A high throughput screen for RGS proteins using steady state monitoring of free phosphate formation.
G-protein coupled receptors are a diverse group that are the target of over 50% of marketed drugs. Activation of these receptors results in the exchange of bound GDP for GTP in the Gα subunit of the heterotrimeric G-protein. The Gα subunit dissociates from the β/γ subunits and both proceed to affect downstream signaling targets. The signal terminates by the hydrolysis of GTP to GDP and is temporally regulated by Regulators of G-protein Signaling (RGS) proteins that act as GTPase Activating Proteins (GAPs). This makes RGS proteins potentially desirable targets for "tuning" the effects of current therapies as well as developing novel pharmacotherapies. Current methods for evaluating RGS activity depend on laborious and/or expensive techniques. In this study we developed a simple and inexpensive assay for the steady state analysis of RGS protein GAP activity, using RGS4, RGS8 and RGS17 as models. Additionally, we report the use of RGS4 as a model for high throughput assay development. After initial setup, this assay can be conducted in a highly parallel fashion with a read time of less than 8 minutes for a 1536-well plate. The assay exhibited a robust Z-factor of 0.6 in a 1536-well plate. We conducted a pilot screen for inhibitors using a small, 2320 compound library. From this screen, 13 compounds were identified as compounds for further analysis. The successful development of this assay for high-throughput screening provides a low cost, high speed, simple method for assessing RGS protein activity.


Lateral mobility of membrane-binding proteins in living cells measured by total internal reflection fluorescence correlation spectroscopy.
Total internal reflection fluorescence correlation spectroscopy (TIR-FCS) allows us to measure diffusion constants and the number of fluorescent molecules in a small area of an evanescent field generated on the objective of a microscope. The application of TIR-FCS makes possible the characterization of reversible association and dissociation rates between fluorescent ligands and their receptors in supported phospholipid bilayers. Here, for the first time, we extend TIR-FCS to a cellular application for measuring the lateral diffusion of a membrane-binding fluorescent protein, farnesylated EGFP, on the plasma membranes of cultured HeLa and COS7 cells. We detected two kinds of diffusional motion-fast three-dimensional diffusion (D(1)) and much slower two-dimensional diffusion (D(2)), simultaneously. Conventional FCS and single-molecule tracking confirmed that D(1) was free diffusion of farnesylated EGFP close to the plasma membrane in cytosol and D(2) was lateral diffusion in the plasma membrane. These results suggest that TIR-FCS is a powerful technique to monitor movement of membrane-localized molecules and membrane dynamics in living cells.


Prevention of MS Requires Intervention on the Causes of the Disease: Reconciling Genes, Epigenetics, and Epstein Barr Virus.
Prevention of multiple sclerosis requires intervention on modifiable causes of the condition making it necessary to establish what those causes are. MS is often stated to be a polygenic disease, with causal contributions from environmental factors and gene-environment interactions, implying an additive and independent relationship of these factors. Mechanistically there are no independent contributions of genes or environmental factors to traits. This model is unrealistic but still useful and underlies the concept of heritability, a foundational parameter in population genetics. However, it perpetuates a debate on an irreconcilable dichotomy about whether MS is primarily genetic or environmental. In particular, epidemiological evidence now exists for a causal, possibly even necessary, role for Epstein Barr Virus in MS. The additive model makes it unintuitive to reconcile MS as a genetic disease but also independently a viral illness. In this perspective it is argued that starting from a realistic interaction only model, based on broadly accepted biological premises, and working forward to explain why the classical additive model gives useful results, there is actually no paradox. An integrated approach using population genetic studies, immunology and molecular virology offers a particularly promising route to establish the elusive role of EBV in MS pathology, as EBV is a large and complex virus and its latency, dysregulated in most EBV-related pathologies, is hard to study in vivo. This approach may offer a route to prevention of MS altogether.


Toad urinary bladder epithelial cells contain an analogue of cytoskeletal protein 4.1.
Epithelial cell polarity and vectorial transport require cytoskeletal proteins that maintain local cell membrane structure and mediate cytoplasmic vesicle movement. The cytoskeleton of leaky epithelia, such as the intestinal mucosa and renal proximal tubule cells, has been extensively studied. However, cytoskeletal studies in tight epithelia such as the mammalian collecting duct and toad urinary bladder generally have been confined to ultrastructural investigation. Recent research in nonepithelial cell types has identified an interesting family of cytoskeletal proteins. Present in multiple cell types, these protein 4.1 analogues share a number of similar functional characteristics, yet are structurally diverse. They are multiply phosphorylated by several different kinases, and phosphorylation regulates their associations with other cytoskeletal constituents, integral membrane components, and cytoplasmic vesicles. Using a combination of immunochemical and immunofluorescent techniques, we have demonstrated that toad bladder epithelial cells contain a 65-kDa analogue of human erythrocyte protein 4.1. Toad bladder epithelial cell protein 4.1 is structurally similar to its erythrocyte counterpart and is phosphorylated. This protein 4.1 species is present throughout the toad bladder granular cell cytoplasm, suggesting that it participates in multiple granular cell functions.


Tiling genomes of pathogenic viruses identifies potent antiviral shRNAs and reveals a role for secondary structure in shRNA efficacy.
shRNAs can trigger effective silencing of gene expression in mammalian cells, thereby providing powerful tools for genetic studies, as well as potential therapeutic strategies. Specific shRNAs can interfere with the replication of pathogenic viruses and are currently being tested as antiviral therapies in clinical trials. However, this effort is hindered by our inability to systematically and accurately identify potent shRNAs for viral genomes. Here we apply a recently developed highly parallel sensor assay to identify potent shRNAs for HIV, hepatitis C virus (HCV), and influenza. We observe known and previously unknown sequence features that dictate shRNAs efficiency. Validation using HIV and HCV cell culture models demonstrates very high potency of the top-scoring shRNAs. Comparing our data with the secondary structure of HIV shows that shRNA efficacy is strongly affected by the secondary structure at the target RNA site. Artificially introducing secondary structure to the target site markedly reduces shRNA silencing. In addition, we observe that HCV has distinct sequence features that bias HCV-targeting shRNAs toward lower efficacy. Our results facilitate further development of shRNA based antiviral therapies and improve our understanding and ability to predict efficient shRNAs.


New models of frontal-subcortical skeletomotor circuit pathology in tardive dyskinesia.
Tardive dyskinesia (TD) is a hyperkinetic movement disorder that can occur as a side effect of treatment with antipsychotic medications. Because antipsychotics block the D2 family of dopamine receptors in the striatum, it has long been suspected this blockade contributes to the development of TD. Specifically, increased sensitivity of the dopamine receptors following chronic blockade has been thought to result in abnormal functioning of the frontal-subcortical (FSC) skeletomotor circuit and the symptoms of TD. However, this hypothesis remains unproven. In recent years, substantial research has focused on the basal ganglia and FSC circuits. This research has resulted in the development of the focused selection model of skeletomotor circuit function. This hypothesis provides a compelling model of neurocircuit abnormalities in TD. A greater understanding of the neuropathology of TD may lead to the development of better treatment and prevention strategies for this disorder. Furthermore, this information may contribute to a more complete understanding of normal skeletomotor circuit function and the role of circuit pathology in numerous neuropsychiatric conditions.


Weak coupling between intracellular feedback loops explains dissociation of clock gene dynamics.
Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this "presumably transient" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.


Scrapie-infected mice and PrP knockout mice share abnormal localization and activity of neuronal nitric oxide synthase.
PrP(Sc), the only identified component of the scrapie prion, is a conformational isoform of PrPc. The physiological role of PrPc, a glycolipid-anchored glycoprotein, is still unknown. We have shown previously that neuronal nitric oxide synthase (nNOS) activity is impaired in the brains of mice sick with experimental scrapie as well as in scrapie-infected neuroblastoma cells. In this work we investigated the cell localization of nNOS in brains of wild-type and scrapie-infected mice as well as in mice in which the PrP gene was ablated. We now report that whereas in wild-type mice, nNOS, like PrPc, is associated with detergent-insoluble cholesterol-rich membranous microdomains (rafts), this is not the case in brains of scrapie-infected or in those of adult PrP(0/0) mice. Also, adult PrP(0/0), like scrapie-infected mice, show reduced nNOS activity. We suggest that PrPc may play a role in the targeting of nNOS to its proper subcellular localization. The similarities of nNOS properties in PrP(0/0) as compared with scrapie-infected mice suggest that at least this role of PrPc may be impaired in scrapie-infected brains.


Separation of 7-methyl- and 7-(2-hydroxyethyl)-guanine adducts in human DNA samples using a combination of TLC and HPLC.
We have used a combination of thin-layer chromatography (TLC) and high pressure liquid chromatography (HPLC) to achieve separation of 32P-postlabelled 7-methylguanine and 7-(2-hydroxyethyl)-guanine adducts. The level of these two adducts was determined in human total white blood cells (mean values 0.7 to 1.5 adducts per 10(7) normal nucleotides) and isolated lymphocytes (mean values 1.1 to 12 adducts per 10(7) normal nucleotides). The separation of these two adducts revealed that the level of 7-(2-hydroxyethyl)-guanine was twice the level of 7-methylguanine adducts in total white blood cells, whereas, in isolated lymphocytes it was at least four times more than the 7-methylguanine adduct. The combined level of these two adducts in the lymphocytes of non-smokers was 1.1 to 8.4 adducts per 10(7) normal nucleotides and in the lymphocytes of smokers, the level was 5.6 to 12 adducts per 10(7) normal nucleotides. We also report detection of three unidentified adducts in the samples analysed, and at least one of these adducts seemed to be related to smoking. The chromatographic behaviour and depurination at neutral pH indicated the probable 7-alkylguanine or 3-alkyladenine nature of these unidentified adducts.


