Inhibition of the MYC-Regulated Glutaminase Metabolic Axis Is an Effective Synthetic Lethal Approach for Treating Chemoresistant Ovarian Cancers.
Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. Here we report that ovarian cancer cells overexpressing glutaminase (GLS), a target of MYC and a key enzyme in glutaminolysis, are intrinsically resistant to platinum-based chemotherapy and are enriched with intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not in low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLShigh cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. These findings suggest consideration of applying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers, especially those with high GLS expression. SIGNIFICANCE: Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/20/4514/F1.large.jpg.


Bile salt/phospholipid mixed micelle precursor pellets prepared by fluid-bed coating.
Bile salt/phospholipid mixed micelles (MMs) are potent carriers used for oral absorption of drugs that are poorly soluble in water; however, there are many limitations associated with liquid formulations. In the current study, the feasibility of preparing bile salt/phospholipid MM precursor (preMM) pellets with high oral bioavailability, using fluid-bed coating technology, was examined. In this study, fenofibrate (FB) and sodium deoxycholate (SDC) were used as the model drug and the bile salt, respectively. To prepare the MMs and to serve as the micellular carrier, a weight ratio of 4:6 was selected for the sodium deoxycholate/phospholipids based on the ternary phase diagram. Polyethylene glycol (PEG) 6000 was selected as the dispersion matrix for precipitation of the MMs onto pellets, since it can enhance the solubilizing ability of the MMs. Coating of the MMs onto the pellets using the fluid-bed coating technology was efficient and the pellets were spherical and intact. MMs could be easily reconstituted from preMM pellets in water. Although they existed in a crystalline state in the preMM pellets, FB could be encapsulated into the reconstituted MMs, and the MMs were redispersed better than solid dispersion pellets (FB:PEG = 1:3) and Lipanthyl®. The redispersibility of the preMM pellets increased with the increase of the FB/PEG/micellar carrier. PreMM pellets with a FB:PEG:micellar carrier ratio of 1:1.5:1.5 showed 284% and 145% bioavailability relative to Lipanthyl® and solid dispersion pellets (FB:PEG = 1:3), respectively. Fluid-bed coating technology has considerable potential for use in preparing sodium deoxycholate/phospholipid preMM pellets, with enhanced oral bioavailability for poorly water-soluble drugs.


Cervical cancer screening in Korean American women: findings from focus group interviews.
Korean American women have twice the rate of cervical cancer than white women and demonstrate low rates in participation in cervical cancer screening. This study was to describe the perceptions about cervical cancer and factors related to cervical cancer screening among Korean American women. Focus group methods. Five themes emerged. First, knowledge about cervical cancer; misconceptions about cervical cancer, its causes, reproductive anatomy and the treatment. Second, perceived meanings of having cervical cancer; most of the women felt that cervical cancer represented a loss of femininity and existential value of womanhood. Third, knowledge about cervical cancer screening ; regular medical check-ups were necessary for early detection and prevention of cervical cancer. Fourth, experiences and perceived meanings of cervical cancer screening; the participants expressed their feelings; embarrassment, fear, shame and shyness. Fifth, practices of cervical cancer screening; various intervals in participating in cervical cancer screening. But they mentioned several deterrents, language, insurance, time constraint, embarrassment, fear of the screening results, misbelief about susceptibility, lack of health prevention behavior, and lack of information written in Korean. Results emphasize the critical need for culturally appropriate health education to encourage participation of Korean American women in cervical cancer screening.


Characterizations of matrix and operator-valued Φ-entropies, and operator Efron-Stein inequalities.
We derive new characterizations of the matrix Φ-entropy functionals introduced in Chen & Tropp (Chen, Tropp 2014 Electron. J. Prob.19, 1-30. (doi:10.1214/ejp.v19-2964)). These characterizations help us to better understand the properties of matrix Φ-entropies, and are a powerful tool for establishing matrix concentration inequalities for random matrices. Then, we propose an operator-valued generalization of matrix Φ-entropy functionals, and prove the subadditivity under Löwner partial ordering. Our results demonstrate that the subadditivity of operator-valued Φ-entropies is equivalent to the convexity. As an application, we derive the operator Efron-Stein inequality.


Serologic evidence of canine parvovirus in domestic dogs, wild carnivores, and marsupials in the Argentinean Chaco.
The transmission of pathogens between domestic dogs and generalist wildlife species may be modified by environmental degradation, biodiversity losses, host densities, and increased contact rates in remnant forest patches. A serologic survey of canine parvovirus (CPV) in rural domestic dogs and wild mammals was conducted in two neighboring rural areas (disturbed and protected) from Pampa del Indio, northeastern Argentina, between 2008 and 2011. A total of 174 domestic dogs and 26 wild mammals-4 crab-eating foxes (Cerdocyon thous), 3 crab-eating raccoons (Procyon cancrivorus), 17 white-eared opossums (Didelphis albiventris), and 2 gray four-eyed opossums (Philander opossum)-were examined for antibodies to CPV using a hemagglutination inhibition assay. Domestic dogs were numerous and their movements unrestricted. The main function of dogs differed significantly between areas, with more dogs used for herding or hunting around the protected area. The seroprevalence of antibodies to CPV in dogs from both areas was very high (93.9-94.6%) and increased steeply with age. Nearly all carnivores and marsupials showed high exposure to CPV. Although a higher exposure to CPV was expected in wild mammals from disturbed areas as a result of enhanced contact between dogs and wildlife, no significant differences were found between areas. To the authors' knowledge, this study is the first to document exposure to CPV of free-ranging Pr. cancrivorus, D. albiventris, and Ph. opossum, and include a detailed demographic study of the domestic dog populations living in the area. This study highlights that dogs and wildlife have potential opportunities for contact and shows that the edges of the protected area may be as suitable as other fragmented areas for the transmission of CPV. Rural domestic dogs may pose serious threats to the health and conservation of wild carnivores in both disturbed and protected areas, especially in the Gran Chaco, where habitat fragmentation is severely increasing.


Effect of implant design in immediate loading. A randomized, controlled, split-mouth, prospective clinical trial.
The aim of this study was to evaluate the effect of two different designs, tapered vs cylindrical, on the primary stability of implants placed with an immediate loading protocol in edentulous mandibles to support fixed prostheses within occlusal contacts during the first 48 h. Tapered and cylindrical implants were placed in a split-mouth study using the same implant protocol in ten patients with edentulous jaws. A total of 20 tapered implants (test group) and 20 cylindrical implants (control group) were placed. All implants were loaded immediately with provisional fixed prostheses during the healing period before the final restoration. The implants were evaluated at the implant placement by analyzing the insertion torque values (ITVs) and the resonance frequency analysis (RFA) and after the healing period of three months, the success of those implants and the marginal bone loss were evaluated. Two cylindrical implants were mobile within the same patient and no tapered implants failed, resulting in implant survival rates of 90% and 100%, respectively after three months. The ITVs were statistically significantly different (P = 0.0210) for the tapered implants than for the cylindrical implants. However, no statistically significant differences in RFA values were found (P = 0.6063) when comparing the implant designs and the primary stability measured with implant stability quotient (ISQ) values. The control group resulted in a mean bone loss after three months of 0.91 mm while the test group resulted 0.42 mm. The tapered implant achieved greater primary stability values measured with ITVs and less marginal bone loss than the cylindrical implants.


Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment.
To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR). A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 10(3) cells/microl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit.


Drug therapy for diarrheal diseases: a look ahead.
The gastrointestinal tract is involved in both absorption and secretion of electrolytes and water, with absorption as the predominant process. In diarrheal diseases this balance is disturbed, and the result is net secretion. Most of the drugs used for the treatment of diarrhea at least partially act by stimulating absorption only, both stimulating absorption and inhibiting secretion, or inhibiting secretion only. The therapeutic usefulness of an antidiarrheal agent depends on how efficiently it alters secretion and/or absorption and on how few systemic adverse reactions it causes. When more information on the regulation of absorption and secretion has been accumulated, it may be possible to develop new drugs that can be aimed directly at these processes.


Formation and coalescence of cosmological supermassive-black-hole binaries in supermassive-star collapse.
We study the collapse of rapidly rotating supermassive stars that may have formed in the early Universe. By self-consistently simulating the dynamics from the onset of collapse using three-dimensional general-relativistic hydrodynamics with fully dynamical spacetime evolution, we show that seed perturbations in the progenitor can lead to the formation of a system of two high-spin supermassive black holes, which inspiral and merge under the emission of powerful gravitational radiation that could be observed at redshifts z is approximately equal or > to 10 with the DECIGO or Big Bang Observer gravitational-wave observatories, assuming supermassive stars in the mass range 10(4)-10(6)M[symbol: see text]. The remnant is rapidly spinning with dimensionless spin a*=0.9. The surrounding accretion disk contains ~10% of the initial mass.


Internalisation of isotope-coupled somatostatin analogues.
With the technique of in vivo somatostatin (SRIF) receptor (sst) scintigraphy a variety of human sst-positive tumours can be visualised 24-48 h after intravenous injection of the radiolabelled (SRIF) analogue [111In-DTPA-D-Phe1]octreotide. This rather long residence time of radioactivity on tumours suggests that the radioligand is internalised by the tumour cells; literature data for normal pituitary and pancreatic islet cells agree with this. Internalised SRIF has been found to be associated with cytoplasmic organelles, especially the Golgi apparatus, lysosomes and secretory granules. We have found that mouse AtT20 and primary cultures of human growth-hormone-secreting pituitary adenoma cells internalised a high amount of radio-iodinated [Tyr3]octreotide. Since octreotide binds with high affinity to the sst2 and sst5 subtypes and because both sst subtypes are expressed in these cells, one or both subtypes may be involved in this process. We also found that unlabelled octreotide, SRIF-14 or SRIF-28 can increase the internalisation of the radioligand. These observations, together with other studies on the manipulation of sst expression, may help to optimise the uptake of radioligand in in vivo sst scintigraphy in humans and improve the potential effect of radiotherapy with radiolabelled (subtype-specific) SRIF analogues.


