinical usage.


Antoine Ferrein (1693-1769)-His Life and Contribution to Anatomy and Physiology: The Description of the Vocal Chords and Their Function.
The purpose of this study is to summarize the life and work of the French anatomist and surgeon Antoine Ferrein (1693-1769). Ferrein made an impact in the history of anatomy and physiology through his work and especially with the description of phonation, renal anatomy, and liver and biliary structure. He also made an impact on ophthalmology with the description of the eyelid and its diseases. After a thorough review of the literature, we present in this review his life and his main discoveries with special emphasis on the anatomic description of the vocal chords resembling the chords of a violin tempered by the air exhaled from the lungs and how the physiology of phonation and the surgery of the larynx were revolutionized after that.


Bacteraemia caused by periodontal probing.
Bacteraemia of oral origin may result in infective endocarditis in susceptible individuals. The aim of this pilot study was to investigate the occurrence of bacteraemia due to periodontal probing. Thirty patients (15 male, 15 female; mean age 42.7 years) with untreated periodontitis were investigated. All were free of significant medical disorders and none had taken antibiotics in the previous month. Prior to and immediately following periodontal probing, 20 mL of venous blood were obtained from each patient and inoculated into aerobic and anaerobic blood culture bottles and incubated. Negative bottles were monitored continuously for three weeks before being discarded. Periodontal probing consisted of measuring pockets at six points around each tooth and recording the presence or absence of bleeding. A positive bacteraemia was recorded for three of the patients prior to probing. One patient exhibited Prevotella species whilst two exhibited skin commensals. Following probing, 13 patients (43 per cent) exhibited bacteraemia of oral origin. Viridans streptococci were the most common isolates (45 per cent). No significant correlations were found between bacteraemia and the severity of periodontitis or extent of bleeding on probing. The results indicate that periodontal probing can cause bacteraemia in patients with periodontitis. It would be advisable for patients considered at risk of developing infective endocarditis to receive antibiotic prophylaxis for periodontal probing if they have radiographic evidence of periodontitis.


Time-course analysis of changes in calcitonin gene-related peptide-and methionine-enkephalin-immunoreactivity in the female rat preoptic area after estrogen treatment.
The time-course effects of one month of estrogen upon calcitonin gene-related peptide - and methionine-enkephalin-immunoreactivity in the periventricular preoptic nucleus and medial preoptic nucleus were semi-quantitatively investigated with a computer-based image analysis system. Female Wistar rats were ovariectomized and implanted subcutaneously with a 10-mm-long silastic capsule containing estradiol-17 beta, or with a blank capsule, as a control. Estradiol-17 beta-treated rats were killed at days 1, 4, 7, 10, 14 and 28 after the implantation of estradiol-17 beta. To investigate the details of changes in calcitonin gene-related peptide- and methionine-enkephalin-immunoreactive fibers in the periventricular preoptic nucleus and medial preoptic nucleus, a grid, made up of 8 x 16 squares (one square corresponding to 50 x 50 microns in the true section), was set on the wall of the third ventricle, and immunoreactivity within each square was measured with an image analyser. In the control rats, calcitonin gene-related peptide- and methionine-enkephalin-immunoreactive fibers were distributed in the periventricular preoptic nucleus and medial preoptic nucleus. In the estradiol-17 beta-treated rats, calcitonin gene-related peptide-immunoreactive fibers increased prominently at day 1, day 7 and day 10 in the periventricular preoptic nucleus, whereas methionine-enkephalin-immunoreactive fibers increased at day 1, day 14 and day 28 in the periventricular preoptic nucleus and medial preoptic nucleus. These findings suggest that the mechanism underlying the increases in these calcitonin gene-related peptide- and methionine-enkephalin-immunoreactive fibers after estrogen treatment might be different.


Latency variability of the components of auditory event-related potentials to infrequent stimuli in aging, Alzheimer-type dementia, and depression.
Auditory event-related potentials (ERPs) were investigated in 15 demented (12 presumed Alzheimer's, 3 cerebrovascular), 8 depressed, and 15 normal older, and 12 normal young, subjects. Both latencies from conventional averages and latency variability measures from single trials were derived for the N100, P200, N200, and P300 components of the ERP recorded from Fz, Cz and Pz scalp placements in a task requiring detection of an infrequent target tone among a series of frequent non-target tones. The P300 component most consistently separated the groups. Demented subjects had longer P300 latencies and greater P300 latency variability than both control groups and the depressed group. Age differences were observed for P300 latency, but not for P300 latency variability. Amplitudes were not significantly different among the groups. Reaction times (RTs) to the targets were longest for the demented subjects and shortest for the young controls, with the depressed and normal older control groups falling in between. Correlations between RT and P300 latency from single trials did not differentiate the groups. Using regression analysis to evaluate the deviation of P300 latency and latency variability for the patients from the predicted values for normal controls, no misclassifications of depressed patients occurred, but only 27% of the demented individuals were correctly classified using P300 variability, and 13% using P300 latency. These findings indicate that ERP measures using the 'oddball' target detection paradigm were useful in describing group differences, but were not sufficiently sensitive to be used in differentiating demented persons on an individual basis for clinical diagnosis.


Amino acid residues conferring the nucleotide binding properties of N-acetyl-D-glucosamine 2-epimerase (renin binding protein).
Our recent studies have demonstrated that the middle domain of N-acetyl-D-glucosamine (GlcNAc) 2-epimerase participates in the specificity for and binding of nucleotides. To identify the residue conferring nucleotide binding, amino acid substitutions were introduced in the human and rat GlcNAc 2-epimerases. The mutational analyses indicate that residue 171 of GlcNAc 2-epimerase is critical for the nucleotide binding of GlcNAc 2-epimerase.


Determination of arsenic species in rice samples using CPE and ETAAS.
A highly sensitive and selective procedure for the determination of arsenate and total arsenic in food by electrothermal atomic absorption spectrometry after cloud point extraction (ETAAS/CPE) was developed. The procedure is based on the formation of a complex of As(V) ions with molybdate in the presence of 50.0 mmol L(-1) sulfuric acid. The complex was extracted into the surfactant-rich phase of 0.06% (w/v) Triton X-114. The variables affecting the complex formation, extraction and phase separation were optimized using factorial designs. Under the optimal conditions, the calibration graph was linear in the range of 0.05-10.0 μg L(-1). The detection and quantification limits were 10 and 33 ng L(-1), respectively and the corresponding value for the relative standard deviation for 10 replicates was below 5%. Recovery values of between 90.8% and 113.1% were obtained for spiked samples. The accuracy of the method was evaluated by comparison with the results obtained for the analysis of a rice flour sample (certified material IRMM-804) and no significant difference at the 95% confidence level was observed. The method was successfully applied to the determination of As(V) and total arsenic in rice samples.


Your ideas about participation and environment: a new self-report instrument.
To examine the meaningfulness, usefulness and acceptability of a new self-report instrument: "your ideas about participation and environment" (YIPE). Cognitive interviewing was employed with 10 adults with disabilities to explore YIPE questions and formatting. Thematic content procedures were used in data analysis. The instrument was revised; participants were re-interviewed and data were re-examined. Participants considered the YIPE as a helpful tool to assist with developing person-centred goals and communicating their needs to health professionals, thus establishing its meaningfulness. They believed it could be useful at various points in the intervention process (e.g. preparation, monitoring, and evaluation). Participants also endorsed the YIPE's computer-based format, thus confirming its acceptability. The findings support the meaningfulness, acceptability and usefulness of the YIPE and consequently its potential for empowering service users and promoting person-centred care. Using the International Classification of Functioning, Disability and Health as the basis resulted in an instrument that was appropriate for understanding the interrelationship between participation and the supportiveness of the usual environment in which participation generally takes place. The YIPE is a useful tool to assist with developing person-centred goals, communicate needs with health professionals and it can be used at various points in a therapy process (preparation, monitoring or evaluation). The interrelationship between participation and the environment is important to consider when measuring functioning. Self-report empowers people to play an active role in interactions with health professionals and promote their own care.


Exposure characterization and estimation of benchmark dose for cancer biomarkers in an occupational cohort of diesel engine testers.
Exposure to diesel engine exhaust (DEE) was associated with various adverse health effects including lung cancer. Particle size distribution and profiles of organic compounds in both particle and gas phases of DEE that could provide valuable insights into related health effects were measured in a diesel engine testing workshop. Concentrations of urinary 6 mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in 137 DEE-exposed workers and 127 non-DEE-exposed workers were determined. Benchmark dose method was applied to estimate lower limit of benchmark dose (BMDL) of urinary OH-PAHs most specific to DEE exposure for previously reported cancer biomarkers. We found that 84.3% of diesel exhaust particles were ultrafine particles. Indeno[123-cd]pyrene and phenanthrene were the most abundant carcinogenic and noncarcinogenic PAHs in the particle phase of DEE, respectively. Principal component analysis demonstrated that urinary hydroxyphenanthrene (OHPhe) had highest loading value on principal component (PC) representative of DEE exposure and lowest loading value on PC representative of smoking status. BMDLs of urinary OHPhe from best-fitting models for cancer biomarkers including micronucleus and 1,N6-ethenodeoxyadenosine were 1.08 μg/g creatinine and 2.82 μg/g creatinine, respectively. These results provided basis for understanding DEE exposure induced health effects and potential threshold for regulating DEE levels in an occupational setting.