Network Analysis Identifies Regulators of Basal-Like Breast Cancer Reprogramming and Endocrine Therapy Vulnerability.
Basal-like breast cancer is the most aggressive breast cancer subtype with the worst prognosis. Despite its high recurrence rate, chemotherapy is the only treatment for basal-like breast cancer, which lacks expression of hormone receptors. In contrast, luminal A tumors express ERα and can undergo endocrine therapy for treatment. Previous studies have tried to develop effective treatments for basal-like patients using various therapeutics but failed due to the complex and dynamic nature of the disease. In this study, we performed a transcriptomic analysis of patients with breast cancer to construct a simplified but essential molecular regulatory network model. Network control analysis identified potential targets and elucidated the underlying mechanisms of reprogramming basal-like cancer cells into luminal A cells. Inhibition of BCL11A and HDAC1/2 effectively drove basal-like cells to transition to luminal A cells and increased ERα expression, leading to increased tamoxifen sensitivity. High expression of BCL11A and HDAC1/2 correlated with poor prognosis in patients with breast cancer. These findings identify mechanisms regulating breast cancer phenotypes and suggest the potential to reprogram basal-like breast cancer cells to enhance their targetability. SIGNIFICANCE: A network model enables investigation of mechanisms regulating the basal-to-luminal transition in breast cancer, identifying BCL11A and HDAC1/2 as optimal targets that can induce basal-like breast cancer reprogramming and endocrine therapy sensitivity.


Non-Gaussian space-variant resolution modelling for list-mode reconstruction.
Partial volume effect is an important source of bias in PET images that can be lowered by accounting for the point spread function (PSF) of the scanner. We measured such a PSF in various points of a clinical PET scanner and modelled it as a product of matrices acting in image space, taking the asymmetrical, shift-varying and non-Gaussian character of the PSF into account (AMP modelling), and we integrated this accurate image space modelling into a conventional list-mode OSEM algorithm (EM-AMP reconstruction). We showed on the one hand that when a sufficiently high number of iterations are considered, the AMP modelling lead to better recovery coefficients at reduced background noise compared to reconstruction where no or only partial resolution modelling is performed, and on the other hand that for a small number of iterations, a Gaussian modelling gave the best recovery coefficients. Moreover, we have demonstrated that a deconvolution based on the AMP system response model leads to the same recovery coefficients as the corresponding EM-AMP reconstruction, but at the expense of an increased background noise.


Direct compaction properties of Zingiberis Rhizoma extracted powders coated with various shell materials: Improvements and mechanism analysis.
Direct compaction (DC) attracts more and more attention for tablet manufacturing; however, its application in natural plant product (NPP) tablets is still extremely limited. In this study, 8 kinds of composite particles (CPs) based on the Zingiberis Rhizoma extracted powder (ZR) (a natural plant product powder with poor DC properties) were prepared with different shell materials, including hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), dextran, inulin, mannitol, silica, and their combinations. Their physical properties and compacting parameters were characterized comprehensively. The results demonstrated that (i) fluid bed coating was not a simple process of superposition and transmission of the physical properties of raw materials; and (ii) all the shell materials studied could improve the DC properties of problematic ZR to some degree and the combination of 7% HPMC and 1% silica showed to be the best to markedly improve both the compactibility and flowability of ZR. As a whole, by virtue of the design of core-shell particles, qualified tablets with high ZR loadings were successfully produced via continuous DC in this study. These findings are beneficial to boosting the development of natural plant tablets through DC.


Ozonation and Depolymerization of Extracellular Polymeric Substances (EPS) Extracted from a Biofilter Treating Gaseous Toluene.
Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters. In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study. EPS was sequestered from the biofilm, obtained from a biofilter treating gaseous toluene, and then it was exposed to gaseous ozone at 272 ± 22 ppm continuously for 12 h. The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely. The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain. High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone. During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS. Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation. Additionally, this can be used to study the composition of biofilm EPS from biofilters.


Postoperative treatment of patients submitted to reconstruction with massive homoplastic grafting.
Over the last 10 years at the Ist Orthopaedic Clinic of the Rizzoli Institute more than 350 cases of massive bone homoplastic cadaver-retrieved reconstruction were carried out, after bone tumor resection. We reported the postoperative management indicated to the patient to prevent complications and to improve functional results. The indications protocol includes time required for immobilization, motion, and partial and total loading; functional and radiographic results expected. Finally, these indications are specified for site of reconstruction and fixation chosen.


The risk of occupational tuberculosis in Serbian health care workers.
Health care workers in the Clinical Center of Serbia. To evaluate tuberculosis (TB) incidence by job category comparing the rates of TB in health care workers (HCWs) working in pulmonary departments, other (non-pulmonary) departments, and in the general population in Serbia. Prospective cohort study from 1992 to 2004. Assessment of the relationship between employment in different departments and TB incidence was expressed by relative risk (RR), which was calculated using the annual TB incidence in the population of Serbia as the baseline rate. A total of 24 HCWs developed active TB in the study period. The mean incidence rate was 413.2 per 100000 persons (RR = 12.2) for hospital staff in the pulmonary department and 20.3/100000 (RR = 0.6) for other departments. Nurses and technicians were at 7.8 times higher risk of developing TB than doctors. The mean working period before the onset of illness was 15.1 years (95%CI 5.1-25.1) for HCWs in pulmonary departments and 8.1 years (95%CI 4.6-11.6) in non-pulmonary departments (P = 0.006). This study indicates that HCWs were at an increased risk of TB, most likely from nosocomial transmission in high-risk departments.


In vivo antiplaque efficacy of combined antimicrobial dentifrice and rinse hygiene regimens.
To evaluate using digital plaque image analysis the antiplaque efficacy of oral care regimens including use of antimicrobial toothpaste in combination with antimicrobial mouthrinse. 16 subjects completed the study protocol including: (1) initial treatment phase, all subjects used a standard sodium fluoride dentifrice with 2x/day brushing, (2) second treatment phase, subjects were randomized to two treatment groups: stannous fluoride/sodium hexametaphosphate dentifrice or sodium fluoride triclosan/copolymer dentifrice; (3) third treatment phase, the group using stannous fluoride dentifrice rinsed with alcohol-free cetylpyridinium chloride mouthrinse and the group using triclosan dentifrice rinsed with essential oil mouthrinse. During each phase, plaque levels were assessed in the morning before toothbrushing (AM), post-brushing in the morning (PB) and in the afternoon (PM). Stannous fluoride dentifrice was superior to triclosan dentifrice in plaque growth inhibition between toothbrushing. Both mouthrinses provided additional plaque prevention benefits when used with antimicrobial dentifrices. The cetylpyridinium chloride mouthrinse and stannous fluoride dentifrice regimen was particularly effective, building accretive efficacy over time. Average plaque reductions exceeded 50% vs. sodium fluoride dentifrice alone. Chemotherapeutic dentifrices and rinses increase plaque control used alone and particularly in combination. The stannous fluoride-cetylpyridinium chloride regimen showed the greatest benefits.


Role of phosphorolytic cleavage in cellobiose and cellodextrin metabolism by the ruminal bacterium Prevotella ruminicola.
In bacteria, cellobiose and cellodextrins are usually degraded by either hydrolytic or phosphorolytic cleavage. Prevotella ruminicola B(1)4 is a noncellulolytic ruminal bacterium which has the ability to utilize the products of cellulose degradation. In this organism, cellobiose hydrolytic cleavage activity was threefold greater than phosphorolytic cleavage activity (113 versus 34 nmol/min/mg of protein), as measured by an enzymatic assay. Cellobiose phosphorylase activity (measured as the release of P(i)) was found in cellobiose-, mannose-, xylose-, lactose-, and cellodextrin-grown cells (> 92 nmol of P(i)/min/mg of protein), but the activity was reduced by more than 74% for cells grown on fructose, L-arabinose, sucrose, maltose, or glucose. A small amount of cellodextrin phosphorylase activity (19 nmol/min/mg of protein) was also detected, and both phosphorylase activities were located in the cytoplasm. Degradation involving phosphorolytic cleavage conserves more metabolic energy than simple hydrolysis, and such degradation is consistent with substrate-limiting conditions such as those often found in the rumen.


New guidance on long-term oxygen therapy management and delivery.
New guidance on how long-term oxygen therapy is managed and delivered will be implemented in 2005 (Box 1). One of its aims is to reduce the number of patients who receive the treatment inappropriately. The guidance comes in response to a Department of Health review of domiciliary oxygen therapy back in 2000. This looked at supply arrangements and whether patients should continue to access the service via GP prescription. It included the views of royal colleges, patient groups and oxygen suppliers.


Alcoholic cardiomyopathy: clinical and experimental pathological changes.
In this review we survey the features of alcohol-induced lesions in the heart, in both the clinical and laboratory-animal setting. The data indicates a diverse range of lesions that contribute to the genesis of the entity alcoholic cardiomyopathy (also referred to as alcoholic heart muscle disease). Biopsies of affected patients reveal lesions similar to dilated cardiomyopathy though quantitative morphometry can distinguish between the two disorders. Biochemical analysis reveals an increase in the activities of some enzymes, though the pathogenetic nature of these alterations are unknown, but may well be adaptive. The induction of ischaemia in acute ethanol exposure may contribute to the heart muscle damage, though long term experimental studies indicate that heat shock proteins are reduced, making the heart more vulnerable to cardiac dysfunction. Changes in the rate of protein turnover induced by alcohol appear to be a central feature in animal studies and it is very likely that similar changes occur in man.


Angiogenesis Inhibition in Prostate Cancer: An Update.
Prostate cancer (PCa), like all other solid tumors, relies on angiogenesis for growth, progression, and the dissemination of tumor cells to other parts of the body. Despite data from in vitro and in vivo preclinical studies, as well as human specimen studies indicating the crucial role played by angiogenesis in PCa, angiogenesis inhibition in clinical settings has not shown significant benefits to patients, thus challenging the inclusion and usefulness of antiangiogenic agents for the treatment of PCa. However, one of the apparent reasons why these antiangiogenic agents failed to meet expectations in PCa can be due to the choice of the antiangiogenic agents, because the majority of these drugs target vascular endothelial growth factor-A (VEGFA) and its receptors. The other relevant causes might be inappropriate drug combinations, the duration of treatment, and the method of endpoint determination. In this review, we will first discuss the role of angiogenesis in PCa growth and progression. We will then summarize the different angiogenic growth factors that influence PCa growth dynamics and review the outcomes of clinical trials conducted with antiangiogenic agents in PCa patients and, finally, critically assess the current status and fate of antiangiogenic therapy in this disease.