Ciprofloxacin Pharmacokinetics/Pharmacodynamics against Susceptible and Low-Level Resistant Escherichia coli Isolates in an Experimental Ascending Urinary Tract Infection Model in Mice.
The mouse ascending urinary tract infection model was used to study the pharmacokinetic/pharmacodynamic (PKPD) relationships of the effect of ciprofloxacin in subcutaneous treatment for 3 days with varying doses and dosing intervals against a susceptible Escherichia coli strain (MIC, 0.032 mg/liter). Further, a humanized dose of ciprofloxacin was administered for 3 days against three E. coli strains with low-level resistance, i.e., MICs of 0.06, 0.25, and 1 mg/liter, respectively. Against the susceptible isolate, ciprofloxacin was highly effective in clearing the urine with daily doses from 10 mg/kg, but the dosing regimen had to be divided into at least two doses for optimal effect. Ciprofloxacin could not clear the urine or kidneys for the low-level-resistant strains. PKPD correlations with all strains combined showed that for the AUC24/MIC there was a slightly higher correlation with effect in urine and kidneys (R2, 0.71 and 0.69, respectively) than the %T>MIC (R2, 0.41 and 0.61, respectively). Equal correlations for the two PKPD indices were found for reduction of colony counts (CFU) in the bladder tissue, but not even the highest dose of 28 mg/kg × 6 could clear the bladder tissue. In conclusion, ciprofloxacin is highly effective in clearing the urine and kidney tissue for fully susceptible E. coli, while even low-level resistance in E. coli obscures this effect. While the effect of ciprofloxacin is mostly AUC/MIC driven against E. coli infection in the urinary tract, the effect in urine depends on the presence of ciprofloxacin in the urine during most of a 24-h period.


Radiographic changes around immediately restored dental implants in periodontally susceptible patients: 1-year results.
There is little information available about radiographic bone changes around immediately restored implants in periodontally compromised patients. The aims of this study were to evaluate the effect of immediate restoration on radiographic bone changes and to compare radiographic changes between arches and between healed and extraction sites in periodontally susceptible patients. Patients received periodontal treatment. "All in one" implant surgery was then performed: Hopeless teeth were extracted, debridement around remaining adjacent teeth was performed, implants were inserted guided by a surgical stent, and a prefabricated screwed provisional restoration was immediately delivered on selected implants. Periapical radiographs using a parallelism appliance were taken at implant surgery and 6 and 12 months postsurgery. The distance between the alveolar crest and the implant shoulder was measured at the mesial and distal aspect of each implant. Bone changes were compared between immediately restored, submerged, and nonrestored implants; between arches; and between healed and extraction sites. Nineteen patients received 74 implants. Twelve implants in 4 patients failed within the first 6 months. Mean bone changes (+/- SE) between baseline and 12 months ranged between -1.19 +/- 0.19 mm and -1.88 +/- 0.3 mm. No difference was found between restored versus nonrestored sites or between maxillary and mandibular sites. Bone loss was slightly higher in healed sites. First-year bone changes around immediately restored dental implants in periodontally susceptible patients were slightly higher than most reports in the literature. This indicates a potential influence of periodontal disease on the success rate of dental implants.


Incidence of osmophilic yeasts and Zygosaccharomyces rouxii during the production of concentrate grape juices.
Zygosaccharomyces rouxii is the main spoilage yeast of grape juice concentrates. Detection and identification of Z. rouxii during the production of grape juice concentrate is critical to prevent spoilage in the final product. In this work, three grape juice concentrate processing plants were assessed by identifying osmophilic yeasts in juices and surfaces during different stages of a complete production line. Subsequently, molecular typing of Z. rouxii isolates was done to determine the strain distribution of this spoilage yeast. Osmotolerant yeast species, other than Z. rouxii, were mainly recovered from processing plant environments. Z. rouxii was only isolated from surface samples with grape juice remains. Z. rouxii was largely isolated from grape juice samples with some degree of concentration. Storage of grape juice pre-concentrate and concentrate allowed an increase in the Z. rouxii population. A widely distributed dominant molecular Z. rouxii pattern was found in samples from all three processing plants, suggesting resident microbes inside the plant.


Cardiovascular event rates in atorvastatin patients versus patients switching from atorvastatin to simvastatin.
Statin dose, adherence, and cardiovascular (CV) outcomes are important factors when considering switching statin therapies. The objective of the study was to compare CV event rates and risk in managed care patients receiving atorvastatin versus those switched to simvastatin from atorvastatin. Patients 18-64 years, with ≥3 continuous pharmacy claims for atorvastatin between 1/1/05-11/30/07 and ≥12 months pre- and ≥3 months post-index continuous eligibility were identified using HealthCore Integrated Research Database (HIRD). Patients were stratified into two cohorts: one continued atorvastatin without interruption and the other switched to simvastatin. Patients were matched 1:10 (continue atorvastatin/switch simvastatin) on five variables, excluding lipid parameters due to limited data availability. Descriptive statistics were reported for sample characteristics. A multivariate Cox proportional hazards model was developed to evaluate adjusted CV risk. In total 73,960 atorvastatin patients and 7396 simvastatin-switch patients were analyzed. The mean age was 54 ± 7 years (both cohorts). Mean follow-up was 440 days for atorvastatin patients and 237 days for simvastatin-switch patients. Mean dose and therapy duration for atorvastatin was 20 mg and 321 days compared with 33 mg and 195 days for simvastatin-switch, respectively. Of the simvastatin-switch patients, 32% were switched to a less potent simvastatin dose (<2× prior atorvastatin dose). After adjusting for demographic/clinical characteristics, no significant differences were found in CV risk between cohorts. Limitations include use of administrative claims data without lipid level laboratory results data and the length of follow-up which may not have been sufficient to demonstrate significant differences in event rates between groups. In this managed care population, no significant differences were found in risk of CV events among patients switching to simvastatin compared to patients continuing atorvastatin. Switched patients may differ from controls for reasons not captured in the database.


Microvascular disease in children and adolescents with type 1 diabetes and obesity.
The incidence of type 1 diabetes (T1D) is increasing worldwide and is associated with a significant burden, mainly related to the development of vascular complications. Over the last decades, concomitant with the epidemic of childhood obesity, there has been an increasing number of cases of type 2 diabetes (T2D) among children and adolescents. Microvascular complications of diabetes, which include nephropathy, retinopathy and neuropathy, are characterized by damage to the microvasculature of the kidney, retina and neurons. Although clinically evident microvascular complications are rarely seen among children and adolescents with diabetes, there is clear evidence that their pathogenesis and early signs develop during childhood and accelerate during puberty. Diabetic vascular complications are often asymptomatic during their early stages, and once symptoms develop, there is little to be done to cure them. Therefore, screening needs to be started early during adolescence and, in the case of T2D, already at diagnosis. Identification of risk factors and subclinical signs of complications is essential for the early implementation of preventive and therapeutic strategies, which could change the course of vascular complications and improve the prognosis of children, adolescents and young adults with diabetes.


White sturgeon tissue fatty acid compositions are affected by dietary lipids.
Juvenile white sturgeon (Acipenser transmontanus) were fed eight isonitrogenous and isoenergetic purified diets for 9 wk to study their ability to utilize different dietary lipids. Each diet contained 15% of control oil mixture (corn oil-cold liver oil-lard, 1:1:1), corn oil, cod liver oil, lard, linseed oil, soybean oil, safflower oil or canola oil. No significant (P > 0.05) differences in percentage of body weight increase, feed efficiency or body composition were observed among sturgeon fed the different lipids. Tissue fatty acid compositions most sensitive to dietary lipids were those of muscle and liver, whereas brain fatty acid composition was the least sensitive. Results of this study indicate that it is possible to increase the levels of (n-3) polyunsaturated and highly unsaturated fatty acids in sturgeon muscle by feeding the fish lipids high in these fatty acids for 9 wk.


The right hippocampus leads the bilateral integration of gamma-parsed lateralized information.
It is unclear whether the two hippocampal lobes convey similar or different activities and how they cooperate. Spatial discrimination of electric fields in anesthetized rats allowed us to compare the pathway-specific field potentials corresponding to the gamma-paced CA3 output (CA1 Schaffer potentials) and CA3 somatic inhibition within and between sides. Bilateral excitatory Schaffer gamma waves are generally larger and lead from the right hemisphere with only moderate covariation of amplitude, and drive CA1 pyramidal units more strongly than unilateral waves. CA3 waves lock to the ipsilateral Schaffer potentials, although bilateral coherence was weak. Notably, Schaffer activity may run laterally, as seen after the disruption of the connecting pathways. Thus, asymmetric operations promote the entrainment of CA3-autonomous gamma oscillators bilaterally, synchronizing lateralized gamma strings to converge optimally on CA1 targets. The findings support the view that interhippocampal connections integrate different aspects of information that flow through the left and right lobes.


Recurrent herpes simplex virus infections in the adult hand.
Ten adult patients referred to the Department of Dermatology and Venereology at Akademiska Hospital, Uppsala, from different surgical units due to recurrent herpes simplex virus (HSV) infections in the hand, were investigated. At recurrence, virus isolation and typing revealed genital HSV type 2 virus in nine out of ten patients indicating that recurrent HSV infections located in the hand should be looked upon as a part of a venereal disease.


Cobalt-doped hematite thin films for electrocatalytic water oxidation in highly acidic media.
Earth-abundant cobalt-doped hematite thin-film electrocatalysts were explored for acidic water oxidation. The strategically doped hematite produced a stable geometric current density of 10 mA cm-2 for up to 50 h at pH 0.3, as a result of Co-enhanced intrinsic catalytic activity and charge transport properties across the film matrix.