Mitosis in milk secreting epithelial cells of mammary gland: an ultrastructural study.
In all stages of lactation mitotic configurations were observed in mammary gland epithelial cells of rats. An electron microscopic study is presented which shows that ultrastructure of such mitotic stages is normal and that mitotic cells contain typical products of milk secreting cells such as casein micelle-containing vesicles and milk fat droplets. Such secretory products can even be observed in the immediate vicinity of the chromosomes and microtubules of the spindle apparatus. The endoplasmic reticulum of mitotic cells appeared altered in that it did not show typical cisternal stacks characteristic of interphase cells. While the numbers of such mitotic cells were very low, especially from the second week of lactation on (always less than 0.1% of the milk secreting epithelial cells encountered), the observations clearly demonstrate that differentiation for milk secretory activity and cells division are not mutually exclusive. We conclude that postpartum growth of mammary gland epithelium and replacement of epithelial cells lost during desquamation into the milk liquids can occur by division of existing differentiated milk secreting cells and does not require mitotic activity of non-lactating 'stem cells' which are not observed in lactating alveoli.


Determinants of work ability and its predictive value for disability.
Maintaining the ability of workers to cope with physical and psychosocial demands at work becomes increasingly important in prolonging working life. To analyse the effects of work-related factors and individual characteristics on work ability and to determine the predictive value of work ability on receiving a work-related disability pension. A longitudinal study was conducted among 850 construction workers aged 40 years and older, with average follow-up period of 23 months. Disability was defined as receiving a disability pension, granted to workers unable to continue working in their regular job. Work ability was assessed using the work ability index (WAI). Associations between work-related factors and individual characteristics with work ability at baseline were evaluated using linear regression analysis, and Cox regression analysis was used to evaluate the predictive value of work ability for disability. Work-related factors were associated with a lower work ability at baseline, but had little prognostic value for disability during follow-up. The hazard ratios for disability among workers with a moderate and poor work ability at baseline were 8 and 32, respectively. All separate scales in the WAI had predictive power for future disability with the highest influence of current work ability in relation to job demands and lowest influence of diseases diagnosed by a physician. A moderate or poor work ability was highly predictive for receiving a disability pension. Preventive measures should facilitate a good balance between work performance and health in order to prevent quitting labour participation.


Orthodontic movement into bone defects augmented with bovine bone mineral and fibrin sealer: a reentry case report.
Periodontal disease can lead to migration of anterior teeth with the presence of infrabony defects. This creates the opportunity for treating such patients with a combined orthodontic-periodontic treatment. In the presented clinical case, an adult periodontal patient with extrusion of the maxillary central incisors and an infrabony defect on their lingual aspects was treated. During the surgical procedure, the bone defects were augmented with a combination of porous bovine bone mineral (Bio-Oss) and a fibrin-fibronectin sealing system (Tissucol). Ten days after surgery, the active orthodontic treatment started, and the teeth were intruded and realigned, moving the roots into the defects. After 6 months, the orthodontic appliances were removed and the teeth were retained by means of a resin-bonded splint. At this time, reduction in probing pocket depth and gingival recession was detected. Twelve months after the initial surgery, a reentry procedure was performed, showing complete filling of the predisposing defects with the presence of bone-like hard tissue. These clinical results suggest that teeth can be successfully moved and intruded into bone defects previously augmented with bovine bone substitute and fibrin glue. During the orthodontic treatment, this combined augmentation material was able to be replaced by bone-like hard tissue. At the end of the therapy, an improvement in esthetics and periodontal health status was registered.


Up-regulation of IL-23 p19 expression in human periodontal ligament fibroblasts by IL-1β via concurrent activation of the NF-κB and MAPKs/AP-1 pathways.
Interleukin (IL)-23 is an essential cytokine involved in the expansion of a novel CD4(+) T helper subset known as Th17, which has been implicated in the pathogenesis of periodontitis recently. Our previous study first identified specialized human periodontal ligament fibroblasts (hPDLFs) as an important production source of IL-23. The present study was undertaken to investigate the effects of the pro-inflammatory and Th17-polarizing mediator IL-1β on hPDLFs-mediated IL-23 p19 production, and the molecular mechanism involved. IL-23 p19 expression was in situ detected in IL-1β-stimulated hPDLFs. IL-1β was capable of stimulating the expression of IL-23 p19 mRNA and protein in cultured hPDLFs, which was attenuated by IL-1 receptor antagonist (IL-1Ra) or myeloid differentiation primary response gene 88 (MyD88) inhibitor. Meanwhile, inhibitors of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2, c-Jun-N-terminal kinase (JNK), activator protein-1 (AP-1), or nuclear factor-kappaB (NF-κB) significantly suppressed IL-23 p19 production from IL-1β-stimulated hPDLFs. Moreover, IL-1β-initiated AP-1 activation was blocked by p38 MAPK, ERK 1/2, or JNK inhibition, whereas NF-κB activity remained unaltered by all the above pathway specific inhibitors. Thus, these results provide evidence that Th17-polarizing mediator IL-1β up-regulated the expression of IL-23 p19 in hPDLFs via NF-κB signaling and MAPKs-dependent AP-1 pathways. Taken together, our findings indicate that IL-1Ra may be used therapeutically to inhibit Th17-driven inflammatory diseases including periodontitis.


Are donor lymphocytes a barrier to transplantation tolerance?
Following solid organ transplantation (SOT), populations of donor lymphocytes are frequently found in the recipient circulation. Their impact on host alloimmunity has long been debated but remains unclear, and it has been suggested that transferred donor lymphocytes may either promote tolerance to the graft or hasten its rejection. We discuss possible mechanisms by which the interaction of donor passenger lymphocytes with recipient immune cells may either augment the host alloimmune response or inhibit it. Recent work has highlighted that donor T lymphocytes are the most numerous of the donor leukocyte populations within a SOT and that these may be transferred to the recipient after transplantation. Surprisingly, graft-versus-host recognition of major histocompatibility complex class II on host B cells by transferred donor CD4 T cells can result in marked augmentation of host humoral alloimmunity and lead to early graft failure. Killing of donor CD4 T cells by host natural killer cells is critical in preventing this augmentation. The ability of passenger donor CD4 T cells to effect long-term augmentation of the host humoral alloimmune response raises the possibility that ex-vivo treatment or modification of the donor organ prior to implantation may improve long-term transplant outcomes.


Chk1 is haploinsufficient for multiple functions critical to tumor suppression.
The haploinsufficient tumor suppressor Chk1 is essential for embryonic cells, but the consequences of Chk1 loss in adult tissues are unknown. Using conditional Chk1 mice, we find that proliferating mammary cells lacking Chk1 undergo apoptosis leading to developmental defects. Conditional Chk1 heterozygosity increased the number of S phase cells and caused spontaneous DNA damage. Chk1+/- epithelia also exhibit a miscoordinated cell cycle in which S phase cells display an early mitotic phenotype. These cells maintain high levels of Cdc25A, which can promote inappropriate cell cycle transitions. Thus, Chk1 heterozygosity results in three distinct haploinsufficient phenotypes that can contribute to tumorigenesis: inappropriate S phase entry, accumulation of DNA damage during replication, and failure to restrain mitotic entry.


The effect of oral contraceptives on uterine contractility and menstrual pain: an assessment with cine MR imaging.
Low-dose oral contraceptives (OC) have been reported to control primary dysmenorrhea. Furthermore, a close relationship between dysmenorrhea and uterine contractions has been visualized with magnetic resonance imaging (MRI). This study aimed to use cine MR to demonstrate the effects of OC on myometrial contractility during menstruation and to associate the findings with dysmenorrhea. MR studies were obtained of 21 healthy female volunteers (22-47 years old) taking OC, and 20 control women (24-39 years old) not taking OC. Cine- and static MR images were obtained with a 1.5 T magnet during menstruation. Uterine contractility was assessed by the presence of endometrial distortion on cine MR, the area of the mid-sagittal uterine myometrium, and the thickness of the subendometrial low-intensity area on static images. Dysmenorrhea were assessed via a questionnaire. A total of 21 OC users and 20 controls were included in the analysis. Endometrial distortion was significantly less prominent and the subendometrial low-intensity area was significantly thinner in the OC group. Furthermore in the OC group, the uterine myometrial area was larger (although not significantly) and the degree of assessed pain was significantly lower. Both cine- and static MR images demonstrate that myometrial contractility was relatively suppressed in OC users, which may represent one of the reasons explaining the reduced menstrual pain experienced by OC users.


A novel in vitro human microglia model: characterization of human monocyte-derived microglia.
Microglia are the innate immune cells of the central nervous system. They help maintaining physiological homeostasis and contribute significantly to inflammatory responses in the course of infection, injury and degenerative processes. To date, there is no standardized simple model available to investigate the biology of human microglia. The aim of this study was to establish a new human microglia model. For that purpose, human peripheral blood monocytes were cultured in serum free medium in the presence of M-CSF, GM-CSF, NGF and CCL2 to generate monocyte-derived microglia (M-MG). M-MG were clearly different in morphology, phenotype and function from freshly isolated monocytes, cultured monocytes in the absence of the cytokines and monocyte-derived dendritic cells (M-DC) cultured in the presence of GM-CSF and IL-4. M-MG acquired a ramified morphology with primary and secondary processes. M-MG displayed a comparable phenotype to the human microglia cell line HMC3, expressing very low levels of CD45, CD14 and HLA-DR, CD11b and CD11c; and undetectable levels of CD40, CD80 and CD83, and a distinct pattern of chemokine receptors (positive for CCR1, CCR2, CCR4, CCR5, CXCR1, CXCR3, CX3CR1; negative for CCR6 and CCR7). In comparison with M-DC, M-MG displayed lower T-lymphocyte stimulatory capacity, as well as lower phagocytosis activity. The described protocol for the generation of human monocyte-derived microglia is feasible, well standardized and reliable, as it uses well defined culture medium and recombinant cytokines, but no serum or conditioned medium. This protocol will certainly be very helpful for future studies investigating the biology and pathology of human microglia.