Efficient search for a face by chimpanzees (Pan troglodytes).
The face is quite an important stimulus category for human and nonhuman primates in their social lives. Recent advances in comparative-cognitive research clearly indicate that chimpanzees and humans process faces in a special manner; that is, using holistic or configural processing. Both species exhibit the face-inversion effect in which the inverted presentation of a face deteriorates their perception and recognition. Furthermore, recent studies have shown that humans detect human faces among non-facial objects rapidly. We report that chimpanzees detected chimpanzee faces among non-facial objects quite efficiently. This efficient search was not limited to own-species faces. They also found human adult and baby faces--but not monkey faces--efficiently. Additional testing showed that a front-view face was more readily detected than a profile, suggesting the important role of eye-to-eye contact. Chimpanzees also detected a photograph of a banana as efficiently as a face, but a further examination clearly indicated that the banana was detected mainly due to a low-level feature (i.e., color). Efficient face detection was hampered by an inverted presentation, suggesting that configural processing of faces is a critical element of efficient face detection in both species. This conclusion was supported by a simple simulation experiment using the saliency model.


The response to second-line induction with bortezomib and dexamethasone is predictive of long-term outcomes prior to high-dose chemotherapy with autologous stem cell transplantation for multiple myeloma.
We retrospectively investigated the efficacy and predictive factors for the treatment outcomes of bortezomib plus dexamethasone (BD) as second-line induction therapy prior to high-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) in multiple myeloma (MM) patients. Sixty-six transplant eligible MM patients treated by the Kyoto Clinical Hematology Study Group between 2006 and 2011 were investigated. Conventional induction chemotherapy, including vincristine, doxorubicin and dexamethasone (VAD) and high-dose dexamethasone (HDD), was used as first-line induction therapy in all patients, seven (10.6%) of whom attained a very good partial response (VGPR). Of the 59 patients who did not attain VGPR with VAD or HDD, 33 were given BD as second-line induction therapy prior to HDT/ASCT. Patients not treated with BD induction showed an overall response rate (ORR, i.e., better than partial response) of 85.3% after induction therapy, while the ORR of patients treated with BD induction improved from 42.4% after conventional induction therapy to 84.8% after BD. The overall survival (OS) and progression-free survival (PFS) of patients not treated with BD induction were not significantly influenced by the response to induction therapy. Among the patients treated with BD, failure in attaining VGPR prior to ASCT was associated with a significantly shorter PFS and it also tended to show a shorter OS, while the disease stage and achievement of a complete response after HDT/ASCT had no impact on OS or PFS. The achievement of at least VGPR with second-line BD induction therapy is a prerequisite for attaining longer OS and PFS after HDT/ASCT.


Physical forces regulating hemostasis and thrombosis: Vessels, cells, and molecules in illustrated review.
This illustrated review focuses on the physical forces that regulate hemostasis and thrombosis. These phenomena span from the vessel to the cellular to the molecular scales. Blood is a complex fluid with a viscosity that varies with how fast it flows and the size of the vessel through which it flows. Blood flow imposes forces on the vessel wall and blood cells that dictates the kinetics, structure, and stability of thrombi. The mechanical properties of blood cells create a segmented flowing fluid whereby red blood cells concentrate in the vessel core and platelets marginate to the near-wall region. At the vessel wall, shear stresses are highest, which requires a repertoire of receptors with different bond kinetics to roll, tether, adhere, and activate on inflamed endothelium and extracellular matrices. As a thrombus grows and then contracts, forces regulate platelet aggregation as well as von Willebrand factor function and fibrin mechanics. Forces can also originate from platelets as they respond to the external forces and sense the stiffness of their local environment.


EEG alpha oscillations: the inhibition-timing hypothesis.
The traditional belief is that the event-related alpha response can solely be described in terms of suppression or event-related desynchronization (ERD). Recent research, however, has shown that under certain conditions alpha responds reliably with an increase in amplitudes (event-related synchronization or ERS). ERS is elicited in situations, where subjects withhold or control the execution of a response and is obtained over sites that probably are under, or exert top-down control. Thus, we assume that alpha ERS reflects top-down, inhibitory control processes. This assumption leads over to the timing aspect of our hypothesis. By the very nature of an oscillation, rhythmic amplitude changes reflect rhythmic changes in excitation of a population of neurons. Thus, the time and direction of a change - described by phase - is functionally related to the timing of neuronal activation processes. A variety of findings supports this view and shows, e.g., that alpha phase coherence increases between task-relevant sites and that phase lag lies within a time range that is consistent with neuronal transmission speed. Another implication is that phase reset will be a powerful mechanism for the event-related timing of cortical processes. Empirical evidence suggests that the extent of phase locking is a functionally sensitive measure that is related to cognitive performance. Our general conclusion is that alpha ERS plays an active role for the inhibitory control and timing of cortical processing whereas ERD reflects the gradual release of inhibition associated with the emergence of complex spreading activation processes.


Awareness among barbers about health hazards associated with their profession.
Barbers are important professionals of the community which are still owned, cared and financed by the community especially the rural one. Barbers besides performing duties in social events like marriage, circumcision etc is also responsible for hair and nail cutting. In urban settings they have developed their profession by incorporating facial massage and make-up. It is the need of their profession to utilize instruments like knife, blades etc. The objective of the study was to assess awareness among barbers regarding health hazards related to their profession and to identify professional practices linked with infection transmission. This descriptive cross sectional study was conducted in Kharian city of district Gujrat, located almost mid-way between Lahore and Islamabad, from June 2003 to September 2003. Sample of 50 barbers were selected by simple random sampling technique. Data was collected by using a semi-structured questionnaire and a checklist. Data was analyzed using SPSS 10. The mean age of barbers interviewed was 33.3 years with SD +/- 8.3. It was found that 29 (58%) barbers denied about any health hazards associated with their profession whereas 21 (42%) had knew about hepatitis, AIDS; they also described the role of contaminated blades, clips, towels, apron, and combs in causing skin problems. It was observed that 90% of barbers did not wash hands, 80% did not change the apron, 66% did not change towel during barbering services to different customers. Besides 7 (14%) barbers were also performing minor surgeries like circumcision, in growing toe nail excision and abscess drainage. There was significant difference in level of awareness among barbers in respect of age; educational status and duration of working. Age group (15-25) had better knowledge about the health hazards than barbers in age group (26-50). There is a significant difference (p < 0.05) in the awareness of those who got formal education. As for the effect of media on the knowledge of these workers, it was observed that 78% of them had the access to TV and out of these 69% had significant knowledge about health hazards related to barbering profession. The level of knowledge among barbers about health hazards associated with their profession is very poor. Majority of them do not have any perception of unhealthy working practices in barbering. Awareness about threat of receiving hazardous infection from their customers is also unsatisfactory.


Atrial fibrillation: beyond irregularly irregular: the basis for acute and chronic treatment.
Today atrial fibrillation is the most prevalent sustained arrhythmia encountered in clinical practice; it places a heavy burden on the healthcare system. The purpose of this article is to explore the principles underlying the treatment of both acute and chronic atrial fibrillation.


Deaths in free-living barn owls (Tyto alba).
Pathological examinations were made on 20 free-living barn owls, Tyto alba, that died during winter-spring 1985 Victoria, Australia. Starvation was the likely cause of the deaths with all the birds being in poor condition and markedly underweight (235 to 265 g). The owls had suffered a massive decline in the abundance of their prey, the house mouse, Mus musculus, following the end of a mouse plague. The life cycle of the barn owl makes it susceptible to deaths due to starvation following seasonal variability in prey availability. A secondary finding was localised erosions of the gizzard mucosa associated with infestation by cestodes of the genus Choanataenia.


Essential oil composition and biological activities of Ononis alba Poir (Fabaceae).
The phytochemical and biological properties of Ononis alba Poir L. (Fabaceae) were investigated for the first time in this study. The chemical composition of the essential oil obtained from the aerial parts was analysed by GC-MS. The phenolic contents of extracts obtained with different solvents were determined by the Folin-Ciocalteu assay and the antioxidant activity was evaluated through DPPH and CUPRAC methods. The inhibitory potential of these extracts was evaluated on α-amylase and α-glucosidase, whereas the antimicrobial effect was verified against some bacteria and fungi through the well diffusion method. Ketones and carboxylic acids were the main essential oil constituents. The highest total phenolic and flavonoid content as well as the best antioxidant capacity were noticed on the n-butanol extract. All the extracts showed a greater efficiency than acarbose in the inhibition of α-amylase. On the other hand, they demonstrated a mild inhibition effect against Staphylococcus aureus and Fusarium oxysporum.


Chlamydia pneumoniae in community-acquired pneumonia.
Chlamydia pneumoniae has been established recently as an important human respiratory pathogen. The aim of this study was to define the prevalence of C. pneumoniae in community-acquired pneumonia. We prospectively investigated adult patients who were treated as inpatients and outpatients. Acute and convalescent serum samples were obtained from each patient. Serological diagnosis of C. pneumoniae infection was determined by enzyme-linked immunosorbent assay (ELISA). Eighty paired sera were tested for C. pneumoniae-specific IgM, IgG and IgA. Twenty-one patients (26.2%) had serological results compatible with acute C. pneumoniae infection. Eighteen (85.7%) of these infected patients were C. pneumoniae-specific IgM positive, three had a seroconversion of IgA and two had a four-fold or greater increase in C. pneumoniae-specific IgG antibody titer. The most common clinical manifestations of community-acquired pneumonia due to C. pneumoniae were fever (100%), cough (100%), chest pain (47.6%) and shortness of breath (42.9%). Physical examination revealed crackle in 85.7 per cent of the cases. These findings suggest that C. pneumoniae is a common cause of community-acquired pneumonia in Thailand.