A Novel Unsupervised Segmentation Quality Evaluation Method for Remote Sensing Images.
The segmentation of a high spatial resolution remote sensing image is a critical step in geographic object-based image analysis (GEOBIA). Evaluating the performance of segmentation without ground truth data, i.e., unsupervised evaluation, is important for the comparison of segmentation algorithms and the automatic selection of optimal parameters. This unsupervised strategy currently faces several challenges in practice, such as difficulties in designing effective indicators and limitations of the spectral values in the feature representation. This study proposes a novel unsupervised evaluation method to quantitatively measure the quality of segmentation results to overcome these problems. In this method, multiple spectral and spatial features of images are first extracted simultaneously and then integrated into a feature set to improve the quality of the feature representation of ground objects. The indicators designed for spatial stratified heterogeneity and spatial autocorrelation are included to estimate the properties of the segments in this integrated feature set. These two indicators are then combined into a global assessment metric as the final quality score. The trade-offs of the combined indicators are accounted for using a strategy based on the Mahalanobis distance, which can be exhibited geometrically. The method is tested on two segmentation algorithms and three testing images. The proposed method is compared with two existing unsupervised methods and a supervised method to confirm its capabilities. Through comparison and visual analysis, the results verified the effectiveness of the proposed method and demonstrated the reliability and improvements of this method with respect to other methods.


Synthesis, biological evaluation, and pharmacophore generation of new pyridazinone derivatives with affinity toward alpha(1)- and alpha(2)-adrenoceptors.
A series of new pyridazin-3(2H)-one derivatives (3 and 4) were evaluated for their in vitro affinity toward both alpha(1)- and alpha(2)-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the alpha(1)-adrenoceptor, with K(i) values in the low nanomolar range. The polymethylene chain constituting the spacer between the furoylpiperazinyl pyridazinone and the arylpiperazine moiety was shown to influence the affinity and selectivity of these compounds. Particularly, a gradual increase in affinity was observed by lengthening the polymethylene chain up to a maximum of seven carbon atoms. In addition, compound 3k, characterized by a very interesting alpha(1)-AR affinity (1.9 nM), was also shown to be a highly selective alpha(1)-AR antagonist, the affinity ratio for alpha(2)- and alpha(1)-adrenoceptors being 274. To gain insight into the structural features required for alpha(1) antagonist activity, the pyridazinone derivatives were submitted to a pharmacophore generation procedure using the program Catalyst. The resulting pharmacophore model showed high correlation and predictive power. It also rationalized the relationships between structural properties and biological data of, and external to, the pyridazinone class.


Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines.
The development of cell culture systems for virus propagation has led to major advances in virus vaccine development. Primary and diploid cell culture systems are now being replaced by the use of continuous cell lines (CCLs). These substrates are gaining increasing acceptance from regulatory authorities as improved screening technologies remove fears regarding their potential oncogenic properties. The Vero cell line is the most widely accepted CCL by regulatory authorities and has been used for over 30 years for the production of polio and rabies virus vaccines. The recent licensure of a Vero cell-derived live virus vaccine (ACAM2000, smallpox vaccine) has coincided with an explosion in the development of a range of new viral vaccines, ranging from live-attenuated pediatric vaccines against rotavirus infections to inactivated whole-virus vaccines against H5N1 pandemic influenza. These developments have illustrated the value of this cell culture platform in the rapid development of vaccines against a range of virus diseases.


In vivo visualization of synaptic vesicles within Drosophila larval segmental axons.
Elucidating the mechanisms of axonal transport has shown to be very important in determining how defects in long distance transport affect different neurological diseases. Defects in this essential process can have detrimental effects on neuronal functioning and development. We have developed a dissection protocol that is designed to expose the Drosophila larval segmental nerves to view axonal transport in real time. We have adapted this protocol for live imaging from the one published by Hurd and Saxton (1996) used for immunolocalization of larval segmental nerves. Careful dissection and proper buffer conditions are critical for maximizing the lifespan of the dissected larvae. When properly done, dissected larvae have shown robust vesicle transport for 2-3 hours under physiological conditions. We use the UAS-GAL4 method to express GFP-tagged APP or synaptotagmin vesicles within a single axon or many axons in larval segmental nerves by using different neuronal GAL4 drivers. Other fluorescently tagged markers, for example mitochondria (MitoTracker) or lysosomes (LysoTracker), can be also applied to the larvae before viewing. GFP-vesicle movement and particle movement can be viewed simultaneously using separate wavelengths.


Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity.
Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein involved in neutrophil apoptosis and the resolution of inflammation. Given the numerous pathophysiologic roles of neutrophils in the acute respiratory distress syndrome (ARDS), we postulated that neutrophil GILZ expression might be induced during ARDS, to modulate the inflammatory process and participate in lung repair. This single-center, prospective, observational cohort study took place in the surgical intensive care unit of Bichat Hospital (Paris, France) and involved 17 ARDS patients meeting the Berlin criteria at inclusion, and 14 ventilated controls without ARDS. Serial blood samples were obtained every 2 days until extubation or death (from 1 to 9 samples per patient). GILZ protein and gene expression was quantified in blood neutrophils, along with markers of inflammation (CRP, extracellular DNA) or its resolution (Annexin A1). Neutrophil GILZ expression was detected at the transcriptional and/or translational level in 9/17 ARDS patients (in particular 7/10 severe ARDS) and in 2/14 ventilated controls. The highest mRNA levels were observed in the most severely ill patients (p < 0.028). GILZ was expressed in about ¾ of the corticosteroid-treated patients and its expression could also occur independently of corticosteroids, suggesting that inflammatory signals may also induce neutrophil GILZ expression in vivo. In this pilot study, we show for the first time that blood neutrophils from patients with ARDS can express GILZ, in keeping with an anti-inflammatory and regulatory endogenous role of GILZ in humans. Contrary to some markers of inflammation or its resolution, the levels of gilz gene expression were related to ARDS severity.


Intracellular glutathione level and efflux in human melanoma and cervical cancer cells differing in doxorubicin resistance.
Drug resistance continues to be a major problem in cancer treatment. Occurrence of this phenomenon is often associated with altered levels of glutathione (GSH) and GSH-related enzymes. The aim of the study was to evaluate the possible involvement of GSH and GSH-related enzymes in doxorubicin (DOX) resistance in two types of cancer cells of different etiology, from both parental and DOX-resistant sublines. The human melanoma (ME18 and ME18/R) and cervical cancer cells (HeLa and KB-V1) were tested in terms of their DOX sensitivity (EZ4U test), GSH level (HPLC) and its efflux (spectrofluorometrically). The effects of inhibition of the GSH-related enzymes γ-glutamylcysteine synthetase (γ-GCS) and glutathione S-transferase (GST) were also evaluated. Exposure to DOX caused an increase of GSH levels in all tested cells except for HeLa cells. However, depletion of GSH did not have a significant influence on the sensitivity of the cells to DOX. Inhibition of the activity of GST also did not have a major effect on DOX sensitivity, although it caused changes of the GSH content. Our attempts to use the spectrofluorometric method for measurements of GSH efflux were not successful. It could be suggested that in ME18 and HeLa cells treated with DOX, GSH efflux does occur. The obtained results seem to refute the hypothesis of a central role of GSH in DOX resistance of the tested cells. Despite observations of different effects related to GSH, they do not seem to be essential in terms of DOX resistance. The mechanisms underlying DOX resistance are highly cell-specific.


Dose-response effects of inactivated Newcastle disease vaccines: influence of serologic assay, time after vaccination, and type of chickens.
Knowledge of the dose-response relation of inactivated vaccines and of the factors that influence this relation is essential for the evaluation of existing vaccine potency assays and the development of new potency assays that are based on the antigen content of the inactivated vaccines. We quantified the relation between vaccine dose, serologic response, and clinical protection after vaccination for three different inactivated Newcastle disease (ND) vaccines. Qualitatively, similar dose-response curves were obtained for the three vaccines when either the serologic response or the clinical protection of specific-pathogen-free (SPF) chickens was plotted against the different vaccine doses applied. However, the vaccines differed quantitatively: doses of vaccines that induced similar antibody titers or clinical protection differed 2-8-fold. In contrast with the narrow range of antibody titers induced by a full vaccine dose, a very broad range of titers was obtained after dilution of the vaccines. At least 95% of the SPF chickens with detectable antibody in the serum were protected against a challenge with virulent Herts ND virus. The relation between the dosage of two different ND vaccines and the serum antibody titers remained markedly constant between 3 and 18 wk after vaccination. Vaccination of broilers instead of layers with a dilution series of inactivated ND vaccine resulted in significantly lower antibody levels and less clinical protection against virulent challenge. In conclusion, despite quantitative differences, we found comparable dose-response relations for the three inactivated ND vaccines studied.


Experiences of expressing and storing colostrum antenatally: A qualitative study of mothers in regional Western Australia.
This qualitative study explored the experiences and breastfeeding outcomes of a group of mothers who expressed colostrum in the antenatal period. In-depth interviews were conducted over the telephone with 12 women who had attended a unique antenatal lactation clinic appointment at 37 weeks' gestation. Seven main response themes were identified. Most women reflected positively upon their attendance and reported that the experience of expressing colostrum allowed them to become familiar with their breasts and gave them a sense of security by having a supply of colostrum stored for possible use after birth. The main negative emotions reported were a sense of embarrassment at expressing the colostrum, particularly in front of another person, the difficulties with expressing colostrum and in one instance, the physical pain associated with the process. Antenatal expression of colostrum may improve maternal breastfeeding confidence. Further research using long-term records will determine whether this practice improves breastfeeding outcomes.