Transient activation in a network of coupled map neurons.
The focus of this Letter is on the activity of a network of neurons pairwise coupled by inhibitory connections. Each neuron is represented by a two-dimensional map capable, when isolated, of a rich variety of complex dynamical regimes. It is shown that the network exhibits a stimulus-dependent sequential activation and inactivation of subgroups of neurons. This complex behavior is rather similar to some spatiotemporal features observed in the first stages of the olfaction process in some insects and suggests the possibility of large scale simulation of these processes by using reasonable computational capabilities.


Severe neurotoxicity despite "therapeutic" serum lithium levels.
One may not rely solely on serum lithium levels to detect or prevent lithium intoxication. A review of the reported cases of serious lithium intoxication despite "therapeutic" blood levels of lithium is presented, along with a discussion of possible explanations for the phenomenon. Possible alternate means of following a patient on lithium carbonate are discussed.


In vitro assays for the evaluation of drug resistance in tumor cells.
Oncologic diseases are among leading cause of mortality in developed countries. Despite significant progress, the use of standard cytotoxic chemotherapy has reached a therapeutical plateau. Currently, the process of selecting chemotherapy represents a trial and error method neglecting biological individuality of tumor and its bearer. The improvement of treatment results is expected from ex vivo drug sensitivity testing which may allow to choose the most effective drug for individual patient and to exclude agents to which the tumor cells exert resistance. New techniques and rapidly increasing knowledge about the molecular basis of malignant diseases provide important opportunities for the future of chemotherapy. This paper reviews current methods used to test the resistance of tumor cells to a panel of anticancer agents in vitro. In addition, we focused on the in vitro MTT assay which represents one of major technique for testing of tumor cell resistance to anticancer agents.


Determinants of blood pressure among Indonesian elderly individuals who are of normal and over-weight: a cross sectional study in an urban population.
Cardiovascular disease has become the first cause of death in Indonesia. The highest morbidity is found in the aged, and among cardiovascular disorders or diseases, the prevalence of hypertension is the highest. Many studies of the relationship between nutritional factors and hypertension have been conducted, especially with reference to the metabolic syndrome, but studies to understand determinants of blood pressure in Indonesia are lacking. There is an urgent need to gather information about various blood pressure risk factors in Indonesian elderly, which will allow policy makers to provide appropriate intervention programs. The primary purpose of this study was to investigate various determinants of blood pressure in Indonesian elderly using multistage random sampling. Data were collected through interview using structured questionnaires, anthropometric measurements, biochemical blood analysis, and blood pressure measurements. Daily nutrient intake was analyzed using the World Food 2 Dietary Assessment Program. General Linear Model and Multiple linear regression analysis were performed to determine determinants of systolic and diastolic blood pressure. Monounsaturated fatty acid, saturated fatty acid, and sodium intake, plasma total cholesterol level, the ratio of total cholesterol to HDL-cholesterol and a sport Index were determinants of blood pressure in the normal weight elderly individuals, while potassium intake, calcium intake and BMI were determination of blood pressure in the overweight elderly individuals.


Current concepts in the management of intracranial atherosclerotic disease.
Medically refractory, symptomatic intracranial atherosclerotic disease has a poor prognosis. Based on the results of the Warfarin-Aspirin Symptomatic Intracranial Disease study, the risk of ipsilateral stroke at 1.8 years is between 13 and 14% in patients with symptomatic intracranial atherosclerosis. Synergistic advances in intracranial angioplasty and stenting, modern neuroimaging techniques, and periprocedural and postprocedural antithrombotic regimens are creating new models for the diagnosis and successful endovascular treatment of intracranial stenosis. In this article, the most recent clinical developments and concepts for the diagnosis and endovascular treatment of intracranial atherosclerotic disease are discussed.


Deep tunneling dominates the biologically important hydride transfer reaction from NADH to FMN in morphinone reductase.
The temperature dependence of the primary kinetic isotope effect (KIE), combined temperature-pressure studies of the primary KIE, and studies of the alpha-secondary KIE previously led us to infer that hydride transfer from nicotinamide adenine dinucleotide to flavin mononucleotide in morphinone reductase proceeds via environmentally coupled hydride tunneling. We present here a computational analysis of this hydride transfer reaction using QM/MM molecular dynamics simulations and variational transition-state theory calculations. Our calculated primary and secondary KIEs are in good agreement with the corresponding experimental values. Although the experimentally observed KIE lies below the semiclassical limit, our calculations suggest that approximately 99% of the reaction proceeds via tunneling: this is the first "deep tunneling" reaction observed for hydride transfer. We also show that the dominant tunneling mechanism is controlled by the isotope at the primary rather than the secondary position: with protium in the primary position, large-curvature tunneling dominates, whereas with deuterium in this position, small-curvature tunneling dominates. Also, our study is consistent with tunneling being preceded by reorganization: in the reactant, the rings of the nicotinamide and isoalloxazine moieties are stacked roughly parallel to each other, and as the system moves toward a "tunneling-ready" configuration, the nicotinamide ring rotates to become almost perpendicular to the isoalloxazine ring.


Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma.
The prognostic value of vascular endothelial growth factor (VEGF) protein, known to stimulate endothelial growth and angiogenesis, was evaluated in node-negative breast carcinoma (NNBC) and compared with established prognostic factors. In 525 consecutive patients with primary invasive NNBC (T1-2N0M0; tumor, node, metastasis stage), of whom 500 patients did not receive any systemic therapy, the cytosolic levels of VEGF165 were measured by using a quantitative enzyme-linked immunosorbent assay. The median follow-up was 46 months. Univariate and multivariate analyses were performed. VEGF level was significantly inversely correlated with estrogen receptor (ER) positivity but positively associated with tumor size and histologic grade. Patients with VEGF levels above the median value (2.40 pg/microg of DNA) showed a significantly shorter survival time (P=.0012) than patients with levels less than the median value, also when analyzed as a continuous variable (P=.0277). Tumor size, grade, and ER expression were all statistically significant for overall survival in univariate analyses (P=.0069, P=.014, and P < .001, respectively). Multivariate analysis showed that VEGF level was the strongest predictor of overall survival (P=.0199). Histologic grade was also an independent predictor of survival (P=.0477). Among the 381 patients with ER-positive tumors, a group in general considered to have a good prognosis, we found a significant reduction in survival for those with levels of VEGF greater than the median value (P=.0009). The results suggest that the level of VEGF165 protein is an independent, strong prognostic factor for survival in patients with NNBC, especially in the subgroup of patients with ER positivity. Thus, cytosolic VEGF165 might be useful to select patients for adjuvant systemic therapy.


Blood loss with mifepristone--misoprostol abortion: measures from a trial in China, Cuba and India.
We compared bleeding patterns following early mifepristone-misoprostol abortion with those following early surgical abortions ( < or = 56 days gestation LMP). We analyzed women's reports of their bleeding and clinical measures of blood loss, and modeled the relationships between different bleeding measures and indicators of success and satisfaction. Using data from a multicenter trial held in China, Cuba and India, we fit bivariate and multivariate models to analyze bleeding patterns, controlling for a range of demographic, experiential and medical factors (n = 1373). Medical abortion patients perceived their bleeding to be heavier than did the surgical patients; however, there were few statistically significant differences in clinical measures of blood loss between the two groups, and blood loss rarely represented a medical problem. Nationality, far more than actual levels of bleeding, influenced women's impressions about blood loss. Although medical abortion patients saw their bleeding as heavier than did the surgical patients, their perceptions of heavier bleeding did not prevent them from having higher satisfaction levels. One exception was that if bleeding exceeded prior expectations, women with the medical method were more likely to be dissatisfied. Pain and cramps, which often accompanied bleeding, were an independently significant factor in predicting satisfaction with the method. In order for women to know what to expect with medical abortion, they must be informed beforehand about the level of bleeding that generally accompanies the procedure vs. excessive bleeding that would signal a clinical problem.


Case study: effect of handrim diameter on performance in a paralympic wheelchair athlete.
This study, with a top T-52 class athlete, determines the relationship between stroke frequency (SF) and push time (PT) and wheelchair velocity (Wv) using different handrim diameters (HD) and the effect of different HDs on the athlete's heart rate (HR) and blood lactate (LACT) at competition speeds. Wv shows a linear-direct relationship with SF but a linear-inverse relationship with PT (p < .001 in both cases). Using bigger handrims (0.37 m instead of 0.36 m), SF increases 6%, while PT decreases 27% (at 24 Km.h(-1)). HR (p < .0001) increases with Wv and is also affected by HD with differences between the 0.34 m-0.36 m handrim group (lower values) and the 0.37 m handrim (higher values). Significant interaction (p < .0001) is identified between HD and Wv. LACT results seem to follow the same direction as HR. This methodology helped the athlete to choose the optimum HD, and his achievements (some world records) indicate that HD optimization could be highly profitable in sport terms.


Luteolin suppresses TCDD-induced wasting syndrome in a cultured adipocyte model.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various toxic effects, including wasting syndrome, through activation of an aryl hydrocarbon receptor (AhR). Our previous report demonstrated that certain flavonoids inhibit the activation of AhR and suppress its DNA binding activity. In this study, we searched for an active compound among 13 flavonoids that suppressed TCDD-induced loss of lipid accumulation using 3T3-L1 adipocytes as a cell culture model for wasting syndrome. Two flavonoids, luteolin and epigallocatechin gallate, suppressed TCDD-induced loss of lipid accumulation in this model. We further investigated luteolin to clarify the underlying molecular mechanism and confirmed that luteolin inhibited nuclear translocation of AhR caused by TCDD. Luteolin also inhibited the TCDD-driven decrease in protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Although TCDD alone did not change protein expression of C/EBPβ and C/EBPδ, luteolin and TCDD up-regulated C/EBPδ expression in a dose-dependent manner. On the other hand, TCDD significantly decreased DNA binding of C/EBPβ and C/EBPδ, and luteolin completely canceled TCDD-decreased DNA binding of them. We conclude that luteolin suppresses the TCDD-induced loss of lipid accumulation in 3T3-L1 adipocytes by preventing a decrease in protein expression of PPARγ and C/EBPα, the master regulators of adipocyte differentiation and in DNA binding of C/EBPβ and C/EBPδ. Moreover, luteolin was rapidly incorporated and accumulated in 3T3-L1 adipocytes. Thus, luteolin is an attractive compound for the prevention of TCDD-induced wasting syndrome.