High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes.
Water and protein dynamics on a nanometer scale were measured by quasi-elastic neutron scattering in the piezophile archaeon Thermococcus barophilus and the closely related pressure-sensitive Thermococcus kodakarensis, at 0.1 and 40 MPa. We show that cells of the pressure sensitive organism exhibit higher intrinsic stability. Both the hydration water dynamics and the fast protein and lipid dynamics are reduced under pressure. In contrast, the proteome of T. barophilus is more pressure sensitive than that of T. kodakarensis. The diffusion coefficient of hydration water is reduced, while the fast protein and lipid dynamics are slightly enhanced with increasing pressure. These findings show that the coupling between hydration water and cellular constituents might not be simply a master-slave relationship. We propose that the high flexibility of the T. barophilus proteome associated with reduced hydration water may be the keys to the molecular adaptation of the cells to high hydrostatic pressure.


[ASSESSMENT OF THE FEASIBILITY OF USING CONE-BEAM COMPUTED TOMOGRAPHY IN CHILDREN FOR DIAGNOSTICS, 3D CEPHALOMETRY AND PLANNING ORTHODONTIC TREATMENT (REVIEW)].
Objective diagnostics and orthodontic treatment planning are of paramount importance for both pediatric and adult patients. Traditionally, two-dimensional (2D) X-ray images such as panoramic, lateral and front cephalograms are widely used by orthodontists for diagnostics. However, alongside with 2D images causing a lot of questions, it is usually required to obtain several 2D X-ray images in different views at the same time, which by itself is increasing the radiation dosage and the stochastic effect. The spread of cone-beam computed tomography (CBCT) to visualize the cranio-maxillofacial area marks a real paradigm shift from two-dimensional (2D) to three-dimensional (3D) imaging in dentistry. CBCT with 3D reconstruction and 3D cephalometry capabilities is currently replacing traditional 2D visualization and is becoming widely used in orthodontics. However, full scull volume CBCT should only be used for children with strict clinical indication since growing patients are particularly sensitive to ionizing radiation. In this review article we consider such questions: what minimal volume of CBCT with minimal effective dosage of radiation is justified for diagnosing of growing patients in orthodontic practice, criteria for the possibility of using medium field of view CBCT with the purpose of cephalometric analysis, as well as outlining advantages and evidence-based indications for CBCT in pediatric orthodontic.


Ventilator-associated pneumonia in a tertiary care hospital in India: incidence and risk factors.
Knowledge of the incidence of ventilator-associated pneumonia (VAP) and its associated risk factors is imperative for the development and use of more effective preventive measures. We performed a prospective study over a period of 15 months to determine the incidence and the risk factors for development of VAP in critically ill adult patients admitted in different intensive care units (ICUs) of Jawaharlal Institute of Post-graduate Medical Education and Research (JIPMER), a tertiary care hospital in Pondicherry, India. The incidence of VAP was 30.67 and 15.87 per 1,000 ventilator days in the two different ICUs. In our study 58.3% of the cases were late-onset VAP, while 41.7% were early-onset VAP. Univariate analysis indicated that the following were significantly associated with VAP: impaired consciousness, tracheostomy, re-intubation, emergency intubation, and nasogastric tube. Emergency intubation and intravenous sedatives were found to be the specific risk factors for early onset VAP, while tracheostomy and re-intubation were the independent predictors of late-onset VAP by multivariate logistic regression analysis. Knowledge of these risk factors may be useful in implementing simple and effective preventive measures including non-invasive ventilation, precaution during emergency intubation, minimizing the occurrence of reintubation, avoidance of tracheostomy as far as possible, and minimization of sedation.


Cognitive function and risk of stroke in elderly men.
Vascular risk factors are associated with ischemic changes in the cerebral white matter. We studied the predictive value of cognitive test performance especially related to subcortico-frontal pathways, together with a cognitive screening test, for later incidence of fatal or nonfatal stroke or TIAs and stroke subtypes. A sample of 930 70-year-old men without previous stroke/TIA from the community-based Uppsala Longitudinal Study of Adult Men was investigated at baseline using Trail Making Tests (TMT) A and B and the Mini-Mental State Examination (MMSE). During up to 13 years of follow-up, 166 men developed a stroke or TIA; 105 participants had a brain infarction. In Cox proportional hazards analyses adjusting for education, social group, and traditional cardiovascular risk factors, a 1-SD increase in TMT-B time was associated with a higher risk for brain infarction (hazard ratio 1.48, 95% confidence interval 1.11-1.97). The risk of brain infarction was more than threefold higher in the highest (TMT-B = 146-240 s) compared to the lowest (TMT-B = 43-84 s) TMT-B quartile. TMT-A and MMSE results were not consistently related to stroke outcomes. Impaired performance in elderly men measured by Trail Making Test B, a cognitive test especially reflecting subcortico-frontal activities, was an independent predictor of subsequent brain infarction in this community-based sample of elderly men. Our results extend previous findings of cognitive decline as an independent predictor of stroke and indicate that the risk of brain infarction is increased already in the subclinical phase of cognitive deficit.


Comparative field evaluation of repellent formulations containing deet and IR3535 against mosquitoes in Queensland, Australia.
Field trials comparing repellent formulations containing IR3535 (ethyl butylacetylaminopropionate) and deet (N,N-diethyl-3-methylbenzamide) against mosquitoes in Queensland, Australia, were conducted. Two repellents were compared: Avon Bug Guard, containing 7.5% IR3535; and Australian Defense Force (ADF) deet, containing 35% deet in a gel. Two tests were conducted, one in February-March 2006, and the second in February 2007. In the 1st test, the predominant mosquito species collected were Mansonia uniformis (58.9% of collection) and Culex annulirostris (33.4%), and in the 2nd test, the predominant species was Aedes vigilax (85.7% of collection). In the 1st test, Avon Bug Guard provided >95% protection against all mosquitoes for only 1 h, and ADF deet provided the same level of protection for 5 h. In the 2nd field test, Avon Bug Guard provided only 85% protection against all mosquitoes 1 h after repellent application, while ADF deet provided 5 h of protection. The study showed that ADF deet provided significantly better protection against mosquitoes than Avon Bug Guard (IR3535).


See you at London Vet Show.
London Vet Show is fast approaching: it takes place from November 17 to 18 and is being held at ExCeL London for the first time. Zoe Davies, marketing manager, highlights some of what BVA is offering at the event.


Safety and Survival Benefit of Surgical Management for Elderly Gastric Cancer Patients.
To study the safety and survival outcome of surgical management for elderly gastric cancer patients. Patients proven of gastric cancer who aged 80 years during November 2002 to July 2011 were retrospectively analyzed. The detailed information of patients' characteristics and surgical management was retrieved. Follow-up of overall survival status was performed to analyze the surgical effectiveness. Totally, 92 (48 in surgery and 44 in non-surgery group) out of 187 eligible patients recorded adequate information and analyzed finally. Median ages were 81 years in surgery group and 83 year in non-surgery group. There were 34 patients undergone radical gastrectomy, 6 palliative gastrectomy, 1 gastrojejunostomy and 7 exploratory laparotomy. Median follow-up durations were 25 (9-111) and 28 (8-114) months in surgery and non-surgery groups, respectively (p = 0.797). Clinical-pathological T stage was 6 T1, 5 T2, 14 T3 and 23 T4 cases for surgery and 7 T1, 6 T2, 3 T3, 7 T4 and 21 TX cases for non-surgery. Clinical-pathological node status was 18 N0, 7 N1, 6 N2, 7 N3 and 10 NX cases for surgery and 10 N0, 3 N1, 3 N2, 3 N3 and 25 NX cases for non-surgery. Clinical-pathological distal metastasis status was 15 and 26 M1 cases for surgery and non-surgery, respectively (p = 0.006). Incidence of postoperative complications was 25.0% and postoperative hospital mortality was 2.1%. The 2-year survival rates were 30.8% and 8.0% for surgery and none-surgery, respectively (HR = 3.023, p = 0.001), and the 3-year survival rates were 17.6% and 0% for surgery and non-surgery, respectively (HR = 3.680, p = 0.001). In M0 subgroup, 2-year survival rate was 35.7% and 0.0% for surgery and non-surgery groups, respectively (HR = 3.98, p = 0.022). The safety of surgery for well-selected ≥ 80-year elderly gastric cancer patients was potentially acceptable and the patients of early or locally advanced diseases could obtain survival benefits by surgery.


Reynolds-number dependence of the dimensionless dissipation rate in homogeneous magnetohydrodynamic turbulence.
This paper examines the behavior of the dimensionless dissipation rate C_{ɛ} for stationary and nonstationary magnetohydrodynamic (MHD) turbulence in the presence of external forces. By combining with previous studies for freely decaying MHD turbulence, we obtain here both the most general model equation for C_{ɛ} applicable to homogeneous MHD turbulence and a comprehensive numerical study of the Reynolds number dependence of the dimensionless total energy dissipation rate at unity magnetic Prandtl number. We carry out a series of medium to high resolution direct numerical simulations of mechanically forced stationary MHD turbulence in order to verify the predictions of the model equation for the stationary case. Furthermore, questions of nonuniversality are discussed in terms of the effect of external forces as well as the level of cross- and magnetic helicity. The measured values of the asymptote C_{ɛ,∞} lie between 0.193≤C_{ɛ,∞}≤0.268 for free decay, where the value depends on the initial level of cross- and magnetic helicities. In the stationary case we measure C_{ɛ,∞}=0.223.


Risk of chromosomal abnormalities in patients with idiopathic polyhydramnios.
This prospective investigation was designed to assess the incidence of chromosomal abnormalities in patients with idiopathic polyhydramnios. Polyhydramnios was defined as 25 cm or greater in total vertical height in all four quadrants (amniotic fluid index) in any nonreferral patient (ie, primary care population) undergoing sonographic examination with a singleton pregnancy, normal fetal anatomical survey, normal glucose screening, and negative antibody screen. During the 2-year period from May 1, 1988 through April 30, 1990, 5038 gravidas delivered at Madigan Army Hospital Center. Unexplained polyhydramnios was detected sonographically in 125 patients, an incidence of 2.5%. After obtaining informed written consent, amniocentesis was performed in all patients. Within this group (N = 125), four chromosomal abnormalities (incidence of 3.2%) were detected. There were two trisomy 18 and two trisomy 21 fetuses. None of the four patients had maternal serum alpha-fetoprotein screening performed. The incidence of aneuploidy in patients with idiopathic polyhydramnios (3.2%) is much higher than the reported incidence of major karyotype abnormalities in live births (0.59%). We conclude that fetal chromosomal analysis should be considered in all obstetric patients with sonographic evidence of idiopathic polyhydramnios.