Energy and amino acid utilization in expeller-extracted canola meal fed to growing pigs.
Two experiments were conducted to determine the nutritive value of expeller-extracted canola meal (EECM) for growing pigs. In Exp. 1, a total of 6 ileally cannulated barrows (average initial BW = 26.8 kg) were fed 3 diets in a replicated 3 x 3 Latin square design to determine the apparent and standardized ileal digestibility (SID) values of N and AA and the SID AA contents of EECM. The 3 diets were a cornstarch-based diet with either solvent-extracted canola meal (SECM) or EECM as the sole source of protein, and a low-casein cornstarch-based diet, which was used to estimate basal endogenous N and AA losses to determine the SID of N and AA. All 3 diets contained chromic oxide as an indigestible marker for determining nutrient digestibility by the indicator method. In Exp. 2, a total of 18 intact barrows (average initial BW = 25.9 kg) were fed 3 diets in a completely randomized design (6 pigs per diet) to determine apparent total tract digestibility and retention of nutrients and the DE and ME contents of EECM. The diets were a basal corn-based diet or the basal diet with corn replaced by 35% SECM or EECM. The basal diet was used for determining the total tract digestible nutrient content by the difference method. Solvent-extracted canola meal, which is commonly used in the formulation of swine diets, was fed in both experiments for comparison with EECM. The SECM and EECM were similar in CP content (41.8 vs. 41.4%). Expeller-extracted canola meal was, however, greater in ether extract content (12.03 vs. 5.54%) and decreased in NDF content (23.8 vs. 29.9%) compared with SECM. The EECM also had a greater content of all the AA except Met, Cys, and Ser, by approximately 6.6%; Cys was greater in SECM, whereas Met and Ser were similar between the 2 meals. The EECM had greater (P < 0.05) SID of N, Arg, Ile, Leu, Phe, Glu, and Pro. The SID contents of Arg, His, Ile, Leu, Phe, Val, Ala, Asp, Glu, Gly, Pro, and Tyr were also greater (P < 0.05) for EECM than for SECM by an average of 15%. The EECM had greater (P < 0.01) DE (4,107 vs. 3,790 kcal/kg) and ME (3,978 vs. 3,564 kcal/kg) values compared with SECM. The results show that the EECM used in the current study had greater digestible AA and energy and a greater ME content than the SECM; hence, it may be a better source of protein and energy for growing pigs than SECM.


[Immediately placed front tooth implants 1. Analysis with cone beam computed tomography after remodelling of the buccal plate].
In the period 1 January 2008 to 1 January 2012, an implant was installed in 186 patients immediately after the removal of a maxillary incisor. Subsequent to the placement of the implant, the 2 mm gap between implant and buccal plate was filled with a bone substitute. In the case of 16 patients, in addition to a preoperative and immediately postoperative cone beam computer tomogram, a late-postoperative cone beam computer tomogram was also produced.Immediately post-operative, the buccal plate thickness increased by 1.5 mmfrom 0.9 mm to 2.4 mm. During the evaluation period of 1 to 4 years a reduction took place resulting in a final buccal plate thickness of 1.8 mm on average. Surprisingly, the buccal plate bone height increased by 1.6 mm, to an average of 1.2 mm above the implant shoulder. It was crucial in this case that the implant was placed in such a way that a gap of a minimum of 2.0 mm was created between the original buccal plate and the implant, and that this gap was filled with a bone substitute.


[Improvement of Analytical Method of PCBs by GC-MS/MS Using an Accelerated Solvent Extractor and Expansion of Target Food Products].
We examined the expansion of target food products for the analysis of polychlorinated biphenyls (PCBs). From our studies in fish using an accelerated solvent extractor (ASE) and GC-MS/MS, we found that recovery of low-chlorinated PCBs (some isomer of 3 or 4 chlorinated PCBs) in specific food products was low. Therefore, we attempted to improve the analytical method. In Japanese sea perch (Suzuki) and milk, freeze drying before extracting with ASE did not sufficiently improve the recovery of low-chlorinated PCBs; however, it was significantly improved by changing the column to a silica gel/H2SO4 silica gel multilayer column. To evaluate this method for other food products, PCBs in fish, meat, eggs, milk, and dairy products were analyzed. The samples were extracted using ASE at 125℃ with n-hexane, cleaned up using a silica gel/H2SO4 silica gel multilayer column, and analyzed by GC-MS/MS for 3-7 chlorinated PCBs. The limit of quantification for this method was was 0.03-0.16 μg/kg for the 3-7 chlorinated PCBs. The recovery and the coefficient of variation of 3-7 chlorinated PCBs from each of the food products (n=5) was in the range of 84%-112% and 1%-9%, respectively.


[Re-evaluation of the diagnosis in congenital hypothyroidism].
Newborn screening for congenital hypothyroidism (CH) has become routine in Italy. It provided new information regarding the epidemiology, diagnosis and treatment of CH infants and allowed to identify transient disorders of thyroid function in infancy. In fact, when the permanence of hypothyroidism has not been established in the newborn period, a confirmation of the diagnosis at 2-3 years of life should be performed. In this study results regarding the diagnosis reevaluation performed in 23 out of 184 CH children followed at the follow-up center for CH of the University of Rome "La Sapienza", are reported. Eleven of 23 reevaluated children had transient hypothyroidism (TH) and permanent CH was confirmed in the others. Four of the 11 TH children had law gestational age at birth, 1 had high antithyroid peroxidase titre due to maternal autoimmune thyroiditis and 2 were resident in iodine deficient areas. Our results show the importance of diagnosis reevaluation to identify transient disorders of thyroid function in infancy and confirm the role of neonatal, maternal and environmental factors in the etiopathogenesis of TH.


Inhibitors of ATP-binding cassette transporters suppress interleukin-12 p40 production and major histocompatibility complex II up-regulation in macrophages.
ATP-binding cassette (ABC) transporters are a large family of proteins whose role is to translocate various substances across biological membranes. They include the Tangier disease protein ABC1, sulfonylurea receptors (SUR), multidrug resistance protein (MDR), and cystic fibrosis transmembrane regulator (CFTR). In the current study, we investigated the involvement of ABC transporters in the regulation of lipopolysaccharide (LPS) and/or interferon (IFN)-gamma-induced interleukin (IL)-12 p40 and tumor necrosis factor (TNF)-alpha production, nitric oxide formation, as well as major histocompatibility complex II up-regulation in macrophages. The general ABC transporter inhibitor glibenclamide suppressed both IL-12 p40 and nitric oxide production. However, glibenclamide failed to affect the production of TNF-alpha. The selective ABC1 inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and sulfobromophthalein mimicked the suppressive effect of glibenclamide on IL-12 p40 production. On the other hand, both the MDR inhibitor verapamil and CFTR blocker 2,2'-iminodibenzoic acid failed to suppress the production of IL-12 p40. Furthermore, selective inhibitors and activators of SURs were without effect. In agreement with the pharmacological data, macrophages expressed mRNA for ABC1, but not SURs or CFTR. Intracellular levels of IL-12 p40 were decreased by glibenclamide, suggesting that glibenclamide does not affect IL-12 p40 secretion. The effect of glibenclamide did not involve an interference with the activation of the p38 and p42/44 mitogen-activated protein kinases or c-Jun kinase. Glibenclamide also suppressed IFN-gamma-induced up-regulation of major histocompatibility complex II. Taken together, our results indicate that ABC proteins regulate LPS and/or IFN-gamma-induced macrophage activation.


Association of the metabolic syndrome with severe periodontitis in a large U.S. population-based survey.
Metabolic syndrome and periodontitis both have an increasing prevalence worldwide; however, limited information is available on their association. The objective of the study was to assess the association between periodontitis and the metabolic syndrome in a cross-sectional survey of a nationally representative sample of the noninstitutionalized civilians in the United States. Data analysis from the Third National Health and Nutrition Examination Survey on 13,994 men and women aged 17 yr or older who received periodontal examination were studied. Association of diagnosis and extent of periodontitis (gingival bleeding, probing pocket depths) with the metabolic syndrome and its individual component conditions (central obesity, hypertriglyceridemia, low high-density lipoprotein-cholesterol, hypertension, and insulin resistance) were measured. Adjustment for age, sex, years of education, poverty to income ratio, ethnicity, general conditions, and smoking were considered. The prevalence of the metabolic syndrome was 18% [95% confidence interval (CI) 16-19], 34% (95% CI 29-38), and 37% (95% CI 28-48) among individuals with no-mild, moderate, and severe periodontitis, respectively. After adjusting for confounders, participants aged older than 45 yr suffering from severe periodontitis were 2.31 times (95% CI 1.13-4.73) more likely to have the metabolic syndrome than unaffected individuals. Diagnosis of metabolic syndrome increased by 1.12 times (95% CI 1.07-1.18) per 10% increase in gingival bleeding and 1.13 times (95% CI 1.03-1.24) per 10% increase in the proportion of periodontal pockets. Severe periodontitis is associated with metabolic syndrome in middle-aged individuals. Further studies are required to test whether improvements in oral health lead to reductions in cardiometabolic traits and the risk of metabolic syndrome or vice versa.


Practical value of Ki-67 and p53 labeling indexes in stereotactic biopsies of diffuse and pilocytic astrocytomas.
Stereotactic biopsies are increasingly being used for the diagnosis and grading of astrocytomas, and there is a growing need to obtain maximum information from these tissue samples. In everyday practice, p53 protein and Ki-67 immunohistochemical analyses are the most frequently used ancillary studies to aid in diagnosis and grading, but their exact role is not clearly established. This study was undertaken to evaluate the practical value of these markers in stereotactic biopsy samples from diffuse astrocytomas as well as pilocytic astrocytomas. Methods/Results.-We analyzed the Ki-67 (MIB-1) and p53 labeling indexes in the stereotactic biopsy specimens from 11 pilocytic astrocytomas; 8 grade 2, 15 grade 3, and 16 grade 4 diffuse astrocytomas. Pilocytic astrocytomas and diffuse astrocytomas were evaluated as 2 separate groups. There was a strong correlation with poor outcome when both labeling indexes were higher than 15% in the same tumor for diffuse astrocytomas (P < 0.01). The indexes did not correlate with outcome in pilocytic astrocytomas. Combined Ki-67 and p53 labeling indexes higher than 15% indicated a worse outcome than suggested by the histologic grading. The analysis aided or improved histologic evaluation of stereotactic biopsies in our patients. We believe that a realistic prognostic upgrading of diffuse astrocytomas should be made only when labeling indexes for both markers are greater than 15%.