Peg and dowel fusion of the proximal interphalangeal joint.
The clawtoe or hammertoe deformity if frequently encountered in office practice. The etiology of this condition remains obscure, although intrinsic atrophy or imbalance was suspected as early as 1863 by Duchenne. Arthrodesing the proximal interphalangeal joint converts the more powerful flexor tendon to a flexor of the metatarsophalangeal joint, thereby alleviating pressure on the metatarsal head and distributing the weight more evenly on the forefoot. Arthrodesing is accomplished by the peg and dowel method, with the fourth toe presenting the most technical difficulties. An extensor tenotomy or dorsal capsulotomy of the metatarsophalangeal joint is frequently necessary to realign the toe with the corresponding metatarsal ray. A collodion dressing is used to immobilize the toe for a period of 4 to 6 weeks, with a fusion rate of 97% in 73 toes. All patients were contacted, with 87% responding favorably and stating that they had relief of their pain and were able to resume wearing normal footwear.


Fascia suturing of large access sites after endovascular treatment of aortic aneurysms and dissections.
To evaluate a technique for closure of a femoral artery access in which the cribriform fascia covering the common femoral artery is sutured. A consecutive series of 127 patients (103 men; median age 74 years, range 45- 89) underwent endovascular aortic aneurysm repair between August 2001 and September 2004. Twelve patients underwent a secondary intervention for a total of 139 procedures in the group. Sixty-one (43.9%) of the 139 operations were acute. Among the 257 femoral arteries used for access, a fascia suturing technique was performed in 131 (51.0%). Data were collected for analysis of access site complications, bleeding, thrombosis, pseudoaneurysm, and stenosis. A subgroup of 72 patients had ankle-brachial indexes (ABI) recorded; another subgroup of 50 patients were also investigated by duplex ultrasonography. Complications occurred in 18 (13.7%) of the 131 sutured cases. The majority (n = 16) arose within 24 hours: 8 cases of perioperative bleeding or thrombosis required open surgery and 8 cases were reoperated within 24 hours for bleeding (n = 4), thrombosis (n = 3), and 1 intimal dissection. The acute failure rate was 12.2%. Two patients had late complications: 1 case of neuralgia and 1 pseudoaneurysm that required acute surgery 28 months postoperatively. The ABI did not change significantly from pre- to postoperatively in the 72 patients examined. Five patients with stenoses did not have a reduction in ABI. In the 66 sites examined with ultrasound in 50 patients, 3 minor pseudoaneurysms were detected. The fascia suturing technique for closure of a femoral artery access during endovascular repair of aortic diseases is feasible, even in acute situations. Failures can be managed easily. Late complications requiring additional procedures are rare.


In vitro properties of red cells prepared from half-strength citrate CPD/RAS-2 (Erythro-sol) donations in PL-146 plastic.
Whole blood donations were collected into 0.5CPD anticoagulant in PL-146 plastic. This was shown to improve the stability of plasma FVIII levels when compared with CPD. RAS-2 was used as additive and this improved the in vitro properties of the red cells, such that post processing 2,3-DPG levels were maintained for 21 days and ATP levels were maintained for 28 days. Whether or not such improvements in red cell properties yield a benefit in clinical use remains to be established.


Is estimated intra-operative blood loss a reliable predictor of surgical outcomes in laparoscopic colorectal cancer surgery?
Studies have shown that laparoscopic surgery for colorectal cancer is often associated with significantly reduced intra-operative blood loss compared to the corresponding open procedures. Increased intra-operative blood loss can be associated with increased risk of post-operative morbidity and mortality. We sought to determine whether estimated intra-operative blood loss was a reliable predictor of post-operative surgical outcomes. Prospective data were collected for patients undergoing elective laparoscopic colorectal cancer resections from July 2011 to November 2013. Weighing swabs and measuring blood volume in suction devices calculated the estimated intra-operative blood loss. The operative outcome data including post-operative 30 day morbidity and mortality, length of hospital stay, re-admission and re-operation within 30 days were collected. The operative blood loss was grouped into Group 1 (less than 50 ml, Group 2 (50-150 ml) and Group 3 (over 150 ml). Patients who underwent open operations and laparoscopic conversions were excluded. The median age, length of hospital stay, male to female ratio and body mass index were similar in the three groups. There was no 30-day mortality in any of the groups. The number of re-admissions within 30 days was similar in all groups. The re-operation rates within 30 days were higher in Groups 2 and 3 at 11% and 8.6%, respectively. The post-operative complications were 12.5%, 16.7%, and 26% in groups 1, 2 and 3, respectively. There were no anastomotic leaks requiring re-operation noted in Group 3. This study has shown that intra-operative blood loss was not associated with increased median length of stay nor did it increase the 30 day re-admission rate. However, increased intra-operative blood loss was associated with increased incidence of post-operative morbidity and risk of reoperation within 30 days.


Orbital lymphangiomas: surgical treatment and clinical outcomes.
Orbital lymphangiomas (OL) are rare benign lesions that represent less than 4% of all space-occupying orbital lesions. Total surgical resection is usually difficult because of its infiltrative nature. Our objective was to analyze the indications for surgical treatment, the selection of surgical approach, and the clinical outcome after surgical treatment of OL. Five patients with OL who were surgically treated between January 2003 and December 2009 were included. Clinical, surgical, and follow-up data were retrospectively analyzed. Mean age was 32 years, with two patients treated when they were adults. Proptosis was present in all patients, and the mean duration of symptoms was 9.4 years. Two patients had clinically relevant hemorrhagic episodes. Three patients presenting with large retrobulbar tumors were submitted to the pterional approach with superolateral orbitotomy; in one patient, a lateral approach was used and in another an anterior superomedial approach was used. In all cases a subtotal removal was achieved. There was no permanent morbidity. With a mean follow-up of 3.2 years, no patient presented new hemorrhagic episodes or tumor recurrence. Subtotal resection of OL is an effective and safe treatment option, may prevent new hemorrhagic episodes, and is not associated with a high recurrence rate after a relatively short-term follow-up. Progressive proptosis, visual or oculomotor impairment, and repeated symptomatic hemorrhagic episodes are considered indications for surgery. Transcranial access should be performed in large tumors extending posteriorly.


Improved brilliant blue G staining of the internal limiting membrane with sharp cut filters of a novel viewing filter system.
We developed a new artificial image enhancement system aimed at intraoperative visibility improvement as a clinical prototype. We examined each optical characteristic and change in intraoperative visibility using brilliant blue G (BBG) staining with various sharp cut filters (SCFs). This was a retrospective and observational study. The system was composed of several filters attached to the operating microscope. Six eyes from 6 patients who presented with macular hole and underwent surgery using this system were studied. As a clinical examination, the intraoperative visibility of BBG staining intensities was compared for 4 kinds of SCFs during vitrectomy. Quantitative evaluation was calculated using the International Commission on Illumination 1976 (L*, a*, b*) color space (CIELAB) method. Furthermore, we evaluated each optical characteristic of 4 types of SCFs using extracted porcine eyes and a spectroradiometer as a clinical simulation. Suitable filter selection was possible for this system. The observed color tone and spectral irradiance changes with SCF insertion changed dynamically. In macular hole cases, the color intensities between BBG-stained and nonstained areas were improved using SCF-455 and SCF-520, which was statistically significant (p < 0.05) by CIELAB. The system improved BBG staining intensity with the use of selective SCFs.


The funny current: cellular basis for the control of heart rate.
The 'funny' (pacemaker, I(f)) current, first described almost 30 years ago in sinoatrial node (SAN) myocytes, is a mixed sodium/potassium inward current, activated on hyperpolarisation in the diastolic range of voltages. 'Funny' (f) channels are activated by intracellular cyclic adenosine monophosphate (cAMP) concentrations according to a mechanism mediating regulation of heart rate by the autonomic nervous system, as well as by voltage hyperpolarisation. Structural subunits of native f-channels are the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels; of the four HCN isoforms known, HCN4 is the most highly expressed in SAN tissue. The I(f) current is a natural target in the search for drugs aimed specifically at affecting heart rate, given its function in pacemaking. Increased heart rate has a negative influence on clinical outcome in patients with cardiovascular disease, and indeed is also an established risk factor for cardiovascular and all-cause mortality in the general population. Clearly, therefore, independent reduction of heart rate, through inhibition of the I(f) current, appears to be a suitable therapeutic option for patients with ischaemic heart disease.beta-Adrenoceptor antagonists (beta-blockers) reduce intracellular cAMP levels, and a substantial part of their negative chronotropic effect is therefore attributable to a reduction of the I(f) current. However, neither beta-blockers nor Ca(2+) channel antagonists, both of which have traditionally been used to reduce myocardial ischaemia, are 'pure' heart rate-lowering drugs. These agents may, in fact, have adverse cardiovascular and noncardiovascular effects.Conversely, the novel heart rate-reducing agent ivabradine is a specific blocker of f-channels, hence a selective inhibitor of the pacemaker I(f) current in the SAN. Ivabradine slows heart rate by reducing the I(f) current-regulated steepness of the diastolic depolarisation in SAN myocytes, thereby increasing diastolic duration, without altering action potential duration or causing negative inotropy. As such, ivabradine is particularly useful in patients with chronic stable angina pectoris. Further clinical studies are ongoing to evaluate the efficacy of ivabradine in patients with coronary heart disease, left ventricular dysfunction and heart failure. This short article reviews the current state of knowledge of the properties of the 'funny' current in relation to exploitation of the I(f) function in pacemaking generation and modulation for the pharmacological control of heart rate.


Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis.
A 2.1-year prospective study of 1373 patients given oral 8-methoxypsoralen photochemotherapy for psoriasis revealed 30 patients with a total of 48 basal-cell and squamous-cell carcinomas. The observed incidence of cutaneous carcinoma was 2.63 (95 per cent confidence limits = 1.91 to 3.90) times that expected for an age, sex and geographically matched population. Relative risk to patients with history of ionizing radiation was 3.68 (99 per cent confidence limits, 2.42 to 8.69). Patients with a previous cutaneous carcinoma had a relative risk of 10.22 (99 per cent confidence limits, 4.78 to 37.08). A higher than expected proportion of squamous-cell carcinomas and an excess of squamous-cell carcinomas in areas not exposed to sun were seen. New patients with known histories of ionizing-radiation exposure or of skin tumors should be given 8-methyoxypsoralen photochemotherapy only if they understand the risks and have disabling psoriasis untreatable by other means.


A new way to lower blood pressure: pass the chili peppers please!
Activation of TRPV1 channels in sensory nerves by capsaicin promotes neuropeptide release, leading to the perception of pain and inflammation. In this issue, Yang et al. (2010) demonstrate that vascular TRPV1 mediates a beneficial effect of capsaicin in the cardiovascular system, promoting nitric oxide release and lowering blood pressure.


Proline-rich polypeptide-1 protects the cells in vitro from genotoxic effects of mitomycin C.
A new proline-rich polypeptide (PRP-1) has been earlier shown to possess a broad spectrum of biological activities and seems to be a potential medicine. The potential genotoxic properties of PRP-1 and protective effect of PRP-1 against genotoxic action of Mitomycin C (MMC) were analyzed in details in the present work. DNA and chromosome damages were studied in KCL-22 cell line of human myeloid leukemia by the Comet assay and micronucleus induction test, respectively. The results suggest that DNA damages are, at least partly, transient and reparable. PRP-1 at the doses 0.5-2.0 microg/ml does not possess genotoxic activity. Moreover, this peptide expresses both preventive and therapeutic effects against MMC-induced DNA damage. Pre-treatment of cells with PRP-1 also prevents the appearance of daughter cells bearing as heavy MMC-induced DNA/chromosome damages as MNs. Thus, the polypeptide studied is able to protect the cells from genotoxic action of MMC. This defense includes not only DNA but also heritable chromosome damage in post-mitotic cells. Possible mechanisms of PRP-1 protective action are discussed.


The Effect of the Cartridge Used in Laparoscopic Sleeve Gastrectomy on the Development of a Staple-Line Leak.
Morbid obesity surgery has increased by 450 per cent in the past decade. Preferred surgical techniques have also changed, and since 2014, the most common surgical procedure worldwide has been laparoscopic sleeve gastrectomy (LSG). The most serious complication of this surgery is staple-line leaks, which leads to significant increases in cost and a considerable rate of mortality. This study aimed to investigate the effects of staples used in LSG on the development of staple-line leaks. The sample of the study comprised 70 patients that consecutively underwent surgery at Dokuz Eylül University Hospital between March 2014 and June 2015. The patients were divided into two equal groups. For the first group, resection was performed using blue-green EndoGIA™ cartridges (BGC) (Medtronic, Norwalk, CT). In the other group, purple Tri-Staple™ cartridges (TSC) (Medtronic) were used. To examine the effect of the cartridge type, the point and pressure of leak was determined from fresh specimens following saline infusion. No statistically significant difference was found between the two groups in terms of mean age, body mass index, gender distribution or comorbidity. The median number of cartridges used was five in both groups. The resistance of the staple line to intragastric pressure was found to be significantly higher in the TSC group compared with the BGC group [51.94 (±18.34) mmHg and 39.77 (±17.09) mmHg, respectively, P = 0.005]. Most applications undertaken to reduce the risk of leak development in LSG aim to reinforce the staple line. There are very few studies that investigated the quality of staple line, and none examined the effect of staple cartridges on the development of leaks. Therefore, we conducted this study to fill this gap in the literature. The results revealed that tissue thickness cartridge compatibility had a role in the development of leaks during the resection of gastric tissue in which the thickness is reduced from the distal to the proximal portion. We conclude that during vertical sleeve gastrectomy, using TSC that are compatible with a wider range of tissue thickness results in more durable staple lines than EndoGIA™ cartridges.


Use of Colistin in Critically Ill Patients.
Due to lack of better therapeutic options, colistin use for extensively drug-resistant Gram-negative organisms was revived in the past two decades, including in patients in intensive-care units (ICU). There are multiple knowledge gaps pertaining to the clinical use and utility of colistin in critically-ill patients, but due to lack of options, it is used in these high risk patients. In this chapter, we critically review the various topics pertaining to colistin use in critically-ill patients, while highlighting the (lack of) controlled evidence supporting common current practices pertaining to colistin use by clinicians.


Synthesis of α-Alkenyl α,β-Unsaturated Ketones via Dehydrogermylation of Oxagermacycles with Regeneration of the Germanium(II) Species.
The synthesis of α-alkenyl α,β-unsaturated ketones using germanium(II) salts is reported. Oxagermacycles derived from α,β-unsaturated ketones with germanium(II) salts and aldehydes can be transformed into α-alkenyl α,β-unsaturated ketones. Ammonium salts promoted the elimination of Ge(II) species to afford the two classes of α-alkenyl α,β-unsaturated ketones in good yields. The α-alkenyl α,β-unsaturated ketones are precursors for multisubstituted heterocycles.


Equation of Motion for a Grain Boundary.
Grain boundary (GB) migration controls many forms of microstructural evolution in polycrystalline materials. Recent theory, simulations, and experiments demonstrate that GB migration is controlled by the motion of discrete line defects or disconnections. We present a continuum equation of motion for grain boundary derived from the underlying discrete disconnection mechanism. We also present an equation of motion for the junctions where multiple grain boundaries meet-as is always the case in a polycrystal. The resulting equation of motion naturally exhibits junction drag-a widely observed phenomena in junction dynamics in solids and liquids.


Sick sinus syndrome and AV node re-entry.
A 69-year-old man presented with recurrent palpitations since childhood. Electrophysiology studies performed on two separate occasions revealed the combination of sick sinus syndrome and AV node re-entrant tachycardia. The case is reported because it illustrates marked temporal variability in the electrophysiological properties of the dual AV node pathways, and also deleterious effects of verapamil on sinoatrial node function.


Sedation in the emergency department.
The recent year's literature is reviewed concerning the use of sedation in the emergency department. The use of moderate to deep sedation is becoming common in emergency medicine for many reasons, including progressive hospital crowding, limited availability of anesthesia, and increased training in residency. This is performed for a wide variety of procedures, most commonly orthopedic. The literature discussed medications, monitoring, and the safety of current sedation practice in the emergency department. Emergency department procedural sedation and analgesia is performed with a number of medications, including propofol, etomidate, midazolam, fentanyl, ketamine, and nitrous oxide. Cardiac monitoring, pulse oximetry and capnography are used, often without strong evidence-based support of need. Complications do occur and are higher in prospective studies than in retrospective series. This suggests a degree of underreporting. Nevertheless, clinically important complications are uncommon. The year's literature reflects the reality that the performance of sedation in the emergency department is advantageous. As the era of evidence-based medicine continues to provide us with more and better information, the combined efforts of both anesthesiology and emergency medicine can hopefully contribute to improving patient safety with respect to procedural sedation.


Nonlinear transport in hybrid Polypyrrole-gold nanostructures.
We have studied charge transport in nanometer scale films of polypyrrole (PPy) that were grown electrochemically onto discontinuous ultrathin films of gold. The gold films consisted of 100 nm size islands, separated from each other by nanometer-size gaps. The thickness of PPy can be varied from 30 to 200 nm. The I-V characteristics of these hybrid PPy-Au nanostructures show strong non-linearity at low temperatures, and in particular for the more insulating samples. The hopping transport is further verified from the log I versus V(1/4) plots. Furthermore, the I-V data follow an empirical relation dlogI/dV(1/4) - T(-1/2).


Effect of gravity on learning and memory of prism adaptation.
Our body motion is adjusted properly under 1G on the earth. Thus changes in gravitational environment have significant impact on our motor control. Further, it may affect on our ability in motor learning and memory. Although some astronauts informally reported difficulties in their body control under microgravity, no quantitative research on this issue has been conducted. Here we performed the prism adaptation of a hand-reaching task under different gravitational environments. We compared learning and forgetting curves, and memory retention rates of the prism adaptation performed in upright vs. supine position under 1G, and those under 1G vs. 2G in upright position. We demonstrate that quicker learning, less forgetting and greater memory retention rates are obtained in supine position and under 2G in comparison with their counter part.


Double versus single autotransplantation in multiple myeloma; a single center experience of 100 patients.
One hundred patients with newly diagnosed multiple myeloma (MM) were treated with high-dose chemotherapy followed by single or double autologous stem cell transplantation (ASCT). Up-front treatment with a double ASCT tended to prolong progression-free and overall survival.