Binucleating behaviour of a proximally-diphosphinated calix[4]arene.
The long diphosphine 5,11-diphenylphosphanyl-25,26-dipropyloxy-27,28-bis(2-propenyloxy) calix[4]arene (cone) (5), in which the two phosphorus atoms are separated by a semi-rigid linking unit, was prepared in four steps starting from calix[4]arene. Reaction of 5 with AuCl(SEt(2)) or [RuCl(2)(p-cymene)](2) led to calixarenes bearing two metallated pendant arms, [5·(AuCl)(2)] and [5·{RuCl(2)(p-cymene)}(2)], respectively. In the presence of AgBF(4) or [Ni(C(5)H(5))(1,5-cyclooctadiene)]BF(4), diphosphine 5 displayed a marked tendency to form oligomeric material, but under high dilution conditions dimeric species were obtained selectively. The inability of 5 to form chelate complexes was further illustrated by its reaction with [PdCl(2)(1,5-cyclooctadiene)(2)], which led quantitatively to a rare complex in which a diphosphine spans across the dinuclear [PdCl(μ-Cl)(2)PdCl] unit.


Integral Valorization of Two-Phase Olive Mill Solid Waste (OMSW) and Related Washing Waters by Anaerobic Co-digestion of OMSW and the Microalga Raphidocelis subcapitata Cultivated in These Effluents.
This study evaluates the comprehensive valorization of the byproducts derived from the two-phase olive oil elaboration process [i.e., olive washing water (OWW), olive oil washing water (OOWW), and olive mill solid waste (OMSW)] in a closed-loop process. Initially, the microalga Raphidocelis subcapitata was grown using a mixture of OWW and OOWW as the culture medium, allowing phosphate, nitrate, sugars, and soluble chemical oxygen demand removal. In a second step, the microalgal biomass grown in the mixture of washing waters was used as a co-substrate together with OMSW for an anaerobic co-digestion process. The anaerobic co-digestion of the combination of 75% OMSW-25% R. subcapitata enhanced the methane yield by 7.0 and 64.5% compared to the anaerobic digestion of the OMSW and R. subcapitata individually. This schedule of operation allowed for integration of all of the byproducts generated from the two-phase olive oil elaboration process in a full valorization system and the establishment of a circular economy concept for the olive oil industry.


HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma.
The MYCN proto-oncogene is amplified in a number of advanced-stage human tumors, such as neuroblastomas. Similar to other members of the MYC family of oncoproteins, MYCN (also known as N-Myc) is a transcription factor, and its stability and activity are tightly controlled by ubiquitination-dependent proteasome degradation. Although numerous studies have demonstrated that N-Myc is a driver of neuroblastoma tumorigenesis, therapies that directly suppress N-Myc activity in human tumors are limited. Here we have identified ubiquitin-specific protease 7 (USP7; also known as HAUSP) as a regulator of N-Myc function in neuroblastoma. HAUSP interacts with N-Myc, and HAUSP expression induces deubiquitination and subsequent stabilization of N-Myc. Conversely, RNA interference (RNAi)-mediated knockdown of USP7 in neuroblastoma cancer cell lines, or genetic ablation of Usp7 in the mouse brain, destabilizes N-Myc, which leads to inhibition of N-Myc function. Notably, HAUSP is more abundant in patients with neuroblastoma who have poorer prognosis, and HAUSP expression substantially correlates with N-Myc transcriptional activity. Furthermore, small-molecule inhibitors of HAUSP's deubiquitinase activity markedly suppress the growth of MYCN-amplified human neuroblastoma cell lines in xenograft mouse models. Taken together, our findings demonstrate a crucial role of HAUSP in regulating N-Myc function in vivo and suggest that HAUSP inhibition is a potential therapy for MYCN-amplified tumors.


Polygalacturonase Gene Expression in Rutgers, rin, nor, and Nr Tomato Fruits.
Polygalacturonase (PG) gene expression was studied in normally ripening tomato fruit (Lycopersicon esculentum Mill, cv Rutgers) and in three ripening-impaired mutants, rin, nor, and Nr. Normal and mutant fruit of identical chronological age were analyzed at 41, 49, and 62 days after pollination. These stages corresponded to mature-green, ripe, and overripe, respectively, for Rutgers. The amount of PG mRNA in Rutgers was highest at 49 days and accounted for 2.3% of the total mRNA mass but at 62 days had decreased to 0.004% of the total mRNA mass. In Nr, the amount of PG mRNA steadily increased between 41 and 62 days after pollination, reaching a maximum level of 0.5% of the total mRNA mass. The mutant nor exhibited barely detectable levels of PG mRNA at all stages tested. Surprisingly, PG mRNA, comprising approximately 0.06% of the mRNA mass, was detected in 49 day rin fruit. This mRNA accumulation occurred in the absence of elevated ethylene production by the fruit and resulted in the synthesis of enzymically active PG I. The different patterns of PG mRNA accumulation in the three mutants suggests that distinct molecular mechanisms contribute to reduced PG expression in each ripening-impaired mutant.


Maternal cardiac function in preeclampsia.
Acute cardiovascular complications affect 6% of severe preeclampsia and epidemiological studies demonstrate a strong association between preeclampsia and subsequent cardiovascular morbidity and mortality. This data suggests that not only can preeclampsia acutely impair cardiac function, but also it has the potential to provoke myocardial ischaemia and affect long-term cardiovascular health. This review highlights the recent insights on cardiovascular impairment in preeclampsia and postpartum. Recent studies on preeclampsia have used newer echocardiographic indices that are more sensitive at detecting asymptomatic myocardial damage, better correlated to invasive indices of myocardial function and are predictive for subsequent cardiovascular morbidity. Current findings indicate an unexpectedly high prevalence of cardiac impairment in preeclampsia and postpartum. These findings have important implications for the long-term cardiovascular health of women whose pregnancies were complicated by preeclampsia. Preeclampsia is associated with stage B heart failure (asymptomatic left ventricular dysfunction/hypertrophy), a high prevalence of essential hypertension and an increased cardiovascular risk status within few years postpartum. These findings are more prevalent with early onset/preterm preeclampsia. These cardiovascular findings are consistent with epidemiological studies showing a 'dose-dependent' relationship between preeclampsia and long-term cardiovascular morbidity and mortality. There is increasing evidence supporting the concept that a history of early onset/preterm preeclampsia should be taken into account to identify women at high cardiovascular risk even in the absence of other concomitant risk factors.


Microelectrode Array Recording of Sinoatrial Node Firing Rate to Identify Intrinsic Cardiac Pacemaking Defects in Mice.
The sinoatrial node (SAN), located in the right atrium, contains the pacemaker cells of the heart, and dysfunction of this region can cause tachycardia or bradycardia. Reliable identification of cardiac pacemaking defects requires the measurement of intrinsic heart rates by largely preventing the influence of the autonomic nervous system, which can mask rate deficits. Traditional methods to analyze intrinsic cardiac pacemaker function include drug-induced autonomic blockade to measure in vivo heart rates, isolated heart recordings to measure intrinsic heart rates, and sinoatrial strip or single-cell patch-clamp recordings of sinoatrial pacemaker cells to measure spontaneous action potential firing rates. However, these more traditional techniques can be technically challenging and difficult to perform. Here, we present a new methodology to measure intrinsic cardiac firing rate by performing microelectrode array (MEA) recordings of whole-mount sinoatrial node preparations from mice. MEAs are composed of multiple microelectrodes arranged in a grid-like pattern for recording in vitro extracellular field potentials. The method described herein has the combined advantage of being relatively faster, simpler, and more precise than previous approaches for recording intrinsic heart rates, while also allowing easy pharmacological interrogation.


Worksite Food and Physical Activity Environments and Wellness Supports Reported by Employed Adults in the United States, 2013.
To examine the workplace food and physical activity (PA) environments and wellness culture reported by employed United States adults, overall and by employer size. Cross-sectional study using web-based survey on wellness policies and environmental supports for healthy eating and PA. Worksites in the United States. A total of 2101 adults employed outside the home. Survey items were based on the Centers for Disease Control and Prevention Worksite Health ScoreCard and Checklist of Health Promotion Environments and included the availability and promotion of healthy food items, nutrition education, promotion of breast-feeding, availability of PA amenities and programs, facility discounts, time for PA, stairwell signage, health promotion programs, and health risk assessments. Descriptive statistics were used to examine the prevalence of worksite environmental and facility supports by employer size (<100 or ≥100 employees). Chi-square tests were used to examine the differences by employer size. Among employed respondents with workplace food or drink vending machines, approximately 35% indicated the availability of healthy items. Regarding PA, 30.9% of respondents reported that their employer provided opportunities to be physically active and 17.6% reported worksite exercise facilities. Wellness programs were reported by 53.2% working for large employers, compared to 18.1% for smaller employers. Employee reports suggested that workplace supports for healthy eating, PA, and wellness were limited and were less common among smaller employers.


Quantitative determination of isoflurane enantiomers in blood samples during and after surgery via headspace gas chromatography-mass spectrometry.
The quantitative analysis of the chiral volatile anesthetic isoflurane (1) for biomedical applications by means of enantioselective gas chromatography (mass sensitive detector, selected ion monitoring) was studied. Two methods for the quantification of the enantiomers in blood samples drawn during and after narcosis were compared. Either the isomeric enflurane (2) was selected as an internal standard or a single enantiomer of 1 was used for the standard addition method, an approach referred to as 'enantiomer labeling'. Concentrations up to 0.3 micromol/l of the single enantiomers could be differentiated two days after anesthesia. The presented data imply that the body clearance for (+)-(S)-1 and (-)-(R)-1 proceeds to a measurable degree of enantioselectivity.