Analysis of the YouTube videos on pelvic floor muscle exercise training in terms of their reliability and quality.
The aim of this study was to evaluate the content, reliability and quality of YouTube videos related to pelvic floor muscle exercise training. This study was carried out on the descriptive model in order to evaluate the content, reliability and quality of the videos on YouTube related to pelvic floor muscle exercise training. "Pelvic floor muscle exercise" was searched on YouTube in English in March 2020, and a total of 107 videos were watched. Quality Criteria for Consumer Health Information (DISCERN) survey was used to analyze the videos in terms of their reliabilities, and Global Quality Score (GQS) was used to evaluate their qualities. When the contents of 59 videos included in the study were examined, it was determined that 52 of them contained useful information and 7 of them contained misleading information. Comprehensiveness mean scores, DISCERN mean scores and GQS means of the useful videos were found to be statistically higher than that of the moderate and misleading videos (p < 0.05).When videos were analyzed according to the publishing sources, 84.62% (44/52) of the useful videos and 85.71% (6/7) of misleading video were observed to be published by independent health information websites. No statistically significant difference was found between the overall comprehensiveness mean scores, DISCERN mean scores, GQS means and the features of the videos according to their publishing sources. In this study, it was observed that the vast majority of YouTube videos on pelvic floor muscle exercise training were useful videos; the vast majority of these videos were published by independent health information websites and contained moderately safe, accurate and quality information.


Fiber-optic large-depth 3D chromatic confocal endomicroscopy.
Current endoscopy techniques have difficulties to provide both high resolution and large imaging depth, which significantly hinders the early diagnosis of gastric cancer. Here, we developed a label-free, large-depth, three-dimensional (3D) chromatic reflectance confocal endomicroscopy. In order to solve the problem of insufficient imaging depth of traditional chromatic confocal microscopy, a customized miniature objective lens both with large chromatic focal shift and correction for spherical aberration was used to focus light of different wavelengths at different depths of the sample simultaneously, and a fiber bundle containing 50000 single-mode cores was used to collect the confocal reflectance signal. To acquire detailed information along the axial direction at a faster speed, a high-speed multi-pixel spectrometer was used to realize simultaneous detection of multi-depth signals. Specifically, we have built up a label-free fiber-optic 3D chromatic reflectance confocal endomicroscopy, with 2.3 µm lateral resolution, imaging depth of 570 µm in 3D phantom and 220 µm in tissue, and 1.5 Hz 3D volumetric frame rate. We have demonstrated that the fiber-optic 3D chromatic confocal endomicroscopy can be used to image human gastric tissues ex vivo, and provide important morphological information for diagnosis without labeling. These results show the great potential of the fiber-optic 3D chromatic confocal endomicroscopy for gastric cancer diagnosis.


Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium.
Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-α and interleukin-1β via extracellular-signal-regulated kinases phosphorylation and nuclear factor-κB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.


Penile reconstruction for extramammary Paget's disease.
The authors report their experience of an extremely rare case of extramammary Paget's disease presenting a deformational change of the penis, which required penile reconstruction after tumor resection. Tumor cells had invaded the dermis beyond the basement membrane of the epidermis. Tumor cells were found at the epithelium of the urethra, but had not invaded the corpus cavernosum. However, fibrotic changes were found in the corpus cavernosum. More than half the length of the penis was resected. Penile reconstruction was performed using a free sensory radial forearm flap. The defects in the mons pubis, scrotum, and the remaining corpus cavernosum were covered using a meshed split skin graft or sheeted split skin graft. Ten months after the operation, the tumor had not recurred and no metastasis was found. The urinary stream was narrow compared with that of a healthy man, but urinary voiding had not been disturbed. Sensory recovery was 12 mm with the two-point discrimination test at the distal end of the reconstructed penis.


Modified Enskog kinetic theory for strongly coupled plasmas.
Concepts underlying the Enskog kinetic theory of hard-spheres are applied to include short-range correlation effects in a model for transport coefficients of strongly coupled plasmas. The approach is based on an extension of the effective potential transport theory [S. D. Baalrud and J. Daligault, Phys. Rev. Lett. 110, 235001 (2013)] to include an exclusion radius surrounding individual charged particles that is associated with Coulomb repulsion. This is obtained by analogy with the finite size of hard spheres in Enskog's theory. Predictions for the self-diffusion and shear viscosity coefficients of the one-component plasma are tested against molecular dynamics simulations. The theory is found to accurately capture the kinetic contributions to the transport coefficients, but not the potential contributions that arise at very strong coupling (Γ≳30). Considerations related to a first-principles generalization of Enskog's kinetic equation to continuous potentials are also discussed.


[A case report of Kimura's disease causing visual dysfunction with remarkable eyelid swelling].
We report a case of Kimura's disease involving the eyelids, presenting with bilateral eyelid swelling so severe that the eyelids could not be opened. A 37-year-old man presented with eyelid swelling and was unable to open both eyelids. He noted swelling and mass of bilateral eyelids since a year previously, and the masses enlarged gradually impairing eye-opening. Hard soft elastic tumors were palpated in both eyelids. Blood examination revealed marked peripheral blood eosinophilia and an increased serum IgE level. On T 1-weighted MR images, the tumors were observed as isointense masses compared to the extraocular muscles. On T 2-weighted images, the tumors showed hypointense signals while some parts were hyperintense compared to the extraocular muscles. On Gd-enhanced T 1-weighted images, the tumors demonstrated marked enhancement. The tumors in both eyelids were extirpated en bloc. Histopathology of the tumors demonstrated many lymphoid follicles and infiltration of large numbers of eosinophils and lymphocytes. Eosinophilic abscess and proliferation of blood capillaries were observed between the lymphoid follicles. These findings led to a diagnosis of Kimura's disease. PCR revealed clonal rearrangement of the T cell receptor gene. Kimura's disease may cause remarkable eyelid swelling and lead to visual dysfunction. Since recurrence of Kimura's disease is known to be associated with clonal rearrangement of T cell receptor genes, similar cases should be followed carefully for recurrence.


A volume-based description of transport in incompressible liquid electrolytes and its application to ionic liquids.
Transference numbers play an important role in understanding the dynamics of electrolytes and assessing their performance in batteries. Unfortunately, these transport parameters are difficult to measure in highly concentrated liquid electrolytes such as ionic liquids. Also, the interpretation of their sign and magnitude has provoked an ongoing debate in the literature further complicated by the use of different languages. In this work, we highlight the role of the reference frame for the interpretation of transport parameters using our novel thermodynamically consistent theory for highly correlated electrolytes. We argue that local volume conservation is a key principle in incompressible liquid electrolytes and use the volume-based drift velocity as a reference. We apply our general framework to electrophoretic NMR experiments. For ionic liquid based electrolytes, we find that the results of the eNMR measurements can be best described using this volume-based description. This highlights the limitations of the widely used center-of-mass reference frame which for example forms the basis for molecular dynamics simulations - a standard tool for the theoretical calculation of transport parameters. It shows that the assumption of local momentum conservation is incorrect in those systems on the macroscopic scale.


[Sialographic follow-up study of patients with Sjögren's syndrome].
Sialographic follow-up studies of 36 cases of Sjögren's syndrome (SS) were performed with the duration of 5-72 months (mean 25 months). Three groups were divided according to the intenational criteria: secondary group, 14 cases (xerophthalmia, or/and xerostomia, and connective tissue diseases), primary group, 14 cases (xerostomia and xerophthalmia), and possible group, 8 cases (xerophthalmia or xerostomia only). Sialographic findings at follow-up examination included (1) delayed evacuation, which may occur as early as 5 months later; (2) increased punctate sialectasis; (3) decreased punctate sialectasis with globular increase; (4) Punctate, globular, and cavity sialectasis with radiolucent sialolith; and (5) centripetal atrophy. The cases with secondary and possible SS without xerostomia demonstrated little involvement of the parotid gland, without sialectasis. But sialodochitis was shown when radiolucent sialolith formed. The stimulated whole salivary flow rate (SWSFR) was closely related to sialographic appearance, i.e., the cases with lower value of SWSFR showed more sialectasis sialographically, but with higher SWSFR value, and less sialectasis.


[Comparation of low-temperature plasm radiofrequency and high-intensity focused ultrasound therapy on allergic rhinitis patients with nasal septal deviation].
To compare the therapeutic effects of low-temperature plasm radiofrequency and high-intensity focused ultrasound in treatment of perennial allergic rhinitis (PAR) complicated with nasal septum deviation. A total of 224 cases of identified PAR who treated in our hospital were randomly divided into 2 matched groups: low-temperature plasm radiofrequency group (n = 140) and high-intensity focused ultrasound group (n = 84). The therapeutic affection were evaluated by clinical symptoms controlled counting-scores. Inferior turbinate mucosa were collected and examined pathologically before and at 15 days and 6 months after the therapy. The follow-up data indicated the effective rate in 15 days was 97.1% in high-intensity focused ultrasound group, and 90.4% in low-temperature plasm radiofrequency group, in 6 months was 90.7% and 85.4% respectively. The treatment of high-intensity focused ultrasound in PAR is minimally invasive and safe with reliable efficacy.