Effects of automated prompts for logging symptom and exercise data on mobile devices in patients with chronic obstructive pulmonary disease.
Traditional approaches to patient-reported outcomes diaries have been largely paper based. However, paper-based approaches have inherent inefficiencies such as an inability to communicate the entries in real time to the healthcare team, issues related to transport and mobility, and no tailored output related to what is entered. Traditional paper-based approaches also lack the ability to prompt users at regular intervals to record data. This lack of prompting may lead to delays in entering symptoms and exercises (diary hoarding). Electronic mobile devices have addressed some of these limitations. However, until recently these electronic devices have not been able to deliver the data in real time, thus limiting the ability of the care team to interact and respond. With the emergence of wireless mobile devices, which provide real-time linkages between the patient and the researchers, these limitations are largely eliminated. Yet, it is unclear (whether diary hoarding still occurs and) whether prompts are effective in reducing hoarding over the course of many months. The purpose of this analysis was to conduct a summative evaluation of 7474 automated prompts sent to participants with chronic obstructive pulmonary disease (n = 19). These participants were provided with mobile devices for logging exercise and symptom data over a 6-month period as part of a clinical trial. We found a marginal association between length in the study and delay in submission of exercise and symptom data in response to electronic prompts. Factors associated with delayed response to the prompts included older age, limited computer skills, and reports of no exercise. We recommend that future investigators who are using mobile devices in their research pay careful attention to usability issues as well as strategies that might keep patients engaged and motivated.


The use of abusable prescription drugs: the role of gender.
It is well documented that women face greater medical exposure to psychotropic drugs than do men, but little research examines whether women also have increased use of prescription drugs with abuse potential. The objectives were to examine gender differences in the use of abusable prescription drugs and to assess how use varies by gender and if patterns of use vary across therapeutic drug classes. With data from the 1987 National Medical Expenditures Survey (NMES), logistic regression analysis is used to model the influence of gender and other sociodemographic and diagnostic variables on the probability of drug use. Women are 48% more likely than men to use any abusable prescription drug, controlling for demographics, health status, economic status, and diagnosis. Additional analyses reveal that being female is a statistically significant predictor of anxiolytic and narcotic analgesic use but not of sedative-hypnotic or stimulant use. Marital status, age, urbanicity, employment status, and having a regular source of care explain gender differences in the use of abusable prescription drugs. Both healthcare and substance abuse treatment providers should be cognizant that women may have greater exposure to these potent prescription medicines.


Nile Red-adsorbed gold nanoparticle matrixes for determining aminothiols through surface-assisted laser desorption/ionization mass spectrometry.
This paper describes the use of Nile Red-adsorbed gold nanoparticles (NRAuNPs) as selective probes and matrixes for the determination of aminothiols through surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). The binding of three aminothiols-glutathione (GSH), cysteine (Cys), and homocysteine (HCys)-to the surfaces of these NRAuNPs induces their aggregation, which causes asubsequent changes in their color and fluorescence. Because arginine-a non-thiol amino acid-does not induce such aggregation, it is a straightforward process to use the NRAuNPs to selectively concentrate the aminothiols from a solution containing all four of these analytes; we were able to identify the three aminothiols in the precipitate, and arginine in the supernatant, directly through SALDI-MS measurements. Without using this preconcentration approach, the limits of detection (LODs) at a signal-to-noise ratio of 3 were 1.0, 2.0, and 1.3 microM for GSH, Cys, and HCys, respectively. In comparison, selective concentration using the NRAuNPs provided LODs of 25, 54, and 34 nM, for the determinations of GSH, Cys, and HCys, respectively. NRAuNP matrixes provide a number of advantages over the use of conventional organic matrixes (e.g., 2,5-dihydroxybenzoic acid), such as ease of preparation, selectivity, sensitivity, and repeatability. We validated the applicability of our method through the analyses of GSH in red blood cells and of Cys in plasma; we believe that this approach has great potential for diagnosis.


Sample preparation procedure using extraction and derivatization of carboxylic acids from aqueous samples by means of deep eutectic solvents for gas chromatographic-mass spectrometric analysis.
The paper presents a new procedure for the determination of organic acids in a complex aqueous matrix using ultrasound-assisted dispersive liquid-liquid microextraction followed by injection port derivatization and GC-MS analysis. A deep eutectic solvent (choline chloride: 4-methylphenol in a 1:2 mol ratio) was used both as an extracting solvent and as a derivatizing agent to yield ion pairs which were next converted to methyl esters of organic acids in a hot GC injection port. The procedure was optimized in terms of selection of a deep eutectic solvent, disperser solvent, and the ratio of their volumes, pH, salting out effect, extraction time, injection port temperature and time of opening the split valve. The developed procedure is characterized by low LOD (1.7-8.3 μg/L) and LOQ (5.1-25 μg/L) values, good repeatability (RSD ranging from 4.0 to 6.7%), good recoveries for most of the studied analyte (81,5-106%) and a wide linear range. The procedure was used for the determination of carboxylic acids in real effluents from the production of petroleum bitumens. A total of ten analytes at concentrations ranging from 0.33 to 43.3 μg/mL were identified and determined in the effluents before and after chemical treatment. The study revealed that in effluents treated by hydrodynamic cavitation an increase in concentration of benzoic acid and related compounds was observed.


[The interference of miocamycin on the adhesiveness and coaggregation of the bacteria responsible for periodontopathies].
The authors studied the effect miocamycin has on the adherence and coaggregation of pathogenic bacteria in periodontopathy. The data obtained by optic microscopy, after treatment of the strains with doses of miocamycin equal to 1/4 and 1/8 of the MIC after 3 and 6 hours, shows the interference effect on the coaggregation and adhesivity of the antibiotic. These results have been confirmed by the observations obtained by scanning electron microscope (SEM).


Multifocal ERG reveals long distance effects of a local bleach in the retina.
To examine the distribution of ERG-activity in the central visual field after local bleaching of the fovea, multifocal electroretinograms were recorded in eight normal volunteers before, during and after recurrent light exposure. During bleaching (90% bleached pigment), the response density (scalar product) of the foveal area (0-2 degrees eccentricity) decreased from 10.7 +/- 3.5 to 4.1 +/- 1.9 nV/degree2 (P < 0.001). The average activity in the extrafoveal macular area was unchanged, while the amplitudes were frequently (in 53 of 54 areas) enhanced at 5-30.5 degrees eccentricity. Here the average response density changed from 3.1 +/- 0.9 to 3.5 +/- 1.0 nV/degree2 (P < 0.001). A fast recovery of foveal responses after cessation of bleaching occurred. Besides a strong decrease of response in the directly bleached area, local bleaching led to enhanced activity mainly 3-27 degrees distant from the bleached area.


Lactose malabsorption among adult Indians of the Great Basin and American Southwest.
The prevalence of primary adult lactose malabsorption and the pattern of milk use were studied among 109 Indians from various tribes of the American Great Basin and Southwest. Included were 100 persons who reported being full-blooded Indians as well as three with Mexican admixture and 6 with some European ancestry. Lactose malabsorption was found in 92% of the full-blooded Indians but in only 50% Indians who acknowledged European admixture. These results agree with those of studies of native Americans done elsewhere which show very high prevalences of such lactose malabsorption among adults reported as fullblooded and lower prevalences among individuals with admitted European ancestors. The suggestion made is that in pre-Colombian times, before interbreeding with Europeans began on any scale, such lactose malabsorption may have been nearly universal among native American adults. Most of the Indians studied consumed abundant milk since childhood but were nevertheless predominantly malabsorbers as adults. This argues against the induction hypothesis advanced by some to explain the striking ethnic differences that occur around the world in primary adult lactose malabsorption.


Splenic macrophages and B cells mediate immunosuppression following abrupt withdrawal from morphine.
We have previously shown that abrupt withdrawal (AW) from morphine induces greater than 80% immunosuppression in murine spleen cells, as assessed by the capacity to mount an in vitro plaque-forming cell response to sheep red blood cells. Present studies about the mechanisms of immunosuppression following AW showed that addition of highly enriched (CD11b+) splenic macrophages (obtained by cell sorting or magnetic separation) from AW mice to cultures of normal, unfractionated spleen cells suppressed immune responses. Further, addition of highly enriched (CD19+) B cells (but not T cells) from AW mice to normal cells was also immunosuppressive. B cells from AW mice were also able to inhibit the proliferative response of normal spleen cells to concanavalin A but not to lipopolysaccharide. Overall, the data suggest that immunosuppression by AW spleen cells is a result of active suppression by macrophages and B cells.


A Bioprocessed Polysaccharide from Lentinus edodes Mycelia Cultures with Turmeric Protects Chicks from a Lethal Challenge of Salmonella Gallinarum.
Our previous studies demonstrated that a bioprocessed polysaccharide (BPP) isolated from Lentinus edodes mushroom mycelia cultures supplemented with black rice bran can protect mice against Salmonella lipopolysaccharide-induced endotoxemia and reduce the mortality from Salmonella Typhimurium infection through upregulated T-helper 1 immunity. Here, we report that a BPP from L. edodes mushroom mycelia liquid cultures supplemented with turmeric (referred to as BPP-turmeric) alters chicken macrophage responses against avian-adapted Salmonella Gallinarum and protects chicks against a lethal challenge from Salmonella Gallinarum. In vitro analyses revealed that the water extract of BPP-turmeric (i) changed the protein expression or secretion profile of Salmonella Gallinarum, although it was not bactericidal, (ii) reduced the phagocytic activity of the chicken-derived macrophage cell line HD-11 when infected with Salmonella Gallinarum, and (iii) significantly activated the transcription expression of interleukin (IL)-1β, IL-10, tumor necrosis factor α, and inducible nitric oxide synthase in response to various Salmonella infections, whereas it repressed that of IL-4, IL-6, interferon-β, and interferon-γ. We also found that BPP-turmeric (0.1 g/kg of feed) as a feed additive provided significant protection to 1-day-old chicks infected with a lethal dose of Salmonella Gallinarum. Collectively, these results imply that BPP-turmeric contains biologically active component(s) that protect chicks against Salmonella Gallinarum infection, possibly by regulating macrophage immune responses. Further studies are needed to evaluate the potential efficacy of BPP-turmeric as a livestock feed additive for the preharvest control of fowl typhoid or foodborne salmonellosis.