The decision to donate: a model of decision making among individuals and families.
Fifty years ago, the first successful kidney transplantation was performed. Since then significant advances in transplantation have been made. Unfortunately, the number of people needing transplants far surpasses the number willing to donate. The literature addresses a plethora of variables influencing whether individuals will become donors themselves or whether family members will donate a loved one's organs. However, to date, no model has examined similarities and differences in the processes by which individuals and families go about making decisions to donate their own or another's organs. In this article, individual and family donation decisions are discussed using Janis' 5-stage model of decision making. We suggest that the weighty nature of donation decisions levels the playing field for decisions made for self and for others. Although the specifics (eg, micro-level) may vary slightly, the processes by which people go about deciding to donate their own organs or those of another individual are similar (eg, macro-level).


Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group.
To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis. This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety. At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms. Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation.


Change in membrane permeability induced by amyloid beta-protein fragment 25-35 in brain neurons dissociated from rats.
Effects of amyloid beta-protein fragment 25-35, A beta P(25-35), on the membrane permeability of organic molecules were examined in the brain neurons dissociated from rats by using an argon laser (equipped in flow cytometer and laser microscope) and a combination of two fluorescent dyes, fluo-3-AM and ethidium bromide. A beta P(25-35) at concentrations of 1 microM or greater induced both leakage of fluo-3 from the neurons and permeation of ethidium across the membrane in a dose-dependent manner, although both dyes are highly impermeant to the intact plasma membrane. Thus, A beta P(25-35) seems to increase not only membrane permeability of inorganic ions such as Ca2+, Na+ and K+, as previously suggested, but also that of organic molecules. Therefore, the brain neuron membrane is suggested to lose its integrity in the presence of A beta P(25-35) that leads to neuronal death.


Mediators in the asthmatic child.
Prostaglandins (PGF) are known to occur in premature babies with hyaline membrane disease and so the levels of PGE during growth have been investigated. The levels are lower in children than in adults; but this fact cannot explain the high resistance to air flow in infants. The release of mediators has been shown in children and in adults. Release of histamine from circulating basophils occurs when the suspected allergenic extract is mixed with the blood of the asthmatic child. Other mediators have not been found in young children. Cutaneous tests and respiratory challenges demonstrate indirectly the action of mediators in children, but not in infants. Between 5 and 15 years of age, the frequency and type of response to these tests are not significantly different. One may assume that, at least within these age limits, release of mediators is similar qualitatively.


Snack patterns are associated with biomarkers of glucose metabolism in US men.
Few studies have made distinctions between dietary intake from meals and snacks in relating them to biomarkers. We aimed to examine if snack patterns are associated with biomarkers of glucose metabolism, specifically hemoglobin A1c and HOMA-IR in US adults. Using 24-h dietary recall data from National Health and Nutrition Examination Survey (NHANES) in 2007-2008, we derived snack patterns using factor analyses. Multivariate logistic regressions were performed to estimate adjusted odds ratios (AOR) for biomarkers of glucose metabolism by quintiles of snack pattern scores. Men in the highest quintile of dairy and sugary snack pattern had higher risk of having hemoglobin A1c ≥ 6.5% (AOR: 2.06; 95% CI: 1.20-3.51) and HOMA-IR > 3.0 (AOR: 1.73; 95% CI: 1.01-2.95) than did those in the lowest quintile. No significant association was found in women between snack patterns and biomarkers of glucose metabolism. Dairy and sugary snack patterns of US men had the greatest association with poor control of glucose metabolism.


Laryngeal mask airway positioning is related to Mallampati grading in adults.
The Mallampati classification is a commonly used means of preoperatively predicting a difficult endotracheal intubation. As the laryngeal portion of the laryngeal mask airway (LMA) must sit over the larynx, we wondered whether the Mallampati classification also predicts difficulty in achieving adequate seating of the LMA. LMA positioning was assessed prospectively in 100 adult patients by fiberoptic bronchoscopy to determine whether there was a relationship between the ease of seating of the LMA and the Mallampati classification. In 72 patients, optimal seating of the LMA was achieved on the first attempt at insertion, and all these patients were classified as Mallampati class 1 or 2. In all 28 cases of difficulty with LMA insertion, the patients were Mallampati class 2 or 3. In two cases the LMA was abandoned, and in these cases both patients were Mallampati class 3, (P = 0.0001 by chi 2 analysis). We conclude that the Mallampati classification indicates difficulty not only in tracheal intubation but also in achieving an adequate airway with the LMA.


Comparison of antihyperglycemic effects of creatine and metformin in type II diabetic patients.
To compare the antihyperglycemic effects of metformin and creatine in recently detected type II diabetics in a short-term clinical study. In a 14 day simmetrically randomized crossover study, recently detected type II diabetics received either creatine (2x3 g/day) or metformin (2x500 mg/day) for five days, followed by two days of washout, followed by cross-over to the opposite treatment for the next five days. Fasting and post-prandial (-15, 60, 90, 120, 180 and 240 min) blood glucose, insulin, c-peptide, creatine and lactate were measured every other day for the duration of treatment, and HbA1c only at the begining and at the end of the study. Both creatine and metformin decreased glucose concentrations to similar levels at all time points vs. basal glucose values [-15, 60, 90, 120, 180, and 240 min]: 11.1+/-0.75 vs 9.1+/-0.55a vs 8.8+/-0.59b, 14.4+/-0.6 vs 12.9+/-0.47a vs 13.1+/-0.55a, 14.8+/-0.58 vs 13.0+/-0.46b vs 13.3+/-0.55a, 14.1+/-0.6 vs 11.9+/-0.42b vs 12.5+/-0.51a, 12.2+/-0.6 vs 9.6+/-0.36c vs 9.9+/-0.38c, and 10.1+/-0.47 vs 7.8+/-0.36c vs 8.4+/-0.4b; (aP < 0.05; bP < 0.01; cP < 0.001 vs. basal glucose values). Neither treatment altered insulin, c-peptide, or HbA1c. Lactate varied during the day, but never reached the upper level of the safety reference range. Short-term treatment with creatine and metformin elicits similar glucose lowering effects in recently detected type II diabetics. Further studies are necessary to determine the effect of creatine on long-term glucose and insulin regulation.


Jejunal diverticulosis: a potentially dangerous entity.
Although jejunal diverticulosis is a rare entity and usually asymptomatic, it may cause chronic symptoms and acute complications. Because of the rarity of the entity, diagnosis is often delayed, resulting in unnecessary morbidity and mortality. The purpose of this study was to draw attention to jejunal diverticula and their complications. The medical records of 8 consecutive patients with complications due to small-bowel diverticula treated at our department during the past 4 years were reviewed. All diverticula were located in the jejunum. Seven patients had acute complications, 3 patients had an intra-abdominal abscess, 2 had free perforation with diffuse peritonitis, 1 had a bowel occlusion and 1 patient had concomitant bleeding and occlusion. One patient presented with chronic symptoms. A preoperative diagnosis of jejunal diverticula, before explorative laparotomy, was not reached in any of the 7 patients with acute symptoms. In the patient with chronic symptoms, multiple jejunal diverticula complicated by a jejuno-colic fistula and foreign body were found at laparotomy. On patient died of multiorgan failure. Small-bowel diverticulosis is a rare entity, but it should not be regarded as a clinically insignificant finding. It may be difficult to make a preoperative diagnosis. Patients with incidentally detected proximal jejunal diverticula, at imaging studies or at laparotomy, warrant close observation and awareness that the diverticula may cause serious complications.


Uptake of apoptotic DC converts immature DC into tolerogenic DC that induce differentiation of Foxp3+ Treg.
DC apoptosis has been observed in patients with cancer and sepsis, and defects in DC apoptosis have been implicated in the development of autoimmune diseases. However, the mechanisms of how DC apoptosis affects immune responses, are unclear. In this study, we showed that immature viable DC have the ability to uptake apoptotic DC as well as necrotic DC without it being recognized as an inflammatory event by immature viable DC. However, the specific uptake of apoptotic DC converted immature viable DC into tolerogenic DC, which were resistant to LPS-induced maturation. These tolerogenic DC secreted increased levels of TGF-beta1, which induced differentiation of naïve T cells into Foxp3(+) Treg. Furthermore, induction of Treg differentiation only occurred upon uptake of apoptotic DC and not apoptotic splenocytes by viable DC, indicating that it is specifically the uptake of apoptotic DC that gives viable immature DC the potential to induce Foxp3(+) Treg. Taken together, these findings identify uptake of apoptotic DC by viable immature DC as an immunologically tolerogenic event.


Low-energy diode laser irradiation reduced plasminogen activator activity in human periodontal ligament cells.
The plasminogen activator (PA)-plasmin proteolytic system is implicated in the degradation of the extracellular matrix in inflammation. Since human periodontal ligament (PDL) cells produced high PA activity in response to mechanical stress, excessive mechanical stress to PDL cells such as occlusal trauma may induce collagen breakdown through activation of the PA-plasmin system. As low-energy laser irradiation has anti-inflammatory effects, we examined the effects of low-energy laser irradiation on the PA-plasmin system in stretched PDL cells in vitro. Human PDL cells obtained from healthy premolars were mechanically stretched and Ga-Al-As low-energy laser was irradiated (830 nm, 3.95 to 7.90 J/cm2) to the stretched cells. PDL cells showed a marked elevation in PA activity in response to stretching, which was significantly inhibited by a laser irradiation in a dose-dependent manner (55-86%, p < 0.001). This effect could involve transcriptional events of tissue type (t) PA gene. These results suggests that laser irradiation may reduce collagen breakdown around the PDL associated with traumatic occlusion.


Human Factors for More Usable and Safer Health Information Technology: Where Are We Now and Where do We Go from Here?
A wide range of human factors approaches have been developed and adapted to healthcare for detecting and mitigating negative unexpected consequences associated with technology in healthcare (i.e. technology-induced errors). However, greater knowledge and wider dissemination of human factors methods is needed to ensure more usable and safer health information technology (IT) systems. This paper reports on work done by the IMIA Human Factors Working Group and discusses some successful approaches that have been applied in using human factors to mitigate negative unintended consequences of health IT. The paper addresses challenges in bringing human factors approaches into mainstream health IT development. A framework for bringing human factors into the improvement of health IT is described that involves a multi-layered systematic approach to detecting technology-induced errors at all stages of a IT system development life cycle (SDLC). Such an approach has been shown to be needed and can lead to reduced risks associated with the release of health IT systems into live use with mitigation of risks of negative unintended consequences. Negative unintended consequences of the introduction of IT into healthcare (i.e. potential for technology-induced errors) continue to be reported. It is concluded that methods and approaches from the human factors and usability engineering literatures need to be more widely applied, both in the vendor community and in local and regional hospital and healthcare settings. This will require greater efforts at dissemination and knowledge translation, as well as greater interaction between the academic and vendor communities.