Infection with Babesia microti in humans with non-specific symptoms in North East Poland.
The aim of the study was to evaluate the clinical course and effectiveness of diagnostics tools for Babesia spp. infection in patients bitten by ticks. Five hundred and forty-eight patients hospitalised or seen in outpatients department because of various symptoms after a tick bite were included in the study. PCR, nucleotide sequencing of Babesia 18S rRNA gene fragment, blood smears and serological tests for Babesia spp., TBEV, A. phagocytophilum and B. burgdorferi were performed in all patients. Six patients infected with Babesia were included in the final analysis. They had PCR, Babesia 18S rRNA gene fragment nucleotide sequencing, blood smears and serological tests for Babesia spp., TBEV, A. phagocytophilum and B. burgdorferi performed twice. Tick-borne infection with Babesia microti in six immunocompetent patients with non-specific symptoms was confirmed for the first time in Poland. No severe course of the disease was seen. No piroplasm forms were noticed within erythrocytes on blood smear. Three patients developed a serological response. Immunocompetent patients may be unaware of infection with Babesia microti after a tick bite. It must be included in the differential diagnosis after the tick bite. In patients with low parasitaemia PCR and serology seem useful when blood smear is negative. Self-elimination of Babesia spp. is possible, especially in cases with low parasitaemia.


Oral health status and its inequality among education groups: comparing seven international study sites.
This study compares oral health status and its inequality among education groups across seven study sites in five countries: Erfurt, Germany; Lodz, Poland; Yamanashi, Japan; New Zealand; and Baltimore and the Lakota and Navajo Indian Health Service sites in the United States. The data, from the International Collaborative Study of Oral Health Outcomes, were collected through personal interviews and clinical examinations. The research group measured the study sites' overall oral health, examining the percentage of the population with five or more missing and two or more decayed teeth. The group also assessed the magnitude of inequality among education groups by using indices of excess morbidity. Baltimore had the lowest percentage (10.8 percent) of decayed teeth and second lowest percentage (17.3 percent) of missing teeth, but the greatest indices of excess morbidity (79.2 percent for missing, 73.1 percent for decayed). Lodz, by contrast, had the worst overall dentition status (75.3 percent for missing, 70.3 percent for decayed) but the lowest inequality indices (10.6 percent for missing, 13.8 percent for decayed). This study demonstrates the need for policymakers in the study countries to consider not only overall levels but also the distribution of oral health, and it presents various challenges for oral health professionals in designing and implementing oral health programs.


The use of pulsatile perfusion during aortic valve replacement in pregnancy.
Cardiac operations are occasionally required during pregnancy. Despite a low maternal mortality, fetal mortality remains high. Previous reports have suggested maintenance of high perfusion pressure and flow rate as protective measures to maintain fetal viability. Recent experimental data suggest pulsatile perfusion may help preserve placental hemodynamic function. The successful use of pulsatile bypass to replace the aortic valve in a 25-year-old female at 14 weeks gestation, with both maternal and fetal survival, is presented.


Development of Defatted Soy Flour-Based Adhesives by Acid Hydrolysis of Carbohydrates.
Soy-based adhesives are attracting increasing attention in recent years because they are a renewable and environmentally friendly raw material. Defatted soy flour (DSF), comprised of 50% protein and 40% carbohydrate, is the most widely used raw material for the preparation of soy-based adhesives that are unfortunately hampered by poor gluability and water resistance. In the present study, we developed a self-crosslinking approach to prepare a formaldehyde-free defatted soy flour-based adhesive (SBA). Carbohydrates in the DSF were hydrolyzed with 0% (controls), 0.5%, 1.0%, 2.0%, 3.0% and 5.0% hydrochloric acid, and cross-linked with proteins to prepare the SBA. The effect of hydrolyzed carbohydrates on the performance of the SBA was investigated, and hydrolyzed carbohydrates significantly increased the amount of reducing sugars, but decreased insoluble substances. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses revealed an enhanced cross-linking structure with fewer hydrophilic groups in cured SBAs. Maillard reactions between hydrolyzed carbohydrates and proteins resulted in SBAs with better gluability, rheological properties and thermal stability than controls. Scanning electron microscopy (SEM) images showed that plywood bonded with SBA had a higher wood failure rate than controls. This approach has potential for preparing bio-adhesives with enhanced properties from other natural resources with a similar polysaccharides and protein composition.


Upper and lower cluster headache: clinical and pathogenetic observations in 608 patients.
OBJECTIVE, BACKGROUND, AND METHODS: Ever since it was proposed by Ekbom and Kugelberg back in 1968 on the basis of the different location of head pain during attacks, the differentiation of cluster headache into an upper syndrome (US) and a lower syndrome (LS) has been regarded as a purely academic distinction. To evaluate whether this differentiation is indeed well founded and to understand its possible significance in the light of current pathogenetic knowledge, we rigorously applied Ekbom and Kugelberg's classification criteria to a sample of 608 patients with cluster headache (CH; 440 men and 168 women), including 483 with episodic CH, 69 with chronic CH, and 56 with CH periodicity undetermined. Of these patients, 278 could be classified as US sufferers and 330 as LS sufferers. Our data analysis showed statistically significant clinical differences between the two syndromes: pain location was more common in the ocular, temporal, and nuchal regions among LS sufferers; in addition, patients with LS reported not only a higher rate of autonomic symptoms, but also a higher predominance of nasal congestion, ptosis, and forehead and facial sweating among these symptoms. Based on current anatomofunctional knowledge and on the most recent pathogenetic findings, we believe that changes in hypothalamic activity posteroinferiorly may lead to activation of the caudal part of the spinal trigeminal nucleus by way of the hypothalamus, midbrain, and trigeminal nerve fibers and consequently to activation of the trigeminovascular system with a different location in the two syndromes. More specifically, there seems to be a larger and more extensive involvement of the subnucleus caudalis in LS compared with US, where only its ventrocaudal portions are likely to be affected.


Rupture of the left main-stem bronchus by the tracheal portion of a double-lumen endobronchial tube.
We report a rupture of the left main-stem bronchus following the insertion of a left-sided double-lumen endobronchial tube in a 76-yr-old woman with a short trachea. A fiberoptic bronchoscope was not used during the initial insertion of the tube and the depth of insertion resulted in approximately 5 cm in excess of the optimal level for this patient. The rupture had been caused by the tracheal portion of the double-lumen tube. This damage may have been avoided if a fiberoptic bronchoscope was used routinely as an introducer and for positioning of the endobronchial tube under direct vision.


The effect of sivelestat sodium hydrate on severe respiratory failure after thoracic aortic surgery with deep hypothermia.
Patients who undergo thoracic aortic surgery with deep hypothermia frequently have postoperative respiratory failure as a complication. Severe lung injury in these patients results in a fatal outcome. A specific neutrophil elastase inhibitor, sivelestat sodium hydrate, is an innovative therapeutic drug for acute lung injury. We evaluated the protective effects of sivelestat sodium hydrate on severe lung injury after thoracic aortic surgery with deep hypothermia. From January 2002 to July 2007, 71 consecutive patients underwent thoracic aortic surgery with deep hypothermia. Of these patients, 22 had postoperative respiratory failure with PaO₂/FiO₂ ratios of less than 150. They were randomly assigned to one of two groups. The first group (Group S, n = 10) was administered sivelestat sodium hydrate continuously at 0.2 mg/kg/h until weaning from mechanical ventilation; the second group (Group C, n = 12) was not administered sivelestat sodium hydrate. The groups were comparable with respect to clinical data. There were no significant differences between the two groups in age, operation duration, total cardiopulmonary bypass time, circulatory ischemia time, cardiac arrest time, intraoperative blood loss, and total transfusion volume. The improvement of pulmonary function was observed in the both groups, but more marked in Group S by statistical analysis using analysis of variance for repeated measurements. Especially, in the early phase, pulmonary function improvement was more marked in Group S. The duration of mechanical ventilation, the length of stay in the intensive care unit, and the length of hospital stay were shorter in Group S, but not significantly. Sivelestat sodium hydrate is a specific neutrophil elastase inhibitor that improves pulmonary function in patients with severe postoperative respiratory failure following thoracic aortic surgery with deep hypothermia. The drug may shorten the duration of postoperative ventilation, intensive care unit stay, and hospital stay.


Chloroplast Biogenesis 49 : Differences among Angiosperms in the Biosynthesis and Accumulation of Monovinyl and Divinyl Protochlorophyllide during Photoperiodic Greening.
Various angiosperms differed in their monovinyl and divinyl protochlorophyllide biosynthetic capabilities during the dark and light phases of photoperiodic growth. Some plant species such as Cucumis sativus L., Brassica juncea (L.) Coss., Brassica kaber (DC.) Wheeler, and Portulaca oleracea L. accumulated mainly divinyl protochlorophyllide at night. Monocotyledonous species such as Avena sativa L., Hordeum vulgare L., Triticum secale L., Zea mays L., and some dicotyledonous species such as Phaseolus vulgaris L., Glycine max (L.) Merr., Chenopodium album L., and Lycopersicon esculentum L. accumulated mainly monovinyl protochlorophyllide at night.Under low light intensities meant to simulate the first 60 to 80 minutes following daybreak divinyl protochlorophyllide appeared to contribute much more to chlorophyll formation than monovinyl protochlorophyllide in species such as Cucumis sativus L. Under the same light conditions, species which accumulated mainly monovinyl protochlorophyllide at night appeared to form chlorophyll preferably via monovinyl protochlorophyllide.THESE RESULTS WERE INTERPRETED IN TERMS OF: (a) a differential contribution of monovinyl and divinyl protochlorophyllide to chlorophyll formation at daybreak in various plant species; and (b) a differential regulation of the monovinyl and divinyl protochlorophyllide biosynthetic routes by light and darkness.