Untangling the wiring of the Drosophila visual system: developmental principles and molecular strategies.
The assembly of neural circuits relies on the accurate establishment of connections between synaptic partners. Precise wiring results from responses that neurons elicit to environmental cues and cell-cell contact events during development. A common design principle in both invertebrate and vertebrate adult nervous systems is the orderly array of columnar and layered synaptic units of certain neuropils. This similarity is particularly striking in the visual system, both at the structural and cell-type levels. Given the powerful genetic approaches and tools available in Drosophila, the fly visual system has been extensively used to probe how specific wiring patterns are achieved during development. In this review, we cover the developmental principles and molecular strategies that govern the assembly of columnar units (lamina cartridges and medulla columns), the formation of layers, afferent specific layer selection, and synaptogenesis in Drosophila. The mechanisms include: sequential developmental steps that ensure coordinated assembly of synaptic partners; anterograde and autocrine signaling; interactions between cell-surface molecules, or secreted molecules and their receptors that take place among neurons; and glia signaling to neurons.


Mechanisms of decreased bradykinin- induced vasodilation in experimental hyperlipemia-hyperglycemia: contribution of nitric oxide and Ca2+-activated K+ channels.
Common complications of diabetes are accelerated atherosclerosis and vascular disturbances. We investigated whether the simultaneous insult of hyperlipemia-hyperglycemia affects the reactivity of the resistance arteries to bradykinin (BK), and if so, what are the mechanisms responsible for this disturbance. Experiments were conducted on male Golden Syrian hamsters rendered hyperlipemic (H) by a fat-rich diet, diabetic (D) by streptozotocin injection, or simultaneously hyperlipemic-diabetic (HD). Normal age-matched animals were used as controls (C). At 24 weeks after the induction of disease(s) the vascular reactivity of the mesenteric resistance arteries to BK (10(-8)-10(-4) M) was assayed by the myograph technique. To explore the role of nitric oxide (NO) in modulating the endothelium-dependent BK-induced relaxation, two experimental approaches were employed: (i) in vivo administration of L-arginine (622.14 mg/kg bw) to H, D, and HD hamsters (for 12 weeks); (ii) in vitro blockage of nitric oxide synthase by N(omega)-nitro- L-arginine methyl ester (10(-4) M). To evaluate the contribution of Ca2+-activated K+ channel(s) to BK-induced relaxation, the resistance arteries were exposed to 10(-3) M tetraethylammonium. Comparatively, the endothelium-independent relaxation was assayed using sodium nitroprusside (10(-8)-10(-4) M). The results showed that compared to the H and D groups, the HD hamsters exhibited the most reduced vasodilation of the resistance arteries to BK (34.09 +/- 1.5%). The diminished vasodilation was found to be due to a dual mechanism: an L-arginine:NO pathway and a NO-independent process, mediated via Ca2+-activated K+ channels. In vivo administration of L-arginine had favourable effects especially in the HD group, which manifested (i) an; 30% improvement of attenuated BK relaxation, (ii) an increase in sensitivity of the response to BK, (iii) a 3-fold diminishment of plasma hyperglycemia. Collectively, these data explain in part, the mechanisms and possible ways to correct the arterial endothelial dysfunction when diabetes is complicated with hyperlipemia.


Efficacy of supplementary vitamins C and E on anxiety, depression and stress in type 2 diabetic patients: a randomized, single-blind, placebo-controlled trial.
Diabetes mellitus as one of the most prevalent endocrine disease is associated with high oxidative stress. Anxiety, stress and depression are common neuropsychiatric features in diabetic patients. Hyperglycemia leads to increased oxidative stress which in turn diminishes antioxidant defense system. On the other hand oxidative stress is the leading cause of depression and anxiety disorders. Thus, it seems that diabetes could accelerate the trend of psychiatric diseases. In this randomized single-blind study, evaluation of the effects of two antioxidants (vitamin C and vitamin E) was done on Stress, depression and anxiety levels in 45 diabetic patients for six weeks. The patients were randomly divided in three groups of vitamin E (400 IU day(-1)), vitamin C (1000 mg day(-1)) and placebo. DASS-21 (Depression Anxiety Stress Scales 21-item) questionnaire items were read to each patient and completed by the main investigator of this study before and after six weeks of supplementation. The scores of depression, anxiety and stress were evaluated separately based on the DASS questionnaire. The results showed a significant decrease in anxiety level (p = 0.005) in vitamin C group compared to other groups but there were no significant differences between groups in terms of changes in stress and depression scores. In conclusion, this study suggests that short-term supplementation of vitamin C is safe and beneficial for reducing anxiety levels in diabetic patients through alleviating oxidative damage.


Role of the dsRNA-dependent protein kinase (PKR) in the attenuation of protein loss from muscle by insulin and insulin-like growth factor-I (IGF-I).
Proteolysis-inducing factor (PIF), a tumour-produced cachectic factor, induced a dose-dependent decrease in protein synthesis in murine myotubes, together with an increase in phosphorylation of eucaryotic initiation factor 2 (eIF2) on the alpha-subunit. Both insulin (1 nM) and insulin-like growth factor I (IGF-I) (13.2 nM) attenuated the depression of protein synthesis by PIF and the increased phosphorylation of eIF2alpha, by inhibiting the activation (autophosphorylation) of the dsRNA-dependent protein kinase (PKR) by induction of protein phosphatase 1. A low-molecular weight inhibitor of PKR also reversed the depression of protein synthesis by PIF to the same extent, as did insulin and IGF-I. Both insulin and IGF-I-stimulated protein synthesis in the presence of PIF, and this was attenuated by Salubrinal, an inhibitor of phospho eIF2alpha phosphatase, suggesting that at least part of this action was due to their ability to inhibit phosphorylation of eIF2alpha. Both insulin and IGF-I also attenuated the induction of protein degradation in myotubes induced by PIF, this effect was also attenuated by Salubrinal. These results suggest an alternative mechanism involving PKR to explain the effect of insulin and IGF-I on protein synthesis and degradation in skeletal muscle in the presence of catabolic factors.


Pharmacokinetic variability of routinely administered bisoprolol in middle-aged and elderly Japanese patients.
The nonlinear mixed effects model (NONMEM) was used to analyze the pharmacokinetics of routinely administered bisoprolol in middle-aged and elderly Japanese patients. The subjects consisted of 29 males and 11 females with a mean age of 63.5+/-10.1. Data on the plasma concentration of bisoprolol from 94 blood samples obtained at steady-state following repetitive oral administration were analyzed using the NONMEM program, where a one-compartment model with repetitive bolus dosing was parameterized in terms of oral clearance (CL/F) and apparent volume of distribution (V/F). Individual CL/F values were correlated with body weight (WT) and creatinine clearance (CLcr). The relation between CLcr and the CL/F of bisoprolol was not altered by the CYP2D6 and CYP2C19 genotypes, gender, or age. The mean CL/F value estimated with NONMEM was 0.0612.WT+1.15.CLcr (l/h), and the mean V/F value was 2.61.WT (l). The residual interindividual variability of CL/F and V/F were 22.0% and 12.6%, respectively. The pharmacokinetic variability of bisoprolol is small even in routinely treated Japanese patients, provided that both body weight and renal function are taken into account for the prediction of oral clearance of the drug.


Mucosa-associated lymphoid tissue lymphoma with intraocular involvement.
To report the clinicopathologic features of a patient with mucosa-associated lymphoid tissue (MALT) lymphoma of the conjunctiva and associated intraocular involvement. This study is a retrospective clinicopathologic correlative case report summarizing the clinical, radiologic, and histopathologic findings of a patient with conjunctival MALT lymphoma and associated intraocular involvement. Ophthalmic examination and fluorescein angiography demonstrated progressive conjunctival infiltration bilaterally, marked uveal effusions in the left eye, and cellular white infiltrates of the choroid in the right eye. MRI of the orbit revealed a diffusely infiltrating intra- and extraocular lesion extending around the globe and optic nerve in the left eye without evidence of intracranial extension. Conjunctival biopsy showed low-grade tumor cells, consistent with the diagnosis of MALT lymphoma. The patient was successfully treated with external beam radiation with marked clinical improvement. Conjunctival MALT lymphomas, typically indolent and localized tumors, may extend into the orbit and invade local tissues such as the choroid with devastating consequences. A conjunctival biopsy can provide an easy diagnosis of this treatable entity.


A novel saturation transfer contrast method for 3D time-of-flight magnetic resonance angiography: a slice-selective off-resonance sinc pulse (SORS) technique.
Saturation transfer contrast (STC) techniques have been employed to decrease the signal intensity of observed water by saturating a broad proton component. The STC pulse, generally spatially nonselective, reduces the signal of brain background tissues as well as inflowing blood in 3D time-of-flight (TOF) angiography. We present a novel technique, a slice-selective off-resonance sinc pulse (SORS), which is employed to enhance inflowing blood and to suppress the signal of stationary background tissues. The STC effects of the SORS and other spatially nonselective methods influencing inflowing blood is discussed in detail. Angiograms using the SORS method are also presented to demonstrate improved vessel conspicuity. In addition, the SORS method is applicable to imagers with a whole-body RF transmitter system.