Tailoring Computer-Based Training for Latino Immigrant Workers: Pilot Test of the NIOSH Mouse Tutorial.
An interactive tutorial on using a mouse for first-time computer users was developed as part of a training CD-ROM tailored for Latino immigrant workers in trenching and excavation. It was designed for Spanish-speaking users with varying levels of formal education. The tutorial was tested in focus groups with workers who had little or no previous experience using a computer. Findings revealed that while users with less than a fourth-grade education and/or low proficiency in Spanish had some difficulties with the tutorial, they still scored above 67 percent on the performance evaluation; participants with at least a fourth-grade education (the majority) completed it with minimal assistance and scored 80%-100% on the performance evaluation. Feedback from participant focus groups following the computer sessions supported these findings. The results of this study suggest that computer-based training may be able to be made accessible for low computer literacy Latino immigrant workers, if it is tailored to their needs.


Newer antihypertensive drugs.
We review three new classes of antihypertensive drugs: imidazolines, monatepil, and neutral endopeptidase inhibitors. Imidazolines are a new generation of central acting drugs. Because of their greater affinity for imidazoline receptors rather than alpha 2-adrenoreceptors, they cause less fatigue and dry mouth than the older central acting drugs. Monatepil is a single drug with both calcium antagonist and peripheral alpha 1-antagonist properties. This agent not only lowers blood pressure but also lowers serum cholesterol, an effect mediated by its alpha-antagonism, and has anti-lipid peroxidation properties. Monatepil might become an effective antiatherosclerosis drug. Neutral endopeptidase inhibitors lower blood pressure by inhibiting the metabolism of atrial natriuretic peptide and other vasoactive peptides.


The reliability of questionnaire-derived historical dietary information and temporal stability of food habits in individuals.
Thirty-four males and 45 females who participated in household surveys 15 or 25 years earlier in rural Denmark were interviewed in 1982 about present and past food habits. Comparison of the information from the survey and the two interviews indicates that recall of past diet is strongly influenced by present dietary habits. As the relative classification of individuals according to their food habits appears to have changed little over time, information on current diet, perhaps supplemented by information on particular changes, can provide useful classification of individuals for epidemiologic purposes.


Mediating Effect of Cognitive Function on the Relationship Between Geriatric Oral Health and Quality of Life Among Korean Seniors.
Previous studies have found that the oral health of seniors can affect their physical nutrition and quality of life (QoL). Additionally, poor oral health can lead to the development of dementia, which is associated with decreased cognitive function. This study aimed to examine the impact of geriatric oral health (GOH) on the QoL of Korean seniors and the mediating effects of cognitive function. We used data from the seventh Korean Longitudinal Study of Aging conducted in 2018. In total, 4049 seniors were included in our study. We analyzed the impact of GOH on QoL according to 5 mediating domains of cognitive function and control variables. To examine each path of mediating effects, bootstrapping with 5000 iterations was performed with 95% confidence intervals. Our findings revealed that good GOH had a positive effect on the QoL of seniors. Also, better GOH corresponded to a higher degree of cognitive function within all 5 domains: orientation, memory registration, attention/calculation, memory recall, and language and visuospatial ability. In addition, 3 domains of the 5 domains (attention/calculation, memory recall, and language and visuospatial ability) had significant mediating effects on the relationship between GOH and QoL. This study suggests that adequate management of GOH is crucial for promoting a better QoL and a high degree of cognitive function among seniors. To prevent cognitive impairment, such as dementia, future studies should take a more targeted approach by examining data according to each cognitive domain and various socio-demographic factors.


Human cathepsin V functional expression, tissue distribution, electrostatic surface potential, enzymatic characterization, and chromosomal localization.
Cathepsin V, a thymus and testis-specific human cysteine protease, was expressed in Pichia pastoris, and its physicokinetic properties were determined. Recombinant procathepsin V is autocatalytically activated at acidic pH and is effectively inhibited by various cysteine protease class-specific inhibitors. The S2P2 subsite specificity of cathepsin V was found to be intermediate between those of cathepsins S and L. The substrate binding pocket, S2, accepted both aromatic and nonaromatic hydrophobic residues, whereas cathepsins L and S preferred either an aromatic or nonaromatic hydrophobic residue, respectively. In contrast to cathepsin L, but similar to cathepsin S, cathepsin V exhibited only a very weak collagenolytic activity. Furthermore, cathepsin V was determined to be significantly more stable at mildly acidic and neutral pH than cathepsin L, but distinctly less stable than cathepsin S. A homology structure model of cathepsin V revealed completely different electrostatic potentials on the molecular surface when compared with human cathepsin L. The model-based electrostatic potential of human cathepsin V was neutral to weakly positive at and in the vicinity of the active site cleft, whereas that of cathepsin L was negative over extended regions of the surface. Surprisingly, the electrostatic potential of the human cathepsin V model structure resembled that of the model structure of mouse cathepsin L. These differences in the electrostatic potential at the molecular surfaces provide a reactivity determinant that may be the source of differences in substrate selectivity and pH stability. Cathepsin V was mapped to the chromosomal region 9q22.2, a site adjacent to the cathepsin L locus. The high sequence identity and the overlapping chromosomal gene loci suggest that both proteases evolved from an ancestral cathepsin L-like precursor by gene duplication.


A comparison of the risk of stillbirth associated with paternal pre-conception irradiation in the Sellafield workforce with that of stillbirth and untoward pregnancy outcome among Japanese atomic bomb survivors.
A comparison is made of the relative risks associated with paternal preconception irradiation of stillbirth and untoward pregnancy outcome (stillbirths, congenital malformations, neonatal deaths) in the offspring of the Japanese atomic bomb survivors and of stillbirth in the offspring of Sellafield workers. It is concluded that the pre-conception exposure risks of stillbirth in the offspring of Sellafield workers are statistically incompatible with the Japanese data at the 5% level. Other human and experimental data relating to the induction of congenital abnormalities are briefly reviewed.


Monochloropropanediol in edible vegetable oils from Hangzhou market in China: occurrence and exposure risk assessment.
In this study, 241 vegetable-oil food samples were collected from the Hangzhou market in China and analysed for fatty acid esters of 3- and 2-monochloropropanediol (3-MCPD and 2-MCPD) using non-derivative gas chromatography tandem mass spectrometry (GC-MS/MS). Food consumption data were taken from a food consumption survey of urban and rural residents in Hangzhou city performed in 2010-2011. Levels of 3-MCPD esters in edible oil ranged from not detected to 7.98 mg/kg, and the highest mean levels were found in tea seed oil, with concentrations of 2.94 mg/kg. Esters of 2-MCPD levels ranged from not detected to 4.03 mg/kg, and the highest mean levels were also found in tea seed oil, containing 1.49 mg/kg. The range of mean dietary intake of 3-MCPD esters in different groups of edible oil was from 0.096 to 1.54 μg/kg body weight (bw) per day, which is lower than the tolerable daily intake (TDI) established by the European Food Safety Authority (EFSA) (2 μg/kg bw/day). For people aged above 6 years old, the dietary intake of 3-MCPD from edible oil was 0.42 μg/kg bw per day (mean) and 1.22 μg/kg bw per day (P97.5). The range of mean dietary intake of 2-MCPD esters in different groups of edible oil was from 0.025 to 0.79 μg/kg bw/day, and 2-MCPD esters intake was 0.20 μg/kg bw per day (mean) and 0.60 μg/kg bw per day (P97.5). In addition, the dietary intake exposure to 3-MCPD and 2-MCPD esters for urban residents was lower than that for rural residents. The findings indicate that the potential health risks caused by dietary 3-MCPD esters from edible oils were of low concern for most of the Hangzhou residents. However, the exposure risk for consumers with excessive consumption of certain kind of edible oil calls for attention.


Steady-state deformation behavior of confined composite droplets under shear flow.
The shear-induced dynamics of two-dimensional composite droplets in a narrow channel is investigated numerically. The droplets consist of a viscous inner droplet (core) and shell immersed in a continuous Newtonian fluid. Attention is focused on studying the effects of confinement at different core-to-shell radii ratios, relative viscosities of the medium components, and interfacial tensions on the steady-state deformation and orientation of a composite droplet. The role of the "sustaining" effect due to the internal core and competition between the near-wall shear flow and downward and upward secondary streams is discussed.


Structural Insights into the Interactions of Candidal Enolase with Human Vitronectin, Fibronectin and Plasminogen.
Significant amounts of enolase-a cytosolic enzyme involved in the glycolysis pathway-are exposed on the cell surface of Candida yeast. It has been hypothesized that this exposed enolase form contributes to infection-related phenomena such as fungal adhesion to human tissues, and the activation of fibrinolysis and extracellular matrix degradation. The aim of the present study was to characterize, in structural terms, the protein-protein interactions underlying these moonlighting functions of enolase. The tight binding of human vitronectin, fibronectin and plasminogen by purified C. albicans and C. tropicalis enolases was quantitatively analyzed by surface plasmon resonance measurements, and the dissociation constants of the formed complexes were determined to be in the 10-7-10-8 M range. In contrast, the binding of human proteins by the S.cerevisiae enzyme was much weaker. The chemical cross-linking method was used to map the sites on enolase molecules that come into direct contact with human proteins. An internal motif 235DKAGYKGKVGIAMDVASSEFYKDGK259 in C. albicans enolase was suggested to contribute to the binding of all three human proteins tested. Models for these interactions were developed and revealed the sites on the enolase molecule that bind human proteins, extensively overlap for these ligands, and are well-separated from the catalytic activity center.