Managing performance and performance management: information strategy and service user involvement.
The involvement of service users is extolled in National Service Frameworks and, in Wales, is one of seven standards set out in the National Service Framework for mental health services. National Service Frameworks have an important role in the UK government's performance management strategies. The strategies are retrospective in effect and offer insufficient help for service managers and others seeking to change and improve service performance. Draws on research conducted at intervals over the past four years in Swansea. In today's devolved UK, the details will be different in Wales from elsewhere but the focus is on how a number of organisations with differing responsibilities can work together to manage performance improvement. Demonstrates that change requires leadership to be dispersed across organisational boundaries. Accountability and responsibility must be horizontal and even downwards, not just upwards to government Service users can b e involved in their own care. Surveys that involve service users in their planning stages can gather information about the service issues that matter to them. Managing performance is different from performance management. It can ultimately enable services users to initiate and direct some of the improvements they want to see and to take part in the processes of change. The information systems must be locally useful for all involved, and must offer information about performance in time to affect improvement and change.


Is sex necessary?
Fungal sexual reproductive modes have markedly high diversity and plasticity, and asexual species have been hypothesized to arise frequently from sexual fungal species. A recent study on the red yeasts provides further support for the notion that sexual ancestors may give rise to shorter-lived asexual species. However, presumed asexual species may also be cryptically sexual, as revealed by other recent studies.


Bacterial chromosome segregation.
Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.


Effects of GSTP1 and GPX1 Polymorphisms on the Risk of Preeclampsia in Chinese Han Women.
Increasing evidence shows that oxidative stress plays an important part in the pathophysiological mechanisms of preeclampsia (PE). Polymorphic variants of oxidative stress-related candidate genes GST1 and GPX1 can affect the antioxidant activities of their encoded enzymes. Therefore, this study aimed to explore the associational analysis between GSTP1 and GPX1 single nucleotide polymorphisms (SNPs) and susceptibility to PE in Chinese Han women. DNA from 1130 PE patients and 1226 healthy individuals was genotyped for SNPs rs1695 in GSTP1 and rs1050450 in GPX1 using a predesigned TaqMan SNP genotyping assay. The χ2 test compared differences in genetic distributions between the two groups in a case-control study. No significant differences in allelic or genotypic frequencies of GSTP1 rs1695 or GPX1 rs1050450 were detected between cases and controls (GSTP1 rs1695: χ2=1.122, p=0.571 by genotype, χ2=0.138, p=0.710, odds ratio=1.027, 95% confidence interval 0.892-1.183 by allele; GPX1 rs1050450: χ2=0.036, p=0.982 by genotype, χ2=0.002, p=0.960, odds ratio=1.005, 95% confidence interval 0.822-1.229 by allele). Moreover, no significant differences in genetic distribution were found between early/late-onset PE or mild/severe PE and control subgroups. Our results suggest that GSTP1 rs1695 and GPX1 rs1050450 SNPs have no effects on the risk of PE in the Chinese Han population. However, these results should be confirmed by replication in different populations.


Antibiotic use: A cross-sectional survey assessing the knowledge, attitudes, and practices amongst students of Punjab, Pakistan.
Objective: The aim of the study was to assess the knowledge, attitudes and practices of students regarding the use of antibiotics in Punjab, Pakistan. Participants: 525 medical and non-medical students from Punjab in Pakistan. Methods: The t-test and ANOVA were used to compare the average response of respondents. Chi-square test was used to measure the association of different elements. Results: The mean age was 20.78 ± 2.10%. About 14% of the students agreed about the appropriateness of antibiotics for viral infections, and 15% of students said they stopped taking the drugs when symptoms subsided. 65.7% of students took antibiotics only when prescribed by a doctor and 54% bought antibiotics without prescription. Statistically significant results were found among the students who had heard about the antibiotic resistance (p < 0.05). Conclusion: This study will help assess the adequacy of current educational campaigns, maximize rationalization of antibiotic use, and minimize gaps in knowledge and attitudes.


The role of surgery and transplantation in neuroendocrine tumours.
Surgery represents the only chance of cure for a patient with a neuroendocrine tumour (NET). The main indications for surgery lie in the risk of developing metastatic disease with increasing tumour diameter and for a functioning NET also in control of the hormonal syndrome. However, only a small minority of patients presents with a potentially resectable primary NET without metastatic disease. An R0-resection is mandatory, which may be achieved in selected cases by tissue sparing surgical techniques. Most patients unfortunately present with a locally advanced or metastatic disease. For patients with an advanced functioning NET, control of the hormonal syndrome may also represent a surgical indication. Various cytoreductive techniques or, in highly selected cases, liver transplantation can be applied. For locally advanced non-functioning tumours, there is an indication for surgery in large tumours which tend to create local complications because of bleeding or bowel obstruction. Especially in ileal NETs aggressive surgical therapy is recommended because of prevention of long-term complications, which may improve survival.


Acute rheumatic fever.
During the first half of this century rheumatic fever was a common disease with significant morbidity and mortality in the United States. In the 1980s, when many clinicians were hoping this disease was a disease of the past, anxieties were renewed when outbreaks were reported in several areas around the country. Although the etiology still eludes us, insight has been gained. Environmental and genetic factors are believed to play a role in the epidemiology of this disease. Additionally, the implicated organism, the group A streptococcus, has many strains, and differences in its many proteins may determine their potential for rheumatic fever. The mechanisms leading to disease are not clear, but the streptococcus has been implicated as a source of antigens with cross-reactivity with human tissues and has been shown to modify immune mechanisms. Clinical aspects are briefly reviewed and physicians are reminded to consider rheumatic fever as a diagnostic possibility in the appropriate settings.


Peritoneal CD5+ B-1 cells have signaling properties similar to tolerant B cells.
CD5(+) B (or B-1) cells are the normal precursors of B cell chronic lymphocytic leukemia. They differ from conventional B (B-2) cells with respect to their phenotype and mitogenic responses and are often secretors of the natural polyreactive antibodies in the serum. The origin of B-1 cells remains controversial, and the relationship between B-1 cells and autoreactive B cells is unclear. Here, we compare the signaling pathways that are activated by the engagement of the B cell antigen receptor (BCR) in B-1 and B-2 cells. Stimulation of the BCR leads to the induced activation of the three major classes of mitogen-activated protein kinases (MAPKs), ERK, JNK, and p38 MAPK, as well as the Akt kinase and the transcription factors nuclear factor of activated T cells (NF-AT) and NF-kappaB in B-2 cells. In contrast, B-1 cells have constitutive activation of ERK and NF-AT but exhibit delayed JNK and lack p38 MAPK and NF-kappaB induction upon BCR cross-linking. The lack of NF-kappaB activation in B-1 cells may be due to a lack of Akt activation in these cells. Furthermore, our study using specific inhibitors reveals that the extended survival of B-1 cells in culture is not due to the constitutive activation of ERK; nor is it due to Akt signaling or Bcl-x(L) up-regulation, since these are not induced in B-1 cells. The current findings of altered MAPK and NF-AT activation and lack of NF-kappaB induction in B-1 cells indicate that these cells have signaling properties similar to tolerant B cells that are chronically exposed to self-antigens. Indeed, BCR stimulation of B-1 cells does not lead to their full activation as indicated by their lack of maximal up-regulation of specific markers such as CD25, CD69, and CD86.


The influence of verbatim versus gist formatting on younger and older adults' information acquisition and decision-making.
Fuzzy-Trace Theory suggests that decision makers encode gist representations (bottom-line meaning) and verbatim representations (details) of information but rely more on gist, a tendency that increases with age. The present study examined implications for age differences in information seeking and decision-making by presenting gist and verbatim formatted choice scenarios. Participants comprised 68 younger and 66 older adults. Predecisional information seeking, indices of decision outcomes and recall, and relevant covariates were assessed. In line with theory, older adults self-reported and demonstrated stronger preferences for gist-based processing than younger adults did. Consistent with hypotheses, the total number of reviewed grid cells (including repeat views) was higher for gist than verbatim conditions, and this effect was stronger among older adults. Also, the proportion of unique cells reviewed and the accuracy of decision attribute recall were higher in the verbatim than gist condition and these effects were stronger among younger versus older adults. Further, gist formatting was associated with stronger use of option-wise information search, more value-concordant decisions (i.e., choices aligning with self-reported choice preferences), and decreased choice satisfaction, but these effects did not vary by age. Covariates, including information-processing preferences, partially accounted for these effects. Consistent with Fuzzy-Trace Theory, this suggests that information formatting and preferences modulate age differences in predecisional information acquisition: Depending on age, using either verbatim or gist formatting to communicate information can offer different benefits. Across age groups, however, gist formatting may facilitate value-concordant (and arguably higher-quality) decision-making. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Rapid Identification of SARS-CoV-2 Variants of Concern Using a Portable peakPCR Platform.
The need for tools that facilitate rapid detection and continuous monitoring of SARS-CoV-2 variants of concern (VOCs) is greater than ever, as these variants are more transmissible and therefore increase the pressure of COVID-19 on healthcare systems. To address this demand, we aimed at developing and evaluating a robust and fast diagnostic approach for the identification of SARS-CoV-2 VOC-associated spike gene mutations. Our diagnostic assays detect the E484K and N501Y single-nucleotide polymorphisms (SNPs) as well as a spike gene deletion (HV69/70) and can be run on standard laboratory equipment or on the portable rapid diagnostic technology platform peakPCR. The assays achieved excellent diagnostic performance when tested with RNA extracted from culture-derived SARS-CoV-2 VOC lineages and clinical samples collected in Equatorial Guinea, Central-West Africa. Simplicity of usage and the relatively low cost are advantages that make our approach well suitable for decentralized and rapid testing, especially in resource-limited settings.