Effect of a patent foramen ovale in humans on thermal responses to passive cooling and heating.
Humans with a patent foramen ovale (PFO) have a higher esophageal temperature (Tesoph) than humans without a PFO (PFO-). Thus the presence of a PFO might also be associated with differences in thermal responsiveness to passive cooling and heating such as shivering and hyperpnea, respectively. The purpose of this study was to determine whether thermal responses to passive cooling and heating are different between PFO- subjects and subjects with a PFO (PFO+). We hypothesized that compared with PFO- subjects PFO+ subjects would cool down more rapidly and heat up slower and that PFO+ subjects who experienced thermal hyperpnea would have a blunted increase in ventilation. Twenty-seven men (13 PFO+) completed two trials separated by >48 h: 1) 60 min of cold water immersion (19.5 ± 0.9°C) and 2) 30 min of hot water immersion (40.5 ± 0.2°C). PFO+ subjects had a higher Tesoph before and during cold water and hot water immersion (P < 0.05). However, the rate of temperature change was similar between groups for each condition. Within a subset of 18 subjects (8 PFO+) who experienced thermal hyperpnea, PFO+ subjects experienced thermal hyperpnea at a higher absolute Tesoph but with a blunted magnitude compared with PFO- subjects. These data suggest that PFO+ subjects have a higher Tesoph at rest and have blunted thermal hyperpnea during passive heating.NEW & NOTEWORTHY Patent foramen ovale (PFO) is found in ~25-40% of the population. The presence of a PFO appears to be associated with a greater core body temperature and blunted ventilatory responses during passive heating. The reason for this blunted ventilatory response to passive heating is unknown but may suggest differences in thermal sensitivity in PFO+ subjects compared with PFO- subjects.


[Characteristics of the serum lipids in workers of lead industry].
The study covered peculiarities of lipid metabolism in workers engaged into lead production. Most the examinees showed reliable increase of total blood cholesterol, low and extremely low density lipoproteins cholesterol, triglycerides and atherogenic coefficient, combined with decreased high density lipoproteins cholesterol. Occupational factor was proved dominant in atherosclerosis formation in lead production workers. Those workers demonstrated also significant comedown of Apo A-1 amount, reliable increase of Apo B level and Apo B/Apo A-1 ratio.


Lack of relevant cross-resistance to Bt insecticide XenTari in strains of Spodoptera frugiperda (J. E. Smith) resistant to Bt maize.
The resistance of fall armyworm, Spodoptera frugiperda, has been characterized to Cry and Vip3A proteins of Bacillus thuringiensis (Bt) expressed in maize in Brazil. Here, we investigate the cross-resistance to Bt-insecticide XenTari in selected fall armyworm strains resistant to Bt maize varieties. The LC50 of XenTari in neonates of resistant strains ranged from 0.28 to 0.68 µg a.i./cm2, while for the susceptible reference strain (Sus), LC50 was 0.21 µg a.i./cm2. This indicated a resistance ratio lower than 3.2-fold. A similar variation in susceptibility was detected in EC50 values, which ranged from 0.04 to 0.13 µg a.i./cm2, demonstrating a maximum resistance ratio of 4.3-fold relative to the Sus strain (EC50 = 0.03 µg a.i./cm2). In the F1 progeny from reciprocal crosses, the LC50 ranged from 0.28 to 0.64 µg a.i./cm2 and EC50 from 0.03 to 0.18 µg a.i./cm2, similar to the values verified in parental resistant strains and representing a maximum resistance ratio of 3.0 and 6.0-fold, respectively. We also determined that susceptibility of third instar larvae to XenTari decreased when compared to neonates, however the variation remained similar. For third instar larvae from resistant strains, LC50 of XenTari ranged from 10.79 to 39.85 µg a.i./cm2, while for the Sus strain, LC50 was 9.25 µg a.i./cm2 (resistance ratio inferior to 4.3-fold). At the same stage, in heterozygous strains the LC50 ranged from 14.75 to 58.47 µg a.i./cm2 (resistance ratio inferior to 6.3-fold). Our data demonstrate a lack of significant cross-resistance to Bt-based insecticide XenTari in fall armyworm strains with resistance to Bt maize varieties.


Does simulation improve patient safety? Self-efficacy, competence, operational performance, and patient safety.
Simulation training is an essential educational strategy for health care systems to improve patient safety. The strength of simulation training is its suitability for multidisciplinary team training. There is good evidence that simulation training improves provider and team self-efficacy and competence on manikins. There is also good evidence that procedural simulation improves actual operational performance in clinical settings. However, no evidence yet shows that crew resource management training through simulation, despite its promise, improves team operational performance at the bedside. Also, no evidence to date proves that simulation training actually improves patient outcome. Even so, confidence is growing in the validity of medical simulation as the training tool of the future. The use of medical simulation will continue to grow in the context of multidisciplinary team training for patient safety.


A General Formulation for Unidimensional Unfolding and Pairwise Preference Models: Making Explicit the Latitude of Acceptance.
Probabilistic unfolding models for direct responses of persons to statements are characterised by single peaked response functions. The range in which a positive response is most likely is termed the latitude of acceptance, a well known but little researched concept in the modelling of attitude measurement. This paper derives a general form for probabilistic unfolding models in which a natural parameter characterises the latitude of acceptance. It is shown that a number of already known models for unfolding can be reexpressed in this general form with different operational functions and that, in doing so, the implied latitude of acceptance for these models is identified. It is also shown that other unfolding models can be generated readily by specifying the operational function of the general form. A general form for pairwise preference models is also presented. A discussion on the latitude of acceptance parameter as a scale parameter is also provided. Copyright 1998 Academic Press.


Preparation and in vivo degradation of controlled biodegradability of electrospun silk fibroin nanofiber mats.
Controlled biodegradability of biomaterials is very important because different functionality and durability are required for various purposes and for specific tissues and organs. From this point of view, silk-based biomaterials have poor usability because of uncontrollable degradability, even though silk fibroin (SF) is highly biocompatible and a number of studies on silk biomaterials have been published to date. In this study, we prepared SF nanofiber mats that were recrystallized in different ways. These mats were fabricated by electrospinning with ethanol/propanol mixtures of various blend ratios, and their biodegradabilities in vitro and in vivo were evaluated using rats. As a result, we can suggest an established method to modulate the degradability of SF nanofibrous materials based on long-term (12 months) observations. In particular, we elucidated how the SF nanofibers are degraded and incorporated with surrounding tissue by observation of fluorescein isothiocyanate-labeled SF nanofiber in vivo. Our findings suggest a method for controlling the degradation rate of SF for medical applications.


Assignments of the genes for rat pituitary adenylate cyclase activating polypeptide (Adcyap1) and its receptor subtypes (Adcyap1r1, Adcyap1r2, and Adcyap1r3).
Chromosomal assignments of the genes for rat pituitary adenylate cyclase activating polypeptide (Adcyap1) and all of its receptor subtypes (Adcyap1r1, Adcyap1r2, and Adcyap1r3) were performed by PCR analysis of somatic cell hybrid DNAs. Adcyap1r1, Adcyap1r2, and Adcyap1r3 were localized to rat chromosomes 9, 4, 8, and 4, respectively.


Peripheral Manifestations in Spondyloarthritis and their Effect: An Ancillary Analysis of the ASAS-COMOSPA Study.
To determine the factors associated with the presence of peripheral manifestations in patients with spondyloarthritis (SpA) from the Assessment in SpondyloArthritis international Society (ASAS)-COMOSPA study, and to evaluate the effect of these symptoms on treatment and patient-reported outcomes (PRO). All patients from the ASAS-COMOSPA study were included. All patients had an SpA diagnosis according to the rheumatologist. Patients and disease characteristics associated with the presence of these peripheral manifestations (peripheral arthritis, peripheral enthesitis, or dactylitis) were analyzed by univariate and multivariate logistic regression. Patients who reported peripheral manifestations were divided into 3 categories: current, history, and no history. The effect of peripheral involvement on PRO was evaluated through the use of 1-factor ANOVA. Out of the 3984 patients included in ASAS-COMOSPA, 2562 (64.3%) reported at least 1 peripheral manifestation, with a prevalence of 51.5%, 37.8%, and 15.6% for peripheral arthritis, peripheral enthesitis, and dactylitis, respectively. Being from South America, having a history of uveitis, having a current case or history of psoriasis, and the absence of HLA-B27 were associated with higher prevalence of peripheral manifestations. Patients with peripheral involvement showed greater use of drugs, and those with "current" peripheral manifestations showed higher levels in all PRO, in contrast to those with past or no history. Peripheral manifestations appear in 64% of patients with SpA. Psoriasis and the absence of HLA-B27 are associated with the development of peripheral symptoms. The presence of any peripheral symptom at the time of the visit was associated with higher scores in all PRO.


Changes of circulatory-metabolic indices and skull biomechanics with brain activity during aging.
The cerebral blood flow values used in experimental and clinical investigations as the informative criteria for brain blood supply are often misleading. The correlation between the cerebral blood supply and brain function is not proven in all cases. An increase of brain activity is known to be accompanied by a rise of blood flow in activated regions, while a decreased activity results in a decreased blood flow. This demonstrates the close correlation between the brain blood supply and its activity. Such a correlation had not been noted in the age-dependent decrease of cerebral blood flow, suggesting the existence of special age-related mechanisms that develop with age to maintain brain metabolism. The biomechanical properties are of special significance as predicted in the early 20th century. Only recently were they validated by the simultaneous recording of Transcranial Dopplerogram and Rheoencephalogram with in-depth analysis focused on single cardiac cycles. Functioning of the intracranial blood and cerebrospinal fluid dynamics was integrated with a special physiological test "Prognosis-2" to measure brain cognitive function. Correlation was demonstrated with the circulatory-metabolic state of brain activity, especially in people with changing cognitive function. The data supports a conceptual model of adequate circulatory-metabolic supply of brain activity, showing the functional unity, which follows from integration of the mentioned systems.