The stability of nucleosomes at the replication fork.
Purified simian virus (SV40) minichromosomes were photoreacted with psoralen under various conditions that moderately destabilize nucleosomes. This assay allows indirect distinction between stable nucleosomes, partially unravelled nucleosomes and nucleosomes containing (or lacking) histone H1. In replicating molecules the passage of the replication machinery destabilizes the nucleosomal organization of the chromatin fiber over a distance of 650 to 1100 bp. In front of the fork, an average of two nucleosomes are destabilized presumably by the dissociation of histone H1 and the advancing replication machinery. On daughter strands, the first nucleosome is detected at a distance of about 260 nucleotides from the elongation point. This nucleosome is interpreted to contain no histone H1, while no stepwise association of (H3-H4)2 tetramers with H2A/H2B dimers on nascent DNA can be detected in vivo. The second nucleosome after the replication fork appears to contain histone H1. The prolonged nuclease sensitivity of newly replicated chromatin described in the literature therefore may not be due to a slow reassociation of histone H1.


"Mr. Health" programme on sex education for the adolescents.
30 years ago, late Premier Zhou Enlai pointed out: "Adolescents must be informed about sex knowledge." But unfortunately, for many years, authorities were too timid to popularize sex education among adolescents. According to a survey, only 37.6% of sex education was provided through formal ways. Another survey of 2071 sex offenders showed that 89.3% of them were teenagers. Besides, the cases of early romance increased dramatically in recent years. According to a survey in Beijing, Shanghai, Guangzhou and Chengdu, half of the high school students have had love affairs. Many of the adolescents have a hazy understanding of sex. Lacking contraceptive knowledge and measures, girls are likely to get pregnant, which make them feel so uneasy that some even committed suicide. Facing the above situation, "Mr. Health" Program on Sex Education for the Adolescents is underway. The program will comprise various activities. A column of "Mailbox of Mr. Health" is to be developed in the Science and Technology of Chinese Youth, a journal with national influence. Specialists will introduce the systematic knowledge of and proper attitudes toward sex in that column. Special educational radio programs are to be produced in the China Central Broadcasting Station to popularize the "Mr. Health" Program on Sex Education for the Adolescents. A hotline of counseling on sex knowledge is to be set by the Service Center of the Adolescents under the Central Committee of the Communist Youth League. And a large-scale exhibition of the "Mr. Health" Program on Popularizing Sex Education will be held throughout the country.


Preliminary Screening of a Classical Ayurvedic Formulation for Anticonvulsant Activity.
Epilepsy is a serious and complex central nervous system disorder associated with recurrent episodes of convulsive seizures due to the imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmitters level in the brain. The available treatments are neither competent to control the seizures nor prevent progress of disease. Since ages, Herbal medicines have remained important sources of medicines in many parts of world which is evidenced through their uses in traditional systems of medicine i.e. Ayurveda, Siddha, Unani, Homeopathy and Chinese etc. A polyherbal formulation (containing Terminalia chebula Retz., Asparagus racemosus Willd., Embelia ribes Burm. F, Acorus calamus L., Tinospora cordifolia (Willd.) Miers, Convolvulus pluricaulis Choisy, Saussurea lappa C.B.Clarke, Achyranthes aspera L.) is mentioned in Ayurvedic classics Bhaiṣajya Ratnāvali. The aim of the study was to evaluate the anticonvulsant activity of the formulation in Maximum electroshock and Pentylenetetrazole induced convulsions in rats. In the present study, a polyherbal formulation was developed as directed by classical text and evaluated for the anticonvulsant activity using Maximal Electroshock Shock (MES) and Pentylenetetrazole (PTZ) induced convulsions in rats. Statistical comparison was done by one way ANOVA followed by the Tukey's multiple comparison test. The obtained results showed that the PHF had a protective role on epilepsy. Treatment with PHF significantly improves antioxidant enzymes activities of superoxide dismutase (SOD) and glutathione (GSH) levels significantly as compared to controls. PHF also significantly decreased malonaldialdehyde (MDA) levels in the brain. Moreover, it also attenuated the PTZ-induced increase in the activity of GABA-T in the rat brain. These findings suggest that PHF might have possible efficacy in the treatment of epilepsy.


Cystic endocervical tunnel clusters. A clinicopathologic study of 29 cases of so-called adenomatous hyperplasia.
The clinical and histologic features of cystic endocervical tunnel clusters (CETC) are not well known. Unwary pathologists have sometimes mistaken CETC for endocervical adenocarcinoma or interpreted them as "adenomatous hyperplasia." In this study, CETC were identified in 19 (5.9%) of 322 consecutive hysterectomy specimens and three (9.7%) of 31 consecutive cervical conization specimens accessioned during a 1-year period. These 22 cases were analyzed along with seven consultation cases. The 29 patients' ages ranged from 33 to 72 years (mean, 55). All but one (96.6%) were multigravida. Almost 80% of the patients had had at least three previous pregnancies. The mean gravidity and age of the hysterectomy patients with CETC were significantly greater than those without them. CETC typically were discovered incidentally during routine examination of the cervix. The clusters ranged from 0.5 to 18.8 mm (mean, 2.4 mm) in greatest dimension; they were multifocal in 82.8% of cases. CETC consisted of orderly, lobular aggregates of closely packed, dilated tubular endocervical "glands" within the superficial endocervix. The deepest clusters extended to a depth of 9.0 mm. They were commonly associated with multiple Nabothian cysts, which occasionally also penetrated deeply. The lining epithelium was a single layer of flattened or cuboidal endocervical cells. Mitotic figures and significant cytologic atypia were absent. None of the cases had intracytoplasmic CEA immunoreactivity, but in 52% focal positive CEA staining was noted along the luminal border of the endocervical cells. CETC are believed to result from subinvolution of previous episodes of physiologic hyperplasia of the endocervical mucosa, usually due to prior pregnancies. They are unrelated to cervical neoplasms and must be distinguished from adenocarcinoma and other glandular lesions of the endocervix.


Mothers' experiences with breastfeeding management and support: a quality improvement study.
The purpose of this study was to examine the experiences on mothers with regard to the breastfeeding support and management provided by healthcare professionals on an acute care postpartum unit in a multiethnic obstetrical referral center in Montreal, Canada. The study survey was largely based on the UNICEF/World Health Organization's (1998) ten steps to successful breastfeeding. The convenience sample included 60 recently-delivered mothers. Findings indicated that primiparous women and women who delivered by caesarean section consistently received more information about breastfeeding management than multiparous women and women who delivered vaginally. However, the study does suggest that all women, regardless of parity or type of delivery, have information and support needs related to breastfeeding. A total of 29 mothers (67%), who intended to breastfeed exclusively, supplemented with artificial baby milk. Of these mothers, 16 (55%) stated 'milk insufficiency' as their primary reasons for supplementing. Overall, respondents perceived healthcare professionals to be encouraging of breastfeeding, and 48 mothers (80%) were 'moderately' to 'very' satisfied with the breastfeeding education and support received. These findings suggest that overall adherence to breastfeeding best practices in the current study hospital are below targets set by the World Health Organization for 'Baby Friendly' status. Results from the study can be used to target areas for improvement.


Expression and purification of non-glycosylated Trypanosoma brucei transferrin receptor in insect cells.
The transferrin receptor of the parasite Trypanosoma brucei is a heterodimeric protein complex encoded by the 2 expression site-associated genes (ESAGs) 6 and 7. ESAG6 is a heterogeneously glycosylated protein of 50-60kDa modified by a glycosylphosphatidylinositol anchor at the C-terminus, while ESAG7 is a 40-42kDa glycoprotein carrying an unmodified C-terminus. In order to determine whether glycosylation is necessary for dimer formation and ligand binding, the receptor was expressed in insect cells in the presence of tunicamycin. When insect cells were infected with recombinant ESAG6/ESAG7 double expressor baculovirus and grown in the presence of tunicamycin, non-glycosylated forms of ESAG6 and ESAG7 of 46 and 36kDa, respectively, were synthesized. The non-glycosylated ESAG6 and ESAG7 were capable of forming a heterodimer and of binding transferrin. This results shows that glycosylation is not necessary for synthesis of a functional T. brucei transferrin receptor.


Can sleep disturbance be a cue of mood spectrum comorbidity? A preliminary study in panic disorder.
To investigate if sleep disturbances may affect treatment outcomes of patients with panic disorder (PD). Eighty-five PD outpatients with no Axis I comorbidity for mood disorders completed a baseline assessment (T1) and were evaluated after 3 (T2), 6 (T3) and 12 months (T4), with the Panic Disorder Severity Scale (PDSS) total score as outcome measure during a 12-month naturalistic follow-up. Patients were assessed with the Mood Spectrum Self-Report (MOODS-SR, Lifetime Version), and the PDSS. Forty-three patients (50.5%) met criteria for remission (PDSS<5) and 42 (49.5%) for no remission. In a logistic regression model with remission as the dependent variable, MOODS-SR sleep disturbances was the only determinant for a lower likelihood of PD remission. The items accounting for this result were the following: Repeated difficulty falling asleep (chi-square = 4.4; df = 1; p = 0.036), and Repeatedly waking up in the middle of the night (chi-square = 5.2; df = 1; p = 0.022). Lifetime sleep disturbances would represent a cue of mood spectrum (in absence of overt affective comorbidity) that may impair remission in PD.


A material-sparing method for assessment of powder deformation characteristics using data collected during a single compression-decompression cycle.
Compressibility profiles, or functions of solid fraction versus applied pressure, are used to provide insight into the fundamental mechanical behavior of powders during compaction. These functions, collected during compression (in-die) or post ejection (out-of-die), indicate the amount of pressure that a given powder formulation requires to be compressed to a given density or thickness. To take advantage of the benefits offered by both methods, the data collected in-die during a single compression-decompression cycle will be used to generate the equivalent of a complete out-of-die compressibility profile that has been corrected for both elastic and viscoelastic recovery of the powder. This method has been found to be both a precise and accurate means of evaluating out-of-die compressibility for four common tableting excipients. Using this method, a comprehensive characterization of powder compaction behavior, specifically in relation to plastic/brittle, elastic and viscoelastic deformation, can be obtained. Not only is the method computationally simple, but it is also material-sparing. The ability to characterize powder compressibility using this approach can improve productivity and streamline tablet development studies.