Riparian Ficus tree communities: the distribution and abundance of riparian fig trees in northern Thailand.
Fig trees (Ficus) are often ecologically significant keystone species because they sustain populations of the many seed-dispersing animals that feed on their fruits. They are prominent components of riparian zones where they may also contribute to bank stability as well as supporting associated animals. The diversity and distributions of riparian fig trees in deciduous and evergreen forests in Chiang Mai Province, Northern Thailand were investigated in 2010-2012. To record the diversity and abundance of riparian fig trees, we (1) calculated stem density, species richness, and diversity indices in 20×50 m randomly selected quadrats along four streams and (2) measured the distances of individual trees from four streams to determine if species exhibit distinct distribution patterns within riparian zones. A total of 1169 individuals (from c. 4 ha) were recorded in the quadrats, representing 33 Ficus species (13 monoecious and 20 dioecious) from six sub-genera and about 70% of all the species recorded from northern Thailand. All 33 species had at least some stems in close proximity to the streams, but they varied in their typical proximity, with F. squamosa Roxb. and F. ischnopoda Miq the most strictly stream-side species. The riparian forests in Northern Thailand support a rich diversity and high density of Ficus species and our results emphasise the importance of fig tree within the broader priorities of riparian area conservation. Plans to maintain or restore properly functioning riparian forests need to take into account their significance.


Rapamycin reverses NPM-ALK-induced glucocorticoid resistance in lymphoid tumor cells by inhibiting mTOR signaling pathway, enhancing G1 cell cycle arrest and apoptosis.
The anaplastic lymphoma kinase (ALK) is an oncogene product involved in hematopoietic and non-hematopoietic malignancies. Recent studies have demonstrated that nucleophosmin (NPM)-ALK, originated from the fusion of NPM and ALK genes, causes cell transformation through diverse mechanisms. Here, we show a novel mechanism by which NPM-ALK transforms lymphoid tumor cells to become resistant to glucocorticoid (GC) or dexamethasone (Dex) treatment. Transformed BaF3 cells by NPM-ALK were much more resistant to Dex compared with their parental cells, and concurrently had a constitutive activation of mammalian target of rapamycin (mTOR) signaling, as evidenced by hyperphosphorylation of its downstream effectors, p70 S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). The mTOR inhibitor rapamycin suppressed activation of p70S6K in BaF3/NPM-ALK cells and reversed GC resistance by synergistically inhibiting mTOR signaling pathway, enhancing cell cycle arrest at G(1) phase and promoting apoptotic cell death. In conclusion, our data indicate that the ALK fusion kinase, NPM-ALK, induces GC resistance by activating mTOR signaling, and addition of mTOR inhibitors to the chemotherapeutic regimen of ALK+ lymphomas may improve the prognosis.


Late response and item nonresponse in the Finbalt Health Monitor survey.
The Finbalt Health Monitor is a collaborative system for monitoring the health-related behaviour, practices and lifestyles in Estonia, Finland, Latvia and Lithuania. This system is based on nationally representative samples and self-administered mailed questionnaires. In comparing the results of national surveys, the awareness of the direction and socioeconomic patterning of the response bias is essential. The data were gathered from the cross-sectional surveys conducted in 1998 from Estonia (n = 1362), Finland (n = 3504), Latvia (n = 2322) and Lithuania (n = 1874). An analysis was made of the prevalence of late response, completeness of information obtained from respondents and the magnitude of response bias on the prevalence estimates of health behaviour indicators. The response rates were comparatively high: 68% in Estonia, 70% in Finland, 77% in Latvia and 62% in Lithuania. Late response was weakly related to age, education or place of residence. The total proportion of missing information was below 10% and the sociodemographic patterning for this missing information was similar in all countries. Thus, older and less-educated respondents had more missing information on their questionnaires. Response bias of the prevalence estimates was minimal when it was calculated by using information obtained from late respondents. The level of nonresponse and missing information was comparable in different countries, not information on health behaviour. Therefore special efforts are needed to design a questionnaire form which appears equally relevant to all respondent groups. The follow-up mailings were an effective way to increase the total response rate, but it was unlikely that they provided an effective way to reach the 'hard core' nonrespondents.


Prevalence of dipterous flies associated with human and animal diseases in Matruh and South Sinai Governorates, Egypt.
The present study identified the dipterous flies associated with human and animal diseases in Matruh and South Sinai Governorates. The results indicated that 49817 belonging to 13 families, 24 genera and 33 species were trapped from Matruh Governorate and 3708 flies belonging to 9 families, 13 genera and 16 species were trapped from South Sinai Governorate from January to December 2009. M. domestica was the most abundant in both Governorates. Statistical analysis showed that species of all families were significantly higher in Matruh Governorate than South Sinai Governorate due to spread of garbage, fermented fruits and human & animal excreta.


Evidence of ancient papillomavirus recombination.
An open question amongst papillomavirus taxonomists is whether recombination has featured in the evolutionary history of these viruses. Since the onset of the global AIDS epidemic, the question is somewhat less academic, because immune-compromised human immunodeficiency virus patients are often co-infected with extraordinarily diverse mixtures of human papillomavirus (HPV) types. It is expected that these conditions may facilitate the emergence of HPV recombinants, some of which might have novel pathogenic properties. Here, a range of rigorous analyses is applied to full-genome sequences of papillomaviruses to provide convincing statistical and phylogenetic evidence that evolutionarily relevant papillomavirus recombination can occur.


When to operate: online patient-reported outcome measures (PROMs) can help decide.
We present a report on use of a web-based electronic patient-reported outcome measures (ePROMs) system to support decision-making for a patient with an osteoarthritic knee. After being placed on a waiting list for knee arthroplasty, the use of preoperative PROMs allowed the patient and surgical team to review ongoing disability, and, as a result, alter the management plan by deferring surgery. Ongoing clinical review and symptom management has been centred on ePROMs and has been tailored to the specific needs of the individual. PROMs data are increasingly becoming a necessary component of outcome measurement in many surgical areas. Often, these data are available to neither patient nor clinician in a way that prospectively allows meaningful management. This case highlights how ePROMs can directly influence patient care in real time.


Feeding patterns in breast-fed and formula-fed infants.
The intention of this study performed in healthy breast- and formula-fed infants was to characterize physiological feeding patterns as a basis for counseling parents to feed their infants on demand. Ingested milk volumes of 10 breast-fed and 14 formula-fed infants were measured during five 72-hour investigation periods during the 3rd, 6th, 9th, 13th, and 17th weeks of life. A comparable diurnal distribution of feeds was observed in both groups during the first 9 weeks of life, with a day-night asymmetry of feeding first observed at the age of 6 weeks. Thereafter, formula-fed infants showed a further decrease in their nightly milk intake. Within the investigation period, the milk volume per feed rose from 100 (range 40-200) g to 140 (range 30-300) g in the breast-fed group and from 100 (range 20-200) g to 200 (range 20-450) g in formula-fed infants. From the 6th week of life onwards, formula-fed infants had significantly higher feeding volumes. Parents should be informed about the variability of infant demands per feed and of feeding at night observed in breast-fed infants. The results suggest that feeding patterns similar to those of breast-fed infants are difficult to accomplish in formula-fed infants.


Minimal access left ventricular reconstruction.
The Revivent TC™ Transcatheter Ventricular Enhancement System (BioVentrix Inc.) is intended for use in heart failure with cardiac dysfunction a previous myocardial infarction. The resultant increased left ventricular systolic volume and discrete, contiguous, noncontractile (akinetic and/or dyskinetic) scar located in the anteroseptal, apical (may extend laterally) region of the left ventricle (LV) lends itself to Revivent. The procedure, called Less Invasive Ventricular Enhancement, consists of the implantation of a series of microanchors pairs to exclude the scarred myocardium, to reduce and reshape the LV. We present the procedure step-by-step, as team coordination between the cardiac surgeon and the interventional cardiologist is essential to ensure good procedural outcomes. This is a novel and new technique to address heart failure secondary to myocardial infarction.


Short antibacterial peptides with significantly reduced hemolytic activity can be identified by a systematic L-to-D exchange scan of their amino acid residues.
High systemic toxicity of antimicrobial peptides (AMPs) limits their clinical application to the treatment of topical infections; in parenteral systemic application of AMPs the problem of hemolysis is one of the first to be tackled. We now show that the selectivity of lipidated short synthetic AMPs can be optimized substantially by reducing their hemolytic activity without affecting their activity against methicillin resistant Staphylococcus aureus (MRSA). In order to identify the optimized peptides, two sets of 32 diastereomeric H-(D)Arg-WRWRW-(L)Lys(C(O)CnH2n+1)-NH2 (n = 7 or 9) peptides were prepared using a split-split procedure to perform a systematic L-to-D exchange scan on the central WRWRW-fragment. Compared to the all-L C8-lipidated lead sequence, diastereomeric peptides had very similar antibacterial properties, but were over 30 times less hemolytic. We show that the observed hemolysis and antibacterial activity is affected by both differences in lipophilicity of the different peptides and specific combinations of L- and D-amino acid residues. This study identified several peptides that can be used as tools to precisely unravel the origin of hemolysis and thus help to design even further optimized nontoxic very active short antibacterial peptides.


Individual Differences in Spontaneous Expressive Suppression Predict Amygdala Responses to Fearful Stimuli: The Role of Suppression Priming.
Though the spontaneous emotion regulation has received long discussions, few studies have explored the regulatory effects of spontaneous expressive suppression in neural activations, especially in collectivistic cultural context. The functional magnetic resonance imaging (fMRI) study aimed to examine whether individual differences in the tendency to use suppression are correlated with amygdala responses to negative situations when individuals are unconsciously primed with expressive suppression. Twenty-three healthy Chinese undergraduates completed an fMRI paradigm involving fear processing, and a synonym matching task was added to prime participants with the unconscious (automatic) expressive suppression goal. Participants completed measures of typical emotion regulation use (reappraisal and suppression), trait anxiety, and neuroticism. Results indicated that only in emotion suppression prime condition, greater use of suppression in everyday life was related to decreased amygdala activity. These associations were not attributable to variation in trait anxiety, neuroticism, or the habitual use of reappraisal. These findings suggest that in collectivistic cultural settings, individual differences in expressive suppression do not alter fear-related neural activation during suppression-irrelevant context. However, unconscious suppression priming facilitates the manifestation of individual differences in the neural consequence of expressive suppression, as reflected by the priming-specific decrease of emotional subcortical activations with more use of expressive suppression.